synthesisofnovelvo(ii)-perimidinecomplexes:spectral...

Research ArticleSynthesis of Novel VO(II)-Perimidine Complexes SpectralComputational and Antitumor Studies

Gamil A Al-Hazmi12 Khlood S Abou-Melha1 Nashwa M El-Metwaly 34

and Kamel A Saleh5

1Chemistry Department Faculty of Science King Khalid University PO Box 9004 Abha Saudi Arabia2Chemistry Department Faculty of Applied Sciences Taiz University PO Box 82 Taiz Yemen3Chemistry Department College of Applied Sciences Umm Al-Qura University Makkah Saudi Arabia4Chemistry Department Faculty of Science Mansoura University Mansoura Egypt5Biology Department Faculty of Science King Khalid University PO Box 9004 Abha Saudi Arabia

Correspondence should be addressed to Nashwa M El-Metwaly n_elmetwaly00yahoocom

Received 12 January 2018 Accepted 26 April 2018 Published 6 September 2018

Academic Editor Spyros P Perlepes

Copyright copy 2018 Gamil A Al-Hazmi et al -is is an open access article distributed under the Creative Commons AttributionLicense which permits unrestricted use distribution and reproduction in any medium provided the original work isproperly cited

A series of perimidine derivatives (L1ndash5) were prepared and characterized by IR 1HmiddotNMR mass spectroscopy UV-Vis XRDthermal and SEM analysis Five VO(II) complexes were synthesized and investigated by most previous tools besides thetheoretical usage A neutral tetradentate mode of bonding is the general approach for all binding ligands towards bi-vanadylatoms A square-pyramidal is the configuration proposed for all complexes XRD analysis introduces the nanocrystalline nature ofthe ligand while the amorphous appearance of its metal ion complexes -e rocky shape is the observable surface morphologyfrom SEM images-ermal analysis verifies the presence of water of crystallization with all coordination spheres-e optimizationprocess was accomplished using the Gaussian 09 software by different methods-emost stable configurations were extracted anddisplayed Essential parameters were computed based on frontier energy gaps with all compounds QSAR parameters were alsoobtained to give another side of view about the biological approach with the priority of the L3 ligand Applying AutoDockTools 42program over all perimidine derivatives introduces efficiency against 4c3p protein of breast cancer Antitumor activity wasscreened for all compounds by a comparative view over breast colon and liver carcinoma cell lines IC50 values representpromising efficiency of the L4-VO(II) complex against breast colon and liver carcinoma cell lines -e binding efficiency ofligands towards CT-DNA was tested Binding constant (Kb) values are in agreement with the electron-drawing character of thep-substituent which offers high Kb values Also variable Hammettrsquos relations were drawn

1 Introduction

Vanadium was widely used as a therapeutic agent in the lateeighteenth century treating a variety of ailments includinganemia tuberculosis rheumatism and diabetes [1 2] Va-nadium compounds exhibit various biological and physio-logical effects in the human body Vanadium compoundshave been extensively studied for their diverse biologicalactivities such as antitumor antibacterial and insulin-enhancing effects and potential capabilities as DNAstructural probes [3 4] -e coordination chemistry of

oxovanadium is highly ligand dependent and more im-portant in biological systems [5] as well as catalytic systems[6 7] Due to the d1 configuration vanadium(IV) ionicspecies are easily identified by EPR spectroscopy Due to lesstoxicity [8 9] the Schiff base complexes of the vanadyl ionare topic of many research reports [10 11] In Europevanadium is often used as a natural treatment for diabetesVanadium has been found in human studies to imitate theeffects of insulin in our bodies -is ability may be useful forsome of those with diabetes a natural method to help lowerblood sugar take less insulin or in some instances stop

HindawiBioinorganic Chemistry and ApplicationsVolume 2018 Article ID 7176040 22 pageshttpsdoiorg10115520187176040

taking insulin altogether [12 13] It is noticeable thatcomplexation of vanadium with organic ligands minimizesunfavorable effects of its inorganic salts such as vanadylsulfate while even maintains its potential benefits [14]Furthermore mimicking the biological activities in naturalsystems can be achieved by vanadium complexes whichcontain oxygen and nitrogen donor ligands so identificationof the structure of these complexes is regarded important[15ndash17] Bioinorganic chemistry is a fast developing field ofmodern chemistry that uses Schiff bases and their transitionmetal complexes for a variety of applications eg in bi-ological medical and environmental sciences -is work isinterested in preparation of a series of perimidine derivativesby various substituents New vanadyl complexes will beprepared and well characterized by using different tech-niques CT-DNA binding will be tested along the organicseries -eoretical implementation will be accomplishedover all prepared compounds by different standard pro-grams Antitumor activity will be scanned over all newprepared compounds for comparison

2 Experimental Work

21 Chemicals Used Chemicals essential for preparation ofperimidine derivatives such as 18-diaminonaphthaleneethylbenzoyl acetate 4-methoxyaniline aniline 4-chlor-oaniline 3-chloroaniline 4-nitroaniline NaNO2 NaOHHCl and dioxane were purchased from Fluka and usedwithout previous treatments Also VOSO4middotxH2O salt usedfor the complexation process was commercially availablefrom Sigma-Aldrich All handled solvents were from Merckand used without previous purification

22 Synthesis

221 Synthesis of Compounds 3andashe (Perimidine Derivatives)Ligands 3andashe were synthesized as reported in the literature[18] from coupling reaction of compound 1 (25mmol) inethanol (20mL) with the appropriate arenediazoniumchloride 2 in the presence of sodium hydroxide (25mmol)in the ice bath at 0ndash5degC -e whole mixture was then left ina refrigerator overnight -e precipitated solid was filteredoff washed with water and finally crystallized fromdioxaneEtOH to give the respective hydrazones 3andashe(Scheme 1) 1HmiddotNMR and mass spectra are displayed inFigures 1 2 S1 and S2 -e analysis is matching completelywith that reported in the literature [16] -e structural formsof new perimidine compounds are displayed in Figures 3(a)and 3(b)

(1) 2-[N-phenyl-2-oxo-2-phenylethanehydrazonoyl]-1H-perimidine ( 3a ) (L1) IR υ 3402 3194 (2NH) and1616 (CO) cmminus1 1HmiddotNMR (DMSO-d6) d 672ndash780(m 16H ArndashH) and 1362 (s 2H 2NH) MS mz() 390 (M 22) 285 (2) 166 (5) 140 (7) 127 (1) 105(100) 93 (8) and 77 (35) Anal calcd for C25H18N4O(39042)

(2) 2-[N-(4-methoxyphenyl)-2-oxo-2-phenylethanehydrazonoyl]-1H-perimidine ( 3b ) (L2) IR υ 3333 3167

(2NH) and 1680 (CO) cmminus1 1HmiddotNMR (DMSO-d6) δ358 (s 3H OCH3) 759ndash797 (m 15H ArH) and1220 (br s 2H 2NH) MS mz () 420 (M 5) 419(9) 193 (12) 166 (12) 126 (14) 107(17) 105 (100) 92(31) and 77 (75) Anal calcd for C26H20N4O2(42047)

(3) 2-[N-(4-chlorophenyl)-2-oxo-2-phenylethanehydrazonoyl]-1H-perimidine ( 3c ) (L3) IR υ 3422 3206 (2NH)and 1612 (CO) cmminus1 1HmiddotNMR (DMSO-d6) d 673ndash777 (m 15H ArndashH) and 1327 (s 2H 2NH) MSmz() 426 (M2 5) 425 (M 1 6) 424 (M 14) 140 (4) 127(5) 111 (2) 105 (100) and 77 (37) Anal calcd forC25H17ClN4O (43544)

(4) 2-[N-(4-nitrophenyl)-2-oxo-2-phenylethanehydrazonoyl]-1H-perimidine ( 3d ) (L4) IR υ 3356 3198(2NH) and 1670 (CO) cmminus1 1HmiddotNMR (DMSO-d6) d664ndash821 (m 15H ArndashH) and 1260 (s 2H 2NH)MS mz () 435 (M 8) 238 (34) 138 (13) 167 (11)106 (45) 105 (58) 93 (100) 77 (44) and 66 (76)Anal calcd for C25H17N5O3 (42488)

(5) 2-[N-(3-chlorophenyl)-2-oxo-2-phenylethanehydrazonoyl]-1H-perimidine ( 3e ) (L5) IR υ 3229 3167 (2NH)and 1622 (CO) cmminus1 1HmiddotNMR (DMSO-d6) d 670ndash791 (m 15H ArndashH) and 1302 (s 2H 2NH) MSmz() 426 (M2 7) 425 (M1 9) 424 (M 16) 194 (7) 166(7) 140 (5) 127 (4) 105 (100) 111 (4) and 77 (36)Anal calcd for C25H17ClN4O (42488)

222 Synthesis of VO(II) Complexes New VO(II) complexseries was synthesized by using variable derivatives fromperimidine ligands Equimolar (3mmol) values were usedfrom the perimidine ligand and dissolved fully in dioxaneafter that it wasmixed with VOSO4middotxH2Owhich dissolves inthe dioxaneH2O mixture -e weighted molar ratio valuefrom vanadyl salt was calculated attributing to its anhydrousweight After asymp5 h reflux 05 g sodium acetate was addedafter dissolving in a little amount of bi-distilled water toprecipitate the complexes Each precipitate was separatedout on hot filtered off washed several times with ethanoland diethyl ether and finally dried in a vacuum desiccator

23DNABindingStudy -ebinding attitudes of perimidinederivatives towards calf thymus DNA (CT-DNA) will bestudied by using the spectroscopy method CT-DNA(50mg) was dissolved by stirring overnight in doubledeionized water (pH 70) and must be kept at 4degC Bi-distilled water was used to prepare the buffer (50mM tris(hydroxymethyl)-aminomethane and 50mM NaCl pH

72) Tris-HCl buffer was prepared in deionized water DNAbuffering solution gave absorbance ratio at 260280 nmby 18ndash19 and this indicates the absence of protein fromDNA [19 20] Applying the UV-Vis technique the DNAconcentration was determined (510times10minus4M) using itsknown molar absorptivity coefficient value (6600Mminus1middotcmminus1at 260 nm) At room temperature 200ndash900 nm is the

2 Bioinorganic Chemistry and Applications

wavelength range used and in 1 cm quartz cuvette a fixedconcentration (20times10minus5M in dioxane) from each ligandwas utilized A scanning process was done after adding CT-DNA by a gradual way from 000 to asymp218times 0minus4molmiddotLminus1 -esame DNA amount added to the ligand solution was addedalso to the reference cell to delete the absorbance of freeDNA A significant binding constant (Kb) for interactionbetween ligands towards CT-DNA was determined by usingthe following equation [DNA](єaminus єf ) [DNA](єbminus єf )+ 1Kb (єaminus єf ) [21] where [DNA] is the concentration ofCT-DNA in base pairs єa is the extinction coefficient ob-served for A[compound] at the used DNA concentrationand єf is the extinction coefficient for each free compound(HL1minus5) in the solution Moreover єb is the extinction co-efficient of the compound when fully bond to DNA In plotsof [DNA](єaminus єf ) vs [DNA] Kb is given by the followingratio slopeintercept

24 Antitumor Influence -e evaluation of cytotoxicity ofcandidate anticancer drugs will be performed using themost effective available SRB method All molecules and

their derivatives will be tested for their toxicity on differentcancer cell lines In an attempt to evaluate the impact thesamples were prepared with different concentrations 00101 1 10 and 100 microgml respectively -e cells were cul-tured in the mixture of samples and media (RPMI-FBS+ samples) for 72 h after that cytotoxicity impact wasevaluated compared to the response of doxorubicin asa positive control

-e cytotoxic effect of the composites and ligands will betested against different cancer cell lines (HepG2MCF-7 andHCT116) as donor cancer cell lines by means of the SRBcytotoxicity test To avoid the contamination the RPMImedia of the cells were supplemented with 100 microgmlstreptomycin and 100 unitsml penicillin with 10 FBSand incubated at a 5 CO2 incubator Growing cells werecollected using the trypsin enzyme and then counted usingthe cell counter in order to distribute equally the number ofcells to each well of 69-well plates -e cells will incubateunder sterile conditions with different concentrations ofboth ligands and composites for 72 hours and subsequentlytreated cells and untreated cells and the positive control werefixed with 10 TCA (trichloroacetic acid) and kept at 4degC for

16 14 12 10

NH

N N NH

7801

7776

7550

7526

7370

7345

7300

7274

7202

7178

7147

7134

7121

6749

6725

3340

2500

2585

3266

OPh

Ph

8 6 4 2

1079 12897101530

Figure 1 1HmiddotNMR of L1 ligand (as example)

X a H b 4-MeO c 4-CI d 4-NO2 e 3-CI

1

HN

NH O

Ph

+

23

X

N N CI

NaOH 0degC

EtOH

+

N

NH

N NH

O

Ph

X

ndash

Scheme 1 Synthesis of perimidine compounds 3andashe

Bioinorganic Chemistry and Applications 3

Figure 2 Mass spectra of L1 and L4 ligands

HNCl

H

NN

N

OHN

Cl

H

NN

N

O

L4 L5

HN

H

L1 L2 L3

N

N

N

O HN

H

N

NN

N

O

O

OHN

H

N N

N

O O

H3C

(a)

Figure 3 Continued


1 h After washing few times fixed and washed cells werestained with 04 SRB stain solution for ten minutes andsubsequently the cells were washed with 1 glacial aceticacid To dissolve SRB-stained cells Tris-HCl was used Todetect the density of remaining colors a plate reader will be

used at 540 nm wavelength In order to determine the IC50value statistical analysis was accomplished through Sig-maPlot version 140 -e advantage of prepared com-pounds as potential drugs against different cancer cells wasinvestigated

LH

LOMe

LNO2

LCIP

LCIM

LH

LOMe

LNO2

LCIP

LCIM

(b)

Figure 3 (a) Structures of perimidine ligands (L1ndash5) (b) Optimized structures of five perimidine ligands


25 Physical Techniques

251 Elemental Analysis -e element contents (carbonhydrogen and nitrogen) were determined at the Micro-Analytical Unit of Cairo University Vanadium sulfate andchloride contents were evaluated by known standardmethods [22] through complexometric and precipitationmethods

252 Conductivity Measurements Applying the Jenway4010 conductivity meter the molar conductivity of freshlyprepared 10times10minus3molcm3 in DMSO solutions wasestimated

253 X-Ray Diffraction and SEM X-ray diffraction man-ners were recorded on the Rigaku diffractometer usingCuKα radiation Scanning electron microscopy (SEM)images were obtained by using Joel JSM-6390 equipment

254 IR 1HmiddotNMR and 13CNMR Spectra IR spectra wereobtained using the JASCO FTIR-4100 spectrophotometerfrom 400 to 4000 cmminus1 in the KBr disc while 1HmiddotNMRspectra were recorded in deuterated dimethyl sulfoxideusing the Varian Gemini 300NMR spectrometer

255 Mass spectra Mass spectra were recorded on GCMS-QP1000 EX (Shimadzu) and GCMS 5988-A

256 ESR Analysis ESR spectra of VO(II)-powderedcomplexes were obtained on the Bruker EMX spectrome-ter working in the X-band (960GHz) with 100 kHz mod-ulation frequency -e microwave power was set at 1mWand modulation amplitude was set at 4Gauss -e low fieldsignal was obtained after 4 scans with a 10-fold increase inthe receiver gain A powder spectrum was obtained ina 2mm quartz capillary at ordinary temperature

257 UV-Vis Spectra and Magnetic MeasurementsElectronic spectra for all compounds were recorded usingthe UV2 Unicam UVVis spectrophotometer in the DMSOsolvent Magnetic susceptibility values for VO(II) complexeswere conducted by the Johnson Matthey magnetic suscep-tibility balance at room temperature

258 Fermal Analysis -e Shimadzu thermogravimetricanalyzer (20ndash900degC) at 10degCmiddotminminus1 heating rate under ni-trogen was used for thermal analysis -eoretical treatments(modeling and docking) were accomplished by knownstandard programs

259 Antitumor Activity Antitumor activity was con-ducted at the Regional Center for Mycology andBiotechnology

26 Computational

261 DFTHartreendashFock Study Implementing the Gaussian09 software [23] the structural optimization process wasaccomplished over pyrimidine ligands and their VO(II)complexes in the gas phase Two knownmethods were foundas the most suitable one for the optimization process -eoutput files were visualized by the GaussView program [24]According to the numbering scheme DFT parameters wereextracted using frontier energy gaps (EHOMO and ELUMO) forall investigated compounds Moreover other significantcomputations were taken from log files as oscillator strengthexcitation energy charges assigned for coordinating atomsand some bond lengths

262 QSAR Computation New perimidine compoundswere treated for the optimization process to give the beststructural forms HyperChem (v81) software is the tool usedfor such a purpose -e preoptimization process was exe-cuted by molecular mechanics force field (MM+) accom-panied by semiempirical AM1 for the soft adjustmentprocedure -is process was accomplished without fixingany parameter till the equilibrium state for geometricstructures A system for minimizing energy was employedthe PolakndashRibiere conjugated gradient algorithm-eQSARprocess leads to computing essential parameters includingthe partition coefficient (log P) Log P value is considered theessential indicator used to predict the biological activity foroptimized compounds [25]

263 Docking Computation Applying AutoDockTools 42by using Gasteiger partial charges which added over theelements of pyrimidine ligands the simulation procedurewas executed to give a view on the biological behavior ofcompounds Rotatable bonds were cleared and nonpolarhydrogen atoms were conjoined Interaction occurredbetween inhibitors (ligands) and protein receptors (4c3p3bch and 4zdr) for breast colon and liver cancerproteins -e docking process was accomplished afteraddition of fundamental hydrogen atoms Kollmanunited atom-type charges and salvation parameters [26]Affinity (grid) maps of timestimes A grid points and 0375 Aspacing were generated applying the AutoGrid program[27] Van der Waals forces and electrostatic terms wereobtained -is is done by applying autodock parameterset-dependent and distance-dependent dielectric func-tions respectively -e docking process was executedusing the Solis and Wets local search method and La-marckian genetic algorithm (LGA) [28] Initial positionorientation and torsions of the inhibitor molecule wereset indiscriminately All rotatable torsions were expelledduring the docking process Each experiment is the meanvalue of 10 different runs that are set close after themaximum of 250000 energy assessments 150 is the usedpopulation size During the process the translationalstep of 02 A quaternion and torsion steps of 5 wereapplied


3 Results and Discussion

31 Physical Properties Essential analytical and physicaldata for ligands and their VO(II) complexes are summarizedin Table 1 All investigated complexes are nonhygroscopic innature having high melting point (gt300degC) -e elementalanalysis proposes 1 2 (HL M) molar ratio as the generalformula for all complexes All complexes are completelysoluble in DMSO or DMF solvents -e conductivitymeasured is 566ndash1422Ωminus1middotcm2middotmolminus1 Such conductivityvalues are attributed to the nonconducting character oftested complexes [29] -is coincides with sulfate anionwhich favors covalent attachment with metal ions inside thecoordination sphere

32 Comparative IR Study -e assignments of all charac-teristic bands for five perimidine ligands and their VO(II)complexes are summarized in Table 2 ](NH) δ(NH)](CN) and ](CO) are the significant functional bands forcoordinating groups which appear in narrow regions ob-served in all derivatives -is may refer to the far effect ofthe aromatic substituent on bond movement inside suchgroups A comparative study of ligands and their VO(II)complexes reveals the following observations (1) lower-shifted appearance of former bands is considered a strongevidence for contribution of CO NH and CN groups incoordination towards two central atoms (2) New bandsappeared at 1368ndash1434 and 1140ndash1179 cmminus1 assigned for]as(SO4) and ]s(SO4) respectively through bidentateattachment [30] (3) Other bands appearing at asymp760 andasymp690 cmminus1 are attributed to δr(H2O) and δw(H2O) re-spectively for crystal water molecules (4) ](M-L) bandsappeared at the low wavenumber region belonging to M-Oand M-N bonds -ese spectral observations suggest a tet-radentate mod of coordination towards two vanadyl atomsAlso the band observed at 966ndash1074 cmminus1 range assigns for](VO) significantly pointing to the square-pyramidalconfiguration [31]

33 Electronic Spectra and Magnetic MeasurementsElectronic transition bands andmagnetic moment values areaggregated in Table 3 UV-Vis spectra were recordedqualitatively in the DMSO solvent to gain smoothly ab-sorption curves Intraligand transition bands appearing at31250ndash38168 25974ndash30769 and 17544ndash19157 cmminus1 areattributed to n⟶σlowast π⟶ πlowast and n⟶ πlowast transitionsrespectively inside variable groups [32] A structural con-densed conjugation of chromophores leads to appearance ofdeep colors for all perimidine ligands -is is accompaniedwith the appearance of the n⟶ πlowast band in the middle ofthe visible region VO(II) complex spectra display intra-ligand transitions suffer shift due to coordination -e ap-pearance of charge transfer bands attributes to O⟶V andN⟶V transitions Also new significant d-d transitionbands were observed at asymp15300 and 12800 cmminus1 assigned for2B2g⟶ 2B1g (E2 υ2) and 2B1g⟶ 2Eg (E1 υ1) respectively-ese bands are attributed to transition inside the square-pyramidal configuration (Figure 4) Reduced magnetic

moment values (μeff 165ndash168 BM) recorded for all com-plexes support the proposal of binuclear complexes [33]

34 ESR Spectra ESR spectra (Figure 5 for example) ofVO(II) solid complexes were obtained and investigated toverify the structural forms of them All spectra demon-strated an eight-line pattern which attributes to theanalogous and vertical ingredients g-tensors and hyper-fine (hf ) A-tensors Spin Hamiltonian parameters andmolecular orbital values were calculated and are repre-sented in Table 4 -e analogous and vertical ingredientsare well resolved Nitrogen super-hyperfine splitting is notobserved which points to the presence of single electronin the dxy orbital -e pattern suggests that g and A areaxially symmetric in nature -e factors A and g appear tobe in covenant with the values commonly known forvanadyl complex in the square-pyramidal geometry G

factor which is expressed by G (g minus 20023)(gperpminus 20023) 4 measures the exchange interaction be-tween metal centers In agreement with Hathaway[34 35] Ggt 4 shows negligible exchange interactionwhile Glt 4 is the vice versa An observable reduction ofthe values calculated (171ndash279) proposes strong in-teraction inside binuclear complexes [36 37] -is in-teraction affects the magnetic moment value of complexeswhich suffers observable reduction-e tendency of A11 todecrease with increasing g11 is an index for tetrahedraldistortion (f gA) [38ndash40] -e molecular orbitalcoefficients α2 and β2 are calculated by

β2 76minus

A11

P+

AperpP

+ g11 minus514

gperp minus914

ge1113874 1113875

α2 20023minusΔg

8β2λ where Δg gperp minusg||1113872 1113873 times 10minus3

(1)

-e hyperfine conjunction disciplinarians were calcu-lated by taking A and Aperp as negative which gave positivevalues of β2 and α2-e calculated α2 and β2 values introducethe highly ionic character of in-plane σ- and π-bonding -eelectronic transition spectra display two significant bands atasymp15300 and 12800 cmminus1 assigned for 2B2g⟶ 2B1g (E2 υ2)and 2B1g⟶ 2Eg (E1 υ1) respectively Assume pure d-or-bitals by using first- and second-order perturbation theories-e parameters attributing to transition energy are called thespin Hamiltonian parameters and calculated by the fol-lowing expression gperp ge minus (2λE2) where ge is the free-electron g value (20023) Using E2 value the spin-orbitalcoupling constant (λ) was evaluated (13818) A value for λ of250 cmminus1 is reported [41] for free V+4 ion -e high re-duction in the magnitude of λ for the double-bondedoxovanadium complex (VO)+2 is attributed to sub-stantial π-bonding However the value falls inside the logicalborders announced -e orbital reduction factors namelyK and Kperp are also calculated using 2K (gminus 200277)E8 λ and 2Kperp (gperp minus 200277) E2 λ For pure σ-bondingKasympKperpasympminus077 while 2Kgt 2Kperp signifies in-planeσ-bonding with 2Kperplt 2K accounting for out-of-planeπ-bonding [42]


341 Calculation of Dipole Term (p) Dipolar term valuescan be determined by

p 7 A11 minusAperp( 1113857

6 +(32) λE1( 1113857 (2)

If A11 is taken to be negative and Aperp positive the value ofp will be more than 270G which is far from the expectedvalue-us the signs of bothA11 andAperp are used as negativeand are indicated in the form of the isotropic hf constant(Ao) McGarvey theoretically accomplished the p value as

Table 1 Significant analytical and physical data of perimidine compounds and their VO(II) complexes

Compounds (formula weight)(calcdfound) Color

Elemental analysis () calcd (found)C H N SO4Cl V

(1) (C25H18N4O) (L1) (3904439042)Darkbrown

7691(7690)

465(466)

1435(1435) mdash mdash

(2) [(VO)2 (SO4)2 (L1)]H2O (73446) Darkbrown

4088(4088)

274(273) 763 (765) 2616 (2616) 1387

(1388)

(3) (C26H20N4O2) (L2) (4204742044)Darkbrown

7427(7427)

479(479)


(4) [(VO)2 (SO4)2 (L2)]2H2O (78251) Dark green 3991(3990) 309 (310) 716 (717) 2455 (2454) 1302

(1303)

(5) (C25H17N5O3) (L3) (4354443542)Darkbrown

6896(6895)

393(393)


(6) [(VO)2 (SO4)2 (L3)]H2O (77946) Dark green 3852(3852)

246(246) 899 (897) 2465 (2466) 1307

(1305)

(7) (C25H17N4OCl) (L4) (4248842486)Darkbrown

7067(7066)

403(402) 1319 (1318) 834 (835) mdash


249(248) 729 (728) 2499 (2502)461

(463)1325(1326)


7067(7068)

403(405) 1319 (1318) 834 (835) mdash

(10) [(VO)2 (SO4)2 (L5)]3H2O (80493) Darkbrown

3730(3731)

288(288) 696 (695) 2387 (2388)440

(441)1266(1267)

Table 2 Significant IR spectral bands (cmminus1) of perimidine compounds and their VO(II) complexes

Compounds ]NH ]OH δNH υCO ]CN ]as(SO4) ]s(SO4) δr(H2O) δw(H2O) ]VO ]M-O ]M-N

(1) (C25H18N4O) (L1) 3155 1473 1618 1518 mdash mdash mdash mdash mdash mdash(2) [(VO)2 (SO4)2 (L1)]H2O 3110 3350 1470 1596 1514 1420 1142 765 670 966 588 476(3) (C26H20N4O2) (L2) 3177 1470 1597 1508 mdashmdash mdash mdash mdash mdash(4) [(VO)2 (SO4)2 (L2)]2H2O 3100 3372 1447 1592 1502 1411 1146 765 697 1074 572 515(5) (C25H17N5O3) (L3) 3150 1473 1620 1538 mdash mdash mdash mdash mdash mdash(6) [(VO)2 (SO4)2 (L3)]H2O 3105 3382 1447 1616 1517 1411 1179 743 697 966 600 508(7) (C25H17N4OCl) (L4) 3160 1474 1614 1518 mdash mdash mdash mdash mdash mdash(8) [(VO)2 (SO4)2 (L4)]H2O 3100 3420 1471 1624 1510 1434 1150 755 637 985 610 550(9) (C25H17N4OCl) (L5) 3150 1473 1620 1518 mdash mdash mdash mdash mdash mdash(10) [(VO)2 (SO4)2 (L5)]3H2O 3054 3384 1446 1616 1512 1368 1140 754 689 1074 589 508

Table 3 Electronic transitions of perimidine compounds and their VO(II) complexes

Compounds μeff (BM) d-d transition bands (cmminus1) Intraligand and charge transfer (cmminus1)(1) (C25H18N4O) (L1) mdash mdash 31746 26316 23923 18868(2) [(VO)2 (SO4)2 (L1)]H2O 166 15290 12800 35714 29412 25641 24272 17857(3) (C26H20N4O2) (L2) mdash mdash 38168 28249 23810 19048(4) [(VO)2 (SO4)2 (L2)]2H2O 168 15393 12750 37037 30769 26316 23256 17544(5) (C25H17N5O3) (L3) mdash mdash 36364 30303 26316 23810 19157(6) [(VO)2 (SO4)2 (L3)]H2O 166 15873 12830 37037 28571 26667 18182(7) (C25H17N4OCl) (L4) mdash mdash 31746 25974 18587(8) [(VO)2 (SO4)2 (L4)]H2O 167 15385 12800 35714 30303 25974 24390 17857(9) (C25H17N4OCl) (L5) mdash mdash 31250 26316 24390 18182(10) [(VO)2 (SO4)2 (L5)]3H2O 165 15873 12780 35714 30769 25000 23256 18868


+136G for vanadyl complexes which does not deviate muchfrom the expected value

342 Calculation of MO Coe13cients and BondingParameters e g values observed are dierent from theelectronic value (20023) is assigns to spin-orbit in-teraction of the dxy ground state level e isotropic andanisotropic g and A parameters were calculated using thefollowing equations Ao (A + 2Aperp)3 andgo (g + 2gperp)3 Taking A11 and Aperp to be negative valuesthe K expression is Kminus(Aop)minus (geminusgo)

us K (Fermi contact term) can be determined eFermi contact term k is a sense of polarization exerted by

(a) (b)

(c) (d)

(e)

Figure 4 Geometry optimization of VO(II)-perimidine complexes (andashe respectively)

1000

500

0

ndash500

ndash1000

ndash1500

ndash2000

Sign

al in

tens

ity

2800 2900 3000 3100 3200 3300 3400 3500 3600 3700Magnetic field (Gauss)

Figure 5 ESR spectrum of L1 +VO(II)complex


the uneven apportionment of d-electron density on the innercore s-electron

35 X-Ray Diraction X-ray diraction patterns were ex-ecuted over 10deglt 2θlt 90deg range (Figures 6 and S3) for li-gands under study is technique gives a considerable viewabout dynamics of the crystal lattice in solid compoundsUsing standard methods a comparative study of patternswith reactants reects the purity of isolated compounds [43]Also signicant parameters related to crystalline com-pounds can be calculated using the high-intense peak (fullwidth at half maximum (FWHM)) e crystallinityappearing with the LH ligand reects the isolation ofa strictly known irregular crystallite while the amorphousappearance of others reects the indiscriminate orientationof atoms inside the 3D space 2θ (2118) d spacing (41910)FWHM (02454) relative intensity () (857) and particlesize (6003Ε) were calculated for LH compounds ecrystallite size was computed by utilizing the DebyendashScherrer equation β 094 λ(S cos θ) where S is the

crystallite size θ is the diraction angle β is FWHM andCuKα (λ) 15406 A e d-spacing between inner crystalplanes was extracted from the Bragg equation nλ 2dsin(θ)at n 1 e size calculated falls in the nanometer range(nm) which expects a widespread application especially forthe biological eld Also crystal strain (ε 5027) was cal-culated by β (λS cos θ)minus ε tan θ while dislocation den-sity (δ 00277) was computed by δ 1S2 [44] edislocation density and strain are the aspects for networkdislocation in compoundse lower values of them indicatehigh quality of compounds e SEM tool is used to givea clear view about the habit and surface morphology of allstudied compounds (Figure S4)e images of paramagneticcompounds are not strictly resolved because an insuumlcientelectron beam can meet the surface to provide well reso-lution Subsequently the determination of particle size in anaccurate way is strongly absent It was known about thisstudy that the crystals were grown up from just a single oneto several accumulated distributables with particle sizesstarting with few nanometers to many hundreds e for-mation of extended crystals over a rocky shape may happen

rel

1000950900850800750700650600550500450400350300250200150100

50

2000 3000 4000 5000 6000 7000 8000 90002θCu-Ka1 (1540598A)

(LH)

Figure 6 X-ray diraction pattern of high crystalline ligand

Table 4 Spin Hamiltonian parameters of all VO(II) complexes (A and p x10minus4)

Complex g gperp go A11 F Aperp Ao G p k 2K2Kperp α2 β2

(1) 193 196 195 167 11557 66 9967 171 11752 0796 minus0843 minus1981 1959 09357(2) 194 197 196 170 11412 71 10400 193 11519 0861 minus0724 minus1512 1490 09435(3) 192 196 195 168 11428 69 10567 195 11519 0865 minus0961 minus1985 1964 09243(4) 194 198 197 171 11345 73 10567 279 11400 0895 minus0727 minus1055 1033 09395(5) 193 197 196 171 11286 72 10500 224 11519 0869 minus0841 minus1515 1494 09318


by two nucleation processes by distribution and by piling upof layers which are grown It was pointed to that if the rate ofgrowth along the C-axis is fast and a great number of grownnuclei are active across the axis in comparison with verticalto the C-axis the crystals will be extended over patches [45]-e attitude displayed on different crystals may be due to thegrowth along the strongest bond through anisotropy in-cluded in crystal structures When the amount exceeds toa certain limit the result is evolution of plates and rockshapes It is credible to assume that the environmentalconditions change the nature and shape of the morphologyMoreover the rock and plates shaping compounds may haveexcellent activity towards different applications due to theirbroad surface area [46] -e homogeneous morphologyobserved indicates the obtained strict-defined crystals arefree from metal ions on the external surface

36 Fermal Study -e degradation behaviors of all peri-midine compounds and their VO(II) complexes were tested-e proposed degradation insights corresponding to alldecomposition stages are tabulated (Table 5) -e treatedperimidine compounds start their successive decompositionat low temperature (asymp60degC) in three stages A sequencedcomplete degradation of the organic compound wasrecorded with or without carbon atoms residue VO(II)-perimidine complexes display an observable thermal sta-bility for the organic compounds coordinated -e degra-dation stages varied in between three and four stages -efirst degradation process starts at 40ndash80degC temperaturerange which starts with the removal of water molecules andis followed by decomposition of the coordinating ligandVariable residue was proposed with the complexes degra-dation process but all agree with the presence of biatomicmetals An acceptable conformity between calculated andfound weight losses percentage may reflect the exact de-termination of stage borders

37 DNABinding Appling the spectrophotometric titrationmethod the binding mod of perimidine derivatives towardsCT-DNA was investigated Electronic absorption of freshlyprepared solutions was obtained at 25degC over 200ndash800 nmrange with a reference solution for each concentrationScanned solutions include fixed ligand concentration(2times10minus5M) with a regular increase of DNA added -eeffective binding constant for the interaction of the organicderivatives with DNA was obtained based on observablechanges in absorption at 418 420 420 385 and 410 nm forLH LOMe LNO2 L4 and L5 respectively A regular in-crease of DNA amount added to the ligand solution leads tothe bathochromic effect for the significant ligand bandassigned for transition inside interacting groups -is bandis minimized gradually as appeared clearly with the aggre-gated spectra for each derivative -is minimization isfollowed by appearance of the slightly shifted peak (1-2 nm)from the free ligand peak which assigns for the bindingcomplex and suffers a gradual increase in absorbance-is isconsidered as a sufficient indicator of coupled DNA helixstabilization after the interaction process Such an

investigation suggests the coupling for binding sites throughelectrostatic attraction or occluded in major and minorgrooves inside DNA Also the bathochromic effect can beinvestigated and explained based on two bases broad surfacearea of perimidine molecules and the presence of planararomatic chromophore which facilitate well binding to-wards CT-DNA -is groove binding leads to structuralreorganization of CT-DNA -is requires a partial dis-assembling or deterioration of double helix at the exteriorphosphate which leads to formation of cavity suitable forentering compounds [47] -e bathochromic feature ob-served is directly proportional to electron withdrawingcharacter for substituents and their position -e bindingconstants (Kb) for the five derivatives were calculated byknown spectral relationships [19] for L1 L2 L3 L4 and L5 as610times104 607times104 675times104 799times104 and880times104Mminus1 According to Hammettrsquos constants (σR)essential correlation against intrinsic constants will beconducted (Figure 7) and the relation verifies the directrelation in between [48]

38 Computational

381 DFTHartreendashFock Study Applying the Gaussian 09software the optimization process was executed over allnew compounds till reaching the best configuration Aknown standard method was used for this purpose Es-sential parameters will be extracted from the energy levelsof frontiers (HOMO and LUMO) -e energy gap betweenEHOMO and ELUMO will give an excellent view about thecharacter of the tested compound -e biological behaviorand the ligational mode are most significant featuresconcluded -e frontier images of perimidine ligands andtheir VO(II) complexes are shown in Figures 8(a) and 8(b)respectively HOMO-level images display the concentra-tion over the perimidine ring which includes two donorcenters while the LUMO-level images display the con-centration over the other side in molecules including theother two coordination sites -is view introduces a goodelectron relocation between donor atoms which smoothensthe donation of coordinating centers On the other side thetwo levels in VO(II) complexes represent the concentrationaround the two central atoms mainly -is may offer thegood role of VO atoms in the application feature interestedin this research -is may happen through the smoothcharge transfer process that includes the complexesElectronegativity (χ) chemical potential (μ) global hard-ness (η) global softness (S) global electrophilicity index(ω) and absolute softness (ϭ) were calculated by usingknown standard equations [49 50] Toxicity and reactivityof compounds can be clarified by using the electrophilicityindex (ω) value -is index gives a clear insight about theexpected biological attitude of tested perimidine com-pounds in comparison with their VO(II) complexes andalso measures the firmness of the compound which takesan extra negative charge from the environment Also thefirmness and reactivity of compounds can be tested fromtwo opposite indexes (η and ϭ) [42 51]


(1) Some Quantum Parameters Some important quantumparameters are calculated for all treated compounds at-tributing to frontier energy gaps and are displayed in Table 6-e computed results of ligands introduce the followingnotices (i) the degree of converged softness recorded forperimidines offers their compatible flexibility towards thecoordination (ii) Electrophilicity index (χ) and electronicchemical potential index (μ) have two different signs -is isevidence for the ability of compounds to acquire electronsfrom the surrounding by the following orderL4gt L3gt L5gt L1gt L2 ligands -is arrangement agrees by anexcellent way with the priority of electron withdrawingsubstituents (Cl and NO2) in para position which facilitatesthe compound electron affinity

Whenever the extracted data assigning for VO(II)complexes introduce the following observations (i) frontierenergy gaps are completely minimized from original

LNO2LCIM

LCIP

LHLOMe

ndash04 ndash02 00 02 04 06 08

50000

55000

60000

65000

70000

75000

80000

85000

90000

σR

K b (M

ndash1)

Figure 7 Hammettrsquos relation between the effect of p-substituent(σR) and intrinsic binding constants (Kb) of the ligands

Table 5 Estimated TG data of perimidine compounds and all VO(II) complexes

Compound Steps Temp range (degC) Decomposed Weight loss calcd (found )

L11st 451ndash1205 -[C6H6+N2] 2718 (2716)2nd 1222ndash4101 -[C6H5+CO] 2692 (2695)3rd 4103ndash6702 -[C8H7N2] 3359 (3354)

Residue 4C 1231 (1235)

[(VO)2 (SO4)2 (L1)]H2O

1st 803ndash1203 -[H2O+ SO4] 1553 (1555)2nd 1206ndash3917 -[SO4+C6H6+N2] 2753 (2755)3rd 3919ndash7988 -[C19H12N2] 3653 (3650)

Residue V2O3 2041 (2040)

L21st 656ndash1561 -[C6H5OCH3] 2572 (2571)2nd 1566ndash2999 -[C6H5+CO+N2] 3166 (3169)3rd 3010ndash6632 -[C9H7N2] 3405 (3389)

Residue 3C 857 (871)

[(VO)2 (SO4)2 (L2)]2H2O

1st 421ndash1351 -[2H2O+ 2SO4] 2916 (2916)2nd 1361ndash2701 -[C6H5OCH3+N2] 1740 (1729)3rd 2710ndash4854 -[C6H5] 985 (994)4th 4856ndash7979 -[C13H7N2] 2443 (2445)

Residue V2O3 1915 (1916)

L31st 6366ndash23051 -[C6H6 +NO2] 2850 (2790)2nd 23121ndash41011 -[C7H5+CO+N2] 3333 (3331)3rd 41052ndash65064 -[C11H6N2] 3816 (3879)

[(VO)2 (SO4)2 (L3)]H2O

1st 792ndash1406 -[H2O+ SO4] 1463 (1462)2nd 1419ndash2789 -[SO4 +C6H5+CO] 2581 (2578)3rd 2791ndash4795 -[NO2+C6H6+N2] 1952 (1953)4th 48011ndash7988 -[C12H6N2] 2286 (2290)

Residue V2O2 1718 (1717)

L41st 6465ndash14546 -[C6H5Cl +CO+N2] 3968 (3968)2nd 14568ndash32678 -[C6H5+N2] 2474 (2475)3rd 33012ndash68023 -[C12H7] 3558 (3557)

[(VO)2 (SO4)2 (L4)]H2O

1st 691ndash2561 -[H2O+C6H5Cl + SO4] 2948 (2965)2nd 2569ndash4841 -[SO4 +CON2+C6H5] 2980 (2981)3rd 4846ndash7894 -[C10H7N2] 2018 (1998)

Residue V2O2+ 2C 2054 (2056)

L51st 623ndash1696 -[C6H5+N2] 2474 (2471)2nd 1601ndash3719 -[C6H5Cl +CO+N2] 3968 (3959)3rd 3726ndash6668 -[C9H7] 2710 (2719)


[(VO)2 (SO4)2 (L5)]3H2O

1st 421ndash2663 -[3H2O+C6H5Cl] 2070 (2071)2nd 26638ndash4825 -[2SO4 +CON2+C6H5] 4041 (4061)3rd 4829ndash7935 -[C8H7N2] 1629 (1636)

Residue V2O2+ 4C 2260 (2232)


LCIM2

LCIP1 LCIP2 LCIM1

LH1LH2 LOMe1

LOMe2 LNO21 LNO22

(a)

Figure 8 Continued


(a1)

(b1)

(c1)

(a2)

(b2)

(c2)

(d1) (d2)

(e1) (e2)

(b)

Figure 8 (a) Frontier molecular orbitals of HOMO(1)and LUMO(2) pictures of perimidine ligands (b) Frontier molecular orbitals ofHOMO(1) and LUMO(2) pictures of VO(II)-perimidine complexes (AndashE respectively)


perimidines leading to red shift inside electronic transitionsSuch a behavior may clarify the effect of metal atoms(vanadyl) in stabilizing the compounds -is reduction ispreferable in biological attitude of compounds [52] (ii) -eabsolute softness values in complexes were enhanced thanthe ligand values which predicated their high biologicalactivity From calculated energy gaps Hammettrsquos relationdisplays a significant effect of the p-substituent on δE valuesof ligands or their complexes by two reverse features(Figure 9)

(2) Some Log File Parameters Essential log file data aresummarized and presented in Table 7 -e allowed data arevaried in between the free ligands and their complexes dueto the difference in methods used for the treatment Asuitable method used for the organic ligand appeared un-suitable for its VO(II) complex A comparative investigationintroduced the following notices (i) a general reduction inthe charges computed for coordinating atoms (O19 N11 N15and N16) -is is due to their participation in coordinationwith VO(II) atoms (ii) -e computed bond lengthsappearing with four perimidine derivatives are comparablewith each other except for the L3 ligand -is displays theinductive effect of the p-substituent (nitro group) on theelongation of bond lengths attributing to the affectedfunction groups (iii) Oscillator strength values (range 0ndash1)of complexes are commonly minimized than those of theircorresponding ligands -is may indicate the effect of themetal atom (vanadyl) in facilitating the absorption or ree-mission of electromagnetic radiations inside complexmolecules [53] -e values are close to zero and not 1 thismay suggest low excitation energy values needed for elec-tronic transitions (iv) Also an increase in dipole momentvalues of complexes over ligands indicates high polarity ofcovalent bonds surrounding two central atoms except for theL2 complex -is may refer to the significant differencebetween all substituents from the methoxy group which haselectron-donating feature in opposite with the others [54]

382 QSAR Calculations Using the HyperChem (v81)program essential QSAR parameters are calculated andtabulated (Table 8) -is computation gives a clear viewabout some statistics belonging to coordinating agentsLogP value is an indication for the biological feature of the

tested compound by a reverse relation [55] -e values arearranged by the following order L1 (253)gt L4 L5 (231)gt L2 (153)gt L3 (minus164) Partition coefficient (logP) valuesintroduce a distinguish biological activity may appear withthe L3 ligand

383 Docking Computation Simulation technique is a newrevolution process served in different applications Drugdesign is a complicated process that needs significant fa-cilities to establish a view about the expected efficiency ofproposed drugs In last decades the docking computationprocess between the proposed drug (inhibitor) and theinfected cell proteins is the concern in drug industrial re-search AutoDockTools 42 software was used for this ap-proach 4c3p 3bch and 4zdr are the BDP files for breastcolon and liver cancer cell proteins which are used for thedocking process with five perimidine derivatives -eextracted energies over PDB files (a format using theGaussian 09 software) are presented in Table 9 Scanning forthe energy values introduces the following observations (i)there is no interaction observed with the five inhibitorstowards 3bch colon cancer protein (ii) -e degree of in-teraction towards breast colon protein (4c3p) is arranged asL5gt L1gt L2gt L4 while the arrangement towards 4zdr (livercancer protein) is as L5gt L1gt L4gt L3gt L2 -is result dis-plays the priority of L5 and L1 ligands in the inhibition

Table 6 Energy parameters (eV) using the DFTB3LYP method of optimized structures

Compound EH EL (EHminusEL) ELminus EH x micro η S (eV-1) ω ϭL1 minus017417 minus007574 minus00984 009843 0124955 minus012496 0049215 0024608 0158628 2031900843L1+VO(II) minus020433 minus019545 minus00089 000888 019989 minus019989 000444 000222 4499551 2252252252L2 minus017142 minus007426 minus00972 009716 012284 minus012284 004858 002429 0155307 2058460272L2 +VO(II) minus020163 minus019237 minus00093 000926 0197 minus0197 000463 0002315 4191037 2159827214L3 minus021252 minus005654 minus0156 015598 013453 minus013453 007799 0038995 011603 1282215669L3 +VO(II) minus021881 minus021008 minus00087 000873 0214445 minus021445 0004365 0002183 5267658 2290950745L4 minus025291 minus005654 minus01964 019637 0154725 minus015473 0098185 0049093 0121912 1018485512L4 +VO(II) minus020433 minus019545 minus00089 000888 019989 minus019989 000444 000222 4499551 2252252252L5 minus017808 minus00842 minus00939 009388 013114 minus013114 004694 002347 0183188 2130379207L5 +VO(II) minus019719 minus016607 minus00311 003112 018163 minus018163 001556 000778 1060073 6426735219

LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015

ndash04 ndash02 00 02σR

04 06 08

VO(II) complexes

LNO2

ΔE

Figure 9 Hammettrsquos relation between the effect of p-substituent(σR) and energy gaps (δE) of ligands and their VO(II) complexes


Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom

ent(D)oscillatorstreng

th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002


process towards breast and liver carcinoma cell lines througha strong interaction (Figures 10 and S5) [55] Dissociationconstant (pKa) calculated is considered the bio-pharmaceutical measure of drug-likeness compounds -isconstant helps in understanding the ionic form of the drugalong the pH range High pKa values (gt10) reflect theirionization which facilitates their diffusion across the cellmembrane to give a well inhibition process Also highlyreduced energies were recorded for 4c3p and 4zdr receptorsPositive sign of electrostatic energy recorded clarifies highstability of interacting complexes HP plots (Figures 11 andS6) as well as 2D plots (Figure S7) display prolongedH-bonding appearing with L5 and LH ligands -is verifiesthe degree of interaction proposed on extracted energiesAlso high surface area recorded with breast or liver cancerprotein complexes introduces a good degree of H-in-teraction And hp 2D and surface area data verify theabsence of interaction recorded with colon cancer protein

39 Antitumor Efficiency -e results obtained by screeningall prepared compounds for comparison confirmed that the

complexes exhibit more cytotoxicity against HepG2MCF-7and HCT116 in vitro -e IC50 values are displayed in Ta-ble 10 and in Figures 12 and S8 Cells were treated withvarious concentrations of compounds and incubated for48 h [56] Cytotoxicity is considered as a good anticancerparameter if the influence induced apoptotic pathways in-side the cell Apoptotic may be detected by many parameterslike the activation of caspase family DNA fragmentation ormorphology of the cell -e sample L4 +VO(II) was the bestimpacted complex on liver breast and colon cancer celllines with IC50 values of 166 342 and 127 respectivelywhile its relative ligand (L4) impact was moderate at allcancer types Hence these results showed that the presentstudyrsquos effort to improve and enhance the effect of newcomplexes has achieved a clear acceptable and respectablesuccess because the effect was enhanced for 15 7 and 22times respectively compared to the ligand with clear signsthat it is going to be very close to the positive control On thecontrary unfortunately the same results were not detectedin other complexes they went in the contrary way insteadthey increased the impact they decreased it dramaticallyWhat our results tell us clearly is that neither VO(II) nor

Table 8 QSAR computation for optimized structures of perimidine compounds

Function L1 L2 L3 L4 L5

Surface area (approx) (A2) 42573 48836 49679 46404 46553Surface area (grid) (A2) 62302 66115 66191 64429 64282Volume (A3) 106057 113887 113404 110599 110572Hydration energy (kcalmol) minus829 minus997 minus1783 minus800 minus802Log P 253 153 minus164 231 231Reactivity (A3) 13287 13925 13892 13759 13759Polarizability (A3) 4532 4780 4762 4725 4725Mass (amu) 39044 42047 43645 42489 42489

Table 9 Docking energy values (kcalmol) of perimidine compounds (HL) and protein receptors complexes

Ligands pKa ReceptorEst freeenergy ofbinding

Est inhibitionconstant (Ki) (microM)

vdW+bond+ desolvingenergy

Electrostaticenergy

Totalintercooledenergy

Frequency Interactingsurface

L1 10964c3p minus792 157 minus929 minus006 minus934 30 8597783bch +35537 mdash +34942 +006 +34948 10 665364zdr minus472 34545 minus597 minus005 minus602 20 723695


L3 10954c3p +64756 mdash +64474 +001 +64475 10 7183183bch +70910 mdash +69961 minus005 +69956 10 661434zdr minus466 38521 minus646 +007 minus639 10 621389

L4 10964c3p minus728 462 minus857 minus003 minus860 20 9297473bch +55225 mdash +54959 minus003 +54956 30 7106054zdr minus467 37604 minus613 minus019 minus632 20 595541

L5 10954c3p minus841 68374 minus981 minus000 minus981 20 9251613bch +66387 mdash +66194 +001 +66195 10 7035984zdr minus484 28449 minus639 +004 minus635 10 690838


ligands alone can act as an anticancer candidate drug whileonly one complex can present that effect So the mechanismof action is not related to the ligand or to VO(II) itself as faras related to the complex itself

4 Conclusion

-is paper presents new VO(II) complexes derived froma series of perimidine ligands -is study focuses on theeffect of substituents on the chemistry and applicability of

complexes All the new compounds were well characterizedby all possible tools -e complexes were found in a nano-scale comfortably -e different theoretical implementationsgave a view about the biological feature of the investigatedcompounds in a comparative way -e docking processdisplays the high interaction of organic derivatives againstbreast cancer while the experimental investigation displaysthe priority of the L4-VO(II) complex against all carcinomastested -e binding efficiency of ligands towards CT-DNAwas tested Binding constant (Kb) values are in agreement

(a) (b)

(c) (d)

(e)

Figure 10 Interacting protein-inhibitor complexes (a) L1 (b) L2 (c) L3 (d) L4 and (e) L5 with 4zdr receptor (andashe respectively)


2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)

Figure 11 Interacting complexes hp plot for (a) L1 (b) L2 (c) L3 (d) L4 and (e) L5 with 4zdr receptor (andashe respectively)

Table 10 IC50 of some tested compounds against liver (HepG2) breast (MCF-7) and colon (HCT116) cancer cell lines

Cell typeIC50 (microgml)

L1 VO(II)-L1 L2 VO(II)-L2 L3 VO(II)-L3 L4 VO(II)-L4 L5 VO(II)-L5 DoxorubicinMCF-7 1968 2306 2592 9392 1550 gt100 2496 342 1144 gt100 060HepG2 1979 1994 2723 5567 1101 gt100 2825 127 991 gt100 034HCT116 1915 2293 1327 9517 1553 gt100 2624 166 2330 gt100 039


with the electron-drawing character of the p-substituentwhich displayed high Kb values

Data Availability

e data used to support the ndings of this study areavailable from the corresponding author upon request

Conflicts of Interest

e authors declare that they have no conicts of interestregarding the publication of this paper

Acknowledgments

e authors extend their appreciation to the Deanship ofScientic Research at King Khalid University for fundingthis work through General Research project under grantnumber (GRP-124-38)

Supplementary Materials

Figure S1 1HmiddotNMR spectra of L4 and L5 perimidine ligandsFigure S2 mass spectra of L3 and L4 ligands Figure S3 X-raypatterns of four perimidine ligands Figure S4 SEM imagesof perimidine ligands and their VO(II) complexes Figure S5interacting protein-inhibitor complexes for L1 L2 L3 L4and L5 with 4c3p (1) and 3bch (2) receptors (AndashE re-spectively) Figure S6 interacting hp plot LH LOMe LNO2LClP and LClM with 4c3p(1) and 3bch(2) receptors (AndashErespectively) Figure S7 2D plot forms L1 L2 L3 L4 and L5with 4c3p (1) 3bch (2) and 4zdr (3) receptors (AndashE re-spectively) Figure S8 dose response curves of perimidine-VO(II) complexes against MCF-7 HCT116 and HepG2cancer cells (Supplementary Materials)

References

[1] M S Refat ldquoSynthesis characterization thermal and anti-microbial studies of diabetic drug models complexes ofvanadyl(II) sulfate with ascorbic acid (vitamin C) riboavin(vitamin B2) and nicotinamide (vitamin B3)rdquo Journal ofMolecular Structure vol 969 no 1ndash3 pp 163ndash171 2010

[2] G R illsky ldquoSynthesis characterization thermal and anti-microbial studies of diabetic drug models complexes ofvanadyl(II) sulfate with ascorbic acid (vitamin C) riboavin(vitamin B2) and nicotinamide (vitamin B3)rdquo inVanadium inBiological Systems Physiology and BiochemistryN D Chasteen Ed Kluwer Academic Publishers DordrectNetherlands 1990

[3] Z Ye G Yan J Tang Q Fu J Lu and N Yang ldquoSynthesis andbiological evaluation of two oxidovanadium (IV) complexes asDNA-binding and apoptosis-inducing agentsrdquo AmericanJournal of Biological Chemistry vol 4 no 1 pp 6ndash13 2016

[4] J Farzanfar K Ghasemi A R Rezvani et al ldquoSynthesischaracterization X-ray crystal structure DFT calculation andantibacterial activities of new vanadium(IV V) complexescontaining chelidamic acid and novel thiourea derivativesrdquoJournal of Inorganic Biochemistry vol 147 pp 54ndash64 2015

[5] K Kanmani Raja L Lekha R HariharanD Easwaramoorthy and G Rajagopal ldquoSynthesis structuralspectral electrochemical and catalytic properties of VO (IV)complexes containing N O donorsrdquo Journal of MolecularStructure vol 1075 pp 227ndash233 2014

[6] D M Boghaei and S Mohebi ldquoSynthesis characterizationand study of vanadyl tetradentate Schi base complexes ascatalyst in aerobic selective oxidation of olensrdquo Journal ofMolecular Catalysis A Chemical vol 179 no 1-2 pp 41ndash512002

[7] J-Q Wu and Y-S Li ldquoWell-dened vanadium complexes asthe catalysts for olen polymerizationrdquo CoordinationChemistry Reviews vol 255 no 19-20 pp 2303ndash2314 2011

[8] G Micera and D Sanna Vanadium in the Environment PartOne Chemistry and Biochemistry J O Nriagu Ed JohnWiley amp Sons New York NY USA 1998

0 001 01 1 10 100Concentration (μgml)

L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)

Figure 12 Dose response curves of perimidine ligands againstMCF-7 (a) HCT116 (b) and HepG2 (c) cancer cells


[9] F T G Hudson Vanadium Toxicology and Biological Sig-nificance Elsevier NewYork NY USA 1996

[10] R C Maurya and S Rajput ldquoOxovanadium(IV) complexesof bioinorganic and medicinal relevance synthesis charac-terization and 3D molecular modeling and analysis of someoxovanadium(IV) complexes involving the O N-donor envi-ronment of pyrazolone-based sulfa drug Schiff basesrdquo Journalof Molecular Structure vol 794 no 1ndash3 pp 24ndash34 2006

[11] D M Boghaei A Bezaatpour and M Behzad ldquoSynthesischaracterization and catalytic activity of novel monomericand polymeric vanadyl Schiff base complexesrdquo Journal ofMolecular Catalysis A Chemical vol 245 no 1-2 pp 12ndash162006

[12] M S Refat M A A Moussa and S F Mohamed ldquoSynthesisspectroscopic characterization thermal analysis and electricalconductivity studies of Mg(II) Ca(II) Sr(II) and Ba(II) vi-tamin B2 complexesrdquo Journal of Molecular Structure vol 994no 1ndash3 pp 194ndash201 2011

[13] M S Refat and S A El-Shazly ldquoIdentification of a new anti-diabetic agent by combining VOSO4 and vitamin E in a singlemolecule studies on its spectral thermal and pharmacologicalpropertiesrdquo European Journal of Medicinal Chemistry vol 45no 7 pp 3070ndash3079 2010

[14] R Takjoo A Akbari S Yousef Ebrahimipour M KubickiM Mohamadi and N Mollania ldquoSynthesis spectral char-acterization DFT calculations antimicrobial activity andmolecular docking of 4-bromo-2-((2-hydroxy-5-methylphenylimino)methyl)phenol and its V(V) complexrdquoInorganica Chimica Acta vol 455 pp 173ndash182 2017

[15] V Kraehmer and D Rehder ldquoModelling the site of bromidebinding in vanadate-dependent bromoperoxidasesrdquo DaltonTransactions vol 41 no 17 pp 5225ndash5234 2012

[16] P Sathyadevi P Krishnamoorthy R R ButoracA H Cowley and N Dharmaraj ldquoSynthesis of novel het-erobimetallic copper(I) hydrazone Schiff base complexesa comparative study on the effect of heterocyclic hydrazidestowards interaction with DNAprotein free radical scav-enging and cytotoxicityrdquo Metallomics vol 4 no 5pp 498ndash511 2012

[17] R Pradhan M Banik D B Cordes A M Z Slawin andN C Saha ldquoSynthesis characterization X-ray crystallographyand DNA binding activities of Co(III) and Cu(II) complexeswith a pyrimidine-based Schiff base ligandrdquo InorganicaChimica Acta vol 442 pp 70ndash80 2016

[18] T A Farghaly and H K Mahmoud ldquoSynthesis tautomericstructures and antitumor activity of new perimidinesrdquoArchivder Pharmazie vol 346 no 5 pp 392ndash402 2013

[19] M E Reichmann S A Rice C A -omos and P Doty ldquoAfurther examination of the molecular weight and size ofdesoxypentose nucleic acidrdquo Journal of the AmericanChemical Society vol 76 no 11 pp 3047ndash3053 1954

[20] J Marmur ldquoA procedure for the isolation of deoxyribonucleicacid from micro-organismsrdquo Journal of Molecular Biologyvol 3 no 2 pp 208ndash218 1961

[21] A Wolfe G H Shimer and T Meehan ldquoPolycyclic aromatichydrocarbons physically intercalate into duplex regions ofdenatured DNArdquo Biochemistry vol 26 no 20 pp 6392ndash6396 1987

[22] A I Vogel Text Book of Quantitative Inorganic AnalysisLongman London UK 1986

[23] M J Frisch G W Trucks H B Schlegel et al Gaussian 09Revision D Gaussian Inc Wallingford CT USA 2010

[24] R Dennington II T Keith and J Millam Gauss ViewVersion 412 Semichem Inc Shawnee KS USA 2007

[25] M M Al-Iede J Karpelowsky and D A Fitzgerald ldquoRe-current diaphragmatic hernia modifiable and non-modifiablerisk factorsrdquo Pediatric Pulmonology vol 51 no 4 pp 394ndash401 2015

[26] T A Halgren ldquoMerck molecular force field I Basis formscope parametrization and performance of MMFF94rdquoJournal of Computational Chemistry vol 17 no 5-6pp 490ndash519 1998

[27] G M Morris D S Goodsell R S Halliday et al ldquoAutomateddocking using a Lamarckian genetic algorithm and an em-pirical binding free energy functionrdquo Journal of Computa-tional Chemistry vol 19 no 14 pp 1639ndash1662 1998

[28] F J Solis and R J B Wets ldquoMinimization by random searchtechniquesrdquoMathematics of Operations Research vol 6 no 1pp 19ndash30 1981

[29] W J Geary ldquo-e use of conductivity measurements in or-ganic solvents for the characterisation of coordinationcompoundsrdquo Coordination Chemistry Reviews vol 7 no 1pp 81ndash122 1971

[30] N M El-Metwaly R M El-shazly I M Gabr and A A El-Asmy ldquoPhysical and spectroscopic studies on novel vanadylcomplexes of some substituted thiosemicarbazidesrdquo Spec-trochimica Acta Part A Molecular and Biomolecular Spec-troscopy vol 61 no 16 pp 1113ndash1119 2005

[31] K S Abu-Melha and N M El-Metwally ldquoSpectral andthermal studies for some transition metal complexes of bis(benzylthiocarbohydrazone) focusing on EPR study for Cu(II)and VO2+rdquo Spectrochimica Acta Part A Molecular andBiomolecular Spectroscopy vol 70 no 2 pp 277ndash283 2008

[32] A A Abou-Hussen N M El-Metwaly E M Saad andA A El-Asmy ldquoSpectral magnetic thermal and electro-chemical studies on phthaloyl bis(thiosemicarbazide) com-plexesrdquo Journal of Coordination Chemistry vol 58 no 18pp 1735ndash1749 2005

[33] A B P Lever Inorganic Electronic Spectroscopy ElsevierAmsterdam Netherlands 1986

[34] B J Hathaway and D E Billing ldquo-e electronic propertiesand stereochemistry of mono-nuclear complexes of thecopper(II) ionrdquo Coordination Chemistry Reviews vol 5 no 2pp 143ndash207 1970

[35] B J Hathaway ldquoA new look at the stereochemistry andelectronic properties of complexes of the copper(II) ionrdquoStructure and Bonding vol 57 pp 55ndash118 1984

[36] H Montgomery and E C Lingefetter ldquo-e crystal structureof Tuttonrsquos salts IV Cadmium ammonium sulfate hexahy-draterdquo Acta Crystallographica vol 20 no 6 pp 728ndash7301966

[37] D Kivelson and R Neiman ldquoESR studies on the bonding incopper complexesrdquo Journal of Chemical Physics vol 35 no 1pp 149ndash155 1961

[38] J A Wellman F B Hulsbergen J Verbiest and J ReedijkldquoInfluence of alkyl chain length in N-alkyl imidazoles uponthe complex formation with transition-metal saltsrdquo Journal ofInorganic and Nuclear Chemistry vol 40 pp 143ndash147 1978

[39] U Sagakuchi and A W Addison ldquoSpectroscopic and redoxstudies of some copper(II) complexes with biomimetic donoratoms implications for protein copper centresrdquo Journal of theChemical Society Dalton Transactions p 600 1979

[40] H Yokoi and A W Addison ldquoSpectroscopic and redoxproperties of pseudotetrahedralcopper(II) complexes -eirrelation to copper proteinsrdquo Inorganic Chemistry vol 16no 6 pp 1341ndash1349 1977

[41] B R Mc Garvey ldquo-e isotropic hyperfine interactionrdquoJournal of Physical Chemistry vol 71 no 1 pp 51ndash66 1967


[42] R C Chikate and S B padhye ldquoTransition metalquinonendashthiosemicarbazone complexes 2 magnetism ESRand redox behavior of iron (II) iron (III) cobalt (II) andcopper (II) complexes of 2-thiosemicarbazido-1 4-naph-thoquinonerdquo Polyhedron vol 24 no 13 pp 1689ndash1700 2005

[43] B D Cullity Elements of X-Ray Diffraction AddisonndashWesleyInc Boston MA USA 2nd edition 1993

[44] S Velumani X Mathew P J Sebastian S K Narayandassand D Mangalaraj ldquoStructural and optical properties of hotwall deposited CdSe thin filmsrdquo Solar Energy Materials andSolar Cells vol 76 no 3 pp 347ndash358 2003

[45] F A Saad N M El-Metwaly T A Farghaly et al ldquoIllus-tration for series of new metal ion complexes extracted frompyrazolone derivative spectral thermal QSAR DFTB3LYPdocking and antitumor investigationsrdquo Journal of MolecularLiquids vol 229 pp 614ndash627 2017

[46] J H Al-Fahemi F A Saad NM El-Metwaly et al ldquoSynthesisof Co(II) Cu(II) Hg(II) UO2(II) and Pb(II) binuclearnanometric complexes from multi-donor ligand spectralmodeling quantitative structurendashactivity relationship dock-ing and antitumor studiesrdquo Applied Organometallic Chem-istry vol 31 no 11 p e3787 2017

[47] J M ChenWWei W X L Feng and T B Lu ldquoCO2 fixationand transformation by a dinuclear copper cryptate underacidic conditionsrdquo ChemistryndashAn Asian Journal vol 2 no 6pp 710ndash714 2007

[48] A Z El-Sonbati M A Diab A A El-BindaryM M Ghoneim M T Mohesien and M K Abd El-KaderldquoPolymeric complexesmdashLXI Supramolecular structurethermal properties SS-DNA binding activity and antimi-crobial activities of polymeric complexes of rhodaninehydrazone compoundsrdquo Journal of Molecular Liquidsvol 215 pp 711ndash739 2016

[49] U El-Ayaan N M El-Metwally M M Youssef andS A A El Bialy ldquoPerchlorate mixedndashligand copper(II)complexes of β-diketone and ethylene diamine derivativesthermal spectroscopic and biochemical studiesrdquo Spec-trochimicaActa Part A vol 68 no 5 pp 1278ndash1286 2007

[50] R K Ray and G R Kauffman ldquoEPR spectra and covalency ofbis(amidinoureao-alkyl-1-amidinourea)copper (II) com-plexes Part II Properties of the CuN 42-chromophorerdquoInorganica Chimica Acta vol 173 no 12 pp 207ndash214 1990

[51] S Sagdinc B Koksoy F Kandemirli and S H Bayarildquo-eoretical and spectroscopic studies of 5-fluoro-isatin-3-(N-benzylthiosemicarbazone) and its zinc(II) complexrdquoJournal of Molecular Structure vol 917 no 2-3 pp 63ndash702009

[52] I Fleming Frontier Orbitalrsquos and Organic Chemical ReactionsWiley London UK 1976

[53] S K Tripathi R Muttineni and S K Singh ldquoExtra precisiondocking free energy calculation and molecular dynamicssimulation studies of CDK2 inhibitorsrdquo Journal of FeoreticalBiology vol 334 pp 87ndash100 2013


[55] N Terakado S Shintani and Y Nakahara ldquoExpression of CuZn-SOD Mn-SOD and GST-pi in oral cancer treated withpreoperative radiation therapyrdquo Oncology Reports vol 7no 5 pp 1113ndash1120 2000

[56] C Fosset B A McGaw and M D Reid ldquoA non-radioactivemethod for measuring Cu uptake in HepG2 cellsrdquo Journal ofInorganic Biochemistry vol 99 no 5 pp 1018ndash1022 2005


TribologyAdvances in

Hindawiwwwhindawicom Volume 2018


International Journal ofInternational Journal ofPhotoenergy


Journal of

Chemistry


Advances inPhysical Chemistry

Hindawiwwwhindawicom

Analytical Methods in Chemistry

Journal of

Volume 2018

Bioinorganic Chemistry and ApplicationsHindawiwwwhindawicom Volume 2018

SpectroscopyInternational Journal of


Hindawi Publishing Corporation httpwwwhindawicom Volume 2013Hindawiwwwhindawicom

The Scientific World Journal

Volume 2018

Medicinal ChemistryInternational Journal of


NanotechnologyHindawiwwwhindawicom Volume 2018

Journal of

Applied ChemistryJournal of



Biochemistry Research International


Enzyme Research


Journal of

SpectroscopyAnalytical ChemistryInternational Journal of


MaterialsJournal of



BioMed Research International Electrochemistry

International Journal of


Na

nom

ate

ria

ls


Journal ofNanomaterials

Submit your manuscripts atwwwhindawicom

taking insulin altogether [12 13] It is noticeable thatcomplexation of vanadium with organic ligands minimizesunfavorable effects of its inorganic salts such as vanadylsulfate while even maintains its potential benefits [14]Furthermore mimicking the biological activities in naturalsystems can be achieved by vanadium complexes whichcontain oxygen and nitrogen donor ligands so identificationof the structure of these complexes is regarded important[15ndash17] Bioinorganic chemistry is a fast developing field ofmodern chemistry that uses Schiff bases and their transitionmetal complexes for a variety of applications eg in bi-ological medical and environmental sciences -is work isinterested in preparation of a series of perimidine derivativesby various substituents New vanadyl complexes will beprepared and well characterized by using different tech-niques CT-DNA binding will be tested along the organicseries -eoretical implementation will be accomplishedover all prepared compounds by different standard pro-grams Antitumor activity will be scanned over all newprepared compounds for comparison

2 Experimental Work

21 Chemicals Used Chemicals essential for preparation ofperimidine derivatives such as 18-diaminonaphthaleneethylbenzoyl acetate 4-methoxyaniline aniline 4-chlor-oaniline 3-chloroaniline 4-nitroaniline NaNO2 NaOHHCl and dioxane were purchased from Fluka and usedwithout previous treatments Also VOSO4middotxH2O salt usedfor the complexation process was commercially availablefrom Sigma-Aldrich All handled solvents were from Merckand used without previous purification

22 Synthesis

221 Synthesis of Compounds 3andashe (Perimidine Derivatives)Ligands 3andashe were synthesized as reported in the literature[18] from coupling reaction of compound 1 (25mmol) inethanol (20mL) with the appropriate arenediazoniumchloride 2 in the presence of sodium hydroxide (25mmol)in the ice bath at 0ndash5degC -e whole mixture was then left ina refrigerator overnight -e precipitated solid was filteredoff washed with water and finally crystallized fromdioxaneEtOH to give the respective hydrazones 3andashe(Scheme 1) 1HmiddotNMR and mass spectra are displayed inFigures 1 2 S1 and S2 -e analysis is matching completelywith that reported in the literature [16] -e structural formsof new perimidine compounds are displayed in Figures 3(a)and 3(b)

(1) 2-[N-phenyl-2-oxo-2-phenylethanehydrazonoyl]-1H-perimidine ( 3a ) (L1) IR υ 3402 3194 (2NH) and1616 (CO) cmminus1 1HmiddotNMR (DMSO-d6) d 672ndash780(m 16H ArndashH) and 1362 (s 2H 2NH) MS mz() 390 (M 22) 285 (2) 166 (5) 140 (7) 127 (1) 105(100) 93 (8) and 77 (35) Anal calcd for C25H18N4O(39042)

(2) 2-[N-(4-methoxyphenyl)-2-oxo-2-phenylethanehydrazonoyl]-1H-perimidine ( 3b ) (L2) IR υ 3333 3167

(2NH) and 1680 (CO) cmminus1 1HmiddotNMR (DMSO-d6) δ358 (s 3H OCH3) 759ndash797 (m 15H ArH) and1220 (br s 2H 2NH) MS mz () 420 (M 5) 419(9) 193 (12) 166 (12) 126 (14) 107(17) 105 (100) 92(31) and 77 (75) Anal calcd for C26H20N4O2(42047)

(3) 2-[N-(4-chlorophenyl)-2-oxo-2-phenylethanehydrazonoyl]-1H-perimidine ( 3c ) (L3) IR υ 3422 3206 (2NH)and 1612 (CO) cmminus1 1HmiddotNMR (DMSO-d6) d 673ndash777 (m 15H ArndashH) and 1327 (s 2H 2NH) MSmz() 426 (M2 5) 425 (M 1 6) 424 (M 14) 140 (4) 127(5) 111 (2) 105 (100) and 77 (37) Anal calcd forC25H17ClN4O (43544)

(4) 2-[N-(4-nitrophenyl)-2-oxo-2-phenylethanehydrazonoyl]-1H-perimidine ( 3d ) (L4) IR υ 3356 3198(2NH) and 1670 (CO) cmminus1 1HmiddotNMR (DMSO-d6) d664ndash821 (m 15H ArndashH) and 1260 (s 2H 2NH)MS mz () 435 (M 8) 238 (34) 138 (13) 167 (11)106 (45) 105 (58) 93 (100) 77 (44) and 66 (76)Anal calcd for C25H17N5O3 (42488)

(5) 2-[N-(3-chlorophenyl)-2-oxo-2-phenylethanehydrazonoyl]-1H-perimidine ( 3e ) (L5) IR υ 3229 3167 (2NH)and 1622 (CO) cmminus1 1HmiddotNMR (DMSO-d6) d 670ndash791 (m 15H ArndashH) and 1302 (s 2H 2NH) MSmz() 426 (M2 7) 425 (M1 9) 424 (M 16) 194 (7) 166(7) 140 (5) 127 (4) 105 (100) 111 (4) and 77 (36)Anal calcd for C25H17ClN4O (42488)

222 Synthesis of VO(II) Complexes New VO(II) complexseries was synthesized by using variable derivatives fromperimidine ligands Equimolar (3mmol) values were usedfrom the perimidine ligand and dissolved fully in dioxaneafter that it wasmixed with VOSO4middotxH2Owhich dissolves inthe dioxaneH2O mixture -e weighted molar ratio valuefrom vanadyl salt was calculated attributing to its anhydrousweight After asymp5 h reflux 05 g sodium acetate was addedafter dissolving in a little amount of bi-distilled water toprecipitate the complexes Each precipitate was separatedout on hot filtered off washed several times with ethanoland diethyl ether and finally dried in a vacuum desiccator

23DNABindingStudy -ebinding attitudes of perimidinederivatives towards calf thymus DNA (CT-DNA) will bestudied by using the spectroscopy method CT-DNA(50mg) was dissolved by stirring overnight in doubledeionized water (pH 70) and must be kept at 4degC Bi-distilled water was used to prepare the buffer (50mM tris(hydroxymethyl)-aminomethane and 50mM NaCl pH

72) Tris-HCl buffer was prepared in deionized water DNAbuffering solution gave absorbance ratio at 260280 nmby 18ndash19 and this indicates the absence of protein fromDNA [19 20] Applying the UV-Vis technique the DNAconcentration was determined (510times10minus4M) using itsknown molar absorptivity coefficient value (6600Mminus1middotcmminus1at 260 nm) At room temperature 200ndash900 nm is the






16 14 12 10

NH

N N NH

7801

7776

7550

7526

7370

7345

7300

7274

7202

7178

7147

7134

7121

6749

6725

3340

2500

2585

3266

OPh

Ph

8 6 4 2

1079 12897101530



1

HN

NH O

Ph

+

23

X

N N CI

NaOH 0degC

EtOH

+

N

NH

N NH

O

Ph

X

ndash




HNCl

H

NN

N

OHN

Cl

H

NN

N

O

L4 L5

HN

H

L1 L2 L3

N

N

N

O HN

H

N

NN

N

O

O

OHN

H

N N

N

O O

H3C

(a)

Figure 3 Continued




LH

LOMe

LNO2

LCIP

LCIM

LH

LOMe

LNO2

LCIP

LCIM

(b)













26 Computational












β2 76minus

A11

P+

AperpP

+ g11 minus514

gperp minus914

ge1113874 1113875

α2 20023minusΔg


(1)





6 +(32) λE1( 1113857 (2)





(1) (C25H18N4O) (L1) (3904439042)Darkbrown

7691(7690)

465(466)



4088(4088)

274(273) 763 (765) 2616 (2616) 1387

(1388)

(3) (C26H20N4O2) (L2) (4204742044)Darkbrown

7427(7427)

479(479)



(1303)

(5) (C25H17N5O3) (L3) (4354443542)Darkbrown

6896(6895)

393(393)



246(246) 899 (897) 2465 (2466) 1307

(1305)


7067(7066)

403(402) 1319 (1318) 834 (835) mdash


249(248) 729 (728) 2499 (2502)461

(463)1325(1326)


7067(7068)

403(405) 1319 (1318) 834 (835) mdash


3730(3731)

288(288) 696 (695) 2387 (2388)440

(441)1266(1267)










(a) (b)

(c) (d)

(e)


1000

500

0

ndash500

ndash1000

ndash1500

ndash2000

Sign

al in

tens

ity







rel

1000950900850800750700650600550500450400350300250200150100

50

2000 3000 4000 5000 6000 7000 8000 90002θCu-Ka1 (1540598A)

(LH)










38 Computational





LNO2LCIM

LCIP

LHLOMe

ndash04 ndash02 00 02 04 06 08

50000

55000

60000

65000

70000

75000

80000

85000

90000

σR

K b (M

ndash1)





Residue 4C 1231 (1235)

[(VO)2 (SO4)2 (L1)]H2O


Residue V2O3 2041 (2040)



[(VO)2 (SO4)2 (L2)]2H2O


Residue V2O3 1915 (1916)


[(VO)2 (SO4)2 (L3)]H2O


Residue V2O2 1718 (1717)


[(VO)2 (SO4)2 (L4)]H2O


Residue V2O2+ 2C 2054 (2056)



[(VO)2 (SO4)2 (L5)]3H2O


Residue V2O2+ 4C 2260 (2232)


LCIM2

LCIP1 LCIP2 LCIM1

LH1LH2 LOMe1

LOMe2 LNO21 LNO22

(a)

Figure 8 Continued


(a1)

(b1)

(c1)

(a2)

(b2)

(c2)

(d1) (d2)

(e1) (e2)

(b)










LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015


04 06 08

VO(II) complexes

LNO2

ΔE



Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls








16 14 12 10

NH

N N NH

7801

7776

7550

7526

7370

7345

7300

7274

7202

7178

7147

7134

7121

6749

6725

3340

2500

2585

3266

OPh

Ph

8 6 4 2

1079 12897101530



1

HN

NH O

Ph

+

23

X

N N CI

NaOH 0degC

EtOH

+

N

NH

N NH

O

Ph

X

ndash




HNCl

H

NN

N

OHN

Cl

H

NN

N

O

L4 L5

HN

H

L1 L2 L3

N

N

N

O HN

H

N

NN

N

O

O

OHN

H

N N

N

O O

H3C

(a)

Figure 3 Continued




LH

LOMe

LNO2

LCIP

LCIM

LH

LOMe

LNO2

LCIP

LCIM

(b)













26 Computational












β2 76minus

A11

P+

AperpP

+ g11 minus514

gperp minus914

ge1113874 1113875

α2 20023minusΔg


(1)





6 +(32) λE1( 1113857 (2)





(1) (C25H18N4O) (L1) (3904439042)Darkbrown

7691(7690)

465(466)



4088(4088)

274(273) 763 (765) 2616 (2616) 1387

(1388)

(3) (C26H20N4O2) (L2) (4204742044)Darkbrown

7427(7427)

479(479)



(1303)

(5) (C25H17N5O3) (L3) (4354443542)Darkbrown

6896(6895)

393(393)



246(246) 899 (897) 2465 (2466) 1307

(1305)


7067(7066)

403(402) 1319 (1318) 834 (835) mdash


249(248) 729 (728) 2499 (2502)461

(463)1325(1326)


7067(7068)

403(405) 1319 (1318) 834 (835) mdash


3730(3731)

288(288) 696 (695) 2387 (2388)440

(441)1266(1267)










(a) (b)

(c) (d)

(e)


1000

500

0

ndash500

ndash1000

ndash1500

ndash2000

Sign

al in

tens

ity







rel

1000950900850800750700650600550500450400350300250200150100

50

2000 3000 4000 5000 6000 7000 8000 90002θCu-Ka1 (1540598A)

(LH)










38 Computational





LNO2LCIM

LCIP

LHLOMe

ndash04 ndash02 00 02 04 06 08

50000

55000

60000

65000

70000

75000

80000

85000

90000

σR

K b (M

ndash1)





Residue 4C 1231 (1235)

[(VO)2 (SO4)2 (L1)]H2O


Residue V2O3 2041 (2040)



[(VO)2 (SO4)2 (L2)]2H2O


Residue V2O3 1915 (1916)


[(VO)2 (SO4)2 (L3)]H2O


Residue V2O2 1718 (1717)


[(VO)2 (SO4)2 (L4)]H2O


Residue V2O2+ 2C 2054 (2056)



[(VO)2 (SO4)2 (L5)]3H2O


Residue V2O2+ 4C 2260 (2232)


LCIM2

LCIP1 LCIP2 LCIM1

LH1LH2 LOMe1

LOMe2 LNO21 LNO22

(a)

Figure 8 Continued


(a1)

(b1)

(c1)

(a2)

(b2)

(c2)

(d1) (d2)

(e1) (e2)

(b)










LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015


04 06 08

VO(II) complexes

LNO2

ΔE



Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls





HNCl

H

NN

N

OHN

Cl

H

NN

N

O

L4 L5

HN

H

L1 L2 L3

N

N

N

O HN

H

N

NN

N

O

O

OHN

H

N N

N

O O

H3C

(a)

Figure 3 Continued




LH

LOMe

LNO2

LCIP

LCIM

LH

LOMe

LNO2

LCIP

LCIM

(b)













26 Computational












β2 76minus

A11

P+

AperpP

+ g11 minus514

gperp minus914

ge1113874 1113875

α2 20023minusΔg


(1)





6 +(32) λE1( 1113857 (2)





(1) (C25H18N4O) (L1) (3904439042)Darkbrown

7691(7690)

465(466)



4088(4088)

274(273) 763 (765) 2616 (2616) 1387

(1388)

(3) (C26H20N4O2) (L2) (4204742044)Darkbrown

7427(7427)

479(479)



(1303)

(5) (C25H17N5O3) (L3) (4354443542)Darkbrown

6896(6895)

393(393)



246(246) 899 (897) 2465 (2466) 1307

(1305)


7067(7066)

403(402) 1319 (1318) 834 (835) mdash


249(248) 729 (728) 2499 (2502)461

(463)1325(1326)


7067(7068)

403(405) 1319 (1318) 834 (835) mdash


3730(3731)

288(288) 696 (695) 2387 (2388)440

(441)1266(1267)










(a) (b)

(c) (d)

(e)


1000

500

0

ndash500

ndash1000

ndash1500

ndash2000

Sign

al in

tens

ity







rel

1000950900850800750700650600550500450400350300250200150100

50

2000 3000 4000 5000 6000 7000 8000 90002θCu-Ka1 (1540598A)

(LH)










38 Computational





LNO2LCIM

LCIP

LHLOMe

ndash04 ndash02 00 02 04 06 08

50000

55000

60000

65000

70000

75000

80000

85000

90000

σR

K b (M

ndash1)





Residue 4C 1231 (1235)

[(VO)2 (SO4)2 (L1)]H2O


Residue V2O3 2041 (2040)



[(VO)2 (SO4)2 (L2)]2H2O


Residue V2O3 1915 (1916)


[(VO)2 (SO4)2 (L3)]H2O


Residue V2O2 1718 (1717)


[(VO)2 (SO4)2 (L4)]H2O


Residue V2O2+ 2C 2054 (2056)



[(VO)2 (SO4)2 (L5)]3H2O


Residue V2O2+ 4C 2260 (2232)


LCIM2

LCIP1 LCIP2 LCIM1

LH1LH2 LOMe1

LOMe2 LNO21 LNO22

(a)

Figure 8 Continued


(a1)

(b1)

(c1)

(a2)

(b2)

(c2)

(d1) (d2)

(e1) (e2)

(b)










LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015


04 06 08

VO(II) complexes

LNO2

ΔE



Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls






LH

LOMe

LNO2

LCIP

LCIM

LH

LOMe

LNO2

LCIP

LCIM

(b)













26 Computational












β2 76minus

A11

P+

AperpP

+ g11 minus514

gperp minus914

ge1113874 1113875

α2 20023minusΔg


(1)





6 +(32) λE1( 1113857 (2)





(1) (C25H18N4O) (L1) (3904439042)Darkbrown

7691(7690)

465(466)



4088(4088)

274(273) 763 (765) 2616 (2616) 1387

(1388)

(3) (C26H20N4O2) (L2) (4204742044)Darkbrown

7427(7427)

479(479)



(1303)

(5) (C25H17N5O3) (L3) (4354443542)Darkbrown

6896(6895)

393(393)



246(246) 899 (897) 2465 (2466) 1307

(1305)


7067(7066)

403(402) 1319 (1318) 834 (835) mdash


249(248) 729 (728) 2499 (2502)461

(463)1325(1326)


7067(7068)

403(405) 1319 (1318) 834 (835) mdash


3730(3731)

288(288) 696 (695) 2387 (2388)440

(441)1266(1267)










(a) (b)

(c) (d)

(e)


1000

500

0

ndash500

ndash1000

ndash1500

ndash2000

Sign

al in

tens

ity







rel

1000950900850800750700650600550500450400350300250200150100

50

2000 3000 4000 5000 6000 7000 8000 90002θCu-Ka1 (1540598A)

(LH)










38 Computational





LNO2LCIM

LCIP

LHLOMe

ndash04 ndash02 00 02 04 06 08

50000

55000

60000

65000

70000

75000

80000

85000

90000

σR

K b (M

ndash1)





Residue 4C 1231 (1235)

[(VO)2 (SO4)2 (L1)]H2O


Residue V2O3 2041 (2040)



[(VO)2 (SO4)2 (L2)]2H2O


Residue V2O3 1915 (1916)


[(VO)2 (SO4)2 (L3)]H2O


Residue V2O2 1718 (1717)


[(VO)2 (SO4)2 (L4)]H2O


Residue V2O2+ 2C 2054 (2056)



[(VO)2 (SO4)2 (L5)]3H2O


Residue V2O2+ 4C 2260 (2232)


LCIM2

LCIP1 LCIP2 LCIM1

LH1LH2 LOMe1

LOMe2 LNO21 LNO22

(a)

Figure 8 Continued


(a1)

(b1)

(c1)

(a2)

(b2)

(c2)

(d1) (d2)

(e1) (e2)

(b)










LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015


04 06 08

VO(II) complexes

LNO2

ΔE



Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls














26 Computational












β2 76minus

A11

P+

AperpP

+ g11 minus514

gperp minus914

ge1113874 1113875

α2 20023minusΔg


(1)





6 +(32) λE1( 1113857 (2)





(1) (C25H18N4O) (L1) (3904439042)Darkbrown

7691(7690)

465(466)



4088(4088)

274(273) 763 (765) 2616 (2616) 1387

(1388)

(3) (C26H20N4O2) (L2) (4204742044)Darkbrown

7427(7427)

479(479)



(1303)

(5) (C25H17N5O3) (L3) (4354443542)Darkbrown

6896(6895)

393(393)



246(246) 899 (897) 2465 (2466) 1307

(1305)


7067(7066)

403(402) 1319 (1318) 834 (835) mdash


249(248) 729 (728) 2499 (2502)461

(463)1325(1326)


7067(7068)

403(405) 1319 (1318) 834 (835) mdash


3730(3731)

288(288) 696 (695) 2387 (2388)440

(441)1266(1267)










(a) (b)

(c) (d)

(e)


1000

500

0

ndash500

ndash1000

ndash1500

ndash2000

Sign

al in

tens

ity







rel

1000950900850800750700650600550500450400350300250200150100

50

2000 3000 4000 5000 6000 7000 8000 90002θCu-Ka1 (1540598A)

(LH)










38 Computational





LNO2LCIM

LCIP

LHLOMe

ndash04 ndash02 00 02 04 06 08

50000

55000

60000

65000

70000

75000

80000

85000

90000

σR

K b (M

ndash1)





Residue 4C 1231 (1235)

[(VO)2 (SO4)2 (L1)]H2O


Residue V2O3 2041 (2040)



[(VO)2 (SO4)2 (L2)]2H2O


Residue V2O3 1915 (1916)


[(VO)2 (SO4)2 (L3)]H2O


Residue V2O2 1718 (1717)


[(VO)2 (SO4)2 (L4)]H2O


Residue V2O2+ 2C 2054 (2056)



[(VO)2 (SO4)2 (L5)]3H2O


Residue V2O2+ 4C 2260 (2232)


LCIM2

LCIP1 LCIP2 LCIM1

LH1LH2 LOMe1

LOMe2 LNO21 LNO22

(a)

Figure 8 Continued


(a1)

(b1)

(c1)

(a2)

(b2)

(c2)

(d1) (d2)

(e1) (e2)

(b)










LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015


04 06 08

VO(II) complexes

LNO2

ΔE



Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls











β2 76minus

A11

P+

AperpP

+ g11 minus514

gperp minus914

ge1113874 1113875

α2 20023minusΔg


(1)





6 +(32) λE1( 1113857 (2)





(1) (C25H18N4O) (L1) (3904439042)Darkbrown

7691(7690)

465(466)



4088(4088)

274(273) 763 (765) 2616 (2616) 1387

(1388)

(3) (C26H20N4O2) (L2) (4204742044)Darkbrown

7427(7427)

479(479)



(1303)

(5) (C25H17N5O3) (L3) (4354443542)Darkbrown

6896(6895)

393(393)



246(246) 899 (897) 2465 (2466) 1307

(1305)


7067(7066)

403(402) 1319 (1318) 834 (835) mdash


249(248) 729 (728) 2499 (2502)461

(463)1325(1326)


7067(7068)

403(405) 1319 (1318) 834 (835) mdash


3730(3731)

288(288) 696 (695) 2387 (2388)440

(441)1266(1267)










(a) (b)

(c) (d)

(e)


1000

500

0

ndash500

ndash1000

ndash1500

ndash2000

Sign

al in

tens

ity







rel

1000950900850800750700650600550500450400350300250200150100

50

2000 3000 4000 5000 6000 7000 8000 90002θCu-Ka1 (1540598A)

(LH)










38 Computational





LNO2LCIM

LCIP

LHLOMe

ndash04 ndash02 00 02 04 06 08

50000

55000

60000

65000

70000

75000

80000

85000

90000

σR

K b (M

ndash1)





Residue 4C 1231 (1235)

[(VO)2 (SO4)2 (L1)]H2O


Residue V2O3 2041 (2040)



[(VO)2 (SO4)2 (L2)]2H2O


Residue V2O3 1915 (1916)


[(VO)2 (SO4)2 (L3)]H2O


Residue V2O2 1718 (1717)


[(VO)2 (SO4)2 (L4)]H2O


Residue V2O2+ 2C 2054 (2056)



[(VO)2 (SO4)2 (L5)]3H2O


Residue V2O2+ 4C 2260 (2232)


LCIM2

LCIP1 LCIP2 LCIM1

LH1LH2 LOMe1

LOMe2 LNO21 LNO22

(a)

Figure 8 Continued


(a1)

(b1)

(c1)

(a2)

(b2)

(c2)

(d1) (d2)

(e1) (e2)

(b)










LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015


04 06 08

VO(II) complexes

LNO2

ΔE



Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls






6 +(32) λE1( 1113857 (2)





(1) (C25H18N4O) (L1) (3904439042)Darkbrown

7691(7690)

465(466)



4088(4088)

274(273) 763 (765) 2616 (2616) 1387

(1388)

(3) (C26H20N4O2) (L2) (4204742044)Darkbrown

7427(7427)

479(479)



(1303)

(5) (C25H17N5O3) (L3) (4354443542)Darkbrown

6896(6895)

393(393)



246(246) 899 (897) 2465 (2466) 1307

(1305)


7067(7066)

403(402) 1319 (1318) 834 (835) mdash


249(248) 729 (728) 2499 (2502)461

(463)1325(1326)


7067(7068)

403(405) 1319 (1318) 834 (835) mdash


3730(3731)

288(288) 696 (695) 2387 (2388)440

(441)1266(1267)










(a) (b)

(c) (d)

(e)


1000

500

0

ndash500

ndash1000

ndash1500

ndash2000

Sign

al in

tens

ity







rel

1000950900850800750700650600550500450400350300250200150100

50

2000 3000 4000 5000 6000 7000 8000 90002θCu-Ka1 (1540598A)

(LH)










38 Computational





LNO2LCIM

LCIP

LHLOMe

ndash04 ndash02 00 02 04 06 08

50000

55000

60000

65000

70000

75000

80000

85000

90000

σR

K b (M

ndash1)





Residue 4C 1231 (1235)

[(VO)2 (SO4)2 (L1)]H2O


Residue V2O3 2041 (2040)



[(VO)2 (SO4)2 (L2)]2H2O


Residue V2O3 1915 (1916)


[(VO)2 (SO4)2 (L3)]H2O


Residue V2O2 1718 (1717)


[(VO)2 (SO4)2 (L4)]H2O


Residue V2O2+ 2C 2054 (2056)



[(VO)2 (SO4)2 (L5)]3H2O


Residue V2O2+ 4C 2260 (2232)


LCIM2

LCIP1 LCIP2 LCIM1

LH1LH2 LOMe1

LOMe2 LNO21 LNO22

(a)

Figure 8 Continued


(a1)

(b1)

(c1)

(a2)

(b2)

(c2)

(d1) (d2)

(e1) (e2)

(b)










LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015


04 06 08

VO(II) complexes

LNO2

ΔE



Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls







(a) (b)

(c) (d)

(e)


1000

500

0

ndash500

ndash1000

ndash1500

ndash2000

Sign

al in

tens

ity







rel

1000950900850800750700650600550500450400350300250200150100

50

2000 3000 4000 5000 6000 7000 8000 90002θCu-Ka1 (1540598A)

(LH)










38 Computational





LNO2LCIM

LCIP

LHLOMe

ndash04 ndash02 00 02 04 06 08

50000

55000

60000

65000

70000

75000

80000

85000

90000

σR

K b (M

ndash1)





Residue 4C 1231 (1235)

[(VO)2 (SO4)2 (L1)]H2O


Residue V2O3 2041 (2040)



[(VO)2 (SO4)2 (L2)]2H2O


Residue V2O3 1915 (1916)


[(VO)2 (SO4)2 (L3)]H2O


Residue V2O2 1718 (1717)


[(VO)2 (SO4)2 (L4)]H2O


Residue V2O2+ 2C 2054 (2056)



[(VO)2 (SO4)2 (L5)]3H2O


Residue V2O2+ 4C 2260 (2232)


LCIM2

LCIP1 LCIP2 LCIM1

LH1LH2 LOMe1

LOMe2 LNO21 LNO22

(a)

Figure 8 Continued


(a1)

(b1)

(c1)

(a2)

(b2)

(c2)

(d1) (d2)

(e1) (e2)

(b)










LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015


04 06 08

VO(II) complexes

LNO2

ΔE



Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls







rel

1000950900850800750700650600550500450400350300250200150100

50

2000 3000 4000 5000 6000 7000 8000 90002θCu-Ka1 (1540598A)

(LH)










38 Computational





LNO2LCIM

LCIP

LHLOMe

ndash04 ndash02 00 02 04 06 08

50000

55000

60000

65000

70000

75000

80000

85000

90000

σR

K b (M

ndash1)





Residue 4C 1231 (1235)

[(VO)2 (SO4)2 (L1)]H2O


Residue V2O3 2041 (2040)



[(VO)2 (SO4)2 (L2)]2H2O


Residue V2O3 1915 (1916)


[(VO)2 (SO4)2 (L3)]H2O


Residue V2O2 1718 (1717)


[(VO)2 (SO4)2 (L4)]H2O


Residue V2O2+ 2C 2054 (2056)



[(VO)2 (SO4)2 (L5)]3H2O


Residue V2O2+ 4C 2260 (2232)


LCIM2

LCIP1 LCIP2 LCIM1

LH1LH2 LOMe1

LOMe2 LNO21 LNO22

(a)

Figure 8 Continued


(a1)

(b1)

(c1)

(a2)

(b2)

(c2)

(d1) (d2)

(e1) (e2)

(b)










LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015


04 06 08

VO(II) complexes

LNO2

ΔE



Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls








38 Computational





LNO2LCIM

LCIP

LHLOMe

ndash04 ndash02 00 02 04 06 08

50000

55000

60000

65000

70000

75000

80000

85000

90000

σR

K b (M

ndash1)





Residue 4C 1231 (1235)

[(VO)2 (SO4)2 (L1)]H2O


Residue V2O3 2041 (2040)



[(VO)2 (SO4)2 (L2)]2H2O


Residue V2O3 1915 (1916)


[(VO)2 (SO4)2 (L3)]H2O


Residue V2O2 1718 (1717)


[(VO)2 (SO4)2 (L4)]H2O


Residue V2O2+ 2C 2054 (2056)



[(VO)2 (SO4)2 (L5)]3H2O


Residue V2O2+ 4C 2260 (2232)


LCIM2

LCIP1 LCIP2 LCIM1

LH1LH2 LOMe1

LOMe2 LNO21 LNO22

(a)

Figure 8 Continued


(a1)

(b1)

(c1)

(a2)

(b2)

(c2)

(d1) (d2)

(e1) (e2)

(b)










LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015


04 06 08

VO(II) complexes

LNO2

ΔE



Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls






LNO2LCIM

LCIP

LHLOMe

ndash04 ndash02 00 02 04 06 08

50000

55000

60000

65000

70000

75000

80000

85000

90000

σR

K b (M

ndash1)





Residue 4C 1231 (1235)

[(VO)2 (SO4)2 (L1)]H2O


Residue V2O3 2041 (2040)



[(VO)2 (SO4)2 (L2)]2H2O


Residue V2O3 1915 (1916)


[(VO)2 (SO4)2 (L3)]H2O


Residue V2O2 1718 (1717)


[(VO)2 (SO4)2 (L4)]H2O


Residue V2O2+ 2C 2054 (2056)



[(VO)2 (SO4)2 (L5)]3H2O


Residue V2O2+ 4C 2260 (2232)


LCIM2

LCIP1 LCIP2 LCIM1

LH1LH2 LOMe1

LOMe2 LNO21 LNO22

(a)

Figure 8 Continued


(a1)

(b1)

(c1)

(a2)

(b2)

(c2)

(d1) (d2)

(e1) (e2)

(b)










LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015


04 06 08

VO(II) complexes

LNO2

ΔE



Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls




LCIM2

LCIP1 LCIP2 LCIM1

LH1LH2 LOMe1

LOMe2 LNO21 LNO22

(a)

Figure 8 Continued


(a1)

(b1)

(c1)

(a2)

(b2)

(c2)

(d1) (d2)

(e1) (e2)

(b)










LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015


04 06 08

VO(II) complexes

LNO2

ΔE



Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls




(a1)

(b1)

(c1)

(a2)

(b2)

(c2)

(d1) (d2)

(e1) (e2)

(b)










LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015


04 06 08

VO(II) complexes

LNO2

ΔE



Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls











LCIPLCIM

LHLOMe

001002003004005006007008009010011012013014015


04 06 08

VO(II) complexes

LNO2

ΔE



Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls




Tabl

e7

Con

siderable

bond

leng

thschargesdipo

lemom


th(ʄ)a

ndexcitatio

nenergies

(E)

Com

poun

dO19

N11

N15

N16

C18ndashO

19C12ndashN

11C14ndashN

15N15ndashN

16V1

V2

D(D

ebye)

E(nm)

ʄL1

minus0415473minus0

555221minus0

349927minus0

275635

1224561

1384229

1287795

1366391

mdashmdash

51769

56781

00316

L1+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L2minus0

410237minus0

555363minus0

348134minus0

275746

mdashmdash

mdashmdash

mdashmdash

64963

57626

00403

L2+VO(II)minus0

420038minus0

397120minus0

322648minus0

250261

mdashmdash

mdashmdash

0927552

0915069

35504

313877

00008

L3minus0

416751minus0

044378minus0

050930

0113237

1317259

2076019

1772715

1281712

mdashmdash

53595

761339

0002

L3+VO(II)minus0

414856minus0

387699minus0

320321minus0

254947

0955124

0952544

166899

172663

00032

L4minus0

313357minus0

358945minus0

031267minus0

294059

1223609

1404653

1286454

1367672

mdashmdash

44684

31592

04055

L4+VO(II)minus0

410181minus0

282766minus0

316313minus0

248429

mdashmdash

mdashmdash

0933201

0929331

115667

165137

0003

L5minus0

354631minus0

480428minus0

209492minus0

312115

1224058

1384450

1286411

1367122

mdashmdash

39661

60017

0043

L5+VO(II)minus0

405024minus0

408894minus0

304735minus0

210573

mdashmdash

mdashmdash

0905245

0730601

89706

209886

0002












Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls














Electrostaticenergy










4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls





4 Conclusion



(a) (b)

(c) (d)

(e)



2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls




2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(a)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(b)

2402202001801601401201008060402000 20 40 60 80 100120140160180200220240

(c)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(d)

2402202001801601401201008060402000 20 40 60 80 100 120 140 160 180 200 220 240

(e)







Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls





Data Availability




Acknowledgments




References










L2

L3

L1

L4

L5

020406080

100120

Viab

ility

()

(a)

L2

L3

L1

L4

L5


0

50

100

150

Viab

ility

()

(b)

L2

L3

L1

L4

L5


020406080

100120

Viab

ility

()

(c)


























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls



























































Journal of

Chemistry





Journal of

Volume 2018






Volume 2018




Journal of






Enzyme Research


Journal of



MaterialsJournal of






Na

nom

ate

ria

ls




synthesisofnovelvo(ii)-perimidinecomplexes:spectral...

Documents