Ind ian Journal of Chemistry Vol. 40A, October 200 I, pp.1064- I069

Synthesis, characterization and biological activity of the complexes of manganese(III), cobalt(III), nickel(II), copper(II) and zinc(II) with salicylaldehyde

thiobenzhydrazone

N K Singh*, D K Singh & J Singht Department of Chemistry, I3anaras Hindu University, Varanasi 221 005, India

Received 16 October 2000; revised 30 May 2001

A new li gand. salcylaldehyde thiobenzhydrazone (H!STI3) forms the adduct [Cu(H2STBh]Clz and the deprotonated complexes. IM(HSTB)l] (M(II)=Ni , Cu or Zn) , [Mn(HSTBh] and [Co(STB)(HSTI3)], which have been characterized by elemen tal analyses, magnetic susceptibility measurement. IR , UV- Vis, NMR and FAI3 mass spectral data. Magnetic and electronic spectral studies suggest octahedral geometry for [Mn(IISTI3 ).1] and [Co(STI3)(IISTI3)] and square planar geo metry for [M(HSTBh] (M(II)=Ni , Cu) and [Cu(H 2STBhlClz. The antifungal and antibacterial activity of the li gand and the complexes have been screened aga inst seve ral fungi and bacteri a.

Thiosemicarbazones and their 3d-metal complexes have been found to exhibit fungicidal l, bactericidal2

,

ant i viral3 and anti tubercu lar4 activity. The anti fungal activity of these compounds is due to the presence of toxophorically important >N-C=S moieti·6 The metal chelates of the Schiff's bases obtained from the condensation of salicylaldehyde with ethoxythio­carbonyl7 and 2-furanthiocarboxy hydrazinesB

,

thiosemicarbazides9 and S-methyl and S-benzyl dithiocarbazates 1o.1I have been reported. Recently, copper(II) complexes of 5-bromo salicylaldehyde-2-methyl thiosemicarbozonel 2

. 5-nitro salicylaldehyde N(3)-substituted thiosemicarbazones 13 and salicy­laldehyde N(4)-cyclohexyl thiosemicarbazone (HzL)14 have been synthesized and characterized, but no work is reported on the complexes of salicylaldehyde thiobenzhydrazone (HzSTB), having the above said toxophorically important >N-C=S moiety. In view of this , synthesis, characterization and biological activity of manganese(lll), coba1t(I1I), nickel(II) , copper(lI) and zinc(lI) complexes of HzSTB (Structure I) have been undertaken and the results of these investigations are described in the present communication.

Materials and Methods All chemicals used were of analytical or equivalent

grade. Ammonium polysulphide ls and carboxymethyl dithiobenzoate ' 6 were prepared by literature methods. Thiobenzhydrazide was prepared by adding 20 mL of an aqueous solution of 15% (v/v) NzH4.f-hO to a solution of carboxymethyl dithiobenzoate (5.3 g, 25

tDepartment of Chemislry, U.P. (P.O.) College, Varanasi

mmol) in 50 mL of NaOH (1 g, 25 mmol ) and allowing this mixture to stand at room temperature for 2 h. The product precipitated by adding dropwise dilute acetic acid to the reaction mixture was filtered , washed with water and dried in air. The filtrate was extracted with chloroform and on evaporation of the solvent some water soluble thiobenzyhydrazide could also be recovered. Both the fraction s were combined and recrystallized from chloroform, m.p. 73-75°C (Lit. 72_73°C)17.

Salicylaldehyde IhiobellzhydraZOlle (l--hSTB) C6HsCSNHN=CHC6H4(OH) (H2STB) was

prepared by refluxing ethanolic solutions of thiobenzhydrazide (4.5g, 30 mmol) and salicyl­aldehyde (3 mL) for about 30 min. On evaporation of the solvent, the yellow product obtained was suction filtered, washed with 5 mL ethanol and recrystallized from hot ethanol, m.p. 154°C.

[ClI(H2STBh]CI2 alld [Co(STB)(HSTB)] [Cu(H2STBh]CI2 and [Co(STB)(HSTB)] were

prepared by reacting ethanolic solutions (20 mL) of the respective metal(lI) chloride (1 mmol) and H2STB

S 3 II H0;o2:?' 4

6' C N I 5'CX" ""'/2~ 1;:,.. 5 INC 6 4'~ 2' H H

3'

SINGH el al.: METAL COMPLEXES OF SALICYLALDEHYDE THIOBENZHYDRAZONE 1065

(0.512 g, 2 mmol) in the presence of HCI and allowing the solvent to evaporate at room temperature in open air. The precipitated complexes were filtered, washed with a little ethanol and dried in vacuo.

{M(HSTBh} and (Mn(HSTBh l [M(HSTBh] (M(ll) = Ni , Cu or Zn) and

[Mn(HSTBh] were prepared by refluxing 20 ml of an ethanolic solution of H2STB (0.256 g, 1 mmol) and an aqueous - ethanolic solution of the respective M(CH3COOh.nH20 (0.5 mmol) in the presence of CH3COONa (- 1 g) on a water bath for about 30 min. The complexes thus obtained were filtered, washed successively with water and ethanol and dried ill vacuo.

All the complexes were analysed for their metal content, following standard procedures 18. Sulphur was estimated as BaS04. C, Hand N were estimated on a Carlo-Erba microanalyzer. Magnetic susceptibility measurements were made at room temperature on a Cahn-Faraday balance using Hg[Co(NCS)4] as calibrant. Electronic spectra were recorded on CARY-2390 UY-visible spectrophotometer as nujol mUlls l 9

.

IR spectra were recorded in the 4000-400 cm- I region (KBr disc) on a lASCO Ff/IR-5300 spectrophotometer. The IH and 13C NMR spectra were obtained in DMSO-d6 on a JEOl FX-90Q spectrometer using TMS as an inernal reference. E~R spectra were recorded on a X-band spectrometer model EPR-II2 using DPPH as a <g> marker. FAB mass spectra were obtained on lEOl SX 102/DA-6000 mass spectrometer using m-nitrobenzyl alcohol (NBA) as a matrix.

Fungicidal screening Antifungal activity was evaluated by spore

germination technique2o. A stock solution was prepared by dissolving 2 mg/ml of each compound in DMSO and it was serially double diluted with sterilized distilled water up to three dilutions, giving concentrations of 1000, 500 and 250 /lg/mL. Spores of the test fungi, Fusarium udum. Alternaria tennuissima and Helminthosporium sativum grown on potato dextrose agar medium were incorporated into culture tubes containing different concentration of the compounds separately and thoroughly agitated in order to breakup the spore clumps. A drop of the suspensions was transferred on clear slides which were then kept in Petridishes containing moist cotton. A parallel set of control was also maintained without the compound using water and solvent - water

mixture. The Petridishes were incubated at 25 ± 1°C for 24 h. The counts of germinated spores were made from three random microscopic fields of each slide in order to calculate the inhibition percentage using the following formula:

Inhibition percentage=

Germination in treatment x lOO

Germination in control

Bactericidal screening The antibacterial activity of the ligand and its

complexes was evaluated by the Agar plate diffusion technique21. A stock soution of 1000 /lg/mL was made by dissolving I mg/ml of each compound in DMSO. Filter paper (Whatman no. 4) discs (6 mm dia) were soaked in solutions of the test compounds and placed after drying off the solvent on Muller hinton agar plate containing lawn culture of different bacteria. The plates were incubated at an optimum growth temperature of 37°C. The zones of inhibition around the discs were measured after 24 h. The test bacteria included (a) Staphylococcus aureus. (b) Staphylococcus epidermidis. (c) Enterococcus faecalis. (d) Escherichia coli. (e) Pseudomonas aeruginosa. (f) Proteus vulgaris. (g) Shigellaflexneri. (h) Vibrio cholerae and (i) Staphylococcus aureus (ATCC 25923). All experiments were performed in duplicate and gentamicin was used as a standard drug. Zone diameter of inhibition greater than 8 mm was taken as sensitive and is shown as + in Table 3.

Results and Discussion The analyical data (Table 1) show that only

copper(II) chloride forms a 1:2 adduct . [Cu(H2STBh]Ch. The deprotonated complexes, [M(HSTBh] (M(II)=Ni, Cu or Zn) are obained with metal(I1) acetates. However, cobalt(II) chloride and manganese(II) acetate got oxidised to form [Co(STB)(HSTB)] and [Mn(HSTBh] in the presence of HCI and CH3COONa, respectively. All the complexes are insoluble in water but are slightly soluble in ethanol, methanol and acetonitrile and more soluble in polar organic solvents such as DMF and DMSO. All the complexes melt in the temperature range of 230-300 °C, except [Zn(HSTBh] which does not melt upto 300 °C.

[Co(STB)(HSTB)] and [Ni(HSTBh] are diamagnetic (Table I). The former complex shows two bands at 18115 and 22725 cm- I assigned to the

1066 INDIAN J CHEM, SEC A, OCTOBER 2001

I I d I . AI;: -7 Eg an A21! transitions, respectively, in an

octahedral geometry around cobalt(IIl), while the latter shows two d-d bands at 19645 and 20745 cm-' ass igned to the IAI;: -7 IB3;: and IBII! transitions, respectively, in a square planar geometry around nickel(rl). The magnetic moments of [Cu(H2STB)2]Cb and [Cu(HSTBh] are normal and show a broad band at 17480 and 17545 cm-', respectively, which sugges ts a square planar geometry for them. The magnetic moment of 4.8 B.M. for [Mn(HSTBh] shows the presence of four unpaired e lectrons on manganese(l i I) and the occurrence of three bands at 14880, 16835 and 18350 cm-' assigned

'8 'A '8 I 'E . . . I to ' Ig -7 ' I I! ' " 28 ane . ~g transitions, respective y, suggests a distorted octahedral structure for the complex22

. The hi gh energy bands in the regions 23365-245 10 and 34015-34245 cm-' may be assigned to the charge-transfer and intraligand transitions, respecti vely.

The 'H NMR spectrum of H~STB exhibits four signals for the -OH and -NH protons, si nce compound containing the C=N moiety can exist as a mixture of EIZ isomers23 (Structure II). Thus, the signals appearing at 8 14.00 and 11.83 ppm are ass igned to NH and OH protons, respectively, in the Z-form, whereas, those at 8 8.73 and 10. I 6 ppm to the protons of the same groups in the E-form. The signal for the -CH=N- proton appears at 8 9.06 ppm .. The benzene ring protons appear as a multiplet between 8 6.73-8.00 ppm. The spectra of [Ni(HSTB)2], [Co(STB)(HSTB)] and [Zn(HSTB )z] show the absence of NH signals and the presence of a signal at 8 11.23-11.56 ppm for the OH proton, indicat ing loss of NH proton via thioenolisation during complex

formation. The signal due to -CH=N- proton shows a small downfield shift and appears at 8 9. 16-9.40 ppm, indicating coordination through iminic nitrogen24

The l3C NMR spectrum of H2STB shows several signals for the ring carbons. The presence of more signals than the number of ring carbons supports the earlier obevation from' H NMR that the ligand exists as a mixture of E- and Z-isomers in the solution. The assignment for these signals have been made by taking into account the chemical shifts of thiobe­nzhydrazide (TBH) (Structure IlIa) eC'" 131.21; C/

4 ,

129.26; C\s, 128.56 and C/2, C/

6 , 126.88, 127.85 ppm) and salicylaldehyde hydrazone (S H) (Structure IIIb) (C" 119.79; C2, 156.68; C3, 115.83; C4, 128.78, Cs, 119.08 and C6, 128.35 ppm).

The chemical shifts for the various carbons of H2STB are: (8, ppm) C" 119.46; C2, 157.87; C), 11 6.80; C4 , 129.16; Cs, 11 9.02; Cr" 128.67; C/" 132.51; C/

4, 131.22; C\s, 128.18 ; C'2, C/O' 126. 13,

127.75.

Z

E and Z isomers of H2STB

II

Table 1- Analytical data and physical propcrties of 'he complexcs of sa licy laldehyde thiobenzhydra zone

Compou nd Colour/ Found (Ca lcd.) % . ~lcff.

Yield (%) Ill.p. M C H N S CI (BM)

H~STB Yellow (0C) 65. 4.6 10.8 12.8

70 154 (65.t (4.7) ( 10.9) (12.5) [Mn(HSTBhl Black 6.2 60. 3.8 9.8 11.5 4.8

50 240 (6.7) (6 1.~ (4.1 ) (10.2) ( 11.7) ICo(STB)(HSTB )l Brown 10.3 59. 3.5 9.5 11.6 Diamagnetic

55 300 ( 10.4) (59.2 (3.7) (9.9) ( 11.3) [Ni (HSTB)21 Light brown 9.9 59.3 3.7 9.2 11.5 Diamagnetic

55 230 (10.3) (59. 1 (3.9) (9.8) ( 11.3)

[Cu(HSTBhl Yellowish brown 10.9 58. 3.7 9.8 10.9 2.0 40 275 (11.1 ) (58 .t (3.9) (9.8) ( 11.2)

[Cu(H2STB h lCI2 Green 9.2 51.8 3.5 8.0 9.7 10.5 1.8

45 285 (9.4) (52.( (3.7) (8.7) (9.9) (11.0) [Zn(HSTBh] Lemon ye llow 10.8 58. 3.5 9.3 11.3 Diamagnetic

45 >300 ( 11.4) (58A (3 .9) (9.8) ( 11.1 )

SINGH el ai .: METAL COMPLEXES OF SALICYLALDEHYDE THIOB ENZHYDRAZONE 1067

In addition to the ring carbons, H2STB shows two

signals at 8 192.76 and 146.66 ppm due to >C=S and

-CH=N- carbons, respective ly , which undergo

upfield and downfield shifts of 89.8 1-13.33 and 6.77-8.1 2 ppm, respectively, in [Ni (HSTBh ] and [Zn(HSTB)2], indicating bonding through thiolato sulphur and iminic nitrogen.

The ESR spectra of [Cu(H2STBh ]ch and [Cu(HSTBh] at room temperature show four and one

signal(s) in the gil reg ion but g.l lines are not resolved in both the complexes. Various magnetic parameters obtained from the analyses of the spectra are given below which indicates a square planar geometry for the complexes .

Compound

[Cu(H2STB)21Cl2

[Cu(HSTBhl

S II

11 11

2.209 2. 124

50:.)' I ' c" /~ 4 ' I N

"" 2' H )'

(a)

TBH

IlIa

All Rl. ga l' IIO G 2.046 2. 101 - 2.043 2.097

H 6 C NH

SOil ~ / 2 I 2 N 4 ~ OH

(b)

SH IIIb

The IR spectrum of the ligand shows two bands at

3275 and 3200 cm' ) whch may be assigned to v(OH)

and v(NH), respectively . The band at 3200 cm' ) is found absent in all the complexes except [Cu(H2STBh ]Ch, showing loss o f thioamide proton via thioenoli sation and subsequent participation of the

resulting thiolo sulphur in bonding . The v(OH) band is shifted to higher frequency in the complexes, indicating non-involvement of phenolic oxygen in bondng. In the case of [Co(STB )(HSTB)], the ligand behaves as mononegative as well as binegative fashion which is indicated by the presence of bands

due to v(C-S) and v(OH).

The bands occurring at 1620, 1265, 920 and 850 cm' ) in the ligand are assigned to v(C=N), v (C-O)

(phenolic), v(N-N) and v(C=S), respectively. A negative shift of 10-20 cm' ) in v (C=N) and the presence of a new band at 720-740 cm' ), due to v(C­S) indicate bonding through the iminic nitrogen and thiolo sulphur in the deprotonated complexes. The spectrum of [Cu(H2STBh ]ch shows v(NH) almost at the same posi ti on, but v(OH) shows an upward shift due to breaking up of hydrogen bonding, indicating that these groups are not involved in bonding. However, v(C=N) and v(C=S) bands , occurring in the

Table 2- lnhibition (%) of spore germination of HzSTB and its complexes

Compound

[Mn(HSTB hl

[Co(STB)(HSTB)l

[Ni(HSTBhl

[Cu(HSTBhl

[Zn(HSTBhl

Control (water) cont ro l (Solvenl+water)

Conc. (~g/mL)

250 500 1000 250 500 1000 250 500 1000 250 500 1000 250 500 1000 250 500 1000 250 500 1000

Allernaria lelluissima

68 80 83 42 56 59 25 43 57 66 78 82 46 63 60 69 8 1 85 26 54 59

4

Helmilllhosporiull1 Fusarium salivulIl Velum

65 63 68 76 8 1 80 30 49 61 66 65 73 30 52 43 69 58 75 65 75 72 82 84 86 51 65 56 77 64 82 68 80 77 83 85 88 39 45 47 56 58 67 2 2 5 4

1068 INDIAN J CHEM. SEC A, OCTOBER 200 1

ligand at 1620 and 850 em" , respectively, show a negati ve shift of 20 and 35 em", respectively, indicating coordination through iminic nitrogen and thi one sulphur.

The IR spectral studies thus indicate, mononegative bidentate behav iour of the ligand in 1:2 as well as 1:3 deprotonated complexes, neutral bidentate 111

[Cu(H2STBh]CI2 and mononegative as well as binegative tridentate 111 [Co(STB)(HSTB)], (Structure IV).

The FAB mass spec trum of [Co(STB)(HSTB)] shows a peak at m/z = 569 con-esponding to the

((OH

CH II/Ph

/J:-!'" -s-C N ," /' \I " ,>IvI.,.: N /C- S-.-.N/

Ph II

HCX)

HO

(a)

[M(HSTB), ]

M = Cu. Ni

Ph;C_ S

Ii :1" N " H

OCOH \;''In " A' C:O I H AN~ --I'~N~ I C~ 'T -J 1-10

C"'" / Ph (e)

[Zn(HSTB),]

OCOH

CH II Ph

/J:-!" -'S=C/ HN ,\.,/, \

I ' Cu " NH ,;: .. s!' .. :V , Ph \\ L HC):::JJ

HO

(b)

ICu(H,STDJ,]C1,

molecular weight of 568.6 for the complex. It also shows peaks at mlz = 255 and 254 which correspond to the fragments of the ligand formed after the release of one and two protons, rspectively . A peak at mlz = 3 14 is due to the fragment Co(HSTBt. The FAB mass spectrum of [Mn(HSTBh ] shows the molecular ion peak at mlz = 82 I .

Antilllicrobial Screening

The antifungal activity has been found to increase with increasing concentration of the compounds (Table 2). [Cu(H2STB)2]Ch is found to be most active against all the three fungi. [Co(STB)(HSTB)] is found least active against A. telluissillla and H. sativlIlII , whereas, [Zn(HSTBh] shows minimum activity against F. udulII. H2STB is observed to be less acti ve than [Cu(H2STB)2]Ch, but more active than other compounds against A. tenuissill1a.

The results of antibac teri al screening (Table 3) show that H2STB inhibits the growth of only Vibrio cholerae. [Mn(HSTB h ] and [Cu(H2STB2]Ch inhi bit the growth of Staphylococcus aureus, Staphylococcus epidennidis and Pseudomonas aeruginosa. The growth of Vibrio cholerae is checked only by the former complex. The growth of Staphylococcus aureus (ATCC 25923) is checked only by [Cu(H2STBh ]Ch. [Cu(HSTB2] inhibits the growth of Staphylococcus aI/reus, Staphylococcus epidermidis, Vibrio clwlerae and Staphylococcus aureus(A TCC 25923) for which the ligand is found to be inactive. [Co(STB)(HSTB)] inhibits the growth of only Staphylococcus aureus, whereas, [Zn(HSTBh] is found to be inactive against all the bacteria chosen for the screening.

Acknowledgement

The authors thank Dr V B Chauhan, Plant

Table 1--Al1libacterial screening results of H2STB and its complexes

Compou nd Microbi al species

a b c d e f g h

H2STB + [Mn(HSTBhl + + + + [Co(STB)(HSTB)] + [Cu(HSTBhl + + + + [Cu(H2STBhlCI 2 + + + [Zn(HST Bhl

Gentami cin + + + + + Solvent (DMSO)

SINGH et al.: METAL COMPLEXES OF SALICYLALDEHYDE THIOBENZHYDRAZONE 1069

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