photochemical behavior of antibiotics impacted by ... · photochemical behavior of antibiotics...
TRANSCRIPT
Supplementary Infromation
S1
Photochemical Behavior of Antibiotics Impacted by Complexation Effects
of Concomitant Metals: A Case for Ciprofloxacin and Cu(II)†
Xiaoxuan Wei,a Jingwen Chen,∗a Qing Xie,a Siyu Zhang,ab Yingjie Li,a Yifei Zhang,a and
Hongbin Xiea
a Key Laboratory of Industrial Ecology and Environmental Engineering (MOE), School of
Environmental Science and Technology, Dalian University of Technology, Dalian 116024,
China
b Key Laboratory of Pollution Ecology and Environmental Engineering, Institute of Applied
Ecology, Chinese Academy of Science, Shenyang 110016, China
(11 Pages, 3 Texts, 11 Figures, 4 Tables)
Text S1 Determining Kf' for complexation of ciprofloxacin with Cu(II)
The fluorescence spectra of ciprofloxacin (CIP) with different concentrations of
concomitant Cu(II) are shown in Fig. S1(a). The fluorescence intensity at λ = 430 nm was
used to calculate the complex ratio (n) and the conditional stability constant (Kf'):
0f'( )lg lg[Cu(II)] lgF F n K
F−⎡ ⎤ = +⎢ ⎥⎣ ⎦
(S1)
where F0 and F are the fluorescence intensities of CIP and the Cu(II)-CIP mixture,
respectively. As shown in Fig. S1(b), n = 1.05 and lgKf' = 6.09, indicating that Cu(II) and CIP
can form 1:1 complex with a conditional stability constant K'f,Cu(CIP) = 1.23 × 106 in the pH =
7.5 solutions.
† Electronic Supplementary Information (ESI) available: details of the total ion chromatograms and mass spectra of the identified products, the product yields, and the formation and degradation rate constants.
∗ Correspondence to: Jingwen Chen, e-mail: [email protected]; Phone: +86-411-8470 6269
a Dalian University of Technology
b Institute of Applied Ecology, Chinese Academy of Science
Electronic Supplementary Material (ESI) for Environmental Science: Processes & Impacts.This journal is © The Royal Society of Chemistry 2015
Supplementary Infromation
S2
350 400 450 500 5500
25
50
75
100 (a) λex
= 280 nm
10 μmol/L
0 μmol/L
Fluo
resc
ence
Inte
nsity
λ (nm)
[Cu(II)]
-6.0 -5.8 -5.6 -5.4 -5.2 -5.0-0.3
0.0
0.3
0.6
0.9 (b)
lg[(
F 0-F)/F
]
lg[Cu(II)]
y = 1.05x + 6.09r = 0.997p < 0.0001
λex/λem = 280/430 nm
Fig. S1 Effects of Cu(II) on fluorescence intensity of CIP in pH = 7.5 solutions ([CIP] = 0.5
μmol/L, the error bars represent the 95% confidence interval, n = 3)
Text S2 Preparation of Cu(II)-CIP complex
CuCl2 (2.5 mol/L, 20.0 μL) was added to a solution of 1.0 mmol/L CIP (50 mL) with
continuous stirring. pH of the mixed solution was adjusted to 7.5. The formed blue crystals of
the complex were filtered, washed and dried to constant weight. Subsequently, the solid
samples were analyzed by IR, and the results are shown in Fig. S3.
Text S3 DFT calculations of defluorination reactions
The structures of reactants (R), transition states (TS) and products (P) for the C−F bond
cleavage of H2CIP+ at the excited triplet state (T) and [Cu(H2CIP)(H2O)4]3+ at the excited
tripquartet state (4T, where the quartet superscript refers to the total spin of the complex, T
refers to the local multiplicity of H2CIP+) are shown in Fig. S7. Results show that for H2CIP+,
the distance of C12−F was elongated from 1.35 Å in R to 1.48 Å in the TS, and to 3.86 Å in
the P, indicating the rupture of the C−F bond. [Cu(H2CIP)(H2O)4]3+ underwent a similar C−F
bond cleavage process. The distance of C12−F was elongated from 1.34 Å in the R to 1.93 Å
in the TS, and to 3.83 Å in the P. Thus, the Cu(II) complexation has negligible effects on the
C−F bond cleavage process of H2CIP+.
For the reactions of H2CIP+ at the T state and [Cu(H2CIP)(H2O)4]3+ at the 4T state with OH−
at its ground state (Fig. S8), two transition states (TS1 and TS2), and one intermediate (IM)
were identified, indicating that the OH− addition reactions are stepwise. The reactions are
initiated by the formation of reactant complexes (RCs) between the CIP species and OH− with
different interactions. For H2CIP+, intermolecular hydrogen bonds are formed between O in
Supplementary Infromation
S3
OH− and H42 (connected with N15) in CIP, whereas for [Cu(H2CIP)(H2O)4]3+, intermolecular
hydrogen bonds are formed between O in OH− and H40 (connected with C20) in CIP. The
subsequent reaction processes are similar for the two species, that is, O in OH− gradually
approaches C12 and the distances of C12−O in the IM are reduced to 1.39 Å, falling in the
range of a C−O single bond length. In the following step, the distances of C12−F bonds are
elongated to about 2.00 Å in TS2. Finally, F− and hydroxyl products are formed, with the
C12−O bond length being < 1.35 Å and the C12−F bond length being > 3.54 Å. Thus, the Cu(II)
complexation can alter the OH− addition reaction channels of H2CIP+.
0.0 0.5 1.0 1.5 2.00
20
40
60
80
α C
u(C
IP) (%
)
[Cu2+] (μmol/L)
55.2%
Fig. S2 Effects of equilibrium concentrations of Cu2+ on the fraction of Cu(CIP)
020406080
1800 1700 1600 1500 1400 1300 12000
20406080
υCOO- symυCOO- antisym
υC=O carboxylCIP
υC=O ketone
CIP + Cu(II)
Wavenumber (cm-1)
T (%
)
Fig. S3 IR spectra for CIP and mixture of CIP and Cu(II)
Supplementary Infromation
S4
250 275 300 325 350 3750.00
0.05
0.10
0.15
0.20
[CIP] = 5 μmol/L pH = 7.5
[Cu(II)] = 0 μmol/L [Cu(II)] = 5 μmol/L [Cu(II)] = 10 μmol/L [Cu(II)] = 15 μmol/L [Cu(II)] = 20 μmol/L
Abs
orba
nce
λ (nm) Fig. S4 Variation of UV-vis absorbance spectra of CIP with different [Cu(II)]
HOMO ( )
LUMO ( )
H2CIP+ [Cu(H2CIP)(H2O)4]3+
−−
↓−−↑
LUMO ( )−−
HOMO−1 ( )−↓−↑
HOMO ( )−−↑
Fig. S5 Molecular orbital compositions and structures for the main absorption of H2CIP+ and
[Cu(H2CIP)(H2O)4]3+ (Piperazine ring to the left, carboxylic group and Cu atom to the right of
each molecule. HOMO stands for the highest occupied molecular orbital. HOMO−1 is the
second highest occupied molecular orbital. LUMO stands for the lowest unoccupied
molecular orbital)
Supplementary Infromation
S5
×105
0
4
8 MS2/ESI+ CE 20 eV (m/z = 330)
m/z140 160 180 200 220 240 260 280 300 320 340 360 380 400
312
286 330243
O
N
HO
NHN
O
OH
P330M
M − H2O
M − CO2
M − H2O − CO2
M − CO2 − C2H5N
268
×105
0
1
2
MS2/ESI+ CE 20 eV (m/z = 288)
m/z140 160 180 200 220 240 260 280 300 320 340 360 380 400
270
199 288227
O
NNHNH2
O
OH
P288M
M − H2O
M − H2O − C2H5NM − H2O − C2H5N − CO
×105
0
1
1.5 MS2/ESI+ CE 20 eV (m/z = 306)
m/z140 160 180 200 220 240 260 280 300 320 340 360 380 400
0.5
288
268 306245
O
N
F
NHNH2
O
OH
P306M
M − H2O
M − H2O − HFM − H2O − C2H5N
×105
0
1
2 MS2/ESI+ CE 20 eV (m/z = 263)
m/z140 160 180 200 220 240 260 280 300 320 340 360 380120
245
204 217263
O
N
F
H2N
O
OH
P263M
M − H2O
M − H2O − CO
M − H2O − C3H5
Fig. S6 Mass spectral fragmentation patterns determined by triple quadrupole mass
spectrometer for CIP and its photoproducts, where CE stands for collision energy
Supplementary Infromation
S6
0
1
2 MS2/ESI+ CE 30 eV (m/z = 334)
m/z140 160 180 200 220 240 260 280 300 320 340 360 380 400
316217
245 271 298 334
×105
0
1.5
3 MS2/ESI+ CE 20 eV (m/z = 334) 316
334217 245
O
NNH
HN
O
OHF
O P334M
M − H2O
M − 2H2O
M − H2O − CH3NO
M − H2O − C3H5NOM − H2O − C3H5NO − CO
CH3NO = H2N CHO
C3H5NO =HN
O
Continued Fig. S6 Mass spectral fragmentation patterns determined by triple quadrupole
mass spectrometer for CIP and its photoproducts, where CE stands for collision energy
R 12
1.35 Å
qF = −0.33e
\
12
1.34 Å (H2O)
Cu
qF = −0.31e
TS 12
1.48 Å
1.93 Å
12
(H2O)
Cu
P 12
3.86 Å
3.83 Å
12
(H2O)
Cu
H2CIP+ [Cu(H2CIP)(H2O)4]3+
Fig. S7 Optimal structures of the reactants (R), transition states (TS) and products (P) for the
C−F bond cleavage of H2CIP+ at the T state and [Cu(H2CIP)(H2O)4]3+ at the 4T state (Dark
gray: C; Blue: N; Red: O; Light gray: H; Light blue: F; Salmon pink: Cu. qF stands for the
atomic charges on atom F)
Supplementary Infromation
S7
R 10.00 Å
1.35 Å
qC12 = 0.27e
12
10.00 Å
1.34 Å (H2O)
Cu
qC12 = 0.13e
12
RC
2.26 Å2.49 Å
1.36 Å
2.67 Å
2.39 Å
1.35 Å (H2O)
Cu
TS1
2.37 Å
1.35
2.18 Å
1.36 Å
2.15 Å2.37 Å
1.35 Å (H2O)
Cu
IM
1.39 Å
1.47 Å
1.39 Å
1.45 Å(H2O)
Cu
TS2
1.95 Å
1.34 Å 1.33 Å
1.98 Å (H2O)
Cu
P
3.55 Å
1.35 Å
3.54 Å
1.33 Å
(H2O)
Cu
H2CIP+ [Cu(H2CIP)(H2O)4]3+
Fig. S8 Optimal structures of the reactants (R), reactant complexes (RC), transition states
(TS), intermediates (IM) and products (P) for the reactions of H2CIP+ at the T state and
[Cu(H2CIP)(H2O)4]3+ at the 4T state with OH− at its ground state (Dark gray: C; Blue: N; Red:
O; Light gray: H; Light blue: F; Salmon pink: Cu. qC12 stands for the atomic charges on C12)
Supplementary Infromation
S8
2 4.5 7.5 9.5 120.0
0.1
0.2
0.8
1.2
1.6
pH
k (h
-1)
CIP + EDTACIP + Cu(II) + EDTA
CIPCIP + Cu(II)
Fig. S9 Effects of pH, Cu(II) and EDTA on the apparent photolytic rate constants (k) of CIP in
aerated solutions, where [CIP]0 = 5 μmol/L, [Cu(II)] = 10 μmol/L, [EDTA] = 20 μmol/L and
the error bars represent the 95% confidence interval, n = 3
1.0
1.1
1.2
1.3
500502010
CIP + Ca(II)
k
(h-1
)
[Ca(II)] (μmol/L)
0
CIP + EDTA CIP + Ca(II) + EDTA
pH = 7.5
Fig. S10 Effects of Ca(II) and EDTA on the apparent photolytic rate constants (k) of CIP in
aerated solutions ([CIP]0 = 5 μmol/L, [EDTA] = 1 mmol/L. The error bars represent the 95%
confidence interval, n = 3)
Supplementary Infromation
S9
0 5 10 15 200.8
1.0
1.2
1.4 CIP + Fe(III)
k
(h-1
)
[Fe(III)] (μmol/L)
CIP + EDTA CIP + Fe(III) + EDTA
pH = 7.5
Fig. S11 Effects of Fe(III) and EDTA on the apparent photolytic rate constants (k) of CIP in
aerated solutions ([CIP]0 = 5 μmol/L, [EDTA] = 20 μmol/L. The error bars represent the 95%
confidence interval, n = 3)
Table S1 Main light absorption wavelength (λ, nm), orbital compositions, and oscillator
strengths of H2CIP+ and [Cu(H2CIP)(H2O)4]3+
λ (nm) Orbital Components* Oscillator Strengths
H2CIP+
322.3 H→L (0.59) 0.118
273.8 H→L+1 (0.66) 0.158
[Cu(H2CIP)(H2O)4]3+
315.5 H−1→H (0.69); H→L (0.68) 0.244
278.6 H−1→L+1 (0.62); H→L+1 (0.63) 0.106
*The main orbital components of the absorptions are given relative to the highest
occupied (H) and lowest unoccupied (L) molecular orbitals and their respective
contributions.
Supplementary Infromation
S10
Table S2 Accurate mass measurements determined by TOF mass spectrometer for CIP and its
photoproducts
Name Proposed formula
[M + H]+
Experimental
mass (m/z)
Calculated
mass (m/z)
Error
(ppm) DBE*
CIP C17H19FN3O3 332.1400 332.1405 1.50 10
P330 C17H20N3O4 330.1441 330.1448 2.23 10
P288 C15H18N3O3 288.1335 288.1343 2.67 9
P306 C15H17FN3O3 306.1243 306.1248 1.79 9
P334 C16H17FN3O4 334.1197 334.1198 0.18 10
P263 C13H12FN2O3 263.0825 263.0826 0.56 9
* DBE stands for double bond equivalents.
Table S3 Computed Gibbs free energy changes (ΔG, kcal/mol), enthalpy changes (ΔH,
kcal/mol) and activation free energies (ΔG‡, kcal/mol) for the defluorination reactions of
H2CIP+ and [Cu(H2CIP)(H2O)4]3+
ΔG
(kcal/mol)
ΔH
(kcal/mol)
ΔG‡
(kcal/mol)
Cleavage of the C−F Bonds
H2CIP+ −4.8 −2.8 27.3
[Cu(H2CIP)(H2O)4]3+ −1.4 −0.6 32.8
Defluorination caused by OH− Addition
H2CIP+ −68.8 −71.9 0.8, 6.0 *
[Cu(H2CIP)(H2O)4]3+ −51.0 −52.6 4.5, 10.8 *
* OH− addition reactions are stepwise. The two ΔG‡ values correspond to the process of OH−
attack and cleavage of C−F bond, respectively. Cleavage of C−F bond is a rate-limiting step.
Supplementary Infromation
S11
Table S4 Optimized geometries and Mulliken atomic charges of H2CIP+ and
[Cu(H2CIP)(H2O)4]3+ at ground state (Dark gray: C; Blue: N; Red: O; Light gray: H; Light
blue: F; Salmon pink: Cu)
Atom
Atomic Charges
1215
18
109
22
43
521
1411
H2CIP+
(H2O)
12
1518
Cu
109
22
4
32114
5
11
[Cu(H2CIP)(H2O)4]3+
C3 −0.24e 0.43e
C4 −0.33e −0.31e
N5 0.06e 0.12e
C9 −0.34e 0.20e
C10 1.06e 0.30e
C11 −0.04e −0.32e
C12 0.07e 0.08e
C14 −0.10e 0.08e
N15 −0.63e −0.68e
N18 −0.61e −0.59e
C21 −0.50e −0.25e
C22 −0.02e −0.40e