Journal of Chemistry
Volume 2015 (2015), Article ID 136285, 12 pages
http://dx.doi.org/10.1155/2015/136285

Research Article

Spectral Investigation and In Vitro Antibacterial Evaluation of NiII and CuII Complexes of Schiff Base Derived from Amoxicillin and α-Formylthiophene (αft)

Narendra Kumar Chaudhary and Parashuram Mishra

Bio-Inorganic and Materials Chemistry Research Laboratory, Tribhuvan University, M.M.A.M. Campus, Biratnagar 56613, Nepal

Received 3 October 2015; Accepted 8 November 2015

Academic Editor: Liviu Mitu

Copyright © 2015 Narendra Kumar Chaudhary and Parashuram Mishra. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract.

Two new metal complexes of general formula M(Haαft)₂ [M = and ] of asymmetrical Schiff base ligand (HL = Haαft) derived from amoxicillin and α-formylthiophene have been prepared and characterized by various physicochemical and spectral techniques. Molar conductance measurement indicates nonelectrolytic nature of the metal complexes. FT-IR spectral study reveals the ligation of metal ions at two different nitrogen [NN] donor sites of Haαft. FT-IR and electronic absorption spectral evidences suggest distorted tetrahedral and square planar geometry for and complexes, respectively. The structure optimization by molecular mechanics (MM) force field calculation through ArgusLab 4.0.1 version software also supports the concerned geometry of the complexes. The cell dimensions as suggested by XRPD study, (6.753 Å), (13.904 Å), (20.122 Å), α (142.76°), β (106.580°), and γ (72.4343°) for and (24.2547 Å), (6.6371 Å), (5.5047 Å) (α = β = γ = 90°) for complexes, are in good agreement with their triclinic and orthorhombic crystal systems. Particle size calculation by Scherrer’s formula indicates nanocrystalline nature of the complexes. The antibacterial sensitivity study suggests promising activities of Haαft (Ligand) and M(Haαft)₂ complexes against four clinical pathogenic bacteria, namely, E. coli, P. vulgaris, P. aeruginosa, and S. aureus, though being less active than the standard drug amikacin.

1. Introduction

Increasing threat of drug resistance caused by several microorganisms is today’s most debated public health concern. The development and modifications in the design of previous antibiotics, with new modes of action, requires intensive research to overcome these infections [1]. Schiff bases are the chemical compounds prepared by the condensation of active carbonyl groups with primary amines and have active azomethine linkage. Due to simplicity in preparation and wide range of applications in medical, biochemical, and industrial fields, Schiff bases are gaining much popularity in the recent years [2]. Presence of various coordination sites makes them as privileged ligands in the coordination chemistry of transition metals [3]. Schiff bases have important applications in the medical science as a potent antibacterial [4], antitumor [5], antiviral [6], and anti-inflammatory drugs [7]. The pharmacological activity of this class of compounds is often enhanced by complexation with metal ions. Serendipitous finding of cisplatin as a potent anticancer drug opened the gate of unexplored world of metal based chemotherapeutic agents [8, 9]. Recently, metal based drugs are gaining significant importance in medical sciences, due to their increased potentiality that actively interrupts the growth eager mechanism of microorganisms. The central metal ion in metal based drugs is usually the key feature of the mechanism of action. Several medical problems that arise due to free metal ion toxicity may be ameliorated by chelating agents like Schiff bases [10]. Amoxicillin is a very important class of β-lactamic antibiotic used in clinical therapy due to its specific toxicity towards bacterial pathogens [11]. Broad spectrum activity of amoxicillin is related to better oral absorption and high concentrations in blood compared to ampicillin which effectively works against bacteria. However, the failure in its antibacterial activity has been attributed to the formation of β-lactamase enzyme which hydrolyzes the β-lactam ring of the molecule [12]. Several research findings in the medical science put amoxicillin as an abortive drug and require modifications, either by changing the ligand property or by complexation with metal ions. With this expectation, metal complexes of amoxicillin derived Schiff base will be the new hope for better drug substance in clinical practices. In the present investigation, we report here the synthesis, spectral characterization, coordination behavior, X-ray powder diffraction study, and antibacterial evaluation of and complexes of Schiff base ligand (Haαft) derived from amoxicillin and α-formylthiophene. The work has been extended to assure the correct geometry by MM2 calculations supported in CsChemOffice 3D ultra and ArgusLab 4.0.1 version software.

2. Experimental Section

2.1. Materials

All the chemicals and solvents used in the experiment were of analytical reagent grade (AR). They included amoxicillin trihydrate (Duchefa Biochemie, Netherland), α-formylthiophene (Spectrochem, Mumbai, India), and metal salts, namely, NiCl₂6H₂O and CuCl₂2H₂O (Merck). Distilled methanol (Qualigen) was used as solvent for the synthesis. All the glassware used in the research was of high grade borosilicate glass and was cleaned by triple distilled water. For the antibacterial sensitivity study, the bacterial cultures were prepared in Muller Hinton’s nutrient agar media (Himedia Co.).

2.2. Measurements

The elemental microanalysis (C, H, and N) of the complexes was analyzed on Elementar vario EL III (Germany) model Analyzer. Double-check method was done to get the accuracy of the data. The pH measurement was done in Elico-16 pH meter. The electronic absorption spectra that reveal d-d and π-π and  n-π transitions of the ligand and its complexes were recorded in single beam microprocessor Labtronics UV-Vis. spectrophotometer (LT-290 model) using DMSO as the solvent and internal reference chemical in 200–800 nm range. Characteristic shifts in IR band positions had been analyzed by intimate observations of infrared spectra of ligand and metal complexes that were run as KBr discs in the range 4000–400 cm⁻¹ on a Perkin Elmer 783 FT-IR spectrophotometer. ¹H NMR spectra were recorded in DMSO-6 solvent on a Bruker advance 400 MHz instrument using TMS as internal reference. ESI-MS spectra were accomplished on Agilent 6520 Q-TOF mass spectrometer equipped with an electron spray ionization source in the mass range of 200 to 1100. The XRD powder pattern was recorded on a vertical type Philips PW 1130/00 X-ray diffractometer, operated at 40 kV and 50 Ma generator using the monochromatised Cu-Kα line at wavelength 1.54056 Å as the radiation source and measurements were taken over the range of 2θ (10 to 80°). Crystallographic data were analyzed by X′Pert High Score, CRYSFIRE, and CHECKCELL software programme. The powder XRD pattern of the ligand and metal complexes was recorded in Xpowder software. The possible geometries of the metal complexes were evaluated by using the molecular modeling calculation, optimized by CsChem 3D Utra-11 programme and ArgusLab 4.0.1 version software.

2.3. Synthesis of Ligand (HL = Haαft)

To the hot and homogenously stirred solution of amoxicillin trihydrate (5 mmol, 2.097 gm) in distilled methanol (30 mL), α-formylthiophene (5 mmol, 0.47 mL) was added dropwise with constant stirring and the resulting solution was refluxed for about 6 h. The pH of the amoxicillin trihydrate solution had been adjusted to 8 by dropwise addition of alcoholic NaOH solution [13]. The solution was concentrated and allowed to cool. The bright yellow solid product was separated by slow diffusion process, purified by recrystallization from hot methanol and dried under vacuum. The synthetic design for the preparation of ligand (HL) is presented in Scheme 1.

Scheme 1: Proposed route for the synthesis of ligand (HL).

2.4. Synthesis of Metal Complexes

In hot 30 mL methanolic solution of ligand (L) (4 mmol, 1.89 gm), 10 mL methanolic solution of the metal salts (2 mmol, 0.4752 gm NiCl₂6H₂O, and 0.34 gm CuCl₂2H₂O) was added dropwise under constant stirring over magnetic stirrer. The reaction mixture was refluxed for several hours under water bath and alternate stirring of the mixture was also done to facilitate the easy approach of ligand for coordination with metal ion. Colored solid complexes were formed on cooling the solution slowly at room temperature. The solid was filtered, washed with methanol, and dried under vacuum [14, 15]. The general structure of metal complex is presented in Figure 1:

where MX₂ is & chloride salts. HL is Ligand. -complex is Ni(Haαft)₂. -complex is Cu(Haαft)₂.

Figure 1: Structure of metal complex (M = Ni & Cu).

2.5. Antibacterial Assay

The experimental portion of antibacterial study was carried out in microbiology laboratory of MMAM campus Biratnagar. The ligand (HL) and its metal complexes were screened in vitro for antibacterial sensitivity study against three Gram-negative and one Gram-positive bacterial strains using modified Kirby-Bauer paper disc diffusion method [16]. Mueller-Hinton’s nutrient agar media were applied for the bacterial growth. Fresh cultures of standard bacteria, namely, Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa, and Staphylococcus aureus, were inoculated separately in five mL of tryptone soya broth, maintaining pH at 7.4 for better growth. The broth was incubated for 8 h at 37°C until visible growth changes to opaqueness. The broth was spread over nutrient agar media, prepared as usual in Petri plates using sterile stick swab and the well-sterilized paper discs of five mm diameter (Whatman number 1) impregnated with test compounds at two different concentrations, 1 and 0.1 μg/μL, in DMSO were stuck on the previously seeded bacterial culture [17]. The growth inhibition was compared with the standard drug amikacin of 30 μg per disc of six mm size (Himedia Co.). DMSO, which exhibited no antimicrobial activity against the test bacterial pathogens, was used as negative control. Afterwards, the Petri plates were incubated at 37°C and the inhibition of the growth of organisms, evidenced by clearing zone surrounding each disc, was measured by using antibiogram zone measuring scale, after 36 h of incubation [18].

3. Results and Discussion

The carboxylic acid group (-COOH) of amoxicillin undergoes esterification with methanol. Esterified amoxicillin now interacts with α-formylthiophene for the formation of ligand. The ligand was soluble in methanol and polar solvents like DMSO and DMF. The melting points of ligand (195°C) and metal complexes (>210°C) suggested that the complexes are more stable than the ligand and all of them are air and moisture stable. IR spectral measurements are completely consistent with the proposed formulation of the ligand and complexes.

3.1. Physical Data and Microelemental Analysis

The Schiff base ligand and its metal complexes were subjected to elemental analysis. The results of elemental analysis with molecular formula and other physical data like melting points and color change of the compounds are presented in Table 1. The results are in good agreement with suggested molecular formula. Sharp melting point of compounds indicates the purity of the prepared compounds [19].

Table 1: Elemental analysis and physical properties measurement data.

Compound
Mol. formula
Mol. wt.
Colour
m. pt. (°C)
Calculated (found) (%)
pH

C
H
N
O
S
M

HL
C₂₂H₂₃N₃O₅S₂
473.57
Bright yellow
195
55.80 (55.68)
4.90 (4.91)
8.87 (8.82)
16.89 (16.75)
13.54 (13.59)
—
4.97

Ni(Haαft)₂
C₄₄H₄₄N₆NiO₁₀S₄
1003.81
Brown
230
52.65 (52.67)
4.42 (4.421)
8.37 (8.29)
15.94 (15.87)
12.78 (12.75)
5.85 (5.94)
2.98

Cu(Haαft)₂
C₄₄H₄₄CuN₆O₁₀S₄
1008.66
Black
220
52.39 (52.50)
4.45 (4.55)
8.33 (8.21)
15.86 (15.81)
12.72 (12.80)
6.30 (6.15)
2.5

The change in color of the ligand and its metal complexes from the parent compounds used for their preparation is the good indication of formation via chemical reaction [20]. Complexation with metal ions exhibited drop down of pH values due to deprotonation of ligands. In our work, decrease in pH values from ligand to metal complexes also confirms complexation [21].

3.2. Spectral Analysis

3.2.1. FT-IR Analysis

The most significant IR spectral bands are presented in Table 2. The IR spectral data comparison of the reported complexes with those of the uncomplexed ligand provides valuable information about the coordination sites of the ligand. Shift in the positions of strong intensity band at 1661.56 cm⁻¹ characteristic for azomethine (HC=N) stretch for ligand to lower wave numbers 1652.09 and 1651.25 cm⁻¹ for and complexes, respectively, support the coordination of the azomethine nitrogen to the metal centre [22]. This fact is further substantiated by the appearance of new bands below 500 cm⁻¹ assignable for metal-nitrogen coordination. The medium intensity band at 448.82 cm⁻¹ is assignable for Cu-N stretch and similar band for complex appears at 470.18 cm⁻¹. There was no shift in band positions observed for the stretch of carboxylate group (-COO-), which appeared at 1515.18, 1514.20, and 1514.98 cm⁻¹ characteristic for ligand, , and complexes, respectively [23]. This indicates no involvement of carboxylate group for the coordination with metal ions. The negative band shift from 3485.12 cm⁻¹ assignable for N-H stretch in ligand provides good conformity for the coordination of metal ions with deprotonated nitrogen (NH) group of substituted amide [24]. M-N coordination mode is further ensured by the appearance of bands at 3423.36 and 3432.69 cm⁻¹ for and complexes, respectively. A weak sharp band observed at 1599.85 cm⁻¹ assignable for ν(C=O) lactam is restored in the metal complexes [25]. Lactam (C=O) stretch band in and complexes appeared at 1602.88 and 1601.89 cm⁻¹, respectively [26]. The bands in the range of 2961–2965 cm⁻¹ in all the synthesized compounds could be assigned for the C-H stretch of methyl group [27].

Table 2: Characteristic IR band positions (cm⁻¹) of ligand and metal complexes.

Compound
ν(NH)
ν(C=N)
ν(C=O) lactam
ν(CH₃)
ν(COO)
ν(M-N)

HL
3485.12 (br)
1661.56 (s)
1599.85
2965.69 (s)
1515.18
—

Ni(Haαft)₂
3432.69 (br)
1651.25 (s)
1601.89
2963.51 (s)
1514.98
470.18

Cu(Haαft)₂
3423.36 (br)
1652.09 (s)
1602.88
2961.96 (s)
1514.20
448.82

3.2.2. ¹H NMR Analysis

¹H NMR spectral comparison of novel ligand and its metal complexes was made to confirm the binding mode of ligand with metal ions. The ¹H NMR spectra of the ligand are shown in Figure 2 and the spectral data are summarized in Table 3. The ¹H NMR spectral peak at 2.5 ppm in the spectra of ligand is assignable to DMSO solvent protons. The peaks in the region of 0.9–1.4 ppm are suggesting the peak for methyl protons present in the amoxicillin moiety, near the lactam ring [28]. Although complex is diamagnetic, having square planar geometry, it offers nominal changes in the chemical shift values of different types of protons compared to the ligand. The azomethine proton appears as a singlet at 9.95 ppm for the ligand and at 10.038 ppm for complex [29]. All four aromatic protons as a set of two doublets appear in the range of 6.6–7.3 ppm. In addition to this, methyl protons of ester group produced by esterification of carboxylic acid group of amoxicillin with methanol show singlet in the region of 3.3–4.7 ppm [30]. Thiophene ring has three protons which appear as a multiplet in the region of 7.1–8.7 ppm in the spectrum of the ligand. The ligand showed a singlet peak at 8.5 ppm assignable to NH proton [31]. It is important to mention here that no clear appreciable changes in ¹H NMR spectrum had been reported for complex due to paramagnetic effects [32]. All these results indicated the participation of NH proton in the coordination process with metal ions.

Table 3: The ¹H NMR spectral data (δ, ppm) of ligand.

Compound
Chemical shift
δ ppm
Assignment

HL
6.7–7.0
2d, 4H, aromatic protons

9.95
s, 1H, azomethine protons

7.1–8.0
m, 3H, thiophene ring protons

0.9–1.4
s, 6H, methyl protons

3.4–4.1
s, 3H, CH₃ of ester group

8.5
s, 1H, NH proton

Figure 2: ¹H NMR spectrum of HL.

3.2.3. ¹³C NMR Analysis

The ¹³C NMR spectral data for novel ligand has been recorded in DMSO. The measured chemical shifts of all the carbon atoms, as numbered in the structure of novel ligand, are listed in Table 4. As given in Figure 3, the azomethine carbon signal for the ligand appears at 157.594 ppm [33]. The signal for the carbon of carbonyl group (C-3) appears at 172.668 ppm in the spectrum of ligand [34]. Aromatic carbons showed signals in the range of 115–145 ppm. The carbon signal at 170.8 ppm is attributed to lactam carbonyl carbon. Due to resonance effect in diamagnetic and paramagnetic nature of the mentioned metal complexes, there was no marked change in their ¹³C NMR spectra, compared to the ligand.

Table 4: The ¹³C NMR spectral data (δ, ppm) of the free ligand and metal complexes.

Ligand (HL)
Assignment
Chemical shift δ ppm

C-1
157.594

C-3
172.668

C-5
170.8

C-7
26.909

C-8
26.909

C-9
73.378

C-10
178.399

C-11
39.928

Ar-C
115.652, 121.217, 128.318, 129.44, 136.56, 138.423, 145.635

DMSO
39.65

Figure 3: ¹³C NMR spectrum of HL.

3.2.4. ESI-MS Analysis

The ESI mass spectrum of ligand (HL) offered a peak at m/z 473 amu corresponding to its molecular ion peak [M∙+] and it confirms the proposed molecular formula of the ligand. Other peaks in the mass spectrum of HL at m/z 459, 445, 353, 187, and 168 amu are the fragment peaks. Their intensities provide the idea of stability of the fragments. ESI mass spectrum of the complexes indicated the molecular ion peaks at m/z 1003 and 1008 amu characteristic for and complexes, respectively. The mass spectrum of ligand is presented in Figure 4.

Figure 4: Mass spectrum of ligand (HL).

3.2.5. X-Ray Powder Diffraction Study

The X-ray powder diffraction technique was carried to get useful crystal data information to deduce accurate cell parameters, crystal system, and the cell volume. Powder diffraction patterns of the ligand and metal complexes were recorded and crystallographic data are listed in Table 5. X-ray diffraction powder pattern of complex is shown in Figure 5. The crystallite size of the ligand and its metal complexes was calculated from Scherrer’s formula, , where λ is the wavelength, β is the full-width half maximum of the characteristic peak, and θ is the diffraction angle for the hkl plane [35, 36]. The diffractogram of ligand gave 13 reflection peaks with 100% intensity at = 26.7349°. Associated with this, the interplanar distance was = 3.3348 Å. The 26 reflections have been recorded for complex with maxima at = 26.0048° and interplanar distance = 3.4265 Å. Unit cell dimensions of ligand (15.009 Å), (20.077 Å), (20.060 Å), α (55.910°), β (65.330°), and γ (59.920°) confirm its triclinic crystal system. (6.753 Å), (13.904 Å), (20.122 Å), α (142.76°), β (106.580°), and γ (72.4343°) data for the complex also confirms triclinic crystal system. complex has unit cell dimensions (24.2547 Å), (6.6371 Å), and (5.5047 Å) (α = β = γ = 90°) and this confirms orthorhombic crystal system (Table 5). Particle size calculation data, 55.325, 85.451, and 75.231 nm for the ligand, , and complexes, respectively, revealed their nanocrystalline nature.

Table 5: Crystal data and structure refinement.

Compounds
HL
Ni(Haαft)₂
Cu(Haαft)₂

Formula
C₂₂H₂₃N₃O₅S₂
C₄₄H₄₄N₆NiO₁₀S₄
C₄₄H₄₄CuN₆O₁₀S₄

FW
473.57
1003.81
1008.66

Temp (K)
298
298
298

Wavelength
1.54056
1.54056
1.54056

Crystal system
Triclinic
Tetragonal
Triclinic

Space group
P1
P/4 mm
P

Unit cell dimension

(Å)
15.009
24.2547
6.753

(Å)
20.077
6.6371
13.904

(Å)
20.060
5.5047
20.122

55.910
90
142.76

65.330
90
106.580

59.920
90
72.4343

Volume (A³)
4295.95
859.4463
1047.72

θ range (°)
5–75
5–75
5–75

Limiting indices
− 

Particle size (nm)
55.325
75.231
85.451

Figure 5: Powder XRD pattern of Cu(Haαft)₂.

3.2.6. Molar Conductance and Magnetic Properties of the Complexes

Molar conductance values of the soluble complexes in DMSO (1 × 10⁻³ M) at room temperature vary from 5.1 to 20.1 Ω⁻¹ cm² mol⁻¹ revealing their nonelectrolytic nature. The observed range is below 50 Ω⁻¹ cm² mol⁻¹ characteristic for nonelectrolytes [37]. The room temperature magnetic moments for tetra coordinated and complexes indicate their respective diamagnetic and paramagnetic nature. complex has observed magnetic moment value 0 BM, which is consistent with its square planar geometry, using dsp² hybridization in the coordination process. complex in a distorted tetrahedral geometry has observed magnetic moment value = 1.84 BM, which is greater than the theoretical spin only magnetic moment value, = 1.73 BM. This is considered possibly due to orbital contribution that sum up in the spin interaction magnetic momentum [38]. The Jahn-Teller distortion effect in the complex forced it to acquire distorted tetrahedral geometry.

3.2.7. Electronic Absorption Spectra

The electronic spectra of the Schiff base ligand and its metal complexes were recorded in DMSO solution and are presented in Table 6. The absorption peaks at the region of 361 and 391 nm of high intensity for ligand are attributable to intraligand transitions of azomethine and lactam carbonyl group [39, 40]. Similar peaks at 268 and 310 nm for the ligand are assignable to intraligand transitions. These peaks are still present in and complexes, but slightly shifted from the ligand peaks. The complexes of and show the low intensity bands in the visible region at 465 and 450 nm, respectively, which are assignable to the and transitions for ligand metal charge transfer band [41]. The electronic spectrum of the complex exhibits a single band at 520 nm which may be assignable to the , d-d transition typical for the square planar geometry [42]. As this d-d transition is a high energy process, it may probably confirm its square planar geometry. The lack of any electronic transitions at higher wavelengths indicates large crystal field splitting and is consistent with the said geometry for the complex [43]. Absence of d-d transition band in the spectra of complex probably indicates distorted tetrahedral geometry, which is also supported by other spectral studies.

Table 6: The relative peak positions () of the free ligand and metal complexes.

Compound
Peak positions () in nm

transitions
transitions
LMCT band
d-d transition

HL
310–268
391, 361
—
—

Ni(Haαft)₂
307, 272
391, 370
465
520

Cu(Haαft)₂
285
370
450
—

3.3. Antibacterial Sensitivity Study

The pure metals are considered biologically inactive. However, the activity of metal cations depends on their bioavailability and the presence of bioligands [44]. It was, therefore, of great interest to investigate antibacterial activity of Schiff base and its transition metal complexes against some bacterial pathogens. Here, four clinical bacterial pathogens, namely, Escherichia coli, Proteus vulgaris, Pseudomonas aeruginosa (Gram-negative), and Staphylococcus aureus (Gram-positive), have been focused on for the microbiological interaction with the synthesized compounds.

In the present work, the antibacterial activity results presented in Table 7 show that the ligand (HL) and its two metal complexes exhibit potential biological activity. Two different concentrations of the compounds have been selected for the biological interactions with bacterial pathogens. They show increased bactericidal effect at higher concentrations. The graphical charts of the comparable antibacterial sensitivity study of the synthesized compounds are presented in Figures 6 and 7. The results demonstrate better antibacterial activity of metal complexes compared to the free ligand. The azomethine group present in the ligand may be the cause for its remarkable activity. The enhancement in the activity of metal complexes is considered due to coordination of metal ions with the donor sites of ligand that might inhibit the enzyme production, which is suitable for the bacterial growth. The chelation makes the compound lipophilic due to partial sharing of positive charge and π-electrons delocalization within the whole chelate ring [45–47]. This increased lipophilicity enhances the ability of complexes for permeation through the lipid layer of the cell membrane and blocks the metal binding sites in enzymes of the microorganisms. These complexes also disturb the respiration process of the cell and this freezes the synthesis of proteins, which restricts further growth of the organisms [48]. The data also reveals that the activity of free ligand and metal complexes is lesser than standard drug amikacin. Overall comparison of observed data gave information that metal complexes are more active than the free ligand against all bacteria. However, they show better inhibitory effect with S. aureus compared to other bacterial pathogens. The variation in the effectiveness of different compounds against different bacterial pathogens depends on the impermeability through the cell membrane of microorganisms.

Table 7: Antibacterial sensitivity of synthesized compounds.

Compounds
Conc.
Diameter of zone of inhibition in (mm)

(μg/μL)
E. coli
P. vulgaris
P. aeruginosa
S. aureus

L
1
0.5
9
8
10
8
10
9
12
10

Ni(Haαft)₂
1
0.5
12
9
12
10
14
11
15
12

Cu(Haαft)₂
1
0.5
11
9
14
12
13
11
14
11

DMSO

0
0
0
0

Standard

19
18
18
20

Figure 6: Antibacterial sensitivity at the concentration of 1 μg/μL.

Figure 7: Antibacterial sensitivity at the concentration of 0.5 μg/μL.

3.4. Molecular Modeling Analysis

To provide clear and deep perception of the geometry of the ligand and metal complexes, molecular modeling has been carried out by using molecular mechanics and Hartree-Fock (HF) quantum mechanics calculations. The geometry optimization was done by Universal Force Field (UFF) with minimum RMS gradient 0.100, supported in ArgusLab programme [49]. Single point energy calculation of the ligand through Hartree-Fock SCF computation with maximum iteration 200 and convergence rate 10⁻¹⁰ kcal/mol reveals the final SCF energy −121796.5370 kcal/mol and heat of formation −78.0985 kcal/mol. After the geometry optimization by UFF (molecular mechanics) technique, the final geometrical energy of the ligand has been computed to 161.2699 kcal/mol and this provides stability of the molecule [50, 51]. The surface structure of the ligand has been computed through HOMO and LUMO plot. Similar study with the and complexes has assured their final geometrical energy 449.0564 and 752.1825 kcal/mol, respectively. The optimized structures of the metal complexes are presented in Figures 8 and 9 and they reveal square planar geometry for and tetrahedral geometry for complexes. The computational findings are in good support of the proposed structures of the complexes. The selected bond lengths, bond angles, and bond energies of the ligand and metal complexes are given in Tables 8(a)–8(f).

Table 8: (a) Selected bond lengths and bond energies of ligand (HL). (b) Selected bond angles and bond energies of ligand (HL). (c) Selected bond lengths and bond energies of Ni-complex. (d) Selected bond angles and bond energies of Ni-complex. (e) Selected bond lengths and bond energies of Cu-complex. (f) Selected bond angles and bond energies of Cu-complex.

(a)

Bond type
Bond lengths (Å)
Bond energy (kcal/mol)

C₈-N₁₅
1.447
532.154

N₁₅-C₁₆
1.291
749.036

C₁₆-C₁₇
1.464
386.878

C₈-C₂₂
1.489
367.716

C₂₂-N₂₃
1.437
543.390

N₂₃-C₂₄
1.462
515.889

(b)

Bond type
Bond angle (°)
Bond energy (kcal/mol)

C₈-N₁₅-C₁₆
120.00
226.230

N₁₅-C₈-C₂₂
109.47
312.267

N₁₅-C₁₆-C₁₇
120.00
295.502

N₁₅-C₈-H₁₄
109.47
169.990

C₂₂-N₂₃-C₂₄
106.70
261.205

N₂₃-C₂₂-O₂₅
120.00
378.598

(c)

Bond type
Bond lengths (Å)
Bond energy (kcal/mol)

Ni₁-N₂
1.885
306.275

Ni₁-N₃
1.885
306.275

Ni₁-N₄
1.870
313.824

Ni₁-N₅
1.870
313.824

(d)

Bond type
Bond angle (°)
Bond energy (kcal/mol)

N₂-Ni₁-N₃
90.00
340.090

N₂-Ni₁-N₄
90.00
344.228

N₂-Ni₁-N₅
90.00
344.228

Ni₁-N₂-C₉
106.00
212.735

Ni₁-N₂-C₂₄
106.00
208.934

N₃-Ni₁-N₄
90.00
344.228

N₃-Ni₁-N₅
90.00
344.228

N₄-Ni₁-N₅
90.00
348.473

(e)

Bond type
Bond lengths (Å)
Bond energy (kcal/mol)

Cu₁-N₂
2.031
176.938

Cu₁-N₃
2.031
176.938

Cu₁-N₄
2.016
181.007

Cu₁-N₅
2.016
181.007

(f)

Bond type
Bond angle (°)
Bond energy (kcal/mol)

N₂-Cu₁-N₃
109.47
156.977

N₂-Cu₁-N₄
109.47
158.764

N₂-Cu₁-N₅
109.47
158.764

Cu₁-N₂-C₉
106.70
132.072

Cu₁-N₂-C₂₄
106.70
129.991

N₃-Cu₁-N₄
109.47
158.764

N₃-Cu₁-N₅
109.47
158.764

N₄-Cu₁-N₅
109.47
160.587

Figure 8: Molecular modeling structure of Ni(Haαft)₂.

Figure 9: Molecular modeling structure of Cu(Haαft)₂.

4. Conclusion

The present study focuses the microbiological interaction of prepared compounds against clinically important bacterial pathogens. The antibacterial sensitivity data of the compounds presented in this report allowed us to state that the metal complexes have generally better antibacterial activity than uncomplexed ligand, but less active than control drug. The electronic absorption spectral study reveals d-d transition band at 520 nm for complex and this high energy process suggests its square planar geometry. The charge transfer band for complex at 450 nm indicates its tetrahedral geometry. X-ray powder diffraction study reveals triclinic crystal system for the ligand and complex, while it is trigonal crystal system for complex. The particle size calculation by Scherrer’s formula indicates their nanocrystalline nature. The ESI-MS study that provided molecular mass of the ligand and metal complexes truly confirms the ML₂ type of complexes. The FT-IR, ¹H NMR, and ¹³C NMR spectral results are also in good agreement with the proposed molecular and structural formula of the ligand and its metal complexes. The change in pH value occurring in the reaction process greatly supports the deprotonation during complex formation which is further supported by the change in their colors. The sharp melting point of the compounds gives the evidence of purity of the synthesized compounds.

Conflict of Interests

The authors declare no conflict of interests.

Authors’ Contribution

The author Narendra Kumar Chaudhary prepared the paper and designed the whole experimental analysis. The author Parashuram Mishra performed molecular modeling study and proofreading of the final paper.

Acknowledgment

Narendra Kumar Chaudhary would like to acknowledge the University Grants Commission, Nepal, for making this research project successful towards completion by providing financial support.

References

M. S. Butler, M. A. Blaskovich, and M. A. Cooper, “Antibiotics in the clinical pipeline in 2013,” The Journal of Antibiotics, vol. 66, no. 10, pp. 571–591, 2013.

K. Shoaib, W. Rehman, B. Mohammad, and S. Ali, “Synthesis, characterization and biological applications of transition metal complexes of [no] donor schiff bases,” Journal of Proteomics & Bioinformatics, vol. 6, no. 7, pp. 153–157, 2013.

S. M. Saadeh, “Synthesis, characterization and biological properties of Co(II), Ni(II), Cu(II) and Zn(II) complexes with an SNO functionalized ligand,” Arabian Journal of Chemistry, vol. 6, no. 2, pp. 191–196, 2013.

A. A. Osowole and S. A. Balogun, “Spectral, magnetic, thermal and antibacterial properties of some metal (II) complexes of aminoindanyl Schiff base,” European Journal of Applied Sciences, vol. 4, no. 1, pp. 6–13, 2012.

N. Raman, R. Jeyamurugan, R. Senthilkumar, B. Rajkapoor, and S. G. Franzblau, “In vivo and in vitro evaluation of highly specific thiolate carrier group copper(II) and zinc(II) complexes on Ehrlich ascites carcinoma tumor model,” European Journal of Medicinal Chemistry, vol. 45, no. 11, pp. 5438–5451, 2010.

E. Yousif, A. Majeed, K. Al-Sammarrae, N. Salih, J. Salimon, and B. Abdullah, “Metal complexes of Schiff base: preparation, characterization and antibacterial activity,” Arabian Journal of Chemistry, 2013.

C. J. Dhanaraj and M. S. Nair, “Synthesis, characterization, and antimicrobial studies of some Schiff-base metal(II) complexes,” Journal of Coordination Chemistry, vol. 62, no. 24, pp. 4018–4028, 2009.

N. Muhammad and Z. Guo, “Metal-based anticancer chemotherapeutic agents,” Current Opinion in Chemical Biology, vol. 19, no. 1, pp. 144–153, 2014.

Y. Wang and J.-F. Chiu, “Proteomic approaches in understanding action mechanisms of metal-based anticancer drugs,” Metal-Based Drugs, vol. 2008, Article ID 716329, 9 pages, 2008.

N. Farrell, “Metal complexes as drugs and chemotherapeutic agents,” in Comprehensive Coordination Chemistry II, vol. 9, pp. 809–840, Elsevier, 2003.

R. Di Stefano, M. Scopelliti, C. Pellerito et al., “Organometallic complexes with biological molecules: XVII. Triorganotin(IV) complexes with amoxicillin and ampicillin,” Journal of Inorganic Biochemistry, vol. 89, no. 3-4, pp. 279–292, 2002.

A. R. White, C. Kaye, J. Poupard, R. Pypstra, G. Woodnutt, and B. Wynne, “Augmentin (amoxicillin/clavulanate) in the treatment of community-acquired respiratory tract infection: a review of the continuing development of an antimicrobial agent,” Journal of Antimicrobial Chemotherapy, vol. 53, supplement 1, pp. i3–i20, 2004.

M. Usharani, E. Akila, and R. Rajavel, “Synthesis and spectral investigations of binuclear Schiff base metal complexes derived from 1,5-diaminonaphthalene,” Journal of Chemical , Biological and Physical Sciences, vol. 2, no. 2, pp. 677–682, 2012.

H. N. Aliyu and A. S. Mohammed, “Synthesis, spectrophotometric and biological activity of nickel(II) and copper(II) complexes with schiff base derived from acetylacetone and histidine,” Global Advanced Research Journal of Microbiology, vol. 1, no. 5, pp. 67–71, 2012.

M. Amirnasr, A. H. Mahmoudkhani, A. Gorji, S. Dehghanpour, and H. R. Bijanzadeh, “Cobalt(II), nickel(II), and zinc(II) complexes with bidentate N,N ′-bis(β-phenylcinnamaldehyde)-1,2-diiminoethane Schiff base: synthesis and structures,” Polyhedron, vol. 21, no. 27-28, pp. 2733–2742, 2002.

N. K. Chaudhary and P. Mishra, “Synthesis, structure delineation and antibacterial activity study of metal (II) complexes of schiff base derived from kanamycin and methyl ester of amoxicillin,” International Research Journal of Pure and Applied Chemistry, vol. 7, no. 4, pp. 165–180, 2015.

J. Lv, T. Liu, S. Cai, X. Wang, L. Liu, and Y. Wang, “Synthesis, structure and biological activity of cobalt(II) and copper(II) complexes of valine-derived schiff bases,” Journal of Inorganic Biochemistry, vol. 100, no. 11, pp. 1888–1896, 2006.

G. G. Mohamed, M. A. Zayed, and S. M. Abdallah, “Metal complexes of a novel Schiff base derived from sulphametrole and varelaldehyde. Synthesis, spectral, thermal characterization and biological activity,” Journal of Molecular Structure, vol. 979, no. 1–3, pp. 62–71, 2010.

M. S. Iqbal, I. H. Bukhari, and M. Arif, “Preparation, characterization and biological evaluation of copper(II) and zinc(II) complexes with Schiff bases derived from amoxicillin and cephalexin,” Applied Organometallic Chemistry, vol. 19, no. 7, pp. 864–869, 2005.

S. K. Bharti, S. K. Patel, G. Nath, R. Tilak, and S. K. Singh, “Synthesis, characterization, DNA cleavage and in vitro antimicrobial activities of copper(II) complexes of Schiff bases containing a 2,4-disubstituted thiazole,” Transition Metal Chemistry, vol. 35, no. 8, pp. 917–925, 2010.

A. K. Mapari and K. V. Mangaonkar, “Synthesis, characterization and antimicrobial activity of mixed Schiff base ligand complexes of transition metal (II) ions,” International Journal of ChemTech Research, vol. 3, no. 1, pp. 477–482, 2011.

M. S. Nair, D. Arish, and R. S. Joseyphus, “Synthesis, characterization, antifungal, antibacterial and DNA cleavage studies of some heterocyclic Schiff base metal complexes,” Journal of Saudi Chemical Society, vol. 16, no. 1, pp. 83–88, 2012.

S. M. Abdallah, M. A. Zayed, and G. G. Mohamed, “Synthesis and spectroscopic characterization of new tetradentate Schiff base and its coordination compounds of NOON donor atoms and their antibacterial and antifungal activity,” Arabian Journal of Chemistry, vol. 3, no. 2, pp. 103–113, 2010.

F. Rahaman and B. H. M. Mruthyunjayaswamy, “Synthesis, spectral characterization and biological activity studies of transition metal complexes of Schiff base ligand containing indole moiety,” Complex Metals, vol. 1, no. 1, pp. 88–95, 2014.

H. S. Seleem, “Transition metal complexes of an isatinic quinolyl hydrazone,” Chemistry Central Journal, vol. 5, no. 1, article 35, 2011.

M. Al-Jibouri and S. Hasun, “Synthesis, characterization and biological activity of chromium(III), manganese(II), cobalt(II), nickel(II), copper(II) and zinc(II) complexes with new Schiff base derived from 6-methylquinoxaline-2, 3(1H,4H)-dione and diethylenetriamine,” International Research Journal of Pure and Applied Chemistry, vol. 6, no. 4, pp. 147–159, 2015.

J. Coates, “Interpretation of infrared spectra, a practical approach,” in Encyclopedia of Analytical Chemistry, pp. 10815–10837, John Wiley & Sons, Chichester, UK, 2000.

M. A. Zayed and S. M. Abdallah, “Synthesis and structure investigation of the antibiotic amoxicillin complexes of d-block elements,” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 61, no. 9, pp. 2231–2238, 2005.

M. Asadi, S. Torabi, and K. Mohammadi, “Synthesis, characterization, and thermodynamics of some new unsymmetrical Schiff bases of salicylaldehyde with 3,4-diaminopyridine and their cobalt(III) complexes,” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 122, pp. 676–681, 2014.

H. Bayrak, A. Demirbas, S. A. Karaoglu, and N. Demirbas, “Synthesis of some new 1,2,4-triazoles, their Mannich and Schiff bases and evaluation of their antimicrobial activities,” European Journal of Medicinal Chemistry, vol. 44, no. 3, pp. 1057–1066, 2009.

H. L. Singh and J. B. Singh, “Synthesis and characterization of new lead(II) and organotin(IV) complexes of schiff bases derived from histidine and methionine,” International Journal of Inorganic Chemistry, vol. 2012, Article ID 568797, 7 pages, 2012.

I. M. Mustafa, M. A. Hapipah, M. A. Abdulla, and T. R. Ward, “Synthesis, structural characterization, and anti-ulcerogenic activity of schiff base ligands derived from tryptamine and 5-chloro, 5-nitro, 3,5-ditertiarybutyl salicylaldehyde and their nickel(II), copper(II), and zinc(II) complexes,” Polyhedron, vol. 28, no. 18, pp. 3993–3998, 2009.

M. K. Gupta, H. L. Singh, S. Varshney, and A. K. Varshney, “Synthetic and spectroscopic characterization of organotin(IV) complexes of biologically active Schiff bases derived from sulpha drugs,” Bioinorganic Chemistry and Applications, vol. 1, no. 3-4, pp. 309–320, 2003.

P. Ossowicz, E. Janus, G. Schroeder, and Z. Rozwadowski, “Spectroscopic studies of amino acid ionic liquid-supported Schiff bases,” Molecules, vol. 18, no. 5, pp. 4986–5004, 2013.

C. Leelavathy and S. A. Antony, “Synthesis, spectral characterization and biological activity of metal(II) complexes with 4-aminoantipyrine derivatives,” Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, vol. 113, pp. 346–355, 2013.

R. S. Joseyphus and M. S. Nair, “Synthesis, characterization and biological studies of some Co(II), Ni(II) and Cu(II) complexes derived from indole-3-carboxaldehyde and glycylglycine as Schiff base ligand,” Arabian Journal of Chemistry, vol. 3, no. 4, pp. 195–204, 2010.

U. El-Ayaan and A. A.-M. Abdel-Aziz, “Synthesis, antimicrobial activity and molecular modeling of cobalt and nickel complexes containing the bulky ligand: Bis[N-(2,6-diisopropylphenyl)imino] acenaphthene,” European Journal of Medicinal Chemistry, vol. 40, no. 12, pp. 1214–1221, 2005.

M. Rajasekar, S. Sreedaran, R. Prabu et al., “Synthesis, characterization, and antimicrobial activities of nickel(II) and copper(II) Schiff-base complexes,” Journal of Coordination Chemistry, vol. 63, no. 1, pp. 136–146, 2010.

F. Esmadi, O. F. Khabour, A. I. Albarqawi, M. Ababneh, and M. Al-Talib, “Synthesis and characterization of some transition metal complexes of thiocarbohydrazone schiff bases,” Jordan Journal of Chemistry, vol. 8, no. 1, pp. 31–43, 2013.

J. R. Anacona and J. Diaz, “Synthesis, characterization and superoxide dismutase activity of the manganese (II) mixed ligand complexes containing sulfathiazole,” Journal of the Chilean Chemical Society, vol. 53, no. 4, pp. 1702–1704, 2008.

G. G. Mohamed, M. M. Omar, and A. M. Hindy, “Metal complexes of Schiff bases: preparation, characterization, and biological activity,” Turkish Journal of Chemistry, vol. 30, no. 3, pp. 361–382, 2006.

D. Nasrin, M. A. Alam, I. M. M. Rahman, H. Banu, and M. Nazimuddin, “Synthesis, characterization and antimicrobial activity of some metal complexes with schiff base containging O, N and S as the donor atoms,” International Journal of Applied and Natural Sciences, vol. 2, no. 1, pp. 1–8, 2013.

M. I. Ayad and H. A. El-Boraey, “Characterization, thermal and electrical conductivity of some transition metal adducts,” International Journal of ChemTech Research, vol. 6, no. 1, pp. 266–275, 2014.

A. M. Farag, T. S. Guan, H. Osman, A. M. S. A. Majid, M. A. Iqbal, and M. B. K. Ahamed, “Synthesis of metal(II) [M = Cu, Mn, Zn] schiff base complexes and their pro-apoptotic activity in liver tumor cells via caspase activation,” Medicinal Chemistry Research, vol. 22, no. 10, pp. 4727–4736, 2013.

E. L. Chang, C. Simmers, and D. Andrew Knight, “Cobalt complexes as antiviral and antibacterial agents,” Pharmaceuticals, vol. 3, no. 6, pp. 1711–1728, 2010.

I. Kostova and L. Saso, “Advances in research of Schiff-base metal complexes as potent antioxidants,” Current Medicinal Chemistry, vol. 20, no. 36, pp. 4609–4632, 2013.

M. Sunitha, P. Jogi, Ushaiah, and C. Gyanakumari, “Synthesis, structural characterization, molecular modelling and antimicrobial studies of transition metal complexes of Schiff base ligand derived from 5-chlorosalicylaldehyde and 2-(2-aminophenyl) 1H-benzimidazole,” Journal of Chemical and Pharmaceutical Research, vol. 4, no. 3, pp. 1553–1561, 2012.

N. Mahalakshmi and R. Rajavel, “Synthesis, spectroscopic, DNA cleavage and antibacterial activity of binuclear Schiff base complexes,” Arabian Journal of Chemistry, vol. 7, no. 4, pp. 509–517, 2014.

B. B. Mahapatra, R. R. Mishra, and A. K. Sarangi, “Synthesis, characterisation, XRD, molecular modelling and potential antibacterial studies of Co(II), Ni(II), Cu(II), Zn(II), Cd(II) and Hg(II) complexes with bidentate azodye ligand,” Journal of Saudi Chemical Society, 2013.

T. Wróbel, U. Kosikowska, A. Kaczor et al., “Synthesis, structural studies and molecular modelling of a novel imidazoline derivative with antifungal activity,” Molecules, vol. 20, no. 8, pp. 14761–14776, 2015.

E. Akila, M. Usharani, S. Vimala, and R. Rajavel, “Synthesis, spectroscopic characterization and biological evaluation studies of mixed ligand schiff base with metal (II) complexes derived from o-phenylenediamine,” Chemical Science Review and Letters, vol. 1, no. 4, pp. 181–194, 2012.