# Synthesis, Spectroscopic Characterization, Molecular Docking, and Evaluation of Antibacterial Potential of Transition Metal Complexes Obtained Using Triazole Chelating Ligand

Authors: Najlaa S. Al-Radadi; Ehab M. Zayed; Gehad G. Mohamed; Hayam A. Abd El Salam
Journal: Journal of Chemistry
 (2020)

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## Abstract

Mononuclear chelates of Ni(II), Co(II), Fe(III), Cd(II), and Cu(II) derived from triazole novel tridentate ligands were prepared and characterized by different spectroscopic methods. The metal to ligand ratio was 1 : 2, which was revealed by elemental analysis. All the complexes were electrolytic in nature as suggested by the conductivity measurements. IR pointed out that the coordination of the triazole ligand toward the metal ions was carried out through N amino and S thiophenolic atoms. The complexes were found to have octahedral geometry, and their thermal stability was also studied. The XRD spectrum of Co(II) and Fe(III) complexes concluded their crystalline structure. The parent ligand and its chelates were investigated for antimicrobial potential. Bioassay of all triazole complexes showed increased activity as compared to that of the ligand. The complexes having Ni(II), Co(II), and Cu(II) ions as metal center exhibited superior antibacterial activity in opposition to Gram-positive (B. subtilis and S. pyogenes) and Gram-negative (E. coli and P. vulgaris) bacterium as compared to standard.


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## Body

## 1. Introduction

The complexes exhibiting photoluminescence acquire much attention and interest, being utilized for different applications including biological probes, oxygen sensors, and phosphorescent dopants in optoelectronic apparatus [1, 2]. In modern coordination chemistry, compounds which have cyclic imines are of great importance in forming stable complexes with some transition metal ions [3, 4]. Triazole compounds with some transition metals showed significant antibacterial, antitumor, and antifungal activity besides effective antiviral agents [5–8]. We find the metal complexes of ligands which have S,N-heterocycles promising for enhanced biological activities compared to the native ligand [9]. The preparation of metal complexes containing 1,2,4-triazole ligands has good application in recent years [10–14]. A lot of transition metal complexes of 1,2,4-triazoles substituted can be prepared [15]. The 1,2,4-triazoles have been explored for linking ligands among transition metal ions. The target for the linking can be from first N to second N (N1 to N2) atoms. In recent years, preparing coordination ligands using 1,2,4-triazole moiety acquired great attention [16]. A variety of derivatives of 1,2,4-triazole in addition to its own complexes was reported as an excellent compound for constructing many metal coordination polymers [17–21]. Fatty acids containing nitrogen derivatives have good attention recently because of their high biological activity [22].From the above discussion and mentioned facts, our idea was to enhance access to pharmacologically interesting complexes depending on their derivatives with selected metallic cations considered as important feed stocks for the chemical industry with promise of potential advance. In present study we discuss the preparation, characterization, and antibacterial study relating to Ni(II), Cu(II), Fe(III), Cd(II), and Co(II) complexes of 4-amino-5-stearyl-1,2,4-triazole-3-thiol (HL). In the current work, the synthesis of bidentate triazole ligand and its monomeric metal complexes in the company relating to Cd(II), Co(II), Fe(III), Cu(II), and Ni(II) ions is demonstrated. The synthesized complexes were analyzed through state-of-the-art physicochemical techniques including NMR, IR, and EDS and screened for antibacterial potential against some pathogenic species.


## 2. Materials and Methods

All analytical grade reagents having utmost purity were utilized in this work. The ranges of chemicals were CuCl2·2H2O procured from Sigma; COCl2·6H2O, CdCl2·2H2O, and NiCl2·6H2O from BDH; and FeCl3·6H2O from Prolabo. The organic solvents were absolute ethyl alcohol and dimethylformamide (DMF), and they were observed spectroscopically and cleaned using BDH. Every preparation was made in double-distilled water.


### 2.1. Instrumentation

A Jenway 4010 conductivity meter was utilized to record the molar conductance of solid chelates in DMF, while the solid reflectance spectra were recorded using a Shimadzu 3101pc spectrophotometer.ExtensivelH-NMR spectra beginning 0 to 15 ppm recorded on Varian-Oxford Mercury were operated at 300 MHz. The samples for lH-NMR spectra were prepared in DMSod6 (deuterated dimethylsulfoxide). For powder XRD analysis, BV XRD spectrometer from Philips Analytical type PW 1840 controlled at 40 kV plus 25 mA applying 2000 W radiation via copper anode was used. Faraday method was applied for molar magnetic susceptibility analysis of powdered samples. Pascal’s constant diamagnetic corrections were done while calibrations were performed using Hg[Co(SCN)4]. FTIR spectrum was taken among 4000–200 cm−1 using PerkinElmer FTIR type 1650 spectrophotometer by preparing KBr pellets.CHNS-932 (LECO) Vario elemental analyzer was used to analyze the separated solid chelates in duplicate for presence of C, H, N, S, and Cl at Microanalytical Center, Cairo University.Mass spectra were taken on MS-5988 GS-MS HP spectrometer controlled on 70 eV via EI technique at Microanalytical Center, Cairo University. Considering thermal analyses (TG, DTG, and DTA) Shimadzu TG-60 H simultaneous DTA-TG apparatus was used in dynamic nitrogen (20 mL·min−1) atmosphere having 10°C·min−1 rate of heating.


### 2.2. Metal Complexes Synthesis

To a solution of the triazole ligand (0.3 g, 0.847 mM) in ethanol (30 cm3), a solution containing metal (II)/(III) chloride (0.847 mM) in ethanol (15 cm3) was added. Mixed solution was refluxed using a water bath as long as 3 h whereupon the complexes were going to precipitate. The collected precipitate was filtered, clean washing was done using ethanol and diethyl ether, and it was vacuum-dried for later experiments.


### 2.3. [Cu(HL)2(H2O)2]Cl2

Yield 75%; brown solid, Anal. Calcd. for C38H80Cl2CuN8O2S2 (%): C, 51.90; H, 8.85; N, 12.88; S, 6.95; Cu, 6.75. Found (%): C, 51.88; H, 9.17; N, 12.74; S, 7.29; M, 7.22. IR (ν, cm−1): 2755 sh (C-SH), 1630 sh (N-NH2), 830 sh coordinated H2O, 566 s (Cu-O), 447s (Cu-N), 430 s (Cu-S).


### 2.4. [Cd(HL)2(H2O)2]Cl2

Yield 85%; dark green, Anal. Calcd. for C38H80CdCl2N8O2S2 (%): C, 48.88; H, 8.23; N, 12.45; S, 6.55; Cu, 11.76. Found (%): C, 49.15; H, 8.68; N, 12.07; S, 6.91; M, 12.11. IR (ν, cm−1): 2770 sh (C-SH), 1634sh (N-NH2), 740 s coordinated H2O, 565 s (Cd-O), 465 w (Cd-N), 438 s (Cd-S).


### 2.5. [Fe(HL)2(H2O)2]Cl3

Yield 87%; green, Anal. Calcd. for C38H80FeCl3N8O2S2 (%): C, 50.13; H, 8.63; N, 11.54; S, 6.62; Fe, 5.86. Found (%): C, 50.30; H, 8.89; N, 12.35; S, 7.07; M, 6.15. IR (ν, cm−1): 2730 sh (C-SH), 1640 s (N-NH2), 766 sh coordinated H2O, 560 s (Fe-O), 525 s (Fe-N), 462 w (Fe-S).


### 2.6. [Ni(HL)2(H2O)2]Cl2

Yield 82%; pale brown, Anal. Calcd. for C38H80NiCl2N8O2S2 (%): C, 51.69; H, 8.88; N, 13.71; S, 6.90; Ni, 6.45. Found (%): C, 52.17; H, 9.22; N, 12.81; S, 7.33; Ni, 6.71. IR (ν, cm−1): 2780 sh (C-SH), 1625 sh (N-NH2), 835 w coordinated H2O, 580 s (Ni-O), 530 s (Ni-N), 446 sh (Ni-S).


### 2.7. [Co(HL)2(H2O)2]Cl2

Yield 63%; dark blue, Anal. Calcd. for C38H80CoCl2N8O2S2 (%): C, 51.79; H, 9.13; N, 12.46; S, 7.12; Ni, 6.58. Found (%): C, 52.16; H, 9.21; N, 12.81; S, 7.33; Co, 6.73. IR (ν, cm−1): 2760sh (C-SH), 1650 br (N-NH2), 835 s coordinated H2O, 575 m (Co-O), 490 s (Co-N), 427 w (Co-S).


### 2.8. Molecular Modeling Methodology

The optimized structural geometry of the triazole ligand was identified using Gaussian 09 software by applying DFT/B3LYP process having range of base sets [23]. The Gaussian files obtained through this method were visualized using Gauss-View molecular visualization program [24]. They were calculated by using HOMO-LUMO energies; the DFT/B3LYP quantum chemical parameter was calculated in accordance with the numerical pattern appearing in gas phase in the view of the compounds. Additionally, the other parameters of optimized structures such as considerable bond lengths, excitation energies, oscillator strengths, and efficient charges required for coordinating functional groups were figured out.


### 2.9. Molecular Docking

Docking computations were performed using AutoDock tools 4.2 by applying Gasteiger partial charges incorporated into the designed drug (ligand) atoms. Depending on the protein-ligand interaction pattern, the calculations were carried out. Hydrogen atoms with nonpolar nature were conjoined, and bonds which can be rotatable were clarified. Subsequent to the incorporation of fundamental hydrogen atoms, Kollman unified atom style charges, and salvation factors, the AutoDock tools were pertained [25, 26]. Electrostatic and van der Waals terms were determined using distance dependent dielectric functions and AutoDock parameter set, respectively. For simulative docking, Lamarckian genetic algorithm and Solis and Wets local search methodology were applied [27]. Incidentally, properties of the ligand molecule like torsions, primary position, and orientation were positioned. The entire rotatable torsions were excluded throughout docking experiment. Ten diverse runs were performed for every docking experiment, which was positioned toward block subsequent to decisive 250,000 energy assessments while the size was set up to 150. During the experiment, torsion and translational step of 5 and 0.2 Å were utilized, respectively.


### 2.10. Biological Activity

The biological activity of triazole and its corresponding chelates was evaluated using agar well diffusion method againstB. subtilis (ATCC6635), S. pyogenes(ATCC443) (Gram+); E. coli (ATCC25922), P. vulgaris(ATCC33420) (Gram−) bacterium. Total 500 μL spore solution with 10−6–10−7 spores mL−1 concentration was inoculated very soon prior to solidification for every examined organism in sterilized agar preceded with pouring into sterile Petri dishes, having 45 mm radius, later permitted for solidification. Then, a sterile cork borer with 3 mm radius was utilized for creating three wells at different locations to every agar solidified Petri dish. To each well, 100 mg·mL−1 experimental compounds were mixed with DMF poured in the sterile Petri plates and then allowed for 48 h incubation on 37°C. The control was prepared using 0.l mL DMF at the same conditions. The zone of inhibition was calculated for control and experimental Petri dish containing metal complexes or free triazole ligand. For determination of antibacterial activity of these compounds, the experiment was performed in triplicate. The IC50 (the lowest concentration of compound capable of inhibiting 50% growth) was calculated from MIC measurements.


## 2.1. Instrumentation

A Jenway 4010 conductivity meter was utilized to record the molar conductance of solid chelates in DMF, while the solid reflectance spectra were recorded using a Shimadzu 3101pc spectrophotometer.ExtensivelH-NMR spectra beginning 0 to 15 ppm recorded on Varian-Oxford Mercury were operated at 300 MHz. The samples for lH-NMR spectra were prepared in DMSod6 (deuterated dimethylsulfoxide). For powder XRD analysis, BV XRD spectrometer from Philips Analytical type PW 1840 controlled at 40 kV plus 25 mA applying 2000 W radiation via copper anode was used. Faraday method was applied for molar magnetic susceptibility analysis of powdered samples. Pascal’s constant diamagnetic corrections were done while calibrations were performed using Hg[Co(SCN)4]. FTIR spectrum was taken among 4000–200 cm−1 using PerkinElmer FTIR type 1650 spectrophotometer by preparing KBr pellets.CHNS-932 (LECO) Vario elemental analyzer was used to analyze the separated solid chelates in duplicate for presence of C, H, N, S, and Cl at Microanalytical Center, Cairo University.Mass spectra were taken on MS-5988 GS-MS HP spectrometer controlled on 70 eV via EI technique at Microanalytical Center, Cairo University. Considering thermal analyses (TG, DTG, and DTA) Shimadzu TG-60 H simultaneous DTA-TG apparatus was used in dynamic nitrogen (20 mL·min−1) atmosphere having 10°C·min−1 rate of heating.


## 2.2. Metal Complexes Synthesis

To a solution of the triazole ligand (0.3 g, 0.847 mM) in ethanol (30 cm3), a solution containing metal (II)/(III) chloride (0.847 mM) in ethanol (15 cm3) was added. Mixed solution was refluxed using a water bath as long as 3 h whereupon the complexes were going to precipitate. The collected precipitate was filtered, clean washing was done using ethanol and diethyl ether, and it was vacuum-dried for later experiments.


## 2.3. [Cu(HL)2(H2O)2]Cl2

Yield 75%; brown solid, Anal. Calcd. for C38H80Cl2CuN8O2S2 (%): C, 51.90; H, 8.85; N, 12.88; S, 6.95; Cu, 6.75. Found (%): C, 51.88; H, 9.17; N, 12.74; S, 7.29; M, 7.22. IR (ν, cm−1): 2755 sh (C-SH), 1630 sh (N-NH2), 830 sh coordinated H2O, 566 s (Cu-O), 447s (Cu-N), 430 s (Cu-S).


## 2.4. [Cd(HL)2(H2O)2]Cl2

Yield 85%; dark green, Anal. Calcd. for C38H80CdCl2N8O2S2 (%): C, 48.88; H, 8.23; N, 12.45; S, 6.55; Cu, 11.76. Found (%): C, 49.15; H, 8.68; N, 12.07; S, 6.91; M, 12.11. IR (ν, cm−1): 2770 sh (C-SH), 1634sh (N-NH2), 740 s coordinated H2O, 565 s (Cd-O), 465 w (Cd-N), 438 s (Cd-S).


## 2.5. [Fe(HL)2(H2O)2]Cl3

Yield 87%; green, Anal. Calcd. for C38H80FeCl3N8O2S2 (%): C, 50.13; H, 8.63; N, 11.54; S, 6.62; Fe, 5.86. Found (%): C, 50.30; H, 8.89; N, 12.35; S, 7.07; M, 6.15. IR (ν, cm−1): 2730 sh (C-SH), 1640 s (N-NH2), 766 sh coordinated H2O, 560 s (Fe-O), 525 s (Fe-N), 462 w (Fe-S).


## 2.6. [Ni(HL)2(H2O)2]Cl2

Yield 82%; pale brown, Anal. Calcd. for C38H80NiCl2N8O2S2 (%): C, 51.69; H, 8.88; N, 13.71; S, 6.90; Ni, 6.45. Found (%): C, 52.17; H, 9.22; N, 12.81; S, 7.33; Ni, 6.71. IR (ν, cm−1): 2780 sh (C-SH), 1625 sh (N-NH2), 835 w coordinated H2O, 580 s (Ni-O), 530 s (Ni-N), 446 sh (Ni-S).


## 2.7. [Co(HL)2(H2O)2]Cl2

Yield 63%; dark blue, Anal. Calcd. for C38H80CoCl2N8O2S2 (%): C, 51.79; H, 9.13; N, 12.46; S, 7.12; Ni, 6.58. Found (%): C, 52.16; H, 9.21; N, 12.81; S, 7.33; Co, 6.73. IR (ν, cm−1): 2760sh (C-SH), 1650 br (N-NH2), 835 s coordinated H2O, 575 m (Co-O), 490 s (Co-N), 427 w (Co-S).


## 2.8. Molecular Modeling Methodology

The optimized structural geometry of the triazole ligand was identified using Gaussian 09 software by applying DFT/B3LYP process having range of base sets [23]. The Gaussian files obtained through this method were visualized using Gauss-View molecular visualization program [24]. They were calculated by using HOMO-LUMO energies; the DFT/B3LYP quantum chemical parameter was calculated in accordance with the numerical pattern appearing in gas phase in the view of the compounds. Additionally, the other parameters of optimized structures such as considerable bond lengths, excitation energies, oscillator strengths, and efficient charges required for coordinating functional groups were figured out.


## 2.9. Molecular Docking

Docking computations were performed using AutoDock tools 4.2 by applying Gasteiger partial charges incorporated into the designed drug (ligand) atoms. Depending on the protein-ligand interaction pattern, the calculations were carried out. Hydrogen atoms with nonpolar nature were conjoined, and bonds which can be rotatable were clarified. Subsequent to the incorporation of fundamental hydrogen atoms, Kollman unified atom style charges, and salvation factors, the AutoDock tools were pertained [25, 26]. Electrostatic and van der Waals terms were determined using distance dependent dielectric functions and AutoDock parameter set, respectively. For simulative docking, Lamarckian genetic algorithm and Solis and Wets local search methodology were applied [27]. Incidentally, properties of the ligand molecule like torsions, primary position, and orientation were positioned. The entire rotatable torsions were excluded throughout docking experiment. Ten diverse runs were performed for every docking experiment, which was positioned toward block subsequent to decisive 250,000 energy assessments while the size was set up to 150. During the experiment, torsion and translational step of 5 and 0.2 Å were utilized, respectively.


## 2.10. Biological Activity

The biological activity of triazole and its corresponding chelates was evaluated using agar well diffusion method againstB. subtilis (ATCC6635), S. pyogenes(ATCC443) (Gram+); E. coli (ATCC25922), P. vulgaris(ATCC33420) (Gram−) bacterium. Total 500 μL spore solution with 10−6–10−7 spores mL−1 concentration was inoculated very soon prior to solidification for every examined organism in sterilized agar preceded with pouring into sterile Petri dishes, having 45 mm radius, later permitted for solidification. Then, a sterile cork borer with 3 mm radius was utilized for creating three wells at different locations to every agar solidified Petri dish. To each well, 100 mg·mL−1 experimental compounds were mixed with DMF poured in the sterile Petri plates and then allowed for 48 h incubation on 37°C. The control was prepared using 0.l mL DMF at the same conditions. The zone of inhibition was calculated for control and experimental Petri dish containing metal complexes or free triazole ligand. For determination of antibacterial activity of these compounds, the experiment was performed in triplicate. The IC50 (the lowest concentration of compound capable of inhibiting 50% growth) was calculated from MIC measurements.


## 3. Results and Discussion

The elemental analyses of the triazole-thiol and its monomeric chelates were determined, showed good support with the proposed structures of the ligand and its chelates, and have been reported in Table1.Table 1
Elemental and physical data of triazole ligand and its metal complexes.
Compound
% found (calcd.)
μ
eff (B.M)
ΛmΩ−1·mol−l·cm2
C
H
N
S
M
HL
64.12 (64.33)
10.45 (10.80)
15.58 (15.80)
8.75 (9.04)
…
…
…
[Fe(HL)2(H2O)2]Cl3
50.13 (50.30)
8.63 (8.83)
11.54 (12.36)
6.62 (7.06)
5.86 (6.18)
92.20
92.20
[Co(HL)2(H2O)2]Cl2
51.79 (52.17)
9.13 (9.15)
12.46 (12.81)
7.12 (7.32)
6.58 (6.75)
5.30
130
[Ni(HL)2(H2O)2]Cl2
51.69 (52.17)
8.88 (9.15)
13.71 (12.81)
6.90 (7.32)
6.45 (6.75)
3.60
120
[Cu(HL)2(H2O)2]Cl2
51.90 (51.91)
8.85 (9.11)
12.88 (12.75)
6.95 (7.29)
6.75 (7.23)
1.70
43.10
[Cd(HL)2(H2O)2]Cl2
48.88 (49.19)
8.23 (8.63)
12.45 (12.08)
6.55 (6.90)
11.76 (12.08)
Diama
124


### 3.1. Infrared Spectral Analysis of Triazole Ligand and Complexes

IR spectrum of ligand showed an intense signal at 2820 cm−1 pointing out the presence of thiophenolic group (–SH). This sharp signal was shifted in the spectra of complexes (2730–2780 cm−1), indicting that the thiophenolic –SH group still protonated and was involved in coordination with metal ions [28]. The ligand showed an intense band due to stretching vibrations of amino group at 3200–3240 cm−1. This band was embedded within the -OH stretching vibration of coordinated water molecules at 3250–3500 cm−1. The bending vibration of the amino group at 1608 cm−1 was observed consistently with the amino absorption of free triazole ligand [29]. This latter peak was transferred to 1625–1650 cm−1 for spectra of metal chelates, confirming the coordination of amino group to metal ions [29].Besides the above bands, the IR bands, due to triazole ring systems between 1520 and 1566 cm−1 which are almost unaffected in the complexes, have been assigned to C=N. These facts were further confirmed by occurrence of some new signals (M–N) at 447–530 cm−1, (M–S) at 427–462 cm−1, and (M–O) at 565–580 cm−1 in the spectra of complexes [29, 30]. Bands at 745–780 cm−1 may be attributed to rocking and wagging modes of the coordinated water. It was concluded from the significant shift of free ligand (NH2) to lower wave number side, with increased wave number for thiophenolic (C–S) stretching band in complexes, that bonding of the ligand to metal ion is through thiophenolic sulfur and amino nitrogen.


### 3.2.lH NMR Analysis of Ligand and Its Monomeric Complexes

lH NMR spectra of ligand in DMSO exhibited a singlet at δ = 13.34 ppm for thiophenolic –SH, singlet at δ = 5.45 ppm due to NH2 group, multiplets in the region δ = 1.19–2.46 ppm due to -CH2 groups, and CH3 singlet at δ = 0.82 ppm. lH NMR spectrum of Cd(II) complex in DMSO showed small intensity peak at δ = 13.34 ppm corresponding to the presence of thiophenolic –SH, thus indicating remaining of hydrogen and coordination of ligand to metal through thiophenolic SH group. This finding confirmed the IR data. The peak due to NH2 group was found in the Cd(II) complex at 5.35 ppm. This shift confirmed the participation of NH2 in coordination with the metal ions. Peaks corresponding to -CH3 and -CH2 groups are also present in spectrum of Cd(II) complex without any change. Retention of peaks without any formal change indicated the preservation of the formal structure of ligand without any deformation [31].


### 3.3. Molar Conductance Study

The molar conductance values measured in DMF solution were found to be 43.10, 130, 124, 120, and 92.20 Ω−1·mol−lcm2 for Cu(II), Co(II), Cd(II), Ni(II), and Fe(III) complexes, respectively. Respective molar conductance values confirmed that the complexes were electrolytes [32].


### 3.4. Thermogravimetric Analysis

For determination of the general scheme for thermal decomposition of chelates and evaluation of the presence of water molecule either inside or outside the central metal ion, thermogravimetric analysis (TG, DTG, and DTA) was performed. This analysis also helped to determine the thermal stability of the new synthesized complexes. By controlling conditions such as temperature starting from atmospheric temperature to ∼1000°C under N2 gas and controlling the heating rates properly on 10°C min-l, weight loss was calculated. Thermogravimetric and DTA data are provided in Table 2.Table 2
Thermoanalytical results (TG and DTG) of triazole ligand and its metal complexes.
Compound
TG range (°C)
DTGmax (°C)
n
∗
Mass loss total mass loss calcd (estim) %
Assignment
Residue
DTA (°C)
HL
24–200
162, 181
2
28.24 (29.47)
(i) Loss of C7H16
—
60(−), 72(+), 99(−), 110(+), 186(−), 219(−)
200–325
204, 237
2
71.77 (70.54) 100.1 (100.1)
(ii) Loss of C12 H22N4S
[Fe(HL)2(H2O)2]Cl3
25–300
267
1
50.91 (51.44)
(i) Loss of 3HCl and C25H54
½Fe2O3
55(−), 67(+), 152(−), 235(+), 280(+), 500(−), 688(−), 711(−)
300–780
381, 573
2
40.49 (39.73) 91.40 (91.17)
(ii) Loss of 0.5(H2O), C13H25N8S2
[Co(HL)2(H2O)2]Cl2
25–250
150
1
15.67 (15.16)
(i) Loss of 2HCl, CH4, and C3H9
CoO
80(+), 176(−), 199(−), 263(−), 350(+), 415(−)
250–400
359
1
33.75 (33.28)
(ii) Loss of H2O and C20H37
400–680
410
1
44.62 (43.98) 94.04 (92.42)
(iii) Loss of C14H30N8S2
[Ni(HL)2(H2O)2]Cl2
25–200
58
1
18.33 (18.93)
(i) Loss of 2HCl, CH4, and C5H13
NiO
40(−), 63(+), 115(−), 125(+), 208(−), 286(−), 345(−), 370(+), 415(−)
200–250
241
1
19.82 (19.28)
(ii) Loss of C12H25
250–350
287
1
12.95 (13.36)
(iii) Loss of H2O and C7H11
350–600
363
1
41.60 (39.95) 92.70 (91.52)
(iv) Loss of C13H23N8S2
[Cu(HL)2(H2O)2]Cl2
25–150
73,110
2
10.36 (9.04)
(i) Loss of CH4 and 2HCl
CuO
81(+), 95(−), 114(+), 237(−), 273(+), 369(−), 399(+)
150–350
541
1
51.11 (51.49)
(ii) Loss of H2O and C31H61
350–650
393
1
29.71 (30.35) 91.85 (90.88)
(iii) Loss of C6H13N8S2
[Cd(HL)2(H2O)2]Cl2
25–250
233
1
20.01 (22.47)
(i) Loss of CH4, 2HCl, and C8H19
CdO
100(+), 234(−), 306(+), 456(+), 523(+)
250–400
311
1
18.12 (17.43)
(ii) Loss of H2O and C11H18
400–500
442
1
9.06 (9.01)
(iii) Loss of C6H12
500–800
630
1
37.43 (37.31) 84.62 (86.22)
(iv) Loss of C12H27N8S2The TG curves of Fe(III) and Co(II) chelates pointed out the first step decomposition around 25–300 and 25–250°C with 51.44% mass loss (calculated 50.9 l%) and 15.16 mass loss (calculated 15.67%), indicating the 1oss of 3HC1 and C25H54, and 2HC1, CH4, and C3H9 molecules, respectively. The Fe(III) and Co(II) complexes showed weight loss of 39.73% (calculated 40.49%) and 78.37% (calculated 77.26%) at temperature ranges of 300–780 and 250–680°C, which correspond to the removal of remaining ligand molecules, respectively.A weight loss of 18.93% (calculated 18.33%) was observed in the TG curve of Ni(II) complex in 25 and 200°C temperature range which suggested e1imination about 2HC1, CH4, and part of the organic 1igand (C5H13). The weight losses of 72.59% (calculated 74.37%) at temperature range 200–600°C corresponded to the removal of the remaining ligand molecules.Simi1ar1y at a temperature of 25–150°C and 25–250°C, CH4 and 2HC1 or CH4, 2HC1, and C8H19 moieties were eliminated corresponding to a weight loss of 9.04% (calculated 10.36%) and 22.47% (calculated 20.0 l%) for Cu(II) and Cd(II) complexes, respectively. The remaining ligand molecules were eliminated in the subsequent steps and the decomposition was completed at ∼650 and 800°C leading to the formation of the stable metal oxide CuO and CdO.The DTA data listed in Table2 pointed out that the decomposition of the ligand and its metal complexes appeared as exothermic and endothermic peaks.


### 3.5. Magnetic Moment Analysis and Electronic Spectra

The subtle reflectance spectra for Fe(III) complex indicated a signal at 21,362 cm−1, possibly specified toward 6Alg ⟶ T2g (G) conversion into octahedral geometry belonging to complex [33–35]. The transition 6A1g ⟶ 4T2g (G) and 6A1g ⟶ 4T1g was split into two signals at 17,642 and 12,784 cm−1. The Fe(III) complex has magnetic moment 5.30 B.M. Therefore, the produced complex showed octahedral geometry indicating d2sp3 hybridization of Fe(III) [35], while in case of Cu(II) complex broad band was observed at 15,921 cm−1. This signal was generally perfectly symmetric with an octahedral geometry designed for Cu(II) complex. The value of l.70 B.M from magnetic moment pinpointed the octahedral structure [36].The Co(II) complex spectrum of diffused reflectance showed three signals at 13,215, 15,841, and 17,492 cm−1. The octahedral geometry was supported by the value of the magnetic moment of the complex (μeff = 5.06 B.M.) [36]. The spectrum reflectance of Ni(II) complex also showed three spectral peaks at 21,645, 17,377, and 13,542 cm−1. The locations of all three peaks were clearly harmonic by those portended in favor of octahedral geometry [35]. These bands can be assigned, respectively [36], to 3A2g(F) ⟶ 3Tlg(F), 3A2g(F) ⟶ 3T2g(P), and 3A2g(F) ⟶ 3T2g(F) conversion. Octahedral geometry can be additionally supported by the magnetic moment value μeff = 3.30 B.M. The empirical formula of Cd(II) complex indicated that it has diamagnetic and octahedral geometry properties [36].


### 3.6. Mass Spectral (MS) Studies

The mass spectra of the ligands Ni(II), Cd(II), and Co(II) chelates exhibited molecular ionm/z bands at 354, 876, 928, and 880 atomic mass unit, which were in accordance with the molecular weights proposed, 354, 874, 928, and 878.5 amu, respectively. The molecular weights of the ligand and metal chelates agreed with elemental and thermogravimetric analyses, which have been utilized to prove the suggested formula. These prove the stoichiometry of complexes as we suggested in this type [M(Hl)2]. The multipeak type of the spectrum mass indicated the nature of the sequent degradation of base compound having peaks’ series identical to a variety of fractions. The intensity of peaks provides an insight about stability of fragments. The fragmentation pattern of free ligand is shown in Scheme 1.Scheme 1


### 3.7. X-Ray Diffraction Analysis (Powder-XRD)

The synthesized Fe(III) and Co(II) complexes were found to have a crystalline character [37, 38].


#### 3.7.1. Structural Interpretation

Depending on the range of spectral and physicochemical analysis presented here, the structures of ligand and its metal complexes are shown in Figures1 and 2.Figure 1
Proposed structure of triazole ligand.Figure 2
Proposed structure of complexes.


### 3.8. Molecular Modeling

#### 3.8.1. Molecular Parameters

Additional parameters such as chemical potentials (Pi), absolute electronegativities (χ), global softness (S), absolute hardness (η), additional electronic charge (ΔNmax), global electrophilicity (ω), and absolute softness (σ) estimated for the Hl free ligand are listed in Supplementary Table 1. The toxicity and the reactivity of various selective sites could be described by electrophilicity index (ω), which is considered as significant quantum chemical headline. The biological activity of drug-receptor interaction may be quantified by the electrophilicity. Also, the stabilization energy was determined by this index when the system was obtained from the environment on an additional negative charge. The η and σ parameters are scheme of the molecular reactivity and stability, and their perceptions were linked with all others. The softness index was on the contrary to global stiffness. The suggested structures were supported by these parameters, and the mentioned quantum chemical parameters were studied through the recommended equations [39–41]. The calculated data are presented in Supplementary Table 1, and the following study able to illustrate that(i)
The information of HL ligand indicated an enormous possibility in favor of biological action based on elevated ω value.(ii)
η is hardness, whereas S and ω were indexes for softness; as the energy difference between EHOMO and ELUMO increasing the stability of the molecule increases (Figure 3). Therefore, the reactive soft molecule is having pliable contribution to metal ions. Thus, the explored HL ligand was observed soft against coordination.(iii)
It was clear from the negative electronic chemical potential (μ) value and the positive electrophilicity index (χ) value that the HL ligand has a negative electronic chemical potential due to accepting electrons from the environment, which leads to decrease in its energy [42].(iv)
The overall energy for the liberated ligand observed was very tiny, which clearly signified that the isolated ligands were stable.(v)
The very tiny energy space may be related to low kinetic stability, reflecting efficient electronic charge transfer interaction and high chemical reactivity, making the ligand strongly polarizable.Figure 3
HOMO and LUMO patterns of triazole ligand.


#### 3.8.2. The Atomic Charges, Bond Angles, and Bond Lengths

The calculation of atomic charges played a significant role in the application of quantum mechanical calculations [42, 43]. The estimated atomic charge was determined by Mulliken population analysis with optimized geometry and the data are listed in Supplementary Tables 2 and 3 and is shown in Figure 4. Since noticed, the N(II) and N(III) atoms have lower negative atomic charges compared to nitrogen atoms (N6) from the amino group, and also the existence of N2 and N3 beside and attached to N6 and S7 causes higher electronegativity, and from that these atoms were suggested as center of chelation. Results listed in Supplementary Tables 2 and 3 indicated that sulfur (S7) and amino nitrogen N6 atoms in Hl have extra negative charges compared to other atoms.Figure 4
Numbering system for triazole ligand.The suitable places of coordination with metal ions were predicted using Mulliken method existent of triazole ligand HL that was additionally carried through MEP analysis. On the other hand, the bond of (Cl-C24) had more length than the other bonds in triazole ring (N2,N3), (N3,C4), and (C4,N5); the large bond length of (C4,S7) and (N5,N6); and the big bond angle (N3,C4,S7), (Cl,N5,N6), (C4,N5,N6), and (N2,C1,C24), Supplementary Tables (2, 3). Also, the high dihedral bond angles (N3,C4,N5,N6), (S7,C4,N5,C1), (S7,C4,N5,N6), (N3,C4,S7,H27), (N5,C4,S7,H27), (Cl,N5,N6,H25), (Cl,N5,N6,H26), (C4,N5,N6,H25), (C4,N5,N6,H26), (C24,C1,N5,C4), (C24,C1,N5,N6), (N2,C1,C24,C23), (N2,C1,C24,H61), (N2,C1,C24,H62), (N5,C1,C24,C23), (N5,C1,C24,H61), (N5,C1,C24,H62), (N2,N3,C4,S7), and (C24,C1,N2,N3) enhanced the rapture of these bonds firstly, Supplementary Tables 2 and 3. This suggestion was compatible with mass fragmentation and thermal degradation and confirmed the discussion.


#### 3.8.3. Antimicrobial Activity of Ligand and Its Monomeric Complexes

Synthesized triazole and its corresponding metal chelates were investigated againstBacillus subtilis, Proteus vulgaris, Escherichia coli, and Staphylococcus pyogenes to estimate their potential as antimicrobial agents by well-diffusion method, which is well known as the agar ditch method. An observed zone of inhibition is shown in Figure 5. The counted zones of inhibition next to the growth of respective microorganisms are listed in Table 3. It was observed from Table 3 that all complexes showed greater antibacterial activity than that of ligand [44]. All the complexes showed very good results against all bacterial strains. Furthermore, metal complexes showed excellent antibacterial activity against E. coli. In addition, Cd(II), Ni(II), and Co(II) chelates have very good antibacterial activity toward P. vulgaris, while Ni(II) and Cu(II) complexes showed high antibacterial activity against B. subtilis and S. pyogenes organisms Figure 5.Figure 5
Biological activity of triazole ligand and its metal complexes.Table 3
Biological activity of triazole ligand and its metal chelates.
Sample
Inhibition zone (mm sample)
Gram negative
Gram positive
Escherichia coli
Proteus vulgaris
Bacillus subtilis
Staphylococcus pyogenes
Control: DMSO
0
0
0
0
HL
11
12
11
10
[Fe(HL)2(H2O)2]·Cl3
30
22
25
20
[Co(HL)2(H2O)2]·Cl2
44
32
25
27
[Ni(HL)2(H2O)2]·Cl2
40
33
30
32
[Cu(HL)2(H2O)2]·Cl2
40
27
35
30
[Cd(HL)2(H2O)2]·Cl2
22
30
27
25
Amikacin
7
6
7
8The zone of inhibition can be monitored by altering the incubation conditions, culture medium, concentration of the antibacterial agent, and rate of diffusion. The activity of all the synthesized complexes may be demonstrated according to the chelation theory where the polarity of the metal atom decreased by chelation. This reduction in polarity is due to partial share of theπ electron delocalization and positive charge of the donor groups of the coordination sphere (Figure 5). Also, the lipophilic nature of the central atom increased by chelation, serving its penetration to the lipid layer of the cell membrane [45]. The main aim of this work was to utilize these complexes as drug agents in several widespread diseases originated by septicemia, E. coli, e.g., diarrhea, vomiting urinary tract infectivity, and infections obtained from hospitals [46].


### 3.9. Molecular Docking

Antimicrobial features of drugs were explained using AutoDock tools. The triazole ligand (guest) executed had diverse peptide receptors from host:E. coli (3 t88), B. subtilis (5 h67), and P. vulgaris (5i39) by molecular docking (Figures 6–8). The space and energies since most excellent type designed for docking method was examined. Along with computation, a sturdy communication through all receptors having comparable results was illustrated using HB plots (Figures 6–8). This indicated mutable competence for the H-bonding contact via multicentral groups internal docking complexes. All proteins have inter-hydrogen bonding [47,48]. The docking process was evidenced using 2D plots (Figures 6–8). Therefore, the triazole-thiol ligand interrelated with AA (amino acids) of proteins via -H bonding as follows.Figure 6
Three-dimensional plot of interaction of triazole ligand withE. coli (3 t88) receptor.Figure 7
Three-dimensional plot of interaction of triazole ligand withB. subtilis (5 h67) receptor.Figure 8
Three-dimensional plot of interaction of triazole ligand withP. vulgaris (5i39) receptor.In case ofB. subtilis (5h67), amino acid from protein responded to ligand by hydrogen bonding through 5h67-A/GlYʹ34/O (bond length = 2.8 Ǻ) with binding energy = −4.9 kcal·mol−1. In case of E. coli (3 t88), amino acid from protein responded to ligand by hydrogen bonding of 3t88-A/ASPʹ66/ODl (bond length = 3.4 Ǻ), 3t88-A/ASPʹ62/ODl (bond length = 2.2 Ǻ) and 3t88-A/ASPʹ62/OD2 (bond length = 2.6 Ǻ) with binding energy = −3.5 kcal·mol−1.As in case ofP. vulgaris (5i39), amino acid from protein responded to ligand by hydrogen bond of 5i39-A/GlUʹ448/0E2 (bond length = 3.5 Ǻ) and 5i39-A/GlUʹ448/0E2 (bond length = 3.5 Ǻ) with binding energy = −3.8 kcal·mol−1.


## 3.1. Infrared Spectral Analysis of Triazole Ligand and Complexes

IR spectrum of ligand showed an intense signal at 2820 cm−1 pointing out the presence of thiophenolic group (–SH). This sharp signal was shifted in the spectra of complexes (2730–2780 cm−1), indicting that the thiophenolic –SH group still protonated and was involved in coordination with metal ions [28]. The ligand showed an intense band due to stretching vibrations of amino group at 3200–3240 cm−1. This band was embedded within the -OH stretching vibration of coordinated water molecules at 3250–3500 cm−1. The bending vibration of the amino group at 1608 cm−1 was observed consistently with the amino absorption of free triazole ligand [29]. This latter peak was transferred to 1625–1650 cm−1 for spectra of metal chelates, confirming the coordination of amino group to metal ions [29].Besides the above bands, the IR bands, due to triazole ring systems between 1520 and 1566 cm−1 which are almost unaffected in the complexes, have been assigned to C=N. These facts were further confirmed by occurrence of some new signals (M–N) at 447–530 cm−1, (M–S) at 427–462 cm−1, and (M–O) at 565–580 cm−1 in the spectra of complexes [29, 30]. Bands at 745–780 cm−1 may be attributed to rocking and wagging modes of the coordinated water. It was concluded from the significant shift of free ligand (NH2) to lower wave number side, with increased wave number for thiophenolic (C–S) stretching band in complexes, that bonding of the ligand to metal ion is through thiophenolic sulfur and amino nitrogen.


## 3.2.lH NMR Analysis of Ligand and Its Monomeric Complexes

lH NMR spectra of ligand in DMSO exhibited a singlet at δ = 13.34 ppm for thiophenolic –SH, singlet at δ = 5.45 ppm due to NH2 group, multiplets in the region δ = 1.19–2.46 ppm due to -CH2 groups, and CH3 singlet at δ = 0.82 ppm. lH NMR spectrum of Cd(II) complex in DMSO showed small intensity peak at δ = 13.34 ppm corresponding to the presence of thiophenolic –SH, thus indicating remaining of hydrogen and coordination of ligand to metal through thiophenolic SH group. This finding confirmed the IR data. The peak due to NH2 group was found in the Cd(II) complex at 5.35 ppm. This shift confirmed the participation of NH2 in coordination with the metal ions. Peaks corresponding to -CH3 and -CH2 groups are also present in spectrum of Cd(II) complex without any change. Retention of peaks without any formal change indicated the preservation of the formal structure of ligand without any deformation [31].


## 3.3. Molar Conductance Study

The molar conductance values measured in DMF solution were found to be 43.10, 130, 124, 120, and 92.20 Ω−1·mol−lcm2 for Cu(II), Co(II), Cd(II), Ni(II), and Fe(III) complexes, respectively. Respective molar conductance values confirmed that the complexes were electrolytes [32].


## 3.4. Thermogravimetric Analysis

For determination of the general scheme for thermal decomposition of chelates and evaluation of the presence of water molecule either inside or outside the central metal ion, thermogravimetric analysis (TG, DTG, and DTA) was performed. This analysis also helped to determine the thermal stability of the new synthesized complexes. By controlling conditions such as temperature starting from atmospheric temperature to ∼1000°C under N2 gas and controlling the heating rates properly on 10°C min-l, weight loss was calculated. Thermogravimetric and DTA data are provided in Table 2.Table 2
Thermoanalytical results (TG and DTG) of triazole ligand and its metal complexes.
Compound
TG range (°C)
DTGmax (°C)
n
∗
Mass loss total mass loss calcd (estim) %
Assignment
Residue
DTA (°C)
HL
24–200
162, 181
2
28.24 (29.47)
(i) Loss of C7H16
—
60(−), 72(+), 99(−), 110(+), 186(−), 219(−)
200–325
204, 237
2
71.77 (70.54) 100.1 (100.1)
(ii) Loss of C12 H22N4S
[Fe(HL)2(H2O)2]Cl3
25–300
267
1
50.91 (51.44)
(i) Loss of 3HCl and C25H54
½Fe2O3
55(−), 67(+), 152(−), 235(+), 280(+), 500(−), 688(−), 711(−)
300–780
381, 573
2
40.49 (39.73) 91.40 (91.17)
(ii) Loss of 0.5(H2O), C13H25N8S2
[Co(HL)2(H2O)2]Cl2
25–250
150
1
15.67 (15.16)
(i) Loss of 2HCl, CH4, and C3H9
CoO
80(+), 176(−), 199(−), 263(−), 350(+), 415(−)
250–400
359
1
33.75 (33.28)
(ii) Loss of H2O and C20H37
400–680
410
1
44.62 (43.98) 94.04 (92.42)
(iii) Loss of C14H30N8S2
[Ni(HL)2(H2O)2]Cl2
25–200
58
1
18.33 (18.93)
(i) Loss of 2HCl, CH4, and C5H13
NiO
40(−), 63(+), 115(−), 125(+), 208(−), 286(−), 345(−), 370(+), 415(−)
200–250
241
1
19.82 (19.28)
(ii) Loss of C12H25
250–350
287
1
12.95 (13.36)
(iii) Loss of H2O and C7H11
350–600
363
1
41.60 (39.95) 92.70 (91.52)
(iv) Loss of C13H23N8S2
[Cu(HL)2(H2O)2]Cl2
25–150
73,110
2
10.36 (9.04)
(i) Loss of CH4 and 2HCl
CuO
81(+), 95(−), 114(+), 237(−), 273(+), 369(−), 399(+)
150–350
541
1
51.11 (51.49)
(ii) Loss of H2O and C31H61
350–650
393
1
29.71 (30.35) 91.85 (90.88)
(iii) Loss of C6H13N8S2
[Cd(HL)2(H2O)2]Cl2
25–250
233
1
20.01 (22.47)
(i) Loss of CH4, 2HCl, and C8H19
CdO
100(+), 234(−), 306(+), 456(+), 523(+)
250–400
311
1
18.12 (17.43)
(ii) Loss of H2O and C11H18
400–500
442
1
9.06 (9.01)
(iii) Loss of C6H12
500–800
630
1
37.43 (37.31) 84.62 (86.22)
(iv) Loss of C12H27N8S2The TG curves of Fe(III) and Co(II) chelates pointed out the first step decomposition around 25–300 and 25–250°C with 51.44% mass loss (calculated 50.9 l%) and 15.16 mass loss (calculated 15.67%), indicating the 1oss of 3HC1 and C25H54, and 2HC1, CH4, and C3H9 molecules, respectively. The Fe(III) and Co(II) complexes showed weight loss of 39.73% (calculated 40.49%) and 78.37% (calculated 77.26%) at temperature ranges of 300–780 and 250–680°C, which correspond to the removal of remaining ligand molecules, respectively.A weight loss of 18.93% (calculated 18.33%) was observed in the TG curve of Ni(II) complex in 25 and 200°C temperature range which suggested e1imination about 2HC1, CH4, and part of the organic 1igand (C5H13). The weight losses of 72.59% (calculated 74.37%) at temperature range 200–600°C corresponded to the removal of the remaining ligand molecules.Simi1ar1y at a temperature of 25–150°C and 25–250°C, CH4 and 2HC1 or CH4, 2HC1, and C8H19 moieties were eliminated corresponding to a weight loss of 9.04% (calculated 10.36%) and 22.47% (calculated 20.0 l%) for Cu(II) and Cd(II) complexes, respectively. The remaining ligand molecules were eliminated in the subsequent steps and the decomposition was completed at ∼650 and 800°C leading to the formation of the stable metal oxide CuO and CdO.The DTA data listed in Table2 pointed out that the decomposition of the ligand and its metal complexes appeared as exothermic and endothermic peaks.


## 3.5. Magnetic Moment Analysis and Electronic Spectra

The subtle reflectance spectra for Fe(III) complex indicated a signal at 21,362 cm−1, possibly specified toward 6Alg ⟶ T2g (G) conversion into octahedral geometry belonging to complex [33–35]. The transition 6A1g ⟶ 4T2g (G) and 6A1g ⟶ 4T1g was split into two signals at 17,642 and 12,784 cm−1. The Fe(III) complex has magnetic moment 5.30 B.M. Therefore, the produced complex showed octahedral geometry indicating d2sp3 hybridization of Fe(III) [35], while in case of Cu(II) complex broad band was observed at 15,921 cm−1. This signal was generally perfectly symmetric with an octahedral geometry designed for Cu(II) complex. The value of l.70 B.M from magnetic moment pinpointed the octahedral structure [36].The Co(II) complex spectrum of diffused reflectance showed three signals at 13,215, 15,841, and 17,492 cm−1. The octahedral geometry was supported by the value of the magnetic moment of the complex (μeff = 5.06 B.M.) [36]. The spectrum reflectance of Ni(II) complex also showed three spectral peaks at 21,645, 17,377, and 13,542 cm−1. The locations of all three peaks were clearly harmonic by those portended in favor of octahedral geometry [35]. These bands can be assigned, respectively [36], to 3A2g(F) ⟶ 3Tlg(F), 3A2g(F) ⟶ 3T2g(P), and 3A2g(F) ⟶ 3T2g(F) conversion. Octahedral geometry can be additionally supported by the magnetic moment value μeff = 3.30 B.M. The empirical formula of Cd(II) complex indicated that it has diamagnetic and octahedral geometry properties [36].


## 3.6. Mass Spectral (MS) Studies

The mass spectra of the ligands Ni(II), Cd(II), and Co(II) chelates exhibited molecular ionm/z bands at 354, 876, 928, and 880 atomic mass unit, which were in accordance with the molecular weights proposed, 354, 874, 928, and 878.5 amu, respectively. The molecular weights of the ligand and metal chelates agreed with elemental and thermogravimetric analyses, which have been utilized to prove the suggested formula. These prove the stoichiometry of complexes as we suggested in this type [M(Hl)2]. The multipeak type of the spectrum mass indicated the nature of the sequent degradation of base compound having peaks’ series identical to a variety of fractions. The intensity of peaks provides an insight about stability of fragments. The fragmentation pattern of free ligand is shown in Scheme 1.Scheme 1


## 3.7. X-Ray Diffraction Analysis (Powder-XRD)

The synthesized Fe(III) and Co(II) complexes were found to have a crystalline character [37, 38].


### 3.7.1. Structural Interpretation

Depending on the range of spectral and physicochemical analysis presented here, the structures of ligand and its metal complexes are shown in Figures1 and 2.Figure 1
Proposed structure of triazole ligand.Figure 2
Proposed structure of complexes.


## 3.7.1. Structural Interpretation

Depending on the range of spectral and physicochemical analysis presented here, the structures of ligand and its metal complexes are shown in Figures1 and 2.Figure 1
Proposed structure of triazole ligand.Figure 2
Proposed structure of complexes.


## 3.8. Molecular Modeling

### 3.8.1. Molecular Parameters

Additional parameters such as chemical potentials (Pi), absolute electronegativities (χ), global softness (S), absolute hardness (η), additional electronic charge (ΔNmax), global electrophilicity (ω), and absolute softness (σ) estimated for the Hl free ligand are listed in Supplementary Table 1. The toxicity and the reactivity of various selective sites could be described by electrophilicity index (ω), which is considered as significant quantum chemical headline. The biological activity of drug-receptor interaction may be quantified by the electrophilicity. Also, the stabilization energy was determined by this index when the system was obtained from the environment on an additional negative charge. The η and σ parameters are scheme of the molecular reactivity and stability, and their perceptions were linked with all others. The softness index was on the contrary to global stiffness. The suggested structures were supported by these parameters, and the mentioned quantum chemical parameters were studied through the recommended equations [39–41]. The calculated data are presented in Supplementary Table 1, and the following study able to illustrate that(i)
The information of HL ligand indicated an enormous possibility in favor of biological action based on elevated ω value.(ii)
η is hardness, whereas S and ω were indexes for softness; as the energy difference between EHOMO and ELUMO increasing the stability of the molecule increases (Figure 3). Therefore, the reactive soft molecule is having pliable contribution to metal ions. Thus, the explored HL ligand was observed soft against coordination.(iii)
It was clear from the negative electronic chemical potential (μ) value and the positive electrophilicity index (χ) value that the HL ligand has a negative electronic chemical potential due to accepting electrons from the environment, which leads to decrease in its energy [42].(iv)
The overall energy for the liberated ligand observed was very tiny, which clearly signified that the isolated ligands were stable.(v)
The very tiny energy space may be related to low kinetic stability, reflecting efficient electronic charge transfer interaction and high chemical reactivity, making the ligand strongly polarizable.Figure 3
HOMO and LUMO patterns of triazole ligand.


### 3.8.2. The Atomic Charges, Bond Angles, and Bond Lengths

The calculation of atomic charges played a significant role in the application of quantum mechanical calculations [42, 43]. The estimated atomic charge was determined by Mulliken population analysis with optimized geometry and the data are listed in Supplementary Tables 2 and 3 and is shown in Figure 4. Since noticed, the N(II) and N(III) atoms have lower negative atomic charges compared to nitrogen atoms (N6) from the amino group, and also the existence of N2 and N3 beside and attached to N6 and S7 causes higher electronegativity, and from that these atoms were suggested as center of chelation. Results listed in Supplementary Tables 2 and 3 indicated that sulfur (S7) and amino nitrogen N6 atoms in Hl have extra negative charges compared to other atoms.Figure 4
Numbering system for triazole ligand.The suitable places of coordination with metal ions were predicted using Mulliken method existent of triazole ligand HL that was additionally carried through MEP analysis. On the other hand, the bond of (Cl-C24) had more length than the other bonds in triazole ring (N2,N3), (N3,C4), and (C4,N5); the large bond length of (C4,S7) and (N5,N6); and the big bond angle (N3,C4,S7), (Cl,N5,N6), (C4,N5,N6), and (N2,C1,C24), Supplementary Tables (2, 3). Also, the high dihedral bond angles (N3,C4,N5,N6), (S7,C4,N5,C1), (S7,C4,N5,N6), (N3,C4,S7,H27), (N5,C4,S7,H27), (Cl,N5,N6,H25), (Cl,N5,N6,H26), (C4,N5,N6,H25), (C4,N5,N6,H26), (C24,C1,N5,C4), (C24,C1,N5,N6), (N2,C1,C24,C23), (N2,C1,C24,H61), (N2,C1,C24,H62), (N5,C1,C24,C23), (N5,C1,C24,H61), (N5,C1,C24,H62), (N2,N3,C4,S7), and (C24,C1,N2,N3) enhanced the rapture of these bonds firstly, Supplementary Tables 2 and 3. This suggestion was compatible with mass fragmentation and thermal degradation and confirmed the discussion.


### 3.8.3. Antimicrobial Activity of Ligand and Its Monomeric Complexes

Synthesized triazole and its corresponding metal chelates were investigated againstBacillus subtilis, Proteus vulgaris, Escherichia coli, and Staphylococcus pyogenes to estimate their potential as antimicrobial agents by well-diffusion method, which is well known as the agar ditch method. An observed zone of inhibition is shown in Figure 5. The counted zones of inhibition next to the growth of respective microorganisms are listed in Table 3. It was observed from Table 3 that all complexes showed greater antibacterial activity than that of ligand [44]. All the complexes showed very good results against all bacterial strains. Furthermore, metal complexes showed excellent antibacterial activity against E. coli. In addition, Cd(II), Ni(II), and Co(II) chelates have very good antibacterial activity toward P. vulgaris, while Ni(II) and Cu(II) complexes showed high antibacterial activity against B. subtilis and S. pyogenes organisms Figure 5.Figure 5
Biological activity of triazole ligand and its metal complexes.Table 3
Biological activity of triazole ligand and its metal chelates.
Sample
Inhibition zone (mm sample)
Gram negative
Gram positive
Escherichia coli
Proteus vulgaris
Bacillus subtilis
Staphylococcus pyogenes
Control: DMSO
0
0
0
0
HL
11
12
11
10
[Fe(HL)2(H2O)2]·Cl3
30
22
25
20
[Co(HL)2(H2O)2]·Cl2
44
32
25
27
[Ni(HL)2(H2O)2]·Cl2
40
33
30
32
[Cu(HL)2(H2O)2]·Cl2
40
27
35
30
[Cd(HL)2(H2O)2]·Cl2
22
30
27
25
Amikacin
7
6
7
8The zone of inhibition can be monitored by altering the incubation conditions, culture medium, concentration of the antibacterial agent, and rate of diffusion. The activity of all the synthesized complexes may be demonstrated according to the chelation theory where the polarity of the metal atom decreased by chelation. This reduction in polarity is due to partial share of theπ electron delocalization and positive charge of the donor groups of the coordination sphere (Figure 5). Also, the lipophilic nature of the central atom increased by chelation, serving its penetration to the lipid layer of the cell membrane [45]. The main aim of this work was to utilize these complexes as drug agents in several widespread diseases originated by septicemia, E. coli, e.g., diarrhea, vomiting urinary tract infectivity, and infections obtained from hospitals [46].


## 3.8.1. Molecular Parameters

Additional parameters such as chemical potentials (Pi), absolute electronegativities (χ), global softness (S), absolute hardness (η), additional electronic charge (ΔNmax), global electrophilicity (ω), and absolute softness (σ) estimated for the Hl free ligand are listed in Supplementary Table 1. The toxicity and the reactivity of various selective sites could be described by electrophilicity index (ω), which is considered as significant quantum chemical headline. The biological activity of drug-receptor interaction may be quantified by the electrophilicity. Also, the stabilization energy was determined by this index when the system was obtained from the environment on an additional negative charge. The η and σ parameters are scheme of the molecular reactivity and stability, and their perceptions were linked with all others. The softness index was on the contrary to global stiffness. The suggested structures were supported by these parameters, and the mentioned quantum chemical parameters were studied through the recommended equations [39–41]. The calculated data are presented in Supplementary Table 1, and the following study able to illustrate that(i)
The information of HL ligand indicated an enormous possibility in favor of biological action based on elevated ω value.(ii)
η is hardness, whereas S and ω were indexes for softness; as the energy difference between EHOMO and ELUMO increasing the stability of the molecule increases (Figure 3). Therefore, the reactive soft molecule is having pliable contribution to metal ions. Thus, the explored HL ligand was observed soft against coordination.(iii)
It was clear from the negative electronic chemical potential (μ) value and the positive electrophilicity index (χ) value that the HL ligand has a negative electronic chemical potential due to accepting electrons from the environment, which leads to decrease in its energy [42].(iv)
The overall energy for the liberated ligand observed was very tiny, which clearly signified that the isolated ligands were stable.(v)
The very tiny energy space may be related to low kinetic stability, reflecting efficient electronic charge transfer interaction and high chemical reactivity, making the ligand strongly polarizable.Figure 3
HOMO and LUMO patterns of triazole ligand.


## 3.8.2. The Atomic Charges, Bond Angles, and Bond Lengths

The calculation of atomic charges played a significant role in the application of quantum mechanical calculations [42, 43]. The estimated atomic charge was determined by Mulliken population analysis with optimized geometry and the data are listed in Supplementary Tables 2 and 3 and is shown in Figure 4. Since noticed, the N(II) and N(III) atoms have lower negative atomic charges compared to nitrogen atoms (N6) from the amino group, and also the existence of N2 and N3 beside and attached to N6 and S7 causes higher electronegativity, and from that these atoms were suggested as center of chelation. Results listed in Supplementary Tables 2 and 3 indicated that sulfur (S7) and amino nitrogen N6 atoms in Hl have extra negative charges compared to other atoms.Figure 4
Numbering system for triazole ligand.The suitable places of coordination with metal ions were predicted using Mulliken method existent of triazole ligand HL that was additionally carried through MEP analysis. On the other hand, the bond of (Cl-C24) had more length than the other bonds in triazole ring (N2,N3), (N3,C4), and (C4,N5); the large bond length of (C4,S7) and (N5,N6); and the big bond angle (N3,C4,S7), (Cl,N5,N6), (C4,N5,N6), and (N2,C1,C24), Supplementary Tables (2, 3). Also, the high dihedral bond angles (N3,C4,N5,N6), (S7,C4,N5,C1), (S7,C4,N5,N6), (N3,C4,S7,H27), (N5,C4,S7,H27), (Cl,N5,N6,H25), (Cl,N5,N6,H26), (C4,N5,N6,H25), (C4,N5,N6,H26), (C24,C1,N5,C4), (C24,C1,N5,N6), (N2,C1,C24,C23), (N2,C1,C24,H61), (N2,C1,C24,H62), (N5,C1,C24,C23), (N5,C1,C24,H61), (N5,C1,C24,H62), (N2,N3,C4,S7), and (C24,C1,N2,N3) enhanced the rapture of these bonds firstly, Supplementary Tables 2 and 3. This suggestion was compatible with mass fragmentation and thermal degradation and confirmed the discussion.


## 3.8.3. Antimicrobial Activity of Ligand and Its Monomeric Complexes

Synthesized triazole and its corresponding metal chelates were investigated againstBacillus subtilis, Proteus vulgaris, Escherichia coli, and Staphylococcus pyogenes to estimate their potential as antimicrobial agents by well-diffusion method, which is well known as the agar ditch method. An observed zone of inhibition is shown in Figure 5. The counted zones of inhibition next to the growth of respective microorganisms are listed in Table 3. It was observed from Table 3 that all complexes showed greater antibacterial activity than that of ligand [44]. All the complexes showed very good results against all bacterial strains. Furthermore, metal complexes showed excellent antibacterial activity against E. coli. In addition, Cd(II), Ni(II), and Co(II) chelates have very good antibacterial activity toward P. vulgaris, while Ni(II) and Cu(II) complexes showed high antibacterial activity against B. subtilis and S. pyogenes organisms Figure 5.Figure 5
Biological activity of triazole ligand and its metal complexes.Table 3
Biological activity of triazole ligand and its metal chelates.
Sample
Inhibition zone (mm sample)
Gram negative
Gram positive
Escherichia coli
Proteus vulgaris
Bacillus subtilis
Staphylococcus pyogenes
Control: DMSO
0
0
0
0
HL
11
12
11
10
[Fe(HL)2(H2O)2]·Cl3
30
22
25
20
[Co(HL)2(H2O)2]·Cl2
44
32
25
27
[Ni(HL)2(H2O)2]·Cl2
40
33
30
32
[Cu(HL)2(H2O)2]·Cl2
40
27
35
30
[Cd(HL)2(H2O)2]·Cl2
22
30
27
25
Amikacin
7
6
7
8The zone of inhibition can be monitored by altering the incubation conditions, culture medium, concentration of the antibacterial agent, and rate of diffusion. The activity of all the synthesized complexes may be demonstrated according to the chelation theory where the polarity of the metal atom decreased by chelation. This reduction in polarity is due to partial share of theπ electron delocalization and positive charge of the donor groups of the coordination sphere (Figure 5). Also, the lipophilic nature of the central atom increased by chelation, serving its penetration to the lipid layer of the cell membrane [45]. The main aim of this work was to utilize these complexes as drug agents in several widespread diseases originated by septicemia, E. coli, e.g., diarrhea, vomiting urinary tract infectivity, and infections obtained from hospitals [46].


## 3.9. Molecular Docking

Antimicrobial features of drugs were explained using AutoDock tools. The triazole ligand (guest) executed had diverse peptide receptors from host:E. coli (3 t88), B. subtilis (5 h67), and P. vulgaris (5i39) by molecular docking (Figures 6–8). The space and energies since most excellent type designed for docking method was examined. Along with computation, a sturdy communication through all receptors having comparable results was illustrated using HB plots (Figures 6–8). This indicated mutable competence for the H-bonding contact via multicentral groups internal docking complexes. All proteins have inter-hydrogen bonding [47,48]. The docking process was evidenced using 2D plots (Figures 6–8). Therefore, the triazole-thiol ligand interrelated with AA (amino acids) of proteins via -H bonding as follows.Figure 6
Three-dimensional plot of interaction of triazole ligand withE. coli (3 t88) receptor.Figure 7
Three-dimensional plot of interaction of triazole ligand withB. subtilis (5 h67) receptor.Figure 8
Three-dimensional plot of interaction of triazole ligand withP. vulgaris (5i39) receptor.In case ofB. subtilis (5h67), amino acid from protein responded to ligand by hydrogen bonding through 5h67-A/GlYʹ34/O (bond length = 2.8 Ǻ) with binding energy = −4.9 kcal·mol−1. In case of E. coli (3 t88), amino acid from protein responded to ligand by hydrogen bonding of 3t88-A/ASPʹ66/ODl (bond length = 3.4 Ǻ), 3t88-A/ASPʹ62/ODl (bond length = 2.2 Ǻ) and 3t88-A/ASPʹ62/OD2 (bond length = 2.6 Ǻ) with binding energy = −3.5 kcal·mol−1.As in case ofP. vulgaris (5i39), amino acid from protein responded to ligand by hydrogen bond of 5i39-A/GlUʹ448/0E2 (bond length = 3.5 Ǻ) and 5i39-A/GlUʹ448/0E2 (bond length = 3.5 Ǻ) with binding energy = −3.8 kcal·mol−1.


## 4. Conclusions

Structural and molecular properties of triazole-thiol (HL) toward the transition metal ions, namely, Fe(III), Co(II), Cu(II), Cd(II), and Ni(II), have been studied by elemental analyses, magnetic measurements, electronic spectra, FT-IR,lH-NMR, and thermal analyses (TGA and DTA). The interpretation of all thermal decomposition stages has been evaluated. All computations were carried out using Gaussian 09W software package. The molecular geometry for the triazole-thiol ligand and its metal chelates was fully optimized using density functional theory B3LYP method. The ligand and its metal complexes have been examined against Escherichia coli, Proteus vulgaris, Bacillus subtilis, and Staphylococcus pyogenes. The complexes with Co(II), Ni(II), and Cu(II) ions as the metal center exhibited superior activity against both Gram-positive and Gram-negative bacteria to that of standard. In order to assess their antimicrobial potential and molecular docking, AutoDock tools were utilized.



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