Synthesis, characterization, and biological evaluation of organotin(IV) complexes derived from Schiff bases of 3-methoxybenzohydrazide

Abstract New diorganotin(IV) complexes (R2SnL, where R is Me, Et, Bu, and Ph) of Schiff base ligands N'-(2-hydroxybenzylidene)-3-methoxybenzohydrazide (H2L1), N'-(5-chloro-2-hydroxybenzylidene)-3-methoxybenzohydrazide (H2L2), N'-(2-hydroxy-5-nitrobenzylidene)-3-methoxybenzohydrazide (H2L3), and N'-(4-(diethylamino)-2-hydroxybenzylidene)-3-methoxybenzohydrazidefrom (H2L4) derived from 3-methoxybenzohydrazide with salicylaldehyde and its derivatives were synthesized. The ligands and their metal complexes were structurally characterized by spectroscopic techniques (FT-IR, 1H, 13C, and 119Sn NMR), elemental analysis, mass spectrometry, melting point, and molar conductance studies. The spectral data showed that ligands are coordinated to the tin atom in a tridentate manner with N and O donor sites of the azomethine-N, enolic-O, and aromatic hydroxyl-O to form a penta-coordinated geometry around central tin atom. The molar conductance data revealed that all compounds are non-electrolytes. In vitro antimicrobial activities of compounds were determined against various pathogens with reference to standard antibiotics which showed that compounds (12) (Ph2SnL2) and (16) (Ph2SnL3) are the most potent antimicrobial agents. Furthermore, the compounds were evaluated for antioxidant activity by using DPPH assay. The results obtained emphasized that the phenyl derivatives of complexes have enhanced antimicrobial and antioxidant activities as compared to other complexes. To check the drug-likeness, in silico studies of the synthesized compounds were carried out which described that all the compounds except (12) (Ph2SnL2), (19) (Bu2SnL4), and (20) (Ph2SnL4) can be used as orally active drugs. Graphical Abstract


Introduction
Infectious diseases caused by microbes have been harming human civilizations by reducing immunological systems resulting in higher rates of morbidity and mortality. Therefore, to circumvent these diseases, research on the synthesis and applications of antimicrobial drugs with better efficiency has become a critical requirement for medicinal chemists [1]. Schiff bases with hydrazide moiety are considered as "privileged ligands" due to their facile synthesis, good solubility, and novel structural features [2]. They have good antibacterial, antifungal [3][4][5], anticancer [6], antiplatelet, and anti-inflammatory activities [7,8].
The biocidal activity of Schiff bases becomes enhanced upon complexation with metal atom, and the complexes are supposed to exert their effect by interaction with intracellular biomolecules, inhibition of enzymes, augmentation in lipophilicity, and modification of cell membrane functions [9][10][11]. The biological efficiency of metal complexes depends on the nature of the ligand, organic moiety attached to tin atom, oxidation state, coordination behavior of metal, and kinetic and thermodynamic stability of compounds toward biological receptors [12]. The various organic moieties linked with metal atom affect the solubility of these compounds in the lipid that allows the passive diffusion of the compound across cellular membranes.
Organotin compounds are a potential area of research because of their broad range of medicinal, industrial, and technological applications [13][14][15]. They are used as fungicides, molluscicides, miticides, and in various biocidal formulations [16]. Moreover, they have gained application as antifouling agents and disinfectants for surface materials [17][18][19]. Organotin compounds have been used as preservatives for textiles, wood, leather, electrical equipment, and glass [20]. Organotin compounds have useful catalytic activity in esterification reactions, which may be attributed due to low-energy 5d orbitals of the tin atom [21]. These compounds have also been used as heat stabilizers in poly(vinylidene chloride), paraffins, and modified plastics [22][23][24].
To extend the knowledge in the medical research field, we have synthesized some organotin complexes of Schiff base ligands derived from 3-methoxybenzohydrazide with salicylaldehyde and its derivatives and characterized them by melting point determination, molar conductance measurement, elemental analysis, spectroscopic methods like UV-Vis, FT-IR, ( 1 H, 13 C, and 119 Sn) NMR and mass spectrometry techniques. The synthesized ligands, along with their organotin complexes, were tested for their in vitro antimicrobial activity against two Gram-positive bacteria: Bacillus cereus and Bacillus subtilis, two Gram-negative bacteria: Escherichia coli and Pseudomonas aeruginosa and two fungal strains: Aspergillus niger and Candida albicans by using serial dilution technique and their minimum inhibitory concentration (MIC) values were calculated. The antimicrobial results of the compounds were supported by ADME prediction. The antioxidant activity of compounds was also measured by using the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The results of this study can be useful for researchers to enhance the knowledge of the antimicrobial and antioxidant activities of Schiff base ligands and their organotin complexes.
The spectral data elucidated penta-coordinated geometry around central tin atom with tridentate (NOO) Schiff base ligands. Details of the synthesized compounds along with the numbering pattern of the ligand and alkyl or aryl moieties attached with the central tin atom have been shown in Scheme 1.

Electronic spectra
The UV-Vis spectra of Schiff base ligands and their diorganotin(IV) complexes were performed in absolute methanol. The characteristic UV-Vis spectrum of the ligands contains a strong absorption band at 282-300 nm because of p-p Ã electronic transitions in the phenyl ring which remain unaffected upon complexation, indicating its nonparticipation during complexation and another band at 362-388 nm was attributed to the n-p Ã transition of s > C ¼ N (azomethine) chromophore and during complexation shifted to 395-410 nm which confirmed the donation of electrons from the azomethine nitrogen to central Sn atom [26].

FT-IR spectra
The presence of certain functional groups and binding mode of the synthesized Schiff base ligands to metal could be explored by vibrational spectroscopy. The IR spectra of the Schiff base ligands and organotin(IV) complexes were recorded and compared to understand the binding site of the Schiff base ligands to the central tin atom. A broad absorption band in the range 3413-3436 cm À1 appeared in the spectra of the free ligands due to stretching vibration v(O-H), but it was absent in complexes thereby showing the deprotonation of hydroxyl group which indicates the linkage of Schiff base ligands to the central tin atom through oxygen atom of hydroxyl group [27]. Significant peaks observed in the Schiff base ligand spectra at 1690-1698 cm À1 and 3237-3238 cm À1 which are associated with stretching vibration (C ¼ O) and (N-H), respectively, confirmed the existence of ketonic form in solid state and these peaks disappeared during complexation, disclosed that ligands undergo tautomerization to enolic form, confirmed the linkage of oxygen atom to the central tin atom. A strong band at 1615-1618 cm À1 is due to azomethine (H-C ¼ N-) fragment, got shifted to downward frequencies at 1598-1607 cm À1 , confirming the participation of azomethine nitrogen in complexation processes with tin atom. There are some new bands in the spectra of complexes in the range 600-612 cm À1 , 537-574 cm À1 , and 430-449 cm À1 ascribed to (Sn-O), (Sn-N) and (Sn-C) respectively, assigning the formation of tin complexes [8,28].

H NMR spectra
In 1 H NMR spectra, the number of protons, obtained from the integration, is in accordance with the proposed structure of compounds and further supports the mode of binding of ligands to the metal atom. A singlet at d 11.28-11.97 ppm due to the phenolic proton of the Schiff base ligands disappeared in the spectra of complexes and confirms the linkage of phenolic proton with the central tin atom. The Appearance of another singlet at d 9.68-9.76 ppm in the spectra of Schiff base ligands, attributed to N-H proton which disappeared upon complexation showed tautomerization to the enolic form and involvement of the enolic oxygen in coordination with tin atom [29]. The signal assigned to an imine proton (HC ¼ N) at d 8.29-8.64 ppm in the spectra of free ligands, shifted upfield to d 8.51-8.84 ppm on complexation and, was flanked by a pair of satellite peaks, clearly indicating the involvement of azomethine nitrogen in the complexation process [30]. The heteronuclear coupling constant 3 J( 119 Sn-1 H) corresponding to azomethine satellite peaks lies in the range of 40-48 Hz and confirms the formation of complexes [31]. Aromatic protons of the ligands appeared at d 6.14-8.28 ppm, remain unaltered upon complexation, and showed their noninvolvement in complex formation. New signals are observed in diorganotin(IV) complexes because of the presence of alkyl and aryl groups. The phenyl complexes displayed a complex pattern of peaks in the range d 7.32-7.87 ppm [32,33]. The 1 H NMR spectra of the synthesized compounds are provided in Supplemental Materials Figures S1-S11.

C NMR spectra
To confirm the coordination of the ligands to the central tin atom, 13 C NMR spectra of compounds were documented in CDCl 3 . In the Schiff base ligands spectra, the peak due to 8.64-14.91, and d 9.12-38.48 ppm are assigned to carbon atoms of the methyl, ethyl, and butyl groups, respectively. The resonance at d 109.37-115.24 ppm is observed due to carbons of phenyl ring bonded to the tin atom [34,35]. The heteronuclear coupling 1 J( 13 C- 119 Sn) in organotin(IV) complxes gives supporting information about the coordination environment around the tin atom. For the synthesized complexes, the value of the coupling constant observed is 1 J ( 13 C- 119 Sn) in the range 562-616 Hz which assigns pentacoordinated geometry to organotin (IV) complexes [36]. The 13 C NMR spectra of the synthesized compounds are provided in Supplemental Materials Figures S12-S22. 119 Sn NMR spectra Further structural confirmation of the representative complexes was given by 119 Sn NMR spectra. A sharp singlet suggested that all diorganotindichlorides have been consumed and new complexes were formed. The values of chemical shift depend upon the nature and orientation of the organic groups attached with tin atom. The chemical shift values shifted to upfield with the increase in electron-releasing power of organic group attached with Sn atom. Signals at d À 144 to À146, d À 159 to À162, d À 230 to À235, and d À 326 to À329 ppm are assigned for methyl, ethyl, butyl, and phenyl complexes, respectively. These values showed a penta-coordinated environment around tin atom with trigonal bipyramidal geometry [37][38][39]. The 1 H NMR spectra of the synthesized compounds are presented in Supplemental Materials Figures S23-S37.

Mass spectra
Mass spectroscopic elucidation of the synthesized Schiff base ligands and their diorganotin complexes were performed in methanol solvent. The mass spectra indicated that there is a close agreement between the expected and resultant mass of the compounds. The Schiff base ligand [H 2 L 3 ] (3) displayed the molecular ion peak at m/z 318.3220 which is in agreement with the calculated value. In the mass spectra of diphenyltin(IV) complex, [Ph 2 SnL 3 ] (16), molecular ion peak at m/z 616.5142 was observed, which is also in agreement with the expected value. The obtained mass spectrum was consistent with formation of metal complexes in 1:1 stoichiometry. The 1 H NMR spectra of the synthesized compounds are provided in Supplemental Materials Powder XRD X-ray powder diffraction was used to examine the nature of synthesized compounds and was recorded at room temperature over the range 2h ¼ 10-80 degree at wavelength 1.5406 Å. The XRD of compounds 3 (H 2 L 3 ) and 16 (Ph 2 SnL 3 ) are given in Figure 1 (Supplemental Materials Figure S46). Sharp peaks were observed which revealed the crystalline nature of compounds. D XRD was calculated by using the Debye-Scherrer Equation: The average crystallite size of complexes was 58.23 nm and 51.91 nm, and the maxima was at 2h ¼ 17.48 and 17.01 for compounds 3 (H 2 L 3 ) and 16 (Ph 2 SnL 3 ), respectively.

Antioxidant activity
Oxidative stress arises in our body due to unnecessary generation of free radicals and results in the progression of various diseases [40,41]. Supplementation of various antioxidants causes a significant reduction in the risk for chronic diseases. Keeping in view the above facts, the designed compounds were examined for in vitro antioxidant potential using DPPH assay. The % scavenging activity was enhanced with an increase in concentration of tested compounds as shown in Table S1 and Figure S47 (Supplemental Materials). In the synthesized Schiff base ligands, free phenolic hydrogen is present which gives the hydrogen radical and results in the initiation of radical chain and they serve as an antioxidant agent. Among the synthesized compounds, free ligands showed radical scavenging potential of 41.45-48.45% at 100 mg/mL concentration. Schiff base ligand 2 (H 2 L 2 ) with electronegative chloro atom served as good antioxidant while Schiff base ligand 4 (H 2 L 4 ) with electron releasing diethylamine group, showed poor activity. On complexation, the azomethine nitrogen coordinated with the central tin metal which causes easy abstraction of azomethine hydrogen radical, results in enhancement in the radical scavenging potential upto 60.12% at 100 mg/mL concentration. Phenyl complexes having more conjugated system were found to be most active in all analog complexes due to stabilization of radical by the conjugation with benzene ring. The order of antioxidant activity of diorganotin(IV) complexes is as follow: phenyl > butyl > ethyl > methyl. In all the synthesized compounds, compound 12 (Ph 2 SnL 2 ) was found to be most active (60.12% at 100 mg/mL) and compounds 16 (Ph 2 SnL 3 ) and 20 (Ph 2 SnL 4 ) were also having good scavenging activity.

Antimicrobial activity
The newly designed compounds displayed efficient antioxidant activity, so it is considered worthwhile to explore their other biological activities, like antimicrobial activity. The potential of the synthetic compounds (1-20) for microbial activity was investigated against two gram-positive bacteria (B. cereus, B. subtilis), two gram-negative bacteria (E. coli and P. aeruginosa) and two fungal strains (C. albicans and A. niger). DMSO and standard antimicrobial drug candidates (ciprofloxacin and fluconazole) were taken as negative and positive controls, respectively. The MICs of our synthesized compounds were obtained by using serial dilution technique [42,43] as summarized in Table S2 and Figure S48 (Supplemental Materials).
The antimicrobial screening revealed that free ligands and their metal complexes have independently changeable degrees of inhibitory effects against the growth of the tested microbial species. Metal complexes have significantly higher potential against microbial strains than free ligands, which can be explained by Overtone's concept and Tweedy's chelation theory [44]. As stated by Overtone's concept of cell permeability, lipophilicity of the complexes plays a vital importance in the antimicrobial activity as it favors interaction with the biological target. The lipid membrane surrounding the cell permits the easy passage of lipid-soluble substances, i.e., only hydrophobic material, through the lipid bilayer of cell membrane and blocks the metal binding sites which cause interference in the cell that may lead to cell death. Moreover, Tweedy's chelation theory stated that the polarity of the metal ion is decreased on chelation, owing to partial sharing of the metal positive charge with donor groups. Chelation enhances the delocalization of w -electrons over the chelate ring and therefore increases the lipophilic capacity of the tin metal complexes. This facile the permeation of the metal complexes into the lipid layer, which hindered the growth of the microorganisms. The inhibitory effect of Schiff base ligands may be explained on behalf of the formation of hydrogen bond between active centers of cell constituents and azomethine group (>C ¼ N-), resulting in obstacle in normal cellular processes. It was observed that concentration plays a vital role in inhibition of microbials. On increasing the concentration of title compounds, degree of inhibition of microbials increases.
For all tested bacterial and fungal strains, compounds (Ph 2 SnL 2 ) (12) and (Ph 2 SnL 3 ) (16) were found to be most efficient with MIC value 0.004-0.009 lmol/mL, even more active than standard drug ciprofloxacin (MIC ¼ 0.0047 mmol/mL) and fluconazole (MIC ¼ 0.0102). Complex (Ph 2 SnL 2 ) (8) showed efficient activity toward fungal strains (C. albicans and A. niger), exhibited MIC value 0.005 lmol/ mL, and also showed good activity toward bacterial strains with MIC value 0.010-0.021 lmol/mL. Complexes (Bu 2 SnL 1 ) (7), (Bu 2 SnL 2 ) (11), and (Bu 2 SnL 3 ) (15) also exhibited efficient inhibitory effect with MIC value 0.011-0.023 lmol/mL. Complexes having phenyl group showed better inhibition as compared to the complexes having methyl, ethyl, and butyl groups attached to tin atom. This may be attributed to delocalized p electrons over the planer phenyl group linked with the tin atom which increases the lipophilicity of complexes through the lipid bilayer of the microorganism which hindered the growth of the microorganisms [45]. The obtained results were related with the literature-reported data and concluded that synthesized compounds are equally or even more active than some previously synthesized organotin compounds [46,47]. The antimicrobial activity order of diorganotin(IV) complexes was observed as: phenyl > butyl > ethyl > methyl which is same as followed by antioxidant ability.

Structure-activity relationship
We have attempted a structure-activity relationship on analyzing antimicrobial activity data of Schiff base ligands and their complexes carefully, it was observed that the Schiff base ligands (1, 2, 3, and 4) do not show potent antimicrobial activity but when coordinated with tin metal, the potency was suddenly improved (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20), which revealed that tin metal is effective for research work toward antimicrobial activity. In addition, compounds having electron-withdrawing substituent displayed better activity than those with electron-releasing substituent against bacterial as well as fungal strains. The compounds showed enhanced biological response for fungal strains than bacterial strains. It was also observed that compounds containing phenyl substituent displayed good and broad spectrum activity toward all the bacterial strains under study.

ADME properties
The synthesized ligand and complexes were screened for their bioactivity score by Molinspiration (http:/molinspiration.com/cgi-bin/properties). Bioactivity score of the compounds provoked us to know the drug-like properties and existing number of violations, if any, from well-known Lipinski's rules. Lipinski's rules are: the molecular weight of the compounds should be 500 Dalton, the log p value should be 5, the number of hydrogen bond donor should be 5, and hydrogen bond acceptor should be 10.
Among these, if more than two criteria are violated then the drug is not an orally active drug. The ADME properties were calculated and represented in Table S3 (Supplemental Materials) and, found that all the synthesized compounds have molecular weight 500 Dalton, the number of hydrogen bond donor are 5 and hydrogen bond acceptor are 10. Therefore, all compounds of series are not violating more than two rules. Therefore, they all can be used as orally active drugs in accordance with Lipinski's rule. Lipophilicity of compounds was described by log p values. All compounds except 12, 19, and 20 have log p value 5 that signify good permeability across the cell membrane. Good hydrogen bonding ability of compounds leads to the more total polar surface area, which results in the enhanced transport properties of compounds. All the compounds have TPSA values less than 13 Å 2 which showed that they have strong transport characteristics. To compute the percentage absorption of the compound, we used the formula % Abs ¼ 109 -(0.345 Â TPSA) [48]. It was noted that all the compounds exhibit significant absorption (% Abs ¼ 67.51 À 90.91). The value of % absorbance indicated that the synthesized complexes are better drugs than their parent ligands.

Materials and methods
All the chemicals used for our synthetic work like 3-methoxybenzohydrazide, salicylaldehyde, 5-chlorosalicylaldehyde, 5nitrosalicylaldehyde, 4-N,N-diethylaminosalicylaldehyde and diorganotin(IV)dichloride derivatives were procured from commercial sources and used as received. Solvents used were dried before use according to the previous standard methods [49]. The compounds were synthesized in a dry atmosphere. The reactions were performed in round bottom flask and the progress of reaction was visualized on TLC by using UV light indicator. Shimadzu IR affinity-I 8000 spectrophotometer was used to record the IR-spectra of the ligand and its metal complexes in wavelength range 400-4000 cm À1 using KBr pellets. 1 H, 13 C, and 119 Sn NMR spectra were obtained using Bruker Avance II spectrophotometer with resonance operating at 400, 100.6, and 149.2 MHz, respectively, using TMS as an internal standard in CDCl 3 solvents. The chemical shifts (d) were expressed in parts per million (ppm) relative to tetramethylsilane and tetramethyltin as internal standards and their coupling constants (J) were quoted in Hertz (Hz). To represent the signals splitting pattern in 1 H NMR spectra the following abbreviations are as follows: s, singlet; d, doublet; t, triplet; q, quartet; dd, doublet of doublet; m, multiplet. UV-Vis-NIR Varian Cary 5000 spectrometer was used for carry out the absorption titration of compounds. The Perkin Elmer 2400 elemental analyzer was used for quantitative determination of C, H, and N elements. Tin was assessed gravimetrically as tin oxide after decomposition of the compounds with concentrated nitric acid. Melting points were measured in open capillary by using electrothermal melting point apparatus and were uncorrected. The molar conductance was noted on conductivity bridge model-306 at room temperature. Mass spectrum analysis of compounds was obtained on SCIEX-QTOF instrument in methanol. The Supplemental Materials contain sample 1 H, 13 C, and 119 Sn NMR spectra and mass spectra for the products (Figures S1-S45).

Synthesis of diorganotin(IV) complexes (5-20)
Schiff base ligand H 2 L 1 (1 mmol, 0.270 g)/H 2 L 2 (1 mmol, 0.304 g)/H 2 L 3 (1 mmol, 0.315 g)/H 2 L 4 (1 mmol, 0.341 g) was reacted with few drops of triethylamine in dry THF and stirred for 30 min at room temperature. One equivalent dimethyltin dichloride (1 mmol, 2.190 g)/diethyltin dichloride (1 mmol, 0.240 g)/dibutyltin dichloride (1 mmol, 0.300 g)/ diphenyltin dichloride (1 mmol, 0.340 g) was added and the resulting mixture was refluxed for 9-10 h. The reaction mixture was left overnight to settle. The Et 3 NHCl salt formed along with the desired product which was removed by filtration. The solvent was removed with the help of a vacuum pump. The crude product was pured by recrystallization with dry hexane. Details of the synthesized compounds are described in Scheme 1.

Antimicrobial activity
The evaluation of the synthesized compounds for their antimicrobial activity was performed by serial dilution method toward two Gram-positive bacteria. (Bacillus cereus (MTCC 1305), Bacillus subtilis (MTCC 1427); two Gram-negative bacteria (Escherichia coli (MTCC 732), Pseudomonas aeruginosa (MTCC 424) and two fungal strains (Aspergillus niger (MTCC 9933), Candida albicans (MTCC 227) and their inhibitory effect were noted in term of MIC values [50,51]. The bacterial cultures were grown on nutrient broth and fungal culture were grown on potato dextrose broth. To perform the experiment, the stock solutions were made by dissolving 5 mg of the test compounds in 5 mL of DMSO then 1 mL of these test compounds were transferred to 9 mL of DMSO to make solutions having a concentration of 100 lg mL À1 and these solutions were further serially diluted by adding DMSO to attain the concentrations as follow: 50, 25, 12.5, 6.25, 3.12, and 1.56 lg mL À1 , and 1 mL of these solutions were poured to test tubes containing 1 mL of bacterial/ fungal culture. The bacterial strain test tubes were incubated for one day at 37 C for 24 h and in the case of fungal strain test tubes, were incubated for one week at room temperature. The experimental procedure was performed in triplicate and examined data were noted every time and reported as mean values.

Antioxidant activity
Schiff base ligands and their diorganotin(IV) complexes (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) were assessed for antioxidant activity by measuring the change in the absorbance of DPPH at 517 nm spectrophotometrically [52]. The different concentration of compounds (100, 50, 25, and 12.5 mg/mL) was prepared in DMSO. The 1 mL of above-prepared solution was mixed into the test tube containing 1 mL of DPPH in DMSO (5 mg in 100 mL) and diluted in DMSO to total volume of 3 mL with DMSO. The above-prepared mixture was incubated for 30 min at room temperature in dark. The absorbance of compounds was observed at 517 nm by spectrophotometer using DPPH with DMSO as blank and ascorbic acid as a standard and percentage radical scavenging activity was calculated. The equation used for calculation of radical scavenging activity: where B is absorbance of blank and S is absorbance of sample.

Conclusions
In this research work, we have synthesized new diorganotin(IV) compounds (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20) of Schiff base ligands derived from 3-methoxybenzohydrazide (1-4) and characterized them by various spectral techniques like (FT-IR, UV-Vis, 1 H, 13 C, and 119 Sn NMR), elemental analysis, mass spectrometry, melting points, and molar conductance measurements which indicated coordination of ligands in tridentate manner (NOO) via azomethine-N, enolic-O, and aromatic hydroxyl-O atoms to form penta-coordinated geometry around tin atom. The molar conductance data revealed that compounds are non-electrolytes in nature. The compounds were screened for antioxidant potential against stable free radical 1,1-diphenyl-2-picryl-hydrazyl, and results obtained indicated that complex 12 (Ph 2 SnL 14 ) exhibited the highest radical scavenging efficiency. The antimicrobial activity of compounds studied against bacterial and fungal strains showed that diorganotin(IV) complexes have shown better antimicrobial activity than their respective Schiff base ligands. Complexes (Ph 2 SnL 3 ) (12) and (Ph 2 SnL 4 ) (16), having MIC values 0.005 lmol/mL and 0.004-0.009 lmol/mL, respectively, were most effective antimicrobial agent. As the antimicrobial activity results of some compounds of the current series displayed better activity than the standard drugs ciprofloxacin and fluconazole toward few microbes, so these compounds could be further studied for the augmentation of antimicrobial therapeutic action. In silico studies of the compounds emphasized that percentage absorbance was higher for the complexes than ligands which suggest improved pharmacological properties of complexes as compared to their respective ligands.