2.5    ¹³C NMR

¹³C NMR spectra of the Schiff bases ligand and their complexes were recorded in DMSO-d₆and are given in the experimental part. The ligands HL_I–HL₄ displayed characteristic signal of carbon of carbonyl and azomethine (CH=N) groups at δ 163.2– 163.3 ppm and δ152.3– 152.6 ppm respectively [17].Which shifted towards lower values in the complexes, revealed the participation of carbonyl and azomethine carbon in coordination. The signals at δ 113.5-147 ppm and δ 20.8-74.7 ppm were assigned to carbons of aromatic and aliphatic regions of ligands, respectively. The signals at δ 8.5-8.6 ppm, δ 8.5-13.2 ppm and δ 8.2-28.4 ppm revealed the attachment of methyl, ethyl and n-butyl groups with the central metal atom. Similarly the signal at δ 128.1-129.2 ppm were assigned to the phenyl group attached to the tin.

¹¹⁹Sn NMR is a influential technique to find the coordination number of the central tin atom. The characteristic resonance peaks in the ¹¹⁹Sn NMR spectra of all of the complexes were recorded in CDCl₃and DMSO-d₆. The ¹¹⁹Sn chemical shifts of organotin(IV) derivatives were in the range of -138.5 to -147.6 ppm [18] indicating penta-coordinated environment around tin atom. 

3.      Antimicrobial activity 

The Schiff base ligands and their organotin(IV) complexes were screened for theirin vitro antimicrobial activities along with conventional bactericide norfloxacin and fungicide fluconazole for comparing the activity of the compounds. The microorganisms used in the present study include S. aureus, K. pneumonia, E. coli and E.aerogenes and fungi C. albicansand A. niger 

The antimicrobial activity test results of all the tested compounds revealed their ability to act against bacterial and fungal strains appreciably and some of the compounds exhibited better activity than the standard drugs used in the assay. In the entire series, the pMIC of the compounds ranged between 0.874–2.066 μmol/mL and 0.890–2.066 μmol/mL against Gram-positive and Gram-negative bacteria, respectively. Compounds 12, 16 and 20 showed highest antibacterial activity followed by compounds 7, 8, 11, and 19 in the entire series. Similarly, antifungal data suggested that almost same results were obtained as in the antibacterial assay and compounds 11, 12, 15, 16, 19 and 20 displayed better activities than other compounds of the series and pMIC for antifungal activity of the entire series ranged from 0.890–2.066 μmol/mL.

The antimicrobial data reveals that the organotin (IV) complexes were found to be better antimicrobial agent as compared to their respective free ligands. The enhancement in the antimicrobial activity of complexes may be due to the delocalization of electron over the whole chelate ring, thereby increasing the lipophilicity of the target compound. This increased lipophilicity of the drug molecule favours its permeation through the cell membrane of microorganism [19]. The other factors which may affect the bioactivity of metal complexes include the number and the nature of the organic groups/halogen atoms directly bound to tin atom. The mode of action of metal complexes may be linked with the formation of hydrogen bond with the active centers of the cell constituents by interfering with normal cell processes. 

4.      QSAR analysis

Quantitative structure activity relationship (QSAR) studies between the in vitro antimicrobial activity and descriptors coding for lipophilic, electronic, steric and topological properties of four substituted o-vanillin Schiff bases and their sixteen organotin(IV) complexes were performed to find out the relationship between structural variants and antimicrobial activity using the Linear Free Energy Relationship model (LFER) described by Hansch and Fujita [20]. The dependent variable pMIC (i.e. –log MIC) used as in QSAR study was obtained by taking negative logarithm of observed antimicrobial activities (Table 2).

The different independent variables (molecular descriptors) like log of octanol–water partition coefficient (log P), Molar Refractivity (MR), Kier’s molecular connectivity (⁰c, ⁰c^v, ¹c, ¹c^v, ²c, ²c^v) and shape (k₁, k₂, k₃,ka_1, ka_2,ka₃) topological indices, Randic topological index (R),Balaban topological index (J), Wiener topological index (W), Total energy (Te), energies of Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO), dipole moment (m), Nuclear repulsion Energy (Nu.E) andElectronic Energy (Ele.E), calculated for ligands and their organotin (IV) complexes are presented in (Table 3) [21-26].

High collinearity (r > 0.8) was observed between different parameters i.e. molecular descriptors. The high interrelationship was observed between k₁ and Ele.E (r = 0.996), W and ¹χ (r = 0.995), ⁰χ and Ele.E (r = 0.995) and low interrelationship was observed between HOMO and W (r = 0.022) and HOMO and ¹χ (r = 0.028). The correlation matrix indicated that the antimicrobial activity of synthesized ligands and their organotin (IV) complexes are governed by topological parameters like molecular connectivity, shape indices and electronic energy. 

The antifungal activity of synthesized derivatives against A. nigeris governed by the second order shape attribute (Kappa shape indices), κ₂(Eq. 1).

QSAR model for antifungal activity against A. niger

pMIC_an=0.134 κ₂ – 0.358 Eq. 1       

n = 20                     r = 0.958                r² = 0.918               q²= 0.898               s = 0.095                F = 201.482

Here and thereafter, n - number of data points, r - correlation coefficient, r²-squared correlation coefficient, q² - cross validated r² obtained by leave one out method, s - standard error of the estimate and F - Fischer statistics.

The QSAR model represented by Eq. 1 for antifungal activity against A. nigerdemonstrated the importance of second order Kappa shape indices (κ₂).According to Kier, the shape of a molecule may be partitioned into attributes, each describable by the count of bonds of various path lengths [27]. The basis for devising a relative index of shape is given by the relationship of the number of path of length l in the molecule i, ^lP_i, to some reference values based on molecules with a given number of atoms, n, in which the values of ^lP are maximum and minimum, ^lP_max and ^lP_min[28]. The second order shape attribute, κ₂, is given by the following expression:

κ₂ = (n-1)(n-2)²/(²P_i)²

 The equation 1 highlighted the positive correlation between second order Kappa shape indices (κ₂) for the synthesized compounds and antifungal activity against A.niger which depicts that compounds having high κ₂ values (Table 3) will have high antifungal potential and the results presented in the Table 6 are in concordance with the model expressed by Eq. 1.

The linear regression model expressed by Eq. 1 was cross validated by its high q²values (q²= 0.898) obtained with Leave One Out (LOO) method. The basic requirement for becoming a QSAR model to be valid one is that it must possess q² valuehigher than 0.5 thus supporting the fact that model expressed by Eq. 1 is valid one [29]. The comparison of observed and predicted antifungal activities is presented in (Table 6).

The results of observed and predicted antifungal activities lie close to each other as evidenced by their low residual values (Table 6) which again supported the validity of model expressed by Eq. 1. The statistical validity of QSAR model was also cross checked by plotting the graphs of observed, predicted and residual pMIC activity values. The plot of predicted pMIC_anagainst observed pMIC_an(Figure 1)

QSAR models 2 – 8 were obtained by linear regression of the antibacterial and antifungal activity of synthesized derivatives against S. aureus, C. albicans, K. pneumoniae, E. coli, and E. aerogeneswith molecular descriptors.

QSAR model for antibacterial activity against S. aureus

pMIC_sa =- 0.000025 Ele.E + 0.083                                                                   Eq. 2      

n = 20                     r = 0.941                r² = 0.886               q² = 0.855              s = 0.109                F = 140.08

QSAR model for antifungal activity against C. albicans

pMIC_ca =0.119 ¹χ - 0.565                                                                                                   Eq. 3

n = 20                     r = 0.936                r² = 0.877               q² = 0.830              s = 0.115                F = 127.974

QSAR model for antifungal activity against C. albicans

pMIC_ca =0.119 R - 0.565                                                                                                   Eq. 4

n = 20                     r = 0.936                r² = 0.877               q² = 0.830              s = 0.115                F = 127.974

QSAR model for antibacterial activity against K. pneumoniae

pMIC_kp =0.112 ¹χ – 0.327                                                                                  Eq. 5      

n = 20                     r = 0.924                r² = 0.853               q² = 0.825              s = 0.120                F = 104.331

QSAR model for antibacterial activity against K. pneumoniae

pMIC_kp =0.112 R – 0.327                                                                                  Eq. 6      

n = 20                     r = 0.924                r² = 0.853               q² = 0.825              s = 0.120                F = 104.331

QSAR model for antibacterial activity against E. coli

pMIC_ec =0.123 κ₂ – 0.239                                                                                 Eq. 7      

n = 20                     r = 0.915                r² = 0.837               q²= 0.804               s = 0.128                F = 92.54

QSAR model for antibacterial activity against E. aerogenes

pMIC_ea=0.056 κ₁ – 0.175                                                                                  Eq. 8      

n = 20                     r = 0.900                r² = 0.811               q² = 0.764              s = 0.115                F = 77.022

The linear regression model represented by Eq. 2 revealed that the antibacterial activity against S. aureus is governed by the Electronic Energy of the molecule (Ele.E). As the coefficient of electronic energy is negative, therefore the antibacterial activity against S. aureuswill increase with decrease in Ele.E values, that can be checked from the results presented in Table 3 and 6.

Eq. 3 and 4 were obtained for the regression model describing the antifungal activity of the synthesized derivatives against C. albicans both of which indicated that first order molecular connectivity index (¹χ) and Randic (R) topological parameter were equally affecting the antifungal activity against C. albicans as all the statistical parameters for both these equations were same. The positive coefficient of first order molecular connectivity index (¹χ) and Randic (R) parameter in Eq. 3 and 4 demonstrated that the antifungal of the synthesized derivatives will increase with increase in value of first order molecular connectivity index (¹χ) and Randic (R) parameter.

Similarly the regression analysis for antibacterial activity of synthesized derivatives against K. pneumoniae came out with two models represented by Eq. 5 and 6 thus indicating the fact that antibacterial activity against K. pneumoniae is governed by two parameters viz.first order molecular connectivity index (¹χ) and Randic (R) parameter to an equal extent. Both of these models have same statistical parameters and thus indicated that the predicted antibacterial activity against K. pneumoniae will be same whatever the parameter we use for prediction of activity out of these two molecular descriptors. The outcome of QSAR models represented by Eq. 3 to 6 revealed the fact that K. pneumoniae and C. albicans may have similar type of binding site in their target receptor to which these molecules are binding.

QSAR model represented by Eq. 7 indicated the importance of second order Kappa shape indices(κ₂) in describing the antibacterial activity against E. coli. The positive correlation of the molecular descriptor second order Kappa shape indices (κ₂) with antibacterial activity revealed that increase in the value of κ₂will lead to an increase in antibacterial activity against E. coli.

The antibacterial activity of synthesized derivatives against E. aerogenes was governed by first order Kappa shape indices (κ₁) as demonstrated by Eq. 8. The QSAR models represented by Eq. 2-8 have got high r, r²,q² and F values and low s values which indicated that that the models are valid one. The low residual values obtained after prediction of activity using these models (Table 6)confirmed the fact that models expressed by Eq. 2 – Eq. 8 were also valid ones.

5.      Experimental

5.1 Materials and methods

The chemicals used were of analytical grade (Aldrich) and solvents were purified according to standard procedures. The complexes were synthesized under anhydrous condition in inert atmosphere. The molar conductance was measured in dry DMSO using Systronics conductivity bridge model-306. The IR spectra were recorded using a Spectrum BX Series FT-IR spectrophotometer in the range 400-4000 cm^-1, using KBr pellets.Multinuclear magnetic resonance spectra (¹H, ¹³C, ¹¹⁹Sn) were recorded on a Bruker Avance II 400 MHz NMR Spectrometer and all chemical shifts δ were reported in ppm relative to Tetra Methyl Silane (TMS) as an internal standard in CDCl₃and DMSO-d₆. Elemental analyses were carried out on a Perkin Elmer 2400 analyzer. Tin/chlorine was estimated gravimetrically. Bacterial and fungal strain was procured from Microbial Type Culture Collection (MTCC), IMTECH, Chandigarh.

5.2  Synthesis of Schiff base Ligands

Synthesis of ligands (HL₁-HL₄) were carried out in the following two steps:- 

(i)                  Synthesis of2-(4-methyl/nitro-benzyloxy)-3-methoxy-benzaldehyde (I).

The solution of o-vanillin (10 mmol) and K₂CO₃ (20 mmol) in 26 ml of DMF was stirred and p-methyl benzyl bromide (10 mmol) was added slowly. The mixture was allowed to stir overnight. Benzylation of o-vanillin with p-methyl benzyl bromide took place through Williamson ether formation resulted inthe formation of 2-(4-methyl-benzyloxy)-3-methoxy-benzaldehyde. The reaction mixture was then quenched with ice followed by the addition of 50 ml of water. The solid product obtained was filtered over the vaccum pump and dried. The same procedure was adopted for the synthesis of 2-(4-nitro-benzyloxy)-3-methoxy-benzaldehyde.

(ii)                Synthesis of Schiff base ligands (HL₁-HL₄)

Ligands HL_1-4were synthesized by reacting substituted o-vanillin (I) with p-toluic Hydrazide or benzhydrazide (II) in equimolar ratio in dry methanol. The solid product obtained after refluxing the reaction mixture for about 3-4 hrs was filtered and recrystallized in methanol. The same procedure was adopted for the synthesis of other Schiff base ligands.

Benzoic acid [3-methoxy-2-(4-methyl-benzyloxy)-benzyledene]-hydrazide [(HL₁, C₂₃H₂₂N₂O₃), (1)]

Yield: 82 %; m.p.: 170-171 ^°C; IR (KBr): ν = 3385 (NH), ν = 1689 (C=O), ν = 1550 (C=N) cm^-1; ¹H NMR (DMSO-d₆and CDCl₃):δ = 11.87 (s, 1H, -CH=N),8.71 (s, 1H, -NH ), 7.90-7.92 (d, 2H, C_2’-H & , C_6’-H), 7.49-7.58 (m, 4H, C_3’-H_, C_4’-H, C_5’-H & C₂-H), 7.35-7.37 (d, 2H, C_b-H &C_f-H), 7.16-7.18 (d, 2H, C_c-H & C_e-H), 7.10-7.12 (m, 2H, C₃-H& C₄-H), 4.97 (s, 2H, -OCH₂), 3.88 ( s, 3H, -OCH₃), 2.30 ( s, 3H, -CH₃) ppm; ¹³C NMR: δ = 163.3 (C=O), 152.6 (C=N), 146.4 (C-6), 143.5 (C-5), 137.2 (C-a), 133.8 (C-d), 133.4 (C-1’), 131.4 (C-4’), 128.6 (C-c& C-e), 128.4 (C-3’ & C-5’), 128.2 (C-2 ’& C-6’), 128.1 (C-b & C-f), 127.6 (C-2), 124 (C-3), 117.2 (C-1), 113.7 (C-4), 74.7 (OCH₂), 55.3 (OCH₃), 20.8 (CH₃ at Phring) ppm.

4-Nitro-Benzoic acid [3-methoxy-2-(4-methyl-benzyloxy)-benzyledene]-hydrazide [(HL₂, C₂₂H₁₉N₃O₅), (2)]

Yield: 86 %; m.p.: 174-175 ^°C;IR (KBr): ν = 3412 (NH), ν = 1695 (C=O), ν = 1557 (C=N) cm^-1; ¹H NMR (DMSO-d₆and CDCl₃): δ = 11.86 (s, 1H, -CH=N), 8.73 (s, 1H, -NH ),8.25-8.27 (d, 2H, C_c-H & C_e-H),7.89-7.91 (d, 2H, C_2’-H & , C_6’-H), 7.77-7.79 (d, 2H, C_b-H &C_f-H), 7.49-7.58 (m, 4H, C₂-H, C_3’-H_, C_4’-H& C_5’-H), 7.14-7.17 (m, 2H, C₃-H& C₄-H), 5.16 (s, 2H, -CH₂), 3.87 ( s, 3H, -OCH₃) ppm; ¹³C NMR: δ = 163.3 (C=O), 152.4 (C=N), 147 (C-6), 146.1 (C-5), 144.7 (C-d), 143.2 (C-a), 133.4 (C-1’), 131.5 (C-4’), 128.6 (C-3’& C-5’), 128.2 (C-b & C-f), 128.1 (C-2 ’& C-6’), 127.6 (C-c& C-e), 124.5 (C-2), 123.2 (C-3), 117.3(C-1), 113.8 (C-4), 73.5 (OCH₂), 55.7 (OCH₃) ppm.

4-Methyl-Benzoic acid [3-methoxy-2-(4-methyl-benzyloxy)-benzyledene]-hydrazide [(HL₃, C₂₄H₂₄N₂O₃), (3)]

Yield: 83 %; m.p.: 164-165 ^°C; IR (KBr): ν = 3373 (NH), ν = 1687 (C=O), ν = 1546 (C=N) cm^-1; ¹H NMR (DMSO-d₆and CDCl₃): δ = 11.79 (s, 1H, -CH=N), 8.70 (s, 1H, -NH ), 7.82-7.84 (d, 2H, C_2’-H & C_6’-H), 7.48-7.50 (d, 1H, C₂-H), 7.35-7.37 (d, 2H, C_3’-H& C_5’-H), 7.30-7.32 (d, 2H, C_b-H &C_f-H), 7.16-7.18 (d, 2H, C_c-H & C_e-H), 7.10-7.11 (m, 2H, C₃-H& C₄-H), 4.97 (s, 2H, -OCH₂), 3.88 ( s, 3H, -OCH₃), 2.39 ( s, 3H, -CH₃at Hydrazide ring), 2.30 ( s, 3H, -CH₃ at Ph ring) ppm; ¹³C NMR: δ = 163.2 (C=O), 152.5 (C=N), 146.4 (C-6), 143.3 (C-5), 141.5 (C-4’), 137.2 (C-a), 133.8 (C-d), 130.5 (C-1’), 128.7 (C-c& C-e), 128.6 (C-3’ & C-5’), 128.4 (C-2 ’& C-6’), 128.3 (C-b &C-f), 127.6 (C-2), 124 (C-3), 117.3 (C-1), 113.5 (C-4), 74.7 (OCH₂), 55.5 (OCH₃), 21.1 (CH₃at Hydrazide ring), 20.8 (CH₃at Ph ring) ppm.

4-Methyl-Benzoic acid [3-methoxy-2-(4-nitro-benzyloxy)-benzyledene]-hydrazide [(HL₄, C₂₃H₂₁N₃O₅), (4)]

Yield: 79 %; m.p.: 169-170 ^°C; IR (KBr): ν = 3394 (NH), ν = 1692 (C=O), ν = 1553 (C=N) cm^-1; ¹H NMR (DMSO-d₆ and CDCl₃): δ = 11.78 (s, 1H, -CH=N), 8.74 (s, 1H, -NH ), 8.24-8.27 (d, 2H, C_c-H &C_e-H), 7.77-7.80 (d, 4H, C_2’-H, C_6’-H, C_b-H &C_f-H), 7.54-7.55 (d, 1H, C₂-H), 7.28-7.30 (d, 2H, C_3’-H& C_5’-H), 7.10-7.17 (m, 2H, C₃-H& C₄-H), 5.16 (s, 2H, -OCH₂), 3.87 ( s, 3H, -OCH₃), 2.39 ( s, 3H, -CH₃at Hydrazide ring) ppm; ¹³C NMR: δ = 163.3 (C=O), 152.4 (C=N), 146.8 (C-6), 145.2 (C-5), 144.6 (C-d), 142 (C-a), 140.3 (C-4’), 135.2 (C-1’), 129.4 (C-3’& C-5’), 128.4 (C-b & C-f), 128.1 (C-2 ’& C-6’), 127.6 (C-c & C-e), 122.4 (C-2), 123.2 (C-3), 117.4 (C-1), 113.6 (C-4), 73.5 (OCH₂), 55.6 (OCH₃), 21 (CH₃ at Hydrazide ring) ppm.

7.2.1           General procedure for the synthesis of organotin complexes (5-20)

The sodium salt of Schiff base ligand was prepared by reacting ligand HL₁ (4.56 g, 10 mmol) and sodium metal (0.225 g, 10 mmol) in 30 mL dry methanol followed by the slow addition of Me₂SnCl₂ (2.19 g, 10 mmol) and then the reaction mixture was refluxed for 4h. The precipitated NaCl was filtered and solvent was evaporated on rotary evaporator under reduced pressure. The final product obtained was recrystallized from dry methanol and hexane and finally dried under reduced pressure. The other tin complexes were synthesized by reacting the ligands, HL₂/HL₃/HL₄ with R₂SnCl₂in 1:1 molar ratio by the same procedure.

[(Me₂Sn(L₁)Cl, C₂₅H₂₇ClN₂O₃Sn), (5)]

Yield: 74 %; m.p.: 126-127 ^°C; IR (KBr): ν = 1548 (C=N) cm^-1; ¹H NMR (DMSO-d₆and CDCl₃): δ = 11.98 (s, 1H, -CH=N), 7.94-7.96 (d, 2H, C_2’-H & , C_6’-H), 7.48-7.56 (m, 4H, C_3’-H_, C_4’-H, C_5’-H &C₂-H), 7.36-7.38 (d, 2H, C_b-H &C_f-H), 7.14-7.16 (d, 2H, C_c-H &C_e-H), 7.07-7.10 (m, 2H, C₃-H&C₄-H),4.96 (s, 2H, -OCH₂), 3.86 ( s, 3H, -OCH₃), 2.28 ( s, 3H, -CH₃), 1.19(s, 6H, -CH₃) ppm; ¹³C NMR: δ = 155.6 (C=O), 151.4 (C=N), 146.4 (C-6), 143.6 (C-5), 137.2 (C-a), 133.9 (C-d), 133.4 (C-1’), 131.6 (C-4’), 128.7 (C-c& C-e), 128.5 (C-3’ & C-5’), 128.3 (C-2 ’& C-6’), 128.4 (C-b & C-f), 127.6 (C-2), 124.2 (C-3), 117.2 (C-1), 113.9 (C-4), 74.7 (OCH₂), 55.7 (OCH₃), 20.8 (CH₃at Ph ring), 8.5 (Me)ppm.

 [(Et₂Sn(L₁)Cl, C₂₇H₃₁ClN₂O₃Sn), (6)]

Yield: 72 %; m.p.: 124-125 ^°C; IR (KBr): ν = 1545 (C=N) cm^-1; ¹H NMR (DMSO-d₆and CDCl₃): δ = 11.84 (s, 1H, -CH=N), 7.89-7.91 (d, 2H, C_2’-H & , C_6’-H), 7.50-7.56 (m, 4H, C_3’-H_,C_4’-H_,C_5’-H &C₂-H), 7.33-7.35 (d, 2H, C_b-H &C_f-H), 7.15-7.17 (d, 2H, C_c-H & C_e-H),7.08-7.11 (m, 2H, C₃-H& C₄-H), 5.01 (s, 2H, -OCH₂), 3.87 ( s, 3H, -OCH₃), 2.28 ( s, 3H, -CH₃), 3.06-3.11 (m, 4H,-CH₂), 1.23-1.26 (t, 6H,-CH₃) ppm; ¹³C NMR: δ = 155.6 (C=O), 151.6 (C=N), 147.3 (C-6), 144.3 (C-5), 141.7 (C-a), 138.2 (C-d), 134.9 (C-1’), 130.6 (C-4’), 129.9 (C-c& C-e), 129.1 (C-3’ & C-5’), 128.6 (C-2 ’& C-6’), 128.1 (C-b & C-f), 127.6 (C-2), 123 (C-3), 117.3 (C-1), 113.3 (C-4), 74.9 (OCH₂), 55.4 (OCH₃), 21 (CH₃ at Ph ring), 12.6 (Et), 8.6 (Et) ppm.

[(Bu₂Sn(L₁)Cl, C₃₁H₃₉ClN₂O₃Sn), (7)]

Yield: 66 %; m.p.: 121-122 ^°C; IR (KBr): ν = 1549 (C=N) cm^-1; ¹H NMR (DMSO-d₆ and CDCl₃): δ = 11.99 (s, 1H, -CH=N), 7.94-7.96 (d, 2H, C_2’-H & , C_6’-H), 7.49-7.58 (m, 4H, C_3’-H_, C_4’-H_, C_5’-H & C₂-H), 7.37-7.39 (d, 2H, C_b-H &C_f-H), 7.16-7.18 (d, 2H, C_c-H &C_e-H), 7.09-7.12 (m, 2H, C₃-H& C₄-H), 4.97 (s, 2H, -OCH₂), 3.88 ( s, 3H, -OCH₃), 2.29 ( s, 3H, -CH₃), 3.07-3.11 (m, 4H,-CH₂), 1.20-1.24 (m, 8H,-CH₂), 1.00-1.10 (t, 6H,-CH₃) ppm; ¹³C NMR: δ = 155.6 (C=O), 151.6 (C=N), 146.4 (C-6), 143.3 (C-5), 141.6 (C-a), 137.2 (C-d), 133.9 (C-1’), 130.5 (C-4’), 128.8 (C-c& C-e), 128.7 (C-3’ & C-5’), 128.5 (C-2 ’& C-6’), 128.4 (C-b & C-f), 127.7 (C-2), 124.1 (C-3), 117.2 (C-1), 113.7 (C-4), 74.7 (OCH₂), 55.7 (OCH₃), 26.4 (Bu), 24.5 (Bu),20.8 (CH₃ at Ph ring), 12 (Bu), 8.6 (Bu) ppm.

[(Ph₂Sn(L₁)Cl, C₃₅H₃₁ClN₂O₃Sn), (8)]

Yield: 73 %; m.p.: 139-140 ^°C; IR (KBr): ν = 1548 (C=N) cm^-1; ¹H NMR (DMSO-d₆ and CDCl₃): δ = 11.87(s, 1H, -CH=N), 8.76-8.90 (d, 2H, C_2’-H & , C_6’-H), 8.11-8.51 (m, 4H, C_3’-H_, C_4’-H_, C_5’-H & C₂-H ), 7.85-7.95 (d, 4H, C_b-H, C_f-H, C_c-H & C_e-H), 6.66-7.50 (m, 10H Ph and 2H, C₃-H& C₄-H), 4.97 (s, 2H, -OCH₂), 3.87 (s, 3H, -OCH₃), 2.38 (s, 3H, -CH₃) ppm; ¹³C NMR: δ = 155.7 (C=O), 151.5 (C=N), 146.4 (C-6), 143.3 (C-5), 140.4 (C-a), 134.7 (C-d), 133.9 (C-1’), 131.1 (C-4’), 128.8 (Ph), 128.7 (Ph), 128.6 (Ph), 128.5 (Ph), 128.4 (C-c& C-e), 128.2 (C-3’ & C-5’), 127.7 (C-2 ’& C-6’), 127.6 (C-b & C-f), 127.2 (C-2), 124.1 (C-3), 117.1 (C-1), 113.8 (C-4), 74.7 (OCH₂), 55.7 (OCH₃), 21.1 (CH₃ at Ph ring) ppm.

 [(Me₂Sn(L₂)Cl, C₂₄H₂₄ClN₃O₅Sn), (9)]

Yield: 77 %; m.p.: 128-129 ^°C; IR (KBr): ν = 1553 (C=N) cm^-1; ¹H NMR (DMSO-d₆and CDCl₃): δ= 11.85 (s, 1H, -CH=N),8.24-8.27 (d, 2H, C_c-H & C_e-H), 7.86-7.88 (d, 2H, C_2’-H & , C_6’-H), 7.72-7.74 (d, 2H, C_b-H &C_f-H), 7.52-7.57 (m, 4H,C₂-H, C_3’-H_, C_4’-H& C_5’-H), 7.13-7.17 (m, 2H, C₃-H& C₄-H), 5.01 (s, 2H, -OCH₂), 3.87 ( s, 3H, -OCH₃), 1.23 (s, 6H, -CH₃) ppm; ¹³C NMR: δ= 155.4 (C=O), 151.4 (C=N), 146.9 (C-6), 145.9 (C-5), 144.9 (C-d), 142.9 (C-a), 133.4 (C-1’), 131.6 (C-4’), 128.8, (C-3’& C-5’), 128.1 (C-b & C-f), 127.9 (C-2 ’& C-6’), 127.7 (C-c & C-e), 124.5 (C-2), 123.3 (C-3), 117.5 (C-1), 113.8 (C-4), 73.6 (OCH₂), 55.7 (OCH₃),8.6 (Me) ppm.

[(Et₂Sn(L₂)Cl, C₂₆H₂₈ClN₃O₅Sn), (10)]

Yield: 81 %; m.p.: 126-127 ^°C; IR (KBr): ν = 1555 (C=N) cm^-1;¹H NMR (DMSO-d₆ and CDCl₃): δ = 11.86 (s, 1H, -CH=N),8.25-8.28 (d, 2H, C_c-H &C_e-H), 7.85-7.87 (d, 2H, C_2’-H & , C_6’-H), 7.73-7.75 (d, 2H, C_b-H &C_f-H), 7.51-7.56 (m, 4H,C₂-H, C_3’-H_, C_4’-H& C_5’-H), 7.12-7.15 (m, 2H, C₃-H&C₄-H), 4.98 (s, 2H, -OCH₂), 3.85 ( s, 3H, -OCH₃), 3.08-3.11 (m, 4H,-CH₂), 1.22-1.26 (t, 6H,-CH₃) ppm; ¹³C NMR: δ= 155.3 (C=O), 151.5 (C=N), 145.3 (C-6), 142.3 (C-5), 135.9 (C-d), 132.9 (C-a), 132.2 (C-1’), 131.3 (C-4’), 129.7, (C-3’& C-5’), 128.7 (C-b & C-f), 128.2 (C-2 ’& C-6’), 128 (C-c & C-e), 127.5 (C-2), 125 (C-3), 117.1 (C-1), 113.5 (C-4), 74.7 (OCH₂), 55.5 (OCH₃), 13.2 (Et),8.8 (Et) ppm.

 [(Bu₂Sn(L₂)Cl, C₃₀H₃₆ClN₃O₅Sn), (11)]

Yield: 75 %; m.p.: 123-124 ^°C; IR (KBr): ν = 1554 (C=N) cm^-1;¹H NMR (DMSO-d₆ and CDCl₃): δ = 11.84 (s, 1H, -CH=N),8.23-8.26 (d, 2H, C_c-H & C_e-H), 7.84-7.86 (d, 2H, C_2’-H & , C_6’-H), 7.72-7.74 (d, 2H, C_b-H &C_f-H), 7.54-7.57 (m, 4H,C₂-H, C_3’-H_, C_4’-H& C_5’-H), 7.11-7.16 (m, 2H, C₃-H& C₄-H), 4.99 (s, 2H, -OCH₂), 3.88 ( s, 3H, -OCH₃), 3.08-3.11 (t, 4H,-CH₂), 1.62-1.66 (m, 8H,-CH₂), 1.21-1.24 (t, 6H, -CH₃) ppm; ¹³C NMR: δ = 155.4 (C=O), 151.5 (C=N), 146.8 (C-6), 145.7 (C-5), 144.7 (C-d), 142.8 (C-a), 133.5 (C-1’), 131.5 (C-4’), 128.7, (C-3’& C-5’), 127.9 (C-b & C-f), 127.3 (C-2 ’& C-6’), 127.2 (C-c & C-e), 124.5 (C-2), 123.3 (C-3), 117.4 (C-1), 113.6 (C-4), 73.6 (OCH₂), 55.8 (OCH₃), 28.4 (Bu), 26.4 (Bu), 13.2 (Bu), 7.9 (Bu) ppm.

[(Ph₂Sn(L₂)Cl, C₃₄H₂₈ClN₃O₅Sn), (12)]

Yield: 68 %; m.p.: 144-145 ^°C; IR (KBr): ν = 1555 (C=N) cm^-1; ¹H NMR (DMSO-d₆ and CDCl₃): δ= 11.86 (s, 1H, -CH=N),8.26-8.29 (d, 2H, C_c-H & C_e-H), 7.82-7.91 (d, 4H, C_2’-H , C_6’-H, C_b-H &C_f-H), 7.53-7.56 (m, 4H,C₂-H, C_3’-H_, C_4’-H& C_5’-H), 7.03-7.21 (m, 10H Ph and 2H, C₃-H&C₄-H), 4.97 (s, 2H, -OCH₂), 3.86 (s, 3H, -OCH₃) ppm; ¹³C NMR: δ = 155.4 (C=O), 151.5 (C=N), 146.8 (C-6), 145.6 (C-5), 144.8 (C-d), 142.8 (C-a), 133.5 (C-1’), 131.5 (C-4’), 129.2 (Ph), 128.8 (Ph), 128.4 (Ph), 128.1 (Ph), 128.6, (C-3’& C-5’), 128 (C-b & C-f), 127.3 (C-2 ’& C-6’), 126.9 (C-c & C-e), 124.5 (C-2), 123.3 (C-3), 117.2 (C-1), 113.8 (C-4), 73.5 (OCH₂), 55.9 (OCH₃) ppm.

[(Me₂Sn(L₃)Cl, C₂₆H₂₉ClN₂O₃Sn), (13)]

Yield: 74 %; m.p.: 127-128 ^°C; IR (KBr): ν = 1545 (C=N) cm^-1; ¹H NMR (DMSO-d₆and CDCl₃): δ= 11.78 (s, 1H, -CH=N), 7.83-7.85 (d, 2H, C_2’-H & , C_6’-H), 7.47-7.49 (d, 1H,C₂-H), 7.34-7.36 (d, 2H, C_3’-H& C_5’-H), 7.28-7.30 (d, 2H, C_b-H &C_f-H), 7.18-7.20 (d, 2H, C_c-H &C_e-H), 7.08-7.11 (m, 2H, C₃-H& C₄-H), 5.01 (s, 2H, -OCH₂), 3.87 (s, 3H, -OCH₃), 2.37 (s, 3H, -CH₃at Hydrazide ring), 2.30 (s, 3H, -CH₃at Ph ring), 1.23 (s, 6H, -CH₃) ppm; ¹³C NMR: δ = 155.4 (C=O), 151.6 (C=N), 146.4 (C-6), 143.3 (C-5), 141.5 (C-4’), 137.3 (C-a), 133.8 (C-d), 129.9 (C-1’), 128.5 (C-c& C-e), 128.4 (C-3’ & C-5’), 128.2 (C-2 ’& C-6’), 128.2 (C-b & C-f), 127.6 (C-2), 123.9 (C-3), 117.3 (C-1), 113.4 (C-4), 73.6 (OCH₂), 55.4 (OCH₃), 21.2 (CH₃ at Hydrazide ring), 20.8 (CH₃ at Ph ring), 8.6 (Me) ppm.

[(Et₂Sn(L₃)Cl, C₂₈H₃₃ClN₂O₃Sn), (14)]

Yield: 69 %; m.p.: 124-125 ^°C; IR (KBr): ν = 1542 (C=N) cm^-1; ¹H NMR (DMSO-d₆and CDCl₃): δ = 11.91 (s, 1H, -CH=N), 7.86-7.88 (d, 2H, C_2’-H & , C_6’-H), 7.51-7.53 (d, 1H,C₂-H), 7.37-7.38 (d, 2H, C_3’-H& C_5’-H), 7.28-7.30 (d, 2H, C_b-H &C_f-H), 7.15-7.17 (d, 2H, C_c-H & C_e-H), 7.06-7.09 (m, 2H, C₃-H& C₄-H), 4.9 (s, 2H, -OCH₂), 3.87 (s, 3H, -OCH₃), 2.37 (s, 3H, -CH₃at Hydrazide ring), 2.29 (s, 3H, -CH₃at Ph ring), 3.01-3.07 (m, 4H,-CH₂), 1.22-1.28 (t, 6H,-CH₃) ppm; ¹³C NMR: δ= 155.3 (C=O), 151.7 (C=N), 145.4 (C-6), 143.4 (C-5), 141.6 (C-4’), 137.3 (C-a), 133.6 (C-d), 130.1 (C-1’), 128.8 (C-c& C-e), 128.4 (C-3’ & C-5’), 128.3 (C-2 ’& C-6’), 128.2 (C-b & C-f), 127.8 (C-2), 123.7 (C-3), 117.2 (C-1), 113.4 (C-4), 74.6 (OCH₂), 55.4 (OCH₃), 21.1 (CH₃ at Hydrazide ring), 20.6 (CH₃ at Ph ring), 12.8 (Et), 7.6 (Et) ppm.

[(Bu₂Sn(L₃)Cl, C₃₂H₄₁ClN₂O₃Sn), (15)]

Yield: 73 %; m.p.: 120-121^°C; IR (KBr): ν = 1545 (C=N) cm^-1; ¹H NMR (DMSO-d₆ and CDCl₃): δ = 11.87 (s, 1H, -CH=N), 7.88-7.90 (d, 2H, C_2’-H & , C_6’-H), 7.53-7.55 (d, 1H,C₂-H), 7.35-7.37 (d, 2H, C_3’-H& C_5’-H), 7.25-7.27 (d, 2H, C_b-H &C_f-H), 7.16-7.18 (d, 2H, C_c-H & C_e-H), 7.08-7.11 (m, 2H, C₃-H&C₄-H), 5.00 (s, 2H, -OCH₂), 3.88 (s, 3H, -OCH₃), 2.38 (s, 3H, -CH₃ at Hydrazide ring), 2.29 (s, 3H, -CH₃ at Ph ring), 3.01-3.07 (m, 4H,-CH₂), 1.61-1.66 (m, 8H, -CH₂),1.21-1.26 (t, 6H, -CH₃) ppm; ¹³C NMR: δ = 155.2 (C=O), 151.6 (C=N), 145.4 (C-6), 142.2 (C-5), 135.8 (C-4’), 132.8 (C-a), 132.6 (C-d), 130.9 (C-1’), 129.8 (C-c& C-e), 128.5 (C-3’ & C-5’), 128.2 (C-2 ’& C-6’), 127.6 (C-b & C-f), 127.3 (C-2), 124.2 (C-3), 117.2 (C-1), 113.3 (C-4), 74.6 (OCH₂), 55.4 (OCH₃), 28.4 (Bu), 24.4 (Bu),21.1 (CH₃ at Hydrazide ring), 20.3 (CH₃at Ph ring), 13.1 (Bu), 8.2 (Bu) ppm.

[(Ph₂Sn(L₃)Cl, C₃₆H₃₃ClN₂O₃Sn), (16)]

Yield: 79 %; m.p.: 139-140 ^°C; IR (KBr): ν = 1543 (C=N) cm^-1; ¹H NMR (DMSO-d₆ and CDCl₃): δ = 11.78 (s, 1H, -CH=N), 7.86-7.88 (d,2H, C_2’-H & C_6’-H), 7.50-7.51 (d, 1H, C₂-H), 7.37-7.46 (d, 4H, C_3’-H,C_5’-H, C_b-H &C_f-H), 7.33-7.35 (d, 2H, C_c-H & C_e-H),7.01-7.23 (m, 10H, Ph& m,2H, C₃-H& C₄-H),4.97 (s, 2H, -OCH₂), 3.84 (s, 3H, -OCH₃), 2.38 (s, 3H, -CH₃at Hydrazide ring), 2.30 (s, 3H, -CH₃ at Ph ring) ppm; ¹³C NMR: δ = 155.3 (C=O), 151.7 (C=N), 145.2 (C-6), 143.5 (C-5), 141.5 (C-4’), 137.3 (C-a), 133.7 (C-d), 129.9 (C-1’), 128.8 (Ph), 128.7 (C-c& C-e), 128.6 (Ph), 128.5 (C-3’ & C-5’), 128.4 (Ph), 128.3 (C-2 ’& C-6’), 128.2 (C-b & C-f), 128.2 (Ph), 127.7 (C-2), 123.9 (C-3), 117.3 (C-1), 113.4 (C-4), 74.6 (OCH₂), 55.3 (OCH₃), 21.2 (CH₃ at Hydrazide ring), 20.7 (CH₃ at Ph ring) ppm.

[(Me₂Sn(L₄)Cl, C₂₅H₂₆ClN₃O₅Sn), (17)]

Yield: 67 %; m.p.: 129-130 ^°C; IR (KBr): ν = 1550 (C=N) cm^-1; ¹H NMR (DMSO-d₆and CDCl₃): δ= 11.76 (s, 1H, -CH=N),8.22-8.26 (d, 2H, C_c-H &C_e-H), 7.78-7.81 (d, 4H, C_2’-H, C_6’-H,C_b-H &C_f-H), 7.53-7.56 (d, 1H, C₂-H), 7.24-7.26 (d, 2H,C_3’-H& C_5’-H), 7.12-7.18 (m, 2H, C₃-H& C₄-H), 5.16 (s, 2H, -OCH₂), 3.87 (s, 3H, -OCH₃),2.37 (s, 3H, -CH₃at Hydrazide ring), 1.26 (s,6H, -CH₃) ppm; ¹³C NMR: δ = 155.3 (C=O), 151.7 (C=N), 146.8 (C-6), 145.9 (C-5), 144.6 (C-d), 143 (C-a), 141.5 (C-4’), 130.5 (C-1’), 128.7 (C-3’ & C-5’), 128.5 (C-b & C-f), 128 (C-2’ & C-6’), 127.6 (C-c & C-e),124.5 (C-2), 123.0 (C-3), 117.3 (C-1), 113.8 (C-4), 73.3 (OCH₂), 55.7 (OCH₃), 22.9 (CH₃ at Hydrazide ring) ppm.

[(Et₂Sn(L₄)Cl, C₂₇H₃₀ClN₃O₅Sn), (18)]

Yield: 71 %; m.p.: 127-128 ^°C; IR (KBr): ν = 1552 (C=N) cm^-1; ¹H NMR (DMSO-d₆and CDCl₃): δ = 11.75 (s, 1H, -CH=N), 8.24-8.27 (d, 2H, C_c-H &C_e-H), 7.77-7.80 (d, 4H, C_2’-H, C_6’-H,C_b-H &C_f-H), 7.52-7.55 (m, 1H, C₂-H), 7.23-7.25 (d, 2H,C_3’-H& C_5’-H), 7.13-7.16 (m, 2H, C₃-H&C₄-H), 5.0 (s, 2H, -OCH₂), 3.85 (s, 3H, -OCH₃),2.38 (s, 3H, -CH₃at Hydrazide ring), 3.06-3.10 (m, 4H,-CH₂), 1.21-1.25 (t, 6H,-CH₃) ppm; ¹³C NMR: δ = 155.3 (C=O), 151.8 (C=N), 146.3 (C-6), 145.9 (C-5), 144.6 (C-d), 143 (C-a), 141.6 (C-4’), 130.5 (C-1’), 128.7 (C-3’ & C-5’), 128.5 (C-b & C-f), 128 (C-2’ & C-6’), 127.7 (C-c & C-e),124.3 (C-2), 123.1 (C-3), 117.3 (C-1), 113.8 (C-4), 73.4 (OCH₂), 55.6 (OCH₃), 23 (CH₃ at Hydrazide ring), 12.9 (Et), 8.7 (Et) ppm.

[(Bu₂Sn(L₄)Cl, C₃₁H₃₈ClN₃O₅Sn), (19)]

Yield: 68 %; m.p.: 124-125 ^°C; IR (KBr): ν = 1551 (C=N) cm^-1; ¹H NMR (DMSO-d₆and CDCl₃): δ= 11.74 (s, 1H, -CH=N),8.21-8.25 (d, 2H, C_c-H & C_e-H), 7.76-7.80 (d, 4H, C_2’-H, C_6’-H,C_b-H &C_f-H), 7.51-7.55 (m, 1H, C₂-H), 7.24-7.26 (d, 2H,C_3’-H&C_5’-H), 7.12-7.15 (m, 2H, C₃-H&C₄-H), 4.98 (s, 2H, -OCH₂), 3.89 (s, 3H, -OCH₃),2.37 (s, 3H, -CH₃ at Hydrazide ring), 3.07-3.11 (t, 4H,-CH₂), 1.61-1.65 (m, 8H,-CH₂), 1.23-1.26(t,6H,-CH₃) ppm; ¹³C NMR: δ= 155.3 (C=O), 152 (C=N), 146.2 (C-6), 145.9 (C-5), 144.6 (C-d), 143.1 (C-a), 141.4 (C-4’), 130.5 (C-1’), 128.7 (C-3’ & C-5’), 128.5 (C-b & C-f), 127.9 (C-2’ & C-6’), 127.6 (C-c & C-e),124.4 (C-2), 123 (C-3), 117.3 (C-1), 113.8 (C-4), 73.5 (OCH₂), 55.5 (OCH₃), 27.4 (Bu), 25.4 (Bu), 23.2 (CH₃at Hydrazide ring),12.2 (Bu), 8.2 (Bu) ppm.

[(Ph₂Sn(L₄)Cl, C₃₅H₃₀ClN₃O₅Sn), (20)]

Yield: 75 %; m.p.: 141-142 ^°C; IR (KBr): ν = 1554 (C=N) cm^-1; ¹H NMR (DMSO-d₆and CDCl₃): δ = 11.75 (s, 1H, -CH=N),8.22-8.24 (d, 2H, C_c-H & C_e-H), 7.73-7.81 (d, 4H, C_2’-H, C_6’-H,C_b-H &C_f-H), 7.48-7.50 (d, 1H, C₂-H), 7.27-7.29 (d, 2H,C_3’-H& C_5’-H), 7.12-7.24 (m, 10H, Ph& m,2H, C₃-H&C₄-H), 5.00 (s, 2H, -OCH₂), 3.88 (s, 3H, -OCH₃) , 2.38 (s, 3H, -CH₃at Hydrazide ring) ppm; ¹³C NMR: δ = 155.3 (C=O), 151.5 (C=N), 145.4 (C-6), 142.4 (C-5), 136.2 (C-d), 132.4 (C-a), 132.3 (C-4’), 131.2 (C-1’), 129.8 (C-3’ & C-5’), 129 (Ph),128.7 (Ph),128.7 (C-b & C-f), 128.4 (Ph), 128.1 (Ph), 127.9 (C-2’ & C-6’), 127.6 (C-c & C-e),127.4 (C-2), 123.9 (C-3), 117.4 (C-1), 113.3 (C-4), 74.4 (OCH₂), 55.4 (OCH₃), 20.4 (CH₃ at Hydrazide ring) ppm.

5.3     Antimicrobial activity

5.3.1    Test Microorganisms

Gram positive bacteria (viz. Klebsiellapneumoniae [NCDC No. 138], Staphylococcus aureus[MTCC No. 3160] Gram-negative bacteria (viz. Escherichia coli[MTCC No. 443],Enterobacteraerogenes[NCDC No. 106) and fungus (Aspergillus niger[MTCC No. 282]and Candida albicans[MTCC No. 227]were used for antimicrobial assay. All the microbial strains were procured from Microbial Type Culture Collection (MTCC), Institute of Microbial Technology (IMTECH), Chandigarh.

Ligands and their tin complexes were screened for in-vitro antimicrobial activity using serial dilution technique to find out their Minimum Inhibitory Concentration (MIC) value. The medium was prepared by dissolving weighed amount of nutrient broth/ sabouraud dextrose broth in 1L of distilled water and 1 ml of nutrient medium was transferred to each test tube. The test tubes having nutrient medium were autoclaved for 30 minutes at 120°C. The solution of test compounds was prepared by dissolving 1.0 mg of synthesized compounds in dry DMSO which was further diluted to give a stock solution of 100 µg/ml. The solution of test compounds was transferred to test tubes having sterilized nutrient medium to get a set of five dilutions of test compounds having concentrations 50, 25, 12.5, 6.25 and 3.125 µg/ml.The inoculation of test strains was done with the help of micropipette with sterilized tips as 100 µL of freshly cultured strain was transferred in to test tubes and incubated at 37 °C for 24 hours for bacterial strains, 48 hours for C. albicans and 7 days at 25 °C for A. niger. The DMSO was taken as negative control whereas norfloxacin and fluconazole were taken as positive control for antibacterial and antifungal activity, respectively. The experiments were performed in triplicates and the mean values were observed.

6.      QSAR studies

The structures of 1–20 were first pre-optimized with the Molecular Mechanics Force Field (MM) procedure included in Hyperchem 6.03 [31] And the resulting geometries were further developed by means of the semiempirical method PM3 (Parametric Method-3). A gradient norm limit of 0.01 kcal/A° ´was taken into consideration for the geometry optimization. The lowest energy structure was used for each individual molecule to calculate physicochemical properties using TSAR 3.3 software for Windows [32].Further, the regression analysis was performed using the SPSS software package [33].

7.      Conclusion

A series of novel compounds was synthesized and characterized using elemental analyses, various spectroscopic techniques like UV, IR and (¹H, ¹³C and ¹¹⁹Sn) NMR. The substituted o-vanillin Schiff bases and their organotin(IV) complexes were screened for antimicrobial activity against representative microorganisms and the compounds evaluated had inhibited the growth of all the tested bacterial and fungal strains. The complexes were found to be more active antimicrobial agent in comparison to the Schiff bases. The QSAR studies were carried out to find out the relationship between structural features and antimicrobial activity of synthesized derivatives which revealed the fact that antimicrobial activity of these derivatives is governed by topological descriptors and electronic energy of the molecules.

8.      Acknowledgements

Ankit Ravesh is grateful to the Council of Scientific and Industrial Research (CSIR) New Delhi, for financial support.

9.     Conflict of interest

The authors declare that they have no conflict of interest.

Table 1: Physicochemical characterization and elemental analysis of synthesized compounds.

Table 2 : Antimicrobial activity of synthesized derivatives (µM/ml).

Table 3 P: Value of selected descriptors used in the regression analysis.

Table 5 :Correlation of molecular descriptors with antimicrobial activity of synthesized derivatives.

Table 6:Comparison of observed and predicted antibacterial and antifungal activity obtained by QSAR model.

Table 4 :Correlation matrix for antibacterial activity of synthesized derivatives against K. pneumoniae

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