TIN(IV) SCHIFF BASE COMPLEXES: SYNTHESIS, THERMODYNAMIC AND ANTI BACTERIAL INVESTIGATION, EXPERIMENTAL AND THEORETICAL STUDIES

A series of five coordinated diorganotin(IV) unsymmetrical Schiff base complexes have been synthesized. The structure determination and characterization of these complexes were made on the basis of UVVis, IR, (H and Sn) NMR spectroscopy as well as elemental analysis. The binding site of the ligand was identified by IR spectroscopic measurement. Computational analyses at the level of DFT were performed to study its electronic and molecular structures. The molecular geometry, infrared vibrational frequencies, HOMO-LUMO energy gap, dipole moment, Mulliken charges, HF energies were calculated. The theoretical results were consistent with the experimental data reported. The Schiff base ligands and synthesized tin(IV) complexes were screened for their in vitro growth inhibiting activity against different strains of bacteria. Results indicated that the complexes exhibited good antibacterial activities than the ligands. Also the thermodynamic formation constants of the Schiff bases as donors with Me2SnCl2 as an acceptor were measured using UV-Vis spectrophotometric titration for 1:1 complex formation at constant ionic strength (I = 0.1 M NaClO4) and at 25 oC.


INTRODUCTION
The discovery of several new organotin species and new applications has led to a renewed interest in organotin complexes.A large number of organotin compound are used in several areas such as pharmaceuticals, pesticides, stabilizers, fire retardants, miticides, molluscicides, marine antifouling paints, surface disinfectants and wood preservatives and many more [1][2][3][4].On the other hand, Schiff base ligands received instant and enduring popularity because they have played a seminal role in the development of modern coordination chemistry, as well as they can also be found at key points in the development of inorganic chemistry, catalysis, pigment and dyes, medicinal imaging, optical materials and thin films [5][6][7][8].Schiff base ligands containing hetero atoms such as N, O, and S show a broad biological activity and are of special interest because of their variety of ways in which they are interacted to metal ions.Schiff base in neutral and deprotonated forms react with organotin(IV) halides and the complexes extensively studied because they have some characteristics properties like manifestations of novel structures, thermal stability, high synthesis flexibility, medicinal utility, industrial applications and relevant biological properties [9][10][11][12].In addition to their special antimicrobial activities, organotin(IV) compound with Schiff bases present an interesting variety of structural possibilities, so that a remarkable diversity in structure may be observed even when only a small change in the chemistry occurs [13].
The present study will entail a description of synthesis and characterization of some tin(IV) complexes with Schiff bases containing sulfur, nitrogen and oxygen atoms, and illustration of the geometrical structure by using spectral analysis.By comparing the spectral and thermodynamic properties of Schiff base ligands and their complexes, we aimed to investigate the effects of different electronic and steric behaviors.Moreover, the density functional theory computational calculations were done for tin(IV) Schiff base complexes for comparing with experimental results.Also, the present work involves antibacterial activities against grampositive and gram-negative bacterial for the Schiff base ligand and their complexes.

Materials and physical measurements
All chemicals and reagents were commercially available and were grade quality.All the reagents were used as received.The infrared spectra of the solid compounds were recorded on a Shimadzu FTIR 8300 spectrophotometer in the range 4000-200 cm -1 as KBr discs.The melting points were determined in open capillaries with electronic melting point apparatus.C, H, N, S analyses were carried on a Termo Fininngan-Flash-1200.The 1 H and 119 Sn NMR spectral data were obtained on Bruker Avance DPZ 500 MHz spectrometer using TMS and SnMe 4 as references and chemical shift are expressed in ppm.The conductivity were performed using Jenway 4310 conductivity meter and a diptype cell with a platinized electrode in DMF having 10 -3 M solutions of the metal complexes at room temperature.UV-Vis spectra were recorded in DFT with T80 UV-Vis spectrophotometers.

Preparation of ligands and corresponding complexes
The unsymmetrical Schiff base ligands was synthesized by stirring at room temperature a 1:1 molar ratio mixture of methyl-2-(1-methyl-2'-amino-ethane)amino-1-cyclopentenedithiocarboxylate [HcdMeen] and the substituted salicylaldehyde in methanolic solution following a reported method [14][15][16].The resultant yellow powder was recrystallized from methanol/ chloroform 2: mmol) in 15 mL of chloroform/methanol 2:1(v:v), a solution of Me 2 SnCl 2 (1 mmol) in 15 mL of methanol was added slowly at r.t.The mixture was then stirred for 4-6 h.During this period, the yellow solid precipitate formed was filtered and washed with petroleum ether (Figure 1).

Thermodynamic studies of complex formation
The formation constants, K f , of the Sn(IV) complexes were determined by spectrophotometric titration of the ligands H 2 cdXsalMeen with various concentration of the solution of dimethyltin(IV)dichloride at constant ionic strength (0.1 M NaClO 4 ) at 25 o C. The interaction of NaClO 4 with the ligands was negligible.In a typical measurement, 2.5 mL of the ligand solution (10 -5 M) in DMF was transferred into the thermostated cell compartment of UV-Visible instrument, and was titrated by the dimethyltin(IV)dichloride solution (10 -5 -10 -4 M) in DMF.The titration was performed by adding aliquots of the tin ion with a Hamilton μL syringe to the ligand.The UV-Vis spectra were recorded in the range 290-600 nm about 5 min after each addition.The formed product showed different absorption from the free ligand, while the metal ion solution shows no absorption at those wavelengths.As an example, the variation of the electronic spectra for [H 2 L 5 ] titrated with various concentration of dimethyltin(IV)dichloride at 25 o C in DMF.The same procedure was followed for other systems.The electronic spectra of the formed complexes at the end of titration were the same as the electronic spectra of the separately synthesized complexes.

Determination of bacteriological activity
Bioactivities were investigated using agar-well diffusion method [17].The synthesized Schiff base ligands and their tin(IV) complexes were screened for their biological activities by using two bacteria namely Staphylococcus aureus and Escherichia coli by the reported method.The bacteria were subcultured in agar medium.Recommended concentration (100 μL) of the test sample 1 mg/mL in DMSO was introduced in the respective wells.The Petri dishes were incubated immediately for 24 hours at 37 ºC.Activity was determined by measuring the diameter of the zone showing complete inhibition (mm).Growth inhibition was compared with standard drugs.In order to clarify the role of DMSO on the biological screening, separate studies were carried out with solvent DMSO only and it showed no activity against any microbial strains.

Theoretical methods
The quantum chemical calculations were performed using Gaussian 03 package [18].The local minimum energy, Mulliken charges, dipole moment, HOMO-LUMO energy and its band gap of the optimized structures for Sn(IV) complexes was computed at Becke three parameter hybrid function (B3LYP) using LANL2DZ and 6-311G** basis sets for all atoms including tin [19].By the use of LANL2DZ basis set, computational time and convergence difficulties were considerably reduced.LANL2DZ basis set uses pseudopotential, the results are very close to the experimental data.This does not necessarily substantiate preference of LANL2DZ basis set over 6-311G**.Many descriptors were used to recognize and correlate some physical and chemical properties.The calculated vibrational spectra of the optimized complexes were assigned based on vibrational mode analysis with the aid of the DFT method.

Elemental analysis
The stoichiometry of the tin(IV) complexes were confirmed by their elemental analysis.Experimental and calculated elemental compositions of the complexes are given in Table 1.The analytical data are in good agreement with the proposed structures of the complexes (Figure 1).The metal/ligand ratio was found to be 1:1 has been arrived at by estimating the carbon, hydrogen, nitrogen and sulfur contents of the complexes.Solutions of these complexes no react with silver nitrate indicating the existence of chloride in inside coordination sphere of the tin ion.

Molar conductance
The tin(IV) complexes under investigation are quite stable at ambient temperature.They are sparingly soluble in donor solvents such as DMF and DMSO.The molar conductance of these complexes (Table 1) indicating that it is essentially a non-electrolyte in this solvent [20].The very low conductance for these complexes is strong evidence that the Schiff base is coordinated to the tin atom as an unnegatively charged ligand and that the two chloro ligands are also coordinated to the tin ion.

Infrared spectra
The IR spectra give enough information to elucidate the nature of bonding of the ligand to the metal ions.The IR spectra of free Schiff base were compared with the spectra of the tin(IV) complexes in order to study the binding mode of the Schiff base to Sn(IV) ion in the new complexes.In Table 2 the main infrared bands and their assignments are shown.In this spectra of free ligand and new complexes no band is observed in the region 3500-3600 cm -1 attributable to the stretching vibration of the free phenolic OH group indicating that the ring formed by the intramolecular hydrogen bond in the ligand which, is retained in complexes.Weak broad absorption bands appearing in the range of 2800-2900 cm -1 for the free Schiff base ligands are assigned to (O-H) and (N-H) overlapping with the (C-H) [16].These bands are observed to shift slightly to higher frequency due to the coordination of phenolic oxygen atom with tin and changes in hydrogen bonding [21].The strong bands at 1622-1649 cm -1 , which can be attributed to (C=N) stretching frequency on Schiff base ligands [16].This band showed a major shift to higher frequency (1638-1659 cm -1 ) is suggesting the complex formation and the proton transfer from phenolic oxygen atom to the imine nitrogen atom [22].In the spectra of tin(IV) complexes a sharp peak at 1558-1567 cm -1 due to the (C=O) providing evidence of participation of the phenolic oxygen in the tin-ligand bonding [23].The aromatic (C=C) stretching frequency occurs at 1479-1497 cm -1 [24].The characteristic sulfur vibration of (C-S) appearing at 763-798 cm -1 [16].New bands in the range of 580-590 cm -1 which are not present in the free Schiff base are due to (Sn-O) vibration [25] and the appearance of the vibrations support the involvement of the oxygen atoms of phenolic group complexation with the tin ion under investigations.Two sharp peaks at around 1300 and 1550 cm -1 are typical of nitro group in [Me 2 SnCl 2 .H 2 cd5NO 2 salMeen] [16]. 1

H and 119 Sn NMR spectra
The NMR spectrum is recorded to confirm the binding sites during the complexation.The NMR data are given in Table 3.The chemical shift observed for the -OH and -NH protons in free Schiff base ligands (δ 12.45-14.06ppm) and (δ 12.30-12.38ppm) was observed in all complexes.The deshielding of this group and shifted down field in complexes may be due to bonding of the oxygen to the tin(IV) ion which lead to decrease of the density of electrons on the hydroxyl group.The same results were confirmed by the IR spectroscopy.The signal at 8-9 ppm were assigned to imine proton (HC=N) is not flanked by satellites, this is an indicating that the N atom is not coordinated to tin(IV) [26].The lack of down field shift in the position of the signal attributable to S-CH 3 (δ 2.55-2.57ppm in free ligand) indicates no participitation of the -C=S group in binding [27].The ligand shows multiplet signal in the region δ 6.83-8.23 ppm for the aromatic protons and these values are remains almost same position in the spectra of Sn(IV) complexes. 1H NMR spectra of Schiff base ligands and their complexes show one peak at chemical shift ca.1.39-1.41,this singlet peak with three proton integration has been assigned to the methyl group on diamine bridge.The high field regions in the spectra of dimethyl tin show signal at 1.15 ppm for all complexes and these are due to the methyl groups in the organotin fragment.These signals have satellites due to coupling with tin ( 2 J 119 Sn-H 71.0 and 77.1 Hz).The data describe above are all consistent with those observed for the other five coordinated diorganotin complexes containing Schiff base ligands [28].
The value of chemical shift 119 Sn spectra expresses the coordination number of the nucleus in the related metal complexes.In general, 119 Sn chemical shifts move to lower frequency with increasing coordination number of the nuclei.In order to confirm the geometry of the complexes, 119 Sn NMR spectra were recorded.The spectra in each complex show only a sharp singlet, indicating the formation of a single species.The 119 Sn NMR spectra of all titled complexes [Me 2 SnCl 2 .H 2 L 1-5 ] give sharp signals at -166.65, -163.55,-161.43,-161.76,-168.93 ppm, respectively, which is indicative of five coordinated environment around the tin atom.Thus on the basis of the above evidences it is suggested that the geometry of the resulting tin complexes be characterized as trigonal bipyramidal [21,29,30].The proposed structures of newly synthesized complexes are shown in Figure 1.Therefore, it is clear from these results that the data obtained from the elemental analysis, IR and NMR spectral measurements are in agreement with each other.

UV-Vis absorption spectra
The electronic absorption spectra of all the synthesized ligands and their complexes at very low concentrations (~10 -4 M range) are recorded in DMF solution.The ligands exhibit the band at 312-314 and 395-398 nm can be assigned to intra ligand to π→π* and n→π* transition [16].Complex formation with dimethyltin(IV)dichloride results changes of the spectra took place in the UV-Vis region (250-600 nm) of π→π* and n→π* absorption band upon this interaction.After coordination of Schiff base to Me 2 SnCl 2 , the original peaks of the Schiff base ligands changed and have a red shift.A new peak is appeared in 460-470 nm regions.It seems that this is an LMCT from n O to Sn(IV) via coordination of Schiff base ligand to dimethyltindichloride [31].

The formation constants and the thermodynamic free energy interpretations
To interpret the steric and the electronic parameters of the ligands on the formation constants and the thermodynamic free energy of the complexation, the interaction between five ligands (H 2 L 1-5 ) and dimethyltindichloride (Me 2 SnCl 2 ) was carried out by UV-Vis absorption spectroscopy through titration of the ligands with various concentrations of the Sn(IV) ion at 25 o C. The complex formation constants, K f , were calculated using SQUAD computer program [32], designed to calculate the best values for the formation constants of the proposed equation model (Eq.( 1)) by employing a non-linear, least-squares approach.
Also, the free energy change, ∆G°, of the complexes were determined by ∆G° = -RT ln K f , at 25 o C (Table 4).As the results show, In the para substituted Schiff base ligands, the formation constants varies as can be expected according to the electronic effects of the substituents at position 5. Thus, the formation constants decreases according to the sequence OMe > H > Br > Cl > NO 2 .This is somewhat in agreement with decreasing electron releasing character of the substituents in the same direction, which result in a decrease in basicity of the phenolic oxygen groups of the ligand, and consequently decreased tendency toward complex formation.The withdrawing functional groups make the Schiff base as a poor donor ligand and decrease the formation constants while the electron donor group increasing the formation constants because they leads to increase the donor ability of Schiff base ligands.Therefore, the ligands having NO 2 group, [H 2 L 5 ], have the smallest formation constants while the ligands with OMe group, [H 2 L 2 ], have the highest because OMe is a donating group.Therefore, in the stabilization of the complexes, the donation power of the Schiff base is important, and hence their formation constants, K f , with donation are higher.The numbers in parentheses are the standard deviations.

Antibacterial activity results
The free Schiff base ligands and their corresponding tin(IV) complexes were tasted against the selected bacteria E.coli (G-) and S. aureus (G+).The measured zones of inhibition against of various microorganisms are summarized in Table 5.All the tested compounds showed good biological activity against microorganism.It is found that the complexes have higher antimicrobial activity than the free ligands.This can be explained on the Tweedy's chelation theory [33].The lipid membrane that surrounds the cell favors the passage of only lipid soluble materials due to which lipophilicity is an important factor which controls the antimicrobial activity.On chelation, the polarity of the metal ion will be reduced to a greater extent due to the overlap of the ligand orbital and partial sharing of the positive charge of the metal ion with the donor groups.Further, it increases the delocalization of p-electron over the whole chelate ring and hence enhances the liposolubility of the complexes.This increased liposolubility enhances the penetration of the complexes into the lipid membrance, the lipophilic group to derive the compound through the semipermeable of the cell, and blocks the metal binding sites in the enzymes of the microorganism.

Computational details
The molecular properties of the complex structures under investigation were determined by density functional theory (DFT).The important structural analysis referring to bonding distances, bonding angles and dihedral angles parameters for all optimized structures of Sn(IV) complexes in the ground state configuration are gathered in Table 6.The fully optimized molecular structures of the tin(IV) complexes with atomic numbering are shown in Figure 2.
The structure shows that the complex is monomer in which the tin atom adopts a fivecoordinate geometry being ligated to two chloride ions, two carbon atoms of methyl group and O atom of the H 2 L 1-5 ligands.The Schiff base is coordinated to the tin atom as a neutral chelating agent in it is without deprotonated phenolic form via the hydroxyl oxygen atom.The two Sn-Cl42 and Sn-Cl43 bond lengths are similar and the calculated value is longer than Sn-C44, Sn-C45 and Sn-O38 (0.25-0.63 Å).The DFT estimated bond lengths are generally overestimated.The coordination geometry can be views as a trigonal bipyramidal with the two C atoms and O atom remains in the equatorial position and two Cl atoms in the axial position.In view of the bond angle, Cl42-Sn-Cl43 angles make approximately a 180º angle and the calculated C45-Sn-C44, C45-Sn-O38 and C44-Sn-O38 angles are 120º respectively (Table 6).On the basis of the results the tbp structure was confirmed.
The Sn(IV)-Schiff base ligand interaction is not lead to twisting of the ligand compared to the free ligand.In the optimized structure of the complexes cyclopentene and benzene ring are in the same plane.Their planes make approximately a 2º dihedral angle to each other.The calculated O38-C33-C32-C31 and N13-C4-C3-C6 dihedral angles are near to each other.These molecules are not twisted, so that the 5-X substituents group (5-OMe, 5-H, 5-Br, 5-Cl, 5-NO 2 ) is in opposite orientation.The aromatic rings are essentially planar, where the bond lengths of C=C (142.9-143.7 Å) are in the expected range [34].The two O38-H52 and S7-H20 asymmetrical intramolecular hydrogen bonds with distances 2.046-2.077and 2.226-2.233Å [35].However, the two C-N bond lengths differ significantly of the two types of C-N bonds, the bond length for the imine nitrogen (N24=C31) is 0.038-0.044Å shorter than that for primary amine nitrogen (N13-C4).These C-N bonds are essentially in the same plane with the plane of benzene and cyclopentene ring.The frontier orbital for all titled complex is plotted in Figure S2.The LUMO surface mostly delocalized within the non-metallic atoms, and for the HOMO level, the Sn atom is overlapped.HOMO which can be thought the outermost orbital containing electrons tends to give these electrons such as an electron donor.LUMO can be thought the innermost orbital containing free places to acceptor electron, owing to the interaction between HOMO and LUMO orbitals, transition of π→π* type was observed with regard to the molecular orbital theory.As shown in Figure S2 the HOMO is localized over the azomethine group and cyclopentene ring, while the LUMO is localized over the benzene ring and N13-C4 bond.The energy difference between HOMO and LUMO orbitals so called as energy gap is an important stability for structures [36,37].
The HOMO-LUMO energy gap of the Sn(IV) complexes are shown in Table 7 and revealed that the energy gap reflect to the chemical activity of the complexes.A large HOMO-LUMO gap increases stability and decreases chemical reactivity.The results show the following trend in HOMO-LUMO gap for the complexes: The [Me 2 SnCl 2 .H 2 L 2 ] complex has a large gap between all complexes.A large HOMO-LUMO gap indicate explain the experimental formation constant values.So, the DFT calculations support the experimental formation constant.Absolute hardness is half of the HOMO-LUMO gap.According to the maximum hardness principle, greater hardness ( ) causes more stability in the molecule [38].On the basis of the data in Table 7 [Me 2 SnCl 2 .H 2 L 2 ] complex have a higher hardness and is stable than the other complexes.
In order to obtain reliable and stable structures, vibration frequencies were calculated for all optimized complexes.Selected experimental and calculated FTIR vibration frequencies (cm -1 ) of the complexes were listed in Table 2.The calculated C=C stretching frequency is somewhat different from the experimental data, may be due to the fact that the theoretical data calculated in gas phase.In [Me 2 SnCl 2 .H 2 L 2 ] predict stretching modes at 1750, 1560 and 1477 cm -1 correspond to C=C bond.C=C bond near the 5-OMe group vibrates at a higher frequency compared to the vibration of C=C bond on the ring in the farthest position to 5-OMe.The C=C stretching mode in cyclopentene rings is 1477 cm -1 which occurs at a lower frequency relative to the C=C bond in the ring involving substituent.On the other hand, in [Me 2 SnCl 2 .H 2 L 5 ] complexes C=C bond near the 5-NO 2 group vibrates at a lower frequency (1470 cm -1 ) compared to the vibration of C=C bond on the ring in the farthest position to 5-NO 2 (1490 cm -1 ) and the C=C stretching mode in cyclopentene rings is appeared at 1474 cm -1 .For C-O, C=N and Sn-O stretching frequency showed the agreement between the experimental and scale calculated frequencies.
Base on the optimized structure of the title compound at B3LYP/LANL2DZ level of theory, the atomic charge distributions for all atoms were calculated and the results are listed in Table 8.
Seen from this data, atomic electronegativity plays important roles for atomic charge distributions of the non-hydrogen atoms.Namely, between the two connecting atoms, the atom having bigger electronegativity will carry negative charges, while the atom having smaller electronegativity will carry positive charges.For example, when a carbon atom is connected with a nitrogen atom, the carbon atomic charges are positive values and the nitrogen atomic charges are negative values, since the nitrogen atom has bigger electronegativity than the carbon atom.However, when a nitrogen atom is joined with an oxygen atom, the nitrogen atom has positive charges and the oxygen atom has negative charges, since the oxygen atom has bigger electronegativity than the nitrogen atom.So, for the [Me 2 SnCl 2 .H 2 L 5 ] complexes (Table 8), the carbon atoms in cyclopentene and phenyl rings all carry negative charges, since the hydrogen atom has smaller electronegativity than the carbon atom, but C4, C21, C31, C33 and C36 have positive atomic charges.These carbon atoms were joined to nitrogen (imine and nitro group) and oxygen (phenolic group) atoms that have bigger electronegativity than the carbon atom.The N13 and N24 have negatively atomic charges but N54 carry positive charge, because N54 was joined to two oxygen atoms that have electronegativity than the nitrogen atom.On the other hand, for the non-hydrogen atom in Table 8, although atoms of N13, N22, N54 and the carbon atoms in phenyl and cyclopentene rings have negative charge values, steric effect hinders them to coordinate with Sn(IV) ions further.The phenolic oxygen of the ligand has most negative atomic charges, respectively and there is none steric effect hindered, so the phenolic oxygen donates more electron density to the tin atom which has highest positive atomic charge, leading to rather strong Sn-O bonding.This idea is supported by the IR data.L 5 ].Biological activity of the ligands and their complexes against different bacteria revealed that the complexes have higher antibacterial activity as compared to the free ligands.We have used density functional theory (DFT) to compute the electronic and molecular structures.The calculated structural parameters for complexes are in good agreement with the experimental data, confirming the obtained geometries for them.The FTIR spectra of the complexes were recorded and the important bands were identified and compared.They can use for analysis of complexes, help to explain the behavior of their vibrational modes.The HOMO-LUMO energy gap of the Sn(IV) complexes was calculated.The energy gap reflects to the chemical activity of the complexes.A large HOMO-LUMO gap increases stability and decreases chemical reactivity.The results show the following trend in HOMO

Table 1 .
Physical properties and analytical data of the synthesized tin(IV) complexes.

Table 4 .
The formation constants and the free energy values of tin(IV) complexes at 25 o C in DMF. a

Table 5 .
The Growth inhibition zone of the Schiff base ligands and their Sn(IV) complexes.

Table 7 .
The calculated properties for Sn(IV) complexes at B3LYP/Lan2DZ level of theory.