Di-n-butyltin(IV) Complexes Derived from Heterocyclic β-diketones and N-Phthaloyl Amino Acids: Preparation, Biological Evaluation, Structural Elucidation Based upon Spectral [IR, NMR (1H, 13C, 19F and 119Sn)] Studies

Stable, six coordinated Bu2SnLA type complexes have been prepared [where LH = RCOC:C(OH)N(C6 H5)N:CCH3; R = -4-F-C6H4-(L1H), R = -4-Cl-C6H4-(L2H), R= -4-Br-C6H4-(L3H), R=-CF3(L4H) and AH = C(O)C6 H4 C(O)NCHR'COOH; R'= -H(A1H), -CH3(A2H), -CH(CH3)2(A3H)] by the interaction of 1:1:1 molar ratios of di-n-butyltin(IV) dichloride with corresponding organic moieties in refluxing benzene using two moles of Et3N as a base. In these complexes LH and AH behave as bidentate and coordination is taking place through oxygen, this is inferred from IR and 13C NMR studies. These complexes possess tin atoms in skew trapezoidal bipyramidal geometry with the C-Sn-C angles ranging from 149.88° to 156.84°. Some of these complexes with their corresponding organic moieties (LH, AH) were tested for their antimicrobial activities.


INTRODUCTION
A large number of organotin(IV) complexes using a variety of organic ligands /1-6/ have been synthesised and characterised in recent years due to their significant biological activities/7-9/. Some of these derivatives have been tested for in vitro activity on different type of tumour cells/10-12/. They also possess significant applications in different fields such as lubricating agents /13/, boat paint additives to prevent Bioinorganic Chem&try and Applications Table 1 Synthetic and analytical data of di-n-butyltin(IV) complexes.

Quantitative Antimicrobial Assay
Substances showing positive antimicrobial activity via the disc diffusion assay were subjected to the broth dilution method for the quantitative measurement of microbiostatic (inhibitory) activity as described by

Bu2SnL4A
Complex 12 After filtering off the EhN.HC1 and stripping off the volatile fraction from filtrate, all these derivatives were obtained as coloured solids. These derivatives were found to be soluble in common organic solvents and were recrystallised from CHCl/Pet.-ether mixture. The plausible structures of these newly synthesised mixed ligand complexes of di-n-butyltin(IV) have been proposed on the basis of spectral studies.

IR Spectra
A comparison of the IR spectra of these mixed ligand di-n-butyltin(IV) complexes has been found to be helpful in providing structural assignments of the complexes, vOH absorption has been found to be absent in the region 3400-2600 cm , showing that both the organic moieties are bonded through deprotonated forms which is supported by the presence of vSn-O vibrations in the region 650 + 60 cm -/27,28/. A band appearing at --,1760 cm due to vCO(asym) vibration in the spectra of N-phthaloyl amino acids (AH) does not show any significant shift, suggesting the non-involvement of this group (imido CO) in bonding. A broad band centered at ,--1702 cmin the IR spectra of AH may be assigned to [vCO(sym) + vCOO(asym)] vibrations splits into two after complex formation. The sharp band at 1702 cm and a medium intensity band at 1640 1610 cm 1 may be assigned to vCO(sym) and vCOO,ym) vibrations, respectively. The splitting of this band into two indicates the bidentate behaviour of AH/29, 1590 cm has been observed. These bands may be assigned to v(C=C C =N) and phenyl vibrations, respectively. A medium intensity band in the region 610-590 cm has been assigned to Sn-C vibration/32/. VoL 3, Nos. [3][4]2005 Di-n-butyltin(IV)Complexes Derived from Heterocyclic fl-diketones The presence of only one Sn-C band indicates that the two butyl groups are in trans axial position/33/.
According to group theoretical predictions the trans-SNO4C2 system should exhibit one Sn-O and one Sn-C vibration and the cis isomer two Sn-C and four Sn-O stretching vibrations in the IR spectra/34/ (Fig. 2).
The appearance of one Sn-C and one Sn-O stretching vibration in the IR spectra of these mixed ligand di-nbutyltin(IV) complexes suggests that two butyl groups are in trans configuration.  Table 2. 3C NMR Spectra 3C NMR spectra of di-n-butyltin(IV) complexes have been recorded in CHCI. solution and are tabulated as Table 3. A small shift has been noticed in the positions of C5 and COO carbons of LH and AH,  gF NMR Spectra 19F NMR Spectra of LnH and corresponding di-n-butyltin(IV) complexes (10,11 and 12) have been recorded relative to CFC13. LnH gives a single fluorine resonance peak at 6 -75.2 ppm while 10,11 and 12 show absorption peaks at 5 -70.6 ppm, 5 -71.4 ppm and 6 -72.6 ppm, respectively. Similar downfield shifting in fluorine resonance chemical shift has been reported in literature/44/, which suggests the non-involvement of the fluorine atom in bonding.

llgSn NMR Spectra
These mixed ligand diorganotin(IV) complexes have been subjected to l9Sn NMR studies and their results have been cited in Table 4. These complexes show 9Sn NMR signals in the range 5 -270.81 to 390.57 ppm. l9Sn NMR chemical shift values have been found to be influenced by the coordination number of tin atom/41/. These 19Sn NMR data are consistent with the earlier reported values/37,41,45/for hexa coordinated diorganotin(IV) complexes.

Antimicrobiai Results
Preliminary screening for antimicrobial activities of the stock solutions of metal complexes and corresponding organic moieties (LH,AH) were performed qualitatively using the disc diffusion assay.
Antimicrobial activities were measured from the diameter of clear inhibition zones caused by compounds.
Four compounds (I,4,7 and 10) were found to yield clear inhibition zones around the discs (Table 5).

Qualitative Antimicrobial Activity Results
Almost all the compounds were found to be more active than the heterocyclic [-diketones (LH), Nphthaloyl amino acids (AH) against all the organisms used. It may therefore, be concluded that the Di-n-butyltin(1V)Complexes Derived fi'om Heterocyclic fl-diketones Table 4 119Sn NMR spectral data of some mixed ligand di-n-butyltin(IV) complexes. coli). These mixed ligand di-n-butyltin(IV) complexes are more active as compared to the parent organic moieties which indicates that metallation increases the antimicrobial activity/46/. Although it is difficult to deduce an exact structure-activity relationship between the structure of these complexes and their microbial activities but the high activity of these complexes may be explained on the basis of the chelation theory/47/. Due to chelation of the metal ion, the polarity is reduced considerably on account of the partial sharing of its positive charge with the donor groups and the n electron delocalization over the whole chelate ring system. This, in turn increases the lipophilic character of the metal favouring its permeation through the lipid layer of the fungal membrane.

Quantitative Antimicrobial Activity Results
The MIC values have been recorded for I, 4, 7, 10 and the data have been summarised in Table 6. The MIC values of 1, 4 and 7 against different pathogenic fungi and bacteria suggest that the complexes are strongly antibacterial but poorly antifungal. While 10 is as good an antifungal agent as the commercially available antifungal agent Nystatin, the biological activity of LH,AH and their metal complexes is expected to be a function of steric, electronic and pharmokinetic factors/48/. Vol. 3, Nos. [3][4]2005 Di chelates in which the nBu substituents do not adopt cis or trans geometries about the central tin atom. It is best described as a skew trapezoidal bipyramidal geometry (Fig. 3).