Abstract: The synthesis and spectroscopic investigations like 1H-, 13C-NMR of novel organotin (IV) esters are described. The FT IR study is successfully applied to verify the bonding mode of endo and exo status of tin (IV) of the dimeric nature of organotin (IV) compound 2. In vitro ED50, bactericidal, fungicidal, bioactivities are investigated, which indicate them significantly potential biocides. Based on spectroscopic analysis and literature evidences, the mono-and dimmer organotin (IV) esters are assigned tetrahedral and distorted octahedral cage type geometry.
INTRODUCTION
Organotin (IV) carboxylates exhibit significant bio activities and promising potential in many other fields of life such as fungicides, bactericides, anitifouling agents, PVC stabilizers, catalysts in the polymer chemistry, precursors for SnO2 films on glass, wood preservatives, pesticides and anti-leishminiatic agents[1-5]. The structural chemistry of organotin (IV) complexes of amino acids and protected amino acids has also revealed variety of features and rich diversity of structural motifs. As a continuation of investigation in the field of organotin (IV) carboxylates, we here report the biological activities, syntheses and spectroscopic characterization of the title esters.
MATERIALS AND METHODS
Maleic anhydride, glycine, di-n-butyltin (IV) oxide, and triethylamine are AR Grade Fluka Chemicals used without further purification. The ligands were prepared according to the reported procedures[6]. The monomer compound 1 was prepared by dissolving 1 g (4.0 mmol) dibutyltin oxide to 8.0 mmol ligand in 150 cm3 of toluene and 50 cm3 ethanol. The mixture was refluxed for 6 h and the ternary azeotrope water/ethanol/toluene was distilled off with Dean-Stark funnel. Half of remaining solution was evaporated under vacuum. The oily compound obtained was crystallized from mixture (4:1) of chloroform and hexane. The synthesis of compound 2 occurs similarly but half the amount of the ligand is used, i.e. 4.0 mmol.
Physical measurements: The melting points were measured on a melting point apparatus Reichert Thermovar of F. G. Bode Co. (Table 1) Austria. FT IR spectra were obtained using KBr disc on a Perkin Elmer FT IR1600 Spectrophotometer. Elemental analyses were carried out on a Yanaco MT 3 high speed CHN analyzer with an antipyrene as a reference compound. The 1H NMR spectra were recorded on a multinuclear FT NMR 200 MHz of JEOL and 13C spectra were taken at 50 MHz using a 13C probe. ED50 of the complexes was determined against a brine shrimp hatching method while bactericidal and fungicidal activities were measured by agar-well diffusion and agar-tube dilution methods[7].
RESULTS AND DISCUSSION
Syntheses: The 2-maleimidoacetic acid was synthesized as described in the literature[6]. The synthesis of di-n-butyltin (IV)di-N-maleoylglycinate, compound 1, Tetra-butylbis (N-maleoylglycinato) distannoxane, compound 2, is described in scheme 1.
Spectroscopic characterization: The OH absorption of ligand disappeared in the complexes. Both asymmetric and symmetric stretching of the maleimido (C2O2N), the carbonyl (CO), for Sn-C and Sn-O groups were exhibited as reported in literature[8]. The asymmetric and symmetric stretching of the CO group in monomer exhibit trend like a: vasym (compound) > vasym (ligand), vsym (compound) < vsym (ligand), Δ v (compound) > Δ v (ligand). The monomer tin ester shows unidentate or weak bidentate bonding with Sn (IV) atom. The order of asymmetric and symmetric of CO group of compound 2 with respect to ligand is as: vasym (compound) < vasym (ligand), vsym (compound) < vsym (ligand), Δ v (compound) > Δ v (ligand). In this case, two types of CO absorption bands were observed at 1685 to 1372 cm-1 for bonding behavior and 1714 to 1695 cm-1 for non-bonding behavior, which indicate two tin sites of compound 2 (Table 3). The butyl protons in mono and dimer were resolved on proper positions as reported[9]. The methyl protons of monomer exhibits a single triplet, which indicate one tin site, and two triplets of methyl protons in compound 2 are due to non-equivalent status of methyl protons bonded to endo and exo tin (IV) atoms (Table 4). The 13C NMR signals are properly resolved (Table 5) showing one signal for each methylene carbon in butyl group monomer and a pair of signals in dimer tin ester around exo and endo cyclic Sn (IV), which are easily identified from their nJ (119Sn-13C) coupling constants for both the mono and dimer compounds with well known ranking [1J]>>[3J]>[2J][10]. The 1H-, 13C-NMR and FT IR data of compounds 1 and 2 are in agreement with the structures proposed in Fig. 1 and 2. The %CHN analysis (Table 2) verifies the mono and dimeric composition of compounds 1 and 2.
Biological activities: The compounds 2 and 3 showed the highest toxicity against brine shrimp larvae (Table 7) as well as exhibited strong bactericidal and fungicidal properties (Table 8). Among such compounds, the carboxylate derivatives are used as anti-cancer, anti-tumour agents, fungicides or bactericides in vitro as well as in vivo[11]. It is also reported in the literature[12] that the four coordinated motifs has stronger tendency to increase the coordination numbers through O, S, or N donor groups while the five coordinated species do not undergo further coordination, which play no long term role in vivo chemistry of organotin (IV) esters.
| Fig. 1: | Structure of compound 1 with1H-, 13C-NMR and FT IR data |
| Fig. 2: | Structure of compound 2 with1H-, 13C-NMR and FT IR data |
| Table 1: | Physical properties |
| Table 2: | CHN analyses |
| * Calculated values are in parenthesis | |
| Table 3: | IR Data (cm-1) |
| Abbreviations for IR: asym: asymmetric; b: broad; s: small; sp: sharp; sym: symmetric; w: weak | |
| Table 4: | 1HNMR of complexes |
| NMR data: All spectra were acquired from CDCl3 Abbreviations for coupling patterns: s: singlet; t: triplet; b: broad resonance; m: complex pattern; nv: non visible |
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| Table 5: | 13CNMR data |
| Coupling constants are given in Hz between parenthesis for nJ (119Sn-13C) | |
| Table 6: | Brine shrimp bioassay |
| Where ++++ = Significant and + = Moderate Activity | |
| Table 7: | Bactericidal bioassay |
| a) ++++ = highest, +++ = high, ++ = optimum, + , = no activity.
Incubation period: 8 h., 37°C, Colony forming unit = 104106 Size of well = 5 mm radius. Reference Drug: Amoxicillin (H2O), Ampicillin (H2O), Cephlaxin Na |
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| Table 8: | Fungicidal bioassay |
| a) ++++ = highest, +++ = high, ++ = optimum, +,
-= no activity. Incubation time = 7h., 27°C. Reference Drug : b) Miconazole, Ketoconazole, c) Amphotenicin-B, Flycytosine, d) Benlate, Nabam |
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ACKNOWLEDGMENTS
The Gomal University is gratefully acknowledged for awarding a research grant for this research project. The HEJ Research Institute of Chemistry, University of Karachi is also acknowledged for carrying out all the bioactivities as well as major part of spectroscopic studies of the compounds.