Synthesis, Characterization and Biological Properties of Tridentate NNO, NNS and NNN Donor Thiazole-Derived Furanyl, Thiophenyl and Pyrrolyl Schiff Bases and Their Co(II), Cu(II), Ni(II) and Zn(II) Metal Chelates

2-Aminothiazole undergoes condensation reactions with furane-, thiophene- and pyrrole-2-carboxylaldehyde to give tridentate NNO, NNS and NNN Schiff bases respectively. These tridentate Schiff bases formed complexes of the type [M (L)2]X2 where [M=Co(II), Cu(II), Ni(II) or Zn(II), L=N-(2-furanylmethylene)-2-aminothiazole (L1), N-(2-thiophenylmethylene)-2-aminothiazole (L2, N-(2-pyrrolylmethylene)-2-aminothiazole (L3) and X=Cl. The structures of these Schiff bases and of their complexes have been determined on the basis of their physical, analytical and spectral data. The screening results of these compounds indicated them to possess excellent antibacterial activity against tested pathogenic bacterial organisms e.g., Escherichia coli, Staphylococcus aureous and Pseudomonas aeruginosa. However, in comparison, their metal chelates have been shown to possess more antibacterial activity than the uncomplexed Schiff bases.


INTRODUCTION
Thiazole and related compounds are of considerable interest TM due to their presense in the histidyl residue of proteins. As a ligand it also provides a potential binding site for metal ions. A thorough knowledge is therefore required to understand their coordination properties and the role of metal ions in such systems. A limited amount of work has been published on the complexing properties of such related compounds. This work is an extension of previously reported 5"7 studies on the coordination chemistry and the role of metal ions on such compounds and their bioability as bactericidals. Sherman and Dickson have reported series of 2-amino-4-(5-nitro-2-furyl)thiazoles and their various chloro, hydroxy and methoxy derivatives and observed that these compounds exhibit antibacterial activity in vitro, particularly against Staphylococcus aureus, 910 1I Salmonella and Escherichia coli. Subsequently a number of reports' and patents have described the preparation and antibacterial properties of a variety of hydroxyaryliminomethylthiazole, hydroxynaphthylthiazole-2-yl-thiazolidone and o-substituted benzylaminothiazoles and their derivatives.
However, no work so far, is reported on the synthesis and antibacterial properties of furane-, thiophene-and pyrrole-derived Schiff bases of thiazole. We therefore have made an effort to present, in this paper, the synthesis and biological activity of hitherto some novel Schiff bases (L , L and L3) containing the thiazole nucleus coupled with furane, thiophene and pyrrole moieties ( The Co(II), Cu(II), Ni(ll) and Zn(II) metal chelates of the title thiazole-derived compounds have been synthesised and characterized by their physical, analytical and spectral data. In order to evaluate their antibacterial properties the synthesised Schiff bases and their complexes have been screened against bacterial species Escherichia coli, Staphylococczts aztreozts, Pseudomonas aeruginosa and Klebsiella pneztmonae. The results of these studies have indicated that all these Schiff bases are antibacterial against one or more bacterial species and that, upon complexation, their antibacterial properties become more pronounced.

Antibacterial Studies
The synthesized metal chelates and, for comparison purposes, the free Schiff bases were screened for their antibacterial activity against pathogenic bacterial species, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa and Klebsiella pneumonae The paper disc diffusion method was adopted for the determination of the antibacterial activity as reported z elsewhere.

Physical Properties
Schiff bases were prepared by reacting equimolar amounts of the respective furane-2-, thiophene-2-and pyrrole-2-aldehydes with 2-aminothiazole in ethanol. The structures of these ligands were established with the help of their IR, H NMR, 3C NMR and microanalytical data (Tables and 4) All the metal complexes (1-12) ( Table 2) of these Schiff bases were prepared by the stoichiometric reaction of the respective metals as their chlorides and ligands in molar ratio M:L 1:2. Their elemental analyses and molecular weights shows the monomeric nature of these complexes. All the synthesized complexes are air stable, non-hygroscopic solids and decompose without melting. They are all soluble in DMF and DMSO.
Low conductance values of the complexes in DMF solution (12-28 ohm'cmZmol") indicated 3 that they are all non-electrolytic in nature and v (NHz) stretching vibrations and, instead, the appearance of a strong new band at-1635 cm'l assigned 416 to the azomethine v (C=N) linkage. This suggested that the amino and aldehyde moieties of the starting reagents no more exist and have been converted into the respective Schiff base linkages. The comparison of the infrared spectra of the ligands and their metal chelates indicated that the ligands were coordinated to the metal atom in three ways, thus representing the ligands to act as tridentates. The bands appearing at 1635 and 1615 cm " assigned to azomethine and thiazole ring v (C=N) vibrations shifted to lower frequency by 5-10 cm indicating the participation of the azomethine and thiazole ring nitrogens in chelation. Further conclusive evidence of the co-ordination of these tridentate ligands with the metals was shown by the appearance of weak low frequency new bands at-360-365, 455-460 and 525-530 cm "1 ( Table 2). These were in turn assigned to metal-sulphur v (M-S) (in thienyl compounds), metal-oxygen v (M-O) (in furanyl derivatives) and metal-nitrogen v (M-N) (in the pyrrolyl compounds) stretching vibrations 5 respectively. These new bands were observable only in the spectra of the metal complexes and not in the spectra of their Schiff bases thus confirming the participation of the heteroatoms S, O and N to the coordination.

NMR Spectra
The H NMR and 3C NMR spectra of the free ligand (Table 4) and its metal complexes support the conclusions derived from the IR spectra. The H NMR spectra of the free ligands exhibited 7 peaks at 7.8 ppm due to azomethine proton (CH=N). Other heteroaromatic protons were also found in their expected region. The azomethine proton signal in the spectra of the complexes display an upfield shift indicating in turn, its involvement in coordination A thiazole proton of the free ligand at 5 7.4 ppm also showed a downfield shift in the spectra of complexes providing an evidence for the coordination of the thiazole nitrogen to the metal atom. Similarly, C NMR spectra of the ligands showed azomethine carbon resonance at 165.4 ppm and one of the thiazole carbon resonance at 5 143.3 ppm which shifted downfield in the complexes attributed 8 to the coordination of azomethine and thiazole nitrogens to the metal atom. Similar shifts were observed in the resonance of furyl-, thiophenyl and pyrrolyl moities suggesting the coordination of their heteroatoms to the corresponding metal atom.  The title ligands and their metal chelates were evaluated for their antibacterial activity against the bacterial species Escherichia coli (a), Pseudomonas aeruginosa (b), Staphylococcus aureus (c) and Klebsiella pneumonae (d). The compounds were tested at a concentration of 30 tg/0.01 mL in DMF solution using the paper disc diffusion method. The susceptibility zones were measured in mm and reproduced in Table 5. The susceptibility zones were the clear zones around the discs. All the Schiff bases were found to be biologically active and their metal complexes showed more significant antibacterial activities against one or more bacterial species in comparison to the uncomplexed Schiff bases. It is however definite that in most of the cases chelation tends to make the ligands act as more powerful and potent bactericidals, thus killing more of the bacteria than the parent Schiff bases. It is however suspected that factors such as solubility, conductivity, dipole moment and cell permeability mechanisms (influenced by the presence of metal ions) may be possible reasons for increasing this activity.