Antibacterial Co(II) and Ni(II) Complexes of N-(2-Furanylmethylene)-2-Aminothiadiazole and Role of SO42−, NO3−, C2O42− and CH3CO2− anions on Biological Properties

Co(II) and Ni(II) complexes with a Schiff base, N-(2-furanylmethylene)-2-aminothiadiazole have been prepared and characterized by their physical, spectral and analytical data. The synthesized Schiff-bases act as tridentate ligands during the complexation reaction with Co(II) and Ni(II. metal ions. They possess the composition [M(L)2]Xn (where M=Co(II) or Ni(II), L=, X=NO3−, SO42−, C2O42− or CH3CO2− and n=1 or 2) and show an octahedral geometry. In order to evaluate the effect of anions upon chelation, the Schiff-base and its complexes have been screened for antibacterial activity against bacterial strains e.g., Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa.


INTRODUCTION
Many studies-3 have indicated the relationship between the metal ions and their complexes as antitumour 49 and antibacterial agents. In vivo tests have shown that biologically active compounds become more carcinostatic and bacteriostatic upon chelationS6. Such interactions with metal ions, particularly those of the [13][14][15] transition metal ions with amino acids, peptides and nucleic acids, are of relevant biological importance Several reviews [16][17][18][19] have shown that the coordination of such compounds with metal ions markedly influence their biological action highlighting not only their catalytic function 2--3 but the nature of their chemical action -4-'7 as well. Many potent antibacterial and antifungal compounds are reported -8-'9 by condensation of salicylaldehyde with heterocyclic compounds. Thiadiazole derived compounds of salicylaldehyde were found 3 to be bactericidal/fungicidal against Bacillus cereus and Aspergilhts niger. Several others, incorporating piperazinyl guanidines, when condensed with salicylaldehyde were found to exhibit cardiovascular and vasodepressor activity. 3 Similarly, thiazolidinone-derived salicylaldehydes 3possess antimicrobial activity against many pathogenic strains. Keeping in view the significa.n.ce of thiadiazole or its derived compounds and the role of metals in biology, we have previously reported"" series of biologically active compounds and have evaluated the role of metal ions on their activity. In continuation to the same, we have prepared several other biologically active cobalt(ll) and nickel(II) complexes of the type [M(L).,]X, where M=Co(lI), Ni(ll) or Zn(II), L=N-(2-furanylmethylene)-2-aminothiadiazole (Fig 1), X NO3, SO4 ", C2042" or CI-13CO2 and n=l or 2, having the same metal ion (cation) but, different anions and wish to report the possible biological role of anions against bacterial strains of Escherichia coil, Staphylococcus aureus, and Pseudomonas aeruginosa. All chemicals and solvents used were of Analar grade. The metal(II) salts were used as nitrates, sulfates, oxalates and acetates. IR spectra were recorded on a Philips Analytical PU 9800 FTIR spectrophotometer. UV-Visible spectra were obtained in DMF on a Hitachi U-2000 double-beam spectrophotometer. C, H and N analyses was carried out by Butterworth Laboratories Ltd. Conductance of the metal complexes was determined in DMF on a Hitachi YSI-32 model conductometer. Magnetic measurements were made on solid complexes using the Gouy method. Melting points were recorded on a Gallenkamp apparatus and are  (25 mL). The mixture was refluxed for h and cooled to room temperature. On cooling, precipitates were formed which were filtered, washed with ethanol, acetone and ether, and dried. Crystallization in aqueous ethanol (30:70) gave the desired metal complex. All other metal complexes were prepared respectively following the same method.

Antibacterial Studies
The synthesized metal complexes, in comparison to the uncomplexed Schiff-base ligands were screened for their antibacterial activity against pathogenic bacterial species, E.s,cherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. The paper disc diffusion method"" was adopted for the determination of antibacterial activity.

Physical Properties
The Schiff-base ( Fig. 1) was prepared 4 by refluxing an appropriate amount of 2-amino-1,3,4-thiadiazole and furan-2-carboxaldehyde in ethanol in a 1:1 molar ratio. It was further used for complexation with the Co(II) and Ni(ll) metal ions. All the newly synthesized metal complexes (Table 1) were prepared by the stoichiometric reaction of the corresponding metal salts as their nitrate, sulfate, acetate and oxalate and the corresponding Schiff-base in a molar ratio M:L of 1:2 as shown by Scheme 1. and v(NH2) stretching vibrations and, instead, appearance of a strong new band at 1635 cm" assigned 36 to the azomethine v(HC=N) linkage. It suggested that amino and aldehyde moieties of the starting reagents are absent and have been converted into the azomethine moiety (Fig. 1). The comparison of the IR spectra of the Metal Based Drugs Vol. 8, No. 5,2002 Schiff-base and its metal chelates (Table 2) indicated that the Schiff-base was coordinated to the metal atom in three ways, representing them acting in a tridentate manner. The band appearing at 1625 cm due to the azomethine was shifted to lower frequency by -10-15 cm " indicating 37 participation of the azomethine nitrogen in complexation. The band at 1610 assigned to thiadiazole ring v(C=N) nitrogen also shifted to lower frequency by -15-25 cm that was also indicative of the involvement of ring nitrogen of thiadiazole in chelation.

MX,
Further conclusive evidence of the coordination of the Schiff-base with the metals, was shown by the appearance of weak low frequency new bands at 525-530 and 455-460 cm. These were assigned 3s to the metal-nitrogen v(M-N) and metal-oxygen v(M-O) respectively. These new bands were observable only in the spectra of the metal complexes and not in the spectra of its uncomplexed Schiff-base which in turn, confirmed participation of these hetero groups (oxygen of furane and nitrogen of thiadiazole moieties) in the coordination.  Xmax (cm'l) 26 The UV-Visible spectral bands are recorded in Table 1 The, first three bnds are signed 4 to the spin-allowed transitions "Ag(F)-->'T_g(F)(v), A,g(F) --> T(F)(v_) and Ag(F) --> T,(P)(v) respectively. The fourth band was of-high intensity due to lig-andmetal charge-transfer. The occurrence of three spin-allowed transitions supports the octahedral geometry for Ni(II) complexes (Fig 2).

Antibacterial Properties
The title Schiff-base and its Co(ll) and Ni(ll) metal chelates having the same metal ion (cation) but, different anion were evaluated for their antibacterial activity against bacterial species Escherichia coil (a), Staphylococcus altreus (b) and Pseudomonas aerltginosa (c). The compounds were tested at a concentration of 30 lg/0.01 mL in DMF solution using the paper disc diffusion method. The susceptibility zones were measured in diameter (mm) and the results are reproduced in Table 3. The susceptibility zones measured were the clear zones around the discs killing the bacteria. The Schiff-base and its complexes individually exhibited varying degrees of inhibitory effects on the growth of the tested bacterial species. The antibacterial results evidently show that the activity of the Schiff-base became more pronounced when coordinated to the metal ions. On the basis of the above observations, it is claimed that the process of chelation dominantly affects the biological behavior of the compounds that are potent against some bacterial strains. From these studies, it is also proposed that different anions do play a significant role in the biological behavior of the metal chelates. It is suspected that factors such as solubility, different dipole moment and cell permeability mechanisms may be influenced by the presence of the different anions also affect the mechanism of permeation through the lipid layer of the organisms killing more of them effectively. Table 3. Antibacterial Activity Data of the Schiffbase and its Metal Complexes