Studies on Some Biologically Cobalt(II), Copper(II) and Zinc(II) Complexes With ONO, NNO and SNO Donor Pyrazinoylhydrazine-Derived Ligands

Biologically active complexes of Co(II), Ni(II), Cu(II) and Zn(II) with novel ONO, NNO and SNO donor pyrazinoylhydrazine-derived compounds have been prepared and characterized on the basis of analytical data and various physicochemical studies. Distorted octahedral structures for all the complexes have been proposed. The synthesized ligands and their complexes have been screened for their antibacterial activity against bacterial species Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumonae. The activity data show the metal complexes to be more active than the parent free ligands against one or more bacterial species.


INTRODUCTION
In recent years hydrazines and hydrazones have been actively investigated as donors because of their interesting biological properties 1-5 and varied ligational behaviour 69 towards different metal ions and manifestation of novel structural features in co-ordination chemistry. Much work has been done with their Schiff-base derived pyridine ring system 1. Pyrazine system with an additional nitrogen ring becomes a weaker base 1, but it forms structurally important metal complexesv-9. The present investigation was undertaken to develop and study a novel variety of interactions of such Schiff-base ligands derived from the reaction of pyrazinoylhydrazine with furane-2-aldehyde, thiophene-2-aldehyde and pyrrol-2-aldehyde. 16 The synthesized Schiff-base ligands and their metal complexes have been screened for their possible antibacterial activity against bacterial strains of Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumonae The antibacterial activity data of the ligands are shown to be substantially increased upon chelation against one or more bacterial strains. Vol. 5, No. 5, 1998 Studies on Some Biologically Cobalt(II), Copper(II)  aqueous ethanol (50. %) to give (Ll) (0.92 g). The same methodology was adopted for the preparation of (L2) (0.88 g) and (L) (0.94 g).

Preparation of Metal Complexes
To a hot ethanolic solution (20 mL) of the ligand (0.02 tool) was added an aqueous solution (10 mL) of the respective metal (II)salt (0.01 mol). The mixture was refluxed for 2 h. The resulting mixture was cooled, filtered and reduced to nearly half of its volume. This concentrated solution was left ovemight at room temperature which resulted in the formation of a solid product. The product thus obtained was filtered, washed with ethanol (2x10 mL) and dried. Crystallization from aqueous ethanol (50 %) gave the desired complexes (1-12).

Antibacterial Studies
Preparation of Discs.
The ligand/complex (30 (g) in DMF (0.0 lmL) was applied on a paper disc, [prepared from blotting paper (3 mm diameter)] with the help of a micropipette. The discs were left in an incubator for 48 h at 37 C and then applied on the bacteria grown agar plates. Preparation of Agar Plates. Minimal agar was used for the growth of specific bacterial species. For the preparation of agar plates for Escherichia coli, MacConkey agar (50 g), obtained from Merck Chemical Company, was suspended in freshly distilled water (1 L). It was allowed to soak for 15 minutes and then boiled on a water bath until the agar was completely dissolved. The mixture was autoclaved for 15 minutes at 120 C and then poured into previously washed and sterilized Petri dishes and stored at 40C for inoculation.

Application of Discs.
A sterilized forceps was used for the application of paper disc on tlae already inoculated agar plates. When the discs were applied, they were incubated at 37 C t0r 24 h. he zone of inhibition was then measured (in diameter) around the disc.

RESULTS AND DISCUSSION
The Schiff-base ligands L , L and L were prepared by a simple condensation reaction. The structural determination of these ligands was done with the help of IR, IH-NMR, 3C-NMR and microanalytical data (Tables & 2). The tentative assignment of some of the important infrared bands of ligands are recorded in Table 1. These bands in spectra of the free ligands show characteristic frequencies at 3275, 1714 and 1620 cm1. These are assigned to v(NH), v(C=O) and v(C=N) stretches respectively. protons. C-NMR spectra (Table 2) similarly, showed all carbons in their expected region. Also, the microanalytical data (Table 1) was found to be in agreement with the molecular structures of the title ligands. All the ligands apparently, contain a number of potential donor groups, which can act as co- IR spectra of the ligands also show well defined v(C=O) and v.qNH) modes and no stretching due to the presence ofv(OH) frequency in the region at 3360-3420 cm was found which was indicative of their more probable keto form (A) than the enol form (B). Furthermore, the absence of phenolic proton v(OH) in H-NMR spectra confirmed keto configuration of the ligands.
All the metal complexes (1-12) were prepared by stoichiometric reactions of the respective metal(II) chlorides and respective ligands in the molar ratio M:L 1:2. All complexes are air and moisture stable solids. They are soluble in DMSO, DMF and water and insoluble in other solvents. Molar conductance values of 10 .3 M solutions of the complexes in DMSO (35-52 ohm cm mol) and water (75-87 ohm cm mol) indicated 24 the complexes to be non-electrolytes, although some solvolysis occurred.

Magnetic Susceptibility
The magnetic measurements (  Vol. 5, No. 5, 1998 Studies on Some Biologically Cobalt(II), Copper(II) and Zinc(II) Complexes with ONO, NNO, and SNO Donor Pyrazinoylhydrazine-derived Ligands geometry for Co(II) and Ni(II) and distorted octahedral geometry for Cu(II) complexes. The Zn(II) complexes were found to be diamagnetic.   Infrared Spectra Co-ordination of the ligands with the metal ions was investigated by comparing the infrared spectra of the free ligands with the spectra of their metal complexes (Table 4). IR spectra of the ligands generally show bands at 3275 (s, sh), 1714 (s), 1620 (s) and 1000-1060 cm tentatively assigned to VNH, VC--O, VC--N and VN-N respectively29'3. In their metal complexes, the amide band remains at the same position as in the flee ligand indicating that keto oxygen adjacent to this amide is not co-ordinated. Upward shift of the VN-N band and 31 32 downward shift of azomethine linkage suggested co-ordination throu.h nitrogen of the azomethine group (-CH=N-). The pyrazine ring out of plane bending vibration at 345 cm moved to 367 cm indicating that the ring nitrogen is also involved in co-ordination.  to 4Tg 4T2g (F), Tg 4A2g (F) and Tlg 4Ttg (P) transitions, respectively, and are suggestive -1 -1 ofoctahedral geometry around the cobalt ion. Three bands observed at 9455-10112 cm 16220-17523 cm and 27375-28950 cm in the spectra of the nickel(II) chelates are due to spin-allowed transitions from 3A2g T2g (F), A2g --') Alg (F) and A2g Tg (P), transitions, respectively, in an octahedral 37 a8 environment '". The copper(II) chelates show only one band around 13965-15220 cm corresponding to .39 40 :Eg --:T2g transition, probably due to a distorted octahedral environment