Copper (II) Acylhydrazinates. Their Synthesis and Characterization

Acylhydrazine derived furanyl and thienyl Schiff bases and their Cu(II) complexes have been prepared and characterized on the basis of their physical, spectral and analytical data. The preferred enolic form of the Schiff base function as a tetradentate ligand during coordination to the metal ion yielding a square planar complex. The Schiff bases and their complexes with different anions were tested for their antibacterial activity against bacterial species such as Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa andKlebsiella pneumonae.


INTRODUCTION
Many studies 1have indicated the interesting and varied ligational behavior of hydrazine and hydrazones towards transition metal ions. Their bacteriostatic properties [5][6][7][8][9] were well studied by many researchers1-12. Some hydrazones have also been found to act as potent inhibitors for DNA synthesis in a variety of cultured human cells and in particular, their Cu(II) complexes were shown to produce significant inhibition of tumor growth when administered to mice bearing a transplanted fibrosarcoma a3 '14 Because of such promising results, the antibacterial metallo-organic chemistry of such ligands is yet to be explored. We have previously reported a5"8 some antibacterial acylhydrazine derived Schiff bases and their various transition metal complexes. The present study was undertaken in order to prepare and study the metallo-organic/coordination behavior of Cu(II) with the Schiff base ligands L and L2. 0% /NH _N (20 mL) was added to a stirred hot ethanol solution (30 mL) of oxaloyldihydrazide (1.2 g, 0.01 mol). Then 2-3 drops of cone. H2SO4 were added and the mixture was refluxed for 8 h. The reaction mixture was then cooled and left for 24 h at room temperature. During this period, a light yellow solid was formed which was recrystallized from hot ethanol to give the desired product (L1) (1.8 g). L 2 was prepared according to the same reported 17 method described as for L

Preparation of the Metal Complexes
An ethanol solution (20 mL) of the appropriate Cu(II) salt (0.001 mol) was added to a well-stirred hot ethanol solution (20 mL) of the respective Schiff base (0.001 mol). The mixture was refluxed for 8 h. Then on cooling at room temperature; a precipitated solid product was formed. The product thus obtained was filtered, washed with ethanol, then with ether and dried. Crystallization from aqueous ethanol (50 %) gave the desired metal complexes.

Physicnl Properties
The Schiff bases (L and L2) (  (Table I)   Model studies of these Schiff bases (Fig. 2) show that in no case can these Schiff bases exhibit tridentate behavior. They are only capable of exhibiting tetradentate (Fig. 2) behavior. However, they have a tendency to exhibit different tautomers, either as diketone [ Fig. 2A], dienol [ Fig. 2B] and as well as ketoenol [ Fig. 2C].
In the dienol form, the ligands may coordinate metal ions through X (X=O or S) donor sites of furanyl or thienyl and through the two azomethine nitrogens (HC=N). The diketone and ketoenol forms can also behave similarly, as tetradentate ligands, coordinating through the same coordination sites as dienol form. Infrared Spectra The IR spectra of the Schiff bases and their Cu(II) complexes were recorded in KBr and are reported in Tables with some tentative assignments of their important characteristic bands. All these Schiff bases showed the absence of the bands at -03420 cm q and 1730 cm due to characteristic v(NH) and (C=O) stretching vibrations of the respective hydrazinoamine and aldehyde. Instead, a new band at 1635 cm q assigned z to the omethine (HC=N) linkage appeared in the spectra of all of the proposed Schiff base ligands. Also a band at 1020 cm 1 due to a HN-N vibration appeared in the spectra of L and L2. This observation suggested m that the hydrazinoamine and aldehyde moieties of the starting reagents are no longer present and that condensation to the respective Schiff bases has taken place.
OH C NH --N CH X Fig. 2 Tautomeric forms of the investigated ligands A comparison of the infrared spectra of the Schiff bases and their metal complexes indicated 2'22 that the Schiff bases are tetradentately coordinated to the metal ions. The band due to v(C=O) was absent in the spectra of the complexes suggesting 23 enolization of the Schiff bases during complexation. This is supported by the evidence that the band due to v(OH) in the spectra of these complexes was observed at~3315 cm-1. 2 These facts suggested that t.he Schiff bases L and L remained in the keto form in the solid state as uncomplexed ligands but in solution the keto and enol forms were in equilibrium24, as shown in Fig. 2B. The amide-II band was split, displaced to higher frequency and reduced in intensity. Shift (5-10 cm) to higher frequency of the v(N-N) band at 1025. cm and its splitting indicated coordination of the azomethine nitrogen. Moreover, a low frequency shift (10-15 cm"1) of the band due to the azomethine (HC=N) linkage at 1635 cm "1 indicated involvement of the azom.thine nitrogen in coordination. The appearance of weak, low 25 frequency new bands at~360 and --455 cm" were assigned to metal-sulfur v(M-S) in the thienyl and metal-oxygen v(M-O) in the furanyl ligands. These bands were only observable in the spectra of the metal complexes and not in the spectra of their Schiff bases which in turn confmned the participation of the 22,26 heteroatoms X (S or O) in the coordination. These observations, in turn, suggested a square planar geometry for the Cu(II) complexes (Fig. 3).

NMR Spectra
The NMR spectra of the free ligands and some of their metal complexes have been recorded in DMSO-d6.
The features of the free ligands are already reported 7 elsewhere which have shown the NMR spectra of the free ligands in support to the conclusions derived from the IR spectra as expected. In the spectra of the Cu(II) complexes (Table III), these proton signals appeared much more downfield, as expected, due to increased 28 29 conjugation during coordination Table II. IR  13C NMR (DMSO-d6) (,ppm)

Magnetic Moment and Electronic Spectra
The UV-Visible spectral bands of the Cu(II) complexes are recorded in Table I. The copper(II) complexes exhibited 3 magnetic moment of 1.55-1.65 B.M at room temperature. These values are quite close to the spinallowed values expected for a S=1/2 system and the complexes attain a square planar geometry around the copper(II) ion. These copper(II) complexes (Table II) display a broad band at---14680 cm q due to 2B1 2Eg -1 31 32 and two bands at -16395 and -27320 cm assigned due to d-d transitions and a charge transfer band, confirming their square planar enviroranent 33 (Fig. 3).
Antibacterial Properties Antibacterial properties of the ligands and their metal complexes were studied against bacterial species Escherichia coB, Pseudomonas aeruginosa, Staphylococcus aureus and Klebsiella pneumonae. These were tested at a concentration of 30 xg/0.01 mL in DMF solution using a paper disc diffusion method devised and reported 34"37 earlier. The results of these studies reproduced in Table IV indicated that both the Schiff-base ligands and their metal complexes individually exhibited varying degrees of inhibitory effects on the growth of the testing bacterial species. The antibacterial results evidently show that the activity of the unchelated compounds became more pronounced and prominent when chelated with the metal ion. When the same metal chelate having different anions was individually screened, the degree of bectericidal activity/potency also varied.
L1;X =0 L2; X S Y=NO 3, SO 4, CH3COO, C204 n=l or2 (Fig. 3) Proposed Structure of the Cu(II) Complex From the obtained data, it was generally observed that the order of potency in comparison to the metal chelate having chloride anion evaluated and reported earlier 38 and to the results of the present studies against the same tested bacterial species under the same conditions were found to follow the order as NO3> C204> CH3CO2> CI> SO4 On the basis of these results, it is therefore, strongly claimed 39'4 tha differem anions dominantly effect the biological behavior of the metal chelates. It is, however, expected that factors such as solubility, conductivity, dipole moment and cell permeability mechanisms are certainly influenced by the presence of these anions in the chelate and may cause m increasing this activity. These studies provide a useful information about the biological activity of compounds influenced by the anions which stay outside the coordination sphere of the chelated complex.