Nickel(II) Complexes of Hydrazone of Isoniazid and Their Magneto-Spectral, Electrochemical, Thermal and Antimicrobial Investigations

The synthesis of novel nickel(II) complexes with new ligand derived from hydrazone of isoniazid has been reported. The complexes have general compositions [Ni(L)2X2] or [Ni(L)3](ClO4)2, where L = N-isonicotinamido-furfuraldimine (INH-FFL) and X = Cl− or NCS−. The ligand hydrazone behaves as neutral bidentate (N and O donor) through the carbonyl oxygen and azomethine nitrogen. On the basis of elemental analysis, molecular weight determinations, magnetic susceptibility/moment, thermogravimetric, electrochemical, and spectroscopic studies, the new complexes have been characterized with octahedral geometry. The antibacterial and antifungal studies of the present complexes show that they are moderate antibacterial and antifungal agents.


Experimental
The nickel(II) salt, NiCl 2 ·6H 2 O, was obtained from BDH and used as received. Ni(NCS) 2 and Ni(ClO 4 ) 2 were prepared by methods reported elsewhere [7]. The hydrazone of isoniazid viz. INH-FFL was synthesized by following a general method reported by us [9] (yield ca. 80%). A general method was used for the synthesis of the nickel(II) complexes [7]. A hot ethanolic solution of the corresponding nickel(II) salt was mixed with a hot ethanolic solution of the hydrazone ligand in molar ratio 1:2, and 1:3 for [Ni(L) 2 X 2 ] and [Ni(L) 3 ](ClO 4 ) 2 complexes, respectively. The reaction mixture was refluxed on a water bath for ∼2 hours. On cooling the reaction mixture at room temperature, the colored complexes precipitated out in each case. The complexes were filtered out, recrystallized, washed with ethanol, and dried over P 4 O 10 under vacuum.
The molecular weight of the complexes was determined cryoscopically using Beckmann thermometer. The nickel contents of the complexes were determined complexomet-  [7], while the chlorine was estimated by reported method [10]. The thiocyanate was estimated argentometrically. The perchlorate was estimated by the method reported in our previous work [7]. The percentage of nitrogen was determined by Kjeldahl method. The conductivity and the magnetic measurements of the complexes were performed using a Toshniwal conductivity bridge and Evans magnetic balance, respectively [2,7]. The infrared spectra and diffused reflectance spectra of the solid complexes were recorded on a Perkin Elmer FT-IR infrared spectrophotometer model 521 and Beckmann DK-2A spectrophotometer, respectively. Thermogravimetric analyses of the complexes were performed on Perkin Elmer Pyris Diamond in static air with unlidded small platinum boat sample holder at heating rate 6 • C min −1 . The antibacterial and antifungal activities of the representative nickel(II) complexes and standard drugs (ampicillin and tetracycline) were screened using reported methods [2].

Results and Discussion
The reaction of nickel(II) salts with INH-FFL resulted in the formation of [NiX 2 (L) n ], where X = Cl − or NCS − , n = 2, and [Ni(L) n ]X 2 , while X = ClO 4 − , n = 3. The analytical data, molar conductance in nitrobenzene, and molecular weights of the complexes are presented in Table 1. The complexes were quite stable and could be stored for several weeks without any appreciable change but decomposed on heating beyond 250 • C. The paramagnetism observed for the present complexes ranges from 3.1-3.2 BM (Table 1) and is consistent with the octahedral stereochemistry [7].
The infrared frequencies in the present ligand associated with amide group (carbonyl-oxygen), azomethinenitrogen (C=N), and heterocyclic nitrogen are expected to be influenced on complex formation with nickel(II). Generally, amides show two absorption bands: (i) the carbonyl absorption band near 1640 cm −1 (amide-I band) and (ii) strong band in the 1600-1500 cm −1 region (amide-II band). The amide-I band in INH-derivatives, however, appeared at 1655 cm −1 [11]. In the infrared spectra of the complexes, a considerable negative shift in v(C=O) was observed indicating a decrease in the stretching force constant of (C=O) as a consequence of coordination through the carbonyl oxygen atom of the ligand. Another important band occurs at 1585 cm −1 range is attributed to v(C=N) (azomethine) mode [12]. In spectra of all the complexes, this band is shifted to lower wave number and appears in 1545-1535 cm −1 region indicating the involvement of N-atom of the azomethine group in coordination [12]. The overall infrared spectral evidence suggests that the present ligand acts as bidentate ligand and coordinates through amide oxygen and azomethine nitrogen atoms forming a fivemembered chelate ring. The three fundamental absorptions in [Ni(NCS) 2 (L) 2 ] complex, that is, C-N stretching (v 1 ), C-S stretching (v 3 ), and N-C-S bending (v 2 ) identified at 2040-2035, 845-830, and 470-465 cm −1 region are associated with the terminal N-bonded isothiocyanate ions [7]. In the perchlorato complex, the presence of the v 3 (1100-1090 cm −1 ) and v 4 (625-620 cm −1 ) bands indicates that the T d symmetry of ClO 4 − is maintained in the complex. It suggests the presence of ClO 4 − outside the coordination sphere [13].
The electronic spectra of the octahedral nickel(II) complexes exhibit spectra showing three spin-allowed transitions in 7000-11000 cm −1 (v 1 ), 15000-19000 cm −1 (v 2 ), and 25000-29000 cm −1 (v 3 ) regions [2,7]. In the present complexes, the electronic spectra were very similar to each other and consist of bands in 8200-10930 {v 1 , 3 The antibacterial activities of the nickel(II) complexes and standard drugs (ampicillin and tetracycline) were screened by agar cup method in DMF solvent at a concentration of 50 µg/mL under identical conditions. The results were checked against gram positive bacteria, Bacillus subtilis and Staphylococcus aureus, and gram negative bacteria, Escherichia coli and Salmonella typhi, which show that the nickel(II) complexes of INH-FFL have moderate antibacterial activities against these bacteria ( Table 2). The screened antifungal activities of the complexes against two fungi (Aspergillus niger and Candida albicans) show that they are less active compared to salicylic acid and appear to be moderate antifungal agents ( Table 2). The antibacterial and antifungal activities of the present complexes were also compared with the activity results of some other nickel(II) complexes having different ligands (Table 2) [14][15][16][17]. It was found that the present complexes are less potent bactericides with respect to few reported nickel(II) complexes [14,15], while some other complexes have almost comparable [16,17] or less [17] antibacterial and antifungal activities. However, the experimental conditions for complexes reported in literature are different [14][15][16][17].
The overall experimental evidences thus show that the studied nickel(II) complexes, [Ni(L) 2 X 2 ] and