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 or , where L = N-isonicotinamido-furfuraldimine (INH-FFL) and or . 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.
The synthesis of transition metal complexes with Schiff bases of nitrogen and oxygen donor has stimulated interest due to their vast variety of biological activities ranging from pharmacological, antitumour, fungicide, bactericide, anti-inflammatory, and antiviral activities [1, 2]. We have recently published some lanthanide(III) complexes of semicarbazones  and oxovanadium(IV) [4, 5], platinum(II) , cobalt(II), and nickel(II) [2, 7] complexes of thiosemicarbazones derived from 4-aminoantipyrine. The antibacterial and antifungal properties of the thiosemicarbazone ligands and their cobalt(II) [2, 7], nickel(II) , and oxovanadium(IV)  complexes have also been examined. In continuation of our work on hydrazones of isoniazid (a drug of proven therapeutical importance ) complexes of metal ions , the present work describes the synthesis, magneto-spectral, electrochemical, thermal, and biological studies of a novel series of Ni(II) complexes of N-isonicotinamido-furfuraldimine (INH-FFL) (Figure 1).
The nickel(II) salt, , was obtained from BDH and used as received. and were prepared by methods reported elsewhere . The hydrazone of isoniazid viz. INH-FFL was synthesized by following a general method reported by us  (yield ca. 80%). A general method was used for the synthesis of the nickel(II) complexes . 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 and complexes, respectively. The reaction mixture was refluxed on a water bath for 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 under vacuum.
The molecular weight of the complexes was determined cryoscopically using Beckmann thermometer. The nickel contents of the complexes were determined complexometrically after decomposing with conc. and , while the chlorine was estimated by reported method . The thiocyanate was estimated argentometrically. The perchlorate was estimated by the method reported in our previous work . 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 . The antibacterial and antifungal activities of the representative nickel(II) complexes and standard drugs (ampicillin and tetracycline) were screened using reported methods .
3. Results and Discussion
The reaction of nickel(II) salts with INH-FFL resulted in the formation of , where or , , and , while , . 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. The paramagnetism observed for the present complexes ranges from 3.1–3.2 BM (Table 1) and is consistent with the octahedral stereochemistry .
The infrared frequencies in the present ligand associated with amide group (carbonyl-oxygen), azomethine-nitrogen (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 (amide-I band) and (ii) strong band in the 1600-1500 region (amide-II band). The amide-I band in INH-derivatives, however, appeared at 1655 . In the infrared spectra of the complexes, a considerable negative shift in (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 range is attributed to (C=N) (azomethine) mode . In spectra of all the complexes, this band is shifted to lower wave number and appears in 1545-1535 region indicating the involvement of N-atom of the azomethine group in coordination . 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 five-membered chelate ring. The three fundamental absorptions in complex, that is, C–N stretching , C–S stretching , and N–C–S bending identified at 2040-2035, 845-830, and 470-465 region are associated with the terminal N-bonded isothiocyanate ions . In the perchlorato complex, the presence of the (1100-1090) and (625-620) bands indicates that the symmetry of is maintained in the complex. It suggests the presence of outside the coordination sphere .
The electronic spectra of the octahedral nickel(II) complexes exhibit spectra showing three spin-allowed transitions in 7000–11000, 15000–19000, and 25000–29000 regions [2, 7]. In the present complexes, the electronic spectra were very similar to each other and consist of bands in 8200–10930 , 17540–17700 , and 26950–27500 regions, which clearly indicated the octahedral stereochemistry of the complexes.
The thermogravimetric results of representative complexes clearly suggested the absence of any water molecule in the complexes. During 160–265 temperature range, the weight loss corresponds to 37.21–39.34% indicates the loss of one molecule of INH-FFL, while second ligand molecule evaporated off at ~400. Finally, at ~600, NiO formation takes place according to the following general equation: 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 50g/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) [14–17]. 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  antibacterial and antifungal activities. However, the experimental conditions for complexes reported in literature are different [14–17].
The overall experimental evidences thus show that the studied nickel(II) complexes, and , display a coordination number six and have an octahedral environment around the metal ion. The complexes appear to be moderate antibacterial and antifungal agents.
The authors are thankful to URC of the University of the South Pacific for supporting finance for this research through Project nos. 6395-1321 and 6394-1321 (6C127-1321 and 6C126-1321) and Dr. Abdul Mohammed Hatha, Lecturer, Department of Biology, FST, USP for assisting in studying the biological properties of the compounds.
A. Chaudhary, A. Phor, and R. V. Singh, “Potentially biodynamic tetraaza macrocycles and their manganese complexes : antiandrogen, antimicrobial and PDI studies,” Bioinorganic Chemistry and Applications, vol. 3, no. 3-4, pp. 161–177, 2005.View at: Publisher Site | Google Scholar
S. Prasad and R. K. Agarwal, “Cobalt(II) complexes of various thiosemicarbazones of 4-aminoantipyrine: syntheses, spectral, thermal and antimicrobial studies,” Transition Metal Chemistry, vol. 32, no. 2, pp. 143–149, 2007.View at: Publisher Site | Google Scholar
R. K. Agarwal and B. Prakash, “Studies on the effect of various anions and diphenyl sulfoxide on the stereochemistry of lanthanide(III) coordination compounds of 4[-(-hydroxy--naphthalidene)amino] antipyrinesemicarbazone,” Transition Metal Chemistry, vol. 30, no. 6, pp. 696–705, 2005.View at: Publisher Site | Google Scholar
R. K. Agarwal, S. Prasad, and N. Gahlot, “Synthesis, spectral and thermal properties of some penta-coordinated complexes of oxovanadium(IV) derived from thiosemicarbazones of 4-aminoantipyrine,” Turkish Journal of Chemistry, vol. 28, no. 6, pp. 691–701, 2004.View at: Google Scholar
R. K. Agarwal and S. Prasad, “Synthesis, biological, spectral and thermal properties of oxovanadium(IV) complexes of N,N,S-containing ligands,” Reviews in Inorganic Chemistry, vol. 26, no. 5, pp. 471–492, 2006.View at: Google Scholar
R. K. Agarwal and S. Prasad, “Synthesis and spectral investigations of some platinum metals ions coordination compounds of 4[N-(furan--carboxalidene)amino]antipyrine thiosemicarbazone and 4[N-(,,-trimethoxybenzalidene) amino]antipyrine thiosemicarbazone,” Turkish Journal of Chemistry, vol. 29, no. 3, pp. 289–297, 2005.View at: Google Scholar
R. K. Agarwal and S. Prasad, “Synthesis, spectroscopic and physicochemical characterization and biological activity of Co(II) and Ni(II) coordination compounds with 4-aminoantipyrine thiosemicarbazone,” Bioinorganic Chemistry and Applications, vol. 3, no. 3-4, pp. 271–288, 2005.View at: Publisher Site | Google Scholar
R. P. Sharma, A. K. Kothari, and N. K. Sharma, “Acneform eruptions and antitubercular drugs,” Indian Journal of Dermatology, Venereology and Leprology, vol. 61, no. 1, pp. 26–27, 1995.View at: Google Scholar
R. K. Agarwal, L. Singh, D. K. Sharma, and R. Singh, “Synthesis, spectral and thermal investigations of some oxovanadium(IV) complexes of hydrazones of isonicotinic acid hydrazide,” Turkish Journal of Chemistry, vol. 29, no. 3, pp. 309–316, 2005.View at: Google Scholar
J. Bassett, R. C. Denney, G. H. Jeffery, and J. Mendham, Vogel's Text Book of Quantitative Inorganic Analysis, Longman Scientific & Technical, London, UK, 4th edition, 1986.
R. K. Agarwal and R. K. Sarin, “Synthesis and characterization of some lanthanide(III) perchlorato complexes of hydrazones of isonicotinic acid hydrazide,” Polyhedron, vol. 12, no. 19, pp. 2411–2415, 1993.View at: Publisher Site | Google Scholar
R. K. Agarwal and J. Prakash, “Synthesis and characterization of thorium(IV) and dioxouranium(VI) complexes of 4-[(2-hydroxy-1-naphthalidene)amino]antipyrine,” Polyhedron, vol. 10, no. 20-21, pp. 2399–2403, 1991.View at: Publisher Site | Google Scholar
M. B. Ferrari, G. G. Fava, E. Leporati et al., “Synthesis, characterisation and biological activity of three copper(II) complexes with a modified nitrogenous base: 5-formyluracil thiosemicarbazone,” Journal of Inorganic Biochemistry, vol. 70, no. 2, pp. 145–154, 1998.View at: Publisher Site | Google Scholar
B. Murukan and K. Mohanan, “Synthesis, characterization, electrochemical properties and antibacterial activity of some transiton metal complexes with [(2-hydroxy-1-naphthaldehyde)-3- isatin]-bishydrazone,” Transition Metal Chemistry, vol. 31, no. 4, pp. 441–446, 2006.View at: Publisher Site | Google Scholar
M. Tümer, D. Ekinci, F. Tümer, and A. Bulut, “Synthesis, characterization and properties of some divalent metal(II) complexes: their electrochemical, catalytic, thermal and antimicrobial activity studies,” Spectrochimica Acta Part A, vol. 67, no. 3-4, pp. 916–929, 2007.View at: Publisher Site | Google Scholar
U. El-Ayaan and A. A.-M. Abdel-Aziz, “Synthesis, antimicrobial activity and molecular modeling of cobalt and nickel complexes containing the bulky ligand: bis[-(2,6-diisopropylphenyl) imino] acenaphthene,” European Journal of Medicinal Chemistry, vol. 40, no. 12, pp. 1214–1221, 2005.View at: Publisher Site | Google Scholar
M. A. A. Al-Bari, M. K. B. Chowdhury, M. F. Hossen, M. M. Hossain, C. M. Zakaria, and M. A. U. Islam, “Novel nickel cyclam complexes with potent antimicrobial and cytotoxic properties,” Journal of Applied Sciences Research, vol. 3, no. 11, pp. 1251–1261, 2007.View at: Google Scholar