http://www.e-journals.in Chemical Science Transactions DOI:10.7598/cst2015.1070 2015, 4(3), 677-681 RESEARCH ARTICLE Mixed Ligand-Cu(II) Complexes as Antimicrobial Agents: Preparation and Spectroscopic Studies R. M. NAVEEN KUMAR 1, K. SHIVA PRASAD 2* and N. PRASAD 3 1 VijayaVittala College, Mysore, Karnataka, India 2 Manipal Centre for Natural Sciences, Manipal University, Manipal-576 104, Karnataka, India 3 Department of Chemistry, Government Engineering College, Chamarajanagar, Karnataka, India shivaprasad.k@manipal.edu Received 26 May 2015 / Accepted 4 June 2015 Abstract: Three mixed ligand-complexes of Cu(II) were prepared using Schiff base ligands and characterized using analytical and physical techniques. Antimicrobial activities of the above synthesized Cu(II) complexes were performed against selected species of bacteria and fungi. All the three Cu(II) complexes under study showed good antimicrobial activity which was compared with standard antibacterial and antifungal drug. Keywords: Mixed ligands, Cu(II) complex, Analytical techniques, Antimicrobial activity Introduction Copper is one of the most important metal ions in biological systems, as it plays an important role in the transport and activation of molecular oxygen. Owing to its versatile nature, a considerable amount of work has been published on copper with a variety of ligands. The ardent interest of copper(ii)in this field is mainly due to its wide range of applications in the field of pharmacology, immunology and cancer therapy 1.The chemistry of Cu(II) complexes with heterocyclics containing oxygen and nitrogen as ligands has attracted increased attention and variety of coordination modes have been explored only in recent years. The chemical literature provides information on such ligands with copper to form an interesting series of coordination compounds 2,3. In the present investigation the author has made an effort to synthesize Cu(II) complexes of the Schiff base ligands reported previously 4. The synthesized complexes were characterized by analytical, physical and spectroscopic techniques. The antimicrobial activity of the synthesized Cu(II) complexes were evaluated against two bacteria namely Escherichia coliand Staphylococcus aureusand two fungi namely Aspergillusnigerand Alternariasolani by disc diffusion method.
Chem Sci Trans., 2015, 4(3), 677-681 678 Experimental The solvents and chemicals used in this work were of Analar grade. They included 1,10- phenantroline (Merck); Copper(II) chloride (Sigma). All materials used were of highest purity available and without further purification. Solvents employed were of 99% purity or purified by the known laboratory procedures. Thin layer chromatography was performed using Silica Gel G (Merck Index) pre-coated plates and thespots were visualized by exposure to iodine. All melting points (m.p.) were determined with a Büchi-530 melting point apparatus in open capillaries and are uncorrected. Infrared spectra were recordedin the range 4000-200 cm -1 on a JASCO FTIR- 8400 spectrophotometer using Nujol mulls technique. 1 H NMR spectra were obtained on a Varian AC 400 spectrometer. ESI-MS were determined on Varian 1200L model mass spectrometer. General Procedures Synthesis of Cu(II) complexes A separate methanolic solution of each previously reported Schiff base ligand (1 mmol) and phenanthroline (0.198 g, 1 mmol) in methanol was added drop wise to a methanolic solution of cupric chloride dihydrate (0.170 g, 1 mmol). The reaction mixture was stirred for 30 min and refluxed for 4 h on a water bath. The completion of the reaction was monitored by thin layer chromatography in n-hexane:methanol system (8:2). After the completion of reaction, the volume of the solution was reduced to half of its original volume and precipitated by adding into ice cold water. The solid compound obtained was filtered off, washed with hot water, methanol, then with ether and dried in vacuum over CaCl 2. Antimicrobial activity The in vitro antimicrobial screening effects of the synthesized mixed ligand Cu(II) complexes (1-3) were evaluated against four bacteria namely Bacillus Subtilis, Escherichia coli, Staphylococcus aureus and Ralstonia solanacearum and three fungi namely Aspergillus niger, Aspergillus flavus and Alternaria solani by disc diffusion method using nutrient agar medium for antibacterial studies and potato dextrose agar medium for antifungal studies. Results and Discussion The formation of the copper(ii) complexes was achieved by reaction of the previously synthesized Schiff base ligands(l) and 1,10-phenanthroline (phen) with copper(ii) salt (M) in 1:1:1 [M:L:phen] ratio. The synthesized complexes are very stable at room temperature in the solid state. The Cu(II) complexes were insoluble in water and common organic solvents but soluble in DMF and DMSO. Molar conductance measurements The molar conductivity values of the Cu(II) complexes in DMF (10-3 M solutions) were measured at room temperature and the results are listed in Table 1. The conductance values of all the Cu(II) complexes fall in the 16.5-21.0 Ω -1 cm 2 mol -1 range, indicating the nonelectrolytic nature of the complexes 5. Table 1. Physical data of the Cu(II) complexes. Compound Molecular Yield Molar conductance formula % Ω -1 cm 2 mol -1 1 C 23 H 19 N 5 O 2 SCuCl 59 18.3 2 C 23 H 19 N 5 O 2 SCuBr 63 16.9 3 C 23 H 20 N 5 O 3 SCu 74 20.7
679 Chem Sci Trans., 2015, 4(3), 677-681 Thermal studies The TG/DTG curves of complex 3 are shown in Figure 1. The TGA profiles over the temperature range 30-200 ᴏ C are usually due to loss of water of moisture, hydration and coordination. The first stage in the range 30-100 ᴏ C corresponds to the dehydration. The anhydrous complex is stable up to 210 ᴏ C. The observed weight loss indicates the loss of two lattice water molecules present in the complex. In the second stage, continuous mass loss occurs in the range 210-390 o C (TG=42.1%), suggesting the evaporation of ligand. The third step occurred between 400-480 o C (TG=31.5%). The loss in weight corresponds to the remaining organic ligand molecule leaving behind metal oxide as the end product. Weight, % Derive. Weight, % o C Figure 1. TG/DTG curves of complex 3 IR spectra of copper(ii) complexes Comparison of the infrared spectral data of complexes and their corresponding ligands confirmed that complexation has occurred as significant shifts in the bands of the azomethine group ν C=N. The expected mode of interaction between the Schiff base ligand and the copper(ii) ion was found to be the azomethine nitrogen group 6. The IR spectra of complex 3 is shown in Figure 2. The expected characteristic imine band in the region1582-1596 cm -1, shifted to lower frequencies due to metal coordination. It is also very clear that a broad band in the region 3458 cm -1 due to hydroxyl group in complex 3 remains unchanged confirming the non-participation of OH group in the complexation. 110 100 Temperature, o C T% 50 0 4000 3000 2000 1000 600 Wavenumber, cm -1 Figure 2. Infrared spectrum of complex 3
Chem Sci Trans., 2015, 4(3), 677-681 680 Antimicrobial activity The data pertaining to the antimicrobial potential of mixed ligand-cu(ii) complexes are presented in Table 2. The results indicate that the complexes show more activity than the free ligands against same microorganisms under similar experimental conditions. The remarkable activity was observed for complex 3 may be arisen from the hydroxyl group, which may play an important role in the antibacterial activity as well as the presence of imine group which imparts in elucidating the mechanism of transformation reaction in biological systems. This would suggest that the chelation could facilitate the ability of a complex to cross a cell membrane and can be explained by Tweedy s chelation theory 7,8. All the test compounds show lesser activity than the standard antibiotics. Table 2. Antimicrobial activity of Cu(II) complexes. Zone of inhibition, in mm * Compound Antibacterial activity Antifungal activity S.aureus E. coli A. niger A. solani 1 22 20 19 11 2 11 16 11 14 3 27 25 21 28 Chloramphenicol 32 29 - - Griseofulvin - - 27 31 * Average of three replicates Conclusion Ternary copper(ii) complexes with previously reported Schiff base ligands and 1,10- phenanthroline have been prepared and structurally characterized with the analytical, physical and spectral data. The antimicrobial results of the synthesized mixed ligand-cu(ii) complexes show better activity than their respective ligands but less than the standard drugs. Based on the above obtained data, following structures are assigned for the Cu(II) complexes (Figure 3). Figure 3. Proposed structures of mixed ligand-cu(ii) complexes
681 Chem Sci Trans., 2015, 4(3), 677-681 Acknowledgement One of the authors Dr. K. Shiva Prasad would like to thank Prof. Mohini Gupta, Director, Manipal Centre for Natural Sciences, Manipal University, Manipal for her keen support in providing necessary facilities. References 1. Singhal N K, Balaji R, Vairamani M and Rao C P, Org Lett., 2006, 8(16), 3525 3528; DOI:10.1021/ol061274f 2. Zong-Huijiang, Liao D Z, Hao S Q, Hao J L, Zhang Z Y, Wang G L, Polyhedron, 1991, 10(9), 941-944; DOI:10.1016/S0277-5387(00)86912-0 3. Gave J D and Fenton D E, Polyhedron, 1991, 10(15), 1809-1815; DOI:10.1016/S0277-5387(00)83804-8 4. Naveen Kumar R M, Shiva Prasad K, Chandan S and Prasad N, Der Pharma Chemica, 2014, 6(4), 10-14. 5. Shebl M, Spectrochim Acta Part A, Mole Biomole Spectros., 2008, 70(4), 850-859; DOI:10.1016/j.saa.2007.09.035 6. Chand D K, Schneider H J, Aguilar J A, Escarti F, Garcia Esspara E and Luis S V, Inorg Chim Acta, 2001, 316(1-2), 71-78; DOI:10.1016/S0020-1693(01)00380-2 7. Tweedy B G, Phytopathology, 1964. 55, 910-914. 8. Zhong C Y, Zhao J, Wu Y B, Yin C X and Yang P, J Inorg Biochem., 2007, 101(1), 10-18; DOI:10.1016/j.jinorgbio.2006.07.011