Research Journal of Chemical Sciences ______________________________________________ ISSN 2231-606X Vol. 5(6), 40-45, June (2015) Res. J. Chem. Sci. International Science Congress Association 40 Synthesis, Characterization and Antioxidant studies of Cd(II), Hg(II) and Pb(II) Complexes of some Synthetic Curcuminoids Pallikkavil R, Ummathur M.B2*and Krishnankutty K1 Department of Chemistry, University of Calicut, Thenhipalam, Kerala, INDIA PG Department of Chemistry, KAHM Unity Women’s College, Manjeri, Kerala, INDIAAvailable online at: www.isca.in, www.isca.me Received 23rd May 2015, revised 2nd June 2015, accepted 14th June 2015 AbstractCd (II), Hg (II) and Pb (II) complexes of two synthetic curcuminoid analogues derived from pentane-2,4-dione and aromatic aldehydes (furfural and naphthalene-2-carbaldehyde) have been synthesized and characterized by analytical and spectral data. In all the chelates, ligands behaved as monobasic bidentate where the hydrogen bonded enolic proton is substituted by the metal ion. Antioxidant studies of four synthetic curcuminoids (derived from benzaldehyde, cinnamaldehyde, furfural and naphthalene-2-carbaldehyde) revealed that all the ligands possess significant antioxidant activities. Maximum activity was observed with 2-naphthyl curcumin. Metal complexation enhanced the antioxidant activity of all the compounds and among these Hg(II) complexes showed highest activity. Keywords: Synthetic curcuminoids, metal complexes, spectral data, antioxidant studies. Introduction An imbalance between free radicals and antioxidant systems in our body cause oxidative stress leading to chronic diseases. The formation of free radicals due to normal metabolic processes and other environmental factors harmfully affect the physiological activities of cells2,3. Synthetic organic chemists have developed many effective antioxidants for rubber, hydrocarbon fuels, plastics and food stuffs. Propyl gallate, BHA and BHT are antioxidants used as food additives. Certain vitamins (vitamin E and C), minerals and natural phenolic compounds, flavanoids and carotenoids have the capacity to counteract free radicals by scavenging them9-11. Recent literatures12-14 provides a number of evidences for the antioxidant characteristics of curcuminoids. Both turmeric and curcuminoids prevent the formation of free radicals like superoxide and hydroxyl radicals15The antioxidant properties of curcumin in the prevention of lipid peroxide, another process that generates free radicals, is well recognized16,17As an extension of our research work on synthetic curcuminoids and their metal complexes18-21, we report herein the synthesis, characterization and antioxidant studies of the Cd(II), Hg(II) and Pb(II) chelates some novel curcuminoid analogues. Material and Methods Experimental: Carbon and hydrogen percentages were calculated by microanalyses (Heraeus Elemental Analyzer) and metal contents of the chelates by AAS (Perkin Elmer 2380). The UV spectra of the compounds were recorded in methanol (10–6 M) on a JASCO V-550 UV-Visible spectrophotometer, IR spectra (KBr disks) on a JASCO FT/IR 4100 instrument, H NMR spectra (CDCl3 or DMSO-d) on a JEOL 400 NMR spectrometer and mass spectra on a JEOL-JMS 600H FAB mass spectrometer. The determination of molar conductance of the chelates was carried out in DMF (~10–3 mol/L) at 301 1 K. Magnetic moments of the complexes were determined at room temperature (301 1 K) on a SHERWOOD Scientific Magnetic susceptibility balance with Hg[Co(NCS)] as the standard. The reagents used were Merck and Aldrich or chemically pure grade. Synthesis of curcuminoid analogues (HL): The curcuminoid analogueswere synthesized using pentane-2,4-dione and aromatic aldehydes (benzaldehyde, cinnamaldehyde, furfural and naphthalene-2-carbaldehyde) as reported earlier2224. Synthesis of metal chelates: To a boiling solution of the compound in methanol (0.02 mol, 20 mL) a methanolic solution of the metal (II) acetate (0.01 mol, 15 mL) was poured and the reaction mixture was refluxed for ~2 h. The volume of the solution was reduced to half by concentration and then cooled to room temperature. The precipitated metal chelate was filtered and washed with water. All the chelates were recrystallized from hot methanol. Antioxidant studies: A solution (2.53%) of linoleic acid in 99.5% DMSO and 0.05 M phosphate buffer of pH 7 were prepared. Solution (4 mL) of the test compound (2 mg in 99.5% DMSO) was added to a solution containing linoleic acid (4.1 mL), phosphate buffer (8 mL) and distilled water (3.9 mL) taken in a stoppered Erlenmeyer flask, and incubated at 40 °C in the dark for 7-8 days. At periodic intervals during the incubation, 100 L of the mixture was used for the antioxidant assay by the thiocyanate method25 as described below. The incubated solution (100 L) was added to 75% DMSO (9.7 Research Journal of Chemical Sciences ___________________________________________________________ ISSN 2231-606XVol. 5(6), 40-45, June (2015) Res. J. Chem. Sci. International Science Congress Association 41 mL) and 30% ammonium thiocyanate solution (0.1 mL). Ferrous salt solution (0.1 mL, 2 Χ 10-2 M) in 3.5% HCl was added and precisely after 3 minutes the absorbance of the red colour products was determined at 500 nm. The antioxidant activity was judged from the decrease in the absorbance compared to the absorbance of a control maintained under identical condition. Results and Discussion Structural characterization of metal complexes: The synthesis and structural characterization of the Cd(II), Hg(II) and Pb(II) chelates of the synthetic curcuminoids produced from benzaldehyde and cinnamaldehyde have already been reported earlier21. Hence the curcuminoids derived from furfural and naphthalene-2-carbaldehyde is included in this section. The observed elemental analytical data (table-1) of the metal complexes suggest [ML] stoichiometry as in figure-1. All the chelates were found as non-electrolytes (specific conductance 10 –1cm-1; 10–3 M solution in DMF). The diamagnetic nature of all the chelates was proved from the magnetic measurements. M = Cd(II), Hg(II) and Pb(II) Ar = 2-Furyl (HL) and 2-Naphthyl (HL) Figure-1 Structure of the metal complexes of synthetic curcuminoidsIn the IR spectra of the metal complexes, the band at ~1620cm-1 of the ligand is absent and a strong band appeared at ~1580cm-1 assignable to the stretching of the coordinated carbonyl moiety. The broad band in the 2800-3500 cm-1 region of the ligands was vanished in the spectra of the chelates justifying the replacement of enolic hydrogen by the metal ion during complexation24,26. The band at ~975cm-1 is typical of a trans –CH=CH- group and found unchanged in the spectra of metal complexes24,26. The participation of two keto groups in metal chelate formation as in figure 1 is further proved by the presence of two medium intensity bands at ~420 and ~470 cm-1 due to M-O26,27. Important bands appeared in the IR spectra of the metal complexes are shown in table-1. In the H NMR spectra of the diamagnetic Cd(II) complexes, the signal due to the enolic hydrogen of the ligand was absent indicating its replacement by the metal ion during the formation of chelates24. The deprotonation of the OH group caused the shifting of methine proton signal appreciably to low field. The integrated intensities of the signals appeared in the spectra were in accordance with the figure 1 of the chelates. The spectral data of the chelates are given in table-2. The FAB mass spectra of the Cd(II) complexes displayed intense molecular ion peaks in accordance to their formulae. Peaks correspond to successive removal of aryl groups, [CdL], + and ligand fragments are also found in the spectra. Important fragments appeared in the spectra are given in table-2. The UV spectra of the complexes showed close resemblance to that of the free ligands which indicate that no structural change of the ligand has taken place in the metal chelate formation. But the two spectral absorption maxima were shifted to higher wavelength in the spectra of the chelates confirming the participation of the metal cation19. Table-1 Physical, analytical and IR spectral data of the metal complexes of synthetic curcuminoids Compound/ molecular formula Yield (%) M.P. C) Elemental analysis: found (calculated)%IR stretching bands (cm-1) C H M C=O CH=CH transM–O [Cd(L 3 )2] C 30 H 22 CdO 8 39 172 57.29 (57.84) 3.49 (3.53) 18.57 (18.06) 1582 s 974 m 472 m, 418 m [Cd(L 4 )2] C 54 H 38 CdO 4 42 164 75.00 (75.14) 4.41 (4.41) 13.00 (13.03) 1582 s 978 m 480 m, 424 m [Hg(L 3 )2] C 30 H 22 HgO 8 70 190 50.81 (50.66) 3.05 (3.10) 28.51 (28.23) 1578 s 976 m 476 m, 414 m [Hg(L 4 )2] C 54 H 38 HgO 4 78 136 67.88 (68.18) 4.01 (4.00) 21.61 (21.09) 1574 s 976 m 482 m, 420 m [Pb(L 3 )2] C 30 H 22 O 8 Pb 51 142 50.60 (50.19) 3.04 (3.07) 28.80 (28.89) 1576 s 968 m 474 m, 420 m [Pb(L 4 )2] C 54 H 38 O 4 Pb 56 192 67.69 (67.70) 3.79 (3.77) 21.83 (21.65) 1584 s 980 m 462 m, 418 m Table-2 Research Journal of Chemical Sciences ___________________________________________________________ ISSN 2231-606XVol. 5(6), 40-45, June (2015) Res. J. Chem. Sci. International Science Congress Association 42 H NMR and mass spectral data of the Cd(II) complexes of synthetic curcuminoids Compound 1 H NMR ( d , ppm) Mass spectral data (m/z) Methine CH=CH Aryl [Cd(L 3 ) 2 ] 6.38 8.12, 8.28 7.18-7.90 622, 501, 417, 380, 205, 121, 93 [Cd(L 4 ) 2 ] 6.40 8.25, 8.36 7.22-8.12 862, 681, 500, 487, 375, 181, 153 Antioxidant studies: The antioxidant activity of the phenyl, styryl, 2-furyl and 2-naphthyl curcumins are presented in figure-2. The results clearly indicated that all the ligands possess significant antioxidant activity. Maximum activity was observed in the case of 2-naphthyl curcumin.Metal complexation enhanced the antioxidant activity of all the compounds. The antioxidant activity of the Cd(II), Pb(II) and Hg(II) complexes are shown in figures 3 to 6. In metal complexes the Hg(II) complexes showed highest activity. Figure-2 Antioxidant assay of synthetic curcuminoids 1a = Phenyl curcumin (HL); 1b = Styryl curcumin (HL); 1c = 2-Furyl curcumin (HL); 1d = 2-Naphthyl curcumin (HL) Figure-3 Antioxidant assay of the metal complexes of phenyl curcumin Research Journal of Chemical Sciences ___________________________________________________________ ISSN 2231-606XVol. 5(6), 40-45, June (2015) Res. J. Chem. Sci. International Science Congress Association 43 Figure-4 Antioxidant assay of the metal complexes of styryl curcumin Figure-5 Antioxidant assay of the metal complexes of 2-furyl curcumin Figure-6 Antioxidant assay of the metal complexes of 2-naphthyl curcumin Research Journal of Chemical Sciences ___________________________________________________________ ISSN 2231-606XVol. 5(6), 40-45, June (2015) Res. J. Chem. Sci. International Science Congress Association 44 Conclusion Structural analogues of natural curcuminoids and their Cd(II), Hg(II) and Pb(II) complexes were synthesized and characterized using various physico-chemical and spectral techniques. These metal complexes of [ML] stoichiometry showed enhanced antioxidant activities compared to the free curcuminoids.Acknowledgement The authors are thankful to University Grants Commission, New Delhi, India for financial assistance. References 1.Uttara B., Singh A.V., Zamboni P. and Mahajan R.T., Oxidative Stress and Neurodegenerative Diseases: A Review of Upstream and Downstream Antioxidant Therapeutic Options, Curr. Neuropharmacol.,7(1), 65–74 (2009)2.Lobo V., Patil A., Phatak A. and Chandra N., Free radicals, Antioxidants and Functional Foods: Impact on Human Health, Pharmacogn. Rev.,4(8), 118–126 (2010)3.Sharma P., Jha A.B., Dubey R.S. and Pessarakli M., Reactive Oxygen Species, Oxidative Damage, and Antioxidative Defense Mechanism in Plants under Stressful Conditions, J. Bot., Article ID 217037, 26 pages (2012)4.Komethi M., Othman N, Ismail H. and Sasidharan S., Comparative Study on Natural Antioxidant as an Aging Retardant for Natural Rubber Vulcanizates, J. Appl. Polymer Sci.,124(2), 1490–1500 (2012)5. Shah R., Haidasz E.A., Valgimigli L. and Pratt D.A., Unprecedented Inhibition of Hydrocarbon Autoxidation by Diarylamine Radical-Trapping Antioxidants, J. Am. Chem. Soc., 137 (7), 2440–2443 (2015)6.6. Chan W.H., Lam K.S. and Yu W.K., Antioxidants in Plastic: An instrumental analysis project, J. Chem. Educ.,66(2), 172 (1989)7.Finley J.W., Kong A., Hintze K.J., Jeffery E.H., Ji L.L. and Lei X.G., Antioxidants in Foods: State of the Science Important to the Food Industry, J. Agric. Food Chem., 59 (13), 6837–6846 (2011) 8.Race S., Antioxidants, The Truth about BHA, BHT, TBHQ and Other Antioxidants Used as Food Additives, Tigmor Books (2009) 9.The Alpha-Tocopherol Beta Carotene Cancer Prevention Study Group, The Effect ofVitamin E and Beta Carotene on the Incidence of Lung Cancer and Other Cancers in Male Smokers, New England J. Med.,330 (15), 1029–1035 (1994)10.Rahman K., Studies on Free radicals, Antioxidants, and Co-factors, Clin. Interv. Aging,2(2), 219–236 (2007)11.Li P., Huo L., Su W., Lu R., Deng C., Liu L., Deng Y., Guo N., Lu C. and He C., Free Radical Scavenging Capacity, Antioxidant Activity and Phenolic Content of Pouzolzia zeylanica, J. Serb. Chem. Soc.,76 (5), 709–717 (2011)12.Jayaprakash G.K., Rao L.J. and Sakariah K.K., Antioxidant Activities of Curcumin, Demethoxycurcumin and Bis(demethoxy)curcumin, Food Chem.,98, 720–724 (2006)13.Nagpal M. and Sood S., Role of Curcumin in Systemic and Oral Health: An Overview, J. Nat. Sci. Biol. Med., 4(1), 3–7 (2013)14.Asouri M., Ataee R., Ahmadi A.A., Amini A.H. and Moshaei M.R., Antioxidant and Free Radical Scavenging Activities of Curcumin, Asian J. Chem., 25(13), 7593–7595 (2013)15.Borra S.K., Gurumurthy P., Mahendra J., Jayamathi K.M., Cherian C.N. and Chand R., Antioxidant and Free Radical Scavenging Activity of Curcumin Determined by Using Different in vitro and ex vivo Models, J. Med. Plants Res., 7(36), 2680–2690, (2013)16.Kalpana C. and Menon V.P., Protective Effect of Curcumin on Circulatory Lipid Peroxidation and Antioxidant Status during Nicotine-induced Toxicity, Toxicol. Mech. Methods,14(6)339–43 (2004) 17.Sreejayan and Rao M.N.A. Curcuminoids as Potent Inhibitors of Lipid Peroxidation, J. Pharm. Pharmacol., 46, 1013–16 (1994)18.Pallikkavil R., Ummathur M.B. and Krishnankutty K., Synthesis, Characterization and Fluorescence Study of Phthalhydrazidylazo Derivative of an Unsaturated Diketone and its Metal Complexes, Turk. J. Chem.,37(6), 889–895 (2013) 19.Pallikkavil R., Ummathur M.B., Sreedharan S. and Krishnankutty K., Synthesis, Characterization and Antimicrobial Studies of Cd(II), Hg(II), Pb(II), Sn(II) and Ca(II) Complexes of Curcumin, Main Group Met. Chem.,36(3-4), 123–127 (2013) 20.John V.D., Ummathur M.B. and Krishnankutty K., Synthesis, Characterization and Antitumour Studies of Some Synthetic Curcuminoid Analogues and Their Aluminium Complexes, J. Coord. Chem., 66(9), 1508–1518 (2013) 21.Pallikkavil R., Ummathur M.B. and Krishnankutty K., Cd(II), Hg(II) and Pb(II) Complexes of Some Synthetic Curcuminoid Analogues, Sci. Revs. Chem. Commun.,3(1), 75–80 (2013) 22.Krishnankutty K. and Venugopalan P., Metal Chelates of Curcuminoids, Synth. React. Inorg. Met.-Org. Chem., 28(8), 1313–1325 (1998) Research Journal of Chemical Sciences ___________________________________________________________ ISSN 2231-606XVol. 5(6), 40-45, June (2015) Res. J. Chem. Sci. International Science Congress Association 45 23.John V.D., Kuttan G. and Krishnankutty K., Anti-tumour Studies of Metal Chelates of Synthetic Curcuminoids, J.Exp. Clin. Cancer Res., 21(2), 219–224 (2002) 24.John V.D.and Krishnankutty K., Antitumour Activity of Synthetic Curcuminoid Analogues (1,7-Diaryl-1,6-heptadiene-3,5-diones) and Their Copper Complexes, Appl. Organomet. Chem.,20(8), 477–482 (2006) 25.Rezaeizadeh A., Zuki A., Abdollahi M., Goh Y.M., Noordin M.M., Hamid M. and Azmi T.I, Determination of antioxidant activity in Methanolic and Chloroformic Extracts of Momordica charantia, African J. Biotech.,10(24), 4932–4940 (2011) 26.Nakamoto K., Infrared Spectra of Inorganic and Coordination Compounds, Wiley, New York (1970) 27.Sabah M.M., Synthesis and Characterization of Co+2, Ni+2, Cu+2, Zn+2 and Hg+2 Complexes with 1,1,2,2-tetrakis (Sodium Thioproponate) ethylene, Res. J. Chem. Sci.,3(7), 9-14 (2013)