Introduction: Schiff base ligands are easily synthesized and readily form complexes with a wide range of metal ions. They are favored due to their straightforward preparation, synthetic flexibility, and the distinctive properties of the C=N (azomethine) group. Schiff bases are generally excellent chelating agents, particularly when hydroxyl (–OH) or thiol (–SH) groups are positioned close to the azomethine group, allowing the formation of stable five- or six-membered rings with metal ions. These ligands exhibit diverse biological activities, including antibacterial, antifungal, anticancer, and catalytic properties. Metal complexes of Schiff bases have been extensively studied for their herbicidal activity and serve as models for biologically important species. The imine (-N=CH-) functionality is crucial for elucidating mechanisms such as transamination and racemization in biological systems.
2. Biological Importance of Schiff Base Complexes
The applications of Schiff bases and their metal complexes in biological systems can be summarized as follows:
2.1 Antibacterial Activity
Schiff base complexes of Mn(II), Fe(III), Co(II), Ni(II), Cu(II), and Zn(II), incorporating salicylaldehyde and ethylenediamine, have been screened for antibacterial activity. All compounds exhibited significant activity against E. coli, S. typhimurium, S. aureus, and K. aerogene. Among them, the Cu(II) complex showed the highest activity against S. aureus and K. aerogene, with zones of inhibition measuring 18 mm and 16 mm, respectively. Generally, metal complexes displayed higher antibacterial activity than the free ligands.
Other studies demonstrated that Mn(II) complexes with hydrazine carboxamide or hydrazine carbothiamide ligands were active against S. aureus and Xanthomonas campestris. Schiff base complexes derived from 2,6-diacetylpyridine and 2-pyridinecarboxaldehyde with 4-amino-2,3-dimethyl-1-phenyl-3-pyrazolin-5-one showed antibacterial activity against S. aureus, Klebsiella pneumoniae, Mycobacterium smegmatis, and Pseudomonas aeruginosa. In these studies, metal complexes generally exhibited stronger antibacterial effects than their corresponding free ligands. Fe(III), Co(II), and Ni(II) complexes of Schiff bases derived from 2-thiophene carboxaldehyde and 2-aminobenzoic acid demonstrated activity against P. aeruginosa, E. coli, and Staphylococcus pyogenes. Additionally, Fe(III), Cu(II), and Zn(II) complexes showed significant inhibition of E. coli, highlighting their potential for therapeutic applications. Tridentate Schiff base ligands derived from S-benzyldithiocarbazate and salicylaldehyde, along with their transition metal complexes, also showed notable bioactivity against P. aeruginosa (Gram-negative) and Bacillus aerus (Gram-positive).
2.2 Antifungal Activity
Cu(II), Ni(II), and Co(II) complexes of Schiff bases derived from 3-(2-hydroxy-3-ethoxybenzylideneamino)-5-methylisoxazole and 3-(2-hydroxy-5-nitrobenzylideneamino)-5-methylisoxazole were tested against Aspergillus niger and Rhizoctonia solani. Both the ligands and their metal complexes inhibited fungal growth, with activity increasing upon coordination. Thiazole and benzothiazole Schiff bases demonstrated effective antifungal activity, which was enhanced by methoxy, halogen, or naphthyl substituents. Pyrandione Schiff bases exhibited physiological activity against A. niger, while quinazolinone-derived Schiff bases were active against Candida albicans, Trichophyton rubrum, T. mentagrophytes, A. niger, and Microsporum gypseum. Semicarbazone and thiosemicarbazone Ni(II) complexes showed moderate antifungal activity against 11 pathogenic fungi, although less than the standard fungicide nystatin. Co(II), Ni(II), and Cu(II) complexes with 3,3-thiodipropionic acid bis(4-amino-5-ethylimino-2,3-dimethyl-1-phenyl-3-pyrazoline) exhibited enhanced activity compared to the free ligands against Alternaria brassicae, A. niger, and Fusarium oxysporum.
2.3 Catalytic Activity
Schiff base metal complexes also exhibit high catalytic activity, improving reaction yield and selectivity. Their catalytic efficiency depends on ligand type, coordination sites, and the metal ion. Aromatic Schiff bases and their metal complexes catalyze reactions including oxygenation, hydrolysis, electroreduction, and decomposition. Certain copper complexes derived from amino acids enhance hydrolysis rates 10–50 times compared to simple Cu(II) ions. Synthetic Fe(II) Schiff base complexes are effective catalysts for oxygen electroreduction. Co(II) and Cu(II) complexes derived from hydroxyl-substituted benzaldehydes catalyze the oxidation of cyclohexane to cyclohexanol and cyclohexanone in the presence of hydrogen peroxide. Binuclear complexes of Fe(II), Co(II), Ni(II), and Zn(II) with neutral bis(iminopyridyl)benzene and monoanionic bis(iminopyridyl)phenolate Schiff bases serve as catalysts for ethylene oligomerization.
2.4 Miscellaneous Applications
Some Schiff bases exhibit nonlinear optical properties, such as second harmonic generation. Amido-Schiff bases chelate with Cu(II) and Fe(II), acting as thrombin inhibitors. Carnosine and anserine serve as trans-glycating agents in the decomposition of aldose-derived Schiff bases. Transition metal complexes with 1,10-phenanthroline or 2,2′-bipyridine are utilized in petroleum refining. Copper plays a vital role in liver function and blood/urine levels, affecting diseases such as nephritis, hepatitis, leprosy, anemia, and leukemia. Zn(II) complexes with benzothiazoles are luminescent, while amino acid Schiff base complexes derived from 2-hydroxy-1-naphthaldehyde are used as radiotracers in nuclear medicine.
3. Conclusion
Schiff bases represent an important class of organic compounds, notable for their ability to form stable metal complexes and their versatile applications across multiple fields. Schiff base transition metal complexes have attracted significant interest due to their diverse biological activities and potential in designing new therapeutic agents. Despite extensive research, further studies are needed to explore existing Schiff base metal complexes in greater depth and to synthesize new complexes with enhanced properties and applications.
REFERENCES:
[1] M. Valcarcel and M. D. Laque de Castro, “Flow-Throgh Biochemical Sensors”, Elsevier,1994, Amsterdam.
[2] U. Spichiger-Keller, “Chemical Sesors and Biosensors for Medical and BiologicalApplications”, Wiley-VCH, 1998, Weinheim.
[3] J. F. Lawrence and R. W. Frei, “Chemical Derivatization in Chromatography”, Elsevier,1976, Amsterdam.
[4] S. Patai, Ed., “The Chemistry of the Carbon-Nitrogen Double Bond”, J. Wiley & Sons,1970, London.
[5] E. Jungreis and S. Thabet S, “Analytical Applications of Schiff bases”, Marcell Dekker,1969, New York.
[6] Metzler C M, Cahill A and Metzler D E, J. Am. Chem. Soc., 1980, 102, 6075.
[7] G. O. Dudek and E. P. Dudek, Chem. Commun., 1965. 464.
[8] Z. Cimerman, S. Miljanic and N. Galic, Croatica Chemica Acta, 2000, 73 (1), 81- 95.
[9] D.R. Williams, Chem. Rev., 72, 203 (1972).
[10] A. Campos, J.R. Anacona and M.M. Campos-Vallette, Mian group Metal chem., 22, 283
(1999). [11] N. Sari, S. Arslan, E. Logoglu and I. Sakiyan, G.U.J. Sci, 16, 283 (2003).
[12] M. Verma, S.N. Pandeya, K N. Singh, J P. Stabler and Acta Pharm., 54, 49 (2004).
[13] P.G. Cozzi, Chem. Soc. Rev., 410 (2004).
[14] S. Chandra, J. Sangeetika, J. Indian Chem. Soc, 81, 203 (2004).
[15] K.Y. Lau, A. Mayr, K.K. Cheung, Inorg. Chem. Acta, 285, 223 (1999).
[16] A.S, Shawali, N.M.S. Harb and K.O. Badahdah, J. Heterocylic Chem., 22, 1397(1985).
[17] K. B. Patel and K. S. Nimavat, Der Chemica Sinica, 2012, 3(3), 677-682.
[18] S. A. S. Alazawi and A. A. S. Alhamadani , Um-Salama Science Journal, 2007, 4(1), 102-109
[19] R. K. Dubey, U. K. Dubey and C. M. Mishra, Indian Journal of Chemistry, 2008, 47A,1208-1212.
[20] M. B. Halli, V. B. Patil, R. B. Sumathi and K. Mallikarjun, Der Pharma Chemica, 2012, 4(6):2360-2367
[21] M. Usharani, E. Akila and R. Rajavel, Journal of Chemical and Pharmaceutical Research,2012, 4(1):726-731
[22] Singh R, Gupta N & Fahmi N, Biochemical aspects of dioxomolybdenum(VI) and
manganese (II) complexes, Indian J Chem, 38 A (1999) 1150-1158.
[23] E.Ispir,S.Toroglu, A.Kayraldiz, Trasition Met. Chem 33 (2008) 953.
[24] Mohamed GG, Omar MM, HIndy AMm. Synthesis, characterisation and biological
activity of some transition metals with Schiff base derived from 2-thiophene carboxaldehyde
and aminobenzoic acid. Spectrochim Acta 2005;62A:1140-50
[25] Shaker AM, Nassr I.AE, Adam MSS. Mohamed IMA. Synthesis ,characterisation and
spectrophotometric studies of seven novel antibacterial hydrophilic iron (II) Schiff base
amino acid complexes. J Korean Chem Soc 2013;5:560
[26] M.T.H. Tarafder, M.A.Ali, D.J.Wee, K.Azahari, S.Silong and Karen A.Crouse, Transition
Metal Chemistry, 25 (2000) 456-460
[27] Raman N, Kulandaisamy A, Shanmugasundaram A, Jeyasubramanian K. Trans Met Chem
2001;26:131
[28] Dash B, Mahapatra P K, Panda D & Patnaik J M, Fungicidal activities of Schiff base
derived from p-hydroxybenzaldehydes and their derivatives, J Indian Chem Soc, 61 (1984)
1061-1064.
[29] Rao N R, Rao P V, Reddy G V & Ganorkar M C, Metal chelates of a physiologically active
O:N:S tridentate Schiff base, Indian J Chem, 26A (1987) 887-890.
[30] Mishra P, Gupta P N & Shakya A K,Synthessis of Schiff base of 3-amino-2-methyl-
quinazolin-4(3H)-ones and their antimicrobial activity, J Indian Chem Soc, 68 (1991) 539-541.
[31] Sulekh Chandra, L.K.Gupta, Spectrochimica Acta Part A 62 (2005) 1089-1094.
[32] Sulekh Chandra, Deepali Jain, A.K.Sharma, Pratibha Sharma. Molecules 14 (2009) 174.
[33] Gupta KC, Sutar AK. Catalytic activity of Schiff base metal complexes. Coord Chem Rev
2008;252:1420-50.
[34] Nishinaga A, Yamada T, Fujisawa H & Ishizaki K, Catalysis by cobalt Schiff complexes in
the oxygenation of alkenes on the mechanism of ketonization, J Mol Catal, 48 (1988) 249-
64, (1276); Chem Abstr, 111 (1989) 22902.
[35] Xi Z, Liu W, Cao G, Du W, Huang J, Cai K & Guo H, Catalytic oxidation of naphthol by
metalloporphyrins, Cuihau Xuebao, 7 (1986) 357-63; Chem Abstr, 106 (1987) 140082
[36] Chakraborty H, Paul N & Rahman M L, Catalytic activities of Schiff bases aquo
complexes of Cu(II) in the hydrolysis of aminoacid esters, Trans Met Chem (Lond), 19
(1994)524-526.
[37] Zhao Y D, Pang D W, Zong Z, Cheng J K, Luo Z F, Feng C J, Shen H Y& Zhung X C,
Electochemical studies of antitumor drugs, fundamental electrochemical characteristics of
an iron(III) Schiff base complex and its interaction with DNA, Huaxe Xuebao, 56 (1988)178-
183; Chem Abstr, 128 (1998) 252661.
[38] Sreekala R, Yusuff K K & Mohammed, Catalytic activity of mixed ligand five coordinate
Co (II) complexes of a polymer bound Schiff base, Catal (Pap Natl Symp), (1994) 507-510;
Chem Abstr, 130 (1999) 115551.
[39] M.Tumer, E.Akgun, S.Toroglu, A.Kayralidz, L.Donbak.J.Coord.Chem.61(2008) 2935.
[40] Yohan D.M.Champouret, John Fawcett, W.J.Nodes, K.Singh, G.A Solan.
Inorg.Chem45(2006) 9890.
[41] Chohan, Hussain Z, Pervez & Humayun, Biologically active complexes of Ni(II) , Cu(II)
and Zn(II) with tridentate NNO,NNS and NNN donor pyrazine derived ligands, Synth React
Inorg Met Org Chem, 23 (1993) 1061-1071.
[42] Malik Z A & Alam S, Antimicrobial screening and synthesis of aminoacid esters and their
Schiff bases from indan-1,2,3,-trione, J Pure Appl Sci, 17 (1984) 69-76.
[43] Cohan Z H, Praveen M & Ghaffar A, Strucural and biological behaviour of Co(II),Cu(II)
and Ni(II) aminoacid derived Schiff bases, Met-Based Drugs, 4 (1997) 267-272; Chem Abstr,
128 (1998) 112790.
[44] J.John, H.P. Alexander and J.S.Magret (1976), Chemistry with laboratory, Harcout Bruce,
Johanovich, pp 63.
[45] E.Popora and S.Berova.Bulgaris chemical abstract vol.84(1981) 184.
[46] Y.Hamada, T.Sano, M.Fujita, Y.Nishio, K.Shibata, Jpn.J.Appl.Phys.35 (1996) L1339.
[47] Z.H.Chohan, M.Parveen, A.Ghaffar, Synth.React.Inorg.Met.Org.Chem., 28(1998) 1673.