Biological and protein-binding studies of newly synthesized polymer–cobalt(III) complexes G. Vignesh, a I. Pradeep, a S. Arunachalam, a * S. Vignesh, b R. Arthur James, b R. Arun c and K. Premkumar c ABSTRACT: The polymer–cobalt(III) complexes, [Co(bpy)(dien)BPEI]Cl 3 · 4H 2 O (bpy = 2,2′-bipyridine, dien = diethylentriamine, BPEI = branched polyethyleneimine) were synthesized and characterized. The interaction of these complexes with human serum albumin (HSA) and bovine serum albumin (BSA) was investigated under physiological conditions using various physico-chemical techniques. The results reveal that the fluorescence quenching of serum albumins by polymer–cobalt(III) complexes took place through static quenching. The binding of these complexes changed the molecular conformation of the protein considerably. The polymer–cobalt(III) complex with x = 0.365 shows antimicrobial activity against several human pathogens. This complex also induces cytotoxicity against MCF-7 through apoptotic induction. However, further studies are needed to decipher the molecular mode of action of polymer–cobalt(III) complex and for its possible utilization in anticancer therapy. Copyright © 2015 John Wiley & Sons, Ltd. Additional supporting information may be found in the online version of this article at the publisher’s web site. Keywords: polymer–cobalt(III) complexes; protein binding; static quenching; cytotoxicity; antimicrobial activity Introduction Serum albumins are the major soluble protein constituents of the circulatory system and have many physiological functions, includ- ing acting as transporters for numerous endogenous and exoge- nous ligands (1). The ability of the serum albumins to interact with a wide variety of molecules, has led to exploitation of their favorable properties for the development of novel therapeutics and drug delivery, pharmacokinetics and pharmacodynamics modulation (2,3). The primary structure of these transport proteins has ~ 580 amino acid residues and is characterized by a low trypto- phan content along with a high cysteine content, stabilizing a series of nine loops. The secondary structure of serum albumins has 67% helix of six turns and 17 disulfide bridges (4–13). The ter- tiary structure is composed of three domains, I, II and III, and each domain can be subdivided into two subdomains, A and B. Bovine and human serum albumins (BSA and HSA) display ~ 80% sequence homology and a repeating pattern of disulfides. HSA has a sole tryptophan residue located in subdomain IIA (Trp214) and BSA has two tryptophan residues located in subdomain IB (Trp134) and subdomain IIA (Trp212) (6). Metal complexes that bind with serum albumins under physiological conditions are of current interest for various applications. In fact, metal–protein interactions may have key roles in the biodistribution, mode of action and toxic effects of antitumor metal complexes. Moreover, this subject has gained importance because of the paradigm that DNA is a primary target for antitumor metallodrugs. However, this is rapidly declining, and seems to be no longer valid, at least for some families of non-platinum anticancer metal complexes. Prom- ising developments are emerging with regard to cobalt-based pharmaceuticals. The potential applications of cobalt complexes in medicine to target tumors through bio-reductive activation, has been examined over recent years. Recent drug design research in this connection has focused on the use of the +2 and +3 oxida- tion states of cobalt. In the past few years, there has been great deal of research aimed at improving drug delivery by the use of macromolecule- based drug carriers such as dendrimers, micelles, liposomes and polymers (14–16). Drug–polymer conjugates are potential candi- dates for the selective delivery of anticancer agents to tumor tissues. Among the various polymers, polyethyleneimine (PEI) has appeared as a possible alternative to viral and liposomal routes of gene delivery. PEI exists in linear and branched forms, but for most purposes, branched polyethyleneimine (BPEI) is used due to its greater stability in aqueous solution and it is a promising candidate as a non-viral vector for plasmid and oligonucleotide delivery both in vitro and in vivo (17–21). In addition, the chemistry of polymer–metal complexes in general has been of great interest because these complexes act as excellent models for metalloenzymes (22). We have recently reported the interaction of many polymer–cobalt(III) complexes with DNA. These polymer–cobalt(III) complexes have been shown to have con- siderable antimicrobial and anticancer activity (23,24). The polymer–metal complexes in the studies by Senthil Kumar and * Correspondence to: S. Arunachalam, School of Chemistry, Bharathidasan University, Tiruchirappalli-620 024, Tamil Nadu, India. Tel.: +91-431-240-7053. E-mail: arunasurf@yahoo.com a School of Chemistry, Bharathidasan University, Tiruchirappalli-620 024, Tamil Nadu, India b Department of Marine Science, Bharathidasan University, Tiruchirappalli-620 024, Tamil Nadu, India c Department of Biomedical Science, Bharathidasan University, Tiruchirappalli- 620 024, Tamil Nadu, India Luminescence 2016; 31: 533–543 Copyright © 2015 John Wiley & Sons, Ltd. Research article Received: 11 March 2015, Revised: 2 July 2015, Accepted: 4 July 2015 Published online in Wiley Online Library: 17 August 2015 (wileyonlinelibrary.com) DOI 10.1002/bio.2992 533