DNA/HSA interaction and nuclease activity of an iron(III) amphiphilic sulfonated corrole Yang Zhang, a Jin-Yan Wen, a Mian HR Mahmood, a Xiang-Li Wang, a Biao-Biao Lv, b Xiao Ying, b Hui Wang, c Liang-Nian Ji c,d and Hai-Yang Liu a * ABSTRACT: The DNA binding of amphiphilic iron(III) 2,17-bis(sulfonato)-5,10,15-tris(pentafluorophenyl)corrole complex (Fe–SC) was studied using spectroscopic methods and viscosity measurements. Its nuclease-like activity was examined by using pBR322 DNA as a target. The interaction of Fe–SC with human serum albumin (HSA) in vitro was also examined using multispectroscopic techniques. Experimental results revealed that Fe–SC binds to ct-DNA via an outside binding mode with a binding constant of 1.25 × 10 4 M –1 . This iron corrole also displays good activity during oxidative DNA cleavage by hydrogen peroxide or tert-butyl hydroperoxide oxidants, and high-valent (oxo)iron(V,VI) corrole intermediates may play an important role in DNA cleavage. Fe–SC exhibits much stronger binding affinity to site II than site I of HSA, indicating a selective binding tendency to HSA site II. The HSA conformational change induced by Fe–SC was confirmed by UV/Vis and CD spectroscopy. Copyright © 2015 John Wiley & Sons, Ltd. Keywords: corrole; iron; DNA; nuclease activity; HSA Introduction Metal corrole complexes have received considerable interest because of their close similarity with metal porphyrins (1,2). Successful preparation of water-soluble corroles has promoted the application of corrole derivatives in bioinorganic chemistry (3–10). Because of the amphilicity and bipolarity of water-soluble sulfonated corroles, they may spontaneously form tightly bound conjugates with proteins, such as human serum albumin (HSA) and transferrin (11–13). Gallium and manganese complexes of sulfonated 2,17-bis(sulfonato)-5,10,15-tris(pentafluorophenyl)corrole (SC) are good candidates for cancer treatment and diagnosis (14–16). Fe–SC and Mn–SC were found to be good catalysts for the decomposition of reactive oxygen species (ROS) and reac- tive nitrogen species (RNS), and might even generate an efficient biomimetic asymmetric oxidation system on conjugation with albumin (13–15). Fe–SC is also a very efficient antioxidant and can efficiently control the development of atherosclerotic lesions (17). Moreover, highly fluorescent Ga–SC was shown to penetrate cell membranes easily and accumulate in the cytoplasm only. It may be used in the detection and elimination of tumors in live animals (16). Our previous work demonstrated that Mn–SC and Ga–SC bind with calf thymus DNA (ct-DNA) via outside binding and exhibit oxidative cleavage or photocleavage activity on pBR322 DNA (18,19). Metal complexes that can bind to and cleave DNA are poten- tial antitumor agents (20). Human serum albumin (HSA) is the major soluble protein in the human circulatory system, and can transport and dispose of various endogenous and exoge- nous compounds (21). The distribution, free concentration and metabolism of various drugs may be significantly altered by their binding to HSA, and binding will also decrease their toxicity and prevent them from oxidizing (22,23). The concentration of HSA in a tumor cell is much higher than in a normal cell, and HSA may serve as carrier of various anticancer drugs (24). In vitro investigations into HSA binding with drugs may provide insight into the pharmacokinetics of the reaction (25,26). To date, only a few reports about the binding behavior of corrole with HSA are available (11,13,27,28). In connection with our previous work on the nuclease activity of metal corrole (10,18,19,29,30), we here report the DNA-binding, HSA interaction and nuclease-like activity of an iron-sulfonated corrole Fe–SC (Fig. 1). Experimental Materials and instrumentation All reagents were purchased from commercial sources and used without further purification. Sodium salt of calf thymus (ct-DNA) and HSA were obtained from Sigma-Aldrich (Shanghai, China); agarose, tris-base, NACl, EDTA, boric acid and ethidium bromide (EB) were purchased from Shanghai Sangon Company (Shanghai, China), pBR322 plasmid DNA was from Dalian Takara Company (Dalian, China). Tris/HCl buffer solution was prepared using deionized water. * Correspondence to: Hai-Yang Liu, Department of Chemistry, South China University of Technology, Guangzhou 510640, China. E-mail: chhyliu@scut.edu.cn a Department of Chemistry, South China University of Technology, Guangzhou 510640, China b Department of Applied Phsics, South China University of Technology, Guangzhou 510640, China c State Key Laboratory of Optoelectronics Materials and Technologies, Sun-Yat Sen University, Guangzhou 510275, China d MOE Laboratory of Bioinorganic and Synthetic Chemistry, Sun-Yat Sen University, Guangzhou 510275, China Luminescence 2015 Copyright © 2015 John Wiley & Sons, Ltd. Research article Received: 05 September 2014, Revised: 21 December 2014, Accepted: 29 December 2014 Published online in Wiley Online Library (wileyonlinelibrary.com) DOI 10.1002/bio.2857