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Binding of anticancer drug Ru(η6-C6H5(CH2)2OH)Cl2(DAPTA) to DNA purine bases and amino acid residues: a theoretical study

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Abstract

The hydrolyzed Ru(η6-C6H5(CH2)2OH)Cl2(DAPTA) (DAPTA = 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane) binding to guanine(G), adenine (A), cytosine(C), cysteine (Cys), and histidine (His) residues were explored using the B3LYP hybrid functional and IEF-PCM solvation models. The computed activation barriers for the reactions of diaqua complex were lower than those of chloroaqua complex except for binding to cytosine. For the chloroaqua complex, the activation free energy was lowest when binding to cytosine (10.5 kcal/mol). Whereas, the substitution reaction of diaqua complex binding to cysteine showed the lowest activation free energy with 10.1 kcal/mol, closely followed by histidine (15.8 kcal/mol), adenine (20.1 kcal/mol), cytosine (20.7 kcal/mol), and guanine (24.4 kcal/mol) by turns. It could be deduced that the completely hydrolyzed Ru(η6-C6H5(CH2)2OH)Cl2(DAPTA) compounds might preferentially bind to amino acids residues in vivo. In addition, to simulate the protein and DNA environment in vivo, a detailed investigation of the activation free energies for the substitution reactions in dependence of the dielectric constant ε (4, 24, and 78.39) was systematically performed as well. The calculated results demonstrated that the environmental effect had a little impact on these substitution reactions.

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Acknowledgments

This study was supported by the National Natural Science Foundation of China (Grant no. 20971056 and 21103072).

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  1. Department of Chemistry, Jinan University, Guangzhou, 510632, Guangdong, People’s Republic of China

    Qiulan Fu, Lixin Zhou & Juan Li

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  1. Qiulan Fu
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Correspondence to Lixin Zhou.

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Fu, Q., Zhou, L. & Li, J. Binding of anticancer drug Ru(η6-C6H5(CH2)2OH)Cl2(DAPTA) to DNA purine bases and amino acid residues: a theoretical study. Struct Chem 23, 1931–1940 (2012). https://doi.org/10.1007/s11224-012-0003-5

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