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Binding of piano‐stool Ru(II) complexes to DNA; QM/MM study
Author(s) -
Futera Zdeněk,
Platts James A.,
Burda Jaroslav V.
Publication year - 2012
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.23045
Subject(s) - chemistry , oniom , molecule , exothermic reaction , guanine , ligand (biochemistry) , stereochemistry , benzene , reaction mechanism , ethylenediamine , computational chemistry , catalysis , organic chemistry , nucleotide , biochemistry , receptor , gene
Ru(II) “piano‐stool” complexes belong to group of biologically active metallocomplexes with promising anticancer activity. In this study, we investigate the reaction mechanism of [(η 6 ‐benzene)Ru(II)(en)(H 2 O)] 2+ (en = ethylenediamine) complex binding to DNA by hybrid QM/MM computational techniques. The reaction when the Ru(II) complex is coordinated on N7‐guanine from major groove is explored. Two reaction pathways, direct binding to N7 position and two‐step mechanism passing through O6 position, are considered. It was found that the reaction is exothermic and the direct binding process is preferred kinetically. In analogy to cisplatin, we also explored the possibility of intrastrand cross‐link formation where the Ru(II) complex makes a bridge between two adjacent guanines. Two different pathways were found, leading to a final structure with released benzene ligand. This process is exothermic; however, one pathway is blocked by relatively high initial activation barrier. Geometries, energies, and electronic properties analyzed by atoms in molecules and natural population analysis methods are discussed. © 2012 Wiley Periodicals, Inc.