title: Multiple proton-transfer reactions in DNA base pairs by coordination of pt complex.
abstract: The possibility of multiple proton-transfer reactions in DNA base pairs because of coordination of cisplatin is theoretically elucidated by density functional theory (DFT) and by quantum mechanics/molecular mechanics (QM/MM) methods with an ONIOM method. From the energetics of two base pairs with the cisplatin, it is theoretically confirmed that the Pt complex is likely to bind in the order cis-(CG)-Pt-(GC), cis-(CG)-Pt-(AT), cis-(TA)-Pt-(AT), where G, C, A, and T are guanine, cytosine, adenine, and thymine, respectively, and the Pt atom bonds to the N7 site of G and A. This result supports the experimental evidence, where the structure cis-A-Pt-A is seldom observed at room temperature. The single proton-transfer reaction occurs in one of the two GC pairs. No simultaneous single proton-transfer reaction can occur in both base pairs. Two different single proton-transferred structures (cis-(CG*)(d)-Pt-(GC)(p) and cis-(CG)(d)-Pt-(G*C)(p), where the asterisk means a proton donor of G) are as stable as the original structures (CG)(d)-Pt-(GC)(p). The same tendency was observed with cis-(CG*)-Pt-(AT). In contrast to cisplatin, multiple single proton-transfer reactions occur in the system consisting of two base pairs with transplatin. The optimized structure agrees with the experimental data for Pt-G coordination except for the hydrogen-bonding length.
authors.affiliation: Department of Applied Chemistry, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Matsui
authors.forename: Yasuteru
authors.initials: Y
authors.lastname: Shigeta
authors.forename: Kimihiko
authors.initials: K
authors.lastname: Hirao
mesh_terms: D020029:Base Pairing; D002945:Cisplatin / Q000737:chemistry; D004247:DNA / Q000737:chemistry*; D008956:Models, Chemical; D009944:Organoplatinum Compounds / Q000737:chemistry*; D011522:Protons; D021281:Quantitative Structure-Activity Relationship; D011789:Quantum Theory
chemical_list: D009944:Organoplatinum Compounds; D011522:Protons; D004247:DNA; D002945:Cisplatin