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Kinetics and structural aspects of the cisplatin interactions with guanine: A quantum mechanical description
Author(s) -
Costa Luiz Antônio S.,
Hambley Trevor W.,
Rocha Willian R.,
De Almeida Wagner B.,
Dos Santos Hélio F.
Publication year - 2006
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.20979
Subject(s) - guanine , chemistry , reaction rate constant , density functional theory , adduct , basis set , aqueous solution , ab initio , computational chemistry , hydrogen bond , transition state , transition state theory , reaction mechanism , molecule , kinetics , catalysis , organic chemistry , nucleotide , biochemistry , physics , quantum mechanics , gene
The interaction of cisplatin with guanine DNA bases has been investigated using ab initio Hartree–Fock (HF) and density functional levels of theory in gas phase and aqueous solution. The overall process was divided into three steps: the reaction of the monoaqua [Pt(NH 3 ) 2 Cl(H 2 O)] + species with guanine (G) (reaction 1), the hydrolysis process yielding the adduct [Pt(NH 3 ) 2 (G) (H 2 O)] 2+ (reaction 2) and the reaction with a second guanine leading to the product [Pt(NH 3 ) 2 (G) 2 ] 2+ (reaction 3). The functionals B3LYP, BHandH, and mPW1PW91 were used in the present study, to develop an understanding of the role of the distinct models. The geometries presented for the intermediate structures were obtained by IRC calculations from the transition state structure for each reaction. The structural analysis for the intermediates and transition states showed that hydrogen bonds with the guanine O6 atom play an important role in stabilizing these species. The geometries were not very sensitive to the level of theory applied with the HF level, giving a satisfactory overall performance. However, the energy barriers and the rate constants were found to be strongly dependent on the level of calculation and basis set, with the DFT calculations giving more accurate results. For reaction 1 the rate constant calculated in aqueous solution at PCM‐BHandH/6‐311G* ( k 1 = 7.55 × 10 −1 M −1 s −1 ) was in good agreement with the experiment (5.4 × 10 −1 M −1 s −1 ). The BHandH/6‐31G* calculated gas phase rate constants for reactions 2 and 3 were: k 2 = 0.9 × 10 −6 M −1 s −1 and k 3 = 2.99 × 10 −4 M −1 s −1 in fairly good accordance with the experimental findings for reaction 2 (1.0 × 10 −6 M −1 s −1 ) and reaction 3 (3.0 × 10 −4 M −1 s −1 ). © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006