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Titolo:
Hydrolysis theory for cisplatin and its analogues based on density functional studies
Autore:
Zhang, Y; Guo, ZJ; You, XZ;
Indirizzi:
Nanjing Univ, Inst Coordinat Chem, State Key Lab Coordinat Chem, Nanjing 210093, Peoples R China Nanjing Univ Nanjing Peoples R China 210093 jing 210093, Peoples R China
Titolo Testata:
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
fascicolo: 38, volume: 123, anno: 2001,
pagine: 9378 - 9387
SICI:
0002-7863(20010926)123:38<9378:HTFCAI>2.0.ZU;2-7
Fonte:
ISI
Lingua:
ENG
Soggetto:
POLARIZABLE CONTINUUM MODEL; CHARGE-TRANSFER COMPLEXES; AB-INITIO; VIBRATIONAL FREQUENCIES; SUBSTITUTION-REACTIONS; ADJUSTABLE-PARAMETERS; GEOMETRY OPTIMIZATION; MOLECULAR-STRUCTURES; EXACT-EXCHANGE; HARTREE-FOCK;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Physical, Chemical & Earth Sciences
Citazioni:
72
Recensione:
Indirizzi per estratti:
Indirizzo: You, XZ Nanjing Univ, Inst Coordinat Chem, State Key Lab Coordinat Chem, Nanjing 210093, Peoples R China Nanjing Univ Nanjing Peoples R China 210093 093, Peoples R China
Citazione:
Y. Zhang et al., "Hydrolysis theory for cisplatin and its analogues based on density functional studies", J AM CHEM S, 123(38), 2001, pp. 9378-9387

Abstract

Hydrolysis of cisplatin, the most widely used anticancer drug in the world, is believed to be the key activation step before the drug reaching its intracellular target DNA. To obtain an accurate hydrolysis theory for this important class of square-planar Pt(II) complexes, three typical reactions, i.e., die first and second hydrolyses of cisplatin and the hydrolysis of [Pt(dien)Cl](+) (dien = diethylenetriamine), were studied at the experimental temperature with the solvent effect using mPW1PW91/SDD from a comprehensivemethodological study on the Hartree-Fock (HF) ab initio method, electron correlation methods, pure density functional theory (DFT) methods, and hybrid BF-DFT methods with several basis sets. The true five stationary states in the second-order nucleophilic substitution (S(N)2) pathway for the hydrolysis process, namely, reactant (R) --> intermediate 1 (I1) --> TS --> intermediate 2 (I2) --> product (P) were obtained and characterized theoretically for the first time. The most remarkable structural variations and the associated atomic charge variations in the hydrolysis process were found to occur in the equatorial plane of the five-coordinate trigonal-bipyramidal (TBP)-like structures of I1, TS, and I2. The reaction with the TS structure ofsmaller L-M-E angle and more lengthened M-L and M-E bonds was found to have a smaller Gibbs free energy change and accordingly the better hydrolysis yield. It is found that the sum of the three concentric angles in the TBP'sequator is near 360 degrees in I1 and I2 and is almost 360 degrees in TS in each reaction. The associated energy profiles again demonstrated a typical S(N)2 reaction curve. The computed forward and backward reaction enthalpy(DeltaH double dagger) and reaction entropy (DeltaS double dagger) in the rate-determining step I1 --> TS --> I2 are in good agreement with the experiments. Natural bonding orbital population analysis shows that the charge-separating extent follows the same order of DeltaG in studied reactions. Comparing with the computational results of gas-phase reactions, it can be concluded that the solvent effect should be considered to obtain an accurate hydrolysis picture. The most affected structural parameters after solvation are related to, the equatorial plane of the TBP-like geometry. The results provide theoretical guidance on detailed understanding on the mechanism of the hydrolysis of cisplatin, which could be useful in the design of novel Pt-based anticancer agents.

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Documento generato il 28/09/20 alle ore 14:31:29