Cisplatin interaction with cysteine and methionine in aqueous solution: computational DFT/PCM study.
Cisplatin interaction with cysteine and methionine in aqueous solution: computational DFT/PCM study.
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DOI：
10.1021/jp807645x
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发表时间：
2009-03
期刊：
影响因子：
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通讯作者：
T. Zimmermann;Z. Chval;J. Burda
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文献类型：
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作者：
T. Zimmermann;Z. Chval;J. Burda
在本文中，我们探讨了顺铂与含硫氨基酸的相互作用中的极化连续模型。两种顺铂水合络合物被认为是反应物（氯络合物，cis-[Pt（NH3）2Cl（H2O）]+;羟基络合物，cis-[Pt（NH3）2（OH）（H2O）]+）。我们考虑了以下反应机理：第一步，氨基酸取代水溶性配体;第二步，解离螯合物的形成。对于优化的配合物（在B3 LYP/6-31+G（d）/COSMO水平），采用B3 LYP/6-311++G（2df，2 pd）水平和两种适用于过渡金属配合物的PCM模型COSMO和UAKS/DPCM方法，计算了配合物的能量分布.结果表明，半胱氨酸硫键合的热力学偏好，其次是氨基氮，甲硫氨酸硫醚硫，羧基氧。在氯配合物中，甲硫氨酸稍倾向于Pt-N（Met）配位，但在羟基配合物中，它倾向于Pt-S（Met）配位。从键能得出类似的趋势：BE（Pt-S（Cys））= 80.8 kcal/mol和BE（Pt-N（Met））= 76 kcal/mol。根据实验观察，所发现的最稳定的结构是kappa 2（S，N）螯合物。在甲硫氨酸的情况下，同样的热力学稳定性预测也为kappa 2（N，O）螯合物。这与气相结果不同，其中发现kappa 2（S，N）甚至kappa 2（S，O）比kappa 2（N，O）络合物更稳定。
In this paper we explore cisplatin interactions with sulfur-containing amino acids in a polarizable continuum model. Two cisplatin hydrated complexes were considered as reactants (chloro complex, cis-[Pt(NH3)2Cl(H2O)]+; hydroxo complex, cis-[Pt(NH3)2(OH)(H2O)]+). We considered the following reaction mechanism: first step, substitution of the aqua ligand by amino acid; second step, dissociative chelate formation. For the optimized complex (at the B3LYP/6-31+G(d)/COSMO level), the energy profile was determined using the B3LYP/6-311++G(2df,2pd) level and two different PCM models-COSMO and UAKS/DPCM methods which were adapted for use on transition metal complexes. The results show thermodynamic preference for bonding by cysteine sulfur followed by the amino group nitrogen, methionine thioether sulfur, and carboxyl-group oxygen. Methionine slightly prefers the Pt-N(Met) coordination in the chloro complex, but in the hydroxo complex it prefers the Pt-S(Met) coordination. A similar trend follows from the bonding energies: BE(Pt-S(Cys)) = 80.8 kcal/mol and BE(Pt-N(Met)) = 76 kcal/mol. According to the experimental observations, the most stable structures found are kappa2(S,N) chelates. In the case of methionine, the same thermodynamic stability is predicted also for the kappa2(N,O) chelate. This differs from the gas-phase results, where kappa2(S,N) and even kappa2(S,O) were found to be more stable than kappa2(N,O) complex.