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From Preassociation to Chelation: A Survey of Cisplatin Interaction with Methionine at Molecular Level by IR Ion Spectroscopy and Computations.
Journal of the American Society for Mass Spectrometry ( IF 3.2 ) Pub Date : 2021-07-08 , DOI: 10.1021/jasms.1c00152
Roberto Paciotti 1 , Davide Corinti 2 , Philippe Maitre 3 , Cecilia Coletti 1 , Nazzareno Re 1 , Barbara Chiavarino 2 , Maria Elisa Crestoni 2 , Simonetta Fornarini 2
Affiliation  

Methionine (Met) plays an important role in the metabolism of cisplatin anticancer drug. Yet, methionine platination in aqueous solution presents a highly complex pattern of interconnected paths and intermediates. This study reports on the reaction of methionine with the active aqua form of cisplatin, cis-[PtCl(NH3)2(H2O)]+, isolating the encounter complex of the reactant pair, {cis-[PtCl(NH3)2(H2O)]+·Met}, by electrospray ionization. In the unsolvated state, charged intermediates are characterized for their structure and photofragmentation behavior by IR ion spectroscopy combined with quantum-chemical calculations, obtaining an outline of the cisplatin-methionine reaction at a molecular level. To summarize the major findings: (i) the {cis-[PtCl(NH3)2(H2O)]+·Met} encounter complex, lying on the reaction coordinate of the Eigen-Wilkins preassociation mechanism for ligand substitution, is delivered in the gas phase and characterized by IR ion spectroscopy; (ii) upon vibrational excitation, ligand exchange occurs within {cis-[PtCl(NH3)2(H2O)]+·Met}, releasing water and cis-[PtCl(NH3)2(Met)]+, along the calculated energy profile; (iii) activated cis-[PtCl(NH3)2(Met)]+ ions undergo NH3 departure, forming a chelate complex, [PtCl(NH3)(Met)]+, whose structure is congruent with overwhelming S-Met ligation as the primary coordination step. The latter process involving ammonia loss marks a difference with the prevailing chloride replacement in protic solvent, pointing to the effect of a low-polarity environment.

中文翻译:

从预结合到螯合:通过红外离子光谱和计算在分子水平上对顺铂与甲硫氨酸相互作用的调查。

蛋氨酸(Met)在顺铂抗癌药物的代谢中起重要作用。然而,水溶液中的甲硫氨酸铂化呈现出高度复杂的互连路径和中间体模式。本研究报告了蛋氨酸与顺铂的活性水相形式 cis-[PtCl(NH3)2(H2O)]+ 的反应,分离了反应物对的相遇复合物 {cis-[PtCl(NH3)2(H2O) )]+·Met},通过电喷雾电离。在非溶剂化状态下,带电中间体通过红外离子光谱结合量子化学计算表征其结构和光碎行为,在分子水平上获得顺铂-甲硫氨酸反应的轮廓。总结主要发现:(i) {cis-[PtCl(NH3)2(H2O)]+·Met}遇到复合物,(ii) 在振动激发时,配体交换发生在 {cis-[PtCl(NH3)2(H2O)]+·Met} 中,释放水和顺式-[PtCl(NH3)2(Met)]+,沿着计算的能量轮廓; (iii) 活化的 cis-[PtCl(NH3)2(Met)]+ 离子经历 NH3 离去,形成螯合物 [PtCl(NH3)(Met)]+,其结构与 S-Met 连接一致,作为主要协调步骤。后一个涉及氨损失的过程标志着质子溶剂中氯化物替代的差异,表明低极性环境的影响。(ii) 在振动激发时,配体交换发生在 {cis-[PtCl(NH3)2(H2O)]+·Met} 中,释放水和顺式-[PtCl(NH3)2(Met)]+,沿着计算的能量轮廓; (iii) 活化的 cis-[PtCl(NH3)2(Met)]+ 离子经历 NH3 离去,形成螯合物 [PtCl(NH3)(Met)]+,其结构与 S-Met 连接一致,作为主要协调步骤。后一个涉及氨损失的过程标志着质子溶剂中氯化物替代的差异,表明低极性环境的影响。其结构与作为主要协调步骤的压倒性 S-Met 连接一致。后一个涉及氨损失的过程标志着质子溶剂中氯化物替代的差异,表明低极性环境的影响。其结构与作为主要协调步骤的压倒性 S-Met 连接一致。后一个涉及氨损失的过程标志着质子溶剂中氯化物替代的差异,表明低极性环境的影响。
更新日期:2021-07-08
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