From Preassociation to Chelation: A Survey of Cisplatin Interaction with Methionine at Molecular Level by IR Ion Spectroscopy and Computations.

ABSTRACT: 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.

SUBMITTER: Paciotti R 

PROVIDER: S-EPMC8397306 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature