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. © 2021 The Authors. Published by American Chemical Society.

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

Paciotti R.;Coletti C.;Re N.;Fornarini S.
2021-01-01

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. © 2021 The Authors. Published by American Chemical Society.
File in questo prodotto:
File Dimensione Formato  
jasms.1c00152.pdf

accesso aperto

Descrizione: Research Article
Tipologia: PDF editoriale
Dimensione 3.31 MB
Formato Adobe PDF
3.31 MB Adobe PDF Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11564/756007
Citazioni
  • ???jsp.display-item.citation.pmc??? 2
  • Scopus 7
  • ???jsp.display-item.citation.isi??? 6
social impact