Autor según el artículo: Norjmaa G; Solé-Daura A; Besora M; Ricart JM; Carbó JJ
Departamento: Química Física i Inorgànica
Autor/es de la URV: Besora Bonet, Maria / Carbó Martin, Jorge Juan / Ricart Pla, Jose Manuel
Palabras clave: Soluble oligomers Proteolytic activity Polarization functions Molecular-orbital methods Ins-1 cells Co(iii) complex Cleavage agents Basis-sets Artificial metalloprotease Alzheimers-disease
Resumen: © 2021 American Chemical Society. The mechanism responsible for peptide bond hydrolysis by Co(III) and Cu(II) complexes with (oxa)cyclen ligands has been revisited by means of computational tools. We propose that the mechanism starts by substrate coordination and an outer-sphere attack on the amide C atom of a solvent water molecule assisted by the metal hydroxo moiety as a general base, which occurs through six-membered ring transition states. This new mechanism represents a more likely scenario than the previously proposed mechanisms that involved an inner-sphere nucleophilic attack through more strained four-membered rings transition states. The corresponding computed overall free-energy barrier of 25.2 kcal mol-1 for hydrolysis of the peptide bond in Phe - Ala by a cobalt(III) oxacyclen catalyst (1) is consistent with the experimental values obtained from rate constants. Also, we assessed the influence of the nature of the ligand throughout a systematic replacement of N by O atoms in the (oxa)cyclen ligand. Increasing the number of coordinating O atoms accelerates the reaction by increasing the Lewis acidity of the metal ion. On the other hand, the higher reactivity observed for the copper(II) oxacyclen catalyst with respect to the analogous Co(III) complex can be attributed to the larger Brönsted basicity of the copper(II) hydroxo ligand. Ultimately, the detailed understanding of the ligand and metal nature effects allowed us to identify the double role of the metal hydroxo complexes as Lewis acids and Brönsted bases and to rationalize the observed reactivity trends.
Áreas temáticas: Química Physical and theoretical chemistry Medicina i Materiais Interdisciplinar Inorganic chemistry General medicine Farmacia Engenharias iii Engenharias ii Engenharias i Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências agrárias i Chemistry, inorganic & nuclear Chemistry (miscellaneous) Biotecnología Astronomia / física
Direcció de correo del autor: maria.besora@urv.cat josep.ricart@urv.cat j.carbo@urv.cat
Identificador del autor: 0000-0002-6656-5827 0000-0002-2610-5535 0000-0002-3945-6721
Fecha de alta del registro: 2023-03-05
Versión del articulo depositado: info:eu-repo/semantics/acceptedVersion
Enlace a la fuente original: https://pubs.acs.org/doi/10.1021/acs.inorgchem.0c02859
URL Documento de licencia: http://repositori.urv.cat/ca/proteccio-de-dades/
Referencia al articulo segun fuente origial: Inorganic Chemistry. 60 (2): 808-816
Referencia de l'ítem segons les normes APA: Norjmaa G; Solé-Daura A; Besora M; Ricart JM; Carbó JJ (2021). Peptide Hydrolysis by Metal (Oxa)cyclen Complexes: Revisiting the Mechanism and Assessing Ligand Effects. Inorganic Chemistry, 60(2), 808-816. DOI: 10.1021/acs.inorgchem.0c02859
DOI del artículo: 10.1021/acs.inorgchem.0c02859
Entidad: Universitat Rovira i Virgili
Año de publicación de la revista: 2021
Tipo de publicación: Journal Publications
Repositori URV