Articles producció científica> Química Física i Inorgànica

Peptide Hydrolysis by Metal (Oxa)cyclen Complexes: Revisiting the Mechanism and Assessing Ligand Effects

  • Identification data

    Identifier: imarina:9156782
    Authors:
    Norjmaa GSolé-Daura ABesora MRicart JMCarbó JJ
    Abstract:
    © 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.
  • Others:

    Author, as appears in the article.: Norjmaa G; Solé-Daura A; Besora M; Ricart JM; Carbó JJ
    Department: Química Física i Inorgànica
    URV's Author/s: Besora Bonet, Maria / Carbó Martin, Jorge Juan / Ricart Pla, Jose Manuel
    Keywords: Soluble oligomers Proteolytic activity Polarization functions Molecular-orbital methods Ins-1 cells Co(iii) complex Cleavage agents Basis-sets Artificial metalloprotease Alzheimers-disease
    Abstract: © 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.
    Thematic Areas: 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
    Author's mail: maria.besora@urv.cat j.carbo@urv.cat josep.ricart@urv.cat
    Author identifier: 0000-0002-6656-5827 0000-0002-3945-6721 0000-0002-2610-5535
    Record's date: 2024-07-27
    Papper version: info:eu-repo/semantics/acceptedVersion
    Link to the original source: https://pubs.acs.org/doi/10.1021/acs.inorgchem.0c02859
    Licence document URL: https://repositori.urv.cat/ca/proteccio-de-dades/
    Papper original source: Inorganic Chemistry. 60 (2): 808-816
    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
    Article's DOI: 10.1021/acs.inorgchem.0c02859
    Entity: Universitat Rovira i Virgili
    Journal publication year: 2021
    Publication Type: Journal Publications
  • Keywords:

    Chemistry (Miscellaneous),Chemistry, Inorganic & Nuclear,Inorganic Chemistry,Physical and Theoretical Chemistry
    Soluble oligomers
    Proteolytic activity
    Polarization functions
    Molecular-orbital methods
    Ins-1 cells
    Co(iii) complex
    Cleavage agents
    Basis-sets
    Artificial metalloprotease
    Alzheimers-disease
    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
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