title: Reactivity of Imidazole Derivatives toward Phosphate Triester in DMSO/Water Mixtures: A Comprehensive Study on the Solvent Effect.
abstract: Many imidazole (IMZ) derivatives of pharmaceutical interest, which are potentially catalytic in dephosphorylation reactions, are soluble solely in mixtures of water and organic solvent. In order to understand these poorly explored reactions and properly compare them, a thorough study related to solvent effects for the analogous spontaneous reaction and with common IMZ derivatives is necessary, which is lacking in the literature. Herein, we report a quantitative solvent effect analysis in DMSO/water mixtures for (i) the hydrolysis reaction of diethyl 2,4-dinitrophenylphosphate (DEDNPP) and (ii) the nucleophilic reaction of IMZ and 1-methylimidazole (MEI) with DEDNPP. The solvent effect was fitted satisfactorily with multiple regression analysis, correlating the obtained second-order rate constants with solvent parameters such as acidity, basicity, and polarity/polarizability from Catalán's scale. The contribution of these parameters can be taken into account to elucidate the reactivity in these media. Interestingly, IMZ is more reactive than MEI in DMSO, compared to water alone, which is attributed to the availability of hydrogen-bond formation. Nuclear magnetic resonance spectroscopy ((1)H, (13)C, and (31)P), mass spectrometry, thermodynamic analysis, and density functional theory calculations were carried out to corroborate the proposed nucleophilic mechanism.
authors.affiliation: ‡Departamento de Química, Universidade Federal do Paraná (UFPR), CP 19081, Curitiba, PR, CEP 81531-990, Brazil.
authors.forename: Renan B
authors.initials: RB
authors.lastname: Campos
authors.affiliation: ‡Departamento de Química, Universidade Federal do Paraná (UFPR), CP 19081, Curitiba, PR, CEP 81531-990, Brazil.
authors.forename: Everton H
authors.initials: EH
authors.lastname: Santos
authors.affiliation: ‡Departamento de Química, Universidade Federal do Paraná (UFPR), CP 19081, Curitiba, PR, CEP 81531-990, Brazil.
authors.forename: Alfredo R M
authors.initials: AR
authors.lastname: Oliveira
authors.affiliation: ‡Departamento de Química, Universidade Federal do Paraná (UFPR), CP 19081, Curitiba, PR, CEP 81531-990, Brazil.
authors.forename: Fernanda Maria Marins
authors.initials: FM
authors.lastname: Ocampos
authors.affiliation: §Universidade Federal de Santa Catarina, Florianópolis, SC, 88040-900, Brazil.
authors.forename: Bruno S
authors.initials: BS
authors.lastname: Souza
authors.affiliation: ‡Departamento de Química, Universidade Federal do Paraná (UFPR), CP 19081, Curitiba, PR, CEP 81531-990, Brazil.
authors.forename: Andersson
authors.initials: A
authors.lastname: Barison
authors.affiliation: ‡Departamento de Química, Universidade Federal do Paraná (UFPR), CP 19081, Curitiba, PR, CEP 81531-990, Brazil.
authors.forename: Elisa S
authors.initials: ES
authors.lastname: Orth
mesh_terms: D019297:2,4-Dinitrophenol / Q000031:analogs & derivatives* / Q000737:chemistry; D002384:Catalysis; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D004952:Esters; D007093:Imidazoles / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D010755:Organophosphates / Q000737:chemistry*; D010710:Phosphates / Q000737:chemistry; D012997:Solvents / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D004952:Esters; D007093:Imidazoles; D010755:Organophosphates; D010710:Phosphates; D012997:Solvents; D014867:Water; C047468:2,4-dinitrophenylphosphate; D019297:2,4-Dinitrophenol; D004121:Dimethyl Sulfoxide