title: Theoretical Proposal for the Whole Phosphate Diester Hydrolysis Mechanism Promoted by a Catalytic Promiscuous Dinuclear Copper(II) Complex.
abstract: The catalytic mechanism that involves the cleavage of the phosphate diester model BDNPP (bis(2,4-dinitrophenyl) phosphate) catalyzed through a dinuclear copper complex is investigated in the current study. The metal complex was originally designed to catalyze catechol oxidation, and it showed an interesting catalytic promiscuity case in biomimetic systems. The current study investigates two different reaction mechanisms through quantum mechanics calculations in the gas phase, and it also includes the solvent effect through PCM (polarizable continuum model) single-point calculations using water as solvent. Two mechanisms are presented in order to fully describe the phosphate diester hydrolysis. Mechanism 1 is of the S(N)2 type, which involves the direct attack of the μ-OH bridge between the two copper(II) ions toward the phosphorus center, whereas mechanism 2 is the process in which hydrolysis takes place through proton transfer between the oxygen atom in the bridging hydroxo ligand and the other oxygen atom in the phosphate model. Actually, the present theoretical study shows two possible reaction paths in mechanism 1. Its first reaction path (p1) involves a proton transfer that occurs immediately after the hydrolytic cleavage, so that the proton transfer is the rate-determining step, which is followed by the entry of two water molecules. Its second reaction path (p2) consists of the entry of two water molecules right after the hydrolytic cleavage, but with no proton transfer; thus, hydrolytic cleavage is the rate-limiting step. The most likely catalytic path occurs in mechanism 1, following the second reaction path (p2), since it involves the lowest free energy activation barrier (ΔG(⧧) = 23.7 kcal mol(-1), in aqueous solution). A kinetic analysis showed that the experimental k(obs) value of 1.7 × 10(-5) s(-1) agrees with the calculated value k1 = 2.6 × 10(-5) s(-1); the concerted mechanism is kinetically favorable. The KIE (kinetic isotope effect) analysis applied to the second reaction path (p2) in mechanism 1 was also taken into account to assess the changes that take place in TS1-i (transition state of mechanism 1) and to perfectly characterize the mechanism described herein.
authors.affiliation: NEQC (Núcleo de Estudos em Quı́mica Computacional), Departamento de Quı́mica, Instituto de Ciências Exatas (ICE), Universidade Federal de Juiz de Fora , Campus Universitário Martelos, 36036-900 Juiz de Fora, Minas Gerais, Brazil.
authors.forename: Lucas F
authors.initials: LF
authors.lastname: Esteves
authors.affiliation: Laboratório de Síntese Orgânica e Quı́mica de Coordenação Aplicada a Sistemas Biológicos (LABSO-BIO), Departamento de Quı́mica, Centro Técnico Científico (CTC), PUC-Rio , 22453-900 Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Nicolás A
authors.initials: NA
authors.lastname: Rey
authors.affiliation: NEQC (Núcleo de Estudos em Quı́mica Computacional), Departamento de Quı́mica, Instituto de Ciências Exatas (ICE), Universidade Federal de Juiz de Fora , Campus Universitário Martelos, 36036-900 Juiz de Fora, Minas Gerais, Brazil.
authors.forename: Hélio F
authors.initials: HF
authors.lastname: Dos Santos
authors.affiliation: NEQC (Núcleo de Estudos em Quı́mica Computacional), Departamento de Quı́mica, Instituto de Ciências Exatas (ICE), Universidade Federal de Juiz de Fora , Campus Universitário Martelos, 36036-900 Juiz de Fora, Minas Gerais, Brazil.
authors.forename: Luiz Antônio S
authors.initials: LA
authors.lastname: Costa