Nelaine Mora-Diez

The mechanism of the Baeyer–Villiger rearrangement: quantum chemistry and TST study supported by experimental kinetic data

The mechanism of the Baeyer-Villiger rearrangement is modelled for the reaction of propanone with trifluoroperacetic acid, catalyzed by trifluoroacetic acid in dichloromethane, using three DFT methods (B3LYP, BH&HLYP and MPWB1K) and MP2. These results are refined and used to calculate the overall reaction rate coefficient using conventional Transition State Theory. The excellent agreement between the calculated (1.00 x 10(-3) L mol(-1) s(-1)) and the experimental (1.8 x 10(-3) L mol(-1) s(-1)) rate coefficients at the MPWB1K level strongly supports the mechanism recently proposed by our group. This DFT method is then used to study the mechanism of a larger system: cyclohexanone + trifluoroperacetic acid, for which a very good agreement between the calculated and the experimental rate coefficients is also found (1.37 and 0.32 L mol(-1) s(-1), respectively). The modelled mechanism is not ionic but neutral, and consists of two concerted steps. The first one is strongly catalyzed while the second one, the migration step, seems not to be catalyzed for the systems under study. The results of this work could be of interest for understanding other reactions in non-polar solvents for which ionic mechanisms have been assumed.

Second-harmonic generation optical activity of a polypeptide α-helix at the air∕water interface

Quantitative measurements of second-harmonic generation optical activity (SHG-OA) have been performed for α-helical polypeptides poly-(γ-benzyl-L-glutamate) and poly-(γ-ethyl-L-glutamate) adsorbed at the air∕water interface, with the fundamental frequency ℏω=2.96eV (λ=417nm). The chiral component of the nonlinear susceptibility χXYZ(2) is small for both polymers, being comparable in magnitude with the susceptibility χXXZ(2) of the clean air∕water interface. The microscopic origin of the nonlinear response has been investigated by using semiempirical ZINDO∕S calculations in conjunction with standard time-dependent perturbation theory to evaluate the molecular hyperpolarizability tensor of a model α-helix composed of glycine residues. Calculated nonlinear susceptibilities (per monomer unit) are in good agreement with experimental measurements for both the chiral and achiral response. The computational results indicate that charge transfer transitions of the α-helix have a large influence on the achiral comp...

Thermodynamic Stability of Neutral and Anionic PFOS: A Gas-Phase, n-Octanol, and Water Theoretical Study

The thermodynamic stability of the 89 isomers of the eight-carbon-atom compound perfluorooctane sulfonate (PFOS) in their neutral and anionic forms has been studied in the gas phase, n-octanol, and water using density functional theory (B3LYP/6-311+G(d,p)). The gas-phase calculations are compared with previous semiempirical and partial ab initio studies; the calculations in water and n-octanol are reported for the first time. The results obtained indicate that the thermodynamic stability assessment of this family of persistent organic pollutants is independent of the environment and type of species (neutral or anionic) considered and that it is important to consider other PFOSs outside of the 83-89 set, which is the most frequently studied.

Acid-Catalyzed Nucleophilic Additions to Carbonyl Groups: Is the Accepted Mechanism the Rule or an Exception?

The transesterification reaction, and in particular the methanolysis of ethyl acetate with sulfuric acid as catalyst, is used as a model reaction to study the acid-catalyzed nucleophilic addition to a carbonyl group. Continuum solvation methods (SMD and IEF-PCM) and the MPWB1K functional are used. The reaction mechanism is studied in methanol and in acetonitrile as solvents. Our results indicate that the acid-catalyzed addition mechanism is stepwise, and the transition state (TS) is a contact ion-pair. The counteranion of the acid catalyst remains in the reaction site playing an important role in the TS of this reaction. Changes in the reaction kinetics and the ionic/nonionic nature of the TS with the ionizing ability of the solvent and the strength of the acid catalyst are explored. Additional calculations at the CBS-Q3 level of theory reinforce the conclusions of this paper. The results obtained allow the generalization of important ideas regarding the mechanism of the nucleophilic addition to carbonyl groups.

Amide-imide tautomerism of acetohydroxamic acid in aqueous solution: quantum calculation and SMD simulations

The kinetics and the thermodynamics of the amide-imide tautomerizations of acetohydroxamic acid in aqueous solution are studied from a theoretical point of view. Quantum electronic structure calculations (QCISD//MP2, MP2 and M06-2X, applying two continuum solvation methods) and steered molecular dynamic (SMD) simulations (with solute–solvent interaction potentials derived from AMBER van der Waals parameters and electrostatic charges in solution) are taken into account. The elementary and complex tautomerizations from the E-Amide and Z-Amide forms are studied with and without the explicit assistance of a water molecule. The Gibbs free energy of activation for the E-Amide ⇆ E-Imide and Z-Amide ⇆ Z-Imide processes are considerably reduced when these processes are assisted by one water molecule. The Gibbs free energy of reaction was also reduced, but to a lesser degree, for each of the processes considered when in the presence of an explicit solvent molecule. The Z-Amide ⇆ Z-Imide tautomerization, which occurs in two elementary steps, seems to be slightly more favoured from a thermodynamic point of view; however, the E-Amide ⇆ E-Imide tautomerization, which is an elementary process, is the most kinetically favoured. The SMD simulations led to results which are consistent with those obtained by the three electronic structure methods applied.

Interaction of brassinolide with essential amino acid residues: A theoretical approach

The interaction of the most active natural brassinosteroid, brassinolide, with the twenty natural amino acids is studied applying the multiple minima hypersurface method to model the molecular interactions explicitly. The resulting thermodynamic data gives useful information about the amino acids with the greatest association for brassinolide and the stabilities of such complexes. Density functional theory (DFT) optimizations were further carried out to test the performance of semiempirical calculations. Additional calculations with a more accurate DFT method were performed to explore the formation of this type of molecular complexes. The semiempirical geometries and stability order of these complexes are in good agreement with the DFT calculations. Each group of amino acids possesses a preferential zone of interaction with brassinolide, forming the polar-charged amino acids the most stable complexes. This study could contribute to future investigations of the interaction of brassinosteroids with the receptor protein in plants.

Theoretical study of deuterium isotope effects on acid–base equilibria under ambient and hydrothermal conditions

Quantum electronic structure methods are applied for the first time to the study of deuterium isotope effects (DIE) on pKa values under ambient (25 °C, 101.3 kPa) and hydrothermal (250 °C, 20.0 MPa) conditions. This work focuses on sixteen organic acids and explores several methodologies for calculating pKa values and various pKa differences in H2O and D2O under two sets of conditions. Two functionals are considered (B3LYP and BLYP) and solvent effects are accounted for by means of continuum solvation methods (PCM, CPCM, Onsager and SMD). Excellent agreement with experiment is obtained for the calculated DIE (ΔpKa = pKa(D2O) − pKa(H2O)) at the B3LYP-PCM/6-311++G(d,p) level of theory for the two sets of conditions. These values, which are almost constant for a given set of temperature and pressure conditions, are determined by the difference between the Gibbs free energies of formation of the acid and its deuterated form in each solvent. However, accurate predictions under ambient conditions can also be made from zero-point energy differences. The average calculated ΔpKa values under ambient (experimental average: 0.53) and hydrothermal conditions were 0.65 and 0.37, respectively. The mean absolute error between calculated and experimental ΔpKa values under ambient conditions was 0.11. The methodology applied is a very important tool for accurately predicting DIE on pKa values under both ambient and hydrothermal conditions, which can be used to make accurate pKa predictions in D2O.

Theoretical determination of aqueous acid–base pK values: electronic structure calculations and steered molecular dynamic simulations

The equilibrium constant (K) of several acid–base equilibria involving isomers of acetohydroxamic acid in aqueous solution is studied from a theoretical point of view applying electronic structure methods (at the M06-2X-SMD/6-311++G(d,p) and MP2-PCM/6-311++G(d,p) levels of theory) and steered molecular dynamic (SMD) simulations. The similarity of the results obtained indicates that SMD simulations can be successfully used to evaluate Gibbs energy changes in acid–base reactions in solution and pK values since these properties are in agreement with those found with quantum calculation and thermodynamic cycles. In the process of proton transfer from the imide isomers (the ZI and EI structures) toward the anion Z-amide, the deprotonation of the ZI(COH) molecule is the most favorable process kinetically and thermodynamically. It is observed that pK values are slightly higher for E-isomers and, particularly, for the deprotonation from the oxime group EI(NOH). Finally, we must emphasize the goodness of SMD simulations in solution to calculate this property as an alternative to using continuum solvation methods.

THEORETICAL STUDY OF THE REGIOSELECTIVITY OF THE ADDITION OF THE TRIPLET OXYGEN ATOM TO UNSYMMETRICAL SUBSTITUTED ALKENES

A theoretical study of the reactivity and regioselectivity of the addition of the triplet oxygen atom O(3P) to a series of unsymmetrical substituted alkenes has been performed at the PMP2/6-311++G (d,p) level of theory. Two reaction pathways, namely, the addition to the substituted carbon atom (α-site) and addition to the non-substituted carbon atom (β-site), have been studied. Our calculations show that the β-addition products are kinetically more favored; whereas the α-addition products are found to be thermodynamically more stable. The regioselectivity (α vs. β) of the addition of the O(3P) to the carbon–carbon double bond is predicted by means of the relative energies of the localized transition states and also by the calculation of spin densities of the 3ππ* states of reactants and Fukui indices corresponding to the radical attack to alkenes. Our calculations are in good agreement with experimental outcomes.

Modelling the chemical repair of protein carbon-centered radicals formed via oxidative damage with dihydrolipoic acid

The chemical repair of radical-damaged leucine residues by dihydrolipoic acid (DHLA) in solution has been studied using density functional theory. Because of the low electron affinity of carbon-centered radicals, hydrogen-atom transfer (HAT) reactions were the only ones studied. DHLA was found to repair the radical-damaged leucine residue by HAT from the thiol groups. The calculated rate constants are in the diffusion-controlled regime, which indicates that these reactions are fast enough to be considered a possible repair process for an initially damaged protein with a leucine lateral chain.