Navegando por Palavras-chave "Electronic structure calculations"

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    Estudo químico-computacional sobre o mecanismo de formação da ligação amídica catalisada por ZrCl4
    (Universidade Federal de São Paulo, 2016-12-13) Assad, Felipe Vieira Zauith [UNIFESP]; Sensato, Fabricio Ronil [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    The ZrCl4-catalyzed direct amide bond formation between non-activated carboxylic acids and amines has been theoretically investigated at DFT/B3LYP level of theory. In addition we have also characterized the uncatalyzed mechanism as well as the amide bond formation promoted by the use of carbodiimides. In particular, we have characterized two non-catalyzed mechanism (channels 1-2), six ZrCl4-catalyzed pathways (channels 3-8) and two process promoted by carbodiimides. Solvent effect of toluene is assessed using SMD solvation model.. The favored non-catalyzed process is stepwise with two steps. The corresponding rate-determining step requires a free energy of activation of 11.6 kcal/mol in gas phase and 8.7 kcal/mol in toluene for the N-methylformamide formation. The most favored pathway for zirconium-catalyzed amidation is predicted to be stepwise via four steps. The rate-determining process is related to a free energy of activation of 6.3 kcal/mol in gas phase and 7.3 kcal/mol in toluene. The charge decomposition analysis (CDA) of the calculated transition structures revealed that the C?N bond formation is related to the nucleophilic attack of the amine toward the ?*(C=O) orbital of the carboxylic acid. It has been found that ZrCl4 activates the carboxylic acid by lowering the ?*(C=O) energy level. For the set of amines and carboxylic acids investigated, our results reveal that ?G?, for the rate-determining process, correlates linearly with the pKb of the amines and with the Fukui function for nucleophilic attack on the carbonyl carbon. It decreases with both decreasing pKb and increasing fk+. Zirconium carboxylate generated in situ is also predicted to be an active species in the zirconium-catalyzed direct amide bond formation. The assistance of an additional molecule of carboxylic acid was found to lower the activation energy in both non-catalyzed and ZrCl4-catalyzed process. The intermediate aminodiol plays a very key role in the non-catalyzed as well as in the ZrCl4-catalyzed mechanism. The rate-determining step of amide bond formation mediated by DIC is the carboxylic acid activation, which demands a free energy of activation of 18.9 kcal/mol in both gas phase and toluene. The molecular mechanism of the formation of N-acyl urea, a very pervasive byproduct, has been also elucidated.
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    Síntese e estudo da estabilidade conformacional de S-nitrosotiós derivados de AINEs (anti-inflamatórios não esteróidais)
    (Universidade Federal de São Paulo, 2014-09-30) Reginato, Marcelo Mota [UNIFESP]; Reis, Adriana Karla Cardoso Amorim [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)
    We synthesized and carried out a conformational study of the S-nitrosothiols 2-methyl-2-(nitrososulfanyl) propyl-phenylacetate-para-substituted 9R1, derivative of propanoic 2-(4-isobutylphenyl) acid (Ibuprofen) 9R2 and 2-methyl-2-(nitrososulfanyl) propyl 2-(4-isobutylphenyl) propanoate (Naproxen) 9R3 (S-Nitrosothiols 9R1, 9R2, and 9R3): Two synthetic routes have been proposed for the synthesis of S-Nitrosothiols 9R1, 9R2, and 9R3. In Route A we used brominated intermediates and dicyclohexylcarbodiimide (DCC) as coupling reagent for esterification. In Route B the esterification with an acyl chloride is the last step in the synthetic route. Both routes resulted in good yields of the final product (~ 50%), although only Route B led to the formation of the compounds of interest. S-Nitrosothiols 9R1, 9R2, and 9R3, together with their brominated intermediates were submitted to infrared spectroscopic analysis in solvents of low dielectric constant (CCl4, CH3Cl and CH3CN). For brominated intermediates we observed the presence of two bands in the carbonyl stretch region of the group indicating the existence of two conformations. S-Nitrosothiols 9R1, 9R2, and 9R3 showed only one band in the same region in most cases. We carried out the conformational search for the compounds under study and stable conformations geometries were theoretically optimized, B3LYP DFT / G 6311 + (2df, 2p). Results obtained in the infrared analysis were confronted with the theoretical data showing good agreement with experimental results in CCl4 for isolated molecules. Calculations made using the solvent effect by the method PCM do not indicate agreement with experimental data. The lowest energy conformations of S-Nitrosothiols 9R1, 9R2, and 9R3 and brominated intermediates are mainly stabilized by intra-molecular hydrogen bonds that promote greater stability of conformers. The geometrical analysis of the R-SNO group shows that these compounds are more stable in the trans conformation. Calculations of orbital interactions for the brominated intermediates using the method of Natural Bond Orbital (NBO) showed no electronic interactions capable of stabilizing their conformations. The NBO based calculations for the S-Nitrosothiols 9R1, 9R2, and 9R3 show that their conformers are stabilized by the following interactions: n_(O(OR)) 〖→ σ〗_(C-C(CO))^*, n_(O(OR))→σ_((CO))^*, n_(O(CO))→σ_((CO))^*, n_(O(CO))→〖 π〗_(C14-O15)^*, n_S→π_((NO))^*, e n_(O(NO))→σ_((S-N))^*. NBO results showed that the hyper-conjugative interaction n_(O(NO))→σ_((S-N))^* is very effective, weakening the σ bond resulting in increasing length of the S-N bond in R-SNO. The strong delocalization n_S→π_((NO))^*induces partial π character to the S-N bond. The weak link σ S-N indicates a strong delocalization of the electron pair of O(NO) due to interaction n_(O(NO))→σ_((S-N))^* . This interaction is responsible for the elongation of the S-N bond which increases the ability of the compound in releasing nitric oxide. The molecular mechanism of esterification using DCC was investigated by using electronic structure calculations on DFT-B3LYP / 6 311 + G (2df, 2p) level. We described two pathways for the esterification reaction: (i) concerted model (one step leads to the formation of products) and (ii) non-coordinated model (two steps followed by a [1-3] proton migration leads to the formation of products). Results were discussed in terms of energy, electronic parameters and calculated geometries of reactants under study (carboxylic acid, alcohol and DCC) and the reaction product (ester). The activation energy for the concerted model was lower (G‡ 27.8 kcal.mol-1) than for the non-coordinated model (G‡ 48.9 kcal.mol-1). This step was considered as a determinant of the reaction.