Banca de DEFESA: PEDRO TENDRIH SODRÉ
Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.DISCENTE : PEDRO TENDRIH SODRÉ
DATA : 02/09/2019
HORA: 14:00
LOCAL: Auditório, 8º andar, Bloco B, Campus SA da Fundação Universidade Federal do ABC
TÍTULO:
Macrostructured micellar architetures for selective aldol reactions: A multiscale in silico approach
PÁGINAS: 93
RESUMO:
Supramolecular structures are known to feature interesting properties. The formation of domains, as a result of specific chemical interactions, is related directly to these properties. A particular application include the employment of these structures as catalysts for specific organic reactions. Due to self-assembly into micelles, L-proline containing lipopeptides exhibit catalytic activity towards aldol reactions and are able to function efficiently in aqueous medium.
In this work we investigate, using molecular dynamics simulations, the structural and dynamical properties of lipopetide micelles composed of a short peptidic sequence bound to an alkyl chain. More specifically, we have investigated micelles composed of PRWC16, PRWGC18 and PRWGC18-2 lipopeptides.
PRWGC18 contains a peptide chain comprised of proline, arginine, trypthophan and glycine residues with an amide bonding between peptide and alkyl chain while PRWC16 features an ester bond directly from trypthophan and no glycine residue. Very similar results are obtained for PRWGC18-2 when comparing with PRWGC18.
Initial conditions for the micelle assembly were generated using PACKMOL. Characterization of this system was done by performing molecular dynamics simulations using the amber ff14sb, lipid11 and lipid14 force fields. Characterization of the micellar structures was done using radial distribution function (RDFs), radius of gyration (ROGs) and hydrogen bond analysis (HB). The AMBER14 and AMBER18 suite of codes have been used throughout this work.
Results point to strong structural similarities between micellar aggregates. RDFs shows a very similar residue distribution for PRWC16 and PRWGC18 micelles, with PRWGC18 having a wider distribution when compared to PRWC16. Larger fluctuations are observed for PRWC16 as measured by changes in the ROG. HB analysis points that additional glycine-trypthophan and glycine-arginine hydrogen bonds improves PRWGC18 stability when compared to PRWC16. Addition of ciclohexanone (an aldol reaction reactant) disturbs micellar structure by accumulating in its interior, resulting in a pre-concentration near the proline residue possibly favoring the formation of an enamine intermediate.
Quantum mechanics (QM) was used to build elementary reactions pathways of a model diasteroisomeric aldol reaction between cyclohexanone and p-nitrobenzaldehyde. These reactions are known to be strongly influenced by both solvent and temperature. Four stereoisomers may occur due to the nature of the enamine intermediate formed from L-proline and ciclohexanone. We have employed Density Functional Theory in our calculations with the B3LYP functional, 6-311++G(d,p) basis set and SMD to model the aqueous environment. All calculations have been performed using the Orca 4.1 code.
Diasteroisomeric transition state 6-member ring can be understood in terms of conformers: while (S) isomers are chair, (R) conformations correspond to half-boat. In order to favour (R) isomers, one would need a specific catalyst to stabilize these transition states with respect to both (S,R) and (S,S) isomers.
The smallest energy barrier in water was obtained for the (S,R) isomer (8.3 kcal/mol) in agreement with experiments. This value is 2.6 kcal/mol lower than the barrier for the SS isomer and 3.3 kcal/mol lower than the barrier for the closest R isomer.
MEMBROS DA BANCA:
Presidente - Interno ao Programa - 1544403 - MAURICIO DOMINGUES COUTINHO NETO
Membro Titular - Examinador(a) Interno ao Programa - 1544341 - WENDEL ANDRADE ALVES
Membro Titular - Examinador(a) Externo ao Programa - 1309493 - PEDRO ALVES DA SILVA AUTRETO
Membro Suplente - Examinador(a) Externo ao Programa - 149.405.258-05 - KATHIA MARIA HONORIO - USP
Membro Suplente - Examinador(a) Externo ao Programa - 2218228 - LUANA SUCUPIRA PEDROZA