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Nuclear magnetic resonance to design and chiral discrimination of biocatalytic process

Grant number: 14/23362-8
Support type:Regular Research Grants
Duration: March 01, 2015 - February 28, 2017
Field of knowledge:Physical Sciences and Mathematics - Chemistry
Principal Investigator:Márcio Santos da Silva
Grantee:Márcio Santos da Silva
Home Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Proteins are the most versatile among the various biological building blocks has lead to many industrial and biomedical applications. This scenario is mainly by recognized importance of chirality in biological processes, due to affinity differences for each enantiomer to receptors or enzymes. The design and screening of biocatalytic reactions are based on the same principles as traditional organic reactions (substrate, pH, solvent, temperature, etc.). In contrast, the informations obtained during the design and/or screening of biocatalytic processes are unclear by the inherent complexity of the enzyme. In addition to this, the methods for chiral discrimination, usually based on high performance liquid chromatography with chiral stationary phase (HPLC), are slow and can cause product decomposition, especially in more complex substrates. There are several methodologies for design and screening biocatalytic processes. Kinetic methods are arguably useful tools in the elucidation of reaction mechanisms. However, current methodologies and studies of enzyme-substrate interaction allow for practical, faster and more accurate results. These techniques provide efficient screening achieving a wide amount of information. Successful techniques common to most of experiments applied are mass spectrometry, infrared spectroscopy, electrophoresis and nuclear magnetic resonance - NMR. The project described here shows the development of protocols for design and chiral discrimination of biocatalytic reactions based on non-classical NMR methods. In the first part, will be developed a protocol to design the reaction of enzymatic kinetic resolution of amines by NMR (STD, T1, T2 and Diffusion) measuring the enzyme-substrate interactions. These techniques are distinguished by convenience, speed and different informations obtained, such as the interaction map of the substrate (substrate epitope), the type of enzyme-substrate interaction (the hydrogen interactions, electrostatic, aromatic interaction, among others) and which enantiomer will be formed. The protocol can be applied to verify the catalytic promiscuity of enzymes and inhibitory effect of substrates. The second step in this project is to use 125Te NMR for chiral discrimination by chiral solvation effect (ion pair) for the determination of enantiomeric excesses. The compounds containing Tellurium atom are synthesized from the reaction of enzymatic kinetic resolution of esters. For kinetic optimization of the reaction will be employed 1H NMR. The method reveals advantages as convenience, quickness, precision, no derivatization, recovery of the synthesized compounds and the possibility of working with unstable compounds, such as some alkyl tellurium compounds. (AU)

Scientific publications (5)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
VOGT, ANE GABRIELA; PERIN, GELSON; LUCHESE, CRISTIANE; DA SILVA, PATRICIA CECILIA; WILHELM, ETHEL ANTUNES; SILVA, MARCIO SANTOS. Organylselanyl -Amino Phosphonates: Synthesis, NMR Spectroscopic Study, and Antioxidant and Antinociceptive Activities. EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, n. 5, p. 627-639, FEB 7 2018. Web of Science Citations: 1.
SILVA, MARCIO S. Recent Advances in Multinuclear NMR Spectroscopy for Chiral Recognition of Organic Compounds. Molecules, v. 22, n. 2 FEB 2017. Web of Science Citations: 17.
OLIVEIRA, SAMUEL S.; CUNHA, RODRIGO L. O. R.; SILVA, MARCIO S. Se-77 and Te-125 NMR spectroscopy for enantiopurity determination of chalcogen amines. Tetrahedron Letters, v. 57, n. 41, p. 4556-4559, OCT 12 2016. Web of Science Citations: 5.
SILVA, MARCIO S.; PIETROBOM, DANIEL. Simplification of Lipase Design in the Enzymatic Kinetic Resolution of Amines by Saturation Transfer Difference NMR. Journal of the Brazilian Chemical Society, v. 27, n. 10, p. 1918-1923, OCT 2016. Web of Science Citations: 1.
SILVA, MARCIO S.; PIETROBOM, DANIEL. Chiral discrimination of beta-telluride carboxylic acids by NMR spectroscopy. NEW JOURNAL OF CHEMISTRY, v. 39, n. 11, p. 8240-8244, 2015. Web of Science Citations: 6.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.