Nuclear magnetic resonance spectroscopy: from pulse sequences to structural assignments

Abstract

Since 2015 a thematic proposal (2015/08541-6) is in progress, related to the application of NMR beyond to structure assignments. During this period, our group developed and applied new pulse sequences, including those for DOSY and FESTA experiments to deal with structure assignment of compounds in mixtures, without the need for any physical separation. DOSY experiments were also used to study the effect of solvent ionic liquids, to absorb/capture CO2, and to differentiate enantiomers using a chiral matrixes. We have also explained, for the first time, the correct electronic effect (i.e. the source) responsible for observed experimental behaviour of 1H and 13C chemical shits (d) and even the correct transmission pathway of some coupling constants, and conformational preferences for small organic molecules. The mechanisms of important organic reactions were investigated by a synergistic effort of NMR and theoretical calculations.In the present proposal, we intend to go deeper in NMR methods development to: deal with mixtures introducing new 2D and 3D NMR experiments; apply HR-MAS approach for the measurement of RDC (Residual Dipolar Coupling) and RCSA (Residual Chemical Shift Anisotropy) using a single sample to get both isotropic an anisotropic parameters, avoiding the non-ideal approximations commonly used; HR-MAS NMR experiments will also be applied with chromatographic chiral stationary phase for Matrix-Assisted DOSY (MAD) measurements to differentiate enantiomers and evaluate the enantiomer interaction strength with the chromatographic chiral phases, chiral micelles will also be used an attractive alternative with very favourable NMR properties; measure and investigate the CO2 absorption in the presence of ionic liquid with high-pressure NMR DOSY; state-of-art theoretical calculations to describe, in term of electronic structure, the correct origin of observed NMR parameters; determine stable conformation with theoretical quantum chemistry of targeted fluorinated organic molecules and the interaction responsible for such stability; speeding up NMR experiments to get kinetic information for organic reaction mechanism investigation. In addition to the developments for high-field NMR, we also intend to adapt and further develop key methodologies for benchtop NMR, in collaboration with Nanalysis which is a leading manufacturer of commercial benchtop NMR spectrometers. We intend to continue the important work of delivering a better understanding of fundamental NMR parameters (´ and J) which is essential for a correct application of NMR for structure assignment and new NMR methodologies for the analysis of complex samples. Very important for the Brazilian industry and Academia is the high-level training in modern NMR, obtained by our research students at all levels, including PhD students and post-docs. We believe that the success achieved in the past five years puts us in a very credible position for continued support for the next five years. (AU)