Characterization of supramolecular complexes of pharmaceutical solids by solid state NMR and computational approaches

Abstract

The characterization of supramolecular complexes, either in solution or solid state is of great interest, and one of the areas that most benefits from this type of study is the pharmaceutical one. The diversity of intermolecular interactions is associated to differences in the physical and chemical properties of drugs, interaction of drugs with excipients and macromolecules, etc. Among several techniques used to study these type systems the NMR is certainly one of the most employed because it provides information at the atomic-molecular level. Solid state NMR certainly has been responsible for a very significant contribution in the last 10 years in order to characterize supramolecular complexes in solid form, and the group of Prof. Steven Brown, from the University of Warwick, UK, is certainly one of those who has most contributed in this research area. His main contributions are the development and application of advanced techniques in solid state NMR in order to acquire 1D-NMR spectra and 2D-NMR maps, by observing hydrogen nucleus. These experiments use the contact between nuclei through dipolar interactions reflecting in chemical shift changes and appearance of correlations mediated by dipolar couplings (through space). In addition, these experimental results have been increasingly associated with computational approaches, especially for predicting chemical shifts, through a method known as GIPAW. In this context, our idea is to stay at the Prof. Brown´s group during 10 months to learn more about these advanced techniques (experimental and computational ones) and establish a cooperative relationship, not only to use the infrastructure of Prof. Brown´s laboratory, but also to promote future mobility of our students. For this work we intend to take several samples prepared by two doctoral students of our group, which were so far partially characterized by solid state NMR. This partial characterization is due to limitations of our equipment, which is not properly configured to run several types of experiments that are better performed in equipment such those ones which University of Warwick own under responsibility of Prof. Brown. We expect to return to Brazil with a consolidated line of research, implementing new and advanced NMR techniques, in order to improve the quality of our work.