Characterization of supramolecular complexes by solution and solid state high resolution Nuclear Magnetic Resonance

Abstract

To comprehend the chemistry at the supramolecular level in both solid state and solution is always quite challenging, but of significant importance, since it allows the evaluation of the mechanisms of intermolecular interaction from medium to high complexity. In this area, many systems can be considered as supramolecular complexes, being possible to study several types of mechanisms: the interaction of an enzyme with its inhibitor, the interaction of a drug with the excipient (s) in a formulation, the structure of crystals and salts of a drug, as well as many other interesting examples. Among several analytical techniques used to perform these types of studies, the techniques of Nuclear Magnetic Resonance, NMR (in both solution and solid state modalities) and X-ray diffraction, XRD (solid state only) are the most used, one rather they provide information at the atomic-molecular level. The groups of Prof. Dr. Alzir Azevedo Batista and Prof. Dr. Rose Maria Carlos, from the Department of Chemistry of UFSCar, have been synthesizing metallic complexes that exhibit potent biological activity such as enzymatic inhibitors or even acting as cytotoxic agents. In this context, this project intends to use NMR, which is one of the most consolidated techniques in these types of studies, employing mainly techniques of magnetization transfer through space (STD-NMR, tr-NOESY, ROESY, etc.), relaxometry (T1) and molecular diffusion (DOSY). As results, it is expected to elucidate the target-complex interaction mechanism, providing information that allows us to evaluate how complexes interact with his targets by observing epitope maps and, possibly, to guide synthetic chemists to make structural modifications that lead to more potent biological activity. In terms of solid state, we intend to prepare hesperidin co-crystals using dicarboxylic acids with higher structural rigidity and low pKa, such as oxalic and fumaric acids, etc., to obtain a supramolecular complex which exhibits higher solubility in aqueous medium. For this purpose, we intend to use mainly X-ray diffraction and solid state NMR spectroscopy associated with computational methods for structure optimization and chemical shift calculations to characterize the crystal structure, as well as other techniques, such as thermal analysis and vibrational spectroscopies (Raman and Infrared). (AU)