Chiroptical methods for the characterization of micro- and macromolecules from natural sources

Abstract

The exact orientation of the atoms of a given molecule in space, i.e. the absolute configuration (AC) has been a complex and intriguing problem to be solved. This feature is especially critical for bioactive natural products, which are predominantly chiral. Although there are several methods capable of determining AC of chiral compounds, many present requirements that may limit their application, such as the presence of high quality single crystals for X-ray analysis, and derivatizations for NMR methods and stereoselective organic synthesis. Based on that, the determination of AC of chiral molecules may be a challenge even in well established research institutions such as the Institute of Chemistry of UNESP in Araraquara. Thus, in this project we propose the use of a combination of chiroptical methods, such as optical rotation (OR), optical rotatory dispersion (ORD), electronic circular dichroism (ECD), vibrational circular dichroism (VCD), and Raman optical activity (ROA), all in association with quantum mechanical calculations for reliable predictions of theoretical spectra, in order to determine unambiguously the absolute configuration and solution-state conformations of natural products isolated at NuBBE (Nucleus for Bioassays, Biosynthesis and Ecophysiology of Natural Products) This approach is essential in the identification of new molecular entities (NMEs). Moreover, the use of vibrational optical activity, which is represented by VCD and ROA, will also allow the characterization of secondary structures of peptides and proteins from plant species. Therefore, this project is aimed at the application of chiroptical methods and modern computational tools to solve stereochemical problems of natural products, both scantily explored in Brazil.