Structural Determination of Antioxidant and Anticancer Flavonoid Rutin in Solution through DFT Calculations of 1 H NMR Chemical Shifts.

As the knowledge of the predominant molecular structure of antioxidant and anticancer flavonoid rutin in solution is very important for understanding the mechanism of action, a quantum chemical investigation of plausible rutin structures including solvent effects is of relevance. In this work, DFT calculations were performed to find possible minimum energy structures for the rutin molecule. ¹ H NMR chemical shift DFT calculations were carried out in DMSO solution using the polarizable continuum model (PCM) to simulate the solvent effect. Analysis of the experimental and theoretical ¹ H NMR chemical shift profiles offers a powerful fingerprint criterion to determine the predominant molecular structure in solution. Therefore, our aim is to find the best match between experimental (in DMSO -d ) and theoretical (PCM-DMSO) ¹ H NMR spectrum profiles. Among 34 optimized structures located on the potential energy surface, we found that structure 32 , with a B-ring deviated 30° from a planar configuration (geometry usually assumed for polyphenols), showed an almost perfect agreement with experimental the ¹ H NMR pattern when compared to the corresponding fully optimized planar geometry. This structure is also predicted as the global minimum based on room-temperature Gibbs free energy calculations in solution and, therefore, should be experimentally observed. This is new and valuable structural information regarding structure-activity relationship studies, and such information is hard to obtain by experimentalists without the aid of the X-ray diffraction technique.