The use of residual dipolar couplings for conformational analysis of non-steroidal anti-inflammatory drugs dissolved in weakly ordering media

ABSTRACTThe three-dimensional structure and conformational equilibrium of flexible bioactive molecules in solution are of considerable importance in clarifying their role in chemical and biological activity, since their action takes place in a liquid medium. The use of residual dipolar couplings (RDCs) recently emerged as a promising and effective method to address this kind of investigation. In this brief review, the conformational analysis of several flexible non-steroidal anti-inflammatory drugs, belonging to the class of salicylates and α-arylpropionic acids (profens), is described using the RDCs measured in weakly aligning poly-γ-benzyl-l-glutamate solutions. By combining these experimental parameters, extracted by using different mono- and bi-dimensional nuclear magnetic resonance experiments, with the theoretical additive potential-direct probability description approach, accurate descriptions of the probability distributions have been obtained for all the drug molecules selected.