Theoretical study on the reactive sites and intramolecular interactions in taxol and its four analogues

A density‐functional study of the paclitaxel (Taxol) molecule and its four analogues has been performed. The theory of Bader's atoms in molecules (AIM) was applied to examine the electronic structure of these molecules at their ground state. Topological analysis reveals that the esterification of hydroxyl group attached to the oxetane ring results in great change of conformation of the taxane ring, and thus is responsible for bioactivity of the oxetane oxygen atom. It was found that there exists some intramolecular interactions in the molecule, including normal hydrogen bonds (HBs) and double HBs. Visualization of the molecule shows that the central bodies (the four fused rings) of the molecules are wrapped by the intramolecular interactions. It is supposed that these intramolecular interactions lower the aqueous solubility and protect the flexible oxetane ring, which is regarded as the dominating bioactivity site of the drug, from being opened. Our results provide an extended and consistent set of data to gauge classical force fields in view of the atomistic investigations of the interaction of the bioactive molecules. © 2008 Wiley Periodicals, Inc. Int J Quantum Chem, 2009