HYDROGEN-BONDING EFFECTS, ELECTROSTATIC POTENTIAL, AND THE ANTITUMOR-ACTIVITY OF FLAVONE ACETIC-ACID AND RELATED-COMPOUNDS .3. AB-INITIO STUDIES ON THE CONFORMATION SPACE

Restricted geometry optimizations at the ab initio SCF level with the 3-21G basis set were employed to investigate the conformation space of flavone acetic acid (FAA) and its related compounds. All the conforma tions are produced from a conformation which is, according to our prev ious work, probably the active conformation in terms of antitumor acti vity shown by these compounds. Detailed studies on FAA were carried ou t while only brief discussions are made on the analogs. The main resul ts obtained are that (1) FAA is a very flexible molecule, e.g., with t he energy barrier up to about 3 kcal mol(-1) from the reference confor mation, the important torsional angle tau(1) can change from 27.0 degr ees to 117.0 degrees, tau(2) from - 168.0 degrees to 2.0 degrees and t au(3) from - 50.0 degrees to 30.0 degrees; (2) the hydrogen-bonding ef fect plays an important role in determining lower-energy conformations ; (3) among all the FAA conformations considered, some are active and some are inactive; (4) it seems that the analogs will have similar beh avior to FAA when the torsional angle tau(3) is restricted to the valu es which are around the equilibrium values; and (5) the hypothesis put forward previously has been further developed in this work. Now, we p ostulate that efficient charge transfers will lower the energy and tha t proper charge transfers will activate the molecule. There are mainly two different types of charge transfer corresponding to two different types of conformation, which are specified in this article. (C) 1997 John Wiley & Sons, Inc.