SEMIEMPIRICAL STUDIES OF RING TWISTING IN CIS-STILBENE AND RELATED BIOMOLECULES

The geometric. and energetic predictions of the MNDO, AMI, and SAM1 mo dels as they describe rotation of the dihedral angle between the plane of one of the phenyl rings and the plane of the olefin core of cis-st ilbene (cis-1,2-diphenylethylene) were tested for a variety of constra ints. An three models predict that distortions away from the stable st ructure fixed by a compromise between ir-electron and steric repulsion s lead to small (at most 1-2 kcal/mol) strain energies and geometry re laxations. Extensive peripheral substitution on the phenyl rings prese nt in a prototype natural product having the cis-stilbene structure, C ombretastatin A-4 4,5-trimethoxy-3'-hydroxy-4'-methoxy(Z)-stilbene), d istorted the shapes of the cis-stilbene barriers to conformation chang e only minimally. It is concluded that natural products having the cis -stilbene structure should be expected to interact with other biomolec ules as if the phenyl twists are barrier free. (C) 1999 John Wiley & S ons, Inc.