The conformational flexibility of aromatic retinoids.
AM1 and PM3 complete geometry optimizations were performed on 19 arotinoids congeneric with (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2- naphthalenyl)-1-propenyl] benzoic acid (TTNPB), a very potent agent in carcinoprevention and carcinotherapy. Sixteen TTNPB conformations with close energy were obtained and characterized; four representative conformations were then studied for 14 derivative compounds, for which we found a substantial non-planarity of the two aromatic moieties. Large rotational flexibility of the arotinoid ring fragments was predicted by both methods. Very low barriers (0.4-3.9 kcal/mol) were found for the tetralenyl ring rotation. The two methods also agreed in predicting benzoic acid moiety rotation in a wide range of torsion angle values except those close to 0 or 180 degrees for which the PM3 rotational barriers were found to be considerably lower than the AM1 ones. This high conformational flexibility of arotinoid molecules may facilitate their favorable orientation in the process of fitting to the receptor sites.
Bonchev
D
D
University of Texas M.D. Anderson Cancer Center, Houston 77030.
Mountain
C F
CF
Seitz
W A
WA
D001565:Benzoates / Q000737:chemistry*; D008433:Mathematics; D008968:Molecular Conformation; D015394:Molecular Structure; D012176:Retinoids / Q000737:chemistry*; D013329:Structure-Activity Relationship
D001565:Benzoates; D012176:Retinoids; C038864:4-(2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl)benzoic acid