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United States Department of Agriculture

Agricultural Research Service

Research Project: NEW AND EXPANDED USES OF OILSEED PRODUCTS AND BY-PRODUCTS

Location: Commodity Utilization Research

Title: Conformational Analysis of Gossypol and Its Derivatives by Molecular Mechanics

Authors
item Beisel, C. - IOWA STATE UNIVERSITY
item Dowd, Michael
item Reilly, P. - IOWA STATE UNIVERSITY

Submitted to: Journal of Molecular Structure (Theochem)
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 11, 2005
Publication Date: August 2, 2005
Citation: Beisel, C.L., Dowd, M.K., Reilly, P.J. 2005. Conformational analysis of gossypol and its derivatives by molecular mechanics. Journal of Molecular Structure (Theochem). 730(1-3):51-58.

Interpretive Summary: Gossypol is a natural product of the cotton plant that has a wide spectrum of bioactivity including anti-cancer and anti-fertility effects. The compound exists in two forms that have different biological activity, and research suggests that these forms can be converted into each other under some conditions. Computational chemistry methods were used to study the interconversion of gossypol and several derivatives. The results suggest that the conversion occurs more readily for gossypolone (an oxidation product of gossypol) than for gossypol. The results will be useful to researchers studying the anti-cancer properties of this natural product.

Technical Abstract: Conformations and inversion pathways leading to racemization of all the tautomers of gossypol, gossypolone, anhydrogossypol, and a diethylamine Schiff’s base of gossypol were investigated with MM3(2000). All forms have hindered rotation because of clashes between the methyl carbon atom and oxygen-containing moieties ortho to the bond linking the two naphthalene rings. Inversion energies generally agree with available experimental data. Gossypol preferentially inverts in its dihemiacetal tautomeric form through the cis pathway (where similar groups clash). Gossypolone inverts more easily than gossypol, and preferentially through the trans pathway (where dissimilar groups clash) when one of its outer rings has an enol-keto group and the other has an aldehyde group. Anhydrogossypol racemizes through the cis pathway. The bridge bond and the ortho exo-cyclic bonds in all structures bend from planarity, and the inner naphthalene rings pucker to accommodate the inversion. For gossypol, the transition is achieved through greater bending of the exo-cyclic bonds (up to 12°) and less distortion of the inner benzyl rings (q <= 0.33 Å). For gossypolone the transition occurs with greater distortion of the inner benzyl rings (q <= 0.59 Å) and less out-of-plane bending (up to 8.2°). By isolating individual clashes, their contribution to the overall barrier can be analyzed, as shown for the dialdehyde tautomer of gossypol.

Last Modified: 4/23/2014
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