Supramolecular association of gossypol in the crystalline state

Ибрагимов, Б. Т.; Talipov, S. A.

doi:10.1007/bf02903445

Cited by 11 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Orientations of the hydroxyl and isopropyl groups are consistent with both crystallography [8] and DFT calculations [7]. As was found by the latter, MM3 optimization of the isopropyl methyl groups directed inward toward the center of the molecule had slightly higher energies than when the methyl groups pointed outward away from the center of the molecule.…”

Section: Minimal Structuressupporting

confidence: 81%

“…The lower-energy outward orientation was used throughout this study. The aldehyde groups of gossypols 1, 4, and 5 and gossypolones 1 and 3 are rotated away from the extended naphthalene ring plane by ~40°, which is inconsistent with diffraction data that place the carbonyl oxygen within the extended naphthalene plane [8]. This difference was also evident in the previous MM2 study of gossypol [10] but not in the DFT calculations [7], and this may indicate the need for more accurate parameters to model the benzyl aldehyde torsional angles or some modification to the hydrogen bonding functionality.…”

Section: Minimal Structuresmentioning

confidence: 68%

“…Numerous gossypol crystal structures have been obtained [8] and a recent structure of (-)-gossypol confirms the M-form assignment [9].…”

Section: Introductionmentioning

confidence: 74%

“…In comparison, the angle between the best-fit naphthalene planes of gossypol crystal structures covers from about 70 to 110° [8], essentially spanning the range of modeled values.…”

Section: Minimal Structuresmentioning

confidence: 92%

“…All structures were created with MEDIT, an interactive molecular editing and display program included in the MM3 package, and were studied with the default parameters. The isopropyl groups were oriented with the methyl groups directed outward and away from the center of the molecule, as this has been reported to be the lowest-energy form from a recent DFT calculation [7] and as it is generally found in gossypol crystal forms [8]. Minimal energy structures were initially produced for all thirteen structures by the block-diagonal followed by full matrix minimization method with the default convergence criteria.…”

Section: Methodsmentioning

confidence: 99%

See 4 more Smart Citations

Conformational analysis of gossypol and its derivatives by molecular mechanics

Beisel

Dowd

Reilly

2005

Journal of Molecular Structure: THEOCHEM

View full text Add to dashboard Cite

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 the 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≤0.34 Å), (up to 12.7°) . For gossypolone the transition occurs with greater distortion of the inner benzyl rings (q≤0.63 Å) and less out-of-plane bending (up to 8.4°). By isolating individual clashes, their contribution to the overall barrier can be analyzed, as shown for the dialdehyde tautomer of gossypol.

show abstract

Section: Minimal Structuressupporting

confidence: 81%

Section: Minimal Structuresmentioning

confidence: 68%

“…Numerous gossypol crystal structures have been obtained [8] and a recent structure of (-)-gossypol confirms the M-form assignment [9].…”

Section: Introductionmentioning

confidence: 74%

“…In comparison, the angle between the best-fit naphthalene planes of gossypol crystal structures covers from about 70 to 110° [8], essentially spanning the range of modeled values.…”

Section: Minimal Structuresmentioning

confidence: 92%

Section: Methodsmentioning

confidence: 99%

See 3 more Smart Citations

Conformational analysis of gossypol and its derivatives by molecular mechanics

Beisel

Dowd

Reilly

2005

Journal of Molecular Structure: THEOCHEM

View full text Add to dashboard Cite

show abstract

Covalent Linkage of Gossypol and Dialdehyde Dextran

et al. 2016

View full text Add to dashboard Cite

The structures of the products from addition of gossypol to dialdehyde dextran were studied using 13 C NMR and MALDI-TOF mass spectrometry of model compounds and computer modelling. The model reaction was highly stereo-and regiospecific owing to steric hindrance to adding two E-glucose molecules to one gossypol molecule. The main binding sites to the oxidized polysaccharide were determined.Gossypol (1,6,7-trihydroxy-3-methyl-5-isopropyl-8-naphthaldehyde) is a natural polyphenol and cotton toxin with experimentally confirmed contraceptive, antioxidant, antitrypanosomal, antimicrobial, and other activities [1][2][3][4]. Derivatives with antiviral and antitumor activity are most interesting [4,5]. Chemical modification of gossypol was studied several times with respect to toxicity reduction and activity retention. Substantial progress was made by immobilizing it on polysaccharide substrates that were chemically modified via periodate oxidation [6,7]. However, the chemical structures of these compounds are still little studied.Herein, the chemical structures of the addition products of gossypol to different reactive sites on the dialdehyde dextran macromolecule were studied. The reaction of gossypol with glucose in aqueous and alcoholic solutions was used as a model. Boric acid was used as an orienting agent that could change the course of the condensation of gossypol aldehydes and polysaccharide hydroxyls.Keto-enol tautomerism is typical of gossypol. It can adopt three different forms (aldehyde, lactol, ketol) depending on the solvent and acidity [1].The aldehyde form dominates in the solid state and non-polar solvents. The ketol tautomer occurs in alkaline aqueous solutions. Gossypol lactol and aldehyde forms are in equilibrium in strongly polar solvents. Only two of the three forms (aldehyde and ketol) can react with polysaccharides to give products with different chemical structures [1][2][3][4][5][8][9][10][11][12][13][14].Dextran is a natural polysaccharide that is widely used as a polymer substrate for physiologically active compounds and is suitable for parenteral administration. It is chemically inert to proteins and peptides. Therefore, it is often functionalized using Malaprade periodate oxidation to give dialdehyde dextran. As it turned out, the oxidized units did not contain free aldehydes [6, 7] but were closed into cyclic hemiacetals (1) in both solutions and the solid state.

show abstract