S. A. Talipov

Inclusion complexes of the natural product gossypol. Recognition by gossypol of halogeno methanes. Structure of the dichloromethane complex of gossypol and single crystal conservation after decomposition

The structures of gossypol complexes are extremely sensitive to the halogenomethane present as the guest; e.g. changing the number of Cl atoms in chloromethane derivatives changes the structure of the gossypol complex. The crystals of C30H30O8·CH2Cl2 are monoclinic, space groupC2/c,a=21.320(4),b=19.199(6),c=15.765(2)Å, β=113.05(2)o,V=5916(2)Å3,Z=8,Dx=1.35 g/cm3,T=295 K. The structure has been solved by direct methods and refined to the finalR value of 0.084 for 1828 reflections. In the structure H-bonded gossypol molecules form columns, generating channels in the structure which are filled by guest molecules. After decomposition (desolvation) monocrystals of the complexes are conserved without destruction, in which there are rather wide and empty channels though slightly smaller than in the complex. An attempt is made to explain some peculiarities of the behavior of the gossypol polymorph formed on the basis of its structure with empty channels.

Inclusion complexes of the natural product gossypol

Abstract Gossypol, a biologically active compound with a wide spectrum of action (antiviral, immunosuppressive, antifertile, etc.), is a unique compound in the sense of inclusion complex formation. It gives clathrates with all 110 tested low-molecular organic substances. For 80 clathrates single cyrstals have been obtained and their crystallographic parameters have been determined. By the method of X-ray diffraction the structures of 30 inclusion complexes has been solved. The extreme divergence of gossypol clathrate structures is established: clathrates (H-clathrates) with cavities as isolated cells (cryptates), channels (tubulates), intersecting channels (intercalates), clathrates with mixed host-guest matrix and autoclathrates are observed. The existence of 20 groups of isostructural gossypol clathrates is found.

Inclusion Complexes of the Natural Product Gossypol. Crystal Structure of the 2" 1 Complex of Gossypol with Amyl Acrylate

The crystal structure of a 2: 1 inclusion complex of gossypol withm-xylene has been determined by X-ray structure analysis. The crystals of C30H30O8·0.5C8 H10 are triclinic, space groupPl−,a = 8.478(1),b = 14.087(2),c = 14.411(2) Å, α = 115,39(1), β = 75.11(1), γ = 86.80(1)°,V = 1475.2(4) Å3,Z = 2,Dx = 1.29 g cm−3,T = 295 K, μ(CuKα) = 7.01 cm−1. The structure has been solved by direct methods and refined to the finalR value of 0.079 for 3910 observed reflections. The gossypol molecules are linked by intermolecular hydrogen bonds and form bimolecular layers parallel to the ‘ab’ plane. Disorderedm-xylene molecules occupy cavities between these layers. All polar groups of the gossypol molecule are packed in the interior of the bilayer while non-polar groups are directed outwards. An analysis of the crystal packing of other inclusion complexes of gossypol shows that such bilayers are formed in four complexes and three of those structures are generically related to each other.

Polymorphism of Inclusion Complexes and Unsolvated Hosts. I. Trimorphism of the Host-Guest Complex of Gossypol with Dichloromethane. The Structure of the β-Phase

The formation of host-guest complexes of gossypol at different temperatures has been investigated for the same pressure and concentration. Gossypol forms three different clathrates with dichloromethane within the temperature interval of 22-36 °C. Single crystals of these three modifications (phases) were obtained and their crystallographic parameters measured. The structure of the α-phase has been determined previously and the γ-phase is isostructural to the inclusion complex of gossypol with benzene, while the structure of the β-phase has been solved during the present research. Crystals of C30H30O8·CH2Cl2 are triclinic, space group P1, a = 8.604(1), b = 11.858(2), c = 14.405(2) (Å), α = 84.60(1), β = 89.14(1), γ = 89.73(1)°, V = 1463(1) Å3, Z = 2, R = 0.089 for 2419 observed reflections.Under ambient conditions gossypol forms unstable tubulates of the α-phase; the γ-phase is a stable cage-type clathrate (cryptate) and the host-guest complex of the β-phase is a clathrate of intermediate tubulato-cryptate type.

SORPTION OF AMMONIA, METHYLAMINE AND METHANOL BY THE P3 POLYMORPH OF GOSSYPOL. SYNTHESIS OF UNSYMMETRICAL MONOAMINE DERIVATIVES OF GOSSYPOL BY A SOLID -STATE REACTION

The P3 polymorph of gossypol has wide, empty channels andstrongly absorbs linear amines. One of the two gossypol aldehydegroups is located near the channel wall. This situation allowsreaction of the amines with half of a gossypol molecule,yielding unsymmetric monoaminoderivatives of gossypol in highyield and by a simple, solid-state method.

Inclusion complexes of the natural product gossypol. The formation of different gossypol polymorphs on decomposition of channel type inclusion complexes

The existence of seven gossypol polymorphs has been established. Two of them are obtained by direct crystallization from solution. The remaining five polymorphs are the products of desolvation of channel type complexes (tubulates). Each isostructural group of the complexes on decomposition gives one polymorph. Gossypol thus possesses specific peculiarities in terms of the decomposition of its tubulates, and also the absence of thermotropic polymorphic transitions.

Inclusion complexes of the natural product gossypol. Crystal structures of gossypol complexes with benzene and chloroform as guests

The crystal structures of the lattice inclusion complexes of gossypol with benzene and chloroform have been determined by X-ray structure analysis. The crystals of (C30H30O8)2 · C6H6 (GPBNZ) are triclinic, space groupPI,a = 11.241(3),b = 14.986(4),c = 17.380(4) Å, α = 98.89(2), β = 99.86(2), γ = 98.91(2)°,V = 2800(2) Å3,Z = 2,Dx = 1.32 g cm−3, μ(CuKα) = 7.35 cm−1. The structure has been refined to a finalR value of 0.050 for 6146 observed reflections. The crystals of C30H30O8·CHCl3 (GPCLF) are monoclinic, space groupC2/c,a = 28.464(4),b = 8.948(1),c = 26.480(4) Å, β = 108.93(2)°,V = 6380(2) Å3,Z = 8,Dx = 1.33 g cm−3, μ(CuKα) = 30.42 cm−1. The structure has been refined to a finalR value of 0.100 for 1980 observed reflections.GPCLF forms an intercalate-type structure and GPBNZ a clathrate-type structure. There are, however, some similarities in the packing mode of the host molecules in these two structures. On a basis of comparison of the crystal packing of GPCLF and GPBNZ one can postulate that in the desorption process of the intercalate-type GPCLF complex an intermediate clathrate structure of the GPBNZ-type should be formed.

Inclusion complexes of the natural product gossypol. Clathrate type inclusion complexes of gossypol with carbonyl group containing guests

The crystal structures of 2:1 inclusion complexes of gossypol with methyl propionate (GPMEP) and ethyl acetoacetate (GPEAA) have been determined by X-ray structure analysis. The crystals of GPMEP, C30H30O8⁗l/2 C4H8O2, are monoclinic, space groupC2/c,a=11.079(3),b = 30.724(7), c = 16.515(5) Å, β = 90.46(2)°,V = 5621(3) Å,Z = 8,Dx = 1.33 g cm−3. The structure has been refined to the finalR value of 0.059 for 1899 observed reflections. The crystals of GPEAA, C30H30O8⁗l/2 C6H10O3, are monoclinic, space groupC2/c,a=11.095(2),b=30.604(9),c = 16.955(5) Å, β = 88.27(2)°,V = 5754(3) Å,Z = 8,Dx = 1.35 g cm−3. The structure has been refined to the finalR value of 0.056 for 2502 observed reflections.In contrast to previously investigated inclusion complexes of gossypol the host molecules do not form centrosymmetric dimersvia hydrogen bonds. In the crystal structures the racemic gossypol is separated into enantiomers forming alternating bimolecular layers. Nearly perpendicular to these chiral bilayers run elongated cavities enclosed on each side by layers of opposite chirality. The surface of these layers is hydrophobic, the polar groups are hidden inside the layer. Guest molecules which are hydrogen bonded to the host are included in cylindrically shaped cavities. Possible hydrogen bonds between host and guest are analysed for this isostructural class of complexes.

Synthesis of thiourea derivatives of the alkaloid anabasine and crystal structure of N -(anabasino1-thiocarbonyl)furan-2-carboxamide

A series of new N-acylsubstituted thioureas, the compositions and structures of which were determined by IR and PMR spectroscopy and mass spectrometry, were synthesized from the alkaloid anabasine. The crystal structure of one of the products, N-(anabasino-1-thiocarbonyl)furan-2-carboxamide, was confirmed by x-ray structure analysis. It was also shown that this compound exhibited moderate antibacterial activity.

Membrane-active properties and antiradical activity of gossypol and its derivatives

A novel asymmetric gossypol derivative was synthesized. The antioxidant activity of gossypol and certain of its derivatives at the aldehyde groups and the interaction of these compounds with model membranes were studied. It was shown that the antiradical and membrane activities of the gossypol derivatives were determined by the structure of the substituent and that gossypol and its derivatives were partially localized in the lipid bilayer and possibly induced formation of a new interdigitating phase.