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The acid hydrolysis of a series of 5-aryl-3-(β-thiomorpholinoethyl)-1,2,4-oxadiazoles gave substituted benzoic acids and 2-amino-8-thia-1-aza-5-azoniaspiro[4.5]dec-1-ene chloride hydrate, whose structure was demonstrated by spectral methods and X-ray diffraction structural analysis.

The base form of the local anaesthetic kazcaine (BFK, [1-(2-ethoxyethyl)-4-ethynyl-4-benzoyloxypiperidine, C18H23NO3]) and β-cyclodextrin (β-CD) co-crystallized as BFK:β-CD inclusion complex in 1:2 M ratio from a mixture of water and ethanol while the filtered mother liquor yielded crystals of free BFK. X-ray diffraction showed that the crystals of BFK and its inclusion complex with β-CD belong to monoclinic (P21/c) and triclinic (P1) space groups, respectively. The crystals of free BFK are stabilized by pairs of C–H⋯O, C–H⋯π and ≡C–H⋯O type interactions and van der Waals contacts. In the 1:2 BFK:β-CD complex the two β-CD molecules are in hydrogen-bonding contact with their primary hydroxyl groups, the 1-(2-ethoxyethyl)-4-ethynyl-piperidine moiety being located in one and the benzoyloxy group of BFK in the other β-CD. This crystal structure is of the channel-type, the β-CD molecules of the 1:2 BFK:β-CD complex interacting with their secondary hydroxyl groups. The pharmacological activities of the 1:2 BFK/β-CD inclusion complex have been determined in mice, rats, porpoises and rabbits and compare favourably with those of kazcaine, procaine, dicaine, lidocaine and trimecaine. The methods used include terminal (superficial), infiltration, conduction anaesthesia, and acute toxicity.

Cyclization of O-benzoyl-2-(benzimidazol-1-yl)propioamidoxime under different temperature conditions gave 2-[2-(5-phenyl-1,2,4-oxadiazol-3-yl)ethyl]benzimidazole whose structure has been determined by X-ray analysis.

The structure of dianilinegossypol clathrates is shown to be sensitive to size of the ester molecule included. The change in the guest component from methyl acetate to amyl acetate is accompanied by two morphotropic transitions in the acetic ester clathrate series and one transition into a nonsolvate dianilinegossypol form.

The structures of β-piperidinopropioamidoxime monochloroacetate and O-benzoyl- and O-para-toluyl-β-piperidinopropioamidoxime hydrochlorides have been determined. The geometry of these compounds is analyzed. The N-O bond is in the syn-planar position in β-piperidinopropioamidoxime monochloroacetate, but adopts an anti-orientation relative to the C(2)-C(3) bond of the propioamidoxime fragment in the other two compounds. In β-piperidinopropioamidoxime monochloroacetate crystals, the cation-anion pairs are joined by intermolecular hydrogen bonds into chains; the latter are linked by van der Waals contacts. The crystals of the O-benzoyl- and O-para-toluyl-β-piperidinopropioamidoxime hydrochlorides are characterized by the same system of hydrogen bonds; the cations and anions are linked by hydrogen bonds into layers, and the latter make van der Waals contacts in the structure.

Two clathrates between the 2,2‘-bis(9-hydroxy-9-fluorenyl)biphenyl host and chloroform guest, having 1:2 (α-phase) and 1:1 (β-phase) stoichiometries, have been obtained in the same vial by fast evaporation of a supersaturated solution in chloroform. The structures of the pseudodimorphs were determined by single-crystal X-ray diffraction. Their thermal properties were studied by using combined thermogravimetry-differential scanning calorimetry (TG-DSC), variable temperature X-ray powder diffraction in the temperature interval 20−250 °C, and DSC in the low-temperature interval from −140 to 20 °C. The thermal decomposition behavior of the α- and β-phase pseudodimorphs, a difference in the desolvation onset temperatures, as well as an occurrence of endothermic peaks in the low-temperature DSC curves (order−disorder transition of the guest component) have been explained on the basis of the structural data.

New organosilicon compounds 1–3 featuring bulky triphenylsilyl moieties attached to rigid linear or trigonal spacer units have been synthesized and demonstrated to act as clathrate hosts, yielding crystalline inclusion compounds mostly with apolar and aprotic dipolar guest molecules, while the nonbulky dimethylphenylsilyl or trimethylsilyl substituted analogous compounds 4 and 5, which were also synthesized, proved inefficient. X-ray crystal structures of the inclusion compounds 1·DMF (1:1), 1·pyridine (1:1), 2·1,4-dioxane (2:1), 2·pyridine (2:1), 2·p-xylene (2:1), 2·H2O (2:1) as well as of the unsolvated compounds 2 and 5 are described, and thermal stability studies of selected clathrates are reported.

The solved structures of clathrates between 1,1′-binaphthyl-2,2′-dicarboxylic acid (BNDA) as host and acetic, propionic and butyric acid guests together with previously determined clathrates of BNDA with formic and acetic acid testify that each of the first four representatives of the homologous series of aliphatic monocarboxylic acids has its own association mode with the dicarboxylic host. Acetic acid forms a clathrate specific for it at room temperature and gives a solvate isostructural with the propionic acid inclusion complex at 60 °C. The host–guest complex of butyric acid is isostructural with the clathrate of valeric acid. As a matter of principle, it is shown that (1) the larger the monocarboxylic acid molecule the greater is its ability to disintegrate infinite chains of H-bonded host molecules characteristic for a guest-free host compound—formic acid is not able to cut host chains to smaller fragments and attaches itself to them, acetic acid tends to cut chains to dimers which are then associated to circular tetramers through H-bonds of guest molecules, propionic acid disintegrates host chains to linear tetramers while butyric as well as valeric acid cut the chains to dimeric units. (2) The higher the crystallization temperature of the dicarboxylic host from solutions in acetic acid the stronger is the interaction between the host molecules in the obtained crystal modification.

The 2,2′-bis(9-hydroxy-9-fluorenyl)biphenyl host compound (1) was found to form various crystalline inclusion compounds with acetone depending on the crystallization conditions or on the method of preparation (inclusion of acetone vapour, co-crystallization from solution). In order to understand and control the formation of these pseudopolymorphic phases regarding potential uses, single crystals of the existing phases (two 1:2 and one 1:1 compound) were prepared, their structures were solved by single-crystal x-ray diffraction (XRD) analysis and the desolvation and phase transformations were studied using simultaneous thermogravimetry–differential scanning calorimetry (TG–DSC) and variable-temperature powder XRD. The results explain the inclusion and desolvation behaviour and also clarify the observed, apparently accidental formation of a 1:1 or 1:2 inclusion compound at ambient temperature. Copyright © 2001 John Wiley & Sons, Ltd.

The crystal structures of two 1:2 and 1:1 host–guest compounds between BNDA and acetone have been determined by single crystal X-ray diffraction and are comparatively discussed with reference to recently reported BNDA/ethanol clathrates of different composition. Simultaneous thermogravimetry and differential scanning calorimetry (TG–DSC) in combination with the X-ray powder diffraction (XRD) method reveal that the thermal degradation of the BNDA/ethanol 1:2 α–form clathrate takes place in two steps with the intermediate formation of the 2:1 β–form clathrate. On the other hand, desolvation of the BNDA/acetone 1:2 α–form clathrate gives no indication for the formation of any intermediate phase in the TG–DSC traces unlike the XRD studies showing the existence of the β–form during desolvation. A possible explanation of this latter property is the very similar thermal decomposition temperature of both phases. The TG–DSC results for the isothermal inclusion of vaporous ethanol and acetone indicate that this process takes place in a single step with the formation of the 1:2 BNDA/ethanol and 1:1 BNDA/acetone clathrates, respectively.

The complex formation of 1,1′-binaphthyl-2,2′-dicarboxylic acid (BNDA) with dimethyl sulphoxide (DMSO) at different temperatures was investigated. The crystal structures of the α- and β-form [triclinic, P1, a = 9.614(2), b = 11.743(2), c = 12.029(2) A, α = 99.35(3), β = 93.58(3), γ = 110.51(3)°, V = 1244.5(4) A3, Z = 2, R = 0.053 for 4879 reflections] host–guest complexes obtained at 50 and 60 °C, respectively, were determined by x-ray structure analysis (the crystal structure of the α-form obtained at room temperature was studied previously). There is disorder of the guest molecules characteristic of the α-form of the 1:1 BNDA·DMSO complex obtained at 50 °C and the host carboxylic groups in the β-form of the 1:2 BNDA·DMSO, considered a consequence of the changed conditions for crystal preparation. By disordering of the crystal structure the interaction of the solvent molecule with its environment, especially with nearest BNDA molecules, is improved. The new orientation leads to the formation of a more compact host–guest associate which resists the escape of the guest molecules from the growing crystal during crystallization and may exist even in the nucleation step. Thus disordering of the solvent molecules (α-form) and disordering of the carboxyl groups of the host molecules (β-form) are the two modes of operation in this system. Copyright © 1999 John Wiley & Sons, Ltd.

Crystallization of cyclotriveratrylene (CTV) from solutions in acetone at 40°C gave a new 4 : 1 host-guest complex instead of the conventional 2 : 1 clathrate (β-phase) whose X-ray crystal structure was determined. Data for 2(C27H30O6) · 0.5(CO(CH3)2): monoclinic, P21/c, a = 18.942(4), b = 24.697(5), c = 10.508(2) A, β = 91.10(2)°, V = 4915(2) A3, Z = 8, D x = 1.257 g/cm3, T = 293 K, R = 0.077 (for 2694 reflections). One of the two crystallographically independent CTV molecules (molecule A) is stacked into columns characteristic of the CTV α- or β-phase complexes. Molecules B face each other enclathrating inside around the inversion center disordered acetone molecules giving rise to the molecular capsule. The acetone molecule is H-bonded simultaneously to both host molecules by C(H2)--H ··· O type bonds forming centrosymmetric dimers. Dimers are incorporated together with two A molecules into centrosymmetric units also by C(H2)--H ··· O type H-bonds. Packing of these units gives rise to the crystal structure of the clathrate.

A novel type of two-component H-bonded supramolecular associate (21-membered pseudo-macrocyclic rings) formed between mono- and dicarboxylic acids is found in the crystalline complex of 1,1'-binaphthyl-2,2'-dicarboxylic acid and formic acid. The crystal data are: (C22H14O4)⋅(CH2O 2),a = 12.904(3) A, b = 8.829(2) A, c = 33.348(2) A, V = 3799(2) A3, orthorhombic, Pbca, Z = 8, R = 0.060 (F >03C3;), 2649 reflections.

The molecular and crystalline structures of a tropolone alkaloid of the colchicine series — speciosine — have been determined by x-ray structural analysis. It has been established that the presence of an orthohydroxyphenyl group does not lead to appreciable changes of the colchicine skeleton in the speciosine molecule. In the crystals, the speciosine molecules are linked into zigzag chains through O6−H…O1 intermolecular H-bonds.

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) (A), α = 84.60(1), β = 89.14(1), γ = 89.73(1)°, V = 1463(1) A3, Z = 2, R = 0.089 for 2419 observed reflections.

Dianilinegossypol forms a 1 : 2 host-guest complex with DMSO:monoclinic, space group P21/n, a = 8.522(3), b = 18.034(4), c= 28.462(6) A, β = 94.14(2)°, V = 4362A3, Z = 4, D x = 1.26 g cm-3, T = 295 K.Final R value is 0.102 for 1793 observed reflections. A 1 : 1 : 1 adduct ofdianilinegossypol with 1,4-dioxane and 1,2-dichloroethane is found to beisostructural with the dianilinegossypol complex with DMSO: monoclinic,space group P21/n, a = 8.281(2), b = 19.245(3), c = 27.970(7)A, β = 95.18°, V = 4439 A3, Z = 4, D x =1.28 g cm-3, T = 295 K. Final R value is 0.114 for 2458observed reflections.The host molecules are associated by O(4)—H ...O(3) H-bonds toinfinite chains running in the direction of the c-axis The chains areincorporated into layers through 1,4-dioxane or DMSO molecules havingH-bonds with dianilinegossypol molecules. Another DMSO or 1,2-dichloroethanemolecule is included as a guest in the channels formed between the layers.At 60 °C a cryptate-type inclusion complex of dianilinegossypol isformed with DMSO or 1,4-dioxane. It is isostructural with the acetonecomplex reported in Part IV of the present series.

The alkaloid colchicine forms, in addition to the previously known dihydrate host–guest complex, a monohydrate complex. The crystal structure of the monohydrate was determined by direct methods and refined to a final R value of 0.046 for 1425 observed reflections. Crystal data are: orthorhombic, space group P2 12 12 1, a = 9.145(2) A; b = 13.270(3) A; c = 17.942(4) A, V = 2177(1) A3, Z= 4, Dx = 1.22 g cm-3, T = 293 K. The conformation of the molecule is practically identical with the conformation in the dihydrate inclusion complex. Water molecules show proton donor as well as proton acceptor properties and are hydrogen bonded with the three colchicine molecules giving rise to the three dimensional H-bonded network.

Depending on crystallization conditions, dianilinegossypol and ethylacetate form low (ambient temperature, α-phase) and high temperature (t = 35°C, β-phase) clathrate modifications. The structure of the α-phase has been discussed earlier [1]. Crystals of the 1 : 1 β-phase complex, C42H40O6N2·C4O2H8, are monoclinic, space group P21/c, a = 11.362(6), b = 19.479(9), c = 19.085(9) A, β = 103.21(4)°, V = 4112(3)A3, Z = 4, R = 0.084 for 3210 observed reflections.

Crystal structures of the α- and β-phase inclusion complexes of dianilinegossypol with acetone obtained at 20° and 30 °C, respectively, have been determined by X-ray structure analysis. Crystal data of the α-phase complex are: C42H40O6N2⋅2C3H6O, orthorhombic, space group Pccn, a = 29.501(9), b = 10.866(2), c = 13.756(3) A, V = 4409(1) A3, Z = 4, Dx = 1.18 g cm-3. The structure has been refined to a final R value of 0.117 for 1401 observed reflections. The host–guest ratio for the β-phase complex is the same (1 : 2) and the crystals are monoclinic, space group C2/c, a = 28.352(6), b = 11.836(2), c = 13.196(1) A, β = 93.05(1)°, V = 4422(2) A3, Z = 4, Dx =1.18 g cm-3. The structure has been refined to a final R value of 0.077 for 1414 observed reflections.

The results are given of an x-ray structural investigation of hemigossypolone isolated from the stems of a wiltinfected cotton plant and of gossypolone obtained by oxidizing gossypol.

The structure of the product of condensation of gossypol with (−)-α-phenylethylamine has been determined. It has been shown that a possible cause of the difficulty in separating racemic gossypol into optically active components is not a racemization of (−)-α-phenylethylamine on its condensation with gossypol but the high tendency of gossypol and its derivatives to form dimers.

All three possible stereoisomers of gossypol hexamethyl ether in the dilactol tautomeric form have been separated with the aid of fractional crystallization and have been identified crystallographically. These stereoisomers have been subjected to x-ray stuctural investigation, and their configurations and clathrateforming properties have been determined.

Two bufodienolides have been isolated in the individual form from the Central Asian green toadBufo viridis for the first time. It has been established by1H NMR, mass spectrometry, and x-ray structural analysis that these compounds are gamabufotalin (3β, 11α, 14-trihydroxy-5β, 14s-bufa-20,22-dienolide) and a crystalline modification of arenobufagin (3β, 11α, 14-trihydroxy-12-oxo-5β, 14β-bufa-20,22-dienolide). The biological activity of Bakagin — the total bufadienolides of the venom ofB. viridis, consisting predominantly of the compounds named — has been studied. The promising nature of a further study of Bakagin as a cardiotonic drug has been shown.

The crystal structure of the 1:2 clathrate of dianilinegossypol with 1,2-dichloroethane, which is unstable under ordinary conditions, has been determined. In the clathrate there are two systems of mutually perpendicular channels in which two crystallographically different molecules of the guest are arranged. No intermolecular H bonds of the host-guest type are observed in the structure of the clathrate.

Gossypol forms various complexes with the isomeric dioxanes. The clathrate with 1,4-dioxane is the only complex of gossypol in which the intrinsic symmetry of the gossypol molecule — the symmetry of a twofold axis — is retained. In this complex, two out of the three 1,4-dioxane molecules belonging to each gossypol molecule participate in the construction of a mixed H-bound gossypol -dioxane matrix, while the third molecule plays the part of guest, the guest molecules having no H-bonds with the host matrix and undergoing desolvation at 108–110°C.

The reaction of 5-amino-1,2,3-thiadiazol-4-carbothioamides with methyl iodide basically generates α-diazo-S-methylthioimidates and -carbothioimidolates. It is shown that the reactivity of the latter increases when either alkyl or aryl substituents are introduced at the nitrogen atom of the carbothioamide group

C38H24O, monoclinic, P121/n1 (No. 14), a = 10.737(2) Å, b = 16.963(3) Å, c = 15.246(3) Å, β = 109.30(3)°, V = 2620.8 Å3, Z = 4, Rgt(F) = 0.088, wRref(F2) = 0.252, T = 293 K.

Selectivity of enclathration and desolvation of xylene isomers by a dicarboxylic host depends on temperature.

The lactone of gossypolic acid, obtained by the demethylation of the tetramethyl ether of gossypolic acid, forms with acetic acid a stable complex having the 1∶4 composition. The crystallographic parameters of single crystals are as follows:a=20.251(2) A, b=12.028(3) A, c=15.934(4) A, V=3881.2(2.3) A3,Z=4, Dcalc=1.32 g/cm3, sp. gr. Pbcn. The molecule is characterized by considerable strain because of the formation of the five-membered lactone ring the atoms of which are coplanar with the atoms of the naphthyl fragment. Unlike the clathrates of racemic gossypol and dianilinegossypol, the gossypolic acid lactone — acetic acid comples does not belong to the type of clathrate inclusion compounds.

Polymorphs of dianilinegossypol are obtained by selecting the precipitation medium and the crystallization temperature. Four dianilinegossypol polymorphs are found. Two solvate forms and three polymorphic modifications of dianilinegossypol are prepared from an acetone solution by varying the crystallization temperature from room temperature to 6°C. The crystal structures of the P1, P2, and P4 polymorphs are determined. The P1 and P2 polymorphs are characterized by the same hydrogen-bond system, but their crystal structures differ in the mode of packing of layers formed by dimers of dianilinegossypol molecules. In the P4 polymorph, homochiral hydrogen-bonded dianilinegossypol molecules form trimers. This mode of H-agglomeraton of dianilinegossypol molecules is characteristic only of the P4 polymorph.

The crystal structure of the complex of 18-dehydroglycyrrhetic acid (GLD) with DMSO (C30H41O4·C2H6OS) has been determined by x-ray structural analysis. Syntex P21 diffractometer, CuKα radiation, 1309 reflections, R = 0.080. A conformational analysis has been made of the GLD molecule in comparison with that of glycyrrhetic acid. The conformations of rings A and B in the GLD molecule do not differ from the conformations of the corresponding rings of glycyrrhetic acid. Differences arise in ringsC,D, andE because of the presence of the double bond between the C18 and C19 atoms.