Crystal Solvates Research Articles

Molecular Conformation, Receptor Binding, and Hormone Action of Natural and Synthetic Estrogens and Antiestrogens

The X-ray crystallographic structural determinations of synthetic estrogens and antiestrogens provide reliable information on the global minimum energy conformation of these molecules or a local minimum energy conformation that is within 1 or 2 kcal/mole of the global minimum. In favorable cases, state-of-the-art molecular mechanics calculations provide quantitative agreement with X-ray results and information on the relative energy of other local minimum energy conformations not observed crystallographically. Because the conformation of diethylstilbestrol (DES) observed in solvated crystals has an overall conformation and dipole moment more similar to estradiol it is the form more likely to bind to the receptor and produce hormone activity. Either phenol ring of DES can successfully mimic the estradiol A-ring in binding to the receptor. Indenestrol A (INDA) and indenestrol B (INDB) have nearly identical fully extended planar conformations. Either the alpha or gamma rings of these compounds may mimic the A ring of estradiol and compete for the estrogen receptor. Although there are eight distinct ways in which molecules of a racemic mixture of INDA or INDB can bind to the receptor, not all of them may be able to elicit a hormonal response. This may account for the reduced biological activity of the compounds despite their successful competition for receptor binding. The minimum energy conformations of Z-pseudodiethylstilbestrol (ZPD) and E-pseudodiethylstilbestrol (EPD) are bent in a fashion similar to that of indanestrol (INDC). These molecules have good binding affinity suggesting that the receptor does not require a flat molecule. Therefore these conformations would appear to be compatible with receptor binding, but only the Z isomer has an energetically allowed extended conformation that accounts for its observed biological activity relative to DES.

Molecular conformation, receptor binding, and hormone action of natural and synthetic estrogens and antiestrogens.

The X-ray crystallographic structural determinations of synthetic estrogens and antiestrogens provide reliable information on the global minimum energy conformation of these molecules or a local minimum energy conformation that is within 1 or 2 kcal/mole of the global minimum. In favorable cases, state-of-the-art molecular mechanics calculations provide quantitative agreement with X-ray results and information on the relative energy of other local minimum energy conformations not observed crystallographically. Because the conformation of diethylstilbestrol (DES) observed in solvated crystals has an overall conformation and dipole moment more similar to estradiol it is the form more likely to bind to the receptor and produce hormone activity. Either phenol ring of DES can successfully mimic the estradiol A-ring in binding to the receptor. Indenestrol A (INDA) and indenestrol B (INDB) have nearly identical fully extended planar conformations. Either the alpha or gamma rings of these compounds may mimic the A ring of estradiol and compete for the estrogen receptor. Although there are eight distinct ways in which molecules of a racemic mixture of INDA or INDB can bind to the receptor, not all of them may be able to elicit a hormonal response. This may account for the reduced biological activity of the compounds despite their successful competition for receptor binding. The minimum energy conformations of Z-pseudodiethylstilbestrol (ZPD) and E-pseudodiethylstilbestrol (EPD) are bent in a fashion similar to that of indanestrol (INDC). These molecules have good binding affinity suggesting that the receptor does not require a flat molecule. Therefore these conformations would appear to be compatible with receptor binding, but only the Z isomer has an energetically allowed extended conformation that accounts for its observed biological activity relative to DES.

Aspects of the synthesis of metallophenylsiloxanes using crystal solvates of cyclic sodium organosilanolates

Metallosiloxane (II) is unstable and disproportionates to form insoluble (IIl) with a metal content greater than (II) and siloxane (IV), which does not contain the metal. Found for (III) with M = Co: Si 13.62; Co 28.68%. Calculated: Si 13.76; Co 28.88%. Found for (III) with M = Cu: Si 13.31; Cu 30.28%. Calculated: Si 13.45; Cu 30.45%. Product (IV) is a crystalline octaphenylsilsesquioxane which is a cube having four-unit eyclosiloxane fragments at the base and the sides [2]. The structure of (IV) was supported by x-ray diffraction structural analysis by comparison of the unit cell parameters of crystals of the compound obtained with a reference, (C6HsSiOi.5)e. Comparison of the structure of the starting compound (I) containing trisiloxane cyclic fragments with the structure of (IV), which contains tetrasiloxane rings, indicates complete rearrangement of the siloxane fragments of the starting compound as a result of disproportionation.

4-Chloromercurioandrosta-4,6-diene-3,17-dione: preparation, X-ray structure determination, and potential utility

The novel steroid 4-chloromercurioandrosta-4,6-diene-3,17-dione (2) was obtained as a major side-product during conversions of 6βbromoandrost-4-ene-3,17-dione (1b) into its 6β-fluoro derivative (1a) using HF(pyridine)n and mercuric oxide. Compound (2) was successfully converted into various 4-substituted steroids (using standard vinyl-mercury methodology), including the disteroidal mercury compound (3c). Crystals of the acetone solvate of (2). 2(HgClC19H40O2)· acetone, were monoclinic, space group P21,Z= 2 with dimensions a= 7.295(8),b= 24.12(1),c= 12.215(12)A,β= 108.0(1)°. The two independent molecules have equivalent structures with the mercury atoms strongly bound to a chlorine atom and to carbon atom C(4) of the steroid. The acetone molecule forms a weak bridge between the two mercury atoms.

Molecular and crystal structure of hexazocyclane based on 4,4?-diaminodiphenyl ether

1. Experimental confirmation of the macrocyclic structure of hexazocyclane molecules has been obtained for the first time. 2. In the crystal of the hexazocyclane that has been investigated, the tautomeric structure that is realized is centrosymmetric with the H atoms at the nitrogen atoms bonding the isoindole and ether parts of the molecule. The factors favoring realization of this tautomeric form have been examined. 3. The basic features in the solvation of hexazocyclane molecules have been established: The crystal solvate molecules form H-bonds with the H-groups of the macroring and are located in its semiopen void spaces. 4. The data that we have obtained on the relative constancy of the dihedral angle between the planes of the benzene rings of the diphenyl oxide fragment of the hexazocyclane molecule can provide an explanation for the features of intramolecular cyclization of the hexazocyclane with additional nitrile groups in these fragments, specifically, the actual exclusive formation of the “trans” isomer.

Spectroscopic Investigation of U(DBM) 4 U(TFBA) 4, Th(DBM) 4:U(IV), Th(TFBA) 4:U(IV) single crystals (DBM = 1,4-dibenzoyl-1,3-butane dione, TFBA = 4,4,4-trifluoro-1-phenyl-1,3-butane dione)

Single crystals of U or Th(DBM) 4-solvate, U or Th(TFBA) 4 and Th(DBM) 4-solvate or Th(TFBA) 4 doped with U(IV), few tenths of cubic millimeters in size, have been grown at low temperature from benzene (DBM) or toluene (TFBA) solutions. Other conditions do not lead to so large single crystals. All tetrakis-dibenzoylmethanato crystals exchange benzene molecules giving solvate crystals. They only can be kept unchanged in benzene saturated atomsphere. The yet unknown structure of these solvates are slightly different from the known ‘dry’ orthorhombic U(DBM) 4 (Pccn) [1, 2]. First investigation on U(DMB) 4 solvate essentially shows a 15% increasing of the b parameter and a 20% increasing of the orthorhombic volume cell. Space group is Pcbb. This probably means that benzene molecules insert themselves between the U(DBM) 4 layers of the dry crystals. In both structures, U lies on a C 2 crystallographic axis parallel to z. The structure of the tetrakis-trifluorobenzoylmethanato crystals is known to be tetragonal (I4 1/a) [3]. Polarized high resolution spectra of all these single crystals have been obtained between 4000 and 20000 Å in the temperature range 4−300 K, Some common features appear on these spectra. The thorium chelates show two bands. The Th(DBM) 4:U(IV) and Th(TFBA) 4:U(IV) which are the best resolved spectra among all the recorded ones, show about thirty vibronic bands, some of them having a width of 10 Å at 4 K. A quite god polarization of Th(DBM) 4:U(IV) spectra is surprising for such an orthorhombic lattice. This means that probably the two optical axes are so close together that the crystal appears at 4 K as uniaxial. The 4 K polarized spectra look like very accurately the σ and π U 4+ spectra in β-ThBr 4 and β-ThCl 4 matrix or UCl 4, all of them being uniaxial tetragonal crystals [4, 5] where point group symmetry of U 4+ in D 2d. So, point group symmetry of U(IV) is close to D 2d or another group whose characteristic table is the same. These observations cannot be explained according to the above mentioned insertion of benzene molecules without any other changes in the positions of U in the lattice. In dry U(DBM) 4, point group symmetry of U(IV) is D 4d or C 2 depending on whether the considered environment is a square antiprism of oxygen or the whole molecule. Spectra of Th(DBM) 4:U(IV) have temporarily assigned on the D 2d basis point group symmetry. Broadness of the lines leads to poorly significant values of the F k and B k q parameters. As expected for a tetragonal crystal and a S 4 point group symmetry for U(IV), polarization of Th(TFBA) 4:U(IV) is found and spectra of U(IV) are very different from those of D 2d symmetry. σ lines are more numerous than π lines and this could indicate according to dipole selection rules for S 4, that ground state is two fold degenerate. Unfortunately no spectra of U(IV) have today been assigned in a such symmetry. The spectra we have recorded could be a basis calculations.

Salze der 1.2-Hydrazin-bis(dithiocarbonsäure): Darstellung, Schwingungsspektren und Struktur / Preparation, Vibrational Spectra and Structure of Alkahmetal Salts of the 1,2-Hydrazine-bis(dithiocarboxylic Acid)

The following salts of the 1,2-hydrazine-bis(dithiocarboxylic acid) have been prepared: M2[S2CNH -NHCS2], M = Na, K and M3[S2CN-NHCS2], M = Na, K. In the solvated crystals K2[S2CNH-NHCS2] · 4 CH3OH (a = 718.0(5), b = 1329.3(8), c = 937.7(9) pm, β = 109.26(6)°, space group C2/m, Z = 2) the [S2CNH-NHCS2]2- ion possesses crystallographic C2h symmetry, i.e. a trans planar structure with a N-N bond length of 139.2(3) pm. Vibrational spectra indicate a lower symmetrical anion in the unsolvated crystals. In the trianion [S2CN-NHCS2]3- the C-N stretching vibrations are observed at 1400 and 1310 cm-1.

Cluster chemistry. V. Reactions between [Ru3(CO)11(CNBut)] and [Pt(η-C2H4)(PPh3)2] and related chemistry : Crystal and molecular structures of Di-μ-carbonyl-[μ-carbonyl-bis {(triphenylphosphine)platinum}]dicarbonyl(triphenylphosphine)ruthenium(2Ru-Pt)(Pt-Pt), [RuPt2(CO)5(PPh3)3], and its benzene solvate

The reaction between [Ru3(CO)11(CNBut)] and [Pt(η-C2H4)(PPh3)2] at -30° affords a thermally unstable intermediate complex (A), which decomposes at room temperature affording, inter alia, [Ru2Pt(CO)7(PPhd3)3 (1), [RuPt2(CO)5(PPh3)3] (2), [RuPt2(CO)6(CNBut)(PPh3)] (5) and [Ru2Pt2- (CO)9(CNBut)(PPh3)] (6). The hexanuclear complexes [Ru2Pt4(CO)5-n(CNBut)(PPh3)4+n] [n = 0 (17) and 1 (18)] are obtained, with [Ru2Pt(CO)5(CNBut)(PPh3)4] (16), from reactions at 80°. Related Ru2Pt and RuPt, complexes are obtained from reactions between complex (A) and CO, CNBut, Pme3, P(C6H4Me-p)3, or P(OMe)3; related reactions between [Ru3(CO)11(CNBut)] and [Pt{P(C6H4Me-p)3}4], and between [Ru3(CO)10(CNBut)2] and [Pt(η-C2H4)(PPh3)2, are also described. The crystal structure of [RuPt2(CO)5(PPh3)3] has been determined by single-crystal X-ray diffraction methods at 295(1) K and refined by least squares to a residual of 0.035 for 6774 'observed' reflections. Crystals are triclinic, P 1, a 15.893(5), b 15.400(5), c 12.651(4) Ǻ, α 57.04(2), β 77.09(3), γ 84.10(3)°, Z 2. Crystals of the dibenzene solvate of the complex are monoclinic, P 21/c, a 11.868(4), b 18.647(8), c 29.24(1) A, β 98.35(3)°, Z 4, the structure being refined to a residual of 0.057 for 4530 'observed' reflections. Ligand dispositions are compared in detail with those observed in the analogous compound previously described with the methyldiphenylphosphine Iigand.

Structural features of aromatic polyamide solutions in sulphuric acid

Spectroscopic studies have been carried out on aromatic polyamide (PA) solutions in sulphuric acid. The large enthalpies of complexing (167–230 kJ/unit) indicate that an ionized polymer exists. PA concentrates have shown anisotropy of IR-radiation absorption for amide I and II which has an unusual π-polarization of the amide I line; this indicates the possibility of an imidol-type of PA forming in the solution. The likely shapes of the PA chains and types of intermolecular bonds present in the polymer-polymer and polymer-solvent systems have been examined. Two types of crystal solvates with trans- and cis-conformations of the amidol groups are suggested; these are under stress due to ionic-type intermolecular bonds between the polymer and the sulphuric acid. The formation of a mesomorphic state is associated with the existence of polymer-polymer aggregates having the normal δ-polarization of the amide I line. The part played by the intermolecular H-bond during the realization of the liquid-crystalline state of the aromatic PA solutions is assessed.

Crystal growth in organic solids during desolvation

A study has been carried out of desolvation — the most widely occurring reaction in organic solids. Desolvation occurs together with the growth of solvent-free crystals inside the crystal solvate. The growth of solvent-free crystals is absolutely analogous to crystal growth from liquid media. The reversibility of the process has been established and the effect of some physical factors on the course of the reaction has been studied.

Structure formation in a poly- p-benzamide-sulphuric acid system

Polarization-optical studies of poly- p-benzamide (PB) solutions in sulphuric acid established that relatively concentrated solutions of this polymer (11–13%) at ordinary temperatures may be in non-equilibrium state for a long period of time, which is characterized by the coexistence of three phases: isotropic mobile liquid crystalline and solid. The separation of a solid phase from the isotropic solution corresponds to the equilibrium state. A study of possible types of phase equilibrium and results of electron microscope studies of these systems suggest that PB crystal solvates may be separated in certain temperature and concentration ranges in the form of a solid equilibrium phase.

Stoichiometrically solvated polyalkylbenzimidazole crystals

AbstractUnlike most crystallizable polymers, some polyalkylbenzimidazoles do not crystallize when pure but do crystallize with ionized solvent molecules to produce solid stoichiometrical, solvated crystals. The polymer–solvent interaction is strongly exothermic, and a crosslinked polymer swells in the solvent over hundredfold. This leads to a negative χ1 value for the system. The cocrystallization with stoichiometric amounts of ionized solvent cannot be examined on the assumption that it is a polyelectrolyte gel since ion mobility is precluded. It also cannot be treated according to the corresponding states theory since the latter does not allow for negative χ1. A theoritical derivation, originating from Flory's semiflexible chain treatment, apparently predicts and explains the behavior of the polyalkylbenzimidazole–solvent system.

Solvent-Inclusion Effects on the Structures and Properties of Molecular Complexes and Radical Salts

Abstract Some molecular complexes and radical salts give the crystal forms which contain solvent molecules in their crystal lattices, and these solvated crystals often exhibit physical properties markedly different from those of the solventfree crystals. Two typical examples of such cases, on which we have recently investigated, will be described here to illustrate the characteristic features of solvent-inclusion.

Structure cristalline du pentaphenylantimoine dans le solvate cyclohexanique (C 6H 5) 5Sb· [formula omitted]C 6H 12

Pentaphenylantimony in the solvate crystals has the trigonal bipyramid geometry. The CSbC angles differ by less than 2.2° from their ideal values. The axial bonds (av. 2.24 Å) are significantly longer than the equatorial bonds (av. 2.14 Å ). The cyclohexane molecule is situated halfway along the a axis and it makes no special contacts with neighbouring molecules. The geometry in the solvate suggests that lattice energy is a determining factor in the square pyramidal structure observed for the non-solvated crystals.

Croissance des cristaux de cyanure mercurique orientés par rapport à la matrice de cristaux de leur solvate avec le tétrahydrofuranne

The growth of mercuric cyanide crystals from a crystal of the mercuric cyanide with tetrahydorfuran solvate 5Hg(CN)2 ·4T.H.F. is obtained through slow decomposition of the solvate crystal to the air. The growth occurs in such a way that mercuric cyanide crystals show an orientation in relation to the matrix constituted by the initial solvate crystal. This phenomenon corresponds to tridimensional structural concordances between solvate and pure salt; they appear in the existence in the solvate of buildings of Hg(CN)2 molecules which are to be found again in mercuric cyanide with the same orientation the same structure and the same respective positions.

Loss of Solvent from a Molecular Crystal Solvate. Phenylazotribenzoylmethane Hemietherate

Abstract In a study(1) of the rearrangement in the solid state of phenylazotribenzoylmethane (I) it was discovered that this compound crystallizes from diethyl ether as an etherate (II) with the approximate composition (C6H5CO)3CN[dbnd]NC6H5 · ½[(C2H5)2O]; the ether was lost when the crystals stood for long periods at room temperature. Although many molecules of intermediate size crystallize with the incorporation of solvent molecules,(2) little is known about the loss of solvent from such solvates or the structure remaining after the solvent loss. Since the “de-etherated etherate” remaining after the loss of ether from II might show unusual chemical behavior an investigation of the structure of the etherate and the mechanism of loss of ether from single crystals has been undertaken.

Crystal and molecular structure of the pyridine solvate of bis(8-hydroxyquinoline)silver(I)

Crystals of the pyridine solvate of bis(8-hydroxyquinoline)silver(I), Ag(C9H9NO)C9H6NOHO•C5H5N, are monoclinic, space group P21/a, with cell dimensions a = 10.87 ± 0.01 Å, b = 10.65 ± 0.01 Å, c = 16.70 ± 0.01 Å, β = 92.6 ± 0.2°, Z = 4. Atomic parameters have been determined from a three-dimensional analysis using 2163 independent intensities to which no absorption corrections were applied. Refinement was by observed and calculated differential syntheses using isotropic temperature factors. The final discrepancy index is R = 0.116.The coordination of the silver atom is distorted tetrahedral, with bonds to the phenolic oxygen and ring nitrogen atoms of both 8-hydroxyquinoline molecules. Adjacent bis(8-hydroxyquinoline)silver molecules are linked by a hydrogen bond between two oxygen atoms. The pyridine molecules are held in the lattice by van der Waals' forces.

Borate complexes of erythromycin

Its storage even at low temperature (2-4 ~ involves a loss of biochemical activity of the solution. The optical activity of the solution is unchanged in this case. The inactivation of the antibiotic in borate buffer solution increases with increasing temperature and with decreasing pH value of the solution. The substance isolated upon alkalinization of a borate buffer solution of erythromycin with pH 5.0 after boiling for 12 h or after two clays of standing without heating proved to be a biologically inactive boron-containing compound which, like the active borate complex of erythromycin, can be high-melting (225-227 ~ or low-melting (200203~ depending on the pH of the medium and the moment of precipitation of the product. Like the active borate complexes of erythromycin, the indicated biologically inactive borate complexes are intereonverted under suitable conditions - the low-melting (I) to the high-melting (II) and vice versa. The absence of biological activity in the borate complexes obtained is evidence of a change in the structure in the erythromycin molecule itself, which, in our opinion, should be attributed to reduction of the keto-group. The IR spectra (Figs. 1 and 2) of the compounds studied do not reflect differences in the biologically active and inactive complexes. The absence of an absorption band of the ketone carbonyl in the low-melting borate complex of erythromycin and a very weak band PC=O 1653 cm -1 in the high-melting borate compIex of erythromycin (Fig. 1), in our opinion, are explained by the participation of the keto-groups of these complexes In hydrogen bonds. An investigation of the IR spectra did not reveal the characteristic frequencies of the B-O bond, cited by Gerard for boron compounds [3]. The complexes described are inclined to form crystal solvates with the organic solvent from which they were isolated. The IR spectra contain bands of the vibration of the chloroform ~noleeule (753, 756, 758, and 759 cm -~ [4]), the intensity of which is determined by the content of the solvent remaining after drying of the samples under vacuum at 70 ~ for 12 h. In the ultraviolet region (220-320 mtt), inactive boron-containing compounds have an absorption that grows stronger in the short-wave region, in contrast to the biologically active borate complexes of erythromycin, which exhibit no absorption. This confirmed our hypothesis concerning the nat~lre of the complex product of inactivation of erythromycin. The removal of boron both from the biologically active and from the inactive borate complexes, accomplished under the action of acid medium, actually leads to the formation of dihydroerythromy cin, which was confirmed by a special investigation.

X-Ray investigation of several phorbol derivatives. The crystal and molecular structure of phorbol bromofuroate–chloroform solvate at –160°

The structure and stereochemistry of phorbol has been determined by a three-dimensional X-ray analysis of phorbol 5-bromofuroate–chloroform solvate. The crystals are monoclinic, space group P21, with two molecules of C25H29O8Br,(CHCl3)0·8 in a unit cell of dimensions a= 10·54, b= 10·35, c= 13·80 A, β= 107·6°. The structure was solved by the heavy-atom method and refined by isotropic block-diagonal least-squares calculations from photographic data collected at –160°. The final value of R is 0·151. The molecules are held in the crystal by an intricate network of intermolecular hydrogen bonds involving C–H ⋯ O (C ⋯ O = 3·17 A), O–H ⋯ Br (O ⋯ Br = 3·17 A) and O–H ⋯ O bonds.Details are given of an unsuccessful attempt to solve the phorbol structure by multiple isomorphous replacement methods by use of iodobenzene–, 1,3-dibromobenzene–, and bromothiophen–phorbol triacetate solvate crystals.

Kinetics of the accumulation of free radicals in the radiolysis of solid substances

1. The limiting concentrations of alcohol radicals in irradiated crystal solvates do not depend on the radiation dose rate and decrease slowly with the temperature. 2. Under irradiation, the radicals are destroyed according to a first-order reaction, with a rate constant proportional to the dose rate. The temperature dependence does not obey an Arrhenius law. 3. The hypothesis is advanced that radiation decomposition of radicals and the nonuniformity of their distribution over the substance play a vital role in the process of accumulation.