Solvates of Indomethacin

Indomethacin is known to exhibit polymorphism and solvates, the different forms obtained do not exhibit the same solubility and their bioavailabilities are different. It is of a prime importance to identify the various polymorphic and solvated forms. This study was carried out by: DSC (different scanning calorimetry), TG (thermogravimetric analysis), X-ray diffraction and thermomicroscopy. Seven solvates, with acetone, benzene, dichloromethane, tetrahydrofurane, propanol, chloroform and diethylether, were isolated and studied. Their formulae have been determined by thermogravimetric analysis and their X-ray patterns on powder are presented, by DSC their behaviour after desolvation is recorded, the temperature and the enthalpy of fusion are measured and by this way the form obtained is deduced. This revised version was published online in July 2006 with corrections to the Cover Date.     

Solvates with anomalous low melting points

Single crystals of the N,N-dimethylformamide (DMF) solvate (1:1) of flurbiprofen (FBP) were grown for the first time and characterised by X-ray diffraction, IR spectrophotometry, DSC and solution calorimetric methods. The structure may be characterised as a layer-structure, where DMF double-sheets are arranged between FBP double-sheets. The FBP and DMF molecules are linked to each other by a hydrogen bond, which is formed between the hydroxyl group of FBP and the carbonyl group of DMF. The conformation of FBP molecules in the DMF solvate differs from analogous enantiomers in the unsolvated form. The differences are discussed from the point of view of the influence of the nature of the solvent on selective crystallisation of the enantiomers. A peculiarity of the solvate is its low melting point, 37.3±0.2°C, with respect to the unsolvated phase, 113.5±0.2°C. Based on solution enthalpies of the solvated and unsolvated phases dissolved in DMF, the difference in crystal lattice energies, 9.8 kJ mol^-1, was calculated and the difference in entropies, 33 J mol^-1 K^-1 estimated. A possible mechanism explaining the low melting point of the solvate is discussed. This revised version was published online in August 2006 with corrections to the Cover Date.     

Thermal Stability of C60-Methylnaphthalenes Solvates

The crystalline solvates containing fullerenes and (di)methylnaphthalenes were investigated by thermal analyses and X-ray diffraction methods. It was found that C₆₀ with (di)methylnaphthalenes forms two types of stable solvates: either at the molar ratio 1:2 decomposing at temperatures close to 100°C or at 1:1 molar ratio decomposing in the temperature range 120–214°C. Crystalline lattice and thermal stability of the solvates depends on the structure of the solvent molecules. The strong solute-solvent interaction is also manifested by the modification of the C₆₀ absorption spectra in solution. The results are discussed using semiempirical quantum chemistry methods. This revised version was published online in August 2006 with corrections to the Cover Date.     

Alcohol Solvates of Lanthanoid(III) Trifluoromethanesulfonates

After vacuum dehydration, a number of hydrated trivalent lanthanoid trifluoromethanesulfonates (“triflate”, “OTf” = F₃CSO₃), when recrystallized from various alcohol (ROH) solutions, yield solvates Ln(OTf)₃ · xROH, x = 3, 5 or 6. The following have been defined crystallographically (R/Ln/x): Me/La/3;Me/Gd/6; Et/Sm/3; Et/Gd/5 iPr/Nd,Sm/3. The Me/Gd/6complex, Gd(OTf)₃ · 6MeOH is a mononuclear/ionic form [(MeOH)₆Gd(O–OTf)₂](OTf), the gadolinium environment being octacoordinate, square‐antiprismatic with the O–OTf donors quasi‐trans on different faces of the coordination polyhedron; the Et/Gd/5 complex is neutral, molecular, mononuclear [(EtOH)₅Gd(O–OTf)₃], also with an octacoordinate, square‐antiprismatic coordination sphere, derivative of that of the methanol solvate. The remainder form one‐dimensional polymeric arrays, successive lanthanoid atoms linked by (μ‐O–OTf–O′)₃ triads, at either end of a tricapped trigonal prismatic array, the ROH molecules contributing the capping atoms. A (“baseline”) (re‐)determination of the “parent” Sm(OTf)₃ · 9H₂O is also recorded.     

Solid Solvates of C60 Compositions and Thermodynamics

Compositions of the solid solvates of C₆₀ with 1,2-dichlorobenzene and 1,3,5-trimethylbenzene were determined with the help of experimental procedures developed. Possible correlations between compositions and thermodynamic properties were discussed. This revised version was published online in July 2006 with corrections to the Cover Date.     

Halocyclopropenium-Halide Halogen-Bonded Ion Pairs and Their Hydrogen-Bonded Halide Solvates

A series of salts with a diaminohalocyclopropenium cation and halide anion [C₃(NⁱPr₂)₂X]X (X=Cl ([ 1 ]Cl) or Br ([ 2 ]Br) were isolated with a variety of solvates and, in one case, as a co-crystal with hydronium chloride. In particular, the initial synthesis of [ 1 ]Cl formed a co-crystal with hydronium and with CH₂Cl₂ solvate ([ 1 ]₂[OH₃Cl₃] ⋅ CH₂Cl₂) upon isolation from acetone/CH₂Cl₂. Recrystallization of this from chloroform gave a dichloroform adduct [ 1 ]Cl ⋅ 2CHCl₃, whereas treatment with ICl formed an octahalide cluster [ 1 ]₂I₄Cl₄. The bromine salt [ 2 ]Br ⋅ C₂H₄Br₂ was prepared by treatment of [ 1 ]Cl with dibromoethane and was isolated as a solvate. The hydronium cation was found as part of a hydronium trichloride cluster [OH₃Cl₃]²⁻ and this, along with a partially-deuterated analogue of [OHD₂Cl₃]²⁻ and [OD₃Cl₃]²⁻, was studied computationally and by mid- and far-infrared spectroscopy. Significant halogen bonds were found between 1 ⁺ or 2 ⁺ and chloride or bromide, respectively. On the other hand, the distance to the octahalide [I₄Cl₄]²⁻ is too long for a halogen bond. Hydrogen bonding from the halides to the halomethane solvates is also significantly stronger than to the cation isopropyl groups. The geometries formed at the halide ions with respect to the halogen bond and strong hydrogen bonds are pyramidal with approximately orthogonal angles.     

Thermochemical Investigation of Some Selected Solvates of Calix[4]resorcinarene

Lipophilic calix[4]resorcinarene derived from lauryl aldehyde forms stable crystalline solvates with a range of organic solvents: acetone, 1,4-dioxane, methylethylvketone, dimethylformamide, dimethylacetamide, N-methylpyrrolidinone, butyronitrile, methanol, 1,2-dimethoxybenzene and acetonitrile. The composition and thermal stability of these solvates was followed by thermogravimetric method, indicating a stoichiometry ranging from 1 to 3 (calixresorcinarene/solvent). The activation energy was evaluated for the selected solvates. Molecular modelling, using Hyperchem 5.0 software, was applied to the selected solvates. This revised version was published online in August 2006 with corrections to the Cover Date.     

Solvates of the cycloveratrylene tetramer as studied by solid state13CNMR

The cycloveratrylene tetramer was found to form well-defined solvates with chloroform and methylene chloride which were characterized by their solid state¹³CNMR spectra. Elemental analysis indicates the presence of two molecules of included solvent for every host molecule. Several distinct forms of the solvent-free tetramer were identified as well.     

Synthesis of Non-Aqueous Neptunium(III) Halide Solvates from NpO2

Two Np(III) halides, NpI₃(THF)₄ and NpBr₃(THF)₄, have been prepared and isolated in high yields as described in this work. Starting with neptunia (NpO₂), NpCl₄(DME)₂ was first generated in an updated, higher yielding synthesis than what was previously reported by using HCl/HF. This material was then reduced with KC₈, followed by subsequent ligand exchange, to generate NpBr₃(THF)₄ and NpI₃-(THF)₄. Full characterization by single-crystal X-ray crystallography, ¹H NMR spectroscopy and electronic absorption spectroscopy confirmed the molecular formulas and oxidation states. These trivalent materials are straightforward to synthesize and can be used as starting materials for non-aqueous Np(III) chemistry, obviating the need for rare and restricted Np metal and elemental halogens.     

Desolvaton of Zinc(II)tetra-tert-butylphthalocyanine Crystal Solvates as Probed by Thermogravimetry

Kinetic analysis of the thermal destruction of complexes of zinc(II)tetra-tert-butylphthalocyanine Zn(t-Bu)₄Pc with organic solvent molecules has been carried out. For ligands having high ionization potentials, long refluxing of solution is required for preparing biligand complexes. For molecular ligands whose ionization potentials do not exceed 9.2 eV, the composition of complexes with Zn(t-Bu)₄Pc is independent of the preparation parameters. The destruction of the Zn(t-Bu)₄Pc complexes with n-propylamine, diethylaniline, piperidine (1: 1, cold synthesis), diethylamine, morpholine, quinoline, or cyclopentanone (1: 2, hot synthesis; 1: 2, cold synthesis) obeys fist-order equations; for complexes with pyridine, 1,4-dioxane, DMF, cyclopentanone (1: 1, hot synthesis), 3-dimethylaminopropionitrile, or piperidine (1: 2, hot synthesis), destruction obeys second-order equations. The activation energies of thermal destruction for the first group of molecular complexes fall in the range from 89 to 370 kJ/mol; the rate-controlling stage is nucleation and growth. For the second group, the activation energies fall in the range from 160 to 640 kJ/mol; the rate-controlling stage is a chemical reaction.     

Formation of Solvates of Phosphotungstic and Silicotungstic Heteropoly Acids in the Course of Ethanol Vapor Absorption

Absorption of ethanol vapor with dehydrated solid phosphotungstic and silicotungstic heteropoly acids was studied by a gravimetric adsorption procedure at room temperature. The absorption isotherms are steplike and reflect stepwise formation of proton-alcohol associates in the acid lattices.     

Phase Separation of Ternary Liquid Systems Tetradecane-Cyclohexanone-Lanthanide(III) Nitrate Solvates with Tri-n-butyl Phosphate

The phase separation diagrams of ternary liquid systems tetradecane-cyclohexanone-lanthanide(III) nitrate solvates with tri-n-butyl phosphate {[Ln(NO₃)₃(TBP)₃, Ln is Nd or Sm} at T = 298.15 K were studied.     

Hydrogen Peroxide Solvates of 2,4,6,8,10,12‐Hexanitro‐2,4,6,8,10,12‐hexaazaisowurtzitane

Two polymorphic hydrogen peroxide solvates of 2,4,6,8,10,12‐hexanitro‐2,4,6,8,10,12‐hexaazaisowurtzitane (CL‐20; wurtzitane is an alternative name to iceane) were obtained using hydrated α‐CL‐20 as a guide. These novel H₂O₂ solvates have high crystallographic densities (1.96 and 2.03 g cm^?3, respectively), high predicted detonation velocities/pressures (with one solvate performing better than ?‐CL‐20), and a sensitivity similar to that of ?‐CL‐20. The use of hydrated materials as a guide will be important in the development of other energetic materials with hydrogen peroxide. These solvates represent an area of energetic materials that has yet to be explored.     

Different Spin‐State Behaviors in Isostructural Solvates of a Molecular Iron(II) Complex

The complex [FeL₂][BF₄]₂ ( 1 ; L=4‐(isopropylsulfanyl)‐2,6‐di(pyrazol‐1‐yl)pyridine) forms solvate crystals 1 ?solv (solv=MeNO₂, MeCN, EtCN, or Me₂CO). Most of these materials lose their solvent sluggishly on heating. However, heating 1 ?MeNO₂ at 450 K, or storing 1 ?EtCN under ambient conditions, leads to single‐crystal to single‐crystal exchange of the organic solvent for atmospheric moisture, forming 1 ?H₂O. Solvent‐free 1 ( 1 ?sf) can be generated in situ by annealing 1 ?H₂O at 370 K in the diffractometer or magnetometer. The different forms of 1 are isostructural (P2₁/c, Z=4) and most of them exhibit spin‐crossover (SCO) at 141≤T ≤212 K, depending on their solvent content. The exception is the EtCN solvate, whose pristine crystals remain high‐spin between 3–300 K. The cooperativity of the spin‐transitions depends on the solvent, ranging from gradual and incomplete when solv=acetone to abrupt with 17 K hysteresis when solv=MeCN. Our previously proposed relationship between molecular structure and SCO explains some of these observations, but there is no single structural feature that correlates with SCO in all the 1 ?solv materials. However, changes to the unit cell dimensions during SCO differ significantly between the solvates, and correlate with the SCO cooperativity. In particular, the percentage change in unit cell volume during SCO for the most cooperative material, 1 ?MeCN, is 10 times smaller than for the other 1 ?solv crystals.     

Phase Separation in Ternary Liquid Systems Containing Rare-Earth Metal(III) Nitrate Solvates with Tri-n-butyl Phosphate

Phase diagrams of ternary liquid systems constituted by tetradecane, tri-n-butyl phosphate, and lanthanide(III) nitrate solvates with tri-n-butyl phosphate {[Ln(NO₃)₃(TBP)₃], Ln = La, Pr, Nd, Sm} were studied at 298.15 K. The distribution of the components between the phases under stratification conditions was considered.     

Trans-Effect in Kinetics of Reactions of Mixed Solvates of Cu(II) Acetate with Tetraphenyltetrabenzoporphine in Organic Solvents

The kinetics of complex formation of tetraphenyltetrabenzoporphine with Cu(II) and Zn(II) acetates is studied in individual and mixed coordinating solvents on the basis of DMSO, DMF, and Py. The substantial increase in CuAc₂ reactivity in mixed solvents is explained by the trans-effect of ligands in composition of the metal solvate sphere.     

A reversed-phase high-performance liquid chromatographic method for the determination of zafirlukast in pharmaceutical formulations and human plasma

Zafirlukast (ZAF) is a leukotriene receptor antagonist used in the treatment of chronic asthma. In this study, a simple and sensitive reversed-phase, high-performance liquid chromatographic method was developed for the determination of ZAF in pharmaceutical formulations and human plasma. Piribedil was used as an internal standard. Analysis was carried out on a Nucleosil C18 100 A (150 mm x 4.6 mm id, 5 Vm) column with acetonitrile-pH 3.0 acetate buffer (70 + 30, v/v) as the mobile phase at a flow rate of 0.8 mL/min. The peak was detected by an ultraviolet detector set at a wavelength of 240 nm. The retention times were about 3.9 min for piribedil and 5.8 min for ZAF. The developed method was applied to the determination of ZAF in its pharmaceutical formulation and spiked human plasma. For quantification of ZAF in spiked plasma, proteins were precipitated with ethanol before chromatographic analysis. The calibration range was linear from 49.69-437.50 ng/mL in spiked plasma. The absolute recovery from spiked plasma was 98.73 +/- 0.42% at a concentration of 254.78 ng/mL of ZAF. No endogenous substances from plasma were found to interfere.     

H2O‐Catalyzed Route to Early Lanthanide Tribromide THF and DME Solvates from Oxides

A convenient one‐pot synthetic protocol towards THF and DME solvates of lanthanum and other early lanthanide tribromides was developed using the water‐catalyzed reaction of lanthanide(III) oxides with highly reactive Me₃SiBr in situ formed from commercially available disilane Si₂Me₆ and Br₂. This practical route allows to obtain the target lanthanum tribromide solvates [LaBr₃(thf)₄] ( 1a ) and [LaBr₃(dme)₂]₂ ( 1b ) as well as analogous early lanthanide molecular tribromide solvates [NdBr₃(thf)₄] ( 2a ), [NdBr₃(dme)₂] ( 2b ), [SmBr₃(thf)₂] ( 3a ), and [SmBr₃(dme)₂] ( 3b ) difficult to prepare by other solution‐based procedures. The molecular structure of 1b· 2CH₂Cl₂ was determined by an XRD study.     

Kinetic Substantiation of the Low Activity of Catalysts Based on Isopropanol Solvates of Gadolinium Chloride in the Polymerization of Isoprene

Kinetics and Catalysis - The kinetics was studied for the polymerization of isoprene under the action of a catalyst based on an isopropanol solvate of gadolinium chloride and triisobutylaluminum...     

Crystallization of Pseudopolymorphs of Some Gamboge Pigments. Pyridine,Dimethylformamide and Dimethylsulfoxide Solvates of Morellic Acid,Gambogic Acid and Guttiferic Acid

Abstract

Morellic acid, gambogic acid and guttiferic acid are related naturally-occurring xanthone pigments that yield X-ray quality crystals only from solvents like pyridine, dimethylformamide (dmf) and dimethyl sulfoxide (dmso). The structures of four of these crystals have been determined and are found to contain solvents of crystallization. The solvents hydrogen bond to the carboxyl groups with O—H…O/N motifs previously seen in other carboxylic acids. Distinctive, however, is the presence of an extended though somewhat diffuse array of C—H…O hydrogen bonds that aggregates the entire solute-solvent assemblage in a multi-point manner. Pyridine and dmf are able to mimic each other with respect to their hydrogen bond donating and accepting characteristics and in this respect play equivalent roles in their solvates with morellic acid and gambogic acid. Dmso is seen to self-associate in its guttiferic acid solvate. It is possible that these solvents with multiple hydrogen bonding donor and acceptor capability can act as hydrogen bond nucleators, providing just enough rigidity to the solutes to ensure crystallization.