Crystal forms of a capsaicin derivative analgesic DA-5018

DA-5018 is a new capsaicin derivative and has analgesic effect. The objective of this work was to investigate the existence of polymorphs and pseudopolymorphs of DA-5018 and the transformation of crystal forms. Eight crystal forms of DA-5018 have been isolated by recrystallization and characterized by powder X-ray diffractometry (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TG). The PXRD and DSC patterns of the eight crystal forms were different respectively. In the dissolution studies in simulated intestinal fluid at 37±0.5°C, the solubility of Form 2 was the highest. And the solubility in water decreased in rank order: Form 2>Form 3>Form 1>Form 5>Form 7>Form 4>Form 6>Form 8. Eight crystal forms were shown to have a good physical stability at room temperature for 60 days.     

Thermoanalytical and spectroscopic studies on different crystal forms of nevirapine

This study is aimed at exploring the utility of thermoanalytical methods in the characterization of various polymorphs and solvates of nevirapine. The different forms obtained by recrystallization of nevirapine from various solvents showed morphological differences in SEM. The presence of polymorphic forms is suggested by single sharp melting endotherm different from original sample in DSC and no mass loss in TG, while appearance of desolvation peak in TG indicated the formation of solvates. The higher desolvation temperatures of all the solvates than their respective boiling point indicate tighter binding of solvent. The changes in the crystal lattice were demonstrated by X-ray powder diffraction studies. The enthalpy of fusion rule indicated the existence of monotropy in polymorphic pairs I/O and II/O, while I/II is enantiotropically related. The enthalpy of solution, an indirect measure of the lattice energy of a solid, was well correlated with the crystallinity of all the solid forms obtained. The magnitude of ΔH _sol was found to be ?14.26  kJ mol^?1 for Form V and ?8.29  kJ mol^?1 for Form O, exhibiting maximum ease of molecular release from the lattice in Form V. The transition temperature was found to be higher than the melting of both the forms except for polymorphic pair I/II providing complementary evidence for the existence of monotropy as well as enantiotropy in these polymorphic pairs.     

Role of structural and macrocrystalline factors in the desolvation behaviour of cortisone acetate solvates

A combined analysis of structural data and experimental results (DSC, temperature-resolved XRPD and hot stage optical microscopy) revealed that the dehydration mechanism of cortisone acetate monohydrate (CTA·H₂O) involves a collective and anisotropic departure of water molecules followed by a cooperative structural reorganization toward the anhydrous polymorph CTA (form 2). In spite of the lack of crystal structure data, it can be postulated from experimental data that thermal decomposition of the dihydrated form (CTA·2H₂O) and of the tetrahydrofuran solvate (CTA·THF) toward another polymorph (CTA (form 3)) also proceeds according to a cooperative mechanism, thus giving rise to probable structural filiations between these crystalline forms of CTA. The crystal structure determination of two original solvates (CTA·DMF and CTA·DMSO) indicates that these phases are isomorphous to the previously reported acetone solvate. However, their desolvation behaviour does not involve a cooperative mechanism, as could be expected from structural data only. Instead, the decomposition mechanism of CTA·DMF and CTA·DMSO starts with the formation of a solvent-proof superficial layer, followed by the partial dissolution of the enclosed inner part of crystals. Hot stage optical microscopy observations and DSC measurements showed that dissolved materials (resulting from a peritectic decomposition) is suddenly evacuated through macroscopic cracks about 30°C above the ebullition point of each solvent. From this unusual behaviour, the necessity to investigate rigorously the various aspects (thermodynamics, kinetics, crystal structures and physical factors) of solvate decompositions is highlighted, including factors related to the particular preparation route of each sample.     

Niclosamide methanol solvate and niclosamide hydrate: structure,solvent inclusion mode and implications for properties

Structural studies have been carried out of two solid forms of niclosamide [5‐chloro‐N‐(2‐chloro‐4‐nitrophenyl)‐2‐hydroxybenzamide, NCL], a widely used anthelmintic drug, namely niclosamide methanol monosolvate, C₁₃H₈Cl₂N₂O₄·CH₃OH or NCL·MeOH, and niclosamide monohydrate, denoted H_A. The structure of the methanol solvate obtained from single‐crystal X‐ray diffraction is reported for the first time, elucidating the key host–guest hydrogen‐bonding interactions which lead to solvate formation. The essentially planar NCL host molecules interact viaπ‐stacking and pack in a herringbone‐type arrangement, giving rise to channels along the crystallographic a axis in which the methanol guest molecules are located. The methanol and NCL molecules interact via short O—H...O hydrogen bonds. Laboratory powder X‐ray diffraction (PXRD) measurements reveal that the initially phase‐pure NCL·MeOH solvate readily transforms into NCL monohydrate within hours under ambient conditions. PXRD further suggests that the NCL monohydrate, H_A, is isostructural with the NCL·MeOH solvate. This is consistent with the facile transformation of the methanol solvate into the hydrate when stored in air. The crystal packing and the topology of guest‐molecule inclusion are compared with those of other NCL solvates for which the crystal structures are known, giving a consistent picture which correlates well with known experimentally observed desolvation properties.     

Triclabendazole: An Intriguing Case of Co‐existence of Conformational and Tautomeric Polymorphism

The crystal polymorphism of the anthelmintic drug, triclabendazole ( TCB ), is described. Two anhydrates (Forms I and II), three solvates, and an amorphous form have been previously mentioned. This study reports the crystal structures of Forms I ( 1 ) and II ( 2 ). These structures illustrate the uncommon phenomenon of tautomeric polymorphism. TCB exists as two tautomers A and B. Form I (Z′=2) is composed of two molecules of tautomer A while Form II (Z′=1) contains a 1:1 mixture of A and B. The polymorphs are also characterized by using other solid‐state techniques (differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), PXRD, FT‐IR, and NMR spectroscopy). Form I is the higher melting form (m.p.: 177 °C, ΔH_f=≈105±4 J g^?1) and is the more stable form at room temperature. Form II is the lower melting polymorph (m.p.: 166 °C, ΔH_f=≈86±3 J g^?1) and shows high kinetic stability on storage in comparison to the amorphous form but it transforms readily into Form I in a solution‐mediated process. Crystal structure analysis of co‐crystals 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 further confirms the existence of tautomeric polymorphism in TCB . In 3 and 11 , tautomer A is present whereas in 4 , 5 , 6 , 7 , 8 , 9 , 10 the TCB molecule exists wholly as tautomer B. The DFT calculations suggest that the optimized tautomers A and B have nearly the same energies. Single point energy calculations reveal that tautomer A (in Form I) exists in two low‐energy conformations, whereas in Form II both tautomers A and B exist in an unfavorable high‐energy conformation, stabilized by a five‐point dimer synthon. The structural and thermodynamic features of 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 are discussed in detail. Triclabendazole is an intriguing case in which tautomeric and conformational variations co‐exist in the polymorphs.     

The effect of water molecule on the thermal stability of lanthanide compounds with 1,3-benzeneditetrazol-5-yl

Six lanthanide compounds [Ln(H₂O)₉](m-BDTH)₃·9(H₂O) where Ln = La (1), and [Ln(H₂O)₈](m-BDTH)₃·9(H₂O) (m-BDTH₂ = 1,3-benzeneditetrazol-5-yl) where Ln = Lu (2), Yb (3), Er (4), Ho (5) and Y (6) were hydrothermally synthesized and characterized by elemental analyses, infrared spectra, powder X-ray diffraction (PXRD) and X-ray single crystal diffraction. PXRD indicates that 2–6 are isomorphous. Structural analyses reveal that 1 is coordinated by nine water molecules forming a capped-square antiprism, while 2–6 are coordinated by eight water molecules forming a simple square antiprismatic geometry. Effects of water molecules on thermal stability were also discussed by thermogravimetric (TG), DSC, and PXRD under different temperatures. TG analyses suggest that 1 loses lattice and coordinated water molecules with no diacritical boundary, and 6 removes lattice water molecules first and then coordinated water molecules. DSC and PXRD further confirm the consequence.     

Three solvates of a bis‐mesoionic fluorescent yellow pigment

p‐Phenylenebis(2‐oxo‐3‐phenyl‐1,2‐dihydropyrido[1,2‐a]pyrimidin‐5‐ium‐4‐olate), C₃₄H₂₂N₄O₄, is a bis‐mesoionic yellow pigment that shows fluorescence in the solid state. During a polymorph screening, single crystals of three solvates were grown and their crystal structures determined. Solvent‐free crystals were not obtained. A solvate with N‐methylpyrrolidone (NMP) and propan‐2‐ol, C₃₄H₂₂N₄O₄·2C₅H₉NO·C₃H₈O, (Ia), and an NMP trisolvate, C₃₄H₂₂N₄O₄·3C₅H₉NO, (Ib), crystallize with pigment molecules on inversion centres. The NMP/propan‐2‐ol mixed solvate (Ia) forms O—H...O hydrogen bonds between the different solvent molecules. In both structures, at least one of the solvent molecules is disordered. A third solvate structure, C₃₄H₂₂N₄O₄·0.5C₅H₉NO·C₄H₁₀O, (Ic), was obtained by crystallization from NMP and butan‐1‐ol. In this case, there are two symmetry‐independent pigment molecules, both situated on inversion centres. The solvent molecules are heavily disordered and their contribution to the scattering was suppressed. This solvate displays a channel structure, whereas the other two solvates form layer structures.     

Study of H-bonded assemblies of the solvates of anthracene derivatives: guest effect on the crystal symmetry and spectroscopic properties

Two solvates of title compound 1-acetyl-3-naphthyl-5-(9-anthryl)-2-pyrazoline solvate(ANNP) (1a) with chloroform (1b) and acetic acid (1c) and a single crystal of another title compound 1-acetyl-3-(4-chloro)phenyl-5-(9-anthryl)-2-pyrazoline (ACAP) (2a) and its adduct with phenol (2b) were afforded via solution growth technique. The structure of these solids were confirmed and verified by multiple techniques such as single crystal X-ray diffraction (SCXRD) analysis, PXRD, DSC/TGA and Infrared spectroscopy. Structural analysis indicates that guest inclusion results not only in stronger hydrogen bonds, but also in a larger number of favourable C–H?π interactions between ANNP/ACAP molecules. The solvates show symmetry reduction guest effect comparing with the guest free molecules of ANNP and ACAP. Moreover, characteristic changes have been observed in the Infrared bands of the solvates owing to the formation of hydrogen bonds between host–guest.     

Solvates of zafirlukast

The crystal structures of three solvates of zafirlukast [systematic name: cyclopentyl N‐{1‐methyl‐3‐[2‐methyl‐4‐(o‐tolylsulfonylaminocarbonyl)benzyl]‐1H‐indol‐5‐yl}carbamate], viz. the monohydrate, C₃₁H₃₃N₃O₆S·H₂O, (I), the methanol solvate, C₃₁H₃₃N₃O₆S·CH₃OH, (II), and the ethanol solvate, C₃₁H₃₃N₃O₆S·C₂H₅OH, (III), have been determined by single‐crystal X‐ray diffraction analysis. All three compounds crystallize in the monoclinic crystal system. Zafirlukast adopts a similar Z‐shaped conformation in all three solvates. The methanol and ethanol solvates are isostructural. The packing of the zafirlukast mol­ecules in all three crystal structures is similar and is expressed by hydrogen‐bonded mol­ecules that are related by translation, along (101) in (I) and along the b axis in (II) and (III). The methanol and ethanol solvent mol­ecules are hydrogen bonded to two mol­ecules of zafirlukast. The water mol­ecule, on the other hand, acts as a connector via hydrogen bonds between three mol­ecules of zafirlukast. The solvent mol­ecules are not released at temperatures below the melting points of the solvates.     

Polymorphism and solvatomorphism of bicalutamide

Single crystals of the crystallosolvate [bicalutamide + DMSO] with 1:1 stoichiometry were grown, and their structures were solved by X-ray diffraction methods. Polymorphic modifications I and II, the amorphous state, and the DMSO crystallosolvate of bicalutamide were prepared and thermochemistry of fusion processes was studied by DSC technique. The temperature dependence of the saturated vapor pressure of polymorphic form I was obtained and the thermodynamic characteristics of the sublimation process including the crystal lattice energy were calculated. The solution enthalpies of the forms under consideration and the crystallosolvate were acquired by the solution calorimetry procedure. The phase transition enthalpies estimated for form I, form II, and the amorphous state followed the rank order: form I— > form II, form I— > amorphous state, and form II— > amorphous state. The crystal lattice energy of polymorphic form II was determined using the results of sublimation and solution calorimetric experiments. The difference between the crystal lattice energy of the crystallosolvate and unsolvated phases was observed. The dissolution kinetics of forms I, II, the amorphous state, and DMSO solvate in water were investigated.     

Two furan‐2,5‐dicarboxylic acid solvates crystallized from dimethylformamide and dimethyl sulfoxide

Furan‐2,5‐dicarboxylic acid (FDCA) has been ranked among the top 12 bio‐based building‐block chemicals by the Department of Energy in the US. The molecule was first synthesized in 1876, but large‐scale production has only become possible since the development of modern bio‐ and chemical catalysis techniques. The structures of two FDCA solvates, namely, FDCA dimethylformamide (DMF) disolvate, C₆H₄O₅·2C₃H₇NO, (I), and FDCA dimethyl sulfoxide (DMSO) monosolvate, C₆H₄O₅·C₂H₆OS, (II), are reported. Solvate (I) crystallizes in the orthorhombic Pbcn space group and solvate (II) crystallizes in the monoclinic P space group. In (I), hydrogen bonds form between the carbonyl O atom in DMF and a hydroxy H atom in FDCA. Whilst in (II), the O atom in one DMSO molecule hydrogen bonds with hydroxy H atoms in two FDCA molecules. Combined with intermolecular S…O interactions, FDCA molecules form a two‐dimensional network coordinated by DMSO.     

Crystal structure of three solvated Alpinumisoflavones

Single crystals of alpinumisoflavone, C₂₀H₁₆O₅, {systematic name: 5-hydroxy-7-(4 hydroxyphenyl)-2, 2-dimethyl-2H, 6H-benzo [1, 2-b: 5, 4-b′]-dipyran-6-one}, solvated with water, methanol, and ethanol, have been obtained. The incorporation of the solvent molecules into the crystal structure creates a new short inter-molecular O–H···O and C–H···O contacts between the alpinumisoflavone moiety and its solvate molecule. The temperatures at which the solvated molecules lose their solvent molecules are 53, 54, and 65 °C for water, methanol, and ethanol, respectively. The observed temperatures at which the solvates efflorescence are reflective of the progressive increase in mass of the solvates from water to ethanol in the series. The benzopyrone moiety shows the usual planar conformation with the pyran ring deformed into a half-chair conformer as seen previously in the other analogous compounds with puckering parameters [Å], 0.2656(8), 0.3703(8), and 0.3957(9), respectively, for the water, ethanol, and methanol solvates. These are higher than the non-solvated alpinumisoflavone compound previously studied. The size of a substituent group proximal to the keto group has a more pronounced effect on the degree of puckering than substitution on the terminal phenyl ring. The attached phenyl ring shows consistent out-of-plane twist from the mean plane of the benzopyrone system as observed previously for this class of compounds. The observed dihedral angles are 30.26(3), 37.75(3), and 34.00(3)°, respectively, for the water, methanol, and ethanol solvates.     

An Intermolecular Hydrogen Bridge between a Porphyrinoid μ‐Oxido Diiron(III) Host and a Guest Water Molecule

μ‐Oxido‐bis[(hexaethyldimethyl‐2,2′‐bidipyrrinato)iron(III)] ( 1 ) crystallizes as a mixed dichloromethane/water solvate as black plates in the triclinic system, space group P\bar{1} , with a = 14.536(3), b = 16.194(3), c = 25.883(5) Å, α = 98.89(3)°, β = 91.28(3)°, γ = 90.56(3)°, and Z = 2. In the crystal structure two distinct solvates 1· CH₂Cl₂ and 1· H₂O are present in equal ratio. In both cases the solvent is found in direct vicinity of the Fe–O–Fe subunit and is located within a binding pocket formed by the two helically distorted tetrapyrroles. Whereas the dichloromethane molecule is oriented within this pocket as a dipole with the positive end pointing towards the oxygen atom of the Fe–O–Fe subunit, the water molecule forms a hydrogen bond with this site, supported by additional weak interactions with adjacent N‐donor atoms.     

Characterization and compatibility study of desloratadine

Desloratadine (DL) is a selective antagonist of the histamine H₁ receptor, which has been widely used to treat allergic symptoms, and stands out from other drugs in this therapeutic class because it does not cause sedative effects. In the present study, the physico-chemical properties of DL were fully characterized using six analytical techniques such as Differential Scanning Calorimetry (DSC), Thermogravimetric analysis (TG/DTG), Fourier transform infrared spectroscopy (FT-IR), Raman spectroscopy, Powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). The DSC curve shows a sharp endothermic event at 158.4 °C, and the TG/DTG curve presents two decomposition events between 178.4 and 451.9 °C. A compatibility study involving DL and nine pharmaceutical excipients generally used in pharmaceutical formulations was performed. Physical binary mixtures of DL with each excipient were prepared in a 1:1 (w/w) ratio. After preparation, the samples were analyzed immediately and the results reveal solid-state interaction with anhydrous lactose, microcrystalline cellulose, magnesium stearate, and stearic acid.     

Thermal studies of solvent exchange in isostructural solvates of a tetroxoprim-sulfametrole complex

Isostructural solvates of the 1:1 molecular complex between the antibacterial drugs tetroxoprim (TXP) and sulfametrole (SMTR) with formulae TXP·SMTR·CH₃OH (I), TXP·SMTR·C₂H₅OH (II) and TXP·SMTR·H₂O (III), were investigated to establish their propensity for guest exchange. Separate exposure of powdered (I), (II) and (III) to a saturated atmosphere of each solvent of the complementary solvate pair at ambient temperature resulted in reversible solvent exchange in all cases. DSC and TG were the methods of choice for monitoring the exchange processes since (I)-(III) have distinct onset temperatures of desolvation and characteristic mass losses. Interpretation of the results in terms of the known locations of the solvent molecules in crystals of (I)-(III) led to the conclusion that solvent exchange probably proceeds by a co-operative mechanism involving material transport through channels while the common host framework is maintained. This revised version was published online in July 2006 with corrections to the Cover Date.     

Multicomponent solid forms of the uric acid reabsorption inhibitor lesinurad and cocrystal polymorphs with urea: DFT simulation and solubility study

Lesinurad (systematic name: 2‐{[5‐bromo‐4‐(4‐cyclopropylnaphthalen‐1‐yl)‐4H‐1,2,4‐triazol‐3‐yl]sulfanyl}acetic acid, C₁₇H₁₄BrN₃O₂S) is a selective uric acid reabsorption inhibitor related to gout, which exhibits poor aqueous solubility. High‐throughput solid‐form screening was performed to screen for new solid forms with improved pharmaceutically relevant properties. During polymorph screening, we obtained two solvates with methanol (CH₃OH) and ethanol (C₂H₅OH). Binary systems with caffeine (systematic name: 3,7‐dihydro‐1,3,7‐trimethyl‐1H‐purine‐2,6‐dione, C₈H₁₀N₄O₂) and nicotinamide (C₆H₆N₂O), polymorphs with urea (CH₄N₂O) and eutectics with similar drugs, like allopurinol and febuxostat, were prepared using the crystal engineering approach. All these novel solid forms were confirmed by XRD, DSC and FT–IR. The crystal structures were solved by single‐crystal and powder X‐ray diffraction. The crystal structures indicate that the lesinurad molecule is highly flexible and the triazole moiety, along with the rotatable thioacetic acid (side chain) and cyclopropane ring, is almost perpendicular to the planar naphthalene moiety. The carboxylic acid–triazole heterosynthon in the drug is interrupted by the presence of methanol and ethanol molecules in their crystal structures and forms intermolecular macrocyclic rings. The caffeine cocrystal maintains the consistency of the acid–triazole heterosynthons as in the drug and, in addition, they are bound by several auxiliary interactions. In the binary system of nicotinamide and urea, the acid–triazole heterosynthon is replaced by an acid–amide synthon. Among the urea cocrystal polymorphs, Form I (P, 1:1) consists of an acid–amide (urea) heterodimer, whereas in Form II (P2₁/c, 2:2), both acid–amide heterosynthons and urea–urea dimers co‐exist. Density functional theory (DFT) calculations further support the experimentally observed synthon hierarchies in the cocrystals. Aqueous solubility experiments of lesinurad and its binary solids in pH 5 acetate buffer medium indicate the apparent solubility order lesinurad–urea Form I (43‐fold) > lesinurad–caffeine (20‐fold) > lesinurad–allopurinol (12‐fold) ? lesinurad–nicotinamide (11‐fold) > lesinurad, and this order is correlated with the crystal structures.     

Tautomeric polymorphism of the neuroactive inhibitor kynurenic acid

Kynurenic acid (KYN; systematic name: 4‐hydroxyquinoline‐2‐carboxylic acid, C₁₀H₇NO₃) displays a therapeutic effect in the treatment of some neurological diseases and is used as a broad‐spectrum neuroprotective agent. However, it is understudied with respect to its solid‐state chemistry and only one crystal form (α‐KYN·H₂O) has been reported up to now. Therefore, an attempt to synthesize alternative solid‐state forms of KYN was undertaken and six new species were obtained: five solvates and one salt. One of them is a new polymorph, β‐KYN·H₂O, of the already known KYN monohydrate. All crystal species were further studied by single‐crystal and powder X‐ray diffraction, thermal and spectroscopic methods. In addition to the above methods, differential scanning calorimetry (DSC), in‐situ variable‐temperature powder X‐ray diffraction and Raman microscopy were applied to characterize the phase behaviour of the new forms. All the compounds display a zwitterionic form of KYN and two different enol–keto tautomers are observed depending on the crystallization solvent used.     

Exploring a solvated dimer of Gefitinib: a quantitative analysis

Gefitinib or Iressa is an orally administered anilinoquinazoline used in cancer chemotherapy for the treatment of lung and breast cancer. It is reported to exist in two polymorphic forms, a stable form I and a metastable form II. Both of the forms belong to the triclinic P space group. In this work, we report the crystallization of Gefitinib to form a methanol solvate [systematic name: N‐(3‐chloro‐4‐fluorophenyl)‐7‐methoxy‐6‐[3‐(morpholin‐4‐yl)propoxy]quinazolin‐4‐amine methanol hemisolvate, C₂₂H₂₄ClFN₄O₃·0.5CH₃OH] that was theoretically and experimentally investigated. The unit cell is composed of two independent Gefitinib molecules (A and B) that form a stable molecular complex with methanol in the crystal lattice. To understand the crystal lattice stabilization, a combination of techniques, namely X‐ray diffraction, IR spectroscopy, thermogravimetric/differential scanning calorimetry (TG‐DSC), Hirshfeld surface analysis and CLP‐PIXEL methods were used. The analysis of the crystal structure of this dimer revealed a three‐dimensional isostructurality with the already reported form II. The A and B molecules are connected via trifurcated C—H…O and N—H…O hydrogen bonding. In addition, the presence of the methanol molecule stabilizes the crystal structure via C—H…O, N—H…O and C—H…Cl interactions between the two monomers. The IR analysis of the dimer has shown characteristic fingerprint values when compared to the commercial form. The TG‐DSC analysis of the solvated dimer is in good agreement with the patent reporting cocrystals of Gefitinib. Finally, theoretical calculations by the CLP‐PIXEL method and Hirshfeld surface and two‐dimensional (2D) fingerprint plot analysis were carried out in order to quantify the different intermolecular interactions and their energies in the crystal packing.     

Synthesis,crystal structure and characterization of manganese(III) complex containing a tetradentate Schiff base

N,N′-bis((2-hydroxyphenyl)(phenyl)methylidene)propane-1,2-diaminato-N,N′,O,O′)-(nitrato-O)-manganese(III) methanol solvate ([Mn(C₂₉H₂₄N₂O₂)(NO₃)CH₃OH]) was synthesized and characterized by FTIR, UV–Vis, TG–FTIR, TG/DSC, molar conductivity, magnetic moment measurement and single crystal X-ray analysis. In the structure, the Mn(III) ion adopts a distorted octahedral geometry with two nitrogen and two oxygen atoms from the Schiff base ligand in the equatorial plane, and the nitrate ion and methanol molecule in the axial position. The effects of organic solvents of various polarities on the UV–Vis spectra of the ligand and complex were investigated. The manganese(III) complex is easily dissolved in organic polar aprotic solvents and has moderate solubility in organic polar protic solvents.