Relating solvatochromism and solvatomorphism in organic dyes using high pressure.

By using complementary experimental methods including in situ high-pressure single-crystal X-ray diffraction and UV-Vis spectroscopy, the intricate connection between solvatochromism and solvatomorphism has been elucidated in a recent publication [Sobczak & Katrusiak (2024). IUCrJ, 11, 528-537]. The connection was demonstrated for an important pigment - Reichardt's dye - with potential applications in nonlinear optoelectronics and molecular pressure sensor development.

Structural insight into piezo-solvatochromism of Reichardt's dye.

To date, accurate modelling of the solvation process is challenging, often over-simplifying the solvent-solute interactions. The interplay between the molecular arrangement associated with the solvation process and crystal nucleation has been investigated by analysis of the piezo-solvatochromic behaviour of Reichardt's dye, ET(1), in methanol, ethanol and acetone under high pressure. High-pressure single-crystal X-ray diffraction and UV-Vis spectroscopy reveal the impact of solute-solvent interactions on the optical properties of ET(1). The study underscores the intricate relationship between solvent properties, molecular conformation and crystal packing. The connection between liquid and solid phases emphasizes the capabilities of high-pressure methods for expanding the field of crystal engineering. The high-pressure environment allowed the determination of the crystal structures reported here that are built from organic molecules fourfold solvated with ethanol or methanol: ET(1)·4CH3OH and ET(1)·4C2H5OH·H2O. The observed piezo-solvatochromic effects highlight the potential of ET(1) in nonlinear optoelectronics and expand the application of solvatochromic chemical indicators to pressure sensors.

Photoinduced Puffing with Large Volume Expansion and Photomechanical Motions induced by Topochemical [4+4] Reactions in Molecular Crystal Solvates.

In this work, we report the first example of two crystal solvates of an anthracene-benzhydrazide based molecule (Ant) that display very distinct photo-responsive behaviour when 365 or 405 nm or visible light is illuminated. For the first time, the crystal hydrate that has water molecule in the lattice (hereafter named as Ant-H2O) display fascinating puffing behavior with large volume expansion upto 50 % accompanied with surface modulation when illuminated with 405 nm light, a phenomenon very much similar to the rice or popcorn puffing by thermal treatment. Utilizing the properties of photoconverted Ant-H2O crystals, we have demonstrated their application in photoinduced enhanced liquid absorption using various liquids/solutions. The other crystal solvate having DMF in the crystal lattice (hereafter named as Ant-DMF) responds to 405 nm light by bending, twisting, chopping, jumping or splitting etc. The chopping of Ant-DMF crystal was also observed under ambient/white light but at a slower rate compared to 405 nm light. Single crystal X-ray diffraction study reveals that the photoinduced puffing and photomechanical effects of these materials are rooted to the topochemical [4+4] cycloaddition reaction between the anthracene moieties that facilitate molecular packing change assisted by the reconfiguration of intermolecular non-covalent interactions involving lattice trapped solvent molecules.

Conformational Screening of Arbidol Solvates: Investigation via 2D NOESY.

Understanding of the nucleation process's fundamental principles in saturated solutions is an urgent task. To do this task, it is necessary to control the formation of polymorphic forms of biologically active compounds. In certain cases, a compound can exist in a single polymorphic form, but have several solvates which can appear in different crystal forms, depending on the medium and conditions of formation, and show different pharmaceutical activity. In the present paper, we report on the analysis of Arbidol conformational preferences in two solvents of different polarities-deuterated chloroform and dimethyl sulfoxide-at 25 °C, using the 2D NOESY method. The Arbidol molecule has various solvate forms depending on the molecular conformation. The method based on the nuclear Overhauser effect spectroscopy was shown to be efficient in the analysis of complex heterocyclic compounds possessing conformation-dependent pseudo-polymorphism. It is one of the types of polymorphism observed in compounds forming crystal solvates. Combined use of NMR methods and X-ray data allowed determining of conformer populations of Arbidol in CDCl3 and DMSO-d6 which were found to be 8/92% and 37/63%, respectively. The preferred conformation in solution is the same that appears in stable crystal solvates of Arbidol.

Solvatomorphism of Moxidectin.

The solvatomorphism of the anthelmintic drug moxidectin is investigated, and a new solvatomorph with nitromethane is reported. Moreover, the hitherto unknown crystal structures of the solvatomorphs with ethanol and 2-propanol are reported and discussed. The thermal characterization of these solvatomorphs through variable-temperature powder X-ray diffraction analysis (VT-PXRD) is also described, providing new insights into the crystallochemistry of this active pharmaceutical ingredient.

Solvatomorphism Influence of Porous Organic Cage on C2H2/CO2 Separation.

Porous organic molecular (POM) materials can exhibit solvatomorphs via altering their crystallographic packing in the solid state, but investigating real gas mixture separation by porous materials with such a behavior is still very rare. Herein, we report that a lantern-shaped calix[4]resorcinarene-based porous organic cage (POC, namely, CPOC-101) can exhibit eight distinct solid-state solvatomorphs via crystallization in different solvents. This POC solvatomorphism has a significant influence on their gas sorption capacities as well as separation abilities. Specifically, the apparent Brunauer-Emmett-Teller (BET) surface area determined by nitrogen gas sorption at 77 K for CPOC-101α crystallized from toluene/chloroform is up to 406 m2 g-1, which is much higher than the rest of CPOC-101 solvatomorphs with BET values less than 40 m2 g-1. More interestingly, C2H2 and CO2 adsorbed capacities, in addition to the C2H2/CO2 separation ability at room temperature for CPOC-101α, are superior to those of CPOC-101ß crystalized from nitrobenzene, the representative of POC solvatomorphs with low BET surface areas. These results indicate the possibility of adjusting gas sorption and separation properties of POC materials by controlling their solvatomorphs.

Crystal structures of the anhydrous and two solvated forms of methyl 4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate.

Methyl 4-(4-fluorophenyl)-6-methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5-carboxylate, (I), was found to exhibit solvatomorphism. The compound was prepared using a classic Biginelli reaction under mild conditions, without using catalysts and in a solvent-free environment. Single crystals of two solvatomorphs and one anhydrous form of (I) were obtained through various crystallization methods. The anhydrous form, C13H13FN2O3, was found to crystallize in the monoclinic space group C2/c. It showed one molecule in the asymmetric unit. The solvatomorph with included carbon tetrachloride, C13H13FN2O3·0.25CCl4, was found to crystallize in the monoclinic space group P2/n. The asymmetric unit revealed two molecules of (I) and one disordered carbon tetrachloride solvent molecule that lies on a twofold axis. A solvatomorph including ethyl acetate, C13H13FN2O3·0.5C4H8O2, was found to crystallize in the triclinic space group P-1 with one molecule of (I) and one solvent molecule on an inversion centre in the asymmetric unit. The solvent molecules in the solvatomorphs were found to be disordered, with a unique case of crystallographically induced disorder in (I) crystallized with ethyl acetate. Hydrogen-bonding interactions, for example, N-H...O=C, C-H...O=C, C-H...F and C-H...π, contribute to the crystal packing with the formation of a characteristic dimer through N-H...O=C interactions in all three forms. The solvatomorphs display additional interactions, such as C-F...N and C-Cl...π, which are responsible for their molecular arrangement. The thermal properties of the forms were analysed through differential scanning calorimetry (DSC), hot stage microscopy (HSM) and thermogravimetric analysis (TGA) experiments.

New crystal forms and amorphous phase of sophoricoside: X-ray structures and characterization.

Sophoricoside, which is an isoflavone glycoside found in many plant species, has recently attracted attention because of its anti-fertility activity. One solvent-free form, two solvatomorphs and an amorphous phase of sophoricoside are reported for the first time. X-ray diffractometry, differential scanning calorimetry, thermal gravimetric analysis and Fourier-transform infrared spectroscopy were used to characterize the different forms. The results show that factors such as crystal symmetry, intermolecular arrangement, conformational flexibility, hydrogen-bonding interactions and solvent incorporation lead to different solid-state forms. An investigation of the transformations of the four forms showed that they can interconvert with each other under certain conditions. Amorphous phase and solvatomorphism were unstable but can improve the solubility of sophoricoside in water.

Screening, preparation and characterization of diosgenin versatile solvates.

Solvatomorphism occurred in diosgenin solvates. A series of solvates including DMSO, DMF, DMAC, Methanol of diosgenin were obtained and crystallized in order to compare their structures and properties in the solid state. Single-crystal X-ray diffraction was used to analyze the crystal structures and the solvent types and the stoichiometric ratio of the diosgenin solvates. Hirshfeld surface analyses, especially dnorm surface and fingerprint plots, were used to determine intermolecular interactions in the crystal structure. Powder X-ray diffraction, differential scanning calorimetry, thermogravimetric, Fourier transform Infrared spectroscopy were all used to characterize the diosgenin solvates. And the solvates transformation have been reported for the first time.

The methanol sesquisolvate of sodium naproxen.

The asymmetric unit of the methanol solvate of sodium naproxen, systematic name: sodium (2S)-2-(6-meth-oxy-naphthalen-2-yl)propano-ate methanol sesquisolvate, Na+·C14H13O3 -·1.5CH3OH, comprises two formula units of the mol-ecular salt and three methanol mol-ecules. One of the sodium cations exhibits a coordination number of six and is bonded to three carboxyl-ate O atoms and three methanol OH groups whereas the second sodium cation has a coordination number of seven, defined by five carboxyl-ate O atoms and two methanol OH groups. Both coordination polyhedra around the sodium cations are considerably distorted. The two types of cations are bridged into polymeric chains extending parallel to [010]. This arrangement is stabilized by intrachain O-H⋯O hydrogen bonds between methanol ligands as donor and carboxyl-ate O atoms as acceptor groups. The hydro-phobic 6-meth-oxy-naphthyl moieties flank the hydro-philic sodium oxygen chains into ribbons parallel to [010]. There are no noticeable inter-molecular inter-actions between these ribbons. One of the 6-meth-oxy-naphthyl moieties is disordered over two sets of sites in a 0.723 (3):0.277 (3) ratio.

Solvatomorphism-Induced 45 K Hysteresis Width in a Spin-Crossover Mononuclear Compound.

Spin-transition compounds are coordination complexes that can present two stable or metastable high-spin and low-spin states at a given temperature (thermal hysteresis). The width of the thermal hysteresis (difference between the maximum and minimum temperature between which the compound exhibits bi-stability) depends on the interactions between the coordination complexes within the compound, and which may be modulated by the absence or presence of solvent within the structure. The new compound [Fe(3-bpp)2 ][Au(CN)2 ]2 (1, 3-bpp=2,6-di-(1H-pyrazol-3-yl)pyridine) was synthesized and its properties were compared with those of the solvated compound [Fe(3-bpp)2 ][Au(CN)2 ]2 ⋅2 H2 O (1.H2 O) already described. 1 has a two-steps thermal hysteresis of 45 K, in contrast to the compound 1.H2 O which exhibits a gradual conversion without hysteresis. This hysteretic transition is accompanied by a reversible reconstructive structural transition and twinning. This stepped behaviour is also observed in the photomagnetic properties despite the low efficiency of photoswitching. Single-crystal photocrystallographic investigations confirm this low conversion, which we attributed to the high energy cost to form the high-spin structure, whose symmetry differs from that of the low-spin phase.

Mid-Infrared Spectroscopy of Pharmaceutical Solids.

It is now well established that infrared absorption spectroscopy is a powerful technique for the physical characterization of pharmaceutical solids. Besides being a preferred methodology for identification purposes, one can use trends in the energy values in the spectra as a means to study the solid-state properties of the system. FTIR spectra are often used to evaluate the type of polymorphism existing in a drug substance, can be very useful in studies of the water contained within a hydrate species, and are emerging as a technique of choice for the study of cocrystal systems. In this review, an overview of the theoretical foundations for infrared spectroscopy will be presented, which will be supported by illustrations as to how the methodology can be used.

Study on four polymorphs of bifendate based on X-ray crystallography.

Bifendate, a synthetic anti-hepatitis drug, exhibits polycrystalline mode phenomena with 2 polymorphs reported (forms A and B). Single crystals of the known crystalline form B and 3 new crystallosolvates involving bifendate solvated with tetrahydrofuran (C), dioxane (D), and pyridine (E) in a stoichiometric ratio of 1:1 were obtained and characterized by X-ray crystallography, thermal analysis, and Fourier transform infrared (FT-IR) spectroscopy. The differences in molecular conformation, intermolecular interaction and crystal packing arrangement for the four polymorphs were determined and the basis for the polymorphisms was investigated. The rotation of single bonds resulted in different orientations for the biphenyl, methyl ester and methoxyl groups. All guest solvent molecules interacted with the host molecule via an interesting intercalative mode along the [1 0 0] direction in the channel formed by the host molecules through weak aromatic stacking interactions or non-classical hydrogen bonds, of which the volume and planarity played an important role in the intercalation of the host with the guest. The incorporation of solvent-augmented rotation of the C-C bond of the biphenyl group had a striking effect on the host molecular conformation and contributed to the formation of bifendate polymorphs. Moreover, the simulated powder X-ray diffraction (PXRD) patterns for each form were calculated on the basis of the single-crystal data and proved to be unique. The single-crystal structures of the four crystalline forms are reported in this paper.

Isostructurality Among 5 Solvatomorphs of Betulin: X-Ray Structure and Characterization.

Betulin (BE), a triterpene found in many plant species, has recently attracted the attention of researchers because of its important physiological and pharmacological properties, such as anti-HIV and anticancer activities. Studies have revealed the solvatomorphism of BE (I with dimethyl sulfoxide and III with ethanol, named by author), which means more solvatomorphs may be obtained when different solvents are used during crystallization. After solid-form screening tests, 3 new solvatomorphs of BE with methanol (II), n-propanol (IV), and isopropanol (V) were obtained. In this work, 5 BE solvatomorphs were characterized by X-ray powder diffractometric, thermogravimetric, and Fourier transform infrared spectroscopic analyses. Single-crystal X-ray diffraction was used to analyze the X-ray structures of the compounds, and all 5 solvatomorphs were proven to be isostructral. Change in the crystal symmetry, intermolecular arrangements, stoichiometry, and hydrogen bonding interactions of the solvatomorphs resulted from solvent incorporation to the solvates. Solvatomorphs II, IV, and V, along with their single-crystal structures, were reported for the first time.

Geometry and Spin Change at the Heart of a Cobalt(II) Complex: A Special Case of Solvatomorphism.

Structural analysis and spectroscopic methods revealed a special case of solvatomorphism: hydrogen-bonding-induced geometry and spin change within a same N,O-(bis)chelate of cobalt(II). Solid-state structures are presented for both the tetrahedral and the solvated square-planar forms of the complex. Magnetic-moment measurements and ESR spectroscopy confirmed the high-spin state of the tetrahedral form (µeff =4.7 µB ) and the low-spin state of the square-planar solvatomorph. Specific hydrogen-bonding interactions between the solvent molecules and the complex chelate ring (O1⋅⋅⋅H-CHCl2 (d=2.26 Å, D=3.24 Å, θ=173°); O2⋅⋅⋅H-CHCl2 (d=2.22 Å, D=3.19 Å, θ=165°)) play a pivotal role in biasing the system toward the low-spin ground state.

Heteromorphism of Indomethacin Solvate and Characterization Method / 医药导报

Objective To systematically study solvatomorphism of indomethacin and provide a scientific basis for the quality control of the solvated impurities in this drug. Methods By changing the recrystallization solvent, solvent volume, recrystallization temperature, time and pressure, nine solvates and four non-solvated forms were discovered and prepared. The differential scanning calorimetry (DSC), thermogravimetric analysis ( TGA), X-ray powder diffraction ( PXRD) and infrared spectrometry (IR) were introduced for characterization analysis. Furthermore, the test of influencing factors was used to explore the stability of solvate crystal form and the crystal transformation rules among them. Results Nine solvates were prepared, which including two solvates reported for the first time in this work. Results showed that crystal forms of the 9 solvates have different types or proportions of crystal solvents according to the various results of DSC, TGA, PXRD and IR. Moreover, the nine solvates prepared in this work were metastable crystal forms which could be transformed to non-medicinal forms. Conclusion The composition, thermodynamic property and transformation rule of all the solvates are elucidated in this work. In addition, an effective method for qualitative or quantitative analysis of these solvates was established. The standard graphs and data were used as basic data and scientific basis for the solvate control in the manufacturing of indomethacin.

Studies on solvatomorphism of betulinic acid.

Five solvates of betulinic acid with dimethyl sulfoxide (I), methanol (II), ethanol (III), isopropyl alcohol (IV), and 2-butanol (V) have been described in this work. Methods of X-ray crystallography, thermal analysis, and Fourier transform infrared spectroscopy were introduced for solvatomorphic identifications and characterizations. The orientation of isopropenyl and carboxylic groups might differ because of single-bonding rotations. The incorporation of solvents resulted in changes of the crystal symmetry, intermolecular arrangements, stoichiometry, hydrogen bonding interactions, and so on. Adducted solvents contributed most to the stability of crystal lattices and led to the formation of crystalline forms. Solvates II-V with their single-crystal structures determined have been reported for the first time.