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The concise synthesis of C3-symmetrical [12]CPP-hexacarboxylate has been achieved through macrocyclization by the rhodium-catalyzed intermolecular cross-cyclotrimerization and subsequent reductive aromatization. C3-Symmetrical functionalization of CPP with highly polar alkoxycarbonyl groups enabled the structurally uniform nanotube assembly in the crystalline state through multiple hydrogen-bonding interactions giving a dimer followed by one-dimensional stacking.

By use of the reversible trimerization of boronic acids, the series of boroxine cages 3-mer, 6-mer, and 12-mer were constructed from rationally designed diboronic acids whose bond angles between two C-B bonds are 60°, 84°, and 117°, respectively. Boroxine cages 6-mer and 12-mer have 1.5 and 2.5 nm sized cavities, respectively.

The stable dihydrate crystalline phase (DH) of erythromycin A loses water upon heating to give the anhydrous phase I (AI). Further heating then results in a polymorphic transformation via the amorphous state (melt) to give another anhydrous phase II (AII). The anhydrous phases of AI and AII undergo hydration when increasing the humidity. The crystals of AI showed stoichiometric hydration to give DH, whereas the crystals of AII showed nonstoichiometric hydration to give the humidity dependent nonstoichiometric hydrate phase (NSH). The crystal structures of AI and AII were directly determined from powder X-ray diffraction data using the direct space strategy for the structure solution followed by Rietveld refinement. From the structural properties of AI and AII, aspects of the mechanism of the solid-state transformations of DH and the hydration behavior of AI and AII have been determined, and the importance of the hydrophilicity of the voids has been revealed.

Acyclovir (ACV) has two polymorphs, anhydrate 1 and anhydrate 2, and two hydrates, 2/3 hydrate and dihydrate. The effect of polymorphic transformation of ACV on the temperature and humidity was evaluated by simultaneous XRD-DSC and vapor sorption analysis. Each crystal structure of ACV was analyzed by single crystal analysis and powder X-ray diffraction analysis. On the polymorphic and pseudomorphic transformation, anhydrate 1 did not directly transform to anhydrate 2, but transform through 2/3 hydrate and dihydrate due to relative humidity and temperature. According to the molecular packing for four crystals, there are two packing manners for purine moiety. Anhydrate 1, anhydrate 2, 2/3 hydrate and dihydrate were packed in parallel, anti parallel, mixture of parallel–anti parallel and parallel manners, respectively. Base on the packing manner of ACV, it can be seen why the phase transformation occurs with readily or with difficulty. The thermodynamic relation of anhydrate form 1 and form 2 was evaluated by DSC and microcalorimetry. It was found that these two forms are monotropic forms, with anhydrate form I is stable form and it transform to a new form 3 at 443.2 K.

Lisinopril is extensively used as an ethical anti-hypertensive drug in its dihydrate crystalline phase, where this phase undergoes dehydration to the metastable monohydrate and anhydrous phases upon being heated. The mechanistic aspects of this two-step dehydration process are successfully established from their crystal structures, determined for the first time by ab initio powder X-ray diffraction (PXRD) analysis. Furthermore, the hydration process of the anhydrous phase was investigated by humidity-controlled PXRD and dynamic vapor sorption. Although the dehydration process of the dihydrate phase proceeded in two steps via the metastable monohydrate phase, the hydration process from the anhydrous phase to the dihydrate phase proceeded in a single step. The mechanisms of these different pathways for the dehydration and hydration processes were also established from the crystal structures.

Although acyclovir is one of the most important antiviral drugs used today, there are several problems with its physical properties. The aim of this study is to prepare cocrystals or amorphous complex of acyclovir using drug-excipient interactions to improve the physical properties of the drug, especially its dissolution rate and transdermal absorption. Screening for formation of cocrystals and the presence of amorphous acyclovir was conducted with various pharmaceutical excipinents, with the use of the solution-crystallization method and liquid-assisted cogrinding. The potential cocrystalline phase and the amorphized complex were characterized by PXRD, TG/DTA, IR, DSC and HPLC techniques. The screening indicated that acyclovir formed novel cocrystals with tartaric acid and was amorphized with citric acid. The acyclovir-tartaric acid cocrystal (ACV-TA cocrystal) structure was determined from synchrotron X-ray powder diffraction data. T(g) of the amorphous acyclovir-citric acid compound (ACV-CA amorphous) was determined by DSC. The initial dissolution rate of the ACV-TA cocrystals was considerably faster than that of anhydrous acyclovir. In vitro skin permeation of ACV-CA amorphous from polyethylene glycol (PEG) ointment was remarkably higher than that of the crystalline acyclovir. We successfully improved the physical properties of acyclovir by the cocrystallization and amorphization techniques, using pharmaceutical excipients.

5-Aminoisophthalic acid (AIPA) was found to undergo reversible color change on exposure to solvent vapors, which is called vapochromism, via pseudopolymorphic transformations between the pale-pink hemihydrate and the yellow anhydrous crystals. By exposing methanol, ethanol, or acetonitrile vapor on the hemihydrate crystal, the hemihydrate crystal transformed into a novel anhydrous crystal and the anhydrous crystal returned into the hemihydrate crystal under the existence of water vapor. X-ray structural analysis revealed that the AIPA molecule is in a zwitterionic form in the hemihydrate crystal whereas it is in a nonionic form in the anhydrous phase. Theoretical calculations revealed that the isomerization between nonionic and zwitterionic forms causes a solid-state color difference.

The crystalline state of 2-(2,4,6-triisopropybenzoyl)((S)-1-phenylethyl)benzamide (1) is known to undergo a diastereospecific Norrish type II photocyclization under UV irradiation, giving a single photoproduct (R,S)-cyclobutenol (2). Its polycrystalline form (2A) has a different X-ray diffraction pattern from the known polymorph 2B, which is obtained from recrystallization of the photoproduct. Such a polymorphic phenomenon, which is the result of a solid-state photoreaction, is, in itself, highly interesting and the structure of the photoproduct 2A should directly lead to the photoreaction mechanism. Thus, the crystal structure of 2A has been directly determined from the powder X-ray diffraction data. Interestingly, the crystal packing has been retained during the photoreaction process and, although the powder X-ray diffraction pattern is significantly different, there are only minor structural changes. The comparison of the crystal structures of 1 and 2A reveals the photoreaction mechanism. The lattice energy calculations of the polymorphic forms of 2A and 2B reveals that 2A, which is obtained only by the solid-state photoreaction, is less stable than 2B, which is why it is not reformed on recrystallization.

A scissors-shaped compound, 2,2-bis(4-hydroxy-3-phenylphenyl)-1H-indene-1,3(2H)-dione (1), has been prepared as a new host species for crystalline host–guest complexes. Compound 1 afforded complexes of 1:1 host-to-guest ratio with acetone, EtOH, and CH2Cl2, and a 2:3 complex with benzene. The crystal structures of these complexes were elucidated. In all four crystals, a side-by-side dimer linked by head-to-tail >C═O···HO– hydrogen bonds is formed and functions as the building unit of supramolecular networks. Except for (1)2(benzene)3, the complexes featured intermolecular carbonyl–carbonyl interactions resulting in all-planar antiparallel alignment with markedly short C···O distances (< 3.15 A). In (1)(EtOH), the four-centered interaction including two hydroxyl and two carbonyl groups was observed and designated as a quasi-bifurcated hydrogen bonding motif. Such a four-centered interaction has been observed to occur widely in crystal structures as proved by database searches from the Cambridge Structural ...

The extensively used antibacterial agent acrinol is known to form a monohydrate phase (H) on crystallization from water. We demonstrate here that acrinol also forms two anhydrous polymorphs, denoted form I (AI) and form II (AII). Polymorph AI is obtained directly on heating H, by a solid-state dehydration process, and polymorph AII is obtained subsequently from AI, by a polymorphic transformation. The crystal structures of AI and AII have been determined directly from powder X-ray diffraction data, employing the direct-space genetic algorithm technique for structure solution, followed by Rietveld refinement. From the structural properties of AI and AII, mechanistic aspects of the dehydration process and the polymorphic transformation have been established. From measurements of initial dissolution rates and enthalpies of dissolution, AII is assigned as the thermodynamically stable polymorph, with a monotropic relationship between AI and AII. The hydration properties of AI and AII differ significantly, with...

A new co-crystal (phase H) of 5-methyl-2-pyridone (5MP) and trimesic acid (TMA) has been prepared by grinding a methanol solvate co-crystal (phase M) of 5MP and TMA under ambient conditions. Powder X-ray diffraction indicates that the new co-crystal phase H is structurally different from the methanol solvate co-crystal (phase M) and an unsolvated co-crystal (phase U) of 5MP and TMA reported previously. In the present work, the crystal structure of the new phase H has been determined directly from powder X-ray diffraction data, allowing insights to be gained regarding the mechanism of the transformation from M to H. The structural analysis reveals that phase H is a hydrate of 5MP and TMA, and thus the transformation from M to H is a solvent exchange process. The rate of this process is shown to be accelerated significantly by grinding. Further vapour induced transformations have been investigated for phases M, H, and U, and insights regarding transformation mechanisms have been established from considerati...

The reagent Me3Si(C6F5) was used for the preparation of a series of perfluorinated, pentafluorophenyl-substituted 3,6-dihydro-2H-1,4-oxazines (2–8), which, otherwise, would be very difficult to synthesize. Multiple pentafluorophenylation occurred not only on the heterocyclic ring of the starting compound 1 (Scheme), but also in para position of the introduced C6F5 substituent(s) leading to compounds with one to three nonafluorobiphenyl (C12F9) substituents. While the tris(pentafluorophenyl)-substituted compound 3 could be isolated as the sole product by stoichiometric control of the reagent, the higher-substituted compounds 5–8 could only be obtained as mixtures. The structures of the oligo(perfluoroaryl) compounds were confirmed by 19F- and 13C-NMR, MS, and/or X-ray crystallography. DFT simulations of the 19F- and 13C-NMR chemical shifts were performed at the B3LYP-GIAO/6-31++G(d,p) level for geometries optimized by the B3LYP/6-31G(d) level, a technique that proved to be very useful to accomplish full NMR assignment of these complex products.

A metastable colored species from the photochromic reaction of trans-biindenylidenedione, which only proceeds in the crystalline state, has been directly observed by in situ crystal structure analysis method. The reaction mechanism and observed color change have also been confirmed from the theoretical calculation and the spectral measurement.

Ultraviolet irradiation of a salt crystal of 4-(2,4,6-triisopropylbenzoyl)benzoic acid with ( S )-phenylethylamine promoted single-crystal-to-single-crystal photocyclization to give an enantiopure ( R , R )-cyclopentenol and almost racemic cyclobutenol. The reaction paths were elucidated by X-ray crystallographic analysis of the crystal before and after irradiation.

Coordination polymers have significant potential for new functionality paradigms due to the intrinsic tunability of both their electronic and structural properties. In particular, octacyanometallate-bridged coordination polymers have the extended structural and magnetic diversity to achieve novel functionalities. We demonstrate that [Mn(H2O)][Mn(HCOO)(2/3)(H2O)(2/3)](3/4)[Mo(CN)8]·H2O can exhibit electrochemical alkali-ion insertion/extraction with high durability. The high durability is explained by the small lattice change of less than 1% during the reaction, as evidenced by ex situ X-ray diffraction analysis. The ex situ X-ray absorption spectroscopy revealed reversible redox of the octacyanometallate. Furthermore, the solid state redox of the paramagnetic [Mo(V)(CN)8](3-)/diamagnetic[Mo(IV)(CN)8](4-) couple realizes magnetic switching.

Guest-induced self-assembly of a macrocyclic boronic ester containing photochromic diarylethene units is realized and this macrocycle showed high quantum yield of photoisomerization due to favourable conformational constraint.

The purpose of this study was to develop a sensitive system for detection of crystalline drug substances in intact pharmaceutical tablets by X-ray powder diffractometry (XRPD), using synchrotron X-rays. Fenoprofen calcium dihydrate was used as a model compound. The wavelength and path length of X-rays from synchrotron radiation were optimized in order to maximize the potential of the synchrotron radiation. The optimum wavelength and path length for the measurement of fenoprofen calcium dihydrate were found to be 0.69817 A and 6.0 mm, respectively, based on theoretical calculations. Under the optimized conditions, a limit of quantification of 0.05% (RSD = 9.4%, n = 3) and a limit of detection of 0.02% (RSD = 17.3%, n = 3), results which are approximately 102 times as sensitive as those obtained using conventional XRPD instruments, were achieved. The technique was also applied to fenoprofen calcium dihydrate detection in intact film-coated tablets, which contained Ti in the coating film, and a limit of detection of 0.02% was again attained.

The purpose of the current study was to evaluate the rate of the pseudo-crystalline transformation of thiamine hydrochloride form I to form II depending on the temperature and humidity. Changes in the appearance and weight of form I crystals were observed under humidified conditions using a water vapor sorption system equipped with a CCD camera. The form I crystals and tablets were stored under various temperature and humidity conditions (the saturation salt desiccator method), and the pseudo-crystalline transformation was observed using X-ray powder diffractometry with our laboratory equipment for drug substances and using synchrotron X-ray powder diffractometry for tablets. It was confirmed that the activation energy in the pseudo-crystalline transformation rate from form I to form II was dependent on humidity, and the calculated values were 121—155 kJ/mol at 70—90% relative humidity. Moreover, when thiamine hydrochloride was formulated as tablets, it was confirmed that the transformation rate was slower compared with the drug substances alone. The pseudo-crystalline transformation rate therefore declined after formulation in tablet form, perhaps due to the shielding effects of thiamine hydrochloride crystal from contact with water molecules by excipients, compaction, etc.

The methanol solvate crystalline phase (M) of benzene-1,2,4,5-tetracarboxylic acid transforms selectively to a hydrate phase (H) or a non-solvate phase (N) depending on the presence of atmospheric water vapour; knowledge of the crystal structures of M and N, determined here using single-crystal and powder X-ray diffraction, respectively, yields insights into mechanistic aspects of the solid-state transformations.

The title salt, K+·C8H8NO5− [systematic name: potassium (2R,5R,Z)-3-(2-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo[3.2.0]heptane-2-carboxylate], a widely used β-lactam antibiotic, is usually chemically unstable even in the solid state owing to its tendency to be hydrolysed. In the crystal structure, the potassium cations are arranged along the a axis, forming interactions to the carboxylate and hydroxy groups, resulting in one-dimensional ionic columns. These columns are arranged along the b axis, connected by O—H...O hydrogen bonds, forming a layer in the ab plane.

Thermodynamic stability order of tolbutamide between polymorphs was evaluated using calorimetry and spectroscopic analysis. The heat of solution (DeltaH) of Forms I-III measurements were carried out in dimethylsulfoxide between 298.2K and 319.2K. It was found that the DeltaH of Forms II and III was increased nearly parallel with a temperature rise. However, change of the DeltaH of Form I with a temperature rise was not in correspondence with that of other forms. Solubility data confirmed the change in DeltaH of Form I around 308.2K. XRD-DSC measurement of Form I detected a polymorphic transformation (Form I(L)--unknown form) at 311K. Obtained data suggested that the new crystal form (Form I(H)) would exist above 311K, and the order of thermodynamic stability was "Form IIIForm I(L)Form II" below the transition temperature, on the other hand, the order was changed in "Form I(L) and Form I(H)Form IIIForm II" above the transition temperature. The crystal structure of Form I(H) was determined by measurement of PXRD pattern on BL19B2 at SPring-8, and the change in the solid-state NMR spectrum confirmed the transformation of the crystal structure of Form I(L).

The application of a two-dimensional photon-counting detector based on a micro-pixel gas chamber (µ-PIC) to high-resolution small-angle X-ray scattering (SAXS), and its performance, are reported. The µ-PIC is a micro-pattern gaseous detector fabricated by printed circuit board technology. This article describes the performance of the µ-PIC in SAXS experiments at SPring-8. A dynamic range of >105 was obtained for X-ray scattering from a polystyrene sphere solution. A maximum counting rate of up to 5 MHz was observed with good linearity and without saturation. For a diffraction pattern of collagen, weak peaks were observed in the high-angle region in one accumulation of photons.