Aya Sakon

Mechanisms for Improved Hygroscopicity of L-Arginine Valproate Revealed by X-Ray Single Crystal Structure Analysis

Valproic acid is widely used as an antiepileptic agent. Valproic acid is in liquid phase while sodium valproate is in solid phase at room temperature. Sodium valproate is hard to manufacture because of its hygroscopic and deliquescent properties. To improve these, cocrystal and salt screening for valproic acid was employed in this study. Two solid salt forms, l-arginine valproate and l-lysine valproate, were obtained and characterized. By using dynamic vapor sorption method, the critical relative humidity of sodium valproate, l-arginine valproate, and l-lysine valproate were measured. Critical relative humidity of sodium valproate was 40%, of l-lysine valproate was 60%, and of l-arginine valproate was 70%. Single-crystal X-ray structure determination of l-arginine valproate was employed. l-Lysine valproate was of low diffraction quality, and l-arginine valproate formed a 1:1 salt. Crystal l-arginine valproate has a disorder in the methylene carbon chain that creates 2 conformations. The carboxylate group of valproic acid is connected to the amino group of l-arginine. Crystalline morphologies were calculated from its crystal structure. Adsorption of water molecules to crystal facets was simulated by Material Studio. When comparing adsorption energy per site of these salts, sodium valproate is more capable of adsorption of water molecule than l-arginine valproate.

Crystal-to-crystal photo-reversible polymerization mechanism of bis-thymine derivative

Solid-state photo-polymerization in crystals can produce stereoregular polymer molecules in environmentally friendly solvent-free systems. The polymerization mechanism of bis-thymine derivatives, such as dimethyl-3,3′-(3,3′-(butane-1,4-diyl)bis(5-methyl-2,4-dioxo-3,4-dihydropyrimidine-3,1(2H)-diyl))dipropanoate (1), known as unique molecules that can topochemically and reversibly polymerize in the crystalline state via [2 + 2]-cycloaddition reactions upon UV irradiation, remained to be solved. In this manuscript, the crystal structure of the polymeric photoproduct (1P) from a bis-thymine derivative 1 was determined using ab initio powder X-ray diffraction data and applied to investigate the polymerization mechanism of bis-thymine derivatives. The topochemical polymerization was found to be achieved via [2 + 2]-cycloaddition with the flexible butyl chain between thyminyl rings relieving the distortion of whole structure derived from cyclobutane formation. The crystal structure of 1P also showed that it polymerized stereoregularly with trans–anti cyclobutane conformations.

Crystal structure of γ-methyl l-glutamate N-carb­oxy anhydride

Solid-state polymerization behavior of amino acid N-carboxy anhydrides is explained by the very preferable molecular arrangement for the reaction in the crystal structure.

Crystal structure of γ-methyl L-glutamate N-carboxy anhydride

Solid-state polymerization behavior of amino acid N-carboxy anhydrides is explained by the very preferable molecular arrangement for the reaction in the crystal structure.

Vapochromism of Organic Cocrystal Induced by Crystalline Solvent Exchange

Vapochromic materials, which show color change induced by vapors, are expected to be applied to the sensing of volatile organic compounds or humidity. As for the metal complex crystals, many vapochromic crystals are reported, however, vapochromic organic crystals are not common. Therefore, it is important to find vapochromic organic crystals and to reveal the mechanistic aspects of structure transformations and color change based on the crystal structures. Pale brown Enoxacin-3,5-Diaminobenzoic Acid (ENO3,5DABA) dihydrate cocrystal changed to yellow on exposure to four kinds of alcohol solvent vapors (methanol, ethanol, 1-propanol, 2-propanol), and these yellow crystals returned to pale brown dihydrate crystal by humidity, which is called vapochromism. The single crystals recrystallized from water (pale brown) and methanol (yellow) are equal to the dihydrate and the methanol vapor applied forms, respectively, and their crystal structure determination revealed that the cocrystals are 1:1 salt of ENO and 3,5DABA. Surprisingly, in the methanol vapor applied from, the crystalline solvent was changed to 0.5-methanol-0.5-water solvate (composition is ENO:3,5DABA:MeOH:H2O=2:2:1:1). Thus the dihydrate cocrystal undergoes solvent exchange transformation on exposure to methanol vapor and the color changes from pale brown to yellow. Because the XRD patterns of the yellow 0.5-methanol-0.5-water solvate cocrystal and the forms exposed to other alcohol solvent vapors shows high similarity, they are isostructure crystals. The color change is caused by the π...π interaction formation between the ENO molecule and 3,5DABA molecule in alcohol solvate form via solvent exchange transformations.