Jia-Mei Chen

Virosaines A and B, two new birdcage-shaped Securinega alkaloids with an unprecedented skeleton from Flueggea virosa.

Two new Securinega alkaloids, virosaines A (1) and B (2), were isolated from the twigs and leaves of Flueggea virosa. The structures and absolute configurations were elucidated by means of NMR, X-ray diffraction, and CD analyses. Compounds 1 and 2 represent the first examples of Securinega alkaloids bearing a 7-oxa-1-azabicyclo[3.2.1]octane ring system, whose plausible biogenetic pathways were also proposed.

Crystal engineering approach to improve the solubility of mebendazole

An anthelmintic drug, mebendazole, shows a very low bioavailability (less than 10%) due to its poor aqueous solubility (0.035 mg/mL at 25 °C for form C). To improve its solubility, we combined a group of dicarboxylic acids with mebendazole via liquid-assisted grinding and reaction crystallization methods, and two salts with oxalic and maleic acids, as well as two co-crystals with malonic and glutaric acids, were obtained. These novel multi-component complexes were characterized by powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analyses and infrared spectra. The single-crystal structures of mebendazole-maleate salt, mebendazole-glutaric acid co-crystal, and mebendazole-monomethyl oxalate salt, in which one of the carboxyl groups of oxalic acid was esterified during the single-crystal growth in methanol, were determined. It was observed that mebendazole combines dicarboxylic acid/ester via a R22(8) hydrogen-bonding motif that involves a carbamyl benzimidazole and a carboxyl group, resulting in the 1:1 stoichiometry. The powder dissolution studies revealed that the apparent solubility of the complexes was significantly increased after the formation of co-crystals and salts.

Simultaneously enhancing the solubility and permeability of acyclovir by crystal engineering approach

Three acyclovir complexes including one salt with maleic acid, and two cocrystals with fumaric acid and glutaric acid, were prepared. The results of powder dissolution and in vitro skin permeation experiments revealed that both solubility and permeability of acyclovir were enhanced after the formation of cocrystals.

Direct synthesis of novel SiC@Al2O3 core-shell epitaxial nanowires and field emission characteristics

SiC@Al2O3 core-shell epitaxial nanowires have been synthesized via one-step process by simply heating evaporating Al source and C source on silicon substrate. Energy dispersive X-ray spectroscopy and transmission electron microscopy analysis of as-fabricated samples indicate that the core-shell nanowires consist of single-crystalline β-SiC core and thin cubic γ-Al2O3 shell. Epitaxial relationship is also observed between SiC core and Al2O3 shell. The corresponding growth model is proposed to describe the growth process of the core-shell epitaxial nanowires. Moreover, field emission measurement reveals the core-shell epitaxial nanowires have the excellent field emission property with low threshold electric field of 13.8 V μm−1.

Synthon polymorphs of 1 : 1 co-crystal of 5-fluorouracil and 4-hydroxybenzoic acid: their relative stability and solvent polarity dependence of grinding outcomes

Although polymorphism is a common phenomenon, the polymorphism of co-crystals is not studied extensively as compared to single-component molecules. Herein we report polymorphism in a co-crystal system comprising 5-fluorouracil, and 4-hydroxybenzoic acid with a 1 : 1 stoichiometry. The polymorphs were characterized by single-crystal and powder X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. Crystal structure analysis revealed different synthons of 5-fluorouracil and 4-hydroxybenzoic acid in two forms. The solvent-drop grinding experiments show a high degree of solvent polarity specificity. The theoretical and experimental methods suggest an enantiotropic relationship between the polymorphs.

Mechanism study on stability enhancement of adefovir dipivoxil by cocrystallization: Degradation kinetics and structure-stability correlation.

The purpose of this study is to determine the mechanism by which cocrystallization can enhance the stability of adefovir dipivoxil (AD), a diester prodrug of adefovir with known chemical stability problem. Three multi-component crystals of AD with biologically safe coformers, including gallic acid cocrystal hydrate (1:1:1), salicylate salt (1:1), and maleate salt (1:1) were prepared and characterized by thermal analysis, infrared spectroscopy, powder and single crystal X-ray diffraction. DVS measurements and stability tests were applied to evaluate the stability. The new crystalline phases exhibit improved stability compared to pure drug in the order AD gallic acid cocrystal>AD maleate>AD salicylate>AD form I. Degradation kinetics and structure-stability correlation studies demonstrate that the stability enhancement mechanism by cocrystallization involves (1) inhibition of hydrolysis of AD by replacement of drug-drug homosynthons by stronger drug-coformer heterosynthons at adenine fragments; (2) suppression of dimerization of AD by separation of adenine fragments by inserting coformers in crystal lattices; (3) further reducing rates of hydrolysis by forming hydrogen bonds with hydrate water at phosphoryl fragments. This study has important implications for use of cocrystallization approach to some easily degradable drugs in pharmaceutical.

Two polymorphs and one hydrate of a molecular salt involving phenazopyridine and salicylic acid

Two anhydrous polymorphs (AH-I, AH-II) and one monohydrate (MH) of a molecular salt involving phenazopyridine and salicylic acid, are reported. The charge-assisted N–H⋯O hydrogen bond provides the main driving force for the direct binding of the two compounds. AH-I is the stable anhydrous form with a low hygroscopicity, a high solubility and a simple preparation method.

Synthesis of Al4C3 nanowalls via thermal evaporation and potential application in vacuum microelectronic devices as cold electron emitters

Ceramic Al4C3 nanowalls were fabricated through a VS mechanism via a chemical vapor deposition (CVD) method. XRD (X-ray diffraction), Raman spectra, SEM (scanning electron micrograph) and TEM (transmission electron micrograph) methods were employed to characterize the product. The synthesized 2-D nanostructures are confirmed to be polycrystalline R-Al4C3 with a Al2O3 sheath outside the nanosheet. Field emission (FE) measurements show that the turn-on field (where the emission current reaches 10 μA cm−2) of the as-prepared sample is 6.0–7.0 V μm−1. According to several comparative experiments, we propose an atmosphere-controlled nanowall growth mechanism from self-assembling templates under a low-pressure environment to explain the growth process.

Phenazopyridine-phthalimide nano-cocrystal: Release rate and oral bioavailability enhancement

&NA; Both cocrystal and nanocrystal technologies have been widely used in the pharmaceutical development for poorly soluble drugs. However, the synergistic effects due to the integration of these two technologies have not been well investigated. The aim of this study is to develop a nano‐sized cocrystal of phenazopyridine (PAP) with phthalimide (PI) to enhance the release rate and oral bioavailability of PAP. A PAP–PI nano‐cocrystal with particle diameter of 21.4 ± 0.1 nm was successfully prepared via a sonochemical approach and characterized by powder X‐ray diffraction (PXRD), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and dynamic light scattering (DLS) analysis. An in vitro release study revealed a significant release rate enhancement for PAP–PI nano‐cocrystal as compared to PAP–PI cocrystal and PAP hydrochloride salt. Further, a comparative oral bioavailability study in rats indicated significant improvement in Cmax and oral bioavailability (AUC0 − ∞) by 1.39‐ and 2.44‐fold, respectively. This study demonstrated that this novel nano‐cocrystal technology can be a new promising option to improve release rate and absorption of poorly soluble compounds in the pharmaceutical industry. Graphical Abstract Figure. No caption available.

Pharmaceutical cocrystallization: an effective approach to modulate the physicochemical properties of solid-state drugs

Pharmaceutical cocrystallization affords an opportunity to modify the physicochemical properties of a solid-state drug without covalent modification of its molecular structure. This review presents an update on various applications of pharmaceutical cocrystallization with considerations on both cocrystals and salts, focusing on the property modification relevant to clinical efficacy and safety, and manufacturability of drugs. Some prominent examples of drug cocrystals/salts, which exhibit improved solubility and/or permeability and pharmacokinetics, stability and mechanic properties, are highlighted.