Effective gelation of water by an amphiphilic drug.

We report the formation of aqueous gels at low concentrations (less than 1 wt%) of an amphiphilic drug, a derivative of a chromane-2-carboxylic acid, at pH values 6.2-6.4. Formation of gels in the vicinity of the apparent pK(a) of the drug suggests that on the molecular level, the gels are composed of the aggregates of the ionized and protonated forms of the drug, which are stabilized by hydrogen bonding and hydrophobic interactions. In contrast, its identical analog, which differs by one methylene group, did not form gels or viscous solutions. We believe that additional steric hindrance, brought by the presence of the bulkier ethyl group (as compared to methyl group), prevents efficient interaction between the carboxylic acid groups thus hindering the gelation process.

Development of a pharmaceutical cocrystal of a monophosphate salt with phosphoric acid.

We report the first case of a pharmaceutical cocrystal formed between an inorganic acid and an active pharmaceutical ingredient (API), which enabled us to develop a stable crystalline and bioavailable solid dosage form for pharmaceutical development where otherwise only unstable amorphous free form or salts could have been used.

Enantiospecific synthesis of vicinal stereogenic tertiary and quaternary centers by combination of configurationally-trapped radical pairs in crystalline solids.

[reaction: see text] Photochemical irradiation of crystalline (2R,4S)-2-carbomethoxy-4-cyano-2,4-diphenyl-3-butanone 1 led to highly efficient decarbonylation reactions. Experiments with optically pure and racemic crystals showed that the intermediate radical pairs undergo a highly diastereo- and enantiospecific radical-radical combination that leads to the formation of two adjacent stereogenic centers in good chemical yield and with high chemical control. Reactions with chiral crystals occurred with quantitative enantiomeric yields and >95% diastereomeric yields.