Organic modification of layered zirconium phosphate/phosphonate for controlled release of therapeutic inorganic ions.

The present study aims to develop a layered zirconium phosphate/phosphonate (LZP) powder to control the release of therapeutic inorganic ions. Organically modified LZPs were successfully prepared with various contents of phenyl groups via a reflux method in an aqueous solution containing phosphoric and phenylphosphonic acids. Powder X-ray diffraction analysis and Fourier transform infrared spectroscopy revealed that the crystal structure of the synthesized LZP samples was identical to that of α-zirconium phosphate, even after modification. The amount of incorporated organic molecules increased with increasing molar fractions of phenylphosphonic acid in the starting composition, as determined from the thermal analysis. Cobalt ion (Co2+), a type of therapeutic inorganic ion, was incorporated into the organically modified LZP through treatment with an acetonitrile solution containing tetrabutylammonium ions, followed by treatment with an acetonitrile solution containing CoCl2. The amount of incorporated Co2+ depended on the concentration of the phenyl groups. Furthermore, the highest amount of Co2+ was incorporated in the sample (ZP-Ph-0.5) prepared with equimolar phosphoric/phenylphosphonic acid. The ZP-Ph-0.5 sample additionally showed the ability to incorporate copper or iron ions (Cu2+ or Fe3+). The incorporated ion, either Co2+ or Cu2+, was continuously released from the ZP-Ph-0.5 sample in a saline solution over a period of three weeks, whereas the release of Fe3+ was negligible. The quantity of Co2+ released was higher than that of Cu2+. The controlled release of Co2+ from the ZP-Ph-0.5 sample was also observed in a simulated body fluid that mimicked the ionic concentration of human blood plasma. These results confirm that a specific degree of phenyl modification makes LZP a candidate host material for releasing therapeutic inorganic ions.

Production of 5-hydroxymethylfurfural from Japanese cedar (Cryptomeria japonica) in an ionic liquid, 1-methylimidazolium hydrogen sulfate.

Production of 5-hydroxymethylfurfural (5-HMF) from Japanese cedar (Cryptomeria japonica) using an ionic liquid, 1-methylimidazolium hydrogen sulfate ([MIM]HSO4), was investigated. 5-HMF can be produced from C. japonica at temperatures above 120 °C. The maximum yield of 5-HMF was about 9 wt% after 15 min of treatment at 160 °C. However, 5-HMF produced in this process tended to decompose as the treatment continued. To avoid decomposition and to provide a means of recovering 5-HMF from [MIM]HSO4, three reaction systems based on [MIM]HSO4 were investigated: biphasic [MIM]HSO4/organic solvent system, [MIM]HSO4 with vacuum distillation, and [MIM]HSO4 with vacuum steam distillation. The [MIM]HSO4 reaction system combined with vacuum steam distillation was most effective. The maximum yield of 5-HMF was 17.5 wt% after treatment for 45 min at 160 °C. The combination of [MIM]HSO4 treatment with vacuum steam distillation is suitable for 5-HMF production because it is a one-pot process without the need for catalysts or pretreatment.

NMR-based quantitative studies of the conformational equilibrium between their square and folded forms of ascidiacyclamide and its analogues.

Ascidiacyclamide [cyclo(-Ile1,5-oxazoline2,6-D-Val3,7-thiazole4,8-)] (1) is a cytotoxic cyclic peptide from the ascidian, or sea squirt. Through structural analyses using asymmetric analogues [Xxx1: Ala (2), Val (3), Leu (4), Phe (5), cyclohexylalanine (6) and phenylglycine (7)], we previously showed 1 to exist in a conformational equilibrium between square and folded forms. In the present study, five new asymmetric analogues [Xxx1: 2-aminobutyric acid (8), 2-aminopentyric acid (9), tert-butylalanine (10), cyclohexylglycine (11) and tert-leucine (12)] were synthesized, and their structures were analyzed with X-ray diffraction and CD spectral measurements. Variable temperature 1H NMR measurements were performed to determine their equilibrium constants and their thermodynamic parameters. The use of two reference peptides made these quantitative studies possible. T3ASC, which contains three thiazole rings as a result of replacing oxazoline2 with thiazole, and dASC, in which the two oxazoline rings were deleted, were respectively used as square and folded reference peptides. The estimated parameters enabled more detailed discussion of the relationship between the bulkiness of substituents and the conformational free energies (ΔG°) of the peptides as well as the relationship between structure and cytotoxicity. The ΔG° values for peptides 1, 2, 3, 8, 9 and 11 decreased with decreases in the bulkiness of their substituents. We suggest that spontaneous folding is promoted as the bulkiness of substituents decreases. Peptides 7 and 12, which have large positive ΔG° values independently of temperature, did not exhibit spontaneous folding at any temperature; that is, their conformations were very stable in the square form. Peptides 4, 5, 6 and 10 had negative ΔG° values, despite their bulky substituents. Peptides with a positive ΔG° value showed cytotoxicity, and peptides with a negative ΔG° value showed reduced or no cytotoxicity. However, peptides 5 and 6 showed cytotoxicity equal to or stronger than 1. Those ten peptides except for 5 and 6 showed a clear structure-cytotoxicity relationship based on ΔG° values.