Addressing the challenging field of chemoenzymatic dynamic kinetic resolution (DKR) of tertiary alcohols, for which so far only one example exists in the literature, we combined biocatalytic esterification and oxovanadium-catalyzed racemization, operating both steps in two different compartments of one reactor. The compartmentalization of the two heterogeneous catalysts, namely, immobilized lipase A from Candida antarctica (CAL-A) or its mutant and oxovanadium species on mesoporous silica, was achieved using a polydimethylsiloxane thimble, avoiding contact of the oxovanadium with water, thus maintaining the catalyst’s activity and thereby successfully improving the efficiency of the DKR. Utilizing the immobilized double mutant CAL-A V278S + S429G, the ester was obtained in 62% yield with excellent enantiomeric excess of >99% ee.

Nitric oxide (NO) is involved in numerous physiological activities including vasodilation, neurotransmission, and immune system regulation. NO-releasing small compounds are used to investigate the physiological activity of NO and to treat circulatory diseases, such as hypertension and angina pectoris. Among them, light-controllable NO releasers (caged NOs) enable spatiotemporal control of NO’s bioactivities. We previously reported NORD-1, a photoinduced electron transfer (PeT)-driven NO releaser that responds to red light. In the PeT-driven NO releasers, the NO release is triggered by photoinduced electron transfer from the N-nitrosoaminophenol to the light-harvesting dye. However, additional functionalization of PeT-driven NO releasers is required to enable introduction of tissue targeting groups or novel release triggers. As such, structure–activity relationship studies are needed to identify a suitable site for modification so as not to affect the NO-releasing efficiency of the PeT. Here, we investigated the functional impact of introducing substituents into the linker region connecting the light-harvesting antenna and NO releasing moiety. Although introduction of various substituents elicited only minor changes in NO-releasing efficiency and vasodilation activity, dialkylamino groups induced pH-dependent changes in NO-releasing reactivity. The structure–activity relationship of the linker moiety could provide fruitful information in further functionalizing PeT-driven NO releasers for biological applications.

Alkaline hydrolysis of the crude resin glycoside fraction from the leaves and stems of Ipomoea lacunosa L. (Convolvulaceae) yielded organic acid and glycosidic acid fractions. The organic acid fraction included n-decanoic and n-dodecanoic acids. Acidic hydrolysis of the glycosidic acid fraction yielded 3 monosaccharides (d-glucose, d-fucose, and l-rhamnose) and 2 known hydroxyl fatty acids (11S-hydroxytetradecanoic and 11S-hydroxyhexadecanoic acids). Treatment of the glycosidic acid fraction with trimethylsilyldiazomethane (in hexane) afforded 1 new glycosidic acid methyl ester (lacunosinic acid J methyl ester) and 6 known glycosidic acid methyl esters. Eight new resin glycosides (lacunosins V–XII) were isolated from the leaves and stems, along with 2 known resin glycosides. Their structures were determined using spectroscopic and chemical analyses. Three types of resin glycosides were identified: those with 18-membered macrolactone, those with 19-membered macrolactone, and those with non-macrolactone structures. All these compounds contained n-decanoic and n-dodecanoic acids as the organic acid components. Nine of the isolated resin glycosides were tested for cytotoxic activity against HL-60 human promyelocytic leukemia cells. One compound exhibited activity with an IC₅₀ value of 44.5 μM, while 3 compounds demonstrated moderate activity, with inhibition rates ranging from 53.5 to 68.7% at a concentration of 200 μM. In contrast, the remaining 5 compounds showed negligible effects even at 200 μM.

Characterizing the complex drug release profiles of nanoparticle-based pharmaceuticals is essential to ensure their efficacy and safety. In this study, we investigated the drug release of a representative liposomal drug, Doxil, to explore the applicability of the dynamic dialysis method (DDM), which offers the advantage of simple implementation. The DDM demonstrated considerable doxorubicin release from Doxil in response to increased ammonia concentration, supporting the hypothesis of ammonia-driven drug release from Doxil in tumor environments. To analyze the drug release of liposomal doxorubicin, we developed a mathematical model that (i) does not require strict sink conditions and (ii) avoids introducing numerous kinetic parameters. This model consolidates the complexities of drug partitioning into the liposomal membrane into a single apparent permeability constant. The release profiles of Doxil at 25°C and a physiological temperature of 40°C were successfully reproduced by the kinetic model, yielding reasonable permeability coefficients of 1.4 × 10⁻¹⁰ and 2.1 × 10⁻¹⁰ cm/s, respectively. Our model described the release behavior of the generic product Lipodox, yielding a permeability coefficient of 2.1 × 10⁻¹⁰ cm/s at 40°C, thereby confirming the utility of the DDM across products. Our results demonstrate that, with optimized conditions, the DDM can assess the drug release kinetics of liposomal doxorubicin. Furthermore, we believe that our study provides a valuable framework for evaluating and optimizing drug release phenomena in liposomal formulations.

Lipids, including fatty acids and phospholipids, play crucial roles in biological systems and are widely utilized in pharmaceutical and biomedical applications. However, their inherent hydrophobicity poses significant challenges for formulation and administration. In this study, we aimed to enhance the aqueous solubility of lipidic compounds by leveraging light-responsive molecular design. We synthesized azo-lipids by incorporating azobenzene units into a fatty acid and phosphatidylcholine, hypothesizing that light-induced trans–cis isomerization would improve solubility. The synthesized compounds exhibited reversible photoisomerization upon alternating UV (365 nm) and visible light irradiation, as confirmed by UV-vis spectroscopy and reverse-phase HPLC. The solubilization of these azo-lipids was quantified under UV-unirradiated and irradiated conditions. Azobenzene-incorporated phosphatidylcholine 2 exhibited a drastic increase in solubilization from 2.030 to 1008 µM (496-fold) after UV irradiation. This significant improvement was attributed to efficient photoisomerization and molecular bending in the cis, cis conformation, reducing intermolecular interactions. Our findings suggest that this on-demand aqueous solubilization strategy offers a novel approach for improving the handling, storage, and potential therapeutic administration of lipid-based compounds.