Olefin formation in palladium-catalyzed reactions is commonly rationalized by β-hydride elimination. However, under photoexcited conditions, palladium intermediates can differ substantially from those formed under thermal conditions, raising questions about the operative hydrogen removal pathway. In this study, we performed a computational mechanistic analysis of olefin formation in a ketyl radical-mediated photoexcited palladium-catalyzed reaction. Density functional theory calculations were carried out starting from a common intermediate to compare β-hydride elimination with hydrogen atom transfer (HAT). The lower-energy β-hydride elimination pathway requires ligand dissociation and the formation of an agostic intermediate before Cβ–H bond cleavage, whereas the HAT pathway proceeds more directly while retaining the phosphine coordination environment. Although the HAT pathway was consistently calculated to be energetically favored in the present system, β-hydride elimination can still become competitive when the preceding elementary steps are taken into account. These findings indicate that the operative hydrogen removal pathway in photoexcited palladium catalysis cannot be evaluated solely from the Cβ–H bond-cleavage step but must be considered together with the elementary steps required to reach each transition state.

Hot-melt extrusion (HME) is widely used to prepare polymer-based solid dispersions (SDs), but evaluating trace water-related changes in HME-prepared SDs remains challenging. In this study, time-domain NMR (TD-NMR) was applied to clotrimazole/Polyvinylpyrrolidone-co-vinyl acetate (PVPVA) SDs prepared by HME to evaluate T₂ relaxation behavior associated with low water content. The water content was determined by Karl Fischer titration and thermogravimetry–differential thermal analysis. T₂ relaxation curves were obtained by TD-NMR and analyzed using curve-fitting analysis and partial least squares (PLS) regression. Characteristic oscillatory behavior was observed in the T₂ relaxation curves of the low-moisture samples. Fitting analysis using a Gaussian function with an offset term showed that the offset ratio was associated with the water content measured by both methods. PLS regression analysis using the signal intensities constituting the T₂ relaxation curves as input variables predicted the Karl Fischer water content with relatively good accuracy. The analysis of variable importance in projection, which evaluates the contribution of each input variable to the PLS model, indicated that the time region of the T₂ relaxation curve contributing to the prediction corresponded to the region where oscillatory relaxation behavior was observed. These findings suggest that the oscillatory T₂ relaxation behavior was associated with water content within the present sample set and may reflect markedly restricted molecular mobility under low-moisture conditions, indicating that TD-NMR may be useful as a nondestructive approach for evaluating water-related physical property changes in the HME-prepared clotrimazole/PVPVA SDs.

A 2-methylquinoline-derived, O-benzoylhydroxylamine nitrene precursor underwent unproductive linker cleavage, whereas a related naphthalene analog did not. To clarify the origin of this structure-dependent behavior, we examined the conformations and excited states of the two precursors using density functional theory (DFT) and time-dependent DFT calculations. Both precursors preferentially adopted folded aryl/benzoate conformations, indicating that folding alone is not a sufficient discriminator. Instead, the quinoline precursor showed a lower and more allowed excitation than the naphthalene control, together with a mixed local/partial benzoate-directed electronic density redistribution in the selected excited states. Replacing the benzoyl group of the quinoline precursor with an acetyl group retained the high reactivity, giving the corresponding cyclized product in 83% yield after 3 h, with linker cleavage diminished significantly. These results support a qualitative model in which the folded benzoyl-containing precursor enables an off-pathway electronic response, whereas acyl-group tuning strongly suppresses the cleavage channel.

Excessive salt intake is a major risk factor for cardiovascular, cerebrovascular, and renal diseases, highlighting the need for strategies to reduce intestinal sodium absorption. Ammonium alginate (AAL) suppresses the postprandial increase in blood sodium levels and promotes fecal sodium excretion via ion-exchange and gel-mediated sodium entrapment in the gastrointestinal tract. However, its unpleasant odor and taste, along with its high viscosity upon contact with saliva, cause oral discomfort and limit its practical use in food and clinical settings. In this study, AAL granules were developed to improve their handling and sensory properties while preserving their sodium-sequestration functionality. Granulation with the AQshelax coating was performed using a fluidized-bed granulator, and the process parameters were optimized using a Box–Behnken experimental design. The optimized granules exhibited improved flowability and markedly reduced viscosity upon contact with saliva, resulting in enhanced sensory evaluation scores. In vitro sodium-binding assays demonstrated that the optimized granules retained a sodium-binding capacity comparable to that of unprocessed AAL powder. Furthermore, in salt-loaded mice, granulated AAL maintained its ability to suppress elevated blood sodium levels in vivo. These findings indicate that design-of-experiments-guided granulation successfully overcame key formulation limitations without compromising sodium-sequestration functionality, thereby enabling the practical dietary and clinical application of AAL as a sodium-excreting agent.

Fluorescent isoquinoline derivatives with structurally unique frameworks remain largely unexplored. In this study, a series of CF₂CF₂-containing tetracyclic isoquinoline derivatives bearing methoxy substituents at different positions was synthesized, and their photophysical properties were systematically investigated. Comparison with the corresponding diester analog revealed that replacement of the CH₂C(CO₂Et)₂ moiety with a CF₂CF₂ unit induced a bathochromic shift in the emission spectrum while having only a minor influence on the absorption properties. The position of the methoxy substituent markedly affected both the absorption and emission characteristics, with the 6-methoxy derivative exhibiting the largest Stokes shift owing to hypsochromically shifted absorption and bathochromically shifted emission. Solvatochromic studies demonstrated pronounced positive solvatochromism in the emission spectra, and protonation with trifluoroacetic acid resulted in further bathochromic emission shifts, suggesting the formation of a more polar excited state with charge-transfer character. Time-dependent density functional theory calculations, including natural transition orbital analysis and excited-state geometry optimization, revealed enhanced intramolecular charge-transfer character for the 6-methoxy derivative and suggested that the CF₂CF₂ unit contributes to stabilization of the excited state. These experimental and theoretical results provide new insight into the structure–photophysical property relationships of fluorinated tetracyclic isoquinolines and provide useful guidelines for the design of CF₂CF₂-containing fluorophores with tunable emission and acid-responsive properties.