Application of an Electrochemical Microflow Reactor for Cyanosilylation: Machine Learning-Assisted Exploration of Suitable Reaction Conditions for Semi-Large-Scale Synthesis.

Cyanosilylation of carbonyl compounds provides protected cyanohydrins, which can be converted into many kinds of compounds such as amino alcohols, amides, esters, and carboxylic acids. In particular, the use of trimethylsilyl cyanide as the sole carbon source can avoid the need for more toxic inorganic cyanides. In this paper, we describe an electrochemically initiated cyanosilylation of carbonyl compounds and its application to a microflow reactor. Furthermore, to identify suitable reaction conditions, which reflect considerations beyond simply a high yield, we demonstrate machine learning-assisted optimization. Machine learning can be used to adjust the current and flow rate at the same time and identify the conditions needed to achieve the best productivity.

Homeostatic and pathogenic roles of GM3 ganglioside molecular species in TLR4 signaling in obesity.

Innate immune signaling via TLR4 plays critical roles in pathogenesis of metabolic disorders, but the contribution of different lipid species to metabolic disorders and inflammatory diseases is less clear. GM3 ganglioside in human serum is composed of a variety of fatty acids, including long-chain (LCFA) and very-long-chain (VLCFA). Analysis of circulating levels of human serum GM3 species from patients at different stages of insulin resistance and chronic inflammation reveals that levels of VLCFA-GM3 increase significantly in metabolic disorders, while LCFA-GM3 serum levels decrease. Specific GM3 species also correlates with disease symptoms. VLCFA-GM3 levels increase in the adipose tissue of obese mice, and this is blocked in TLR4-mutant mice. In cultured monocytes, GM3 by itself has no effect on TLR4 activation; however, VLCFA-GM3 synergistically and selectively enhances TLR4 activation by LPS/HMGB1, while LCFA-GM3 and unsaturated VLCFA-GM3 suppresses TLR4 activation. GM3 interacts with the extracellular region of TLR4/MD2 complex to modulate dimerization/oligomerization. Ligand-molecular docking analysis supports that VLCFA-GM3 and LCFA-GM3 act as agonist and antagonist of TLR4 activity, respectively, by differentially binding to the hydrophobic pocket of MD2. Our findings suggest that VLCFA-GM3 is a risk factor for TLR4-mediated disease progression.

Fluorescence behaviour of 2-, 3- and 4-amino-1,8-naphthalimides: effects of the substitution positions of the amino functionality on the photophysical properties.

The absorption and fluorescence spectra of a series of 1,8-naphthalimide derivatives incorporating the amino functionality at the 2-, 3- and 4-positions of the naphthalene ring (2APNI, 3APNI and 4APNI, respectively) were systematically investigated in various solvents and in the solid state. The fluorescence spectra of 2APNI were insensitive to solvent polarity and intermolecular hydrogen-bonding even in a protic medium such as methanol. Thus, 2APNI displayed blue fluorescence with a moderate fluorescence quantum yield (λFmax = 420-445 nm, ΦF 0.2-0.3) in the solvents investigated. In contrast, the fluorescence spectra of 3APNI and 4APNI were strongly solvent dependent showing positive solvatofluorochromism with large Stokes shifts. Upon increasing the solvent polarity, the fluorescence colours changed from blue in hexane (λFmax = 429 nm) to orange-yellow in methanol (λFmax = 564 nm) for 3APNI, and from blue in hexane (λFmax = 460 nm) to yellow in methanol (λFmax = 538 nm) for 4APNI. The fluorescence quantum yields of 3APNI and 4APNI decreased with increasing solvent polarity. In the solid state, APNIs displayed red-shifted fluorescence emission compared to that in solution (λFmax = 541 nm for 2APNI, 575 nm for 3APNI, and 561 nm for 4APNI) and the fluorescence quantum yields in the solid state were lower than those in solution.

Solvent-induced multicolour fluorescence of amino-substituted 2,3-naphthalimides studied by fluorescence and transient absorption measurements.

A series of amino-2,3-naphthalimide derivatives having the amino functionality at 1-, 5- and 6-positions (, and , respectively) were prepared, and their photophysical properties were systematically investigated based on the measurements of steady-state absorption and fluorescence spectra, fluorescence lifetimes as well as transient absorption spectra. The s efficiently fluoresced in solution, and the emission spectra appreciably shifted depending on the solvent polarity. displayed only a slight fluorescence red-shift upon increasing the solvent polarity. In contrast, and showed marked positive solvatofluorochromism with large Stokes shifts displaying multicolour fluorescence; the fluorescence colours of and varied from violet-blue in hexane to orange-red in methanol. and , thus, serve as micro-environment responding fluorophores. In methanol, the intensity of the fluorescence emission band of and significantly reduced. Based on the fluorescence quantum yields and lifetimes, and transient absorption measurements, it has been revealed that internal conversion from the S1 state of s to the ground state was accelerated by the protic medium, resulting in a reduction in their fluorescence efficiency, while intersystem crossing from the S1 state to a triplet state was not responsible for the decrease of fluorescence intensity.

The impact of the experience of childhood poverty on adult health-risk behaviors in Japan: a mediation analysis.

BACKGROUND: The experience of childhood poverty has a long-lasting, adverse impact on physical health outcomes in adulthood. We examined the mediating effects of adult socioeconomic status (SES) and social support on the association between childhood poverty and adult health-risk behaviors. METHODS: Cross-sectional data collected from Japanese community residents (N = 3836) were used. A binary indicator of the experience of childhood poverty was constructed by utilizing retrospectively assessed standard of living at age 15 and a set of parental SES variables. The associations of childhood poverty with smoking, lack of exercise, poor dietary habits, and excessive drinking at the time of survey were examined by logistic regression analysis. A mediation analysis was conducted to estimate the magnitudes of the mediating effects of adult SES and social support on these associations. RESULTS: Adult SES and social support together mediated 64.0, 29.4 and 30.6 % of the impacts of the experience of childhood poverty on smoking, lack of exercise, and poor dietary habits, respectively. Educational attainment had the largest mediating effect (58.2 %) on the impact of the experience of childhood poverty on smoking. CONCLUSIONS: The results suggest that interventions and policies for supporting children living in poverty should aim to enhance their future SES and provide better social support, as this might improve their overall health.