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Sepsis-associated encephalopathy (SAE) is an acute diffuse brain dysfunction, but its clinical treatment just focuses on antibiotics and supportive therapy, which fail to directly limit the development of SAE. Herein, this work highlights the development of pH-triggered small molecule nanodrugs self-assembled from tryptamine (Try)-cinnamaldehyde (CA) and fisetin for targeted SAE therapy. The imine linkage in Try-CA and acid-dependent protonation of Try and fisetin endow the nanodrugs with pH-triggered dynamic changes of particle sizes, surficial charges, and drug release. Moreover, the combined use of Try-CA and fisetin also endows the nanodrugs with superior antioxidative, anti-inflammatory and antibacterial capabilities compared to their individual use. These characteristics of the nanodrugs facilitate long-term circulation stability, effective penetration through BBB, selective accumulation in the brain, and target to central and peripheral focal areas, thereby achieving comprehensive treatment or relief of SAE. Thus, these attractive experimental results illuminate the enormous potential of such pH-triggered small molecule nanodrugs for targeted SAE therapy, advancing their use in clinics. [ABSTRACT FROM AUTHOR]

Fluorescein halogenated dyes are excellent photocatalysts for cross-dehydrogenation-coupled (CDC) reaction. In this paper, seven different halo-fluorescein dyes were selected to investigate the influence of heavy halogen atoms and proton concentrations on halo-fluoresceins for photocatalytic CDC reaction. The results showed that the heavy atoms directly affected intersystem crossing (ISC), which could act as a gatekeeper in the photoredox cycle and also affect photoinduced electron transfer (PET) process. Thus, the photocatalytic performance clearly increased in the following order: fluorescein FL (0.11 mol L−1•h−1)＜dibromo-fluorescein FL-2Br (0.19 mol L−1•h−1)＜diiodo-fluorescein FL-2I (0.29 mol L−1•h−1)＜tetrabromo-fluorescein FL-4Br (0.375 mol L−1•h−1)＜tetrabromo-tetrachloro-fluorescein FL-4Br–4Cl (0.53 mol L−1•h−1)＜tetraiodo-fluorescein FL-4I (0.58 mol L−1•h−1)＜ tetraiodo-tetrachloro-fluorescein FL-4I–4Cl (0.74 mol L−1•h−1). Furthermore, the visible light absorption of halogenated fluorescein dyes varied significantly with pH, thereby affecting their photocatalytic activity of CDC reaction. The dianionic FL-4I–4Cl could fully absorb light energy and exhibit excellent photocatalytic performance under mildly alkaline conditions (pH = 8), achieving a CDC reaction conversion rate of 99.92 %, which was 2.6 times higher than that of the lactone form of FL-4I–4Cl under acidic conditions (pH = 2). The halo-fluorescein dyes for photocatalytic CDC reaction. [Display omitted] • Halo-fluoresceins' heavy atom effect enhanced ISC and CDC photocatalysis. • pH-induced changes in halo-fluoresceins modulated photophysics and CDC photocatalytic efficiency. • A framework for halo-fluorescein photocatalyst design, highlighting pH and heavy atom effects. [ABSTRACT FROM AUTHOR]