Fluorescence sensing with small molecular chemosensors is a versatile technique for elucidation of function of various biological substances. We now report a new fluorescent chemosensor for nucleoside polyphosphates such as ATP using metal-anion coordination chemistry. The chemosensor 1-2Zn(II) is comprised of the two sites of 2,2'-dipicolylamine (Dpa)-Zn(II) as the binding motifs and xanthene as a fluorescent sensing unit for nucleoside polyphosphates. The chemosensor 1-2Zn(II) selectively senses nucleoside polyphosphates with a large fluorescence enhancement (F/F(o) > 15) and strong binding affinity (K(app) approximately = 1 x 10(6) M(-1)), whereas no detectable fluorescence change was induced by monophosphate species and various other anions. The 'turn-on,' fluorescence of 1-2Zn(II) is based on a new mechanism, which involves the binding-induced recovery of the conjugated form of the xanthene ring from its nonfluorescent deconjugated state which was formed by an unprecedented nucleophilic attack of zinc-bound water. The selective and highly sensitive ability of 1-2Zn(II) to detect nucleoside polyphosphates enables its bioanalytical applications in fluorescence visualization of ATP particulate stores in living cells, demonstrating the potential utility of 1-2Zn(II).
Non-coordinative interactions between a metal ion and the aromatic ring of a fluorophore can act as a versatile sensing mechanism for the detection of metal ions with a large emission change of fluorophores. We report the design of fluorescent probes based on arene-metal-ion interactions and their biological applications. This study found that various probes having different fluorophores and metal binding units displayed significant emission redshift upon complexation with metal ions, such as Ag(I), Cd(II), Hg(II), and Pb(II). X-ray crystallography of the complexes confirmed that the metal ions were held in close proximity to the fluorophore to form an arene-metal-ion interaction. Electronic structure calculations based on TDDFT offered a theoretical basis for the sensing mechanism, thus showing that metal ions electrostatically modulate the energy levels of the molecular orbitals of the fluorophore. A fluorescent probe was successfully applied to the ratiometric detection of the uptake of Cd(II) ions and hydrogen sulfide (H2S) in living cells. These results highlight the utility of interactions between arene groups and metal ions in biological analyses.
Immune potentiators,termed adjuvants,trigger early innate immune responses to ensure the generation of robust and long-lasting adaptive immune responses of vaccines. Presented here is as tudy that takes advantage of as elfassembling small-molecule library for the development of an ovel vaccine adjuvant. Cell-based screening of the library and subsequent structural optimization led to the discovery of as imple,c hemically tractable deoxycholate derivative (molecule 6,a lso named cholicamide) whose well-defined nanoassembly potently elicits innate immune responses in macrophages and dendritic cells.F unctional and mechanistic analyses indicate that the virus-like assembly enters the cells and stimulates the innate immune response through Toll-like receptor 7(TLR7), an endosomal TLR that detects singlestranded viral RNA. As an influenza vaccine adjuvant in mice, molecule 6 was as potent as Alum, ac linically used adjuvant. The studies described here pave the way for anew approachto discovering and designing self-assembling small-molecule adjuvants against pathogens,i ncluding emerging viruses.
The concomitant detection of two biological events facilitates the highly selective and sensitive analysis of specific biological functions. In this article, we report an AND logic-gate-type fluorescent probe that can concurrently sense two biological events in living cells: H2 O2 accumulation and acidification. The probe exhibits a unique fluorescence sensing mechanism, in which a xanthene fluorophore is oxidatively transformed to a xanthone derivative by H2 O2 , thereby resulting in a clear dual-emission change. This transformation is significantly accelerated under weak acidic conditions, which enables the selective and sensitive detection of H2 O2 production in an acidic cellular compartment. This unique sensing property was successfully applied to the ratiometric fluorescence imaging of autolysosome formation in selective mitochondrial autophagy (mitophagy), which highlights the utility of this novel probe in autophagy research.
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