Dual-Channel Recognition of Human Serum Albumin and Glutathione by Fluorescent Probes with Site-Dependent Responsive Features

Abstract

Design of chemical probes with high specificity and responses are particularly intriguing. In this work, a fluorescent probe (M–OH–SO 3 ) with dual-channel spectral responses toward human serum albumin (HSA) is presented. By employing dinitrobenzenesulfonate as a recognition site as well as a fluorescence quencher, probe M–OH–SO 3 displayed weak fluorescence, which, nevertheless, exhibits extensive yellow (575 nm) and red (660 nm) fluorescence emissions toward HSA under excitations at 400 and 500 nm, respectively. Interestingly, M–OH–SO 3 displayed the best performance toward HSA with distinctly higher selectivity than that of its counterparts M–SO 3 , M–H–SO 3 , and M–F–SO 3 , which were prepared simply by modulating the functional group at the ortho position of the dicyanoisophorone core. Molecular docking results revealed that M–OH–SO 3 possesses the lowest binding energy among the tested derivatives and accordingly the strongest binding affinity. Probe M–OH–SO 3 showed a good linear relationship toward HSA in a range of 0.5–18 μM with a limit of detection of 35 nM. Cell imaging results demonstrated that probe M–OH–SO 3 could visualize the variation HSA levels in hepatocarcinoma cells. In addition, probe M–OH–SO 3 could also be employed for the recognition of glutathione through the cleavage of the dinitrobenzenesulfonate group along with an enhancement of emission at 575 nm. The site-dependent properties inspired a novel paradigm for design of fluorescent probes with optimized selectivity and responses.

Broad-Specificity Screening of Pyrethroids Enabled by the Catalytic Function of Human Serum Albumin on Coumarin Hydrolysis

“…The ability of HSA to promote various chemical transformations is related to the existence of two highly reactive residues Lys199 and Tyr411, which are strategically located at two sites (site I and site II) . To clarify the mechanism of HSA-catalyzed 1 hydrolysis, the catalytic sites were first explored by adding site-specific inhibitors (warfarin for site I and ibuprofen for site II , ) into HSA. As shown in Figures A,B and S14, as the concentration of warfarin or ibuprofen increases (0 to 60-fold higher than the concentration of 1 ), the capability of HSA to promote 1 hydrolysis is gradually suppressed, indicating that both sites play a role in the catalysis.…”

Human serum albumin-based supramolecular host–guest boronate probe for enhanced peroxynitrite sensing

“…Human serum albumin (HSA) is a biocompatible protein carrier suitable as a host for enhancing the imaging capacity of small-molecule probes, and as such a number of fluorescent dyes with HSA binding capacity have been developed. [35][36][37][38] Besides ONOO − sensing, we have demonstrated the applicability of HSA encapsulation for the enhanced fluorescence imaging of lysosomes based on receptor-directed endocytosis, 25 and intracellular glycosidases using super-resolution microscopy. 27 In addition, we have shown that this strategy could be extended to targeted fluorescence imaging of triple-negative breast cancer in vivo.…”

A novel near‐infrared fluorescent and colorimetric probe for selective detection of Ag+ and Hg2+

“…In order to obtain novel NIR fluorescent probes that are structurally simple and can be facilely synthesised, we abandon the coumarin moiety and resorted to the dicyanoisophorone fluorophore because its derivatives constitute a reservoir of NIR sensors with simple structures by straightforward modification of dicyanoisophorone. [56][57][58][59][60][61][62][63] In this article we envisage to design and synthesise a fluorescently activated NIR probe for the detection of Ag + /Hg 2+ based on intramolecular charge transfer (ICT) effect, by condensation of 4-diethylamino salicylaldehyde with dicyanoisophorone and subsequent esterification with phenyl chlorothionocarbonate. Dicyanoisophorone as a strong electron-withdrawing group and diethylamino as an electron donor were introduced into the NIR fluorescent probe (N-FP) to achieve large Stokes shift, strong luminescence and ICT effect, and the emission wavelength in NIR region.…”

“…Nevertheless, the chemosensor based on coumarin‐dicyanoisophorone dyad suffers from multistep synthesis. In order to obtain novel NIR fluorescent probes that are structurally simple and can be facilely synthesised, we abandon the coumarin moiety and resorted to the dicyanoisophorone fluorophore because its derivatives constitute a reservoir of NIR sensors with simple structures by straightforward modification of dicyanoisophorone 56–63 . In this article we envisage to design and synthesise a fluorescently activated NIR probe for the detection of Ag + /Hg 2+ based on intramolecular charge transfer (ICT) effect, by condensation of 4‐diethylamino salicylaldehyde with dicyanoisophorone and subsequent esterification with phenyl chlorothionocarbonate.…”