A coumarin-based reversible two-photon fluorescence probe for imaging glutathione near N-methyl-D-aspartate (NMDA) receptors.

Glutathione (GSH) is known to play a key role in the modulation of the redox environment in N-methyl-d-aspartate (NMDA) receptors. Coumarin derivative 1 bearing cyanoacrylamide and ifenprodil moieties was synthesized and reported to monitor GSH near NMDA receptors. The cyanoacrylamide moiety allows probe 1 to monitor GSH reversibly at pH 7.4 and the ifenprodil group acts as a directing group for NMDA receptors. Two-photon fluorescence microscopy allows probe 1 to successfully sense endogenous GSH in neuronal cells and hippocampal tissues with excitation at 750 nm. Furthermore, the addition of H2O2 and GSH induced a decrease and an increase in fluorescence emission. Probe 1 can serve as a potential practical imaging tool to get important information on GSH in the brain.

Fluorescence Probe for Imaging N-Methyl-d-aspartate Receptors and Monitoring GSH Selectively Using Two-Photon Microscopy.

N-Methyl-d-aspartate (NMDA) is an excitotoxic amino acid used to identify a specific subset of glutamate receptors. The activity of NMDA receptors is closely related to the redox level of the biological system. Glutathione (GSH) as an antioxidant plays a key role with regard to modulation of the redox environment. In this work we designed and developed a GSH-specific fluorescent probe with the capability of targeting NMDA receptors, which was composed of a two-photon naphthalimide fluorophore, a GSH-reactive group sulfonamide, and an ifenprodil targeting group for the NMDA receptor. This probe exhibited high selectivity toward GSH in comparison to other similar amino acids. Two-photon fluorescence microscopy allowed this probe to successfully monitor GSH in neuronal cells and hippocampal tissues with an excitation at 750 nm. It could serve as a potential practical imaging tool to explore the function of GSH and related biological processes in the brain.

A naphthoimidazolium-cholesterol derivative as a ratiometric fluorescence based chemosensor for the chiral recognition of carboxylates.

Fluorescent chemosensors for sensing chiral molecules have been actively studied in recent years. In the current study, we report a naphthoimidazolium-cholesterol derivative (NI-chol 1) as a fluorescence based chemosensor for chiral recognition, in which the naphthoimidazolium serves not only as a fluorophore but also as a recognition moiety for anions via imidazolium (C-H)+-anion binding and the cholesterol unit acts as a chiral barrier. In particular, NI-chol 1 displayed unique and distinct ratiometric changes with Boc-d-Phe, on the other hand, Boc-l-Phe induced a negligible change. Furthermore, a distinct downfield shift (from 9.64 ppm to 9.96 ppm) of the imidazolium C-H peak was observed for Boc-d-Phe (5 eq.) with severe broadening, which indicates strong ionic hydrogen bonding between the C-H proton and the carboxylate.

A Two-Photon Fluorescent Probe for Imaging Endogenous ONOO- near NMDA Receptors in Neuronal Cells and Hippocampal Tissues.

In this study, we developed a two-photon fluorescent probe for detection of peroxynitrite (ONOO-) near the N-methyl-d-aspartate (NMDA) receptor. This naphthalimide-based probe contains a boronic acid reactive group and an ifenprodil-like tail, which serves as an NMDA receptor targeting unit. The probe displays high sensitivity and selectivity, along with a fast response time in aqueous solution. More importantly, the probe can be employed along with two-photon fluorescence microscopy to detect endogenous ONOO- near NMDA receptors in neuronal cells as well as in hippocampal tissues. The results suggest that the probe has the potential of serving as a useful imaging tool for studying ONOO- related diseases in the nervous system.