‘AND’-based fluorescence scaffold for the detection of ROS/RNS and a second analyte

Abstract

Traditionally, fluorescence probes have focused on the detection of a single biomarker for a specific process. In this work, we set out to develop a number of fluorescence probes that enable the detection of a chosen analyte in the presence of reactive oxygen/nitrogen species (ROS/RNS). These fluorescence probes when activated result in the formation of the highly fluorescent pink dye, resorufin. Therefore, we have labelled these fluorescent probes as 'Pinkments'. Our first 'Pinkment' was shown to detect biologically relevant concentrations of ONOO- and have an excellent selectivity against other ROS/RNS. Pinkment-OH was developed to provide a core unit which could be easily functionalised to produce a range of 'AND' based fluorescence probes for the detection of ROS/RNS and a second analyte. For proof of concept, we synthesised Pinkment-OTBS and Pinkment-OAc. These 'AND'-based probes were successfully shown to detect ROS/RNS and F- or esterase, respectively.

Protein encapsulation: a new approach for improving the capability of small-molecule fluorogenic probes

“…25 Recently, we developed a series 'Pinkment' uorescent probes based on resorun. 26 We designed those 'Pinkment' probes to display 'AND'-logic in the presence of two different biologically important species. 26 In particular the Pinkment-OAc probe was designed to be activated by an esterase 'AND' H 2 O 2 but the probe exhibited poor solubility and low cell permeability limiting its biological applications.…”

Sensing Peroxynitrite in Different Organelles of Murine RAW264.7 Macrophages With Coumarin-Based Fluorescent Probes

“…The development of fluorescent tools to monitor reactive oxygen species (ROS), in particular ONOO − , has lead in recent years to the development of a variety of diagnostic small molecule fluorescent probes (Wu et al, 2017;Wang et al, 2018). Our group has exploited boronic acids and esters as a sensing motif for ONOO − (Odyniec et al, 2018;Weber et al, 2018;Wu et al, 2018). The fluorophore is masked by boronate esters which upon reaction with ONOO − results in fluorophore activation and the emission of a distinctive fluorescence signal (Scheme 1).…”

Boronate ester cross-linked PVA hydrogels for the capture and H2O2-mediated release of active fluorophores

“…Boronic acid and boronate esters have found widespread application in material-based applications, in part because of their propensity to bind reversibly with 1,2-and 1,3-diols. [9][10][11][12][13][14][15][16][17][18][19] Such chemistry has been demonstrated inter alia using commercially available PVA and diboronic acid crosslinkers to afford functional PVA-boronate hydrogels. [20][21][22][23][24][25] Boronic acids and boronate esters are well-known to undergo H 2 O 2 -mediated oxidative transformations to afford their corresponding phenol functionalites.…”

“…However, previous reports have demonstrated the greater reactivity of boronate-based fluorescent probes towards peroxynitrite (ONOO À ). 16,[36][37][38][39] Therefore, it is likely that if used in cellular applications, both PF1 and PT1 could have a role to play in the fluorescence imaging of both ONOO À and H 2 O 2 , albeit not necessarily in a species specific manner.…”