Abstract
Biologically compatible fluorescent ion sensors, particularly those that are reversible, represent a key tool for answering a range of fundamental biological questions. We report a rationally designed probe with a 6′-fluoro spiropyran scaffold (5) for the reversible sensing of zinc (Zn2+) in cells. The 6′-fluoro substituent overcomes several limitations normally associated with spiropyran-based sensors to provide an improved signal-to-background ratio and faster photoswitching times in aqueous solution. In vitro studies were performed with 5 and the 6′-nitro analogues (6) in HEK 293 and endothelial cells. The new spiropyran (5) can detect exogenous Zn2+ inside both cell types and without affecting the proliferation of endothelial cells. Studies were also performed on dying HEK 293 cells, with results demonstrating the ability of the key compound to detect endogenous Zn2+ efflux from cells undergoing apoptosis. Biocompatibility and photoswitching of 5 were demonstrated within endothelial cells but not with 6, suggesting the future applicability of sensor 5 to study intracellular Zn2+ efflux in these systems.
Highlights
Fluorescent chemosensors capable of detecting, quantifying, and imaging specific molecules or ions are essential tools in cell biology and medical diagnostic imaging.[1,2] An important advance in this area would come with the development of reversible sensors that allow continuous or repeated measurement within a biological sample.[3]
These structures are somewhat problematic in biological systems because the photochromic characteristics of 6′-nitro-substituted spiropyrans are highly susceptible to the solvent environment.[14]
Zn2+ is a ubiquitous cellular ion that plays a critical role in the modulation of fundamental cellular processes, and an ability to sense and determine fluctuations of its cellular concentration is central to many biological and medical applications
Summary
Fluorescent chemosensors capable of detecting, quantifying, and imaging specific molecules or ions are essential tools in cell biology and medical diagnostic imaging.[1,2] An important advance in this area would come with the development of reversible sensors that allow continuous or repeated measurement within a biological sample.[3]. The most common spiropyran scaffold used in these applications contains a 6′-nitro group on the chromene moiety (see Scheme 1, 6).[13] This choice has a traditional basis, with these structures being readily prepared from nitro-substituted ohydroxy aromatic aldehydes and because the electron withdrawing NO2 substituent imparts high quantum yields for fluorescence-based sensing Despite widespread use, these structures are somewhat problematic in biological systems because the photochromic characteristics of 6′-nitro-substituted spiropyrans are highly susceptible to the solvent environment.[14] In general, the ring-closed spiro (SP) isomer is favored in nonpolar solvents, whereas the merocyanine isomer (MC) is Received: July 4, 2017 Accepted: September 8, 2017 Published: September 27, 2017.
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