Design synthesis and applications of fluorescent probes for selective detection of thiols

Abstract

Thiols represent class of organic compounds characterized by having sulfhydryl (-SH) functional group. Cysteine (Cys), homocysteine (Hcy) and glutathione (GSH) are three major low molecular weight biothiols which performs various important physiological processes. Abnormal levels of these species are linked to various diseases including Alzheimer’s disease, cardiovascular diseases, cancer, skin lesions, etc. Aromatic thiols, produced from volcanic eruption, petrol refineries and rubber industries, are highly toxic and polluting species. These exert adverse effects on human health by targeting the central nervous system, kidney and liver. Hydrogen sulphide (H2S) on the other hand, is known as the third most important gasotransmitter which has anti-inflammatory, vasculoprotective and cardioprotective effects. Overexposure to H2S leads to unconsciousness, olfactory paralysis and brain damage.

Therefore, selective and quantitative detection of these thiol species is the key to early diagnosis of such diseases and thereby in the prevention of the same. Present work is dedicated towards the development of fluorescent off-on probes for the selective detection of these species. Designs of fluorescent probes were done with the aim of discriminating among biothiols, arylthiols from biothiols, H2S from biothiols, etc. A GSH sensitive probe was developed based on the chromenoquinoline fluorophore while, 4-chloro-7-nitrobenzofurazan probe displayed excellent selectivity for Cys. A rationally designed BODIPY based probe displayed selective localization in lysosomes. A series of probes were also designed for selective response towards arylthiols. Interestingly designed probes with BODIPY, iminocoumarin and naphthaleneimide fluorophores displayed very fast response towards the analyte. In order to achieve H2S selectivity, a cascade reaction based probe was designed successfully. Applications of these probes were demonstrated by either live-cell imaging or analysis of water samples.