A multifunctional fluorescent probe for sequential detection of hydrogen sulfide and pH in foodstuffs, living cells and mice

Abstract

Background: Cancer as a leading cause of premature death worldwide has become a major threat to human health due to the high incidence and mortality. Monitoring tumor markers are reliable and significantly important for early detection of cancers. In complex biological systems, it is of great urgency but still remains challenging to conceive a fluorescent probe with multiple tumor markers detection property. Hydrogen sulfide (H₂S) and pH are two target biomarkers for diagnosis of early cancer. The preparation of a novel probe with H₂S and pH dual detection functions is highly anticipated.

Results: Herein, a novel sequential detection probe HTPQ-HS for H₂S and pH has been developed. In this system, HPQ (2-(2 -hydroxyphenyl)-4(3H)-quinazolinone) structure combined with triphenylamine is applied as the fluorophore, and 2, 4-dinitrophenylsulfonyl group is used as the recognition group. In the presence of H₂S, HTPQ-HS is transformed into product HTPQ-OH which shows fluorescence enhancement (29-fold) at 525 nm in less than 4 min and further displays repeatable acid-base responsive ability. HTPQ-HS is able to sequentially response to H₂S and pH in living cells and does not react directly with pH. Owing to the low cytotoxicity, HTPQ-HS is able to detect exogenous and endogenous H₂S in colon cancer cells and mice, monitor H₂S in inflammation model and in foodstuffs. As the environment changes from acidic to alkaline, the fluorescence intensity ratio (I₄₇₀/I₅₃₀) of product HTPQ-OH changes remarkably, illustrating the ratiometric fluorescent responsiveness to pH.

Significance and novelty: A multifunctional fluorescent probe HTPQ-HS for sequential detection of H₂S and pH is synthesized. Probe HTPQ-OH realizes the monitoring of dynamic changes in intracellular pH and displays prospective application in security printing. We expect that our work could offer an important guidance on the development of multifunctional fluorescent probes for visualizing H₂S and pH in biology and environment.

Keywords: Fluorescent probe; Hydrogen sulfide; Multifunctional; Sequential detection; pH.