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CoordH2S

Tools based on coordination chemistry to study the role of H2S in biology.
Funder: French National Research Agency (ANR)Project code: ANR-10-JCJC-0708
Funder Contribution: 190,000 EUR

CoordH2S

Description

Hydrogen sulfide, which has only been known as an environmental pollutant for decades, has recently emerged as a gas of biological importance. It completes the triumvirate of gaseous mediators / transmitters, along with nitric oxide NO and carbon monoxide CO. However, if the biology of nitric oxide in now pretty well understood, the biology of hydrogen sulfide remains obscure, despite a number of seminal results reported the literature in the past few months. Among the tools used to accelerate our knowledge of the role played by nitric oxide and carbon monoxide in biology, coordination chemistry has been a major player, with metal nitrosyls or carbonyls as donors of NO or CO, and with the development of a fluorescent nitric oxide sensor based on a copper complex which is able to detect the production of nitric oxide in cells. However, the coordination chemistry of hydrogen sulfide remains essentially centered on organometallic chemistry, and its extension to biological problems is so far limited. For example, until our recently published work, no example of hydrogen sulfide-selective probe using this bioinorganic approach was reported, and no example of donor of hydrogen sulfide based on coordination chemistry is found in the literature, while the detection of H2S in biological tissues is one crucial key to our comprehension of its role in biology, and while it is necessary to develop new hydrogen sulfide releasing molecules to replace the only two efficient donors known to date, NaHS and Na2S, which are toxic. Moreover, there is no molecular answer to a number of speculations about the reactivity of hydrogen sulfide towards some reactive species present in-vivo and which could play a role in its regulation. This project proposes to fill this gap, by developing three axes: i) development of selective fluorescent sensors of hydrogen sulfide in solution, ii) development of slowly-releasing hydrogen sulfide in solution, and iii) studies aiming at elucidating the reactivity of H2S towards some species present in biology. These three axes are all centered on coordination chemistry, and the extension to studies with biological material is planned in the medium term.

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