A Synthetic Supramolecular Receptor for the Hydrosulfide Anion

Abstract

Hydrogen sulfide (H 2 S) has emerged as a crucial biomolecule in physiology and cellular signaling. Key challenges associated with developing new chemical tools for understanding the biological roles of H 2 S include developing platforms that enable reversible binding of this important biomolecule. Here we report the first synthetic small molecule receptor for hydrosulfide anion, HS − , solely utilizing reversible, hydrogen-bonding interactions in a series of bis (ethynylaniline) Correspondence to: Michael M. Haley, haley@uoregon.edu; Michael D. Pluth, pluth@uoregon.edu; Darren W. Johnson, dwj@uoregon.edu. ‡ M. D. Hartle and R.J. Hansen contributed equally to this work Supporting information for this article is given via a link at the end of the document. HHS Public Access Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript derivatives. Binding constants up to 90,300 ± 8700 M −1 were obtained. The fundamental science of reversible sulfide binding-in this case featuring a key CH···S hydrogen bond-will expand the possibility for discovery of sulfide protein targets and molecular recognition agents. Graphical AbstractLong known for its malodor and toxicity, hydrogen sulfide is the most recently discovered endogenously produced gasotransmitter. Here we report the first synthetic receptor for reversible binding of HS − as characterized spectroscopically in solution and crystallographically.Keywords anions; supramolecular chemistry; H 2 S; sulfide; anion binding Supramolecular hosts have been developed to selectively bind a variety of anionic species in solution, ranging from inorganic phosphates and phosphorylated biomolecules, to halides, to other anions of environmental and/or biological relevance. [1] These synthetic supramolecular receptors use reversible, mostly non-covalent interactions to select anions based on factors such as their basicity, shape/charge, softness/hardness, position on the Hofmeister series, hydrophobic/solvophobic effects, among others. Notably lacking in the anion binding literature are efforts to target hydrosulfide (HS − ), the smallest monoanionic sulfur species, which has recently gained interest as an important biomolecule. We report here the first examples of synthetic receptors that reversibly bind HS − using solely hydrogen bonding interactions. Importantly, a critical CH···S hydrogen bond is key to the strong binding of hydrosulfide, lending support to the hypothesis that appropriately polarized CH hydrogen bond donors [1f, 2] can target softer anions. [1e, 3] Hydrogen sulfide (H 2 S) plays diverse roles in the global sulfur cycle and has recently been implicated as an important biologically-relevant signaling molecule. [4] In the last decade, H 2 S (and its more prevalent HS − conjugate base form under biological conditions) has emerged as the third endogenously produced gasotransmitter, along with CO and NO. H 2 S is now implicated in diverse (patho)physiological functions in the cardiovascular, immune, gastrointestinal, as well as other systems...

Hydrosulfide-selective ChemFETs for aqueous H2S/HS− measurement

“…These sensors show a favorable selectivity coefficient of 0.12 for hydrosulfide over chloride. Interestingly, the few supramolecular hosts that are able to bind HS − often show similar binding constants for HS − and Cl − , presumably because both ions are of similar size, whereas our sensors show almost an order of magnitude preference for HS − over Cl − [ 34 , 35 ]. The higher selectivity for HS − over Cl − may be due, in part, to the weak CH⋅⋅⋅S hydrogen bonding interactions observed in quaternary ammonium salts with S atoms [ 31 ].…”

Cooperative Noncovalent Interactions Induce Ion Pair Separation in Diphenylsilanides

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