A Synthetic Supramolecular Receptor for the Hydrosulfide Anion

Abstract

Hydrogen sulfide (H2S) 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 H2S 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) 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.

The road to aryl CH⋯anion binding was paved with good intentions: fundamental studies, host design, and historical perspectives in CH hydrogen bonding

“…12c could bind the highly nucleophilic hydrosulfide anion (HS − , conjugate base of hydrogen sulfide, H 2 S). 56 These studies revealed that a short CH•••S contact contributed to the strong association of hydrosulfide in these complexes, and solution phase measurements supported the existence of this HB as well. In a continued attempt to determine the contribution of aryl CH hydrogen bonds in anion binding, the Pluth group published a series of tribenzamide TREN-based receptors (Fig.…”

“…In one case, these pursuits led us to report the first examples of supramolecular receptors for the reversible binding of biologically-critical yet highlyreactive hydrosulfide (HS − ) anion. 56 Subsequent to these studies, new receptors targeting these types of biologically relevant anions through the use of aryl CH HBs have appeared. 49,57 We are now further exploring the use of aryl CH hydrogen bonds to bind other reactive, yet biologically-relevant (hydro)chalcogenide anions, including hydroselenide and hydrogen sulfate.…”

Applications of Synthetic Organic Tetrasulfides as H2S Donors

“…Additional stabilizing forces in the lattice include C-H hydrogen bonds from the methyl (3.7 Å) and meta aryl (3.9 Å) hydrogens, consistent with recent work demonstrating that sulfur is a C-H hydrogen bond acceptor. 27 …”

Bumpy Roads Lead to Beautiful Places: The Twists and Turns in Developing a New Class of PN-Heterocycles

“…Towards this aim, our lab has developed several arylethynyl frameworks (Figure 1) capable of binding a variety of anionic guest molecules, including halides, [14][15][16][17][18] oxoanions, [19][20][21] and hydrochalcogenides. [22][23][24] These hosts take advantage of both their multidentate binding pockets formed from the meta-substitution of the phenyl or pyridyl cores with two arylethynyl arms as well as the fluorescent nature of the -conjugated backbone.…”

“…14 This opened a floodgate of 13 eventual co-advised students and postdocs over the next 14 years who explored anion--interactions, the effect of increasing or reducing the number of urea binding units, the effects of different heterocyclic cores, and the physical organic chemistry of these receptors and their guests. 16,[19][20][21][22][23][24] Along the way, graduate student Blake Tresca further improved upon the early designs by replacing the pH-sensitive pyridine core with a benzene as in 2 and showed that the C-H•••anion interaction could be tuned by installing electron-donating/electron-withdrawing groups para to the CH unit. 26 the National Academy of Inventors.…”