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Lawrence Berkeley National Laboratory Recent Work Title A Synthetic Supramolecular Receptor for the Hydrosulfide Anion Permalink
| Content Provider | Semantic Scholar |
|---|---|
| Author | Hartle, Matthew D. Hansen, Ryan John Tresca, Blakely W. Prakel, Samuel S. Zakharov, Lev N. Haley, Michael M. Pluth, Michael D. Johnson, Darren W. |
| Copyright Year | 2016 |
| 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. The first synthetic small molecule receptor for the hydrosulfide anion, HS@ , using only reversible, hydrogenbonding interactions in a series of bis(ethynylaniline) derivatives, is reported. Binding constants of up to 90300: 8700m@1 were obtained in MeCN. 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. Supramolecular hosts have been developed to selectively bind a variety of anionic species in solution, ranging from inorganic phosphates and phosphorylated biomolecules to halides and other anions of environmental or biological relevance. 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, and hydrophobic/ solvophobic effects. 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. Herein, we report 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 C@H hydrogen-bond donors 2] can target softer anions. Hydrogen sulfide (H2S) plays diverse roles in the global sulfur cycle and has recently been implicated as an important biologically relevant signaling molecule. In the last decade H2S (and its more prevalent conjugate-base form at physiological pH, HS@) has emerged as the third endogenously produced gasotransmitter, along with CO and NO. H2S is now implicated in diverse (patho)physiological functions in the cardiovascular, immune, gastrointestinal, as well as other systems, making its absence in the supramolecular chemistry of anions even more surprising. In parallel to the biological advances in H2S research, chemical tools for detecting and imaging H2S are rapidly emerging and form a cornerstone of the investigative approaches used to study this critical biomolecule. Despite this importance, current detection methods are plagued by irreversibility, which presents a significant problem in developing chemical tools that provide real-time information on biological processes, suggesting that a supramolecular (that is, reversible) approach to HS@ binding would be an important contribution. The pKa of H2S (7.0) ensures that both the neutral (H2S) and monoanionic (HS@) forms are present under physiological conditions, which complicates biological H2S investigations and leads to significant unresolved questions on the specific chemistry and recognition events associated with the individual protonation states. Recently, HS@ was determined to be a viable substrate for Cl/HCO3 @ anion-exchange proteins, and a bacterial ion channel for HS@ transport was identified (Figure 1a,b). Importantly, the recognition events involved in the sulfide transport of these systems rely on non-covalent, reversible interactions with HS@ rather than metal coordination or interaction with the sulfane sulfur pool. Taken together, these examples suggest that HS@ , which has until now been almost entirely overlooked, needs to be included in the complex landscape of biologically relevant anions, such as Cl@ , HCO3 @ , I@ , and NO2 @ . Despite the emerging importance of sulfide, HS@ has only appeared in anion screening sporadically, and we are unaware of any synthetic receptors able to bind H2S or HS @ reversibly through well-defined non-covalent interactions. 9] Systems that could bind H2S or HS @ selectively through reversible interactions would not only provide significant insights into potential HS@-binding environments in biological contexts but also provide new strategies for developing reversible and real-time H2S detection methods. To approach this challenge, we reasoned that synthetic anion receptors could provide a viable platform to develop reversible HS@-binding systems. To optimize selective binding for hydrosulfide, we initially assumed that the ideal receptor should feature hydrogen-bond donors to target the anionic portion of hydrosulfide and a hydrogen-bond acceptor (or suitable pocket of electron density) to accommodate the slightly acidic hydrogen atom. Aligned with these requirements, sulfide has a similar ionic radius to Cl@ (S2@= 1.84 c, Cl@= 1.81 c), and biological examples reveal that HS@ can [*] M. D. Hartle, R. J. Hansen, Dr. B. W. Tresca, S. S. Prakel, L. N. Zakharov, Prof. M. M. Haley, Prof. M. D. Pluth, Prof. D. W. Johnson Department of Chemistry & Biochemistry, Materials Science Institute, and Institute of Molecular Biology, University of Oregon Eugene, OR 97403-1253 (USA) E-mail: haley@uoregon.edu |
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| Alternate Webpage(s) | https://cloudfront.escholarship.org/dist/prd/content/qt24t607j5/qt24t607j5.pdf?t=p8dcqn |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
