Benchmarking the placement of hydrosulfide in the Hofmeister series using a bambus[6]uril-based ChemFET sensor

Abstract

Hydrosulfide (HS⁻) is the conjugate base of gasotransmitter hydrogen sulfide (H₂S) and is a physiologically-relevant small molecule of great interest in the anion sensing community. However, selective sensing and molecular recognition of HS⁻ in water remains difficult because, in addition to the diffuse charge and high solvation energy of anions, HS⁻ is highly nucleophilic and readily oxidizes into other reactive sulfur species. Moreover, the direct placement of HS⁻ in the Hofmeister series remains unclear. Supramolecular host–guest interactions provide a promising platform on which to recognize and bind hydrosulfide, and characterizing the placement of HS⁻ in the Hofmeister series would facilitate the future design of selective receptors for this challenging anion. Few examples of supramolecular HS⁻ binding have been reported, but the Sindelar group reported HS⁻ binding in water using bambus[6]uril macrocycles in 2018. We used this HS⁻ binding platform as a starting point to develop a chemically-sensitive field effect transistor (ChemFET) to facilitate assigning HS⁻ to a specific place in the Hofmeister series. Specifically, we prepared dodeca-n-butyl bambus[6]uril and incorporated it into a ChemFET as the HS⁻ receptor motif. The resultant device provided an amperometric response to HS⁻, and we used this device to measure the response of other anions, including SO₄²⁻, F⁻, Cl⁻, Br⁻, NO₃⁻, ClO₄⁻, and I⁻. Using this response data, we were able to experimentally determine that HS⁻ lies between Cl⁻ and Br⁻ in the Hofmeister series, which matches recent theoretical computational work that predicted a similar placement. Taken together, these results highlight the potential of using molecular recognition coupled with ChemFET architectures to develop new approaches for direct and reversible HS⁻ detection and measurement in water and further advance our understanding of different recognition approaches for this challenging anion.