Tuning Supramolecular Selectivity for Hydrosulfide: Linear Free Energy Relationships Reveal Preferential C–H Hydrogen Bond Interactions

Abstract

Supramolecular anion receptors can be used to study the molecular recognition properties of the reactive yet biologically critical hydrochalcogenide anions (HCh–). Achieving selectivity for HCh– over the halides is challenging but necessary for not only developing future supramolecular probes for HCh– binding and detection, but also for understanding the fundamental properties that govern these binding and recognition events. Here we demonstrate that linear free energy relationships (LFERs)including Hammett and Swain–Lupton plotsreveal a clear difference in sensitivity to the polarity of an aryl C–H hydrogen bond (HB) donor for HS– over other HCh– and halides. Analysis using electrostatic potential maps highlights that this difference in sensitivity results from a preference of the aryl C–H HB donor for HS– in this host scaffold. From this study, we demonstrate that LFERs are a powerful tool to gain interpretative insight into motif design for future anion-selective supramolecular receptors and highlight the importance of C–H HB donors for HS– recognition. From our results, we suggest that aryl C–H HB donors should be investigated in the next generation of HS– selective receptors based on the enhanced HS– selectivity over other competing anions in this system.

The explicit role of electron exchange in the hydrogen bonded molecular complexes

“…The electrostatic potential was one of the first used in non‐covalent bonding studies. It reveals origins of selective binding in supramolecular systems, 53 helps to predict the stoichiometry of two‐component crystals 54 and investigate the features of weak intermolecular interactions 55,56 . Recently the potential acting on an electron in a molecule PAEM 57 and Kohn–Sham effective potential, 58 which account for both electrostatic and exchange‐correlation effects, have also been used to identify the nature and strength of noncovalent interactions 59–61 and to classify them 59 .…”

Deuterium equilibrium isotope effects in a supramolecular receptor for the hydrochalcogenide and halide anions

“…[18][19][20][21] Recently, we used a series of arylethynyl bisurea anion receptors to investigate and demonstrate a linear free energy relationship between the polarity of a non-traditional C-H hydrogen bond donor and the solution binding energy of HS À , HSe À , Cl À and Br À . 14 A major and unexpected nding of this study was that HS À demonstrated a signicant increase in sensitivity towards the polarity of the C-H hydrogen donor over HSe À , Cl À and Br À . Although increasing the polarity of the C-H hydrogen bond donor did not lead to changes in selectivity between Cl À , Br À , and HSe À , we observed a 9-fold increase in selectivity for HS À over Cl À , suggesting a fresh approach to selective HS À recognition using non-covalent interactions.…”

“…To deconvolute and better understand the role of both C-H/D hydrogen bond donor polarity and solvent on the DEIE of Cl À binding in these receptors, a systematic study of these two variables would be required, similar to those previously reported, which we intend to pursue in future work. 14,27,28 Analysis of the data for competitive titrations of 2 H/D with Br À revealed no DEIE at any of the tracked 13 C NMR signals; however, each calculated DEIE has a relatively large percent error (0.99-4.64%, compared to 0.20% for the DEIE of Cl À binding), which could potentially obscure small DEIEs. We attribute these large percent errors to a limitation in the Perrin method that assumes that the hosts are fully bound by guest at saturation.…”

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.…”