Solution-state Experiments Research Articles

Supramolecular Activation of S8 by Cucurbiturils in Water and Mechanism of Reduction to H2S by Thiols: Insights into Biological Sulfane Sulfur Trafficking.

Reactive sulfur species (RSS) play critical roles in diverse chemical environments. Molecules containing sulfane sulfur (S0) have emerged as key species involved in cellular redox buffering as well as RSS generation, translocation, and action. Using cucurbit[7]uril (CB[7]) as a model hydrophobic host, we demonstrate here that S8 can be encapsulated to form a 1:1 host guest complex, which was confirmed by solution state experiments, mass spectrometry, and X-ray crystallography. The solid state structure of CB[7]/S8 shows that the encapsulated S8 is available to nucleophiles through the carbonyl portals of the host. Treatment of CB[7]/S8 with thiols results in efficient reduction of S8 to H2S in water at physiological pH. We establish that encapsulated S8 is attacked by a thiol within the CB[7] host and that the resultant soluble hydropolysulfide is ejected into solution, where it reacts further with thiols to generate soluble sulfane sulfur carriers and ultimately H2S. The formation of these intermediate is supported by observed kinetic saturation behavior, competitive inhibition experiments, and alkylative trapping experiments. We also demonstrate that CB[7]/S8 can be used to increase sulfane sulfur levels in live cells using fluorescence microscopy. More broadly, this work suggests a general activation mechanism of S8 by hydrophobic motifs, which may be applicable to proteins, membranes, or other bimolecular compartments that could transiently bind and solubilize S8 to promote reaction with thiols to solubilize and shuttle S8 back into the redox labile sulfane sulfur pool. Such a mechanism would provide an attractive manifold in which to understand the RSS translocation and trafficking.

First Principles Investigation of Noncovalent Complexation: A [2.2.2]‐Cryptand Ion‐Binding Selectivity Study

A first principles methodology, aimed at understanding the roles of molecular conformation and energetics in host-guest binding interactions, is developed and tested on a system that pushes the practical limits of ab initio methods. The binding behavior between the [2.2.2]-cryptand host (4,7,13,16,21,24-hexaoxa-1,10-diaza-bicyclo[8.8.8]hexacosane) and alkali metal cations (Li(+), Na(+), and K(+)) in gas, water, methanol, and acetonitrile is characterized. Hartree-Fock and density functional theory methods are used in concert with crystallographic information to identify gas phase, energy-minimized conformations. Gas phase free energies of binding, with vibrational contributions, are compared to solution-state binding constants through relative binding selectivity analysis. Calculated relative binding free energies qualitatively correlated with solution state experiments only after gas phase metal desolvation is considered. The B3LYP exchange-correlation functional improves theoretical correlations with experimental relative binding free energies. The relevance of gas phase calculations towards understanding binding in condensed phases is discussed. Natural bond orbital methods highlights previously unidentified intramolecular and intermolecular M(+)(222) chemistries, such as an intramolecular n'(O)-->sigma*(CH) hydrogen bond.