This tutorial review summarizes the continuining exploration of three prominent water-soluble hosts: cucurbiturils, pillar[n]arenes and deep-cavity cavitands. As we describe, these hosts are revealing how orchestrating the Hydrophobic Effect can lead to a broad range of properties and applications, from: nano-reactors, supramolecular polymers, stimuli-responsive biointerfaces, switches, and novel purification devices. We also describe how their study is also revealing more details about the properties of water and aqueous solutions.

Accurately predicting the binding affinities of small organic molecules to biological macro-molecules can greatly accelerate drug discovery by reducing the number of compounds that must be synthesized to realize desired potency and selectivity goals. Unfortunately, the process of assessing the accuracy of current computational approaches to affinity prediction against binding data to biological macro-molecules is frustrated by several challenges, such as slow conformational dynamics, multiple titratable groups, and the lack of high-quality blinded datasets. Over the last several SAMPL blind challenge exercises, host-guest systems have emerged as a practical and effective way to circumvent these challenges in assessing the predictive performance of current-generation quantitative modeling tools, while still providing systems capable of possessing tight binding affinities. Here, we present an overview of the SAMPL6 host-guest binding affinity prediction challenge, which featured three supramolecular hosts: octa-acid (OA), the closely related tetra-endo-methyl-octa-acid (TEMOA), and cucurbit[8]uril (CB8), along with 21 small organic guest molecules. A total of 119 entries were received from 10 participating groups employing a variety of methods that spanned from electronic structure and movable type calculations in implicit solvent to alchemical and potential of mean force strategies using empirical force fields with explicit solvent models. While empirical models tended to obtain better performance than first-principle methods, it was not possible to identify a single approach that consistently provided superior results across all host-guest systems and statistical metrics. Moreover, the accuracy of the methodologies generally displayed a substantial dependence on the system considered, emphasizing the need for host diversity in blind evaluations. Several entries exploited previous experimental measurements of similar host-guest systems in an effort to improve their physical-based predictions via some manner of rudimentary machine learning; while this strategy succeeded in reducing systematic errors, it did not correspond to an improvement in statistical correlation. Comparison to previous rounds of the host-guest binding free energy challenge highlights an overall improvement in the correlation obtained by the affinity predictions for OA and TEMOA systems, but a surprising lack of improvement regarding root mean square error over the past several challenge rounds. The data suggests that further refinement of force field parameters, as well as improved treatment of chemical effects (e.g., buffer salt conditions, protonation states) may be required to further enhance predictive accuracy.

The deep cryogenic temperatures encountered in aerospace present significant challenges for the performance of elastic materials in spacecraft and related apparatus. Reported elastic carbon or ceramic aerogels overcome the low-temperature brittleness in conventional elastic polymers. However, complicated fabrication process and high costs greatly limited their applications. In this work, super-elasticity at a deep cryogenic temperature of covalently crosslinked polyimide (PI) aerogels is achieved based on scalable and low-cost directional dimethyl sulfoxide crystals assisted freeze gelation and freeze-drying strategy. The covalently crosslinked chemical structure, cellular architecture, negative Poisson’s ratio (−0.2), low volume shrinkage (3.1%), and ultralow density (6.1 mg/cm3) endow the PI aerogels with an elastic compressive strain up to 99% even in liquid helium (4 K), almost zero loss of resilience after dramatic thermal shocks (∆T = 569 K), and fatigue resistance over 5000 times compressive cycles. This work provides a new pathway for constructing polymer-based materials with super-elasticity at deep cryogenic temperature, demonstrating much promise for extensive applications in ongoing and near-future aerospace exploration.

The intrinsic structural complexity of proteins makes it hard to identify the contributions of each noncovalent interaction behind the remarkable rate accelerations of enzymes. Coulombic forces are evidently primary, but despite developments in artificial nanoreactor design, a picture of the extent to which these can contribute has not been forthcoming. Here we report on two supramolecular capsules that possess structurally identical inner-spaces that differ in the electrostatic potential (EP) field that envelops them: one positive and one negative. This architecture means that only changes in the EP field influence the chemical properties of encapsulated species. We quantify these influences via acidity and rates of cyclization measurements for encapsulated guests, and we confirm the primary role of Coulombic forces with a simple mathematical model approximating the capsules as Born spheres within a continuum dielectric. These results reveal the reaction rate accelerations possible under Coulombic control and highlight important design criteria for nanoreactors.

Variable scan rate (0.1-500 V s -1 ) cyclic voltammetry experiments were performed on a series of model tocopherol (vitamin E) compounds with differing degrees of methyl substitution around the aromatic (phenolic) ring. R-Tocopherol, with a fully methylated aromatic ring, produced stable phenoxonium cations upon oxidation in CH 3 CN, and was modeled via an ECE mechanism (where "E" represents an electron transfer and "C" a chemical step). Compounds with less methyl substitution around the aromatic ring were more reactive following oxidation, and formed additional oxidation products (hemiketals and p-quinones), and were modeled according to a more complicated ECECC mechanism. The equilibrium and rate constants associated with the chemical steps were estimated by digital simulations of the variable scan rate data over a range of temperatures (T ) 253-313 K) in acetonitrile containing 0.5 M Bu 4 NPF 6 as the supporting electrolyte. The relative lifetimes of the phenoxonium cations of tocol and the tocopherols were compared with theoretical results obtained from molecular orbital calculations.