Molecular Shape and the Hydrophobic Effect

Abstract

This review focuses in papers published since 2000 on the topic of the properties of solutes in water. More specifically, it evaluates the state-of-the-art of our understanding of the complex relationship between the shape of a hydrophobe and the Hydrophobic effect. To highlight this a selection of references covering both empirical and molecular dynamics studies of small (molecular-scale) solutes are presented. These include empirical studies of small molecules, synthetic hosts, crystalline monolayers, and proteins, as well as in silico investigations of entities including idealized hard and soft spheres, small solutes, hydrophobic plates, artificial concavity, molecular hosts, carbon nanotubes and spheres, and proteins. KeywordsWater; non-covalent interactions; supramolecular chemistry; Hydrophobic Effect; hydration ExordiumWater is found in many parts of the universe, but planet Earth truly is a water-world. All four spheres consist to some extent of water: the hydrosphere, biosphere, atmosphere and lithosphere all contain (respectively decreasing) proportions of water. This review pertains to the hydrosphere and biosphere. More specifically, this review concerns the complex relationship between hydrophobic solutes and the solvent of life.(1) For understanding how solute shape and functionality control solvation, and how this solvation folds into measurable spectroscopic and thermodynamic changes, is key to understanding our world.The ubiquity of water is reflected in a massive literature and consequently boundaries must be set for any review. First, although there is a continuum between a hydrophobe and a hard ion, and cases where the Hydrophobic effect (HE) and the Hofmeister effect(2-4) meet,(5; 6) where possible the latter is avoided. Second, this review focuses on the molecular-scale HE(7) and avoids the micro-scale.(8) Third, temperature and pressure can have a considerable effect on the HE,(9) but with only a few exceptions this review concerns ambient conditions. Fourth, bio-membranes are not discussed.(10) Finally, the bulk of this review concerns work performed since 2000.The layout of this review follows the broad types of curvature as defined by mathematics: positive curvature (convex), zero curvature (flat surface) and negative curvature (concave).

Collaborative routes to clarifying the murky waters of aqueous supramolecular chemistry

“…3) Solute shape; from computational and experimental studies, it is evident that the solvation of convex, flat, and concave surfaces are different. [29][30][31][32] For example, within a concave surface, waters cannot make as many contacts with other waters as they can at more open surfaces ( Figure 1). 4) Solute composition; even when focusing on simple non-polar solutes like hexane and benzene, there is a wide variety of polarizabilities and propensities to form van der Waals interactions.…”

“…24 The extent to which water inhibits supramolecular interactions is a function of solute shape, and one important case in point is the solvation of a concavity, where the structure of the host prevents any water within it from forming its full complement of hydrogen bonds ( Figure 1). 30 Within the physical community such a concavity is usually described as being dewetted, or as possessing drying transitions, i.e., in a temporal sense the pocket fluctuates between fully hydrated and dry. There is currently considerable debate within the computational community as to what size or shape of pocket leads to a propensity to remain desolvated.…”

“…28,30,31,49 This issue has been studied computationally to a reasonable extent, but very few systems -primarily cyclodextrins cucurbiturils, and deep-cavity cavitands -have been probed experimentally, and only cyclodextrins in depth. 50,51 These studies reveal a tantalizing picture of how small structural changes in a host can lead to large changes in the thermodynamics of ligand/guest binding.…”

The aqueous supramolecular chemistry of cucurbit[n]urils, pillar[n]arenes and deep-cavity cavitands

“…The first of these pertains to how non-polar molecules dissolve (or do not dissolve) in water, 1 whilst the second pertains to how salts modulate the properties of water and aqueous solutions; one prominent example of which is how salts modulate the Hydrophobic Effect. 2 Though we do not have a full understanding of these phenomena, especially at the molecular level, 3 we do know that the Hydrophobic Effect is dependent on both size 4 and shape 5 of a solute. It also seems to be the case that contrary to previous thoughts, the Hofmeister Effect does not control the Hydrophobic Effect by changing the properties of water itself.…”

Hydrophobicity of proteins and nanostructured solutes is governed by topographical and chemical context

“…ydrophobic interactions drive many important biological and colloidal self-assembly processes (1)(2)(3)(4)(5)(6). During such assembly, the hydration shells of the associating solutes are disrupted, replacing hydrophobic-water contacts with hydrophobic-hydrophobic ones.…”