Real-time monitoring of hydrophobic aggregation reveals a critical role of cooperativity in hydrophobic effect

Abstract

The hydrophobic interaction drives nonpolar solutes to aggregate in aqueous solution, and hence plays a critical role in many fundamental processes in nature. An important property intrinsic to hydrophobic interaction is its cooperative nature, which is originated from the collective motions of water hydrogen bond networks surrounding hydrophobic solutes. This property is widely believed to enhance the formation of hydrophobic core in proteins. However, cooperativity in hydrophobic interactions has not been successfully characterized by experiments. Here, we quantify cooperativity in hydrophobic interactions by real-time monitoring the aggregation of hydrophobic solute (hexaphenylsilole, HPS) in a microfluidic mixer. We show that association of a HPS molecule to its aggregate in water occurs at sub-microsecond, and the free energy change is −5.8 to −13.6 kcal mol−1. Most strikingly, we discover that cooperativity constitutes up to 40% of this free energy. Our results provide quantitative evidence for the critical role of cooperativity in hydrophobic interactions.

Aggregate Science: From Structures to Properties

“…It is well known that proteins are able to form well-ordered spatial structures by virtue of hydrophobic, electrostatic and hydrogen-bonding interactions. [141][142][143] So is it possible for TPE to mimic the helical structures of proteins? Recently, Cai et al synthesized a TPE-peptide through a simple chemical reaction ( Figure 6A).…”

Hierarchical Self‐Assembly Induced by Dilution‐Enhanced Hydrophobic Hydration

“…This study using the molecular model system, complementary to the research focusing on hydrated water, is essential to evaluate and create the theory of HH for an improved understanding of biological events and rational design of waterborne materials …”

“…Hydrophobic hydration (HH) functions inevitably in the solution behaviour of biological assemblies, such as dilution‐induced refolding of denatured proteins . Although HH, sensitive to subtle changes in solution conditions, is being studied via simulation and characterization of hydrated water, the solution behaviour of solutes in response to HH is difficult to study without appropriate model systems . Amphiphiles are commonly used for aqueous assemblies, in which the role of HH is concealed by a strong affiliation of water with water‐soluble heads.…”

Self-assembled materials and supramolecular chemistry within microfluidic environments: from common thermodynamic states to non-equilibrium structures

“…Recently, for example, the thermodynamics and kinetics of supramolecular aggregation processes induced by hydrophobic interactions have been studied in real-time (and on sub-microsecond time scales) employing a microfluidic-based platform. 50 Fluorescence measurements are still the most frequently used detection methods in microfluidic devices, usually being more selective and sensitive than other optical techniques. However, in this example, aggregation-induced emission of the supramolecular assemblies under investigation is required to obtain significant information, which in turn hinders the extension of this microfluidic approach to other systems and materials.…”