Contributions of London Dispersion Forces to Solution-Phase Association Processes.

Abstract

ConspectusDespite their ubiquity and early discovery, London dispersion forces are often overlooked. This is due, in part, to the difficulty in assessing their contributions to molecular and polymeric structure, stability, properties, and reactivities. However, recent advances in modeling have revealed that dispersion interactions play an important role in many important chemical and biological processes. Experimental confirmation of their impact in solution has been challenging, leading to controversies about their relative importance.In the course of studying noncovalent interactions using molecular devices, our understanding and appreciation for the importance of dispersion interactions have evolved. This Account follows this intellectual journey by using examples from the literature. The goals are twofold: to describe recent advances in understanding the interaction and to provide guidance to researchers studying weak noncovalent interactions. However, first, the experimental methods for measuring the effects of dispersion interactions and the strategies for isolating their influence are described. These include the design of molecular devices to measure these weak noncovalent interactions and the strategies to disentangle the solvation, solvophobic, and dispersion components of the resulting equilibria.The literature examples are organized around five fundamental questions. (1) Do dispersion interactions have a measurable effect on solution equilibria? (2) To what extent do solvents attenuate or compensate for dispersion interactions? (3) To what extent do the solvation and solvophobic terms influence the dispersion equilibria? (4) Can we predict whether a system will form attractive dispersion or repulsive steric interactions? (5) Can the dispersion term be isolated and interrogated? We were often surprised by the answers to these questions. In each case, we describe how the systems were designed to address these questions and discuss possible interpretations of the results.While dispersion interactions in solution were weak (usually <1 kcal/mol), their influence on complexation and conformational equilibria can be observed and measured. This underscores the significance of these interactions in molecular recognition, coordination chemistry, reaction design, and catalysis. The solvent components of the dispersion equilibria can also be significant. Therefore, the isolation of the dispersion contributions from the solvation and solvophobic effects represents an ongoing challenge. The experimental studies also provide important benchmarks and offer valuable insights to help refine the next generation of computational solvent models.