Quantification of noncovalent interactions – promises and problems

Abstract

The quantification of noncovalent interactions is of paramount importance for the understanding of binding mechanisms, including biological systems, for the design of drugs and their delivery as well as for the design of host compounds for separations, sensors, actuators, smart materials etc. Although thousands of publications address noncovalent interactions it is often not clear how much these really contribute to complex formation. One complication is that the interaction between molecules is often determined by several different mechanisms. The present review intends to illustrate the presently available methods for the quantification of intermolecular interactions, mostly between organic compounds, and especially based on measurements with supramolecular complexes. Major emphasis will be given to limitations of the present methodology, which present a challenge for future work. The discussion will be grouped into several methods, from small molecule interactions to crystallographic and computational approaches, with highlights of some typical results and problems.