How deeply should we analyze non-covalent interactions?

Abstract

Context Just how much effort and detail should we invest in analyzing interactions of the order of 5 kcal mol−1? This comment attempts to provide a conciliatory overview of what is often a contentious field and to pose some questions that I hope will eventually lead at least to some consensus. Methods This is an opinion article without calculations or data.

Affinity of Telluronium Chalcogen Bond Donors for Lewis Bases in Solution: A Critical Experimental‐Theoretical Joint Study

“…The methodology applied in this study focusses on the extraction of experimental information among which physical observables and their analysis by theoretical means to achieve the most physically sound description of the intermolecular interactions. We therefore adopted a critical and chemical bonding model-"agnostic" or "secular" approach inspired by Clark's recent recommendations, [50] focusing on analyzing with state-of-the-art tools the properties of the electron density topology and considering different models of dispersion correction for their impact on the thermodynamics of association. The methodology disclosed herein therefore consists of (Figure 2):…”

Sigma Hole Potentials as Tools: Quantifying and Partitioning Substituent Effects

“…A computational strategy is provided that allows us to examine the relationship between inductive and mesomeric influences of chemical substituents (on benzene) through an analysis of the induced potential at the sigma hole on a terminal atom on the ring. The investigation allows us to consider further as well the utility of induced electrostatic potentials as diagnostic tools in chemistry, even as we debate the role of electrostatics in accounting for weak interactions such as halogen bonding . We examine the influence of several mono- and polyatomic substituents, R, on the induced σ-holes on terminal I centers in substituted iodobenzene.…”

“…The investigation allows us to consider further as well the utility of induced electrostatic potentials as diagnostic tools in chemistry, even as we debate the role of electrostatics in accounting for weak interactions such as halogen bonding. 73 We examine the influence of several mono- and polyatomic substituents, R, on the induced σ-holes on terminal I centers in substituted iodobenzene. The analysis allows us to probe and better understand the connection between inductive and mesomeric tendencies of substituents and the perturbation of the electron density in molecules and a few charged species.…”

Dispersion Control over Molecule Cohesion: Exploiting and Dissecting the Tipping Power of Aromatic Rings

“…The attraction between molecules is a sum of more or less directional competing forces, which can be physically dissected according to a number of different quantitative decomposition schemes. − Chemists often like to identify primary interaction centers, such as hydrogen bond donors and acceptors or dispersion energy donors, and to construct qualitative networks of these local contacts. Quantum chemical concepts and visualizations which mediate between the global physical decomposition approaches and the local chemical functionalities meet with particular interest. − In the end, hard experimental facts are needed to judge where the simplified models and concepts are productive and where they reach their limits . For noncovalent interactions, the spectroscopy of cold molecular complexes is a valuable source of experimental data, , complemented by the structurally more accessible but computationally and conceptually more demanding solid-state limit.…”

“…Quantum chemical concepts and visualizations which mediate between the global physical decomposition approaches and the local chemical functionalities meet with particular interest. 11 − 14 In the end, hard experimental facts are needed to judge where the simplified models and concepts are productive and where they reach their limits. 15 For noncovalent interactions, the spectroscopy of cold molecular complexes is a valuable source of experimental data, 16 , 17 complemented by the structurally more accessible but computationally and conceptually more demanding solid-state limit.…”