On the reliability of atoms in molecules, noncovalent index, and natural bond orbital to identify and quantify noncovalent bonds

Abstract

Atoms in molecules, noncovalent index, and natural bond orbital methods are commonly invoked to identify the presence of various noncovalent bonds and to measure their strength. However, there are numerous instances in the literature where these methods provide contradictory or apparently erroneous interpretations of the bonding. The range of reliability of these methods is assessed by calculations of a variety of systems, which include an H‐bond, halogen bond, π‐tetrel bond, CH··HC interaction, and a pairing of two anions. While the results appear to be meaningful for the equilibrium geometries, and those where the two subunits are progressively pulled apart, these techniques erroneously predict a progressively stronger bonding interaction as the two units are compressed and the interaction becomes clearly repulsive. The methods falsely indicate a bonding interaction in the CH··HC arrangement, and incorrectly mimic the behavior of the energy when two anions approach. These approaches are also unreliable for understanding angular deformations.

Competition Between the Two σ‐Holes in the Formation of a Chalcogen Bond

“…In both of these instances, where FYF and FYBr interact with NH 3 through the σ‐hole opposite the F atom, the R(Y⋅⋅N) distance is considerably longer for Y=Te. The reduction in ρ BCP on going from Se to Te may thus reflect this ChB lengthening, since ρ BCP is well known to be very sensitive to the interatomic distance [74] …”

“…The reduction in ρ BCP on going from Se to Te may thus reflect this ChB lengthening, since ρ BCP is well known to be very sensitive to the interatomic distance. [74] Certain of the systems also show evidence of a secondary bonding interaction in addition to the primary ChB. As In addition to providing insight into any charge transfers contributing to the stability of these dimers, NBO offers an independent means of identifying and quantifying any secondary bonding interactions.…”

Impacts of noncovalent interactions involving sulfur atoms on protein stability, structure, folding, and bioactivity

“…Note that these tools may provide numbers, but the results should be treated as qualitative in nature, given the issues described below. 32…”

“…Prediction of protein-ligand binding affinity is an indispensable tool in drug discovery. [32][33][34][35][36][37][38][39][40][41][42] Here we are concerned, however, with the strengths of interactions between two protein substructures. Estimating such interaction energies is difficult.…”

“…Note that these tools may provide numbers, but the results should be treated as qualitative in nature, given the issues described below. 32 Noncovalent interaction (NCI) analysis 33 is a popular method for visualizing the noncovalent interaction regions in molecules. Users can generate color-coded reduced density gradient isosurfaces (NCI plots) in which blue, green and red represent strong attraction, weak (typically, van der Waals) attraction, and strong repulsion, respectively (Fig.…”