Short but Weak: The Z‐DNA Lone‐Pair⋅⋅⋅π Conundrum Challenges Standard Carbon Van der Waals Radii

Abstract

Current interest in lone‐pair⋅⋅⋅π (lp⋅⋅⋅π) interactions is gaining momentum in biochemistry and (supramolecular) chemistry. However, the physicochemical origin of the exceptionally short (ca. 2.8 Å) oxygen‐to‐nucleobase plane distances observed in prototypical Z‐DNA CpG steps remains unclear. High‐level quantum mechanical calculations, including SAPT2+3 interaction energy decompositions, demonstrate that lp⋅⋅⋅π contacts do not result from n→π* orbital overlaps but from weak dispersion and electrostatic interactions combined with stereochemical effects imposed by the locally strained structural context. They also suggest that the carbon van der Waals (vdW) radii, originally derived for sp3 carbons, should not be used for smaller sp2 carbons attached to electron‐withdrawing groups. Using a more adapted carbon vdW radius results in these lp⋅⋅⋅π contacts being no longer of the sub‐vdW type. These findings challenge the whole lp⋅⋅⋅π concept that refers to elusive orbital interactions that fail to explain short interatomic contact distances.

Revealing the supramolecular features of two Zn(ii) complexes derived from a new hydrazone ligand: a combined crystallographic, theoretical and antibacterial study

“…8). Here, the oxygen atom (O2) of water molecule is also close to the carbon atom (C5) of the CN bond, i.e., 3.132 Å (shorter than the sum of their van der Waals radii 3.22 Å), 59 which indicates a significant O⋯π-hole interaction.…”

When Are Two Hydrogen Bonds Better than One? Accurate First-Principles Models Explain the Balance of Hydrogen Bond Donors and Acceptors Found in Proteins

“…Similar observations have recently been made in noncovalent interactions in DNA. 60 Although force fields have been noted in recent years to be broadly improving in agreement with experiment 61 , they can fail to describe noncovalent interactions essential for modeling protein structure in globular 55,62 or intrinsically disordered proteins 63 due to inherent limitations in the physics that can be captured by their functional forms [64][65] .…”