On the non-classical contribution in lone-pair–π interaction: IQA perspective

Abstract

In the present work the nature of lone-pair-π interactions between water molecules and a number of π-rings with different substituents/hetero-atoms in the light of quantum chemical topology approaches is studied. The Quantum Theory of Atoms in Molecules (QTAIM) and Interacting Quantum Atoms (IQA) were employed for distinguishing the role of heteroatoms and electron withdrawing substituents in the complex formation between water and π-rings. Our IQA study identified three classes of water-π complexes on the basis of the relative role of electrostatics (classical) and exchange-correlation (non-classical) factors in the interaction energy between the oxygen of water (the lone-pair donor) and the sp(2) atoms of the π-ring, i.e. the primary lp-π interaction. Considering both the primary and secondary (the rest of interatomic interactions except Owater-π-ring atoms) interactions demonstrates that the exchange-correlation is the dominant contributor to the binding energy. This proves a non-negligible contribution of non-classical factors in the stabilization of the lone-pair-π complexes. However, in spite of a relatively large contribution of the exchange-correlation, this part of the interaction energy is virtually counterbalanced by the deformation energy, i.e. the increase in atomic kinetic energy upon complexation. This finding clarifies why water-π interactions can be modelled by simple electrostatics without the need to invoke quantum effects.

Lone-pair–π interactions: analysis of the physical origin and biological implications

“…On perusal of Table 1, we can see that for all these water-π-ring lp-π interactions, the ES component happens to be of similar extent as the total interaction energy, that is, all the other components sum up to approximately zero. 33 We have already reported such mutual cancelling of non-electrostatic components for other water-π-ring lp-π interactions, 24,44 and explained thus previous observations that lp-π interactions involving water, alcohols, or ethers as lp donors can be seemingly described as predominantly electrostatic interactions. 33 We have already reported such mutual cancelling of non-electrostatic components for other water-π-ring lp-π interactions, 24,44 and explained thus previous observations that lp-π interactions involving water, alcohols, or ethers as lp donors can be seemingly described as predominantly electrostatic interactions.…”

Exploiting non-covalent π interactions for catalyst design

“…Like the anion–π interaction, it is typically expected to be more important for electron-deficient π-systems, and can qualitatively be understood as the interaction between regions of negative (the lone pair) and positive (the Q zz component of the traceless quadrupole moment tensor above and below the face of the π system) electrostatic potential 81,82 . However, several studies, both theoretical 83–85 and experimental, have noted the shortcomings of this picture and acknowledge the likely significance of electron correlation, or dispersion effects, with weak attractive interactions having been observed for electron-rich aromatic systems with negative quadrupole moments 86 . Although it is expected to be individually quite weak, the significance of the lp–π interaction has been noted in cooperation with other NCIs such as hydrogen-bonding (see below) 87,88 .…”

Atypical Lone Pair–π Interaction with Quinone Methides in a Series of Imido‐Ferrociphenol Anticancer Drug Candidates

“…[3a] Functionalization of the alkyl chain of 1 by attaching aterminal hydroxy substituent [4] or aheterocyclic group, [5] as in 3 or 4,resulted in extremely low IC 50 values (0.035 mm)on TNBC MDA-MB-231 cells;m oreover,f or the epithelial ovarian cancer cell line A2780 and the cisplatin-resistant species A2780cisR, the IC 50 values were 0.035 and 0.049 mm, respectively.T he first metabolite obtained either in the chemical (Ag + )o re nzymatic oxidation of 1 in cancer cells is the quinone methide 1-QM (Figure 1a), which can react in a1 ,8-Michael addition with selective nucleophiles in the cancer cells. [10] Thes trength and nature of lp-p interactions have been elucidated in only af ew studies, [11] mostly on simplified binding systems of two small molecules, [12] or in rigid structures. First invoked in 1995 for the stabilization of Z-DNA, [7] it is now widely recognised as anew supramolecular bond.…”

“…First invoked in 1995 for the stabilization of Z-DNA, [7] it is now widely recognised as anew supramolecular bond. [10] Thes trength and nature of lp-p interactions have been elucidated in only af ew studies, [11] mostly on simplified binding systems of two small molecules, [12] or in rigid structures. [10] Thes trength and nature of lp-p interactions have been elucidated in only af ew studies, [11] mostly on simplified binding systems of two small molecules, [12] or in rigid structures.…”

“…[8] Although perhaps counterintuitive,a nd rather weak, it has been invoked in biological macromolecules [9] and host-guest systems. [10] Thes trength and nature of lp-p interactions have been elucidated in only af ew studies, [11] mostly on simplified binding systems of two small molecules, [12] or in rigid structures. [13] There are also few virtual applications in medicinal chemistry or organocatalysis.…”