Some Recent Advances in the Design and Use of Molecular Balances for the Experimental Quantification of Intramolecular Noncovalent Interactions of π Systems

Abstract

Herein, various molecular balances used for comparing the strengths of intramolecular noncovalent interactions are reviewed. Our overview indicates that considerable quantitative insight into the strength of noncovalent interactions can be gained through the careful design of molecular balances. Many exciting opportunities certainly exist for the design of further new balances to quantify and dissect the relative strengths of noncovalent interactions as a function of solvation and the importance of the many factors that contribute to overall molecular recognition. However, even simple model molecules can show a multiplicity of intramolecular noncovalent interactions acting in a combined fashion. It is therefore essential to undertake a detailed computational analysis to identify all possible noncovalent interactions present in a selected molecular balance prior to a quantitative experimental assessment of the strength of a particular noncovalent interaction. It is also argued that the words “torsion” and “molecular balance” seem to have become inextricably linked and, in consequence, even top pan and seesaw balances have been mistakenly referred to in these terms.

Toluene Dioxygenase-Catalyzed cis-Dihydroxylation of Quinolines: A Molecular Docking Study and Chemoenzymatic Synthesis of Quinoline Arene Oxides

“…Previous docking studies of arene substrates with TDO indicated that the preferred orientations were controlled by: (i) attractive edge-toface T shaped interactions with the orthogonal phenyl group of Phe-216 and imidazole ring of His 222 and (ii) Van der Waals interactions with the proximate hydrophobic amino acids Ile-276, Leu-272, Ile-324, Val-309, Leu-272, Phe-352 (Hoering et al, 2016;Vila et al, 2016aVila et al, ,b, 2017Boyd et al, 2017Boyd et al, , 2019. Theoretical, crystallographic and experimental support for phenyl-phenyl and phenyl-pyridyl edge-to-face bonding (Tbonding) interactions, between arene and heteroarene rings, has been reported (Jennings et al, 2001;Escudero et al, 2009;Gonzalez-Rosende et al, 2017;Aliev and Motherwell, 2019). Little evidence was available, from crystalline protein structures, for similar edge-to-face interactions between the imidazole ring of histidine with other aromatic residues, e.g., Phe, Tyr, Trp, His (Bhattacharyya et al, 2003).…”

N-Arylimide Molecular Balances: A Comprehensive Platform for Studying Aromatic Interactions in Solution

“…One successful strategy has been to design molecular instruments to measure aromatic interactions via their influence on a conformational equilibrium (Figure A). , Oki and Wilcox pioneered the approach of designing molecular-scale instruments to measure weak noncovalent interactions via their influence on a conformational equilibrium. Since then, there have been a number of successful molecular balance systems reported in the literature. , This article describes the insights and lessons learned in our studies of noncovalent aromatic interactions using the versatile N -arylimide molecular balance platform (Figure B).…”

London Dispersion Helps Refine Steric A-Values: The Halogens

“…Halogens as DEDs in Other Systems. Molecular balances 90,91 are used for the quantification and comparison of weak noncovalent interactions. We came up with two balances that can demonstrate the importance of LD interactions formed by halogens in carbon-based systems, with no strong electron-withdrawing or -donating groups (Figure 9).…”