Reconciling experiment and theory in the use of aryl-extended calix[4]pyrrole receptors for the experimental quantification of chloride-π interactions in solution.

Antonio Bauzá,David Quiñonero,Antonio Frontera,Pablo Ballester

doi:10.3390/ijms16048934

Abstract

In this manuscript we consider from a theoretical point of view the recently reported experimental quantification of anion–π interactions (the attractive force between electron deficient aromatic rings and anions) in solution using aryl extended calix[4]pyrrole receptors as model systems. Experimentally, two series of calix[4]pyrrole receptors functionalized, respectively, with two and four aryl rings at the meso positions, were used to assess the strength of chloride–π interactions in acetonitrile solution. As a result of these studies the contribution of each individual chloride–π interaction was quantified to be very small (<1 kcal/mol). This result is in contrast with the values derived from most theoretical calculations. Herein we report a theoretical study using high-level density functional theory (DFT) calculations that provides a plausible explanation for the observed disagreement between theory and experiment. The study reveals the existence of molecular interactions between solvent molecules and the aromatic walls of the receptors that strongly modulate the chloride–π interaction. In addition, the obtained theoretical results also suggest that the chloride-calix[4]pyrrole complex used as reference to dissect experimentally the contribution of the chloride–π interactions to the total binding energy for both the two and four-wall aryl-extended calix[4]pyrrole model systems is probably not ideal.

Highlights

Non-covalent interactions are prominent players in supramolecular chemistry and biochemistry dominating the many processes of living systems and dictating the functionality of many biological and host-guest systems [1,2,3,4,5,6]
The explanations we provide here are based on the results of high level density functional theory (DFT) studies
The chloride–π interaction is weakened in electron deficient rings but strengthened in electron rich counterparts

Summary

Introduction

Non-covalent interactions are prominent players in supramolecular chemistry and biochemistry dominating the many processes of living systems and dictating the functionality of many biological and host-guest systems [1,2,3,4,5,6]. Theoretical studies demonstrated that anion–π interactions were cumulative, the value for a single chloride–π interaction was experimentally approximated by dividing the measured magnitude differences from the model systems by the number of aromatic rings involved, two or four (statistical correction). We analyzed by means of Bader’s theory of “atoms in molecules” and noncovalent interaction (NCI) plots the presence of important C–H···Cl− interactions in the Cl−@1 complex used as reference for the two model systems. The existence of such interactions helps to explain the modest energy values determined experimentally for chloride–π interaction using the two aryl-extended calix[4]pyrrole model systems

Solvation Effects

Experimental Section

Conclusions