Combined Computational and Experimental NMR Study of Calix[4]arene Derivatives

A combined computational and experimental study of a complex supramolecular system constituted by calix[4]arene derivatives that dimerize upon CO2 binding is presented. The theoretical investigation includes ab initio density functional theory, molecular dynamics, and metadynamics analysis of both monomers and dimers. The ab initio calculation of the dimerization energy demonstrates the exergonic character of the process, due to the formation of a strong hydrogen bond network between ammonium and carbamate groups. The dimerization is driven by -31.1 kcal/mol in the case of the fully outward orientation of the carbamic hydrogens, while it results in a weaker process when different carbamic orientations are considered. The molecular dynamics simulations show the critical conformational degrees of freedom driving monomers and dimers toward common structures. These conformations show tilted orientations of the carbamic groups highlighting the fundamental role of dynamics in evaluating the most stable configurations. Metadynamics simulations describe, in agreement with the other computational tools, the conformational free energy surface of these calix[4]arenes defining three stable conformational families. ROESY and variable temperature H-1 NMR experiments are in agreement with our simulations. The presented approach aims to be the reference for investigating complex supramolecular systems.