Supramolecular Balance: Using Cooperativity To Amplify Weak Interactions

Abstract

Gathering precise knowledge on weak supramolecular interactions is difficult yet is of utmost importance for numerous scientific fields, including catalysis, crystal engineering, ligand binding, and protein folding. We report on a combined theoretical and experimental approach showing that it is possible to vastly improve the sensitivity of current methods to probe weak supramolecular interactions in solution. The concept consists of using a supramolecular platform involving a highly cooperative configurational transition, the perturbation of which (by the modification of the molecular building blocks) can be monitored in a temperature scanning experiment. We tested this concept with a particular bisurea platform, and our first results show that it is possible to detect the presence of interaction differences as low as 60 J/mol, which may be due to steric repulsion between vinyl and alkyl groups or may be the result of solvation effects.

Probing halogen–halogen interactions in solution

“…An additional weak interaction (XX interaction in the present case) that is ideally formed only in one of the assemblies acts as a perturbation that may be detected (and quantified) by measuring the transition temperature (T 1 ) between the two assemblies, as well as the enthalpy of the transition (∆ℎ # ) by calorimetry. 33 Quantification requires a suitable reference compound (0) that assembles in the same competing structures as (1) but that does not form the additional weak interaction. The free energy associated to the weak interaction is then simply related to the enthalpy ∆ℎ # and to the difference between the transition temperatures (T 1 and…”

“…A few years ago, we reported on a supramolecular balance concept that is well suited to quantify weak intermolecular effects in solution 33,34 because of its extreme sensitivity compared to similar approaches. 35,36 We now apply this concept to determine whether XX interactions can be detected and quantified in solution at room temperature.…”

Two-dimensional asynchronous spectrum with auxiliary cross peaks in probing intermolecular interactions

“…For example, non-covalent interactions are at the root of the whole field of supra-molecular chemistry that leads to the formation of highly complex and fascinating structures [23] . In catalysis, the impact of weak interaction between ligand and substrate on controlling the reactivity has been recognized [24] . In the field of pharmaceuticals, a key step is to rationalize and optimize the interactions between a potential drug and a relevant receptor [25] .…”

Probing Weak Intermolecular Interactions in Self-Assembled Nanotubes

“…It is characterized by a peak in the heat capacity and can be pinpointed accurately as a function of concentration, solvent type, etc. 14,15 An example of a state diagram is given in Figure 1. It turns out that the filament−tube transition is extremely sensitive to the solvent in which the bisureas are dissolved.…”

“…Competition between self-assemblies amplifies small differences in interactions that otherwise cannot straightforwardly be measured nor obtained from computer simulation. 14 Figure 2 shows differential scanning calorimetry (DSC) traces measured for bisurea EHUT solutions in toluene/1,3,5-trimethylbenzene (TMB) mixtures. The endothermic transition is characteristic for the transition from the tube to the filament structure.…”