Long-Range Effects on the Capture and Release of a Chiral Guest by a Helical Molecular Capsule

Abstract

Helically folded molecular capsules based on oligoamide sequences of aromatic amino acids which are capable of binding tartaric acid in organic solvents with high affinity and diastereoselectivity have been synthesized, and their structures and binding properties investigated by (1)H NMR, X-ray crystallography, circular dichroism, and molecular modeling. We found that elongating the helices at their extremities by adding monomers remote from the tartaric binding site results in a strong increase of the overall helix stability, but it does not influence the host-guest complex stability. The effect of this elongation on the binding and release rates of the guest molecules follows an unexpected non-monotonous trend. Three independent observations (direct monitoring of exchange over time, 2D-EXSY NMR, and molecular modeling) concur and show that guest exchange rates tend to first increase upon increasing helix length and then decrease when helix length is increased further. This investigation thus reveals the complex effects of adding monomers in a helically folded sequence on a binding event that occurs at a remote site and sheds light on possible binding and release mechanisms.

Spin Exchange Monitoring of the Strong Positive Homotropic Allosteric Binding of a Tetraradical by a Synthetic Receptor in Water

“…Moreover, after ≈ 200 s, half of the signal disappeared (two nitroxides over four have been reduced) and the remaining three-line spectrum remains for more than one hour. The monitoring of the nitrogen coupling constant (supporting information Figure S13) and the line width (supporting information Figure S14 45 have been shown to display new and exciting properties in the context of supramolecular chemistry. The possibility to tune magnetic spin exchange interaction on demand in the present report is particularly attractive for molecular scale information processing and the production of memory devices.…”

Iterative design of a helically folded aromatic oligoamide sequence for the selective encapsulation of fructose

“…The contribution of each monomer to the helix curvature can be predicted with good accuracy based on general force fields and simple energy minimization, thereby allowing initial modelling of the size and shape of the central cavity, as well as the position of groups that line the interior and determine molecular recognition properties. In such constructs, guest capture and release occur via dynamic conformational changes of the backbone 36 . Sequence 1 was designed so that most amide protons and endocyclic nitrogen atoms, as well as two carbonyl groups belonging to novel H monomers, are located on the helix inner rim.…”

On the Nature of the Transition State Characterizing Gated Molecular Encapsulations

“…This, in turn, corroborates the absence of interchange mechanism ( Figure 2C) [19], whereby free guests substitute the one of the same kind trapped in the host. Alternatively, a molecule of solvent 5 could approach [1][2] to via its sizeable side aperture "push" the encapsulated guest out and thereby give complex [1][2][3][4][5] ( Figure 2D); note that, in this situation [28], the gates ought to "open" so that the substitution takes place. In line with this mechanistic hypothesis, varying the size of solvent molecules should have an effect on the rate by which guest 2 departs the basket: more sizeable compounds should create a greater van der Waals strain, while entering or exiting the host (vide infra), to affect the in/out exchange!…”

“…Indeed, elucidating the mechanism of the operation of cavitands [2][3][4][5] has been an interest for controlling the outcome of chemical reactions [6], stabilizing reactive intermediates [7], or delivering useful molecules [8,9]. Accordingly, for the complexation of metal cations with crown ethers, Schneider and Cox reported that the rates by which cations access (k in ) the macrocycles are fast (approaching a diffusion-controlled limit) while their departure from the complex (k out ) is much slower corresponding to the thermodynamic stability (∆G°) of the complex OPEN ACCESS itself [10].…”