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Two limiting cases of molecular recognition, induced fit (IF) and conformational selection (CS), play a central role in allosteric regulation of natural systems. The IF paradigm states that a substrate “instructs” the host to change its shape after complexation, while CS asserts that a guest “selects” the optimal fit from an ensemble of preexisting host conformations. With no studies that quantitatively address the interplay of two limiting pathways in abiotic systems, we herein and for the first time describe the way by which twisted capsuleM‐1, encompassing two conformersM‐1(+) andM‐1(−), trap CX₄(X=Cl, Br) to give CX₄⊂M‐1(+) and CX₄⊂M‐1(−), with all four states being in thermal equilibrium. With the assistance of 2D EXSY, we found that CBr₄would, at its lower concentrations, bindM‐1via aM‐1(+)→M‐1(−)→CBr₄⊂M‐1(−) pathway corresponding to conformational selection. ForM‐1complexing CCl₄though, data from 2D EXSY measurements and 1D NMR line‐shape analysis suggested that lower CCl₄concentrations would favor CS while the IF pathway prevailed at higher proportions of the guest. Since CS and IF are not mutually exclusive, we reason that our work sets the stage for characterizing the dynamics of a wide range of already existing hosts to broaden our fundamental understanding of their action. The objective is to master the way in which encapsulation takes place for designing novel and allosteric sequestering agents, catalysts and chemosensors akin to those found in nature.

Two limiting cases of molecular recognition, induced fit (IF) and conformational selection (CS), play a central role in allosteric regulation of natural systems. The IF paradigm states that a substrate “instructs” the host to change its shape after complexation, while CS asserts that a guest “selects” the optimal fit from an ensemble of preexisting host conformations. With no studies that quantitatively address the interplay of two limiting pathways in abiotic systems, we herein and for the first time describe the way by which twisted capsuleM‐1, encompassing two conformersM‐1(+) andM‐1(−), trap CX₄(X=Cl, Br) to give CX₄⊂M‐1(+) and CX₄⊂M‐1(−), with all four states being in thermal equilibrium. With the assistance of 2D EXSY, we found that CBr₄would, at its lower concentrations, bindM‐1via aM‐1(+)→M‐1(−)→CBr₄⊂M‐1(−) pathway corresponding to conformational selection. ForM‐1complexing CCl₄though, data from 2D EXSY measurements and 1D NMR line‐shape analysis suggested that lower CCl₄concentrations would favor CS while the IF pathway prevailed at higher proportions of the guest. Since CS and IF are not mutually exclusive, we reason that our work sets the stage for characterizing the dynamics of a wide range of already existing hosts to broaden our fundamental understanding of their action. The objective is to master the way in which encapsulation takes place for designing novel and allosteric sequestering agents, catalysts and chemosensors akin to those found in nature.

Covalent capsule1was designed to include two molecular baskets linked with three mobile pyridines tucked into its inner space. On the basis of both theory (DFT) and experiments (NMR and X‐ray crystallography), we found that the pyridine “doors” split the chamber (380 ų) of1so that two equally sizeable compartments (190 ų) became joined through a conformationally flexible aromatic barrier. The compartments of such unique host could be populated with CCl₄(88 ų; PC=46 %), CBr₄(106 ų; 56 %) or their combination CCl₄/CBr₄(PC=51 %), with thermodynamic stabilities ΔG° tracking the values of packing coefficients (PC). Halogen (C−X⋅⋅⋅π) and hydrogen bonding (C−H⋅⋅⋅X) contacts held the haloalkane guests in the cavities of1. The consecutive complexations were found to occur in a negative allosteric manner, which we propose to result from the induced‐fit mode of complexation. Newly designed1opens a way for probing the effects of inner conformational dynamics on noncovalent interactions, reactivity and intramolecular translation in confined spaces of hollow molecules.