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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 capsule M‐1, encompassing two conformers M‐1(+) and M‐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 CBr4 would, at its lower concentrations, bind M‐1 via a M‐1(+)→M‐1(−)→CBr4⊂M‐1(−) pathway corresponding to conformational selection. For M‐1 complexing CCl4 though, data from 2D EXSY measurements and 1D NMR line‐shape analysis suggested that lower CCl4 concentrations 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. [ABSTRACT FROM AUTHOR]

Covalent capsule 1 was 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 Å3) of 1 so that two equally sizeable compartments (190 Å3) became joined through a conformationally flexible aromatic barrier. The compartments of such unique host could be populated with CCl4 (88 Å3; PC=46 %), CBr4 (106 Å3; 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 of 1. 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 designed 1 opens a way for probing the effects of inner conformational dynamics on noncovalent interactions, reactivity and intramolecular translation in confined spaces of hollow molecules. [ABSTRACT FROM AUTHOR]

In this work, we report a mechanism by which stereoisomeric and twisted capsules P/M‐1 direct their dynamic chirality in the presence of haloalkane guests. The capsule comprises a static, but twisted, cage that is linked to a dynamic tris(2‐pyridylmethyl)amine (TPA) lid at its top. From the results of experimental (NMR spectroscopy and X‐ray crystallography) and computational (DFT) studies, the TPA lid was shown to assume clockwise (+) and counterclockwise (−) folds with diastereomeric (but racemic) capsules M‐1(+) and M‐1(−) interconverting at a rapid rate (ΔG≠189K=9.1 kcal mol−1). The relative stability of the capsules was found to be a function of guest(s) residing in their interior (243/262 Å3) with small CH2Cl2 (61 Å3) yielding roughly equal population of diastereomeric inclusion complexes. Larger guests, such as CCl4 (89 Å3) and CBr4 (108 Å3), however, formed M‐1(−)⊂CX4 at the expense of M‐1(+)⊂CX4 in circa 3:1 ratio. To account for the observation, theory (DFT:M06‐2X/6–31+G*) and experiments (1H NMR spectroscopy) were used to deduce that CX4 guests become localized inside the twisted cage of the capsule by forming a C−X⋅⋅⋅π halogen bond [Nc=d/(rH+rX)=0.91–0.92] with the benzene "floor" while encountering electrostatic repulsions with closer naphthalimide boundaries. At last, the TPA lid used its central methylene hydrogens to establish, within the M‐1(−)⊂CX4, three stabilizing C−H⋅⋅⋅X−C interactions with the guest. The same C−H⋅⋅⋅X−C interactions, however, became weaker (or possibly vanished) after the conformational reorganization of the lid and the formation of less stable M‐1(+)⊂CX4 complex. On individual basis, C−H⋅⋅⋅X−C intermolecular contacts are weak and hardly detectable in the solution phase. In the case of capsule P/M‐1, however, these contacts were multivalent and altogether strong enough to direct the host's dynamic chirality. [ABSTRACT FROM AUTHOR]

Front Cover: Multivalent C-H---Cl/Br-C Interactions Directing the Resolution of Dynamic and Twisted Capsules (Chem. Eur. J. 57/2019) On the Front Cover, these weak noncovalent contacts controlling the system's dynamic stereochemistry are shown as a dragon blowing fire at C-H groups. On the Front Cover, these weak noncovalent contacts controlling the system's dynamic stereochemistry are shown as a dragon blowing fire at C-H groups. [Extracted from the article]