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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.

We describe the preparation, dynamic, assembly characteristics of vase‐shaped basket1³⁻along with its ability to form an inclusion complex with anticancer drug mitoxantrone in abiotic and biotic systems. This novel cavitand has a deep nonpolar pocket consisting of three naphthalimide sides fused to a bicyclic platform at the bottom while carrying polar glycines at the top. The results of¹H Nuclear Magnetic Resonance (NMR),¹H NMR Chemical Exchange Saturation Transfer (CEST), Calorimetry, Hybrid Replica Exchange Molecular Dynamics (REMD), and Microcrystal Electron Diffraction (MicroED) measurements are in line with1forming dimer [1₂]⁶⁻, to be in equilibrium with monomers1_(R)³⁻(relaxed) and1_(S)³⁻(squeezed). Through simultaneous line‐shape analysis of¹H NMR data, kinetic and thermodynamic parameters characterizing these equilibria were quantified. Basket1_(R)³⁻includes anticancer drug mitoxantrone (MTO²⁺) in its pocket to give stable binary complex [MTO⊂1]⁻(K_d=2.1 μM) that can be precipitated in vitro with UV light or pH as stimuli. Both in vitro and in vivo studies showed that the basket is nontoxic, while at a higher proportion with respect to MTO it reduced its cytotoxicity in vitro. With well‐characterized internal dynamics and dimerization, the ability to include mitoxantrone, and biocompatibility, the stage is set to develop sequestering agents from deep‐cavity baskets.

In this study, we describe a synthetic method for incorporating arenes into closed tubes that we name capsularenes. First, we prepared vase‐shaped molecular baskets4–7. The baskets comprise a benzene base fused to three bicycle[2.2.1]heptane rings that extend into phthalimide (4), naphthalimide (6), and anthraceneimide sides (7), each carrying a dimethoxyethane acetal group. In the presence of catalytic trifluoroacetic acid (TFA), the acetals at top of4,6and7change into aliphatic aldehydes followed by their intramolecular cyclization into 1,3,5‐trioxane (¹H NMR spectroscopy). Such ring closure is nearly a quantitative process that furnishes differently sized capsularenes1(0.7×0.9 nm),8(0.7×1.1 nm;) and9(0.7×1.4 nm;) characterized by X‐Ray crystallography, microcrystal electron diffraction, UV/Vis, fluorescence, cyclic voltammetry, and thermogravimetry. With exceptional rigidity, unique topology, great thermal stability, and perhaps tuneable optoelectronic characteristics, capsularenes hold promise for the construction of novel organic electronic devices.

In this study, we describe a synthetic method for incorporating arenes into closed tubes that we name capsularenes. First, we prepared vase‐shaped molecular baskets4–7. The baskets comprise a benzene base fused to three bicycle[2.2.1]heptane rings that extend into phthalimide (4), naphthalimide (6), and anthraceneimide sides (7), each carrying a dimethoxyethane acetal group. In the presence of catalytic trifluoroacetic acid (TFA), the acetals at top of4,6and7change into aliphatic aldehydes followed by their intramolecular cyclization into 1,3,5‐trioxane (¹H NMR spectroscopy). Such ring closure is nearly a quantitative process that furnishes differently sized capsularenes1(0.7×0.9 nm),8(0.7×1.1 nm;) and9(0.7×1.4 nm;) characterized by X‐Ray crystallography, microcrystal electron diffraction, UV/Vis, fluorescence, cyclic voltammetry, and thermogravimetry. With exceptional rigidity, unique topology, great thermal stability, and perhaps tuneable optoelectronic characteristics, capsularenes hold promise for the construction of novel organic electronic devices.