Stephen Rieth

Tuning the Rate of Molecular Translocation

Gated molecular baskets can be functionalized to tune the conformational dynamics of the gates, installed at their rim, and thereby to adjust the time that a guest molecule spends inside their cavity.

Molecular Recognition of a Transition State

Self-assembled or covalent hosts capable of enclosing space offer a confined environment for accommodating small to medium-sized molecules. When the isotropic solvent shell around a molecule is substituted by the framework of the host, unique properties can arise, including the stabilization of transient intermediates and catalysis of chemical reactions. The research groups of Cram and Sherman were among the first to observe and characterize the limited rotational mobility of smaller molecules residing in carceplexes, and these seminal studies invoked steric interactions as a source of the retardation. Subsequently, Rebek and co-workers characterized encapsulation complexes with guests having limited translational mobility, thereby establishing the phenomenon of social isomerism and revealing new types of supramolecular chirality. The conformational interconversion of encapsulated guest(s) has also been studied in artificial hosts, 7] and complexation was almost uniformly identified to retard or to have no effect, relative to a proper reference system. The deceleration has been speculated to arise from steric and electronic characteristics of the hosts affecting the reactant as well as the transition state(s) of the interconverting guest. The activation barrier for the ring flipping of 1,4-thioxane and 1,4-dioxane required an additional 1.6–1.8 kcalmol 1 (DDG ) within the restrictive interior of carcerands. The chair–chair interconversion process for cyclohexane was noted to occur slower in “jelly doughnut” (DDG 0.3 kcal mol ) and resorcin[4]arene (DDG = 0.25 0.10 kcal mol ) based cavitands. In the first case, this was rationalized by invoking favorable C H···p interactions to stabilize the chair ground state. Analogous studies on the rotation of the amide bond in encapsulated environments showed such an interconversion occurred at a faster/slower rate in hydrophobic, supramolecular assemblies than in polar or nonpolar (DDG 1–3 kcalmol ) solvents, respectively. In light of such discoveries, we report a rather unusual case of accelerated ring flipping of cyclohexane inside newly developed hosts—gated molecular baskets. We measured the kinetics of the conformational interconversion of [D11]cyclohexane (C6D11H) by quantitative NMR spectroscopy and used electronic structure methods to identify the origin of the observed acceleration. Gated molecular baskets (Figure 1) were designed as models for examining the kinetics of molecular encapsulation. These dynamic hosts comprise a bowl-shaped platform with three pyridine-based gates at its rim. The gates are transiently connected through a seam of intramolecular hydrogen bonds for controlling the in/out trafficking of guests (Figure 1). As a prelude to studies on the relationship

Four-state switching characteristics of a gated molecular basket.

The development of working molecular devices relies on the ability to extrinsically modulate function via structure. We have found that gated molecular basket 1 can be reversibly interconverted among four unique structural states (see above). Controlling the relative population of these states, the recognition characteristics of the basket can be finely tuned.

On the mechanism of action of gated molecular baskets: The synchronicity of the revolving motion of gates and in/out trafficking of guests

Summary We used dynamic 1H NMR spectroscopic methods to examine the kinetics and thermodynamics of CH3CCl3 (2) entering and leaving the gated molecular basket 1. We found that the encapsulation is first-order in basket 1 and guest 2, while the decomplexation is zeroth-order in the guest. Importantly, the interchange mechanism in which a molecule of CH3CCl3 directly displaces the entrapped CH3CCl3 was not observed. Furthermore, the examination of the additivity of free energies characterizing the encapsulation process led to us to deduce that the revolving motion of the gates and in/out trafficking of guests is synchronized, yet still a function of the affinity of the guest for occupying the basket: Specifically, the greater the affinity of the guest for occupying the basket, the less effective the gates are in “sweeping” the guest as the gates undergo their revolving motion.