Does Size Really Matter? The Steric Isotope Effect in a Supramolecular Host–Guest Exchange Reaction

Abstract

an NSF predoctoral fellowship to J.S.M. We thank M. D. Pluth for helpful discussions and Dr. Ulla Andersen for assistance with mass spectrometry experiments.Isotope effects (IEs), which arise from differences in zero point energies (ZPEs) between a parent and isotopically substituted bond, have been used extensively by chemists to probe molecular interactions and reactivity. [1,2] Due to the anharmonicity of the C-H/D vibrational potential energy function and the lower ZPE of a C-D bond, the average C-D bond length is typically ~0.005 Å shorter than an equivalent C-H bond. [3][4][5] It is this difference in size that is often invoked to explain the observation of secondary, inverse kinetic isotope effects (KIEs) in chemical processes which proceed through a sterically strained transition state. This so-called "steric isotope effect" (SIE) has been observed in processes such as the racemization of ortho-substituted biphenyls [6] and phenanthrenes, [7] ring flipping of cyclophanes, [8] and more recently in the deslipping of rotaxanes, [9] where substitution of the sterically less demanding deuterium for protium results in rate accelerations for these processes. [10] Herein, we use deuterium substitution in a cationic guest molecule to probe the sensitivity limits of the guest exchange process from a highly-charged supramolecular host.The self-assembling [Ga 4 L 6 ] 12-supramolecular host (1, Figure 1) is composed of six ligands (L = 1,5-bis(2,3-dihydroxybenzamido)naphthalene) that span the edges of a tetrahedron and four Ga metal centers which sit at the vertices. [11,12] The host assembly 1 has a hydrophobic interior cavity that can encapsulate a variety of monocationic [13,14] and neutral [15,16] guest molecules, and has been shown to mediate the chemical reactivity of encapsulated guests. [17,18] Guest molecules can exchange between the interior and exterior of the host assembly via one of four C 3 -symmetric apertures (Figure 1) in the ligand framework, which expand and contract to accommodate guest exchange without Ga-L bond breakage (Figure 2). [19] Due to the large distortion of the host framework required for guest exchange, drastically different exchange rates are observed for guests of different size and shape. [20] These observations prompted us to investigate whether the tiny difference between C-H and C-D bond lengths is enough to produce a measurable effect on the guest exchange kinetics. In other words, just how much does guest size matter? The KIEs observed in this study demonstrate that host 1 is able to distinguish between guests with even as small a structural difference as isotopic substitution. This is the pre-peer reviewed version of the following article: Angew. Chem. Int. Ed. 2010, 49, 3635 -3637. which has been published in final form at

Topological and AIM analyses beyond the Born–Oppenheimer paradigm: New opportunities

“…Practically, since the quantum nuclei are totally confined within their own atomic basins in the considered species, the electron one-particle density, ( ) q e  ρ , determines the "outer" boundary of atomic basins; the one-electron density has the same role within context of the orthodox QTAIM [32]. In agreement with the orthodox view [19][20][21][22][23][33][34][35], the molecular volume decreases in each class however, in contrast to the orthodox view, the volumes of hydrogen basins expand in each class and the reason behind shrinkage of molecular volumes is the larger shrinkage of the carbon basins. Although, it has recently been speculated that deuterium containing hydrogen atoms may have a larger effective size than proton containing hydrogen atoms in certain cases [36], according to the best of authors' knowledge, this is the first report directly challenging the orthodox view on the relative size of proton and deuterium containing hydrogen atoms.…”

Inner and Outer Beauty

“…The answer to this is illustrated in Fig. 13, which shows the distortion of the stretching of the aperture as the molecule leaves or enters the cavity, much like the pores of many proteins involved in transport or used as gates [22].…”

No Contribution of an Inductive Effect to Secondary Deuterium Isotope Effects on Acidity

“…Isotope effects are observed when a reaction rate or equilibrium constant changes as a result of isotopic substitution 1. They continue to be used as valuable tools to provide insight into molecular structure and reactivity 2. Secondary isotope effects are those in which the bond to the isotope remains intact.…”