A 3-fold “Butterfly Valve” in Command of the Encapsulation’s Kinetic Stability. Molecular Baskets at Work

Abstract

Molecular basket 1, composed of a semirigid tris-norbornadiene framework and three revolving pyridine-based gates at the rim, has been built to "dynamically" enclose space and as such regulate molecular encapsulation. The gates were shown to fold via intramolecular hydrogen bonding and thereby form a C3nu symmetrical receptor: the 1H NMR resonance for the amide N-H protons of the pyridine gates appeared downfield (delta= 10.98 ppm), and the N-H vibrational stretch (IR) was observed at 3176 cm(-1). Accordingly, density functional theory (DFT, B3LYP) investigations revealed for the closed conformers of 1 to be energetically the most stable and dominant. The gearing of the pyridine "gates", about their axis, led to the interconversion of two dynamic enantiomers 1A and 1B comprising the clockwise and counterclockwise seam of intramolecular hydrogen bonds. Dynamic 1H NMR spectroscopic measurements and line-shape simulations suggested that the energy barrier of 10.0 kcal/mol (DeltaG++(A/B), 298 K) is required for the 1A/B interconversion, when CCl4 occupies the cavity of 1. Likewise, the activation free energy for CCl4 departing the basket was found to be 13.1 kcal/mol (DeltaG++, 298 K), whereas the thermodynamic stability of 1:CCl4 complex was -2.7 kcal/mol (DeltaGdegrees, 298 K). In view of that, CCl4 (but also (CH3)3CBr) was proposed to escape from, and a molecule of solvent to enter, the basket when the gates rotate about their axis: the exit of CCl4 requires the activation energy of 12.7 kcal/mol (DeltaG++(A/B) + DeltaGdegrees), similar to the experimentally found 13.1 kcal/mol (DeltaG++).

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

“…1). Furthermore, compound 2 (93 Å 3 , Spartan) occupies 42% of the inner space of 1 (221 ± 9 Å 3 ) [11], which is close to the packing coefficient of liquids and thereby a good indicator of a stable assembly [24]. …”

“…Is there a relationship between the aromatic gates sweeping the space and guests trafficking to and from the basket [11]? That is to say, will the gates expel the entrapped guest each time that they alter their propeller-like orientation (Fig.…”

“…Indeed, the action mechanism of the basket has been addressed [14], yet the exact role of the gates in the process of the in/out guest exchange necessitates additional scrutiny. In particular, a careful inspection of the additivity of free energies [21] pertaining to the constrictive Δ G ‡ in/out and intrinsic Δ G ° binding energies of the guests [11] as well as the racemization of the basket Δ G ‡ rac (i.e., opening and closing, see below in Fig. 6) reveals a systematic disparity (Δ G ° + Δ G ‡ rac + Δ G ‡ sterics ≠ Δ G ‡ out , see below in Fig.…”

Highly diastereoselective synthesis of a novel functionalized benzocyclotrimer

“…[2][3][4][5][6][7][8][9][10][11][12][13][14][15] Amongst these, benzocyclotrimers bearing aromatic rings are characterized by large stiff cavities. The cavities are particularly deep and suitable for supramolecular applications in case of the more symmetrical syn-diastereomer, which is generally obtained in lower yields.…”

On the Nature of the Transition State Characterizing Gated Molecular Encapsulations

“…Three phthalimides extend this structure into a bowl-shaped platform. Three aminopyridine rings [24], containing hydrogen-bonding donor and acceptor sites, are attached to the rim of the platform to, via CH 2 "hinges", act as gates that, by controlling the portal size, regulate the in/out encapsulation of small haloalkanes (V ~ 88-120 Å 3 ) [25]. The formation of basket/guest complex was, in solvophobic CD 2 Cl 2 solvent (V = 61 Å 3 ) [26], found to be first-while the dissociation is zeroth-order in guests ( Figure 1) [20].…”