A 3-fold "butterfly valve" in command of the encapsulation's kinetic stability. Molecular baskets at work.

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++).

Molecular encapsulation via metal-to-ligand coordination in a Cu(I)-folded molecular basket.

A molecular basket, composed of a semirigid C3v symmetric tris-norbornadiene framework and three pyridine flaps at the rim, has been shown to coordinate to a Cu(I) cation and thereby fold in a multivalent fashion. The assembly was effective (Ka = 1.73 +/- 0.08 x 10(5) M(-1)) and driven by enthalpy (DeltaH(o) = -7.2 +/- 0.1 kcal/mol, DeltaS(o) = -0.25 eu). Variable temperature (1)H NMR studies, assisted with 2D COSY and ROESY investigations, revealed the existence of Cu(I)-folded basket 10b with a molecule of acetonitrile occupying its interior and coordinated to the metal. Interestingly, 10b is in equilibrium with Cu(I)-folded 10a , whose inner space is solvated by acetone or chloroform. The incorporation of a molecule of acetonitrile inside 10a was found to be driven by enthalpy (DeltaH(o) = -3.3 +/- 0.1 kcal/mol), with an apparent loss in entropy (DeltaS(o) = -9.4 +/- 0.4 eu); this is congruent with a complete immobilization of acetonitrile and release of a "loosely" encapsulated solvent molecule during 10a/b interconversion. From an Eyring plot, the activation enthalpy for incorporating acetonitrile into 10a was found to be positive (DeltaH(double dagger) = 6.5 +/- 0.5 kcal/mol), while the activation entropy was negative (DeltaS(double dagger) = -20 +/- 2 eu). The results are in agreement with an exchange mechanism whereby acetonitrile "slips" into an "empty" basket through its side aperture. In fact, DFT (BP86) calculations are in favor of such a mechanistic scenario; the calculations suggest that opening of the basket's rim to exchange guests is energetically demanding and therefore less feasible.

Supramolecular catalysis at work: diastereoselective synthesis of a molecular bowl with dynamic inner space.

The supramolecular assistance to Pd(0)/Cu(I)-catalyzed cyclotrimerization of stannylated norbornene 7 has been investigated to give molecular bowl 1syn in a stereoselective fashion. Following a divergent strategy, racemic norbornene 7 was synthesized in satisfactory yield. Self-coupling, promoted by Pd(0)/Cu(I) catalysis acting in synergy with CsF, yielded molecular bowl 1syn in a moderate 30% yield. The reaction diastereoselectivity is affected by the concentration of Cu(I) and Cs+: increasing quantities of the cations enhanced the syn/anti ratio of the isolated cyclotrimer from statistical (1:3) to a more desirable (4.5:1) ratio, in favor of the molecular bowl 1syn. 1H NMR spectroscopic studies suggested the coordinating affinity of 1syn toward transition metals Cu(I), Ag(I), and Au(I), to account for the observed templation effect. In particular, the tridentate 1syn has been shown to bind to one Ag(I) cation in the assembly process that is driven with enthalpy (Delta H degrees = -19 +/- 2 kcal/mol, Delta S degrees = -45 eu). The complete coordination was not cooperative, and was hypothesized to be impeded with the adverse entropy. Accordingly, density functional theory (BP86) calculations of 1syn and its mono-, bis-, and tris-Ag(I) complexes suggested that the coordination of one to three silver cations is highly exothermic. The calculations also revealed that the bowl constriction is necessary for the aromatic arms to become preorganized and bind to a silver cation(s) (Delta E approximately 8 kcal/mol). Ultimately, Ag(I) has been shown to assist the diastereoselective formation of 1syn, lending support to the notion of template-directed synthesis.

Structure-function studies of modular aromatics that form molecular organogels.

Three urea-based aromatics 1-3, each with distinct steric and electronic characteristics, have been synthesized and their ability to undergo hierarchical assembly and gel organic solvents investigated. We have found that compound 1 promotes the sol-gel phase transition in primary alcohols (from CH3OH to C10H21OH; CGC < 15 mg/mL), while 2 and 3 do not. IR spectroscopy, X-ray powder diffraction (XRPD), and transmission electron microscopy (TEM) measurements show that 1 organizes into "cylinders" in primary alcohols, using three-centered hydrogen bonds and pi-pi aromatic interactions. The cylinders further organize into pairs through interdigitation of the methyl groups of the adjacent aromatic rings. Importantly, the lateral packing of the cylinders is enhanced as the bulk solvent polarity increases providing a mechanism for controlling the material's morphology via the solvophobic effect. Molecular mechanics (Amber) and semiempirical (AM1) calculations suggested similar conformational behavior but distinct electronic properties of 1-3. Thus, pi-deficient 2 without the methyl groups and pi-rich 3 without aromatic nitrogen fail to promote the sol-gel phase transition in alcohols due to their inability to undergo effective hierarchical assembly, which is necessary for the formation of a 3D fibrillar network. In addition, we have found that the ultrasonication of a supersaturated solution of 1 is necessary for the gelation. Presumably, a fast exchange of the aggregates of 1 is assisted with sonic waves to allow for the effective and "error free" assembly wherein an entangled net of fibers capable of encapsulating solvent molecules is formed.

Silver(I) mediated folding of a molecular basket.

We have investigated Ag(I) mediated folding of a tridentate compound, containing three pyridine flaps tethered to a semirigid scaffold, into a molecular basket, using both experimental and theoretical methods. The basket formation has been shown to be highly favorable in organic media (Delta G degrees = -7.2 kcal/mol), with the assembly process allowing for another ligand to bind preferentially on the outer side.

Allosteric regulation of the conformational dynamics of a cavitand receptor.

[reaction: see text] Inspired by allostery in nature, we synthesized cavitand 1 and investigated regulation of its conformational dynamics. Quantitative 1H NMR studies have revealed that the rate of the conformational isomerization of 1 can be modulated using the external addition of acid. As 1 maintains its vase-like conformation in an acidic environment, ample opportunities for controlling the kinetics of molecular recognition, and thus reactivity, in this and related receptors have arisen.

Design, synthesis, and conformational dynamics of a gated molecular basket.

We have developed a synthesis and examined the conformational behavior and recognition properties of dynamic molecular containers 1-3. As follows from the 1H NMR dilution, diffusion NMR, and vapor pressure osmometry measurements, compound 1 has a low affinity for intermolecular aggregation and is mostly present in monomeric form in dilute chloroform solutions. Inspecting the O-H chemical shift resonances of 1, 3, and model compound 4 as a function of temperature afforded the deltadelta/deltaT coefficients of 17.0, 17.3, and 4.7 ppb K(-1), respectively. In combination with the results from variable temperature 1H NMR and IR measurements, the existence of conformers of 1 and 3 in equilibrium, each having a different extent of hydrogen bonding, was confirmed. Molecular mechanics calculations suggested 1a as the most favorable conformation, with three additional conformers, 1b, 1c, and 1d, populating local energy minima. Further optimization of each of the four conformers using semiempirical PM3 and ab initio (HF/6-31G) methods allowed a determination of their relative free energies and the corresponding Boltzmann population distributions which were heavily weighted toward 1a. A computed composite IR spectrum of a fraction-weighted mixture of the conformers of 1 reproduced the experimentally observed IR spectrum in its structural features, leading to a conclusion that conformer 1a indeed dominates the equilibrium. The egg-shaped cavity of 1 (136.6 angstroms3) is complementary in size, shape, and electrostatic potential to chloroform (74.9 angstroms3). A single-crystal X-ray study of 2 revealed a disordered chloroform molecule positioned inside the cavitand along its C3 axis.