p Matching Enables Quantum Proton Delocalization in Acid-1-Methylimidazole Binary Mixtures.

Short hydrogen bonds (SHBs), characterized by donor-acceptor heteroatom separations below 2.7 Å, are prevalent in condensed-phase systems. Recently, we identified SHBs in nonaqueous binary mixtures of acetic acid and 1-methylimidazole (MIm), where electronic and nuclear quantum effects facilitate extensive proton delocalization.

Assembly of water-soluble, dynamic, covalent container molecules and their application in the room-temperature stabilization of protoadamantene.

The thermodynamically controlled reactions of water-soluble tetraformylcavitand 2 with two equivalents of H(2)N(CH(2))(n) NH(2) (n=2-4) in the presence of a suitable templating guest give hemicarceplexes 1 a-c⋅guest, the yield of which depends on the match between size and shape of the guest and that of the inner phase. These hemicarceplexes are dynamic and dissociate upon addition of acid and reform upon basification. In water, they exchange guests through temporary hydrolysis of imine bonds.

Transient innermolecular carbene-hemicarcerand complex of fluorophenylcarbene.

Laser flash photolysis of fluorophenyldiazirine incarcerated in hemicarcerand 2 affords incarcerated fluorophenylcarbene [2⊙3], which forms a metastable, innermolecular π-complex with aryl moieties of 2. This carbene complex can be observed spectroscopically. Extensive computational studies provide insights into the structure, spectroscopy, energetics, and kinetics of the 2⊙3 carbene complex.

Rational design of a nanometre-sized covalent octahedron.

The thermodynamically controlled reaction of six tetraformylcavitands with twelve rigid, linear diamines yields quantitatively polyimine octahedrons with diameters of up to 5 nm. The cavitands are optimized to match the ideal geometry of a 60° tetratopic vertex unit and are connected along the octahedron edges with the diamines through 24 newly formed imine bonds.

Multicomponent assembly of cavitand-based polyacylhydrazone nanocapsules.

The thermodynamically controlled syntheses of different di-, tetra-, and hexacavitand polyacylhydrazone nanocapsules are reported. [2+4]-, [4+8]-, and [6+12]-nanocapsules assemble upon reacting a tetraformyl cavitand with two equivalents of isophthalic dihydrazide, or terephthalic dihydrazide in the presence of trifluoroacetic acid, whereby the building blocks are linked together through 8, 16, or 24 newly formed acylhydrazone bonds. Futhermore, the reaction of the tetraformylcavitands with different trigonal planar trihydrazides, simultaneously leads to the formation of [2+4]- and [6+8]-nanocapsules in varying ratios that depend on the cavitand to trihydrazide ratio and the nature of the cavitand and trihydrazide building blocks.

Templated dynamic cryptophane formation in water.

Several dynamic hexaimine cryptophanes, that are built up from two triformylcyclotribenzylene cavitands and three diamino linkers and spontaneously assemble in water in the presence of a suitable templating guest, are reported. X-ray structure, kinetics and thermodynamics of assembly and molecular recognition properties are discussed.

Thermodynamically controlled synthesis of a chiral tetra-cavitand nanocapsule and mechanism of enantiomerization.

The dynamic covalent synthesis, structure and conformational dynamics of a chiral polyimine nanocapsule 1a are reported. Reaction of four tetraformyl cavitands and eight H(2)N(CH(2))(2)NH(2) yields quantitatively 1a, which has a compact, asymmetrically folded, pseudo-C(2)-symmetric structure, as determined by X-ray crystallography, and encapsulates four CHCl(3) and three CH(3)OH guests in the solid state. In solution, 1a enantiomerizes by passing over a barrier of ΔG(298)(double dagger) = 21.

Innermolecular reactions of fluorophenylcarbene inside a hemicarcerand.

Photolysis of fluorophenyldiazirine, incarcerated in hemicarcerand 2, affords fluorophenylcarbene, which attacks an aryl unit of the host, leading (after rearrangement) to a fluoromethoxy/phenyltropone derivative of the hemicarcerand. The incarcerated carbene is probably unstable at temperatures above 100 K.

Edge-directed dynamic covalent synthesis of a chiral nanocube.

The dynamic multicomponent syntheses of nanometer-sized chiral molecular cubes 1a and 1b from 8 tritopic 90 degree corner units and 12 linear spacers using an edge-directed approach is described. Thus, the TFA-catalyzed reaction of 8 equiv C3-trihexadecyloxy-triformylcyclotribenzylene 2 as corner unit with 12 equiv of 1,4-phenylenediamine 3a or benzidine 3b as spacers yields nanocubes 1a and 1b, respectively in close to quantitative yield. The same reactions carried out with enantiomerically pure (P)-2 (>99% ee) gave the homochiral cubes (all-P)-1a and (all-P)-1b.

Multicomponent dynamic covalent assembly of a rhombicuboctahedral nanocapsule.

Molecular container compounds have a range of potential applications in chemical and biological sciences, most notably as nanoreactors, drug delivery devices, and storage materials. We report a highly efficient dynamic covalent chemistry approach for the synthesis of covalent rhombicuboctahedral nanocapsule 1 from 14 square- and triangular-shaped molecular components. The nanocapsule is obtained in a one-pot reaction in high yield and high purity, and has a solvodynamic diameter of 3.

Isotope effects as probe of constrictive and intrinsic binding in hemicarceplexes.

Kinetic isotope effects (KIE) of hemicarceplex dissociation for naphthalene and p-xylene hemicarceplexes with partially and fully deuterated guests have been measured. The KIEs are consistent with the absence of steric effects in the transition states of hemicarceplex dissociation, which supports an earlier interpretation of constrictive binding energy in hemicarceplexes as being primarily controlled by different forms of gating.

A simple one-pot multicomponent synthesis of an octahedral nanocontainer molecule.

A nearly quantitative 18-component synthesis of a nanocontainer, which is built up from six bowl-shaped cavitands that are connected together with 12 -CH=N-CH2CH2-N=CH- linkers, and its subsequent reduction are described. This nanocontainer has an estimated cavity volume of 1,700 A3, large enough to encapsulate several smaller guest molecules or a small-sized biomacromolecule. Potential uses of this nanocontainer and of water-soluble derivatives are in drug delivery, wastewater detoxification, separation technology and as molecular reactor for controlled oligomerizations.

Photochemical and thermal reactions of intermediates in the phenylnitrene rearrangement inside a hemicarcerand.

Broadband irradiation (lambda > 320 nm) of hemicarceplex H(.)1 between -74 degrees C and -84 degrees C, produces encapsulated didehydroazepine (2), triplet phenylnitrene ((3)PN), 2-azabicyclo[3.2.

Solvent effects in thermodynamically controlled multicomponent nanocage syntheses.

The solvent effects on the condensation reaction between tetraformylcavitand 2 and ethylene-1,2-diamine 3 are reported. Earlier, it was found that the trifluoroacetic acid-catalyzed condensation of 2 and 2 equiv of 3 in CHCl(3) provides in 82% yield an octahedral nanocage 1 composed of 6 cavitands that are linked together by 12 -CH=N-CH(2)CH(2)-N=CH- linker groups (Liu, X.; Liu, Y.

Efficacy of cabergoline in restless legs syndrome: a placebo-controlled study with polysomnography (CATOR).

Objective: To assess the efficacy and safety of the dopamine agonist cabergoline in the treatment of patients with idiopathic restless legs syndrome (CATOR study).

Methods: Patients with moderate to severe restless legs syndrome (RLS) were randomly assigned to cabergoline (single evening dose: 2 mg) or placebo and treated for 5 weeks in a double-blind, multicenter polysomnography (PSG) trial. The primary efficacy measures were the periodic leg movements during sleep arousal index (PLMS-AI) and sleep efficiency.

The phenylnitrene rearrangement in the inner phase of a hemicarcerand.

The photochemistry of phenyl azide 1 and 13C-labeled phenyl azide 13C-1 incarcerated inside a hemicarcerand 4 was investigated. Low-temperature photolysis of hemicarceplex 41 and 413C-1 yields incarcerated 1-azacyclohepta-1,2,4,6-tetraene 42 and 413C-2 (18-50%), respectively, which were characterized by low-temperature FT-IR and 1H NMR and 13C NMR spectroscopy. After correction for the hemicarcerand-induced upfield shift, the 13C chemical shifts of incarcerated 13C-2 compare very well (Deltadelta View Article and Find Full Text PDF

Through-shell alkyllithium additions and borane reductions.

The through-shell borane reduction and methyllithium addition to benzaldehyde (1), benzocyclobutenone (2), and benzocyclobutenedione (3) incarcerated inside a hemicarcerand (4) with four tetramethylenedioxy bridges are reported. All guests could be reduced and methylated. Selective monoreduction and monomethylation were observed for 3.

Mapping the potential energy surface of the tolylcarbene rearrangement in the inner phase of a hemicarcerand.

Photolysis of p-tolyldiazirine (6) in the inner phase of a hemicarcerand with four butane-1,4-dioxy linker groups (5) in C(6)D(5)CD(3) at 77 K yields the 5-methylcycloheptatetraene hemicarceplex 5 circle 3b in 41% together with innermolecular reaction products resulting from an insertion of transient p-tolylcarbene (1b) into an acetal C-H or linker C-O bond of 5 and from the addition of 1b to an aryl unit of 5. The yield of incarcerated 3b increased up to 67% if 6 is photolyzed inside a hemicarcerand with deuterated spanners and butane-1,4-dioxy linker groups (d(48)-5). Hemicarceplex 5 circle 3b is not formed if the photolysis is carried out in CDCl(3).

Chemistry and properties of cycloheptatetraene in the inner phase of a hemicarcerand.

Low-temperature photolysis of phenyldiazirine, incarcerated inside a hemicarcerand which is built from two cavitands connected by four butane-1,4-dioxy linker groups, yields transient phenylcarbene; this carbene then undergoes ring photochemical expansion to cycloheptatetraene in low yield. Competitively, the transiently formed phenylcarbene reacts with the surrounding hemicarcerand. The yield of the photochemical ring expansion was increased when the photolysis was carried out inside a partially deuterated hemicarcerand.

Recent highlights in hemicarcerand chemistry.

Since Donald J. Cram's first synthesis of a carcerand, which permanently entrapped a single guest molecule, many other carcerands and hemicarcerands have been synthesized and studied. Slowly, we begin to understand the role of the template in the formation of hemicarceplexes and carceplexes, why some hemicarceplexes are more stable than others, and how guests enter and exit the inner phases of molecular containers.