Chiral NHC Ligands for Enantioselective Gold(I) Catalysis Under Aerobic Conditions: the Importance of Conformational Flexibility and Steric Hindrance of NHC Ligand on Reactivity.

Gold(I) catalysis has been recognized as a valuable tool for the unique transformation of multiple carbon-carbon bonds. Enantioselective π-catalysis based on gold(I) complexes is, however, still underdeveloped due to lack of privileged ligands. Herein, we present an accessible method to a new family of stable yet catalytically active chiral NHC-Au(I)-Cl complexes. The key to preserving a simultaneous fine balance between reactivity and stability in this newly developed family appears to be sterically hindered, but conformationally flexible NHC ligands. These could be easily accessed on a multigram scale by merging sterically hindered anilines with commercially available amino alcohols and amines via a four-steps synthetic sequence without the need for chromatographic purification. Further investigations of the catalytic activity of NHC-Au-Cl complexes identified the OH functionality incorporated into the NHC core as crucial for the level of enantioselectivity as well as the TsO- anion responsible for the activation of NHC-Au(I)-Cl. Finally, NMR studies and X-ray investigations revealed for the first time that the widely accepted ion metathesis (NHC-Au-Cl to NHC-Au-OSO2 R) responsible for the activation of NHC-Au-Cl complexes does not take place (or it is very slow) in commonly used MeNO2 in contrast to DCM.

NHC-BIAN-Cu(I)-Catalyzed Friedländer-Type Annulation of 2-Amino-3-(per)fluoroacetylpyridines with Alkynes on Water.

The direct catalytic alkynylation/dehydrative cyclization of 2-amino-3-trifluoroacetyl-pyridines on water was developed for the efficient synthesis of a broad range of fluorinated 1,8-naphthyridines from terminal alkynes. A novel N-heterocyclic carbene (NHC) ligand system that combines a π-extended acenaphthylene backbone with sterically bulky pentiptycene pendant groups was successfully utilized in a copper- or silver-mediated cyclization. Computational analysis of the reaction pathway supports our explanation of the different experimental conversions and yields for the set of copper and silver catalysts. The impact of steric hindrance at the metal center and the flexibility of substituents on the imidazole ring of the NHC on catalytic performance are also discussed.

Visual discrimination of aromatic acid substitution patterns by supramolecular nanocooperativity.

Physicochemical and, in particular, visual recognition of positional isomers, due to their similar appearance and properties, is an extremely challenging task. Here we present an easy-to-prepare assay for the naked-eye differentiation of all possible isomers of phthalic acids. The desired optical response is attained through specific non-covalent interactions between the acids and a cationic macrocyclic host. These interactions are then translated to and amplified by gold nanoparticles which subsequently aggregate to various extents producing a color palette.

Reversing Chemoselectivity: Simultaneous Positive and Negative Catalysis by Chemically Equivalent Rims of a Cucurbit[7]uril Host.

Enzyme catalysis has always been an inspiration and an unattainable goal for chemists due to features such as high specificity, selectivity, and efficiency. Here, we disclose a feature neither common in enzymes nor ever described for enzyme mimics, but one that could prove crucial for the catalytic performance of the latter, namely the ability to catalyze and inhibit two different reactions at the same time. Remarkably, this can be realized by two identical, spatially resolved catalytic sites. In the future, such a synchronized catalyst action could be used not only for controlling chemoselectivity, as in the present case, but also for regulating other types of chemical reactivity.

Pillar[6]pyridinium: a hexagonally shaped molecular box that selectively recognizes multicharged anionic species.

A sextuply charged cyclic cationic receptor with an extraordinary structure and unprecedented binding properties is presented. The macrocycle consists of six pyridinium ions connected by methylene linkers with an electron-deficient cavity inside. In the solid state, the cavity is padded with an organized water network that gives the macrocycle a hexagonal shape. In water, the cavity is more flexible and selectively accommodates anionic species. Of the ions of similar size the macrocycle binds most strongly those with the largest negative charge. When the net charge is the same, the most preferred are anions with delocalized charge rather that those with localized charge; remarkably, the former form inclusion complexes, while the latter are complexed externally.

Pillar[4]pyridinium: a square-shaped molecular box.

Numerous applications of Stoddart's 'blue-box', a pyridinium containing macrocycle of rectangular shape, encouraged us to seek successors of this amazing molecule. Using a one-step cyclization reaction we synthesized a square-shaped cyclic tetramer consisting of 4-methylenepyridinium units - pillar[4]pyridinium (P[4]P). Pillar[4]pyridinium is a quadruply positively charged water-soluble macrocycle with a highly symmetric, strained structure and an electron-deficient cavity. These features impel the macrocycle to assemble into channel networks in the solid state and render it an effective fluoride receptor in water.

Unprecedented rearrangement of diketopyrrolopyrroles leads to structurally unique chromophores.

Diketopyrrolopyrroles possessing thienyl, furyl and benzofuryl substituents undergo unprecedented skeletal rearrangement in the presence of trimethylsilyl bromide resulting in the formation of thieno[2,3-f]isoindole-5,8-diones and furo[2,3-f]isoindole-5,8-diones. These relatively small dyes possess favorable photophysical properties with the emission maxima within the range of 573-624 nm, large fluorescence quantum yields, moderate sensitivity of emission to solvent polarity and a HOMO-LUMO gap of ca. 1.8 eV.

A Thermo- and Photo-Switchable Ruthenium Initiator For Olefin Metathesis.

A ruthenium carbene complex bearing azobenzene functionality is reported. The complex exists in the form of two isomers differing by the size of the chelate ring. Both isomers were isolated by applying kinetic or thermodynamic control during the synthesis and characterized by X-ray diffraction analysis. The isomerization of the complex was studied by UV/Vis spectroscopy. The stable isomer was tested as a catalyst in olefin metathesis. The complex was activated at about 100 °C to promote ring-closing and ring-opening polymerization metathesis reactions. The activation took place also at room temperature under middle ultraviolet radiation.

Triggering autocatalytic reaction by host-guest interactions.

The acceleration of a sequential reaction through electrostatic alteration of substrate basicity within a supramolecular host is demonstrated. In the presence of the host, the reaction, which is autocatalytic, starts much sooner and exhibits substrate size selectivity.

Self-assembling corroles.

trans-A2B-corroles bearing -OCH2CONHR groups at the ortho position of the meso-phenyl substituent undergo self-organization both in the solid state as well as in solution. The lack of additional donor atoms induces sheet formation, but if the pyridine unit is present in the structure, more complex helical forms are formed.

Kinetic trapping of the host-guest association intermediate and its transformation into a thermodynamic inclusion complex.

The molecular recognition and self-assembly between host cucurbit[6]uril and guest adrenaline led to kinetic trapping and crystallization of the intermediate exclusion complex, which was characterized by X-ray diffraction. The crystalline kinetic complex undergoes slow spontaneous dissolution and subsequently recrystallizes as a thermodynamic inclusion complex.

Monolayers of an amphiphilic para-carboxy-calix[4]arene act as templates for the crystallization of acetaminophen.

The title compound, 5,11,17,23-tetra-carboxy-25,26,27,28-tetradodecyloxy-calix[4]arene, 1, has been studied at the air-water interface, self-assembled as Langmuir monolayers, for its ability to interact with an active pharmaceutical ingredient (API), acetaminophen (APAP), and to initiate its crystallization. The Π/A isotherm study shows that there is a clear interaction between 1 and APAP causing an expansion of the monolayer. In addition to the known phase transition occurring at a surface tension of 38 mN m(-1), an additional kink is observed in the compression isotherm for concentrations of APAP above 40 mM suggesting that this API is causing an additional phase transition of the monolayer. Interface-initiated crystallization studies show that the presence of a monolayer spread on a supersaturated solution of APAP (26 g L(-1)) triggers this API crystal growth from the interface. The transfer of 1-based monolayers on glass surfaces has been carried out using the Langmuir-Blodgett technique. The so-produced monolayers have been shown to template the crystallization of APAP. LB films of 1 have characterized using imaging and spectroscopic ellipsometry. The results suggest that each monolayer has an average thickness of 18 Å, which is consistent with the molecular structure of 1 self-organized parallel to the interface with the alkyl chains pointing out parallel to the axis of the macrocycle and without interdigitation of the alkyl chains. The presence of APAP in the subphase during the LB transfer causes a limited but relevant increase in the layer thickness. The study of the capabilities of the LB films to initiate crystallization of APAP is also demonstrated showing the influence of the monolayer packing on the quantity of formed crystals.

Amidophenol-modified amphiphilic calixarenes: synthesis, interfacial self-assembly, and acetaminophen crystal nucleation properties.

Three amidophenol-modified calixarenes have been produced reacting the parent 5,11,17,23-tetracarboxy-25,26,27,28-tetradodecyloxycalix[4]arene with o-, m-, and p-aminophenol. The produced amphiphiles have been shown to form stable monomolecular Langmuir layers on water. Working on subphases containing 1 mM acetaminophen (APAP), it has been demonstrated that the produced amphiphiles interact with this active pharmaceutically ingredient (API) with a relevant preference for the para-derivative that possesses in its structure substituents that are analogous to the target. Working at supersaturating concentrations of APAP, it has been demonstrated that the so-produced calixarene Langmuir monolayers do favor crystallization of APAP (polymorph I), with a clear effect of the packing density of the amphiphile at the interface on the quantity of produced crystals. Monolayers of the para-derivative have been transferred on solid substrates using the Langmuir-Blodgett technique; the so-produced ultrathin films have been shown to initiate surface crystal nucleation of APAP. The produced solids have been analyzed by single-crystal X-ray crystallography and shown to preferentially grow in the [010] direction.

Solid-state interactions of calixarenes with biorelevant molecules.

Among all crystalline complexes of calix-type calix[n]arenes those with organic molecules which are biologically relevant are especially of interest due to their potential medical and pharmaceutical applications. The co-crystallization of drugs with water-soluble calixarenes offers the opportunity to modify chemical and physical properties of APIs (active pharmaceutical ingredients) and to control drug conformation. Such co-crystallization can improve solubility, bioavailability and stability of pharmaceutically active molecules and/or eliminate polymorphism. In this article the solid-state interactions between calixarene hosts and biologically relevant guest molecules are summarized for the currently available structures solved by single-crystal X-ray crystallography.

Diastereoselective lower rim (1S)-camphorsulfonylation as the shortest way to the inherently chiral calix[4]arene.

[structure: see text]. A diastereomeric mixture of chiral 25-(1S)-camphorsulfonyloxy-26-isopropoxycalix[4]arene 2a (de 15%) and 25-isopropoxy-26-((1S)-10-camphorsulfonyl)calix[4]arene 2b has been obtained by asymmetrical lower rim (1S)-camphorsulfonylation of the monoisopropoxycalix[4]arene. Pure diastereomer 2a has been obtained by simple crystallization, and its absolute configuration has been determinated by X-ray analysis. Enantiomerically pure inherently chiral 5,11-dibromo-26-isopropoxycalix[4]arene 4 has been synthesized by the upper rim dibromination of the diastereomer 2a followed by hydrolytical removal of the auxiliary camphorsulfonyl group.

Assembly of a novel supramolecular synthon of calix[4]arene presenting four carboxylic acids.

An extremely complex solid state structure described by two virtual channels and a 2-D square grid of hydrogen bonds is generated by four carboxylic acids groups of calix[4]arene tetrabutyroxycarboxylic acid.

Head-to-tail self-assembly of a calix[4]arene inclusion polymer controlled by a pendant arm.

A calix[4]arene functionalized at one phenolic group with a pendant ethoxy acetate group, forms an inclusion complex that is stable even in the presence of other potential guest molecules.