Dmitry M. Rudkevich

Pairwise selection of guests in a cylindrical molecular capsule of nanometre dimensions

‘Container’ complexes in which a guest molecule is held mechanically within a cage-like host have been known for over a decade,. They provide a means to stabilize reactive intermediates and to create new forms of stereoisomerism. Molecular capsules held together by hydrogen bonds are more recent; they are formed reversibly on timescales of milliseconds to hours, long enough formolecular motions and even reactions to be seen for the encapsulated species. Here we describe the synthesis and characterization of a hydrogen-bonded molecular capsule of nanometre dimensions, which is large enough to encapsulate two different molecules. This allows us to explore the size- and shape-selectivity of the encapsulation process: we see, for example, the exclusive formation of the hetero-guest pair when benzene and p -xylene are both added to a solution. This presumably reflects optimal occupancy of the capsule—two benzene guests leave too much empty space in the interior, and two p -xylene molecules make it too crowded.

Molecular Recognition within a Self-Assembled Cylindrical Host.

A change in geometry is necessary on entry into the capsule: a supramolecular associate approximately 1.8 nm long (see schematic representation), which consists of two halves stabilized by hydrogen bonds, influences the intra- and intermolecular interactions of the guest molecules encapsulated. Thus tertiary amides and anilides such as 1, which exist in solution preferably as E rotamers, are fixed in the Z conformation inside the capsule for steric reasons.

Self-assembled monolayers of carceplexes on gold

Self-assembled monolayers are an attractive platform to order and orient such molecules in two dimensions. 4,5 Previously, we have shown that self-assembly of molecules in monolayers is a tool to control the orientation of molecular recognition sites. 6,7 Essential in the design of these adsorbates is that the eight alkyl chains fill the space under the recognition site. This is realized via four sulfides and back folding of the alkyl chain. 8

Induced-Fit Molecular Recognition with Water-Soluble Cavitands

Synthesis of novel water-soluble cavitands 1 and 2 and their complexes--the caviplexes--is described. The solubility in water derives from four primary ammonium groups on the lower rim and eight secondary amide groups on the upper rim. Cavitands 1 and 2 exist as D2d velcraplex dimers in aqueous solution but the addition of lipophilic guests 15-24 induces conformational changes to the vase-like structures. The internal cavity dimensions are 8 x 10 A, and the exchange rates of guests in the caviplexes are slow on the NMR time-scale (room temperature and 600 MHz). The direct observation of bound species and the stoichiometry of the complexes is reported. The association constants (Ka) between 0.4 x 10(-1) (-deltaG295= 0.7 kcalmol(-1)) and 1.4 x 10(2)M(-1) (-deltaG295=2.9 kcalmol(-1)) in D2O and 1.4 x 10(1)(-deltaG295= 1.7 kcalmol(-1)) and 2.8 x 10(4)M(-1)(-deltaG295=6.0 kcalmol(-1)) in [D4]methanol for aliphatic guests 16-24 were determined. Guest exchange rates of the new hosts 1 and 2 are considerably slower than rates observed for typical open-ended cavities in aqueous solution.

SYNTHESIS AND CHARACTERIZATION OF A UNIMOLECULAR CAPSULE

There is more than one way to assemble the two halves of a tethered, urea-substituted calix[4]arene dimer (shown schematically): formation of unimolecular capsules (far left), dimers, or oligomers. By combination of NMR spectroscopy and electrospray mass spectrometry, a hexamethylene spacer was shown to be exactly right to permit the preferential formation of a unimolecular capsule under inclusion of solvent or other guest molecules.

Amplification by compartmentalization.

Autocatalysis and chemical amplification are properties of living systems that can lead to increased responsiveness and to self-replication. Here we describe a synthetic system in which a unique form of reagent compartmentalization gives rise to nonlinear kinetics that are subject to the precise size- and shape-selectivity of the host. The reactivity is reminiscent of autocatalytic behaviour, in which there is no direct contact between reagents and products, and our approach offers a general way to impose complex chemical behaviour onto synthetic systems.

Sensing parts per million levels of gaseous NO2 by a optical fiber transducer based on calix[4]arenes.

Calixarenes are interesting building blocks in supramolecular receptor design. They can be easily functionalized to give the desired guest binding and sequestration properties. We demonstrate here the use of simple alkylated calixarenes as novel NO(2) sensors. Upon reacting with gaseous NO(2), alkylated calixarenes form stable calixarene-NO(+) (nitrosonium) complexes that have a deep purple color. This specific and selective formation of the colored complex was used to develop a fiber optic based colorimetric NO(2) sensor. Several alkylated calixarenes are used and tested as sensing materials. The calixarene compound was immobilized on a fine mesh silica-gel coated thin layer chromatography plate. The sensing plate was coupled with a fiber optic based photodetector. Gas samples were sampled in a manner where they impinged on the surface of sensing plate. The light transmission through the plate was continuously monitored. For a 5 min sample, the limit of detection was 0.54 ppmv with 1,3-alternate O-hexyl calix[4]arene (1a). There were no significant response differences between different conformations of calixarenes such as 1,3-alternate or cone. This chemistry can form the basis of a colorimetric sensor that relies on extant filter tape technology. With calixarenes however, such a reaction is potentially reversible - color formed upon reaction with NO(2) can be reversed by flushing the sensing plate by purified air. While we found that the removal of the developed color can be accelerated by simultaneous heating and suction, permitting the reuse of the same sensing area multiple times, we also observed that the sensitivity gradually decreased. The nitrosonium calixarene derivative tends to transform to the nitrated form; this process is catalyzed by light. Several methylated calixarenes were synthesized and tested but a fully satisfactory solution has proven elusive.

Chemical amplification with encapsulated reagents

Autocatalysis and chemical amplification are characteristic properties of living systems, and they give rise to behaviors such as increased sensitivity, responsiveness, and self-replication. Here we report a synthetic system in which a unique form of compartmentalization leads to nonlinear, autocatalytic behavior. The compartment is a reversibly formed capsule in which a reagent is sequestered. Reaction products displace the reagent from the capsule into solution and the reaction rate is accelerated. The resulting self-regulation is sensitive to the highly selective molecular recognition properties of the capsule.

Hydrogen-Bonding Effects in Calix[4]arene Capsules

The synthesis and spectroscopic characterization of self-assembling calix[4]arene based capsules 1a.1a and 1b.1b are described. These compounds feature four urea substituents at the upper rims and four secondary amide fragments at the lower rims that can participate in inter- and intramolecular hydrogen bonding in apolar solution. Communication between the calixarene rims in 1a, b influences the self-assembled cavitys size and shape. Specifically. dimerization results in a perfect cone conformation of the calixarene skeleton in 1a, b and stabilizes a seam of intramolecular amide C=O...H-N hydrogen bonds at the lower rim. This seam is cycloenantiomeric, with either clockwise or counterclockwise arrangements of the head-to-tail amides. Complexation of Na+-cation breaks hydrogen bonds at the lower rim but maintains the capsular assembly. Encapsulation properties of 1a.1a and 1b.1b were studied in nonpolar solvents and their binary mixtures as well as through heterodimerization experiments. The presence of amide groups at the lower rim causes notable differences in the capsules binding affinities when compared to the corresponding tetraester capsules 1c.1c and 1d.1d. In the monomeric state calixarenes 1a, b are in a pinched cone conformation. The solid state X-ray crystallographic studies with monomeric 1a reveal only two intramolecular C=O...H-N hydrogen bonds between the adjacent amides at the lower rim, and an extensive network of intermolecular hydrogen bonds between urea groups at the upper rim.

Molecular Encapsulation of Gases

The principles and techniques of molecular encapsulation, as applied to environmentally, biologically, and commercially important gases, are reviewed. The gases may be trapped within natural (clathrates, cyclodextrins) or synthetic (cryptophanes, carcerands, calixarenes) cavities. The physical and chemical features of the cavities are key to understanding which gases may be trapped and to what extent. These trapping materials possess a host of applications, from gas sensing and separation to acting as storage devices and microreaction vessels.