Supramolecular Reagent Research Articles

Towards Supramolecular Fixation of NOX Gases: Encapsulated Reagents for Nitrosation

The use of simple calix[4]arenes for chemical conversion of NO2/N2O4 gases is demonstrated in solution and in the solid state. Upon reacting with these gases, calixarenes 1 encapsulate nitrosonium (NO+) cations within their cavities with the formation of stable calixarene-NO+ complexes 2. These complexes act as encapsulated nitrosating reagents; cavity effects control their reactivity and selectivity. Complexes 2 were effectively used for nitrosation of secondary amides 5, including chiral derivatives. Unique size-shape selectivity was observed, allowing for exclusive nitrosation of less crowded N-Me amides 5 a-e (up to 95 % yields). Bulkier N-Alk (Alk>Me) substrates 5 did not react due to the hindered approach to the encapsulated NO+ reagents. Robust, silica gel based calixarene material 3 was prepared, which reversibly traps NO2/N2O4 with the formation of NO+-storing silica gel 4. With material 4, similar size-shape selectivity was observed for nitrosation. The N-Me-N-nitroso derivatives 6 d,e were obtained with approximately 30 % yields, while bulkier amides were nitrosated with much lower yields (<8 %). Enantiomerically pure encapsulating reagent 2 d was tested for nitrosation of racemic amide 5 t, showing modest but reproducible stereoselectivity and approximately 15 % ee. Given high affinity to NO+ species, which can be generated by a number of NOX gases, these supramolecular reagents and materials may be useful for NOX entrapment and separation in the environment and biomedical areas.

Supramolecular reagents: versatile tools for non-covalent synthesis

The design and modular synthesis of three ternary co-crystals with desired connectivity, assembled using tailor-made pyridyl/benzimidazol-1-yl-based supramolecular reagents, are described.

Is conformational flexibility in a supramolecular reagent advantageous for high-yielding co-crystallization reactions?

A conformationally flexible tris-carboxylic acid has been employed in the construction of several co-crystals involving a variety of ditopic N-heterocyclic hydrogen-bond acceptors.

Controlling molecular and supramolecular structure of hydrogen-bonded coordination compounds

In order to organize and assemble a variety of octahedral coordination complexes into infinite 1-D chains of desired connectivity, dibenzoylmethane was used as a chelating, “blocking” ligand, and isonicotinamide and 4-(3-carboxamidophenyl)pyridine were employed as structure directing supramolecular reagents. Five M(II) complexes were prepared using this molecular/supramolecular synthetic strategy. The crystal structure determination of these compounds shows the same principal supramolecular motif; infinite 1-D chains. In addition, the presence of the relatively bulky phenyl groups in DBM reduces packing efficiency in this system and provides better opportunities for the construction of solvated host structures.

Directed assembly of dinuclear and mononuclear copper(ii)-carboxylates into infinite 1-D motifs using isonicotinamide as a high-yielding supramolecular reagent

Isonicotinamide has been employed as a supramolecular reagent in the synthesis of five Cu(II) complexes, tetrakis(μ-acetato-O,O′)bis(isonicotinamide-N)dicopper(II) acetonitrile; trans-diaquabis(2-fluorobenzoato-O)-bis(isonicotinamide-N)copper(II), bis{bis(μ2-acetato-O)-acetic acid-O-bis(isonicotinamide-N)copper(II)} bis(methanol), bis(acetato-O)-acetic acid-O-bis(isonicotinamide-N)copper(II) acetic acid, bis(2-fluorobenzoato-O)-2-fluorobenzoic acid-O-bis(isonicotinamide-N)copper(II). The crystal structure determination of these compounds demonstrate that an effective supramolecular reagent can be combined with very different (chemically and structurally) inorganic building blocks and still create a family of inorganic–organic hybrid materials that all display the same principal supramolecular motifs; infinite 1-D chains. This consistency (which can be equated with a high supramolecular synthetic ‘yield’) has been achieved in the presence of several potentially disruptive (in a structural sense) molecules, e.g. water, methanol, and acetic acid. This illustrates that flexible or unpredictable coordination chemistry does not, in itself, necessarily prevent supramolecular synthesis using a reliable supramolecular reagent, in this case the structurally bifunctional isonicotinamide ligand.

A High-Yielding Supramolecular Reaction

The X-ray crystal structure determinations of twelve cocrystals involving iso-nicotinamide and a variety of carboxylic acids have revealed a very consistent pattern of hydrogen-bond preferences. The combination of a monocarboxylic acid, an amide, and a pyridine moiety leads, in every case, to discrete "supermolecules" (consisting of two molecules of iso-nicotinamide and two molecules of the relevant carboxylic acid) with well-defined and robust connectivity. The two dominant (regularly occurring) supramolecular synthons in these crystal structures are (1) the heteromeric carboxylic acid.pyridine hydrogen bond and (2) a self-complementary amide.amide hydrogen-bond interaction, both of which prevail in the presence of widely differing chemical functionalities. In four of these cocrystals, a dicarboxylic acid is employed, which alters the structural outcome from discrete entities to infinite assemblies (or to a hexameric complex in a "U-shaped" dicarboxylic acid), which is fully expected since the two primary supramolecular synthons remain intact. This structural study shows that iso-nicotinamide is a supramolecular reagent that can produce well-defined supermolecules (containing carboxylic acids) in very high yields.

Self-assembly of DNA-streptavidin nanostructures and their use as reagents in immuno-PCR.

The self-assembly of bis-biotinylated double-stranded DNA and the tetravalent biotin-binding protein streptavidin (STV) have been studied by non-denaturing gel electrophoresis and atomic force microscopy (AFM). The rapid self-assembly reproducibly generated populations of individual oligomeric complexes. Most strikingly, the oligomers predominantly contained bivalent STV molecules bridging two adjacent DNA fragments to form linear nanostructures. Trivalent STV branch points occurred with a lower frequency and the presence of tetravalent STV was scarce. However, valency distribution, size and the exchange dynamics of the supramolecular aggregates were highly sensitive to stoichiometric variations in the relative molar coupling ratio of bis-biotinylated DNA and STV. The largest aggregates were obtained from equimolar amounts while excess STV led to the formation of smaller oligomers appearing as fingerprint-like band patterns in electrophoresis. Excess DNA, however, induces a complete breakdown of the oligomers, likely a consequence of the instability of STV conjugates containing more than two biotinylated DNA fragments. It was demonstrated that the oligomers can further be functionalized, for instance by the coupling of biotinylated immunoglobulins. Both pure and also antibody-modified DNA-STV oligomers were used as reagents in immuno-PCR (IPCR), a highly sensitive detection method for proteins and other antigens. Employment of the supramolecular reagents led to an approximately 100-fold enhanced sensitivity compared to the conventional IPCR procedure.