Anthony W. Coleman

Biochemistry of the para-sulfonato-calix[n]arenes

The biochemistry of the para-sulfonato-calix[n]arenes has shown rapid development during the past ten years, the highly diverse biomedical applications of these molecules now include anti-viral, anti-thrombotic activities, enzyme blocking and protein complexation. The future is even more promising as para-sulfonato-calix[n]arenes have, now, been shown to have potential in the diagnosis of prion-based diseases. Their innocuous nature, as far as is known at present, may open up their future use in medications.

Calix[n]arenes as Protein Sensors

The use of calix[n]arene derivatives for the sensing of proteins is described. Initially the properties of the calix[n]arenes are described. In order to better understand how the calix[n]arenes may be used for protein sensors, a detailed survey of the interactions between the molecules and amino acids and peptide is presented. The known complexes between proteins and various calix[n]arene derivatives is described and the biological activity of the molecules summarised. The use of calix[n]arenes as protein sensors observed by Schrader using amphiphilic calix[n]arenes shows that these molecules may allow nanomolar sensing. The major section of the work deals with the development of a para-sulfonato-calix[n]arene-based system for the prion protein responsible for bovine spongiform encephalitis and variant-Creutzfeldt–Jacobs disease(v-CJD) in humans. Initially, the development of the test was based on a Western Blot detection, however, the need for large scale testing after the discovery that blood transfusion may lead to infection with v-CJD led to the transfer of the technology to an ELISA-based test.

Structuring detergents for extracting and stabilizing functional membrane proteins.

Background Membrane proteins are privileged pharmaceutical targets for which the development of structure-based drug design is challenging. One underlying reason is the fact that detergents do not stabilize membrane domains as efficiently as natural lipids in membranes, often leading to a partial to complete loss of activity/stability during protein extraction and purification and preventing crystallization in an active conformation. Methodology/Principal Findings Anionic calix[4]arene based detergents (C4Cn, n = 1–12) were designed to structure the membrane domains through hydrophobic interactions and a network of salt bridges with the basic residues found at the cytosol-membrane interface of membrane proteins. These compounds behave as surfactants, forming micelles of 5–24 nm, with the critical micellar concentration (CMC) being as expected sensitive to pH ranging from 0.05 to 1.5 mM. Both by 1H NMR titration and Surface Tension titration experiments, the interaction of these molecules with the basic amino acids was confirmed. They extract membrane proteins from different origins behaving as mild detergents, leading to partial extraction in some cases. They also retain protein functionality, as shown for BmrA (Bacillus multidrug resistance ATP protein), a membrane multidrug-transporting ATPase, which is particularly sensitive to detergent extraction. These new detergents allow BmrA to bind daunorubicin with a Kd of 12 µM, a value similar to that observed after purification using dodecyl maltoside (DDM). They preserve the ATPase activity of BmrA (which resets the protein to its initial state after drug efflux) much more efficiently than SDS (sodium dodecyl sulphate), FC12 (Foscholine 12) or DDM. They also maintain in a functional state the C4Cn-extracted protein upon detergent exchange with FC12. Finally, they promote 3D-crystallization of the membrane protein. Conclusion/Significance These compounds seem promising to extract in a functional state membrane proteins obeying the positive inside rule. In that context, they may contribute to the membrane protein crystallization field.

Core-shell Au@(TiO2, SiO2) nanoparticles with tunable morphology

A novel approach based on the Stöber method allows breaking of the symmetry of core-shell systems based on metallic core and metal oxide shell. By adjusting the proportion of the TiO(2) precursor with regard to the silica precursor, different morphologies of the particles have been obtained displacing the gold particle from center to eccentric positions leading to acorn-like and raspberry-like structure.

Core-shell gold J-aggregate nanoparticles for highly efficient strong coupling applications

We have developed a straightforward synthetic route to prepare core-shell systems based on gold nanoparticles (NPs) surrounded with J-aggregates molecules. This synthesis allows the direct and efficient coating, at room temperature, of pretreated citrate-stabilized gold NPs with 5, 5′, 6, 6′-tetrachloro-1-1′-diethyl-3, 3′-di (4-sulfobutyl)-benzimidazolocarbocyanine (TDBC), without supplementary adding of salts and bases during the synthesis. As the size of gold particle is tunable, the precise optimization of the strong coupling between the electronic transitions of organic components (TDBC) and the plasmon modes of the gold NPs is achieved corresponding to a Rabi energy of 220 meV, a value not yet obtained in such a system.

Conformational extremes in the supramolecular assemblies of para-sulfonato-calix[8]arene

Two complex solid state structures of para-sulfonato-calix[8]arene are described, showing extremes in the macrocyclic conformation; one is planar and nearly circular, the other an inverted double cone. The differences in the molecular conformations lead to highly different packing arrangements in the structures.

Geometrical and inclusion considerations in the formation of hexagonal nanotubes of calix[4]arene di-methoxycarbonyl methyl ester and acid

The crystal structures of calix[4]arene di-methoxycarbonyl-methyl ester and carboxylic acid have been resolved. Interestingly, the packing for both molecules is in the form of crystal symmetry defined hexagonal helical nanotube architecture, but with the methyl ester derivative showing an extended form of the helix with regard to that formed by the carboxylic acid derivative. The addition of one carbon in the ester group leads to inclusion of the ethyl ester within a neighbouring calixarene cavity, and in consequence the packing becomes radically different.

Solid state structures of the complexes between the antiseptic chlorhexidine and three anionic derivatives of calix[4]arene

The solid state structures of the complexes between antiseptic chlorhexidine and three anionic calix[4]arene derivatives are described. Each of the three calixarenes shows typical self-organisation in the solid-state that will further impose a specific complexation of the active molecule in the co-crystal.

Synthesis, chemical modification and second order non-linear optical properties of a new calixarene copolymer

The synthesis of p-tert-butylcalix[4]arene containing polymerizable groups at the lower rim is reported. A calixarene monomer with one methacryloyloxy group at the phenolic rim was copolymerized with methyl methacrylate, yielding linear polymers with pendant calixarene groups in the cone conformation. Chemical modification of these macrocycles by ipso-nitration is described. Thin films were obtained from these materials and studied using m-lines spectroscopy, AFM, and NLO. These modified polymer films exhibited high and stable NLO responses.

Supramolecular versatility in the solid-state complexes of para-sulphonatocalix[4]arene with phenanthroline

The solid state structures of four complexes between para-sulphonato-calix[4]arene and phenanthroline have been determined. Three are simple complexes between the two molecules however the fourth contains aluminium cations, from a solid state extraction involving aluminium foil used in the weighing step. The phenanthroline cations are involved both in inclusion and also in various assemblies formed by aromatic–aromatic stacking.