Andrew Marsh

THE DESIGN AND SYNTHESIS OF SIMPLE MOLECULAR TETHERS FOR BINDING BIOMEMBRANES TO A GOLD SURFACE

Abstract Molecular tethers have been synthesised for fixing biomembranes to a gold surface. These are comprised of a thiol at one end to bind to the gold, a polyethylenoxy chain of defined length (two, six or twelve ethylenoxy units) in the middle and a cholesteryl residue at the other end to insert into the biomembrane.

A G4·K+ Hydrogel Stabilized by an Anion

Supramolecular hydrogels derived from natural products have promising applications in diagnostics, drug delivery, and tissue engineering. We studied the formation of a long-lived hydrogel made by mixing guanosine (G, 1) with 0.5 equiv of KB(OH)4. This ratio of borate anion to ligand is crucial for gelation as it links two molecules of 1, which facilitates cation-templated assembly of G4·K(+) quartets. The guanosine-borate (GB) hydrogel, which was characterized by cryogenic transmission electron microscopy and circular dichroism and (11)B magic-angle-spinning NMR spectroscopy, is stable in water that contains physiologically relevant concentrations of K(+). Furthermore, non-covalent interactions, such as electrostatics, π-stacking, and hydrogen bonding, enable the incorporation of a cationic dye and nucleosides into the GB hydrogel.

G4-Quartet·M + Borate Hydrogels

The ability to modulate the physical properties of a supramolecular hydrogel may be beneficial for biomaterial and biomedical applications. We find that guanosine (G 1), when combined with 0.5 equiv of potassium borate, forms a strong, self-supporting hydrogel with elastic moduli >10 kPa. The countercation in the borate salt (MB(OH)4) significantly alters the physical properties of the hydrogel. The gelator combination of G 1 and KB(OH)4 formed the strongest hydrogel, while the weakest system was obtained with LiB(OH)4, as judged by (1)H NMR and rheology. Data from powder XRD, (1)H double-quantum solid-state magic-angle spinning (MAS) NMR and small-angle neutron scattering (SANS) were consistent with a structural model that involves formation of borate dimers and G4·K(+) quartets by G 1 and KB(OH)4. Stacking of these G4·M(+) quartets into G4-nanowires gives a hydrogel. We found that the M(+) cation helps stabilize the anionic guanosine-borate (GB) diesters, as well as the G4-quartets. Supplementing the standard gelator mixture of G 1 and 0.5 equiv of KB(OH)4 with additional KCl or KNO3 increased the strength of the hydrogel. We found that thioflavin T fluoresces in the presence of G4·M(+) precursor structures. This fluorescence response for thioflavin T was the greatest for the K(+) GB system, presumably due to the enhanced interaction of the dye with the more stable G4·K(+) quartets. The fluorescence of thioflavin T increased as a function of gelator concentration with an increase that correlated with the systems gel point, as measured by solution viscosity.

Janus molecules: Synthesis of double-headed heterocycles containing two identical hydrogen bonding arrays

Abstract The synthesis of three heterocycles 1–3 presenting identical faces containing a hydrogen bonding code for self-assembly is described. Pyrimidoquinazolinetetrone 1 and diaminopyrimidoquinazolinedione 2 were approached using a double Chapman rearrangement followed by closure to the double uracil-type structure 1 . Diaminopyridoisoquinolinedione 3 was obtained in three steps from pyromellitic anhydride.

High-loading scavenger resins for combinatorial chemistry

Abstract The synthesis of high-loading resins functionalised with triazine dendrimers, suitable for use as scavengers in the purification of combinatorially derived products is described. A comparison of their efficacy with respect to some commercial resins is also presented.

Mesoscopic supramolecular assembly of a ‘Janus’ molecule and a melamine derivative via complementary hydrogen bonds

Irregular rods with a minimum diameter of ca. 150 A and lengths of several tens of µm were formed in methylcyclohexane from complementary hydrogen-bond pairs of an alkylalanate-derivatized melamine and a ‘Janus’ molecule; circular dichroism with exciton coupling was induced for the ‘Janus’ chromophore via hydrogen bonds, probably due to the structural regularity of the molecular assembly.

Concise enantioselective synthesis of abscisic acid and a new analogue

Short and high-yielding syntheses of enantiomerically pure (S)-(+) and (R)-(-)-abscisic acid are described. The syntheses proceed through key intermediates that preferentially recrystallise as single diastereoisomers for each enantiomer. This route allows the preparation of either enantiomer of abscisic acid in ca. 30% overall yield, and as demonstrated, gives access to an enantiomerically pure abscisic acid analogue.

Kinetics of formation of single phospholipid bilayers on self-assembled monolayer supports, as monitored by surface plasmon resonance

Abstract The unrolling of small unilamellar vesicles onto a variety of mixed and single-component self-assembled monolayer surfaces has been studied via surface plasmon resonance. In particular, the effect of varying the vesicle concentration has been explored in order to assess the effects of varying the rate of diffusion of vesicles to the surface on the initial rate of lipid layer formation.

Self-complementary hydrogen bonding heterocycles designed for the enforced self-assembly into supramolecular macrocycles

A series of 2-oxopyrimido[4,5-d] pyrimidin-5(6H)-ones are synthesized that contain a hydrogen bond code that mediates their self-organisation into a hexameric supramolecular macrocylic structure.

Novel polymers from atom transfer polymerisation mediated by copper(I) Schiff base complexes

The use of copper(I) Schiff base complex catalysed atom transfer polymerisation of methacrylates is described. The use of a range of functional and multi-functional initiators enables the synthesis of a range of functional and star polymers to be prepared under undemanding synthetic conditions. End capping with silyl enol ethers allows for ω-functional polymers. The combination of novel initiators, functional monomers and end capping allows an unprecedented array of macromolecular structures to be produced with limited need for protecting group chemistry.