Decoupling the effects of hydrophilic and hydrophobic moieties at the neuron–nanofibre interface

Peptide-based nanofibres are a versatile class of tunable materials with applications in optoelectronics, sensing and tissue engineering. However, the understanding of the nanofibre surface at the molecular level is limited. Here, a series of homologous dilysine–diphenylalnine tetrapeptides were synthesised and shown to self-assemble into water-soluble nanofibres. Despite the peptide nanofibres displaying similar morphologies, as evaluated through atomic force microscopy and neutron scattering, significant differences were observed in their ability to support sensitive primary neurons. Contact angle and labelling experiments revealed that differential presentation of lysine moieties at the fibre surface did not affect neuronal viability; however the mobility of phenylalanine residues at the nanofibre surface, elucidated through solid- and gel-state NMR studies and confirmed through tethered bilayer lipid membrane experiments, was found to be the determining factor in governing the suitability of a given peptide as a scaffold for primary neurons. This work offers new insights into characterising and controlling the nanofibre surface at the molecular level.

The mobility of hydrophobic moieties at a peptide nanofibre surface determines its suitability as a scaffold for sensitive primary cells.     

The synthesis and studies towards the self-replication of bis(capped porphyrins)

Connecting two facially-protected porphyrins was expected to lead to an equal mixture of laterally-bridged doubly-protected bis-porphyrins; one in which the two porphyrin units were protected on the same face (syn) and one with the two prophyrin units protected on opposite faces (anti). Addition of a co-factor (bidentate ligand) was expected to lead predominantly to the syn-bis-porphyrin by a templated self-replication process. This concept was explored using Baldwin's capped porphyrin. Bis(capped porphyrins) were synthesised in several steps starting from zinc(II) capped porphyrin 2. Nitration of 2 followed by reduction and photo-oxidation yields a mixture of zinc(II) porphyrindiones 7 and 8 that can separated by HPLC. The condensation of 2 molar eq. of zinc(II) porphyrin-7,8-dione 8 with 1,2,4,5-benzenetetramine leads to the formation of a 1:1 mixture of syn- and anti-dizinc(II) bis(7,8-capped porphyrins), 11 and 12, respectively, that have almost identical spectroscopic properties. These two geometric isomers were distinguished by significant differences in their molecular recognition properties. Likewise the syn- and anti-dizinc(II) bis(2,3-capped porphyrins), 9 and 10, respectively, are synthesised from the related zinc(II) capped porphyrin-2,3-dione 7, and were also identified using molecular recognition studies. The molecular recognition properties of these bis(capped porphyrins) were utilised in studies of self-replicating porphyrin systems. The results show that tetraazaanthraceno-bis-porphyrins 9-12 can catalyse their own formation but self-replication was not observed. These results highlight the potential that these interesting hosts have as templates in supramolecular chemistry, synthesis and catalysis.     

Polymersomes Prepared from Thermoresponsive Fluorescent Protein–Polymer Bioconjugates: Capture of and Report on Drug and Protein Payloads

Polymersomes provide a good platform for targeted drug delivery and the creation of complex (bio)catalytically active systems for research in synthetic biology. To realize these applications requires both spatial control over the encapsulation components in these polymersomes and a means to report where the components are in the polymersomes. To address these twin challenges, we synthesized the protein–polymer bioconjugate PNIPAM‐b‐amilFP497 composed of thermoresponsive poly(N‐isopropylacrylamide) (PNIPAM) and a green‐fluorescent protein variant (amilFP497). Above 37 °C, this bioconjugate forms polymersomes that can (co‐)encapsulate the fluorescent drug doxorubicin and the fluorescent light‐harvesting protein phycoerythrin 545 (PE545). Using fluorescence lifetime imaging microscopy and Förster resonance energy transfer (FLIM‐FRET), we can distinguish the co‐encapsulated PE545 protein inside the polymersome membrane while doxorubicin is found both in the polymersome core and membrane.     

Photophysical properties of a new series of water soluble iridium bisterpyridine complexes functionalised at the 4' position

Four new hetero- and homo-leptic iridium(III) bisterpyridine complexes have been prepared which incorporate aniline (tpy-φ-NH(2)), benzoic acid (tpy-φ-COOH), and benzyl alcohol (tpy-φ-CH(2)OH) substituents at the 4' positions of the tpy ligands (tpy = 2,2':6',2'-terpyridine, φ = phenylene). The electrochemical behaviour and ground and excited state spectroscopic properties of the complexes are reported, and the X-ray crystal structures of a homoleptic benzyl alcohol [Ir(tpy-φ-CH(2)OH)(2)](PF(6))(3), homoleptic aniline [Ir(tpy-φ-NH(2))(2)](PF(6))(3), and heteroleptic benzyl alcohol/aniline substituted complex [Ir(tpy-φ-CH(2)OH)(tpy-φ-NH(2))](PF(6))(3) have been solved. Complexes with aniline substituents were found to display absorption bands at around 430 nm corresponding to intraligand charge transfer (ILCT) that are sensitive to changes in solvent and pH. Strong emission in the visible region involving the ILCT state is observed in two of the complexes (Φ(e) = 0.7% and 2.6%) in acetonitrile. In the heteroleptic aniline/benzyl alcohol complex the Stokes shift is shown to be linearly related to solvent polarisability according to the Lippert equation, but only for solvents with weak hydrogen bonding interactions. Additionally, in water, emission from the ILCT state is quenched and only weak ligand centred (LC) emission is observed. The long lifetimes and quantum yields of these complexes make them interesting candidates for probes in sensing applications, especially [Ir(tpy-φ-CH(2)OH)(tpy-φ-NH(2))(2)](PF(6))(3) due to its unusual sensitivity to the solvent environment.     

Induced polymersome formation from a diblock PS-b-PAA polymer via encapsulation of positively charged proteins and peptides

In contrast to simple salts or negatively charged macromolecules, positively charged proteins and peptides including cytochrome c (yeast) and poly-L-lysine are efficiently encapsulated while inducing the formation of polymersomes from polystyrene(140)-b-poly(acrylic acid)(48) (PS(140)-b-PAA(48)).     

Porphyrin dyads linked by a rotatable 3,3'-biphenyl scaffold: a new binding motif for small ditopic molecules

Synthetic access to a set of metallo- and free base bis-porphyrins has been provided by a stepwise approach involving sequential peptide and Suzuki couplings. Linking these porphyrins through a 3,3'-biphenyl bridge enables cooperative binding to ditopic ligands such as the bipyridyls. Association constants and binding stoichiometry has been determined by spectroscopic/spectrophotometric means and the differences in the binding affinities of a small series of diaza ligands is discussed in the context of structural fit and microscopic association constants.