Bruce D. Alexander

Metal oxide photoanodes for solar hydrogen production

The development of sustainable hydrogen production is a key target in the further facilitation of a hydrogen economy. Solar hydrogen generation through the photolytic splitting of water sensitised by semiconductor materials is attractive as it is both renewable and does not lead to problematic by-products, unlike current hydrogen sources such as natural gas. Consequently, the development of these semiconductor materials has undergone considerable research since their discovery over 30 years ago and it would seem prescient to review the more practical results of this research. Among the critical factors influencing the choice of semiconductor material for photoelectrolysis of water are the band-gap energies, flat band potentials and stability towards photocorrosion; the latter of these points directs us to focus on metal oxides. Careful design of thin films of photocatalyst material can eliminate potential routes of losses in performance, i.e., recombination at grain boundaries. Methods to overcome these problems are discussed such as coupling a photoanode for photolysis of water to a photovoltaic cell in a “tandem cell” device.

Photoelectrochemical Oxidation of Water at Transparent Ferric Oxide Film Electrodes

Abstract Thin film Fe 2 O 3 photoanodes deposited onto conducting glass substrates were employed for the light-induced splitting of water. The effects of the employed precursor (inorganic or co-ordination compounds), dopants (Ti(IV) and Al(III)) and preparation conditions upon photoelectrochemical characteristics of the films are discussed. A photoelectrolysis cell including an arrangement of three thin film Fe 2 O 3 photoanodes placed one behind another is shown to improve considerably the light harvesting efficiency.

Metal oxide photoanodes for water splitting.

Solar hydrogen production through photocatalytically assisted water splitting has attracted a great deal of attention since its first discovery almost 30 years ago. The publication of investigations into the use of TiO₂ photoanodes has continued apace since and a critical review of current trends is reported herein. Recent advances in the understanding of the behaviour of nanoparticulate TiO₂ films is summarized along with a balanced report into the utility and nature of titania films doped with non-metallic elements and ordered, nanostructured films such as those consisting of nanotubes. Both of these are areas that have generated a not insignificant degree of activity. One goal of doping TiO₂ has been to extend the photoresponse of the material to visible light. A similar goal has seen a resurgence in interest in Fe₂O₃ photoanodes. Herein, the influence of dopants on the photocurrent density observed at Fe₂O₃ photoanodes and, in this regard, the role of silicon has attracted much attention, and a little debate. Finally, we look beyond the binary oxides. Photoanodes made from new materials such as mixed metal oxides, perovskite structured semiconductors, metal (oxy)nitrides or composite electrodes offer the potential to either tailor the optical band gap or tune the conduction or valence band energetics. Recent work in this area is detailed here.

Influence of the preparation method on the physicochemical properties of indomethacin and methyl-β-cyclodextrin complexes.

The main objective of this study was to investigate different manufacturing processes claimed to promote inclusion complexation between indomethacin and cyclodextrins in order to enhance the apparent solubility and dissolution properties of indomethacin. Especially, the effectiveness of supercritical carbon dioxide processing for preparing solid drug-cyclodextrin inclusion complexes was investigated and compared to other preparation methods. The complexes were prepared by physical mixing, co-evaporation, freeze drying from aqueous solution, spray drying and supercritical carbon dioxide processing methods. The prepared complexes were then evaluated by scanning electron microscopy, differential scanning calorimetry, X-ray powder diffraction, solubility and dissolution studies. The method of preparation of the inclusion complexes was shown to influence the physicochemical properties of the formed complexes. Indomethacin exists in a highly crystalline solid form. Physical mixing of indomethacin and methyl-β-cyclodextrin appeared not to reduce the degree of crystallinity of the drug. The co-evaporated and freeze dried complexes had a lower degree of crystallinity than the physical mix; however the lowest degree of crystallinity was achieved in complexes prepared by spray drying and supercritical carbon dioxide processing methods. All systems based on methyl-β-cyclodextrin exhibited better dissolution properties than the drug alone. The greatest improvement in drug dissolution properties was obtained from complexes prepared using supercritical carbon dioxide processing, thereafter by spray drying, freeze drying, co-evaporation and finally by physical mixing. Supercritical carbon dioxide processing is well known as an energy efficient alternative to other pharmaceutical processes and may have application for the preparation of solid-state drug-cyclodextrin inclusion complexes. It is an effective and economic method that allows the formation of solid complexes with a high yield, without the use of organic solvents and problems associated with their residues.

Cyclic α,β-peptoid octamers with differing side chain patterns: synthesis and conformational investigation

The solution-phase synthesis and cyclisation of three α,β-peptoid octamers with differing side chain patterns is reported. One of these, compound C, showed a significantly greater resolution by NMR relative to the other two structurally related octamers. This observation was studied in detail by circular dichroism at a synchrotron light source to facilitate the correlation between the side chain patterns and conformational preference of these three peptoids. The X-ray crystal structure of cyclic octamer C, the first high-resolution structure for the α,β-peptoid backbone, was also obtained from methanol. Combined solid- and solution-phase studies allowed the identification of the N-2-(benzyloxy)ethyl side chain on the β-residue of the heterogeneous backbone as a key structural feature driving the increased conformational stability for octamer C.

Preparation of olanzapine and methyl-β-cyclodextrin complexes using a single-step, organic solvent-free supercritical fluid process: An approach to enhance the solubility and dissolution properties.

The purpose of this study was to evaluate a single-step, organic solvent-free supercritical fluid process for the preparation of olanzapine-methyl-β-cyclodextrin complexes with an express goal to enhance the dissolution properties of olanzapine. The complexes were prepared by supercritical carbon dioxide processing, co-evaporation, freeze drying and physical mixing. The prepared complexes were then analysed by differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, solubility and dissolution studies. Computational molecular docking studies were performed to study the formation of molecular inclusion complexation of olanzapine with methyl-β-cyclodextrin. All the binary mixtures of olanzapine with methyl-β-cyclodextrin, except physical mixture, exhibited a faster and greater extent of drug dissolution than the drug alone. Products obtained by the supercritical carbon dioxide processing method exhibited the highest apparent drug dissolution. The characterisation by different analytical techniques suggests complete complexation or amorphisation of olanzapine and methyl-β-cyclodextrin complexes prepared by supercritical carbon dioxide processing method. Therefore, organic solvent-free supercritical carbon dioxide processing method proved to be novel and efficient for the preparation of solid inclusion complexes of olanzapine with methyl-β-cyclodextrin. The preliminary data also suggests that the complexes of olanzapine with methyl-β-cyclodextrin will lead to better therapeutic efficacy due to better solubility and dissolution properties.

Vibrational spectroscopy and DFT calculations of the di-amino acid peptide L-aspartyl-L-glutamic acid in the zwitterionic state

Solid state IR and Raman as well as aqueous solution state Raman spectra are reported for the linear di-amino acid peptide L-aspartyl-L-glutamic acid (L-Asp-L-Glu); the solution state Raman spectrum has also been obtained for the N,O-deuterated derivative. SCF-DFT calculations at the B3-LYP/cc-pVDZ level established that the structure and vibrational spectra of L-Asp-L-Glu can be interpreted using a model of the peptide with ten hydrogen-bonded water molecules, in conjunction with the conductor-like polarizable continuum solvation method. The DFT calculations resulted in the computation of a stable zwitterionic structure, which displays trans-amide conformation. The vibrational spectra were computed at the optimised molecular geometry, enabling normal coordinate analysis, which yielded satisfactory agreement with the experimental IR and Raman data. Computed potential energy distributions of the normal modes provided detailed vibrational assignments.

Spectroscopic studies of oligomers containing 2,5-trans furanoid sugar amino acids.

Sugar amino acids and their oligomers, known as carbopeptoids, are commonly studied as foldamers. However, study of their conformational preference is often challenging when the adopted conformations are extended and/or disordered. This study is the first to explore the disordered nature of such carbopeptoids by utilizing a family of 2,5-trans carbopeptoids. An array of spectroscopic techniques has been used to investigate the conformational preference of these carbopeptoids. However, using this data alone it has not been possible to assign conformational preference as an ordered extended conformation or as a disordered family of closely related conformations. Computational methods need to be employed to achieve reliable interpretation of the spectroscopic data.

Design, synthesis, characterization and toxicity studies of Poly (N-Iso-Propylacrylamide-co-Lucifer Yellow) particles for drug delivery applications

A novel fluorescent temperature/pH responsive particle was designed, synthesized, characterised and tested for toxicity. Poly (N-iso-propylacrylamide-co-5%-lucifer yellow) (p(NIPAM-co-5% LY)) was prepared using a surfactant free emulsion polymerisation technique. The particles were negatively charged and were approximately 250 nm at 15°C. When the particles de-swell following an increase in temperature, a particle size around 100 nm is obtained. The toxicity of different concentrations of the new particles (p(NIPAM)-co-5% LY, as well as the 100% p(NIPAM) and the main monomer NIPAM was tested on two cell lines (Hela and Vero). The toxicity was tested in comparison to a positive control (dextran sugar) and a negative one (poly(ethylenimine)) (PEI). The results show that the two particles show cell viability over 80% (for both cell lines Hela and Vero) up to a concentration of 3 mg/mL while NIPAM monomer showed cell viability over 80% at a concentration equal to or less than 0.3 mg/mL. The fluorescence property of the novel particles make them traceable. Combining this property (tracing) to the ability of the particles to release their content in response to temperature and pH change can be a potential drug delivery system for cancer treatment.

Solid-state flurbiprofen and methyl-β-cyclodextrin inclusion complexes prepared using a single-step, organic solvent-free supercritical fluid process

The aim of this study was to enhance the apparent solubility and dissolution properties of flurbiprofen through inclusion complexation with cyclodextrins. Especially, the efficacy of supercritical fluid technology as a preparative technique for the preparation of flurbiprofen-methyl-β-cyclodextrin inclusion complexes was evaluated. The complexes were prepared by supercritical carbon dioxide processing and were evaluated by solubility, differential scanning calorimetry, X-ray powder diffraction, scanning electron microscopy, practical yield, drug content estimation and in vitro dissolution studies. Computational molecular docking studies were conducted to study the possibility of molecular arrangement of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin. The studies support the formation of stable molecular inclusion complexes between the drug and cyclodextrin in a 1:1 stoichiometry. In vitro dissolution studies showed that the dissolution properties of flurbiprofen were significantly enhanced by the binary mixtures prepared by supercritical carbon dioxide processing. The amount of flurbiprofen dissolved into solution alone was very low with 1.11±0.09% dissolving at the end of 60min, while the binary mixtures processed by supercritical carbon dioxide at 45°C and 200bar released 99.39±2.34% of the drug at the end of 30min. All the binary mixtures processed by supercritical carbon dioxide at 45°C exhibited a drug release of more than 80% within the first 10min irrespective of the pressure employed. The study demonstrated the single step, organic solvent-free supercritical carbon dioxide process as a promising approach for the preparation of inclusion complexes between flurbiprofen and methyl-β-cyclodextrin in solid-state.