1,3-Bis(hydroxy­meth­yl)benzimidazolin-2-one

The title compound, C9H10N2O3, crystallizes with one and a half mol­ecules in the asymmetric unit, one lying on a general position and the other on a twofold rotation axis. The dihedral angle between the two independent benzimidazole ring systems is 18.96 (5)°. In the crystal, mol­ecules are linked into a three-dimensional network by O—H⋯O hydrogen bonding involving N-hydroxy­methyl and carbonyl groups, and C—H⋯O hydrogen bonds

Spontaneous Self-Assembly of Thermoresponsive Vesicles Using a Zwitterionic and an Anionic Surfactant.

Spontaneous formation of vesicles from the self-assembly of two specific surfactants, one zwitterionic (oleyl amidopropyl betaine, OAPB) and the other anionic (Aerosol-OT, AOT), is explored in water using small-angle scattering techniques. Two factors were found to be critical in the formation of vesicles: surfactant ratio, as AOT concentrations less than equimolar with OAPB result in cylindrical micelles or mixtures of micellar structures, and salt concentration, whereby increasing the amount of NaCl promotes vesicle formation by reducing headgroup repulsions. Small-angle neutron scattering measurements reveal that the vesicles are approximately 30-40 nm in diameter, depending on sample composition. Small-angle X-ray scattering measurements suggest preferential partitioning of OAPB molecules on the vesicle inner layer to support vesicular packing. Heating the vesicles to physiological temperature (37 °C) causes them to collapse into smaller ellipsoidal micelles (2-3 nm), with higher salt concentrations (≥10 mM) inhibiting this transition. These aggregates could serve as responsive carriers for loading or unloading of aqueous cargoes such as drugs and pharmaceuticals, with temperature changes serving as a simple release/uptake mechanism.Australian Research Council Future Fellowship (FT160100191) to Rico Tabor. and a Discovery Early Career Research Award (DE190100531) to Andrew Clulow

A review of a strategic roadmapping exercise to advance clinical translation of photoacoustic imaging: From current barriers to future adoption

Photoacoustic imaging (PAI), also referred to as optoacoustic imaging, has shown promise in early-stage clinical trials in a range of applications from inflammatory diseases to cancer. While the first PAI systems have recently received regulatory approvals, successful adoption of PAI technology into healthcare systems for clinical decision making must still overcome a range of barriers, from education and training to data acquisition and interpretation. The International Photoacoustic Standardisation Consortium (IPASC) undertook an community exercise in 2022 to identify and understand these barriers, then develop a roadmap of strategic plans to address them. Here, we outline the nature and scope of the barriers that were identified, along with short-, medium- and longterm community efforts required to overcome them, both within and beyond the IPASC group

Sigma receptor ligands: a systematic approach in the design and synthesis

The sigma (σ) receptor is a neuromodulatory protein, widely expressed in the central nervous system (CNS) and to a lesser extent, the peripheral nervous system (PNS). Currently, two sigma receptor subtypes are known; sigma-1 receptors (S1R) and sigma-2-receptors (S2R), differing in molecular weight, pharmacological profile, distribution and function. The S1R has been implicated in depression, schizophrenia, Alzheimer’s disease, Parkinson’s disease, drug abuse and more recently for its involvement in analgesia. The design of highly subtype-selective ligands is limited by a lack of information regarding the S1R/S2R binding site, a lack of crystal structure data on S1R until 2016, as well as a large structurally-diverse collection of known ligands. The currently accepted pharmacophore arising from this extensive ligand library proposes an alkylamine core tethered by two hydrophobic groups. Several highly subtype-selective S1R ligands fitting this pharmacophore have been previously synthesised in the Kassiou laboratory. This project investigates the optimisation of the lead 1-(benzofuran-2-ylmethyl)-4-(4-methoxybenzyl)piperazine with considerable focus on the flexibility and basicity of the piperazine core. Furthermore, bioisosteres of piperazine, phenyl, and the size tolerance of the hydrophobic sites of the S1R are also investigated. Binding affinities and sub-type selectivities were determined by in vitro binding assays of both S1R and S2R, with structure-activity relationships drawn from these modifications. This work aims at refining the S1R pharmacophore and to create S1R-selective ligands that can be used as probes to further understand the physiological role, as well as the morphology, of the S1R receptor. Ultimately, they may lead to remedies to treat the CNS diseases associated with this receptor

Evaluation of Tris cationic lipids as transport vehicles for platinum (II) complexes

The objective of this project was to enhance the activity of existing and new platinum(II) complexes against cancer through encapsulation in cationic liposomes. In this study a range of platinum(II) complexes the type [Pt(intercalating ligand)(ancillary ligand)]2+ (where the intercalating ligands were: 1,10-phenanthroline, 5-methyl-1,10-phenanthroline, 5,6-dimethyl-1,10-phenanthroline, 4,7-dimethyl-1,10-phenanthroline, 3,4,7,8-tetramethyl-1,10-phenanthroline or 4- methyl-1,10-phenanthroline and the ancillary ligands were: 1S,2R- and 1R,2Rdiaminocyclohexane, 1,2-diaminoethane, 1,2R- and 1,2S-diaminopropane, 2S,3S-, 2R,3R- and 2S,3R-diaminobutane) were synthesised, characterised and biologically tested. The ligand 2,3-diaminobutane was synthesised and resolved. The resulting platinum compounds were characterised by one and two dimensional 1H, 13C and 195Pt NMR experiments. Complexes were also analysed by ESI-MS, microanalysis, UV-Vis and circular dichroism (CD) including synchrotron radiation circular dichroism (SRCD) spectroscopy. The platinum(II) complexes were tested against a range of cancerous cell lines to determine their cytotoxicity. Selected platinum(II) complexes were combined with K3C6TL3 liposomes and the resulting formulations were characterised by HPLC, DLS (dynamic light scattering), ESI-MS, synchrotron small angle X-ray scattering (SSAXS), 1H Pulsed Gradient Spin Echo (PGSE) NMR and linear dichroism (LD). The formulations were also used in preliminary cytotoxicity assays against a number of cancerous cell lines to determine if encapsulation enhances the activity of platinum(II) complexe

The synthesis of platinum(II) intercalators

The pharmacological properties of any drug are largely dependent on binding interactions with biomolecules. The investigation of such interactions is essential to gain some understanding of the mechanisms of drug action, and to determine which structural characteristics influence the pharmacological properties. Of particular interest are the interactions between anticancer agents and DNA, as DNA is considered to be the major cellular target for a large number of compounds that are effective in the treatment of various types of cancers. It has been reported that the binding of such drugs to DNA can inhibit cellular processes such as DNA replication and transcription, which are vital for the proliferation of cells. The inhibition or prevention of cell division is the primary objective for drug design as it most markedly affects rapidly dividing cells such as tumour cells, and ultimately prevents their spread throughout the body

Mo-doped, Cr-doped, and Mo–Cr codoped TiO2 thin-film photocatalysts by comparative sol-gel spin coating and ion implantation

Uniformly codoped anatase TiO2 thin films of varying (equal) Mo and Cr concentrations (<= 1.00 mol% for each dopant) were fabricated using sol-gel spin coating and deposited on fused silica substrates. All films were annealed at 450 degrees C for 2 h to recrystallise anatase. Undoped anatase films have been subjected to dual ion implantation for the first time, using Mo, Cr, and sequential Mo thorn Cr at 1 x 10(14) atoms/cm(2). The films were characterised by GAXRD, AFM, SIMS, XPS, and UV-Vis and the performance was assessed by dye degradation. Despite the volumetric doping by sol-gel and the directional doping by ion implantation, neither method resulted in homogeneous dopant distributions. Both methods caused decreasing crystallinities and associated partial amorphisation. The XPS signal of the uniformly codoped films is dominated by undissolved dopant ions, which is not the case for the ion-implanted films. Increasing Ti valences are attributed to the fully oxidised condition of the Ti4+ ions that diffuse to the surface from Ti vacancy formation compared to the Ti valence of the bulk lattice, which contains Ti3+. Increasing O valence is attributed to the electronegativity of O2-, which is higher than that of Ti4+. Detailed structural mechanisms for the solubility and energetics mechanisms involve the initial formation of Mo and Cr interstitials that fill the two voids adjacent to the central Ti ion in the TiO6 octahedron, followed by integrated solid solubility (ISS) and intervalence/multivalence charge transfer (IVCT/MVCT). The sequential order of the last two is reversed for the two different doping methods. These two effects are likely to be the source of synergy, if any, between the two dopant ions. The photocatalytic performances of the uniformly codoped films are relatively poor and correlate well with the band gap (E-g). The performances of the ion-implanted films do not correlate with the E-g, where TiO2-Mo performs poorly but TiO2-Cr and TiO2-Mo-Cr outperform the undoped film. These results are interpreted in terms of the competition between the effects of Mo doping, which causes partial amorphisation and/or blockage of active sites, and Cr doping, which may cause Mo-Cr synergism, Cr-based heterojunction formation, and/or improved charge-carrier separation owing to the surface-deposition nature of ion implantation

Advances in platinum chemotherapeutics

The approved platinum(II)-based anticancer agents cisplatin, carboplatin and oxaliplatin are widely utilised in the clinic, although with numerous disadvantages. With the aim of circumventing unwanted side-effects, a great deal of research is being conducted in the areas of cancer-specific targeting, drug administration and drug delivery. The targeting of platinum complexes to cancerous tissues can be achieved by the attachment of small molecules with biological significance. In addition, the administration of platinum complexes in the form of platinum(IV) allows for intracellular reduction to release the active form of the drug, cisplatin. Drug delivery includes such technologies as liposomes, dendrimers, polymers and nanotubes, with all showing promise for the delivery of platinum compounds. In this paper we highlight some of the recent advances in the field of platinum chemotherapeutics, with a focus on the technologies that attempt to utilise the cytotoxic nature of cisplatin, whilst improving drug targeting to reduce side-effects