Optically pure heterobimetallic helicates from self-assembly and click strategies

Single diastereomer, diamagnetic, octahedral Fe(II) tris chelate complexes are synthesised that contain three pendant pyridine proligands pre-organised for coordination to a second metal. They bind Cu(I) and Ag(I) with coordination geometry depending on the identity of the metal and the detail of the ligand structure, but for example homohelical (ΔFe,ΔCu) configured systems with unusual trigonal planar Cu cations are formed exclusively in solution as shown by VT-NMR and supported by DFT calculations. Similar heterobimetallic tris(triazole) complexes are synthesised via clean CuAAC reactions at a tris(alkynyl) complex, although here the configurations of the two metals differ (ΔFe,ΛCu), leading to the first optically pure heterohelicates. A second series of Fe complexes perform less well in either strategy as a result of lack of preorganisation

Asymmetric triplex metallohelices with high and selective activity against cancer cells

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and ​p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 ​p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli. At a glanc

Computations in non-commutative Iwasawa theory

We study special values of L-functions of elliptic curves over Q twisted by Artin representations that factor through a false Tate curve extension $Q(\mu_p^\infty,\sqrt[p^\infty]{m})/Q$. In this setting, we explain how to compute L-functions and the corresponding Iwasawa-theoretic invariants of non-abelian twists of elliptic curves. Our results provide both theoretical and computational evidence for the main conjecture of non-commutative Iwasawa theory.Comment: 60 pages; with appendix by John Coates and Ramdorai Sujath

Uist Lagoons Survey

Scotland has around a hundred saline lagoons, coastal lochs that are not quite as saline as the sea. A small number of organisms are confined to these lochs, but most of these are very small and belong to groups that are difficult to identify. A consortium of specialists in identification at the National Museum of Scotland and ecologists sampled most of the saline lagoons on designated sites (SSSI and SAC) in the Uists, the area believed to have the best biodiversity of lagoon organisms in Scotland. The study not only confirmed the presence of these specialist species, but also that they were more widely distributed in the Uists than had been believed. Samples of the organisms have been placed in the permanent collections of the National Museum of Scotland and (for plants) in the Royal Botanic Gardens Edinburgh, where they will be available for future study

High-Dose Chemotherapy Followed by Peripheral and/or Bone Marrow Stem Cell Transplant in Patients With Advanced Sarcoma: Experience of a Canadian Centre

Purpose: Few reports have been published on the evaluation of stem cell auto transplantation for chemosensitive sarcomas. Some suggest benefit, others do not. We present results of 24 patients with sarcoma undergoing autotransplantation at a Canadian institution