Selective delivery of remarkably high levels of gadolinium to tumour cells using an arsonium salt.

The use of a triphenylarsonium vector for tumour cell-targeting leads to a dramatic increase in Gd uptake in human glioblastoma multiforme cells by up to an order of magnitude over the isosteric triarylphosphonium analogue, with significant implications for 'theranostic' applications involving delivery of this important lanthanoid metal ion to tumour cells.

Oligodendrocyte-encoded Kir4.1 function is required for axonal integrity.

Glial support is critical for normal axon function and can become dysregulated in white matter (WM) disease. In humans, loss-of-function mutations of which encodes the inward-rectifying potassium channel KIR4.1, causes seizures and progressive neurological decline.

Tumor cell uptake and selectivity of gadolinium(III)-phosphonium complexes: The role of delocalisation at the phosphonium centre.

The synthesis of a series of bifunctional Gd(III) complexes 1-3 covalently bound to arylphosphonium cations possessing a varying degree of delocalisation at the phosphonium centre is presented. The influence of the degree of delocalisation was investigated with regards to in vitro cytotoxicity, cellular uptake of Gd, tumor-cell selectivity and intracellular localisation of Gd within human glioblastoma (T98G) and human glial (SVG p12) cells. Cellular uptake and selectivity studies for the Gd(III) complexes indicate that a reduced delocalisation at the phosphonium centre can lead to an enhanced Gd uptake into SVG p12 cells which results in a decrease in the overall tumor cell selectivity.

Synthesis and biological evaluation of a class of mitochondrially-targeted gadolinium(III) agents.

A structure-activity relationship study of a library of novel bifunctional Gd(III) complexes covalently linked to arylphosphonium cations is reported. Such complexes have been designed for potential application in binary cancer therapies such as neutron capture therapy and photon activation therapy. A positive correlation was found between lipophilicity and cytotoxicity of the complexes.

The first CNS-active carborane: A novel P2X7 receptor antagonist with antidepressant activity.

Relative to other polycyclic frameworks (1-3), a carborane cage (4 and Cs·5) exerts a significant biological effect as an inhibitor of the purinergic P2X7 receptor (P2X7R) which allows one to target depression in vivo and thus demonstrate, for the first time, that a carborane has the capacity to modify CNS activity.

High mitochondrial accumulation of new gadolinium(III) agents within tumour cells.

The first bifunctional Gd(III) complexes covalently bound to arylphosphonium cations and the first tumour-cell selective mitochondrial agents designed for potential application in binary cancer therapies are reported. The highest in vitro cellular uptake for any Gd complex reported to date is described, with levels exceeding 10(10) Gd atoms per tumour cell.

Boronated phosphonium salts containing arylboronic acid, closo-carborane, or nido-carborane: synthesis, X-ray diffraction, in vitro cytotoxicity, and cellular uptake.

The preparation of boronated triaryl and tetraaryl phosphonium salts of the type [PPh(3)CH(2)R]Br [R is 4-boronophenyl (1), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-yl)phenyl (2), 3-boronophenyl (3), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-yl)phenyl (4), 2-boronophenyl (5), 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-yl)phenyl (6), and closo-1,2-carboran-1-yl (7)] is described. These compounds were prepared by the reaction of triphenylphosphine with benzylic bromides or 1-bromomethyl-closo-1,2-carborane in acetonitrile solution at 85 °C. The zwitterionic nido-7,8-carborane derivative PPh(3)CH(2)C(2)B(9)H(11) (8) was prepared by treatment of 7 with cesium fluoride in refluxing ethanol.