ABSTRACT
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. Synchrotron X-ray fluorescence (microbeam XRF) imaging has demonstrated for the first time that uniform uptake of Gd(III) complex 2 within a population of T98G cells increased as a function of increasing Gd incubation times. The Gd maps show dispersed spots of high intensity which are consistent with mitochondrial uptake.
Subject(s)
Coordination Complexes/pharmacology , Gadolinium/chemistry , Onium Compounds/pharmacology , Organophosphorus Compounds/pharmacology , Cell Line, Tumor/metabolism , Coordination Complexes/chemistry , Coordination Complexes/metabolism , Coordination Complexes/toxicity , Humans , Mitochondria/metabolism , Molecular Structure , Onium Compounds/chemistry , Onium Compounds/metabolism , Onium Compounds/toxicity , Organophosphorus Compounds/chemistry , Organophosphorus Compounds/metabolism , Organophosphorus Compounds/toxicityABSTRACT
The khmer package is a freely available software library for working efficiently with fixed length DNA words, or k-mers. khmer provides implementations of a probabilistic k-mer counting data structure, a compressible De Bruijn graph representation, De Bruijn graph partitioning, and digital normalization. khmer is implemented in C++ and Python, and is freely available under the BSD license at https://github.com/dib-lab/khmer/.