Arsonium and phosphonium-functionalized gold nanoparticles for mitochondria targeted therapeutics

This thesis presents a body of original research describing the synthesis, characterisation and biological properties of novel arsonium- and phosphonium- alkylthiosulfate zwitterions and thioacetate salts and gold nanoparticles functionalized with triphenylarsoniumpropylthiolate ligands. Chapter 1 presents a systematic literature review of the preparation of functionalized gold nanoparticles, their biomedical properties, the biological applications of phosphonium and arsonium ions and phosphonium-functionalized nanomaterials. Details of the analytical methods employed to characterize all the compounds produced in this study are outlined in chapter 2. Chapter 3 reports the synthesis of the triphenylarsoniopropylthiosulfate zwitterion and ω- thioacetylpropyl(triphenyl)arsonium bromide salt. Both compounds have been characterized spectroscopically and by single crystal X-ray diffraction. The thiosulfate group of the triphenylarsoniopropylthiosulfate zwitterion and the thioacetate group of the ω- thioacetylpropyl(triphenyl)arsonium salt undergo reductive cleavage, forming the corresponding triphenylarsoniumpropylthiolate ions that attach to the surface of gold in a modification of the established Brust-Schiffrin method for preparing gold nanoparticles. TEM studies show the triphenylarsonium-functionalized gold nanoparticles to be spherical with diameters of c.a. 3nm. The presence of the triphenylarsonium groups has been confirmed by Raman and XPS spectroscopy and mass spectrometry. It also describes the synthesis, characterisation and biological properties of a family of phosphoniopropylthiosulfate zwitterions and ω-thioacetylpropyl(triaryl)phosphonium salts derived from tri(4-methoxyphenyl)phosphine, tri(2,6-dimethoxyphenyl)phosphine and tri(2,4,6-trimethoxyphenyl)phosphine. The IC50 values of the triphenylarsoniopropylthiosulfate zwitterion, ω-thioacetylpropyl- (triphenyl)arsonium bromide salt, triphenylarsonium-functionalized gold nanoparticles and family of phosphoniopropylthiosulfate zwitterions and ω- thioacetylpropyl(triaryl)phosphonium salts derived from tri(4-methoxyphenyl)phosphine, tri(2,6-dimethoxyphenyl)phosphine and tri(2,4,6-trimethoxyphenyl)phosphine have been determined against PC3 prostate cancer cells using MTT and CellTiter-Glo assays and are reported in Chapter 4. The uptake of the triphenylarsonium-functionalized gold nanoparticles by PC3 and Human Fibroblast cells has also been determined by ICP-OES spectroscopy

Additional file 1: Figure S1. of RpoN2- and FliA-regulated fliTX is indispensible for flagellar motility and virulence in Xanthomonas oryzae pv. oryzae

Coomassie blue staining of the FliTX protein expressed and extracted from E. coli strain BL21. M: Molecular marker; 1: FliTX in the soluble fraction; 2: purified FliTX; 3: FliTX in the insoluble fraction. (TIFF 424 kb

Additional file 2: Table S1. of RpoN2- and FliA-regulated fliTX is indispensible for flagellar motility and virulence in Xanthomonas oryzae pv. oryzae

The primers used in this study. (DOCX 17 kb

Overview of the workflow.

<p>It shows the pipeline of experimental process and bioinformatics process for this study.</p

SNV Information.

<p>This table revealed that the distribution of SNVS of transition and transversion in different samples.</p

Contrast of SNVs between benign samples and malignant samples.

<p>There are three pairs of circles close together in this figure. The color of green, blue and grey represents the tumor tissue, blood and adjacent normal tissue respectively. In every pair of circle, the inner circle represents malignant sample C080 and the outer circle represents benign sample T009. Each red point is the position of a SNV and the rectangular black box surround the SNVs which share the same position in several samples.</p

Summary of the polymorphisms in HPV genes.

1<p>nonsynonymous mutation.</p>2<p>synonymous mutation.</p>3<p>Transition.</p>4<p>Transversion.</p

Overview of the workflow.

<p>It shows the pipeline of experimental process and bioinformatics process for this study.</p

The display of SNVs in a sample set.

<p><b>A</b>. SNVs for sample set of C080; <b>B</b>. SNVs for sample set of T009. The locations of the genes are shown in different colors. Each red point is the position of a SNV and the rectangular black box surround the SNVs which share the same position in several samples. Genomic positions are numbered. <b>A</b>. It is cancer tumor, blood, lymph nodes and adjacent normal tissue from the outside to the inside. <b>B</b>. There are three green circles and it is tumor tissue, blood and adjacent normal tissue from the outside to the inside.</p