Coordination chemistry and solution behaviour of gold (I) complexes

[摘要] English: The aim of this study was to extend the knowledge base of gold(I) coordination chemistry and investigate the substitution behaviour of these complexes with sulphurdonor ligands. The water-soluble and air-stable ligand 1,3,5-triaza-7- phosphatricyclo[3.3.1.13,7]decane (PTA) with low steric demand was employed in the synthesis of the various complexes in this study. The [Au(PTA)Cl] complex was reacted with S-donor ligands such as SCN¯, thiourea and methyl thiourea and the equilibrium constant determination was done using 31P NMR by monitoring the chemical shift change when stoichiometric amounts of the ligand are added to the [Au(PTA)Cl] solution. The equilibrium constants obtained were 0.070(6), 4.191(1) and 6.734(3) for SCN¯, thiourea and methyl thiourea as entering ligands, respectively. The X-ray crystal structure of the inclusion of the PTA 'guest' molecule into the 'host' b- cyclodextrin (b-CD) was determined. The PTA-b-CD·8H2O inclusion compound crystallises in the monoclinic space group P21 with eight solvent water molecules in an asymmetric unit and was refined to a final R value of 4.35%. The packing within the PTA-b-CD·8H2O inclusion compound is of a 'herring-bone' type motif. An attempt to include auranofin {[Au(PEt3)(Sgluc)]; Sgluc = thioglucose} into the cavity of the b- cyclodextrin resulted in only auranofin crystallising without being included. However, since the data collection for the auranofin compound was done at 100 K, careful observations in parameters such as selected torsion and bond angles were noted to have 1-4° changes as compared to the known auranofin structure investigated at room temperature, which clearly indicated a phase change and a new polymorph at 100 K. The pure auranofin compound investigated in this study crystallises in the monoclinic space group P21 and was refined to a final R value of 1.59%. Further study of the interactions of b-cyclodextrin with PTA and related ligands and gold(I) complexes in this study was investigated with NMR spectroscopy. This was done by the determination of the equilibrium constant when these complexes are included into the b-cyclodextrin. The equilibrium constants calculated for PTA, (PTAMe)+ and PPh3 were 8.7(1) x 102 and 23(4) and 10(6) M-1, respectively, while for the [Au(PTAMe)Cl] and [Au(dppe)2]Cl equilibrium constants of 23(5) and 6(1) M-1 were obtained. The PTA ligand clearly showed the largest 'host-guest' stability. The solubility of the phenyl compounds, following the inclusion, was not improved that much as compared to the PTA compounds which may be due to steric hindrance and orientation of the phenyl groups being too large to be incorporated into the b-cyclodextrin. This phenomenon is also noted in the unsuccessful incorporation of auranofin which may be due the orientation of the ethyl groups into b-cyclodextrin. In an attempt to increase the solubility of these gold(I) complexes, bidentate P-donor ligand systems with a bridging ferrocene group, functionalised by hydrophilic moieties, were synthesised. These complexes were unambiguously characterised by X-ray crystallography. The following dinuclear gold(I) crystal structures are reported, with their general crystal data reported in parenthesis: [(AuCl)2(m-dppf-CH(CH3)N(CH3)2)] (Monoclinic, P21/n, R = 4.94%) [(AuSCN)2(m-dppf-CH(CH3)N(CH3)2)] (Triclinic, P 1 , R = 5.76%) [(AuCl)2(m-dppf-CH(CH3)OAc)] (Orthorhombic, Pbca, R = 4.09%) [(AuSCN)2(m-dppf-CH(CH3)OAc)] (Triclinic, P 1 , R = 4.36%) [(AuSCN)2(m-dppf)] (Monoclinic, C2/c, R = 2.36%) The SCN¯ ligand in the thiocyanato gold(I) dppf structures coordinated to the soft Au(I) metal centre via the softer S atom. An interesting factor was the isomorphism identified for the two [(AuSCN)2(m-dppf-CH(CH3)N(CH3)2)] and [(AuSCN)2(m-dppf-CH(CH3)OAc)] structures while the structure for the [(AuSCN)2(m-dppf)] compound was interlinked by short Au…Au contacts of 2.9798(7) Å of which none were observed for the other structures. Auranofin and its derivative compounds such as PTA-auranofin, PTAMe-auranofin and triethylarsine-auranofin were utilised and tested for biological activity against cancer cell lines. Furthermore, a preliminary chemiluminescence assay was done with the compounds at three different concentrations (0.3, 3.1 and 12.5 mM for each compound) to determine their effect on the chemiluminescence of isolated blood neutrophils. The auranofin compound was included in the investigations as reference. The A2780 human ovarian cancer cell lines are the most sensitive to all derivatives while the arsine-auranofin compound showed good activity against A2780 human ovarian cancer cell lines with an IC50 of only about 0.0076 mg/mL. Generally, auranofin and arsineauranofin gave results closely related to each other with arsine-auranofin having higher toxicity to other cells whereas PTA-auranofin and PTAMe-auranofin showed more correlation to each other and had less activity. For the preliminary chemiluminescence assays it can be mentioned that for all auranofin derivatives, at low concentrations the compounds act as stimulants to the neutrophil chemiluminescence activity and at higher concentrations the compounds act as inhibitors to neutrophil activity. Complex substitution behaviour was observed for selected gold(I) dinuclear {[(AuCl)2(m- dppf-CH(CH3)OAc)]} and mononuclear systems {[Au(PX)Cl]; X = Ph3 or Ph2Fc} when the chloride is substituted with ligands such as L-cysteine and SCN¯ as studied by UVVis and 31P NMR. Furthermore, fast reaction kinetics for the chloride substitution with ligands such as SCN¯ and dimethylthiourea from the mononuclear [Au(PPh3)Cl] complex was investigated with stopped-flow techniques. The overall rate constants for the substitutions from [Au(PPh3)Cl] with SCN¯ and dimethyl thiourea representing the forward reactions were obtained as k1 = 13(1) and 2.17(1) x 103 M-1s-1 respectively. Thus, it was concluded that chloride substitution reactions on linear gold(I) systems are extremely fast reactions.

[发布机构] University of the Free State