Adam Ahmed Abdallah Sulaiman2022-05-182022-05-185909https://drepo.sdl.edu.sa/handle/20.500.14154/2156Recent advancement in the field of drug formulation and discovery of gold(I) compounds is leading to the innovation of new and unusual gold(I) molecules with linear structure and geometry around the cation. The gold(I) dithiocarbamate complexes, (2-17), (18-22), (23-26), (27-30) and (31-34), type ([Au(R3P)(R2NCS2)] (where R2= dimethyl, diethyl and dibenzyl) were prepared by the reaction of R3PAuCl compound with sodium dimethyldithiocarbamate monohydrate and sodium diethyl dithiocarbamate trihydrate and dibenzyldithiocarbamate, respectively. The precusors have been prepared by the reaction of (CH3)2SAuCl (1) with equimolar amount of R3P. In addition, the complexes of gold(I) phosphine (35-37), gold(I) carbene (38-50), gold(I) thione (51-55) and gold(I) carbene (56-65) have been prepared. These complexes were characterized by FT-IR, 1H, 13C, 31P, 77Se NMR spectroscopy and elemental analysis. Complexes 27, 39, 44, 46, 48, 49, 54, 55, 56, 61, 63 and 65 were characterized by X-ray diffraction analysis, showing linear geometrical structure around gold center atom. Gold(I) complex (20-22) (IC50 19.56 ± 0.85, 29.25 ± 1.81 and 34.42 ± 1.02 μM) showed potent in vitro cytotoxicity one-to-two fold higher than cisplatin (IC50 42.2 ± 2.01 μM) against A549 (human lung carcinoma). Furthermore, complex 48 (IC50 27.97 ± 1.67) showed better in vitro cytotoxicity than cisplatin (IC50 32.04 ± 2.12 μM) against HCCT15. All other studied complexes exhibited similar and moderate to lower in vitro cytotoxicity against A549, HCT15 (human colon cancer) and HeLa (human cervical cancer) cell lines. The interactions of the synthesized [Au(cis-DACH)Cl2]Cl and [Au(cis-DACH)2]Cl3 complexes, (DACH=cis-1,2-diaminocyclohexane), with enriched (13C,15N) thiourea and 1,3-diazinane-2-thione ligands were investigated. The progress of these reactions was monitored with NMR (1H, 13C and 15N) and UV-Vis spectroscopy as well as square wave stripping voltammetry. The kinetics of the substitution reactions between the above-mentioned complexes with thione ligands were studied in aqueous solutions containing 30 mM KCl, which is used to suppress hydrolysis of the chloride complex. The reactions were followed under pseudo first-order conditions as a function of ligand concentration, pH and temperature in the range of 15-37 °C. The activation parameters (ΔH#, ΔS#) were calculated from Eyring plot and the negative values of ΔS≠ lend support for an associative mechanism. The kinetic data also indicate a relatively higher reactivity of [Au(cis-DACH)Cl2]Cl than [Au(cis-DACH)2]Cl3 towards the thiones. The interaction of [Au(cis-DACH)Cl2]Cl and [Au(cis-DACH)2]Cl3 complexes [where cis-DACH: is cis-1,2-diaminocyclohexane] with enriched (13C,15N) KCN were carried out in CD3OD and D2O, respectively. The reaction pathways of these complexes were studied by 1H, 13C, 15N NMR, UV spectrophotometry and electrochemistry. The kinetic data of the reaction of cyanide ion with [Au(cis-DACH)2]Cl3 are found to be k = 18 M-1s-1, ΔH≠ = 11 kJmol-1, ΔS≠ = -185 JK-1mol-1, and Ea = 13 kJ mol-1 with SWV peak +1.35 V, whereas the kinetic data for the reaction of cyanide ion with [Au(cis-DACH)Cl2]Cl are found to be k = 148 M-1s-1, ΔH≠ = 39 kJmol-1, ΔS≠ = -80 JK-1mol-1, and Ea= 42 kJmol-1 along with SWV peak +0.82 V, indicating the much higher reactively of [Au(cis-DACH)Cl2]Cl toward cyanide ligand than [Au(cis-DACH)2]Cl3. The interaction of these complexes with potassium cyanide resulted in an unstable [Au(13CN)4]¯ specie, which readily underwent reductive elimination reaction to generate [Au(13CN)2] ̅ and cyanogen (NCCN). Kinetic measurements revealed the rate constants of the interaction between [Au(cis-DACH)Cl2]Cl with Tu and DIAZ are 49.50; 121.70 and 24.31; 46.65 M-1s-1, respectively, at 288 K and 310 K. Similarly, the rate constants for [Au(cis-DACH)2]Cl3 with Tu and DIAZ are found to be 41.88; 64.86 and 21.68; 40.89 M-1s-1, respectively at 288 K and 310 K. [Au(cis-DACH)Cl2]Cl reacted faster towards thione ligands than [Au(cis-DACH)2]Cl3 complex; also Tu reacted faster than DIAZ towards these complexes. The negative values of ΔS≠ for these reactions lend support for an associative mechanism.enThesis