title: The synthesis, chemical and biological properties of dichlorido(azpy)gold(III) chloride (azpy=2-(phenylazo)pyridine) and the gold-induced conversion of the azpy ligand to the chloride of the novel tricyclic pyrido[2,1-c][1,2,4]benzotriazin-11-ium cation.
abstract: A new Au(III) coordination compound with the ligand 2-(phenylazo)pyridine has been synthesized and fully characterized by means of elemental analysis, IR, UV-visible, conductivity measurements, NMR, electrospray ionization (ESI-MS) and inductively coupled plasma optical emission spectrometry (ICP-OES). The chemical stability of the cation in this compound, [Au(azpy)Cl(2)](+) (abbreviated: Au-azpy), was analyzed by means of several physicochemical methods. While stable in the solid state, stability studies performed with the gold compound in solution showed an unexpected and unprecedented reactivity. A cationic organic derivative of 2-(phenylazo)pyridine, (abbreviated: pyrium), was produced from the solution and has been isolated as its chloride salt and characterized by crystal structure determination, elemental analysis, NMR, ESI-MS and conductivity studies in solution. This cyclization reaction is reported for the first time in the case of gold coordination compounds. The Au adduct and the pyrium cation were investigated as potential cytotoxic and anticancer agents, and both show moderate to high cytotoxic properties in cisplatin-sensitive and cisplatin-resistant ovarian carcinoma cell lines, A2780; and cisplatin-sensitive and cisplatin-resistant murine lymphocytic leukemia cell lines, L1210. Significant anticancer activity against the cisplatin resistant cell lines was found for the pyrium salt, ruling out the occurrence of cross resistance phenomena.
authors.affiliation: Leiden Institute of Chemistry, Gorlaeus Laboratories, Leiden University, P.O. Box 9502, 2300 RA Leiden, The Netherlands.
authors.forename: Ariadna
authors.initials: A
authors.lastname: Garza-Ortiz
authors.forename: Hans
authors.initials: H
authors.lastname: den Dulk
authors.forename: Jaap
authors.initials: J
authors.lastname: Brouwer
authors.forename: Huub
authors.initials: H
authors.lastname: Kooijman
authors.forename: Anthony L
authors.initials: AL
authors.lastname: Spek
authors.forename: Jan
authors.initials: J
authors.lastname: Reedijk
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D003500:Cyclization; D019008:Drug Resistance, Neoplasm; D006046:Gold / Q000737:chemistry*; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D050607:Organogold Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
chemical_list: D000970:Antineoplastic Agents; D050607:Organogold Compounds; D011725:Pyridines; D006046:Gold; C023666:pyridine; D002945:Cisplatin