title: Synthesis and Analysis of the Structure, Diffusion and Cytotoxicity of Heterocyclic Platinum(IV) Complexes.
abstract: We have developed six dihydroxidoplatinum(IV) compounds with cytotoxic potential. Each derived from active platinum(II) species, these complexes consist of a heterocyclic ligand (HL) and ancillary ligand (AL) in the form [Pt(HL)(AL)(OH)2](2+), where HL is a methyl-functionalised variant of 1,10-phenanthroline and AL is the S,S or R,R isomer of 1,2-diaminocyclohexane. NMR characterisation and X-ray diffraction studies clearly confirmed the coordination geometry of the octahedral platinum(IV) complexes. The self-stacking of these complexes was determined using pulsed gradient stimulated echo nuclear magnetic resonance. The self-association behaviour of square planar platinum(II) complexes is largely dependent on concentration, whereas platinum(IV) complexes do not aggregate under the same conditions, possibly due to the presence of axial ligands. The cytotoxicity of the most active complex, exhibited in several cell lines, has been retained in the platinum(IV) form.
authors.affiliation: Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, NSW 2560 (Australia).
authors.forename: Freddy J
authors.initials: FJ
authors.lastname: Macias
authors.affiliation: Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, NSW 2560 (Australia).
authors.forename: Krishant M
authors.initials: KM
authors.lastname: Deo
authors.affiliation: Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, NSW 2560 (Australia).
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Pages
authors.affiliation: Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, NSW 2560 (Australia).
authors.forename: Paul
authors.initials: P
authors.lastname: Wormell
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane St. Lucia, QLD 4072 (Australia).
authors.forename: Jack K
authors.initials: JK
authors.lastname: Clegg
authors.affiliation: Australian Nuclear Science and Technology Organisation, Kirrawee DC, NSW 2232 (Australia).
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, NSW 2560 (Australia).
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.affiliation: Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, NSW 2560 (Australia).
authors.forename: Gang
authors.initials: G
authors.lastname: Zheng
authors.affiliation: Calvary Mater Newcastle, Waratah, NSW 2298 (Australia).
authors.forename: Jennette
authors.initials: J
authors.lastname: Sakoff
authors.affiliation: Calvary Mater Newcastle, Waratah, NSW 2298 (Australia).
authors.forename: Jayne
authors.initials: J
authors.lastname: Gilbert
authors.affiliation: Nanoscale Organisation and Dynamics Group, Western Sydney University, Campbelltown, NSW 2560 (Australia). j.aldrich-wright@uws.edu.au.
authors.forename: Janice R
authors.initials: JR
authors.lastname: Aldrich-Wright
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000633:toxicity*; D002460:Cell Line; D018360:Crystallography, X-Ray; D003514:Cyclohexylamines / Q000737:chemistry*; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000032:analysis* / Q000138:chemical synthesis* / Q000633:toxicity*; D010618:Phenanthrolines / Q000737:chemistry*; D010984:Platinum / Q000737:chemistry* / Q000633:toxicity*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
chemical_list: D000970:Antineoplastic Agents; D003514:Cyclohexylamines; D008024:Ligands; D009944:Organoplatinum Compounds; D010618:Phenanthrolines; D010984:Platinum; C030435:1,2-cyclohexanediamine; C025205:1,10-phenanthroline
keywords: X-ray diffraction; antitumor agents; cancer; cytotoxicity; platinum