Gold(I) chloride adducts of 1,3-bis(di-2-pyridylphosphino)propane: synthesis, structural studies and antitumour activity.
The novel water soluble bidentate phosphine ligand 1,3-bis(di-2-pyridylphosphino)propane (d2pypp) has been synthesized by a convenient route involving treatment of 2-pyridyllithium with Cl(2)P(CH(2))(3)PCl(2) and isolation in crystalline form as the hydrochloride salt. The synthesis of the precursor Cl(2)P(CH(2))(3)PCl(2) has been optimized by the use of triphosgene as the chlorinating agent. The 2 : 1 and 1 : 2 AuCl : d2pypp adducts have been synthesized and characterized by NMR spectroscopy and single crystal X-ray studies, and shown to be of the form (AuCl)(2)(mu-d2pypp-P,P') and [Au(d2pypp-P,P')(2)]Cl(.3.75H(2)O), respectively. The latter is more lipophilic than analogous 1 : 2 adducts of gold(I) chloride with the diphosphine ligands 1,2-bis(di-n-pyridylphosphino)ethane (dnpype) for n = 2, 3 and 4, based on measurement of the n-octanol-water partition coefficient (log P = -0.46). A single crystal structure determination of the 1 : 2 Au(I) complex of the 3-pyridyl ethane ligand shows it to be of the form [Au(d3pype-P,P')(2)]Cl.5H(2)O. The in vitro cytotoxic activity of [Au(d2pypp)(2)]Cl was assessed in human normal and cancer breast cells and selective toxicity to the cancer cells found. The significance of these results to the antitumour properties of chelated 1 : 2 Au(I) diphosphine complexes is discussed.
Humphreys
Anthony S
AS
School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
Filipovska
Aleksandra
A
Berners-Price
Susan J
SJ
Koutsantonis
George A
GA
Skelton
Brian W
BW
White
Allan H
AH
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D017612:Gold Compounds / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D011407:Propane / Q000031:analogs & derivatives* / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry*; D016339:Spectrometry, Mass, Fast Atom Bombardment
C526469:1,3-bis(di-2-pyridylphosphino)propane; D000970:Antineoplastic Agents; D017612:Gold Compounds; D011725:Pyridines; C038016:gold chloride; D011407:Propane