Cationic, linear Au(I) N-heterocyclic carbene complexes:: synthesis, structure and anti-mitochondrial activity

被引:240
作者
Baker, Murray V. [1 ]
Barnard, Peter J. [1 ]
Berners-Price, Susan J. [1 ]
Brayshaw, Simon K. [1 ]
Hickey, James L. [1 ]
Skelton, Brian W. [1 ]
White, Allan H. [1 ]
机构
[1] Univ Western Australia, Sch Biomed Biomol & Chem Sci, Crawley, WA 6009, Australia
关键词
D O I
10.1039/b602560a
中图分类号
O61 [无机化学];
学科分类号
070301 ; 081704 ;
摘要
Six linear, two-coordinate cationic Au( I) N-heterocyclic carbene complexes of the form [(R(2)Im)(2)Au](+) (R = Me 1, Me, Et 2, i-Pr 3, n-Bu 4, t-Bu 5 and Cy 6) have been prepared by the reaction of two equivalents of the appropriate dialkylimidazol-2-ylidene (R(2)Im) with (Me2S) AuCl in dmf. Single crystal structural studies for 1 . PF6, 2 . PF6, 3 . Cl and 4 - 6 . PF6 show that for all six complexes the gold( I) centres have quasi-linear C - Au - C coordination, with quasi-parallel pairs of aromatic imidazole planes, except in 5 . PF6 where they are quasi- normal; in the latter, Au - C are 2.038( 3), 2.033( 3) angstrom, cf. ( e. g.) 3 2.027( 2) angstrom. Inter-cation Au center dot center dot center dot Au are close at 3.487( 2), 3.525( 2) angstrom in 1 . PF6 and 2 . PF6. The structural studies and low temperature NMR experiments provide no supportive evidence for the presence of pi back-bonding within this series of complexes. The lipophilicities of the six compounds, as estimated from the logarithm of the n-octanol-water partition coefficients ( log P), varied across the series within the range - 1.09 to 1.73. To investigate their potential as possible anti-mitochondrial anti-tumour agents, five of the compounds have been evaluated for their propensities to induce mitochondrial membrane permeabilization (MMP) in isolated rat liver mitochondria. At concentrations between 1 - 10 mu M compounds 1 . Br and 3 - 6 . Cl induced dose-dependent, Ca2+-sensitive mitochondrial swelling at rates that increased with the lipophilicities of the complexes, with the most lipophilic compounds inducing the most rapid onset of swelling. The swelling was completely inhibited by cyclosporin A, the specific inhibitor of the mitochondrial permeability transition pore.
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页码:3708 / 3715
页数:8
相关论文
共 47 条
  • [1] Albert A., 1979, PHYSIOCHEMICAL BASIS
  • [2] ARDUENGO AJ, 1991, Patent No. 9114678
  • [3] Synthesis and structural characterisation of linear Au(I) N-heterocyclic carbene complexes: New analogues of the Au(I) phosphine drug Auranofin
    Baker, MV
    Barnard, PJ
    Berners-Price, SJ
    Brayshaw, SK
    Hickey, JL
    Skelton, BW
    White, AH
    [J]. JOURNAL OF ORGANOMETALLIC CHEMISTRY, 2005, 690 (24-25) : 5625 - 5635
  • [4] Synthetic, structural and spectroscopic studies of (pseudo)halo(1,3-di-tert-butylimidazol-2-ylidine) gold complexes
    Baker, MV
    Barnard, PJ
    Brayshaw, SK
    Hickey, JL
    Skelton, BW
    White, AH
    [J]. DALTON TRANSACTIONS, 2005, (01) : 37 - 43
  • [5] Mitochondrial permeability transition induced by dinuclear gold(I)-carbene complexes: potential new antimitochondrial antitumour agents
    Barnard, PJ
    Baker, MV
    Berners-Price, SJ
    Day, DA
    [J]. JOURNAL OF INORGANIC BIOCHEMISTRY, 2004, 98 (10) : 1642 - 1647
  • [6] Dinuclear gold(I) complexes of bridging bidentate carbene ligands: synthesis, structure and spectroscopic characterisation
    Barnard, PJ
    Baker, MV
    Berners-Price, SJ
    Skelton, BW
    White, AH
    [J]. DALTON TRANSACTIONS, 2004, (07) : 1038 - 1047
  • [7] BARNARD PJ, 2003, P GOLD 2003 INT C SC
  • [8] Mitochondrial transport of cations: Channels, exchangers, and permeability transition
    Bernardi, P
    [J]. PHYSIOLOGICAL REVIEWS, 1999, 79 (04) : 1127 - 1155
  • [9] Berners-Price SJ, 1998, J CHEM SOC DALTON, P1743
  • [10] NMR and structural studies of gold(I) chloride adducts with bidentate 2-, 3- and 4-pyridyl phosphines
    Berners-Price, SJ
    Bowen, RJ
    Hambley, TW
    Healy, PC
    [J]. JOURNAL OF THE CHEMICAL SOCIETY-DALTON TRANSACTIONS, 1999, (08): : 1337 - 1346