| Summary: | The anti-cancer activity of the water-soluble complexes cis- and trans-
RuCl2(DMSO)4 has led, in this laboratory, to further investigation of disulfoxide complexes
of Ru as potential chemotherapeutic agents.
The dithioether precursors and disulfoxides were synthesized in this work following
literature procedures. The disulfoxides used were of the formula RS(O)(CH2)nS(O)R, where
R = Et (BESE) or Ph (BPhSE) for n = 2; and R = Et (BESP) or Pr (BPSP) for n = 3, and the
dithioether used was BPTP (l,3-bis(propylthio)propane). These compounds/ligands were
reacted with Ru precursors to yield complexes characterized mainly by NMR, elemental
analysis, IR, and conductivity, while three complexes were also characterized by X-ray
crystallography.
A mixed sulfoxide/disulfoxide complex, cis-RuCl2(DMSO)2(BESE), was isolated
during this thesis work. The water-soluble complex was characterized by X-ray
crystallography, the solution chemistry was studied, and preliminary in vitro tests were
performed. The crystal structure shows cis chlorides, one O-bound DMSO, one S-bound
DMSO, and S-bound BESE. The complex does not exhibit significant host toxicity toward
CHO (Chinese hamster ovarian) cells below 1.1 mM, and was found to have essentially no
anti-cancer activity, at concentrations up to 3 mM, toward human mammary cancer cells.
The known complex [RuCl(BESE)(H2O)]2(μ-Cl)2 ionizes in aqueous solution to
generate 2 equiv. of H+ and 2 equiv. Cl per mole of complex, and sulfoxide exchange
reactions with the in situ formed species (thought to be [Ru(BESE)(OH)(H2O)]2(μ-Cl)2) were
briefly studied.
In an attempt to synthesize the previously characterized, dinuclear complex
[RuCl2(BPTP)]2(μ-Cl)2 , trans-RuCl2(BPTP)2 was isolated and characterized by NMR, and
elemental analysis. The synthesis of thioether complexes was performed to attempt a
subsequent oxidation of the coordinated dithioether while retaining the geometry about the
Ru.
This thesis work led to the isolation of three Ru disulfoxide-bridged complexes. One
such complex, [RuCl3(BPhSE)](μ-BPhSE), was characterized by elemental analysis, IR, and
mass spectrometry, and two Ru(p-cymene) complexes with bridging sulfoxides were also
isolated. The first, [RuCl2(p-cymene)]2(μ-BESE), was characterized by X-ray
crystallography and contains S-bound sulfoxide, while the other, [RuCl2(p-cymene)]2(μ-
BESP), characterized by NMR, elemental analysis, and IR, appears to be chemically similar
to the μ-BESE complex. [RuCl2(p-cymene)]2(μ-BESE) was shown in vitro to exhibit no
significant host toxicity below concentrations of 1.1 mM, but did exhibit, in the concentration
range 345-360 μM, anti-cancer activity against human mammary cancer cells.
A third p-cymene complex, [RuCl(p-cymene)(BESE)]PF6 , was characterized by X-ray crystallography and shown to have S-bound sulfoxide. [Scientific formulae used in this abstract could not be reproduced.] === Science, Faculty of === Chemistry, Department of === Graduate
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