Quantitative measurement of the reduction of platinum(IV) complexes using X-ray absorption near-edge spectroscopy (XANES).

The platinum(II) drugs cisplatin, carboplatin and oxaliplatin are usefully employed against a range of malignancies, but toxicities and resistance have spurred the search for improved analogs. This has included investigation of the platinum(IV) oxidation state, which provides greater kinetic inertness. It is generally accepted that Pt(IV) complexes must be reduced to Pt(II) for activation. As such, the ability to monitor reduction of Pt(IV) complexes is critical to guiding the design of candidates, and providing mechanistic understanding. Here we report in full that the white line height of X-ray absorption near-edge spectra (XANES) of Pt complexes, normalized to the post-edge minima, can be used to quantitatively determine the proportion of each oxidation state in a mixture. A series of Pt(IV) complexes based on the Pt(II) complexes cisplatin and transplatin were prepared with chlorido, acetato or hydroxido axial ligands, and studies into their reduction potential and cytotoxicity against A2780 human ovarian cancer cells were performed, demonstrating the relationship between reduction potential and cytotoxicity. Analysis of white line height demonstrated a clear and consistent difference between Pt(II) (1.52 ± 0.05) and Pt(IV) (2.43 ± 0.19) complexes. Reduction of Pt(IV) complexes over time in cell growth media and A2780 cells was observed by XANES, and shown to correspond with their reduction potentials and cytotoxicities. We propose that this method is useful for monitoring reduction of metal-based drug candidates in complex biological systems.

Unique example of flexible phenol coordination in mononuclear manganese compounds.

The synthesis and characterization of six novel mononuclear Mn(II) and Mn(III) complexes are presented. The tripodal ligands 2-((bis(pyridin-2-ylmethyl)amino)methyl)-4-nitrophenol (HL1), 2-[[((6-methylpyridin-2-yl)methyl)(pyridin-2-ylmethyl)amino]methyl]-4-nitrophenol (HL2), (2-pyridylmethyl)(6-methyl-2-pyridylmethyl)(2-hydroxybenzyl)amine (HL3) and 2-((bis(pyridin-2-ylmethyl)amino)methyl)-4-bromophenol were used. All ligands provide an N3O donor set. The compounds [Mn(II)(HL1)Cl2].CH3OH (1), [Mn(III)(L1)Cl2] (2), [Mn(II)(HL2)(EtOH)Cl2] (3), [Mn(II)(HL3)Cl2].CH3OH (4), [Mn(III)(HL4)Br2] (5) and [Mn(III)(L1)(tcc)] (6), with tcc = tetrachlorocatecholate dianion, were synthesized and characterized by various techniques such as X-ray crystallography, mass spectrometry, IR and UV-vis spectroscopy, cyclic voltammetry, and elemental analysis. Compound 1 crystallizes in the triclinic space group P1, compounds 2, 3 and 4 were solved in the monoclinic space group P2(1)/c, whereas the structure determination of and succeeded in the orthorhombic space groups Pbca and P2(1)2(1)2(1), respectively. Notably, the crystal structures of 1 and 3 are the first Mn(II) complexes featuring a non-coordinating phenol moiety. Compound 2 oxidizes 3,5-di-tert-butylcatechol to 3,5-di-tert-butylquinone exhibiting saturation kinetics at high substrate concentrations with a turnover number of kcat = 173 h(-1). The electronic influence of different substituents in para position of the phenol group is lined out.

Catalytic oxidation of 3,5-Di-tert-butylcatechol by a series of mononuclear manganese complexes: synthesis, structure, and kinetic investigation.

The manganese compounds [Mn(bpia)(OAc)(OCH(3))](PF(6)) (1), [Mn(bipa)(OAc)(OCH(3))](PF(6)) (2), [Mn(bpia)(Cl)(2)](ClO(4)) (3), [Mn(bipa)(Cl)(2)](ClO(4)) (4), [Mn(Hmimppa)(Cl)(2)] x CH(3)OH (5), and [Mn(mimppa)(TCC)] x 2CHCl(3) (6) (bpia = bis(picolyl)(N-methylimidazole-2-yl)amine; bipa = bis(N-methylimidazole-2-yl)(picolyl)amine; Hmimppa = ((1-methylimidazole-2-yl)methyl)((2-pyridyl)methyl)(2-hydroxyphenyl)amine; TCC = tetrachlorocatechol) were synthesized and characterized by various techniques such as X-ray crystallography, mass spectrometry, IR, EPR, and UV/vis spectroscopy, cyclic voltammetry, and elemental analysis. 1 and 2 crystallize in the triclinic space group Ponemacr; (No. 2), 4 and 6 crystallize in the monoclinic space group P2(1)/n (No. 14), and 5 crystallizes in the orthorhombic space group Pna2(1). Complexes 1-4 are structurally related to the proposed active site of the manganese-dependent extradiol-cleaving catechol dioxygenase exhibiting an N(4)O(2) donor set (1 and 2) or N(4)Cl(2) donor set (3 and 4). Cyclic voltammetric data show that the substitution of oxygen donor atoms with chloride causes a shift of redox potentials to more positive values. These compounds show high catalytic activity regarding the oxidation of 3,5-di-tert-butylcatechol to 3,5-di-tert-butylquinone exhibiting saturation kinetics at high substrate concentrations. The turnover numbers k(cat) = (86 +/- 7) h(-1) (1), k(cat) = (101 +/- 4) h(-1) (2), k(cat) = (230 +/- 4) h(-1) (3), and k(cat) = (130 +/- 4) h(-1) (4) were determined from the double reciprocal Lineweaver-Burk plot. Compounds 5 and 6 can be regarded as structural and electronic Mn analogues for substituted forms of Fe-containing intradiol-cleaving catechol dioxygenases. To our knowledge 5 is the first mononuclear Mn(II) compound featuring an N(3)OCl(2) donor set.