Investigations of the Kinetics and Mechanism of Reduction of a Carboplatin Pt(IV) Prodrug by the Major Small-Molecule Reductants in Human Plasma.

The development of Pt(IV) anticancer prodrugs to overcome the detrimental side effects of Pt(II)-based anticancer drugs is of current interest. The kinetics and reaction mechanisms of the reductive activation of the carboplatin Pt(IV) prodrug -[Pt(cbdca)(NH)Cl] (cbdca = cyclobutane-1,1-dicarboxylate) by the major small-molecule reductants in human plasma were analyzed in this work. The reductants included ascorbate (Asc), the thiol-containing molecules L-cysteine (Cys), DL-homocysteine (Hcy), and glutathione (GSH), and the dipeptide Cys-Gly.

Reduction of ormaplatin by an extended series of thiols unravels a remarkable correlation.

Ormaplatin ([Pt(dach)Cl4]) represents one of the three primary structural prototypes of Pt(iv) anticancer-active prodrugs. The reduction of ormaplatin by an extended series of thiols has been studied kinetically in a broad pH range. A novel and remarkable correlation between log kRS- and the thiol dissociation constants pKRSH is disclosed: log kRS- = (0.

Kinetics and mechanism of oxidation of the anti-tubercular prodrug isoniazid and its analog by iridium(iv) as models for biological redox systems.

A complex reaction mechanism of oxidation of the anti-tubercular prodrug isoniazid (isonicotinic hydrazide, INH) by [IrCl] as a model for redox processes of such drugs in biological systems has been studied in aqueous solution as a function of pH between 0 and 8.5. Similar experiments have been performed with its isomer nicotinic hydrazide (NH).

Reactivity of the glutathione species towards the reduction of ormaplatin (or tetraplatin).

The reduction of ormaplatin (tetraplatin), a prototype for Pt(IV) anticancer prodrugs, by glutathione (GSH) was kinetically characterized over a wide pH range at 25.0°C and 1.0M ionic strength.

Thermodynamics for complex formation between palladium(ii) and oxalate.

Complex formation between [Pd(H2O)4](2+) and oxalate (ox = C2O4(2-)) has been studied spectrophoto-metrically in aqueous solution at variable temperature, ionic strength and pH. Thermodynamic parameters at 298.2 K and 1.

Structures of polynuclear complexes of palladium(II) and platinum(II) formed by slow hydrolysis in acidic aqueous solution.

The aqua ions of palladium(II) and platinum(II) undergo extremely slow hydrolysis in strongly acidic aqueous solution, resulting in polynuclear complexes. The size and structures of these species have been determined by EXAFS and small angle X-ray scattering, SAXS. For palladium(II), the EXAFS data show that the Pd-O and Pd···Pd distances are identical to those of crystalline palladium(II) oxide, but the intensities of the Pd···Pd distances in the Fourier transform at 3.

Pseudo-rotation mechanism for fast olefin exchange and substitution processes at orthometalated C,N-complexes of platinum(II).

Bridge splitting in chloroform of the orthometalated chloro-bridged complex [Pt(micro-Cl)(2-Me(2)NCH(2)C(6)H(4))](2)(1), with ethene, cyclooctene, allyl alcohol and phosphine according to 1+ 2L --> 2[PtCl(2-Me(2)NCH(2)C(6)H(4))(L)], where L = C(2)H(4)(3a), C(8)H(14), (3b), CH(2)CHCH(2)OH (3c), and PPh(3)(4a and 4b) gives monomeric species with L coordinated trans or cis to aryl. With olefins the thermodynamically stable isomer with L coordinated cis to aryl is formed directly without an observable intermediate. With phosphine and pyridine, the kinetically controlled trans-product isomerizes slowly to the more stable cis-isomer.

Reaction Mechanism for Olefin Exchange at Chloro Ethene Complexes of Platinum(II).

Complex equilibria in methanol/chloroform/dichloromethane solutions containing Zeise's anion, [PtCl(3)(C(2)H(4))](-) (1), the solvento species, trans-[PtCl(2)(C(2)H(4))(MeOH)] (2), and the dinuclear complex, trans-[PtCl(2)(C(2)H(4))](2) (3), have been studied by UV-vis, (1)H, and (195)Pt NMR spectroscopy, giving average values of K(Cl) = (1.6 +/- 0.2)10(3) M(-)(1) and K(S) = (0.

Kinetics and Mechanism for Formation of Olefin Complexes in the Reaction between Palladium(II) and Maleic Acid.

Complex formation between Pd(H(2)O)(4)(2+) and maleic acid (H(2)A) has been studied at 25 degrees C and 2.00 M ionic strength in acidic aqueous solution. Reaction takes place with 1:1 stoichiometry.

Iron-Manganese Redox Processes and Synergism in the Mechanism for Manganese-Catalyzed Autoxidation of Hydrogen Sulfite.

The mechanism for manganese-catalyzed aqueous autoxidation of hydrogen sulfite at pH 2.4 has been revised on the basis of previous comprehensive kinetic studies and thermodynamic data for iron-manganese redox processes and manganese(II) and -(III) protolysis equilibria. The catalytically active manganese species is concluded to be an oxo- (or hydroxo-) bridged mixed-valence complex of composition (OH)Mn(III)OMn(II)(aq) with a formation constant beta' of (3 +/- 1) x 10(4) M(-)(1) from kinetics or ca.

Equilibria, Kinetics, and Mechanism for Rapid Substitution Reactions Trans to Triphenylsilyl in Platinum(II) Complexes.

Fast substitution of chloride for bromide and iodide trans to triphenylsilyl in trans-PtCl(SiPh(3))(PMe(2)Ph)(2) has been studied by stopped-flow spectrophotometry in acetonitrile solution. Substitution is reversible with an observable solvent path via the solvento complex trans-[Pt(SiPh(3))(MeCN)(PMe(2)Ph)(2)](+), which has also been synthesized and characterized in solution. Rate constants for the forward and reverse direct substitution pathways are 2900 +/- 100 and 7500 +/- 300 for bromide and 14300 +/- 1100 and 81000 +/- 11000 M(-)(1) s(-)(1) for iodide as nucleophile.

Protonolysis of Dialkyl- and Alkylarylplatinum(II) Complexes and Geometrical Isomerization of the Derived Monoorgano-Solvento Complexes: Clear-Cut Examples of Associative and Dissociative Pathways in Platinum(II) Chemistry.

Protonolysis of the complexes cis-[PtR(2)(PEt(3))(2)] (R = Me, Et, Pr(n)(), Bu(n)(), CH(2)C(Me)(3), CH(2)Si(Me)(3)) and cis-[Pt(R)(R')(PEt(3))(2)] (R = Ph, 2-MeC(6)H(4), 2,4,6-Me(3)C(6)H(2); R' = Me) in methanol selectively cleaves one alkyl group, yielding cis-[Pt(R)(PEt(3))(2)(MeOH)](+) and alkanes. The reactions occur as single-stage conversions from the substrate to the product. There is no evidence by UV and by low-temperature (1)H and (31)P NMR spectroscopy for the presence of significant amounts of Pt(II) or Pt(IV) intermediate species.

Synthesis, Structure, and Reactivity of Arylchlorobis(dialkyl sulfide)platinum(II) Complexes.

Complexes trans-[PtRCl(SR'(2))(2)], where R = Ph, mesityl, and p-anisyl and R' = Me or Et, have been synthesized and their crystal and molecular structures determined. Crystals of trans-[PtPhCl(SEt(2))(2)] (2) are triclinic (P&onemacr;) with a = 10.112(6) Å, b = 13.

Theoretical Modeling of Water Exchange on [Pd(H(2)O)(4)](2+), [Pt(H(2)O)(4)](2+), and trans-[PtCl(2)(H(2)O)(2)].

Density functional theory is applied to modeling the exchange in aqueous solution of H(2)O on [Pd(H(2)O)(4)](2+), [Pt(H(2)O)(4)](2+), and trans-[PtCl(2)(H(2)O)(2)]. Optimized structures for the starting molecules are reported together with trigonal bipyramidal (tbp) systems relevant to an associative mechanism. While a rigorous tbp geometry cannot by symmetry be the actual transition state, it appears that the energy differences between model tbp structures and the actual transition states are small.

Competitive Substitution and Electron Transfer in Reactions between Haloamminegold(III) and Halocyanoaurate(III) Complexes and Thiocyanate.

Kinetics for reactions between thiocyanate and trans-Au(CN)(2)Cl(2)(-), trans-Au(CN)(2)Br(2)(-), and trans-Au(NH(3))(2)Cl(2)(+) in an acidic, 1.00 M perchlorate aqueous medium have been studied by use of conventional and diode-array UV/vis spectroscopy and high-pressure and sequential-mixing stopped-flow spectrophotometry. Initial, rapid formation of mixed halide-thiocyanate complexes of gold(III) is followed by slower reduction to Au(CN)(2)(-) and Au(NH(3))(2)(+), respectively.