Mimicking Elementary Reactions of Manganese Lipoxygenase Using Mn-hydroxo and Mn-alkylperoxo Complexes

Manganese lipoxygenase (MnLOX) is an enzyme that converts polyunsaturated fatty acids to alkyl hydroperoxides. In proposed mechanisms for this enzyme, the transfer of a hydrogen atom from a substrate C-H bond to an active-site MnIII-hydroxo center initiates substrate oxidation. In some proposed mechanisms, the active-site MnIII-hydroxo complex is regenerated by the reaction of a MnIII-alkylperoxo intermediate with water by a ligand substitution reaction. In a recent study, we described a pair of MnIII-hydroxo and MnIII-alkylperoxo complexes supported by the same amide-containing pentadentate ligand (6Medpaq). In this present work, we describe the reaction of the MnIII-hydroxo unit in C-H and O-H bond oxidation processes, thus mimicking one of the elementary reactions of the MnLOX enzyme. An analysis of kinetic data shows that the MnIII-hydroxo complex [MnIII(OH)(6Medpaq)]+ oxidizes TEMPOH (2,2′-6,6′-tetramethylpiperidine-1-ol) faster than the majority of previously reported MnIII-hydroxo complexes. Using a combination of cyclic voltammetry and electronic structure computations, we demonstrate that the weak MnIII-N(pyridine) bonds lead to a higher MnIII/II reduction potential, increasing the driving force for substrate oxidation reactions and accounting for the faster reaction rate. In addition, we demonstrate that the MnIII-alkylperoxo complex [MnIII(OOtBu)(6Medpaq)]+ reacts with water to obtain the corresponding MnIII-hydroxo species, thus mimicking the ligand substitution step proposed for MnLOX.

Synthesis of no-carrier-added [188, 189, 191Pt]cisplatin from a cyclotron produced 188, 189, 191PtCl42− complex

We developed a novel method for production of no-carrier-added (n.c.a.) [188, 189, 191Pt]PtIICl42− from an Ir target material, and then synthesized n.c.a. [*Pt]cis-[PtIICl2(NH3)2] ([*Pt]cisplatin) from [*Pt]PtIICl42−. [*Pt]PtIICl42− was prepared as a synthetic precursor of n.c.a. *Pt complex by a combination of resin extraction and anion-exchange chromatography after the selective reduction of IrIVCl62− with ascorbic acid. The ligand-substitution reaction of Cl with NH3 was promoted by treating n.c.a. [*Pt]PtIICl42− with excess NH3 and heating the reaction mixture, and n.c.a. [*Pt]cisplatin was successfully produced without employing precipitation routes. After this treatment, [*Pt]cisplatin was isolated through preparative HPLC with a radiochemical purity of 99 + % at the end of synthesis (EOS).

Synthesis of n.c.a. [188, 189, 191pt] Cisplatin From a Cyclotron-produced n.c.a. 188, 189, 191PtCl42- Complex

We developed a novel method for production of no-carrier-added (n.c.a.) [188, 189, 191Pt]PtⅡCl42- from an Ir target material, and then synthesized n.c.a. [*Pt]cis-[PtⅡCl2(NH3)2] ([*Pt]cisplatin) from [*Pt]PtⅡCl42-. [*Pt]PtⅡCl42- was prepared as a synthetic precursor of n.c.a. *Pt complex by a combination of resin extraction and anion-exchange chromatography after the selective reduction of IrⅣCl62- with ascorbic acid. The ligand-substitution reaction of Cl with NH3 was promoted by treating n.c.a. [*Pt]PtⅡCl42- with excess NH3 and heating the reaction mixture, and n.c.a [*Pt]cisplatin was successfully produced without employing precipitation routes. After this treatment, [*Pt]cisplatin was isolated through preparative HPLC with a radiochemical purity of 99+% at the end of synthesis (EOS).

The kinetics and mechanism of the ligand substitution reaction of aquapentacyanoruthenate(II) with d-penicillamine in aqueous medium

The kinetics of the formation of the light orange–coloured complex [Ru(CN)5D-PA]3− are studied spectrophotometrically through substitution of a coordinated H2O molecule in aquapentacyanoruthenate(II) [Ru(CN)5OH2]3− by interaction with D-penicillamine [D-PA] in aqueous medium at 490 nm (λmax of [Ru(CN)5D-PA]3−). The reaction is monitored under pseudo-first-order conditions, taking [D-PA] in excess over [Ru(CN)5OH23−]. The effects of various reaction parameters on the rate of the reaction are investigated. Experimental observations reveal that the variation in [D-PA] obeyed the first-order rate law while it is found to be invariant with [Ru(CN)5OH23−] in the whole experimental range. With ionic strength variation, as the reaction advances a decrease in the reaction rate is noticed. The product stoichiometry is assigned as 1:1. The ease of substitution at an H2O molecule in [Ru(CN)5OH23−] is considered on the basis of the electronic effect generated through interactions of the M–OH2 bond. A provisional mechanism based on the calculated results is proposed based on the slowest step of the reaction.

Kinetics and mechanism of formation of the complex [Ru(CN)5INH]3− through the ligand substitution reaction between the aquapentacyanoruthenate(II) anion and isoniazid

The formation kinetics of the complex, [Ru(CN)5INH]3−, formed through the ligand substitution reaction between isoniazid (INH) and aquapentacyanoruthenate(II) ([Ru(CN)5H2O]3−), have been investigated, under pseudo first-order conditions, as a function of concentrations of [INH] and [Ru(CN)5H2O]3−, ionic strength and temperature at pH = 4.0 ± 0.02 in 0.2 M NaClO4 spectrophotometrically at 502 nm ( λmax of intense yellow colour product [Ru(CN)5INH]3−) corresponding to metal-to-ligand charge-transfer transitions, in aqueous medium. The pseudo first-order condition was maintained by taking at least 10% excess of [INH] over [Ru(CN)5H2O]3−. The stoichiometry of the reaction product was found to be 1:1 which was further supported and characterized using elemental analysis, infrared, nuclear magnetic resonance and mass spectrometric techniques. Thermodynamic and kinetic parameters have also been computed, using the Eyring equation, and the values of ΔH≠, Ea, ΔG≠ and ΔS≠ were found to be 47.3 kJ mol−1, 49.8 kJ mol−1, −8.62 kJ mol−1 and 187.6 J K−1mol−1, respectively. The reaction was found to obey first-order kinetics with respect to [INH]. It exhibited a negative salt effect on the rate upon variation of ionic strength of the medium. A tentative mechanistic scheme was proposed on the basis of experimental findings.

Synthesis, Characterization And Electrolytic Behavior Of Cadmium(II) Complexes Of 5,7,7,12,14,14- Hexamethyl-1,4,8,11-Tetraazacyclotetradeca-4,11- Diene And Isomers Of Its Saturated Analogue

Condensation of ethylendiamine with acetone in the presence of quantitative amount of perchloric acid, yielded the ligand 5,7,7,12,14,14- hexamethyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene dihydroperchlorate (denoted by L.2HClO4). The ligand L.2HClO4 on reduction with NaBH4, yielded an isomeric mixture of saturated macrocycles, the Me6[14]anes, which were resolved into two distinct C-chiral isomers (denoted by ‘tet-a’ and ‘tet-b’). Interaction of ligands L.2HClO4, ‘tet-a’ and ‘tet-b’ with salts CdI2, Cd(NO3)2.4H2O, CdCl2.2H2O and Cd(ClO4)2.6H2O produced different five coordinated square pyramidal and six coordinated octahedral cdmium(II) complexes. Among them the complexes, cis-[Cd(teta)( NO3)](NO3) and cis-[Cd(tet-b)(NO3)](NO3) underwent axial ligand substitution reaction with KCNS; whereas complex [Cd(tet-a)I2] underwent axial ligand substitution reaction and complex [CdLI](ClO4) underwent simultaneous ligand substitution and addition reaction with NaNO2. Characterization of all the complexes were carried out on the basis of elemental analysis; FT-IR, UV-Vis. and 1H-NMR spectroscopy; melting point determination as well as by magnetic moment and conductivity measurements. Molar conductivity measurment of the complexes reavealed that they show different electrolytic behavior in different solvents.