Electrochemistry of [(TMpyP)M(II)]4+ (X-)4 (X- = Cl- or BPh4-) and [(TMpyP)M(III)Cl]4+ (Cl-)4 in N,N-dimethylformamide where M is one of 15 different metal ions.

The electrochemistry of 16 different water-soluble porphyrins of the type [(TMpyP)M(II)]4+ (X-)4 or [(TMpyP)M(III)Cl]4+ (Cl-)4 is reported in nonaqueous media where TMpyP is the dianion of meso-tetrakis(N-methylpyridiniumyl)porphyrin and X- = Cl- or BPh4-. These studies were carried out to examine the effect of the metal ion and porphyrin counterion (X-) on the electrochemical properties of the TMpyP complexes with a special emphasis being given to the overall number of electrons added and the number of electrode processes upon reduction. All of the investigated compounds with electroinactive central metal ions undergo an overall addition of six electrons. This occurs for most compounds via three two-electron-transfer steps, but more than three processes are observed for porphyrins having metal ions with a low electronegativity (e.g., Cd(II)). The first reduction of each porphyrin having an M(II) ion or an electroinactive M(III) ion yields a porphyrin dianion which is characterized by an intense band located close to 800 nm, and this reversible reduction is followed by further reductions of the 1-methyl-4-pyridyl groups at more negative potentials. Four of the compounds with electroactive central metal ions, [(TMpyP)M(III)Cl]4+(Cl-)4 (M = Co, Fe, Mn, or Au), undergo an additional reversible M(III)/M(II) process prior to reactions involving the porphyrin pi-ring system and the 1-methyl-4-pyridyl substituents.

Manganese(III) biliverdin IX dimethyl ester: a powerful catalytic scavenger of superoxide employing the Mn(III)/Mn(IV) redox couple.

A manganese(III) complex of biliverdin IX dimethyl ester, (MnIIIBVDME)2, was prepared and characterized by elemental analysis, UV/vis spectroscopy, cyclic voltammetry, chronocoulometry, electrospray mass spectrometry, freezing-point depression, magnetic susceptibility, and catalytic dismuting of superoxide anion (O2.-). In a dimeric conformation each trivalent manganese is bound to four pyrrolic nitrogens of one biliverdin dimethyl ester molecule and to the enolic oxygen of another molecule. This type of coordination stabilizes the +4 metal oxidation state, whereby the +3/+4 redox cycling of the manganese in aqueous medium was found to be at E1/2 = +0.45 V vs NHE. This potential allows the Mn(III)/Mn(IV) couple to efficiently catalyze the dismutation of O2.- with the catalytic rate constant of kcat = 5.0 x 10(7) M-1 s-1 (concentration calculated per manganese) obtained by cytochrome c assay at pH 7.8 and 25 degrees C. The fifth coordination site of the manganese is occupied by an enolic oxygen, which precludes binding of NO., thus enhancing the specificity of the metal center toward O2.-. For the same reason the (MnIIIBVDME)2 is resistant to attack by H2O2. The compound also proved to be an efficient SOD mimic in vivo, facilitating the aerobic growth of SOD-deficient Escherichia coli.

Use of meso- tetrakis(pentafluorophenyl)porphyrin as a matrix for low molecular weight alkylphenol ethoxylates in laser desorption/ ionization time-of-flight mass spectrometry

The use of UV-absorbing molecules as matrices in matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOFMS) is well documented. The matrices that are currently used have low molecular weights (<300 Da) and thus, for a typical MALDI-TOF spectrum, the low-mass range (m/z 100-500) is dominated by matrix ions. Consequently, the applications of MALDI-TOFMS have been restricted mostly to the analysis of high molecular weight analytes. This report demonstrates the use of meso-tetrakis(pentafluorophenyl)porphyrin (F20TPP, MW 974.57) as a matrix in the MALDI-TOF mass spectrometric analysis of some commercial nonylphenol ethoxylates (4-(C(9)H(19))-C(6)H(4)-(OCH(2)CH(2))(n)-OH), in which the ethoxymer ion distribution ranges from 331-771 Da. When F20TPP was used without a sodium ion dopant, there were no MALDI signals for the ethoxylates. However, addition of sodium acetate to the sample produced MALDI spectra in which the ethoxymer molecules were sodiated to form [M + Na](+) ions. A comparison of the mass spectrometric data with those obtained when alpha-cyano-4-hydroxycinnamic acid (CHCA) was used as the matrix indicated that the F20TPP-induced spectra provided comparable data, with the advantage of having less matrix interference in the low-mass range (m/z 100-500). Thus, the use of F20TPP and similar porphyrins may provide the means to apply MALDI-TOF to the analysis of low molecular weight molecules with minimum interference from matrix signals. Copyright 1999 John Wiley & Sons, Ltd.

Reduction reactions of water soluble cyano-cobalt(III)-porphyrins: metal versus ligand centered processes.

Reduction reactions of dicyano-cobalt(III)-porphyrins [potential in vivo cyanide scavenger drugs] were studied by radiolytic and electrochemical methods using the water soluble tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and tetrakis(N-methyl-4-pyridyl)porphyrin (TMPyP). For [(CN)2CoIIITPPS]-, reduction occurs stepwise to the CoII, CoI, and finally to the phlorin anion. This behavior is similar to that of the cobalt porphyrins in the absence of cyanide, except that the cyanide ligand shifts the reduction potentials to much more negative values. On the other hand, under radiolytic conditions, [(CN)2CoIIITMPyP]- is reduced on the porphyrin macrocycle by one electron to give the CoIII pi-radical anion, which disproportionates into the initial complex and the two-electron ring reduced CoIII phlorin. The radical anion is also formed by intramolecular electron transfer subsequent to the reaction of CoIITMPyP and cyanide. The results are compared with the chemistry of Vitamin B-12.

Cyanide scavengers: kinetics of the reactions of cyanide with a water soluble cobalt(III) porphyrin.

The equilibrium and kinetic aspects of the interaction of cyanide with a model anticyanide drug cobalt(III)-tetrakis(4-sulfonatophenyl)porphyrin [Co-P] were studied at 25 degrees C, I = 0.1 (NaNO3). At the physiologic pH of 7.4, 1.9 +/- 0.1 mol of cyanide were rapidly bound per molecule of Co-P. The dissociation constant of cyanide from Co-P(H2O) (CN) was less than 10(-12), and the formation constant of Co-P(CN)2 from Co-P(H2O) (CN) and CN- was 3.5 X 10(6). From pH 4 to 10.5, the kinetics of mono-cyano Co-P formation were first order in cyanide and porphyrin, with the following specific rate constants (units M-1 s-1): Co-P(H2O)2/CN-, 3.1 X 10(2); Co-P(H2O) (OH)/CN-, 2.4 X 10(3); Co-P(OH)2/CN-, 5.1 X 10(1) and Co-P(H2O)/HCN, 3.1 X 10(-3). At pH 7.4, a second cyanide molecule adds more rapidly than the first: Co-P(H2O) (CN)/CN-, 3 X 10(4) M-1 s-1. It is concluded that low molecular weight water soluble cobalt(III) porphyrins might be used as effectively and at lower dose levels than hydroxocobalamin (B12b), a known in vivo anticyanide agent.

Tissue distribution and stability of metalloporphyrin MRI contrast agents.

Mn(III), Fe(III), and Gd(III) complexes of tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and several other porphyrins were evaluated as potential MRI contrast agents. Based on consideration of relaxivity and stability properties in solution, MnTPPS was found to be the compound of choice. At pH 7 the Gd and Mn complexes significantly enhanced the water proton relaxation rate, while the relaxivity of FeTPPS exhibited a significant loss of relaxivity above pH 6 due to oxy-dimer formation. Although GdTPPS exhibited the highest relaxivity in solution, this property was rapidly lost due to dissociation of the metal ion. By contrast MnTPPS remained stable in human plasma after incubation for 9 days. Upon intravenous injection into athymic mice bearing subcutaneous human colon carcinoma xenografts, MnTPPS provided enhanced relaxation of the tissue water in several excised mouse tissues, notably kidney, liver, and tumor. The results at a fixed field (0.25 T) and relaxation dispersion studies showed decreases in water relaxation rates with time for kidney and liver, but an increase for the tumor, with a maximum near 4 days at the highest dose used.

Metalloporphyrin contrast agents for magnetic resonance imaging of human tumors in mice.

Enhanced contrast of transplanted human colon carcinoma in athymic mice is seen in magnetic resonance images upon iv injection of the complexes of Mn(III) with two water-soluble porphyrins, tetra (4-sulfonatophenyl) porphyrin and tetra (N-methyl-4-pyridyl) porphyrin.

Kinetics of the substitution reaction of thiocyanate with tetrakis (3-N-methylphyridyl)porphinecobalt(III).

The equilibrium constant for the first thiocyanate addition to Co(III)-tetra(3-N-methylpyridyl)porphine is a factor of two smaller than for the less basic 4-N-methylporphine isomer. This effect is primarily due to a larger Co-SCN dissociation rate constant for the 3-isomer.

Chemistry of 99mTc tracers. II. In vitro conversion of tagged HEDP and pyrophosphate (bone-seekers) into gluconate (renal agent). Effects of Ca and Fe (ii) on in vivo distribution.

Sodium gluconate transforms the bone-seekers 99mTc-HEDP and 99mTc-pyrophosphate into the renal agent 99mTc-gluconate. In these in vitro processes, pyrophosphate is displaced faster than HEDP, while the HEDP reaction is accelerated by calcium ions. The in vivo distributions of these bone and kidney agents are altered by the prior local injection of calcium or iron(II). These transformation and translocation phenomena are explained in terms of the mechanistic behavior of Tc(IV) complexes.

Mutant of the yeast Saccharomycopsis lipolytica that accumulates and excretes protorphyrin IX.

The red, water-insoluble pigment excreted by a mutant strain of the yeast Saccharomycopsis lipolytica is show to be protoporphyrin IX. In genetic crosses the red phenotype has the properties characteristic of a defect in a single, recessive nuclear gene. The yield and ease of harvest of protoporphyrin IX from the yeast mutant indicate that this strain or its derivatives may be a valuable source of this substance.

Chemistry of technetium radiopharmaceuticals. I. Exploration of the tissue distribution and oxidation state consequences of technetium (IV) in Tc-Sn-gluconate and Tc-Sn-EHDP using carrier 99Tc.

The distribution in rats of the renal agent Tc-Sn-gluconate using both 99mTc and carrier amounts of 99Tc was similar. The same behavior was shown with the bone agent Tc-Sn-EHDP. The radiopharmaceutical consequences of the observed Tc(IV) oxidation state in these systems are explored.