Peter Hambright

Manganese(III) meso-tetrakis(ortho-N-alkylpyridyl)porphyrins. Synthesis, characterization, and catalysis of O2˙− dismutation

A series of ortho isomers of meso-tetrakis(N-alkylpyridyl)porphyrins (alkyl being methyl, ethyl, n-propyl, n-butyl, n-hexyl, and n-octyl) and their Mn(III) complexes were synthesized and characterized by elemental analysis, uv/vis spectroscopy, electrospray ionization mass spectrometry and electrochemistry. An increase in the number of carbon atoms in the alkyl chains from 1 to 8 is accompanied by an increase in: (a) lipophilicity, as measured by the chromatographic retention factor, Rf; (b) metal-centered redox potential, E1/2 from +220 to +367 mV vs. NHE, and (c) proton dissociation constant, pKa2 from 10.9 to 13.2. A linear correlation was found between E1/2 and Rf of the Mn(III) porphyrins and between the pKa2 and Rf of the metal-free compounds. As the porphyrins become increasingly more lipophilic, the decrease in hydration disfavors the creation of charge, while enhancing the electron-withdrawing effect of the positively charged pyridyl nitrogen atoms. Consequently, E1/2 increases linearly with the increase in pKa2, a trend in porphyrin basicity opposite from the one we previously reported for other water-soluble Mn(III) porphyrins. All of these Mn(III) porphyrins are potent catalysts for superoxide dismutation (disproportionation). Despite the favorable increase of E1/2 with the increase in chain length, the catalytic rate constant decreases from methyl (log kcat = 7.79) to n-butyl, and then increases such that the n-octyl is as potent a SOD mimic as are the methyl and ethyl compounds. The observed behavior originates from an interplay of hydration and steric effects that modulate electronic effects.

The distribution of various water soluble radioactive metalloporphyrins in tumor bearing mice.

Abstract The distribution of a variety of water soluble 109 Pd and 64 Cu porphyrins were studied in mice bearing three types of tumors. While the metalloporphyrins are found to have an affinity for neoplastic tissue, substantial extra-tumor concentrations are also noted. Although this limits their value as specific tumor imaging agents, their use in localized therapy is discussed.

Steric and inductive effects on the basicity of porphyrins and on the site of protonation of porphyrin dianions: radiolytic reduction of porphyrins and metalloporphyrins to chlorins or phlorins

A series of sulfonated, water-soluble, phenyl-substituted porphyrins has been prepared, containing halogen or alkyl groups in the ortho, di-ortho or para positions. While the para-substituted compounds exhibited monomer–dimer behaviour, all the ortho and di-ortho substituted porphyrins were monomeric in aqueous solution at 0.1 mol dm–3 ionic strength. The proton basicities varied over a 105 range along the series, from the strongly basic tetra(4-methoxyphenyl) species to the weakly basic and less deformable sulfonated tetrakis(2,6-dichlorophenyl) porphyrin. Certain of these porphyrins and related metalloporphyrins were reduced by radiolytic methods in aqueous solutions. Pulse radiolysis studies provided the spectra of the short-lived π-radical anions and γ-radiolysis led to formation of stable chlorins or phlorins, the products of two-electron reduction and protonation at the β-pyrrole or at the meso position, respectively. Whereas H2TPPS4[tetrakis(4-sulfonatophenyl)porphyrin] yields phlorin at all pH values, ZnII-, AlIII-, lnIII- and SnIV-TPPS4 form phlorins at high pH but mostly chlorins at lower pH. The ratio of phlorin to chlorin production is enhanced by increased pH and by increased metal electronegativity. 2,6-Disubstitution at the phenyl rings diminishes the likelihood of phlorin formation while N-methyl substitution at one of the central nitrogens of ZnTPPS4 enhances phlorin formation. These and other results indicate that electron withdrawal from the porphyrin π-system enhances the ratio of phlorin/chlorin production. On the other hand, steric crowding around the meso position retards protonation at this site by preventing the geometric reorientation necessary for phlorin formation.

THE EFFECTS OF PERIPHERAL SUBSTITUENTS ON THE KINETICS OF ZINC ION INCORPORATION AND ACID CATALYZED REMOVAL FROM WATER SOLUBLE SULFONATED PORPHYRINS

Abstract The kinetics of Zn2+ and Zn(OH)+ incorporation into and the kinetics of the acid catalyzed removal of Zn(II) from twelve water-soluble, sulfonated derivatives of tetraphenylporphyrin with alkyl or halogen groups in the para, ortho or di-ortho positions were investigated. While the incorporation reactions showed little dependence on porphyrin basicity, the Zn-P (P = porphyrin derivative) acid solvolysis reactions were faster the higher the basicity of the free base (H2-P) compound. Equilibrium constants for the formation of cadmium porphyrins decreased with an increase in porphyrin basicity. The predeformed tetrakis(4-sulfonatophenyl)-β-octabromo-porphyrin reacted with Zn2+ about 103 times faster than porphyrins of similar basicity. These results indicate how substituents on the phenyl and beta-pyrrole rings influence the solution chemistry of water soluble porphyrins.

Synthesis, characterization and copper incorporation into 5-(4-pyridyl)-10,15,20-triphenylporphyrin

Abstract 5-(4-Pyridyl)-10,15,20-triphenylporphyrin, H 2 TriP, and its water insoluble N-Methyl derivative were synthesized. The PMR and phase selective first and second harmonic polarographic studies were consistent with the proposed structure. In either sodium dodecylsulfate or Triton X-100 detergents, only the free base and di-acid porphyrin forms were present. This was confirmed by a copper incorporation study in SDS, which indicated the absence of a mono-cation, reactivity of only the free base form, and no anion catalysis.

Free base porphyrin reduction potentials: A useful structure-reactivity parameter

Abstract Reduction potentials for a series of free-base porphyrins of widely differing basicity have been measured in DMF (dimethylformamide) solution using phase-selective fundamental harmonic and second harmonic ac polarography. The potentials show a good linear correlation with porphyrin properties, such as electrophilic substitution rates and reduction potentials for the corresponding manganese(III) and iron(III) metalloporphyrins, regardless of the nature of the porphyrin substituent or its position on the porphyrin periphery. Examples provided show that the reduction potentials, which are rapidly and accurately obtained, are a reasonable measure of porphyrin electron density, which can be useful in structure-reactivity correlations.

Zinc(II) and cobalt(II) halide interactions with vitamin B1 and certain N-substituted thiazolium salts

Abstract The solid adducts isolated from the reactions of zinc and cobalt halides with derivatives of thiamine and certain other N -alkylthiazolium salts were characterized by i.r., electronic reflectance spectroscopy and magnetic susceptibility studies. The species appear to be complex salts without metal-sulfur or metal-nitrogen interaction.

Oxidation of chromium(III) porphyrins to their π-radical cations or to oxochromium(IV) porphyrins

One-electron oxidation of several chromium(III) porphyrins has been studied by steady-state and pulse radiolysis techniques under different conditions. Two types of products are observed: those exhibiting intense broad absorptions at λ 600 nm, ascribed to the π-radical cations, and others exhibiting minor shifts of the porphyrin bands, ascribed to chromium(IV) porphyrins. CrIIIOEP (octaethylporphyrin), CrIIITPP (tetraphenylporphyrin), and CrIIITMP (tetramesitylporphyrin) in CH2Cl2 undergo one-electron oxidation on the ligand to give π-radical cations, which are stable after ligation, and further oxidation gives the dications. In the presence of KOH, however, they form CrIV-porphyrins and further radiolysis gives Crv-porphyrins. CrIIITSPP [tetrakis (4-sulfonatophenyl)porphyrin], CrIIIT3PyP [tetrakis(3-pyridyl)porphyrin], and CrIIIMSP (mesoporphyrin-IX), oxidized in 1 mol dm–3 aqueous HCl, form unstable π-radical cations which decay by disproportionation. The pulse radiolysis results indicate that the initial step in the oxidation of all CrIIIP and OCrIVP species occurs at the porphyrin π-system and that, under certain conditions, the initial π-radical cation may undergo intramolecular electron transfer from the metal centre to the ligand to form the higher oxidation state Cr-porphyrin.

Thermal, magnetic and mossbauer studies on ferric porphyrin hemichromes

Abstract A current area of bioinorganic interest concerns the behavior of ferric porphyrins in solution with nitrogenous bases. PMR studies have given evidence for (1) low spin (S = 1 2 ) = high spin (S = 5 2 or 2 3 ) equilibria in certain systems [1, 2], and (2) five coordinate (S = 5 2 monoimidazole ferric porphyrins in equilibrium with low spin bisimidazole forms [3] in solution. In contrast, spectrophotometric titrations of Cl-Fe(III)tetraphenylporphin with imidazole in acetone [4] and methylene chloride [5] solvents show an equilibria between only Cl-Fe(III)TPP and TPP, Cl−, with no monoimidazole adducts present. We have begun a program of using thermal means to generate “unusual” metal ion geometries of metalloporphyrins in the solid state as models of the metalloenzymes “entatic state” [6]. We report magnetic, thermal and Mossbauer data on a variety of solid hemichromes, which show certain parallel features with the behavior of hemichromes in solution. In particular, we have synthesized by thermal means high spin monoimidazole Fe(III) porphyrin complexes.

A water soluble “picket fence” porphyrin and its isomers

Abstract The water soluble “picket fence” porphyrin, meso -tetra(α,α,α,α- ortho -(N-methyl-isonicotinamidophenyl)) porphyrin, its three rotational isomers, and the corresponding para and meta derivatives were synthesized. The ortho substituted compounds were one-hundred times less basic and less reactive with metal ions than the para or meta isomers. The reduction potentials of the free base porphyrins indicated electronic interaction between the porphyrin ring and the ortho substituent groups in the isonicotinamidophenyl compounds.