Complexation of 3,4-hydroxypyridinecarboxylic acids with Iron(III)

The chemical interactions of 3-hydroxy-4-pyridinecarboxylic acid (3H4P) and 4-hydroxy-3-pyridinecarboxylic acid (4H3P) with Fe(III) were investigated in aqueous 0.6 m (Na)Cl at 25 °C by means of potentiometric titrations and UV-Vis spectrophotometry. A large number of mononuclear complexes were formed in solution; one of the Fe/3H4P species was obtained as a solid and characterised by elemental analysis. In view of a possible application to iron(III) chelation therapy, the efficiencies of the ligands to chelate iron(III) were evaluated in vitro at physiological pH. Chelation efficiency with iron was low and less than previously observed with aluminium(III).     

Design of novel iron compounds as potential therapeutic agents against tuberculosis

In the search for new therapeutic tools against tuberculosis two novel iron complexes, [Fe(L-H)₃], with 3-aminoquinoxaline-2-carbonitrile N¹,N⁴-dioxide derivatives (L) as ligands, were synthesized, characterized by a combination of techniques, and in vitro evaluated. Results were compared with those previously reported for two analogous iron complexes of other ligands of the same family of quinoxaline derivatives. In addition, the complexes were studied by cyclic voltammetry and EPR spectroscopy. Cyclic voltammograms of the iron compounds showed several cathodic processes which were attributed to the reduction of the metal center (Fe(III)/Fe(II)) and the coordinated ligand. EPR signals were characteristic of magnetically isolated high-spin Fe(III) in a rhombic environment and arise from transitions between m_S = ± 1/2 (g_eff ~ 9) or m_S = ± 3/2 (g_eff ~ 4.3) states. Mössbauer experiments showed hyperfine parameters that are typical of high-spin Fe(III) ions in a not too distorted environment. The novel complexes showed in vitro growth inhibitory activity on Mycobacterium tuberculosis H₃₇Rv (ATCC 27294), together with very low unspecific cytotoxicity on eukaryotic cells (cultured murine cell line J774). Both complexes showed higher inhibitory effects on M. tuberculosis than the “second-line” therapeutic drugs.     

A method for detection of 4-hydroxy-2-nonenal adducts in proteins

We developed a procedure to measure 4-hydroxy-2-nonenal (HNE)-amino acid adducts using the fluorescent probe 2-aminopyridine (2-AP). The method is based on the fact that HNE forms Michael addition-type amino acid adducts possessing an aldehyde functionality, which upon reaction with 2-AP in the presence of NaBH₃CN can be converted to their pyridylaminated derivatives. The HNE-amino acid adducts, namely Michael addition-type HNE-cysteine, HNE-histidine, and HNE-lysine adducts, after pyridylamination were resistant to conventional acid-hydrolysis conditions for protein (6 N HCl/110 °C/24 h) and could be detected by HPLC with a fluorescence detector. The reductive amination-based fluorescent labeling of HNE adducts is a simple and accurate technique that may be widely used to reveal increased levels of covalently modified proteins with HNE and its related aldehydes during aging and disease.     

Nucleophilic Substitution on 4-Nitro- and 4-Methoxy-3-pyridinecarboxylic Acid-1-oxides

1-Oxides of 4-nitro-3-pyridinecarboxylic acid (3) and methyl 4-methoxy-3-pyridinecarboxylate (5) were converted to 4-(diphenylmethyl)amino (7), 4-phenylthio (8), 4-phenylamino (9) and 4-(2-methylpropyl)-amino (6) derivatives by reaction with the corresponding nucleophiles. The 4-phenylamino derivative 9 was alkylated with bromoethane to form the corresponding ethyl ester of the 1-ethoxypyridinium salt 10.     

Redox thermodynamics of lactoperoxidase and eosinophil peroxidase

Eosinophil peroxidase (EPO) and lactoperoxidase (LPO) are important constituents of the innate immune system of mammals. These heme enzymes belong to the peroxidase-cyclooxygenase superfamily and catalyze the oxidation of thiocyanate, bromide and nitrite to hypothiocyanate, hypobromous acid and nitrogen dioxide that are toxic for invading pathogens. In order to gain a better understanding of the observed differences in substrate specificity and oxidation capacity in relation to heme and protein structure, a comprehensive spectro-electrochemical investigation was performed. The reduction potential (E°′) of the Fe(III)/Fe(II) couple of EPO and LPO was determined to be −126 mV and −176 mV, respectively (25 °C, pH 7.0). Variable temperature experiments show that EPO and LPO feature different reduction thermodynamics. In particular, reduction of ferric EPO is enthalpically and entropically disfavored, whereas in LPO the entropic term, which selectively stabilizes the oxidized form, prevails on the enthalpic term that favors reduction of Fe(III). The data are discussed with respect to the architecture of the heme cavity and the substrate channel. Comparison with published data for myeloperoxidase demonstrates the effect of heme to protein linkages and heme distortion on the redox chemistry of mammalian peroxidases and in consequence on the enzymatic properties of these physiologically important oxidoreductases.     

Scalable biocatalytic synthesis of optically pure ethyl (R)-2-hydroxy-4-phenylbutyrate using a recombinant E. coli with high catalyst yield

Ethyl (R)-2-hydroxy-4-phenylbutanoate [(R)-HPBE] is a versatile and important chiral intermediate for the synthesis of angiotensin-converting enzyme (ACE) inhibitors. Recombinant E. coli strain coexpressing a novel NADPH-dependent carbonyl reductase gene iolS and glucose dehydrogenase gene gdh from Bacillus subtilis showed excellent catalytic activity in (R)-HPBE production by asymmetric reduction. IolS exhibited high stereoselectivity (>98.5% ee) toward α-ketoesters substrates, whereas fluctuant ee values (53.2–99.5%) for β-ketoesters with different halogen substitution groups. Strategies including aqueous/organic biphasic system and substrate fed-batch were adopted to improve the biocatalytic process. In a 1-L aqueous/octanol biphasic reaction system, (R)-HPBE was produced in 99.5% ee with an exceptional catalyst yield (gproduct/gcatalyst) of 31.7 via bioreduction of ethyl 2-oxo-4-phenylbutyrate (OPBE) at 330 g/L.     

Antiparasitic activity of prenylated benzoic acid derivatives from Piper species

Fractionation of dichloromethane extracts from the leaves of Piper heterophyllum and P. aduncum afforded three prenylated hydroxybenzoic acids, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid, 3-[(2E,6E,10E)-11-carboxy-13-hydroxy-3,7,15-trimethyl-2,6,10,14-hexadecatetraenyl]-4,5-dihydroxybenzoic acid and 3-[(2E,6E,10E)-11-carboxy-14-hydroxy-3,7,15-trimethyl-2,6,10,15-hexadecatetraenyl]-4,5-dihydroxybenzoic acid, along with the known compounds, 4,5-dihydroxy-3-(E,E,E-11-formyl-3,7,15-trimethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid (arieianal), 3,4-dihydroxy-5-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 4-hydroxy-3-(E,E,E-3,7,11,15-tetramethyl-hexadeca-2,6,10,14-tetraenyl)benzoic acid, 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid, 4-hydroxy-3-(3,7-dimethyl-2,6-octadienyl)benzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid. Their structures were elucidated on the basis of spectroscopic data, including homo- and heteronuclear correlation NMR experiments (COSY, HSQC and HMBC) and comparison with data reported in the literature. Riguera ester reactions and optical rotation measurements established the compounds as racemates. The antiparasitic activity of the compounds were tested against three strains of Leishmania spp., Trypanosoma cruzi and Plasmodium falciparum. The results showed that 3-(3,7-dimethyl-2,6-octadienyl)-4-methoxy-benzoic acid exhibited potent and selective activity against L. braziliensis (IC₅₀ 6.5 μg/ml), higher that pentamidine used as control. Moreover, 3-[(2E,6E,10E)-11-carboxy-3,7,15-trimethyl- 2,6,10,14-hexadecatetraenyl)-4,5-dihydroxybenzoic acid and 4-hydroxy-3-(3-methyl-1-oxo-2-butenyl)-5-(3-methyl-2-butenyl)benzoic acid showed moderate antiplasmodial (IC₅₀ 3.2 μg/ml) and trypanocidal (16.5 μg/ml) activities, respectively.     

Electron flow through metalloproteins

Electron transfers in photosynthesis and respiration commonly occur between metal-containing cofactors that are separated by large molecular distances. Understanding the underlying physics and chemistry of these biological electron transfer processes is the goal of much of the work in our laboratories. Employing laser flash-quench triggering methods, we have shown that 20 Å, coupling-limited Fe(II) to Ru(III) and Cu(I) to Ru(III) electron tunneling in Ru-modified cytochromes and blue copper proteins can occur on the microsecond timescale both in solutions and crystals; and, further, that analysis of these rates suggests that distant donor-acceptor electronic couplings are mediated by a combination of sigma and hydrogen bonds in folded polypeptide structures. Redox equivalents can be transferred even longer distances by multistep tunneling, often called hopping, through intervening amino acid side chains. In recent work, we have found that 20 Å hole hopping through an intervening tryptophan is several hundred-fold faster than single-step electron tunneling in a Re-modified blue copper protein.     

Effect of temperature on rice growth in nutrient solution and in acid sulphate soils from Vietnam

Climatic and soil factors are limiting rice growth in many countries. In Vietnam, a steep gradient of temperature is observed from the North to the South, and acid sulphate soils are frequently devoted to rice production. We have therefore attempted to understand how temperature affects rice growth in these problem soils, by comparison with rice grown in nutrient solution. Two varieties of rice, IR64 and X2, were cultivated in phytotrons at 19/21°C and 28/32°C (day/night) for 56 days, after 3 weeks preculture in optimal conditions. Two soils from the Mekong Delta were tested. Parallel with the growing experiments, these two soils were incubated in order to monitor redox potential (E _h ), pH, soluble Al and Fe, soluble, and available P. Tillering retardation at 20°C compared to 30°C was similar in nutrient solutions and in soils. The effect of temperature on increasing plant biomass was more marked in solutions than in soils. The P concentrations in roots and shoots were higher at 20°C than at 30°C, to such an extent that detrimental effect was suspected in plants grown in solution at the lowest temperature. The translocation of Fe from roots to shoots was stimulated upon rising temperature, both in solutions and in soils. This led to plant death on the most acid soil at 30°C. Indeed, the accumulation of Fe in plants grown on soils was enhanced by the release of Fe²⁺ due to reduction of Fe(III)-oxihydroxides. Severe reducing conditions were created at 30°C: redox potential (E _h ) dropped rapidly down to about 0 V. At 20°C, E _h did not drop below about 0.2 V, which is a value well in the range of Fe(III)/Fe(II) buffering. Parallel to E _h drop, pH increased up to about 6–6.5 at 30°C, which prevented plants from Al toxicity, even in the most acid soil. Phosphate behavior was obviously related to Fe-dynamics: more reducing conditions at 30°C have resulted in enhancement of available P, especially in the most acid soil.     

The aluminium(III)-sialic acid interaction: A potential role in aluminium-induced cellular membrane degeneration

The coordination between Al(III) and sialic acid (N-acetylneuraminic acid, HL, pK_a = 2.58 ± 0.01) was studied by potentiometric titrations at 25 °C in aqueous 0.2 M KCl, by ¹H NMR, and by electrospray ionization mass spectrometry (ESI-MS). The potentiometric measurements gave the following aluminium complex stoichiometries and stability constants: , log β(AlLH₋₂) = −6.34 ± 0.02, and log β(AlL₂H₋₁) = −1.14 ± 0.04. The ¹H NMR spectra yielded structural information on species . The ESI-MS data confirmed the metal-ligand stoichiometry of the complexes.The metal-ligand speciation at micromolar Al(III) concentrations (i.e., under in vivo conditions) at physiological pH values reveals that considerable amount of Al(III) is complexed. This suggests that the toxic effect of Al(III) towards cellular membranes might be due to its coordination by protein-bound sialic acid.     

The binding of aluminum to mugineic acid and related compounds as studied by potentiometric titration

The phytosiderophores, mugineic acid (MA) and epi-hydroxymugineic acid (HMA), together with a related compound, nicotianamine (NA), were investigated for their ability to bind Al(III). Potentiometric titration analysis demonstrated that MA and HMA bind Al(III), in contrast to NA which does not under normal physiological conditions. With MA and HMA, in addition to the Al complex (AlL), the protonated (AlLH) and deprotonated (AlLH₋₁) complexes were identified from an analysis of titration curves, where L denotes the phytosiderophore form in which all the carboxylate functions are ionized. The equilibrium formation constants of the Al(III) phytosiderophore complexes are much smaller than those of the corresponding Fe(III) complexes. The higher selectivity of phytosiderophores for Fe(III) over Al(III) facilitates Fe(III) acquisition in alkaline conditions where free Al(III) levels are higher than free Fe(III) levels.     

Vanillic acid, a metabolite of 4-hydroxy-3-methoxyphenylglycol and 4-hydroxy-3-methoxymandelic acid in man

Abstract: 4-Hydroxy-3-methoxyphenylglycol (HMPG) labelled with ¹⁴C was used to study the metabolic fate of HMPG in six healthy volunteers. Besides conjugation and oxidation to 4-hydroxy-3-methoxymandelic acid (HMMA, VMA) a minor portion, 8.4 ± 1.1% (mean ± SEM) was excreted as ¹⁴C-labelled vantllic acid (VA). To study if VA was formed from HMPG or HMMA (VMA), deuterium-labelled HMPG ([²H₃]HMPG) and HMMA ([²H₆]HMMA) were simultaneously injected intravenously to seven healthy volunteers. The recovery of [²H₃]VA from [²H₃]HMPG was 8.3 ± 2.1% and the recovery of [²H₆]VA from [²H₆]HMMA was 9.0 ± 2.1%. The ²H-labelled VAs were probably formed by a decar boxylation reaction, in the case of HMPG after previous oxidation to HMMA.     

A pilot study on the regeneration of ferrous chelate complex in NOx scrubber solution by a biofilm electrode reactor

A chemical absorption-biological reduction integrated process has been proposed for the removal of nitrogen oxides (NO_x) from flue gases. In this study, we report a new approach using biofilm electrode reactor (BER) to regenerate Fe(II)EDTA via simultaneously reducing Fe(II)EDTA-NO and Fe(III)EDTA in NO_x scrubber solution. Biofilm formed on the surface of the cathode was confirmed by Environmental Scan Electro-Microscope. Experimental results demonstrated that it was effective and feasible to utilize the BER to promote the reduction of Fe(II)EDTA-NO and Fe(III)EDTA simultaneously. The reduction efficiency of Fe(II)EDTA-NO and Fe(III)EDTA was up to 85% and 78%, respectively when the BER was continuously operated with electricity current at 30 mA. The absence of electricity induced an immediate decrease in reduction efficiency, indicating that the bio-regeneration of ferrous chelate complex was electrochemically accelerated. The present approach is considered advantageous for the enhanced bio-reduction in the NO_x scrubber solution.     

Difference in reactivity of triel halides EX3 towards ferrocene

A facile route to the Fe²⁺-arene complex [(C₆H₆)FeCp][AlBr₄] is the reaction of ferrocene with AlBr₃ in benzene. The structure of the Fe²⁺-arene complex [(C₆H₆)FeCp][AlBr₄] · C₆H₆ was found to be isomorphous with those of [FeCp₂][ECl₄] · C₆H₆ (E = Al, Ga). The crystal structures of the [FeCp₂][AlCl₄] · C₆H₆ (E = Al, Ga) presented here show structural features which are different from those of solvent-free ferrocenium salts [FeCp₂][ECl₄] (E = Al, Ga, Fe). However, the cell parameters of solvent-free ferrocenium tetrafluoroborate [FeCp₂][BF₄] are also quite different from those of solvent-free [FeCp₂][ECl₄] (E = Al, Ga, Fe). In contrast to the eclipsed conformation in solvent-free [FeCp₂][ECl₄] (E = Al, Ga, Fe) the cyclopentadiene rings in [FeCp₂][BF₄] and [FeCp₂][ECl₄] · C₆H₆ (E = Al, Ga) are in a staggered conformation.     

Production and characterization of homopolymer poly(3-hydroxyvalerate) (PHV) accumulated by wild type and recombinant Aeromonas hydrophila strain 4AK4

Aeromonas hydrophila 4AK4 normally produces copolyesters (PHBHHx) consisting of 3-hydroxybutyrate (C4) and 3-hydroxyhexanoate (C6). Wild type and recombinant A. hydrophila 4AK4 (pSXW02) expressing vgb and fadD genes encoding Vitreoscilla haemoglobin and Escherichia coli acyl-CoA synthase respectively, were found able to produce homopolyester poly(3-hydroxyvalerate) (PHV) (C5) on undecanoic acid as a single carbon source. The recombinant grew to 5.59 g/L cell dry weight (CDW) containing 47.74 wt% PHV in shake flasks when growth was conducted in LB medium and PHV production in undecanoic acid. The cells grew to 47.12 g/L CDW containing 60.08 wt% PHV in a 6 L fermentor study. Physical characterization of PHV produced by recombinant A. hydrophila 4AK4 (pSXW02) in fermentor showed a weight average molecular weight (M_w) of 230,000 Da, a polydispersity of 3.52, a melting temperature of 103 °C and a glass transition temperature of −15.8 °C. The degradation temperature at 5% weight loss of the PHV was around 258 °C.     

On the structure of the N,N′-dimethylpropyleneurea and dimethylsulfoxide solvated gallium(III) and indium(III) ions and bromide complexes in solution and solid state, and the complex formation of the gallium(III) and indium(III) bromide systems in N,N′-dimethylpropyleneurea

The structures of the N,N′-dimethylpropyleneurea (DMPU) solvated gallium(III) and indium(III) ions have been determined in DMPU solution by means of EXAFS. The gallium(III) ion is five-coordinate with a mean Ga-O bond distance of 1.924(5) Å, while the larger indium(III) ion is octahedrally coordinated with a mean In-O bond distance of 2.146(3) Å. The complex formation equilibria in DMPU for the gallium(III) and indium(III) bromide systems have been studied calorimetrically at 298 K. Three relatively strong complexes are formed in the indium(III) bromide system in DMPU, whereas no stability constants could be established in the gallium(III) bromide system as the heats of complex formation were very close to zero. Gallium(III) bromide is present as DMPU solvated GaBr₃ complexes in solution with three equatorial Ga-Br bonds at 2.328(3) Å, and two Ga-O bonds at 1.92(3) Å in the apical positions of a distorted trigonal bipyramid. The DMPU solvated indium(III) bromide has the same configuration with a mean In-Br bond distance of 2.510(3) Å, and two In-O bonds at 2.201(6) Å. Indium(III) binds three bromides and three Me₂SO molecules through the oxygen atoms in octahedral fac-configuration with mean In-Br and In-O bond distances of 2.630(3) and 2.211(15) Å, respectively.     

Mn(II) complexes of monoanionic bidentate chelators: X-ray crystal structures of Mn(dha)2(CH3OH)2 (Hdha = dehydroacetic acid) and [Mn(ema)2(H2O)]2 · 2H2O (Hema = 2-ethyl-3-hydroxy-4-pyrone)

This report describes synthesis and characterization of bis-ligand Mn(II) complexes of bidentate chelators: maltol (3-hydroxy-2-methyl-4-pyrone), ethylmaltol (2-ethyl-3-hydroxy-4-pyrone), 1,2-dimethyl-3-hydroxy-4-pyridinone (DMHP) and dehydroacetic acid. All four Mn(II) complexes were characterized by elemental analysis, IR, UV/Vis, EPR, cyclic voltammetry, and X-ray crystallography in cases of Mn(dha)₂(CH₃OH)₂ and [Mn(ema)₂(H₂O)]₂ · 2H₂O. The bidentate chelator plays a significant role in the solid state structure of its Mn(II) complex. For example, dha forms the monomeric complex Mn(dha)₂(CH₃OH)₂ while ethylmaltol forms the dimeric complex [Mn(ema)₂(H₂O)]₂. Because of smaller size, maltol ligands in Mn(ma)₂ are able to bridge adjacent Mn(II) centers to give a polymeric structure in solid state. Despite of the difference in their solid state structures, both Mn(ema)₂ and Mn(ma)₂ exist in solution as monomeric Mn(II) species, Mn(ema)₂(H₂O)₂ and Mn(ma)₂(H₂O)₂. This assumption is supported by the similarity in their UV/Vis spectra, EPR data and electrochemical properties. Replacing maltol with DMHP results in a decrease (by ∼100 mV) in the redox potential for the Mn(II)/Mn(III) couple, suggesting that DMHP stabilizes Mn(III) better than maltol. Since Mn(DMHP)₂(H₂O)₂ is readily oxidized to form the more stable Mn(III) complex Mn(DMHP)₃, DMHP has the potential as a chelator for removal of excess Mn(II) from patients with chronic Mn toxicity.     

Electrochemical DNA biosensor based on silver nanoparticles/poly(3-(3-pyridyl) acrylic acid)/carbon nanotubes modified electrode

In this work, we present an electrochemical DNA sensor based on silver nanoparticles/poly(trans-3-(3-pyridyl) acrylic acid) (PPAA)/multiwalled carbon nanotubes with carboxyl groups (MWCNTs-COOH) modified glassy carbon electrode (GCE). The polymer film was electropolymerized onto MWCNTs-COOH modified electrode by cyclic voltammetry (CV), and then silver nanoparticles were electrodeposited on the surface of PPAA/MWCNTs-COOH composite film. Thiol group end single-stranded DNA (HS-ssDNA) probe was easily covalently linked onto the surface of silver nanoparticles through a 5′ thiol linker. The DNA hybridization events were monitored based on the signal of the intercalated adriamycin by differential pulse voltammetry (DPV). Based on the response of adriamycin, only the complementary oligonucleotides gave an obvious current signal compared with the three-base mismatched and noncomplementary oligonucleotides. Under the optimal conditions, the increase of reduction peak current of adriamycin was linear with the logarithm of the concentration of the complementary oligonucleotides from 9.0 × 10⁻¹² to 9.0 × 10⁻⁹ M with a detection limit of 3.2 × 10⁻¹² M. In addition, this DNA sensor exhibited an excellent reproducibility and stability during DNA hybridization assay.     

Redox potentials of Ti(IV) and Fe(III) complexes provide insights into titanium biodistribution mechanisms

Transferrin, the human iron transport protein, binds Ti(IV) even more tightly than it binds Fe(III). However, the fate of titanium bound to transferrin is not well understood. Here we present results which address the fate of titanium once bound to transferrin. We have determined the redox potentials for a series of Ti(IV) complexes and have used these data to develop a linear free energy relationship (LFER) correlating Ti(IV) ? Ti(III) redox processes with Fe(III) ? Fe(II) redox processes. This LFER enables us to compare the redox potentials of Fe(III) complexes and Ti(IV) complexes that mimic the active site of transferrin and allows us to predict the redox potential of titanium-transferrin. Using cyclic voltammetry and discontinuous metalloprotein spectroelectrochemistry (dSEC) in conjunction with the LFER, we report that the redox potential of titanium-transferrin is lower than − 600 mV (lower than that of iron-transferrin) and is predicted to be ca. − 900 mV vs. NHE (normal hydrogen electrode). We conclude that Ti(IV)/Ti(III) reduction in titanium-transferrin is not accessible by biological reducing agents. This observation is discussed in the context of current hypotheses concerning the role of reduction in transferrin mediated iron transport.     

Spectral, electrochemical, and catalytic properties of a homologous series of manganese porphyrins as cytochrome P450 model: the effect of the degree of beta-bromination

A homologous series of β-brominated porphyrins derived from meso-tetrakis(4-carbomethoxyphenyl)porphyrinatomanganese(III) chloride, i.e., Mn(III)(Br_xTCMPP)Cl (x = 0, 2, 4, 6, and 8), was prepared and investigated as cytochrome P450 models. Hydroxylations of cyclohexane by iodosylbenzene (PhIO) and iodobenzene diacetate (PhI(OAc)₂) in the presence or absence of water were carried out as P450 model reactions. The influence of the degree of β-bromination of the macrocycle on the UV-vis spectra, the Mn(III)/Mn(II) reduction potential, and the catalytic properties of the Mn(III)(Br_xTCMPP)Cl (x = 0, 2, 4, 6, and 8) series were examined. The catalytic efficiency does not correlate with the Mn(III)/Mn(II) reduction potential and shows a bell-shaped behavior, where the best results are achieved with the hexabrominated complex. Better hydroxylation yields were achieved by using PhI(OAc)₂ as oxygen donor, but at expenses of catalyst recovery; addition of water to this system resulted in a increase in the reaction rate. Recycling of the more oxidatively robust complexes Mn(III)(Br₆TCMPP)Cl and Mn(III)(Br₈TCMPP)Cl is feasible when using PhIO as oxygen donor. Selectivity and UV-vis data suggested that hydroxylation by both PhIO and PhI(OAc)₂ share closely related active species and mechanism. We also show that the Mn(III)/Mn(II) reduction potentials are inappropriate predictors of P450-type activity of Mn porphyrin-catalyzed oxidations.