Publications (4)18.45 Total impact
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Article: Further insights into the spectroscopic properties, electronic structure, and kinetics of formation of the heme-peroxo-copper complex [(F8TPP)FeIII-(O2(2-)-CuII(TMPA)]+.
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ABSTRACT: In the further development and understanding of heme-copper O2-reduction chemistry inspired by the active-site chemistry in cytochrome c oxidase, we describe a dioxygen adduct, [(F8TPP)FeIII-(O22-)-CuII(TMPA)](ClO4) (3), formed by addition of O2 to a 1:1 mixture of the porphyrinate-iron(II) complex (F8TPP)FeII (1a) {F8TPP = tetrakis(2,6-difluorophenyl)porphyrinate dianion} and the copper(I) complex [(TMPA)CuI(MeCN)](ClO4) (1b) {TMPA = tris(2-pyridylmethyl)amine}. Complex 3 forms in preference to heme-only or copper-only binuclear products, is remarkably stable {t1/2 (RT; MeCN) approximately 20 min; lambda max = 412 (Soret), 558 nm; EPR silent}, and is formulated as a peroxo complex on the basis of manometry {1a/1b/O2 = 1:1:1}, MALDI-TOF mass spectrometry {16O2, m/z 1239 [(3 + MeCN)+]; 18O2, m/z 1243}, and resonance Raman spectroscopy {nu(O-O) = 808 cm-1; Delta16O2/18O2 = 46 cm-1; Delta16O2/16/18O2 = 23 cm-1}. Consistent with a mu-eta2:eta1 bridging peroxide ligand, two metal-O stretching frequencies are observed {nu(Fe-O) = 533 cm-1, nu(Fe-O-Cu) = 511 cm-1}, and supporting normal coordinate analysis is presented. 2H and 19F NMR spectroscopies reveal that 3 is high-spin {also muB = 5.1 +/- 0.2, Evans method} with downfield-shifted pyrrole and upfield-shifted TMPA resonances, similar to the pattern observed for the structurally characterized mu-oxo complex [(F8TPP)FeIII-O-CuII(TMPA)]+ (4) (known S = 2 system, antiferromagnetically coupled high-spin FeIII and CuII). Mössbauer spectroscopy exhibits a sharp quadrupole doublet (zero field; delta = 0.57 mm/s, |DeltaEQ| = 1.14 mm/s) for 3, with isomer shift and magnetic field dependence data indicative of a peroxide ligand and S = 2 formulation. Both UV-visible-monitored stopped-flow kinetics and Mössbauer spectroscopic studies reveal the formation of heme-only superoxide complex (S)(F8TPP)FeIII-(O2-) (2a) (S = solvent molecule) prior to 3. Thermal decomposition of mu-peroxo complex 3 yields mu-oxo complex 4 with concomitant release of approximately 0.5 mol O2 per mol 3. Characterization of the reaction 1a/1b + O2 --> 2 --> 3 --> 4, presented here, advances our understanding and provides new insights to heme/Cu dioxygen-binding and reduction.Inorganic Chemistry 05/2007; 46(10):3889-902. · 4.60 Impact Factor -
Article: Further Insights into the Spectroscopic Properties, Electronic Structure, and Kinetics of Formation of the Heme−Peroxo−Copper Complex [(F8TPP)FeIII−(O22-)−CuII(TMPA)]+
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ABSTRACT: In the further development and understanding of heme−copper O2-reduction chemistry inspired by the active-site chemistry in cytochrome c oxidase, we describe a dioxygen adduct, [(F8TPP)FeIII−(O22-)−CuII(TMPA)](ClO4) (3), formed by addition of O2 to a 1:1 mixture of the porphyrinate−iron(II) complex (F8TPP)FeII (1a) {F8TPP = tetrakis(2,6-difluorophenyl)porphyrinate dianion} and the copper(I) complex [(TMPA)CuI(MeCN)](ClO4) (1b) {TMPA = tris(2-pyridylmethyl)amine}. Complex 3 forms in preference to heme-only or copper-only binuclear products, is remarkably stable {t1/2 (RT; MeCN) ≈ 20 min; λmax = 412 (Soret), 558 nm; EPR silent}, and is formulated as a peroxo complex on the basis of manometry {1a/1b/O2 = 1:1:1}, MALDI-TOF mass spectrometry {16O2, m/z 1239 [(3 + MeCN)+]; 18O2, m/z 1243}, and resonance Raman spectroscopy {ν(O-O) = 808 cm-1; Δ16O2/18O2 = 46 cm-1; Δ16O2/16/18O2 = 23 cm-1}. Consistent with a μ-η2:η1 bridging peroxide ligand, two metal−O stretching frequencies are observed {ν(Fe-O) = 533 cm-1, ν(Fe-O-Cu) = 511 cm-1}, and supporting normal coordinate analysis is presented. 2H and 19F NMR spectroscopies reveal that 3 is high-spin {also μB = 5.1 ± 0.2, Evans method} with downfield-shifted pyrrole and upfield-shifted TMPA resonances, similar to the pattern observed for the structurally characterized μ-oxo complex [(F8TPP)FeIII−O−CuII(TMPA)]+ (4) (known S = 2 system, antiferromagnetically coupled high-spin FeIII and CuII). Mössbauer spectroscopy exhibits a sharp quadrupole doublet (zero field; δ = 0.57 mm/s, |ΔEQ| = 1.14 mm/s) for 3, with isomer shift and magnetic field dependence data indicative of a peroxide ligand and S = 2 formulation. Both UV−visible-monitored stopped-flow kinetics and Mössbauer spectroscopic studies reveal the formation of heme-only superoxide complex (S)(F8TPP)FeIII−(O2-) (2a) (S = solvent molecule) prior to 3. Thermal decomposition of μ-peroxo complex 3 yields μ-oxo complex 4 with concomitant release of 0.5 mol O2 per mol 3. Characterization of the reaction 1a/1b + O2 → 2 → 3 → 4, presented here, advances our understanding and provides new insights to heme/Cu dioxygen-binding and reduction.04/2007; -
Article: Mycobacterial catalase-peroxidase is a tissue antigen and target of the adaptive immune response in systemic sarcoidosis.
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ABSTRACT: Sarcoidosis is a disease of unknown etiology characterized by noncaseating epithelioid granulomas, oligoclonal CD4(+) T cell infiltrates, and immune complex formation. To identify pathogenic antigens relevant to immune-mediated granulomatous inflammation in sarcoidosis, we used a limited proteomics approach to detect tissue antigens that were poorly soluble in neutral detergent and resistant to protease digestion, consistent with the known biochemical properties of granuloma-inducing sarcoidosis tissue extracts. Tissue antigens with these characteristics were detected with immunoglobulin (Ig)G or F(ab')(2) fragments from the sera of sarcoidosis patients in 9 of 12 (75%) sarcoidosis tissues (150-160, 80, or 60-64 kD) but only 3 of 22 (14%) control tissues (all 62-64 kD; P = 0.0006). Matrix-assisted laser desorption/ionization time of flight mass spectrometry identified Mycobacterium tuberculosis catalase-peroxidase (mKatG) as one of these tissue antigens. Protein immunoblotting using anti-mKatG monoclonal antibodies independently confirmed the presence of mKatG in 5 of 9 (55%) sarcoidosis tissues but in none of 14 control tissues (P = 0.0037). IgG antibodies to recombinant mKatG were detected in the sera of 12 of 25 (48%) sarcoidosis patients compared with 0 of 11 (0%) purified protein derivative (PPD)(-) (P = 0.0059) and 4 of 10 (40%) PPD(+) (P = 0.7233) control subjects, suggesting that remnant mycobacterial catalase-peroxidase is one target of the adaptive immune response driving granulomatous inflammation in sarcoidosis.Journal of Experimental Medicine 04/2005; 201(5):755-67. · 13.85 Impact Factor -
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2005
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Johns Hopkins Bloomberg School of Public Health
Baltimore, MD, USA
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