Axial Ligation Modes in Iron(III) Porphyrins. Models for the Oxidized Reaction States of Cytochrome P-450 Enzymes and the Molecular Structure of Iron(III) Protoporphyrin IX Dimethyl Ester p-Nitrobenzenethiolate

S. C. Tang, S. Koch, G. C. Papaefthymiou, S. Foner, R. B. Frankel*, James A. Ibers, R. H. Holm

*Corresponding author for this work

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252 Scopus citations

Abstract

Cytochrome P-450 monooxygenase enzymes contain a protoporphyrin IX prosthetic group and exhibit five reaction states, in each of which the nature of axial ligation to Fe(II, III) is uncertain. The occurrence of sulfur coordination has been a matter of active speculation. The two oxidized states, ox-P-450 (resting, low spin) and ox-P-450•S (substrate bound, high spin), contain Fe(III) with apparent six and five coordination, respectively. In an attempt to develop experimental criteria for identifying axial ligands in iron(IIl) porphyrins, the series of complexes Fe(P)L (high spin) and Fe(P)LL′ (low spin), P = octaethylporphyrin, protoporphyrin IX dimethyl ester (PPIXDME) dianions, have been isolated and generated in situ, respectively, and subjected to detailed physical studies. Axial ligands L and L′ include a variety of oxygen, sulfur, and nitrogen donors intended to model possible protein side chain coordination. Isolable Fe(P)SR complexes were obtained with R = aryl. The crystal structure of Fe(PPIXDME)(SC6H4-p-NO2) has been determined by x-ray diffraction techniques utilizing 6320 observations collected by counter methods. The compound crystallizes in space group Ci1-P[formula ommitted] with two molecules in a cell of dimensions a = 13.585 (6), b = 14.016 (2), c = 13.297 (2) Å, α = 110.83 (2), β = 119.74 (2), and γ = 62.60 (2)°. The observed density of 1.35 (2) g cm-3 compares favorably with the calculated density of 1.378 g cm-3. Refinement of an anisotropic model (497 variables) by full-matrix least-squares methods leads to a conventional R index (on F2) of 0.126 for the 6320 observations and to a conventional R index (on F) of 0.071 for the 3225 observations having Fo> 3σ(Fo). The molecule exhibits near square pyramidal geometry with an Fe-S distance of 2.324 (2) Å and Fe-N distances ranging from 2.042 (5) to 2.081 (5) and averaging to 2.064 Å. The iron atom is 0.448 Å above the mean plane of the porphyrin core, which is nearly planar (mean deviation from the mean plane is 0.038 Å) but exhibits a slight ruffling that corresponds roughly to an S4 distortion. Although the mean dimensions within the porphyrin agree well with previously reported values, there is a perceptible alternation in the lengths of the Cb-Ca bonds around the periphery of the porphyrin as well as an alternation of the Ca-Cm bonds such that there occurs a long-short-long-short… sequence of Cb-Ca, Ca-Cm, Cm-Ca, Ca-Cb bonds. The phenyl ring makes a dihedral angle of 11.1° with the porphyrin plane, and is situated away from the bulky propionic ester substituents. Extensive compilations of results are presented and include (i) electronic spectral data, (ii) principal g values evaluated from EPR spectra, (iii) Mössbauer parameters, (iv) effective magnetic moment values and crystal field parameters obtained from field dependent (≤60 kOe) magnetization data. Of the species Fe(P)L (L = ArS-, ArO-, OAc-) and acidmetmyoglobin or hemoglobin, Fe(PPIXDME)(SAr) complexes provide the closest approach to the optical, EPR, and Mössbauer properties of ox-P-450·S. Of interest are the values of the saturation magnetic hyperfine field at the Fe nucleus, obtained from high-field (≤80 kOe) Mössbauer and magnetization measurements at 4.2 K. For L = O- and N-donor ligands Hhf0 ≳ -500 kOe whereas Hhf0= -476 ± 10 and -448 ± 10 kOe for Fe(PPIXDME)(SC6H4-p-NO2) and ox-P-450cam·S, respectively. Low-temperature optical and EPR spectra of Fe(P)LL′ complexes (L = N-, O-, S-donor ligands) together with data for cytochromes b and c, when compared with corresponding enzyme properties, indicate thiolate sulfur coordination in ox-P-450. With the provisos that not all possible axial ligation modes of the enzyme, simulated by L or L/L′ combinations, could be experimentally tested and that synthetic porphyrins may have limitations as models of biological heme coordination the following conclusions are drawn: (i) the most probable axial ligation mode in the ox-P-450·S state is Cys-S-Fe; (ii) the most probable modes in the ox-P-450 state are Cys-S-Fe-L′, with L′ = His, Lys(Arg), Cys-SH, Met, and Asn(Gln). No further conclusions regarding L could be drawn from the experimental data obtained here.

Original languageEnglish (US)
Pages (from-to)2414-2434
Number of pages21
JournalJournal of the American Chemical Society
Volume98
Issue number9
DOIs
StatePublished - Apr 1 1976

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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