9056 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA J. Am. Chem. SOC. zyxwv 1993,115, 9056-9061 Isolation and Characterization of an Iron Biliverdin-Type Complex That Is Formed along with Verdohemochrome during the Coupled Oxidation of Iron( 11) Octaethylporphyrin+~ll zyxwvutsrqponmlkji Alan L. Balch,’** Lechoshw Latos-Graiyiiski,*Bruce C. No&* Marilyn M. Olmstead,* and Nasser Safari* Contribution from the Department zyxwvu of Chemistry, University of California, Davis, California 9561 6, and Institute of Chemistry, University of Wrockw, Wrockaw zyxwvutsrq 50383, Poland Received January I I, 1993” Abstract: The coupled oxidation process, which is a model for oxidative heme degradation, has been shown to produce not only verdoheme, which was first described in 1930, but also a paramagnetic iron complex. Treatment of (0EP)- FeI1(py)2 (OEP is the dianion of octaethylporphyrin) with air and ascorbic acid in pyridine (py) solution yields 50% diamagnetic zyxwvutsrqp [ zyxwvutsr (octaethyIo~aporphyrin)Fe~~(py)2]Cl, a verdoheme, and 32% paramagnetic {(OEB)Fe111)2 (OEB is the octaethylbilindione trianion, a biliverdin analog). Dimeric ((OEB)Fe111)2 has been identified by a combination of IH NMR and X-ray crystallographic studies. In this dimer, each iron is coordinated to four nitrogen atoms from one OEB trianion and an oxygen from another OEB ligand. Treatment of {(OEB)Fe111)2 with hydrochloric acid gives blue octaethylbilindione in 91% yield. In pyridine-d5 solution, IH N M R studies show that {(OEB)Fe1I1j2 undergoes cleavage of the Fe-O bond to form (OEB)Fe111(py)2. This process is reversible. Introduction Heme oxygenase performs the essential role of destroying unwanted Its action is readily visible in human bruises where the conversion of purple heme to green and then yellow pigments is familiar to all readers. Scheme I shows a typical version of a widely accepted bath for the initial conversion of heme to biliverdin. Biliverdin is then converted to bilirubin by a second enzyme, biliverdin reductase. The coupled oxidation procedure, which involves air oxidation of iron(I1) porphyrins in pyridine solution in the presence of a reducing agent (ascorbic acid or hydrazine), has been extensively employed as a model for the heme oxidase reacti~n.”~ This process readily produces a deep green, diamagnetic complex-verdohemochrome. Recent structural studies from this laboratory have confirmed the long- standing proposals that verdohemochrome and its derivatives t Dedicated to Professor R. H. Holm on this 60th birthday. f University of California, Davis. 8 University of Wroclaw. 11 Abbreviations; OEP, dianion of octaethylporphyrin; OEOP, monoanion of octaethyloxaporphrin; OEB, trianion of octaethylbilindione; py, pyridine; OEPO, trianion of octaethyloxophlorin. e Abstract published in Advance ACS Abstracts. September 1, 1993. (1) OCarra, P. In Porphyrins and Metalloporphyrins; Smith, K. M., Ed.; Elsevier: New York, 1975; p 123. (2) Schmid, R.; McDonagh, A. F. In The Porphyrins; Dolphin, D., Ed.; Academic Press: New York, 1979; Vol. 6, p 258. (3) Bissell, D. M. In Liver: Normal Function and Disease; Ostrow, J. D., Ed.;Marcel Decker, Inc.: New York, 1986; Vol. 4, Bile Pigments and Jaundice, p 133. B138, 386. (4) Warburg, 0.; Negelein, E. Chem. Ber. 1930, 63, 1816. (5) Foulkes, E. C.; Lemberg, R.; Pardonn, P. Proc. R. SOC. London 1951, (6) Lemberg, R. Rev. Pure Appl. Chem. 1956, 6, 1. (7) Levin, E. Y. Biochemistry 1966, 5, 2845. (8) Bonnett, R.; Dimsdale, M. J. J. Chem. SOC., Perkin Trans. 1 1972.79, (9) Saito, S.; Itano, H. A. Proc. Natl. Acad. Sci. U.S.A. 1982, 79, 1393. (10) Lagarias, J. C. Biochim. Biophys. Acta 1982, 717, 12. (1 1) Itano, H. A,; Hirota, T. Tetrahedron Lett. 1983, 24, 995. (12) Sano, S.; Sano, T.; Morishima, I.; Shiro, Y.; Maeda, Y. Proc. Natl. (13) Saito, S.; Itano, H. A. J. Chem. Soc., Perkin Trans. 1 1986, 1. (14) Masuoka, N.; Itano, H. A. Biochemistry 1987, 26, 3672. (15) Saito, S.; Sumita, S.; Iwai, K.; Sano, H. Bull. Chem. SOC. Jpn. 1988, 1393. Acad. Sci. U.S.A. 1986, 531. 61, 3539. Scheme I. Heme Oxygenationa H V H M +2H H Hem Iron oxophlorin veldchem complex M. mthyl v. vinyl -N HN\ R. propionate M Pr H Pr Pr H Pr Biliverdin [ron biliverdin complex Iron oxidation states and axial ligation omitted. contain the planar, oxaporphyrin macrocycle.16 Thus oxidation of (OEP)FeI1(py)2 (1) yields the deep green, octaethyloxapor- - Ascorbic Acid phyrin complex [(OEOP)FeI1(py)2]C1 (2). This is a symmetric analog of verdohemochrome. Despite the attention given to coupled oxidation over a number of years, the fact that verdohemochrome formation rarely accounts for more than 40% (16) Balch, A. L.; Latos-Graiyfiski, L.; NOH, B. C.; Olmstead, M. M.; Szterenberg, L.; Safari, N . J. Am. Chem. SOC. 1993, 115, 1422. 0002-7863/93/1515-9056$04.00/0 zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPONMLKJIHGFEDCBA 0 1993 American Chemical Society