J. Am. Chem. SOC. 1994,116, 12127-12128
12127
Verdoheme-like Oxaporphyrin Formation by Oxygenation of a Co(I1) Porphyrinyl Naphthoic Acid. A New Model of Heme Degradation C. K. Chang,* Gladys AvilBs, and Nillcamal Bag
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Department of Chemistry, Michigan State University East Lansing, Michigan 48824
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Received September 20, 1994 Biological heme degradation catalyzed by heme oxygenases (HO) is the source of bile pigments as well as endogenous carbon monoxide, a putative second neural messenger.'s2 The major events occurring in HO-dependent transformations are 0 2 binding and activation at the heme iron, followed by hydroxylation at the porphyrin meso position to form an a-hydroxyprotoheme, which then reacts with a second mole of 0 2 to give verdoheme with concomitant elimination of the meso carbon as CO. Finally verdoheme reacts with a third molecule of 0 2 to form biliverdin. While recent characterization of H03s4 and model studies based on coupled o ~ i d a t i o d -have ~ shed much light on the first and last stages of this process, mechanistic description for the conversion of meso-hydroxyheme to verdoheme remains poorly defined. Sano and coworkers7 have demonstrated that this conversion can occur spontaneously in solution without enzyme. The driving force is suggested to arise from the facile formation of an oxophlorin radical that promotes oxygen attack at a porphyrin ring carbon. However, without additional evidence, little is certain about how the oxygenation and the elimination of CO actually happen. It would be of great value if a parallel of this reaction could be found. We here report such an example. During the course of our study of H-bonding effects on heme-oxygen binding, we synthesized a naphthoic acid porphyrin l9and observed a curious reaction which bears much similarity to the verdoheme formation. When Co(II) complex l a was exposed to air in CH2C12, the color quickly changed from red to green in less than 1 min. The green product, after being isolated by chromatography, has a molecular ion of 538 (by FAB-MS) consistent with the oxaporphyrin cation 2. The absorption spectral features of 2 are solvent dependent (Figure 1). Even though 2 may become Co(II1) in air, the observation that an EPR-active material can be obtained initially without any reducing agent present during the entire process argues that (1) Maines, M. D. Heme Oxygenase-Clinical Applications and Functions; CRC Press: Boca Raton, FL, 1992. (2),(a) Verma, A.; Hirsch, D. J.; Glatt, C. E.; Ronnett, G. V.; Snyder, S. H. Science 1993, 259, 381-384. (b) Zhuo, M.; Small, S. A,; Kandel, E. R. Hawkins, R. D. Science 1993, 260, 1946-1950. (3) Wilks, A.; Ortiz de Montellano, P. R. J . Biol. Chem. 1993, 268, 22357-22362. (4) (a) Sun, J.; Wilks, A,; Ortiz de Montellano, P. R.; Loehr, T. M. Biochemistrv 1993. 32. 14151-14157. (b) Takahashi. S.: Wane. J.: Rousseau, D. L.; Ishikawa, K.; Yoshida, T.; Host, J. R.; Ike&-Sait& M: J . Biol. Chem. 1994, 269, 1010-1014. (5) (a) O'Carra, P. In Porphyrins and Metalloporphyrins; Smith, K. M., Ed.; Elsevier: New York, 1975; p 122. (b) Schmid, R.; McDonagh, A. F. In The Porphyrins; Dolphin, D., Ed.; Academic Press: New York, 1979; Vol. VI, p-258. (6) Saito, S.; Itano, H. A. Proc. Natl. Acud. Sci. U.SA. 1982, 79, 1393. (7) (a) Sano, S.; Sugiura, Y.; Maeda, Y.;Ogawa, S.; Morishima, I. J . Am. Chem. SOC. 1981,103,2888-2890. (b) Sano, S.; Sano, T.; Morishima, I.; Shiro, Y.; Maeda, Y. Proc. Natl. Acad. Sci. U S A . 1986, 83, 531-535. (8) (a) Balch, A. L.; Latos-Grazydski, L.; Noll, B. C.; Olmstead, M. M.; Szterenberg, L.; Safari, N. J . Am. Chem. SOC. 1993, 115, 1422-1429. (b) Balch, A. L.; Latos-Grazydski, L.; Noll, B. C.; Olmstead, M. M.; Safari, N. J. Am. Chem. SOC. 1993, 115, 9056-9061. (9) Chang, C. K.; Kondylis, M. P. J . Chem. SOC.,Chem. Commun. 1986, 316-918. (10) (a) Balch, A. L.; Mazzanti, M.; Olmstead, M. M. J . Chem. SOC., Chem. Commun. 1994,269-270. (b) A Co(II) oxaporphyrin has also been characterized: Balch, A. L.; Mazzanti, M.; St. Claire, T. N.; Olmstead, M. M. Inorg. Chem., submitted by publication.
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