J. Am. Chem. zyxwvut SOC. zyxwvu 1991, 113, zyxwvu 8485-8492 8485 Structural and Reaction Chemistry of Nickel Complexes in Relation to Carbon Monoxide Dehydrogenase: A Reaction System Simulating Acetyl-Coenzyme A Synthase Activity Pericles Stavropoulos, Mark C. Muetterties, Michel Carrie, and R. H. Holm* Contribution from the Department zyxwvuts of Chemistry, Harvard University, Cambridge, Massachusetts 021 38. Received April 15. 1991 Abstract: A series of nickel complexes [Ni(NSjR)L]' derived from the tripodal ligand NS3R zyxw = N(CH2CH2SR)3 (R = i-Pr, t-Bu) has been prepared in order to investigate the stabilities and reactions of certain species potentially relevant to the nickel sites in carbon monoxide dehydrogenase (CODH). Reaction of [Ni(NS3R)Cl]+ with MeMgCl affords [Ni(NS,R)Me]+, which with CO yields [Ni(NS3R)COMe]+.Reaction of [Ni(NSJtsu)CI]+with NaBH, gives [Ni(NS3'BU)H]+ and the Ni(1) species [Ni(NSiBU)]+. The hydride complex was obtained with minimal Ni(1) contamination by removal of ethylene from the equilibrium system zyxwvutsrq [Ni(NS,'Bu)Et]+/[Ni(NS~BY)H]+/C2H4. Reaction of [Ni(NS3'BU)]+ with CO affords [Ni(NSIItBU)CO]+, whereas [Ni(NSiBU)H]+ under the same conditions gives Ni(C0)4and protonated ligand. All reactions were performed in THF, and all complexes were isolated as BPhL salts. This series includes rare examples of the stabilization of Ni-methyl, -acyl, -hydride, and -carbonyl ligands in the absence of nonphysiological (C/P/As) coligands. Trigonal-bipyramidal stereochemistry has been demonstrated for five complexes with L = CI, Me, COMe, H, and CO by X-ray crystallography. The methyl/acyl transformations with carbon monoxide and the formation in high yield of the thioesters R'SCOMe (R' = Et, CH2Ph, Ph) upon reaction of [Ni(NS,R)COMe]+ with thiols in THF are two previously undocumented processes mediated at Ni(I1) sites lacking non- physiological (C/P/As) ligation. These are relevant to current views of the catalytic reaction cycle of Clostridium thermoaceticum CODH, which is presented. The Ni"-H and NiI-CO species may be pertinent to the CO/C02 activity of CODH. Full details of all preparations, other reactions, and structures are presented. This work is an initial attempt to place the reaction chemistry of CODH on a rational basis, and provides some viability for the present reaction cycle of the enzyme. Introduction One of the major developments in bioinorganic chemistry in the last decade is the demonstration of a stoichiometric require- ment for nickel in four enzymes: urease, carbon monoxide de- hydrogenase (CODH), hydrogenase, and methyl-S-coenzyme-M reductase.'-' Our interest here is with the chemistry of CODH enzymes, which have been isolated from acetogenic, methanogenic, photosynthetic, and sulfate-reducing bacteria. These enzymes catalyze reaction 1, the interconversion of CO and C 0 2 via an (1) (2) CO + H20 F+ [C,] C02 + 2H+ + 2e- CH,-THF + COASH + CO + COASCOCH~ + THF CoAS*COCH, + CO * COASCOCH, + *CO (3) intermediate CI species in the presence of an electron carrier. In addition to this reaction, the enzymes of Clostridium thermo- aceticum (Ct) and other acetogenic and methanogenic organisms catalyze the synthesis of acetyl-coenzyme A, reaction 2 (THF = tetrahydrofolate), and related exchange processes including re- action 3. Thus, these enzymes are also acetyl-coA synthases."' Reaction 2 is a sum of the final steps in autotrophic C 0 2 or CO fixation via acetyl-coA synthesis, also known as the Wood pathway, which has been reviewed.4d The key elements in this anaerobic carbon cycle are summarized in the proposed scheme of Figure 1, which is based largely on the extensive and incisive investigations of Ct CODH by Ragsdale, Wood, and co-work- e r ~ . ~ * ~ ~ ~ By means of reaction 1, both C O and [ C 0 2 + H2] can (I) Hausinger, R. P. Microbiol. Reo. 1987, 51, 22. (2) Walsh, C. T.; Orme-Johnson, W. H. Biochemistry 1987, 26, 4901. (3) The Bioinorganic Chemistry of Nickel; Lancaster, J. R., Ed.; VCH (4) Wood, H. G.; Ragsdalc, S. W.; Pezacka, E. Biochem. Int. 1986, 12, (5) Ljungdahl, L. G. Annu. Rev. Microbiol. 1986, 40, 415. (6) Ragsdale, S. W.; Wood, H. G.; Morton, T. A.; Ljungdahl, L. G.; DerVartanian, D. V. In ref 3, Chapter 14. (7) Ragsdale, S. W.; Wood, H. G. J. Biol. Chem. 1985, 260, 3970. (8) (a) Ragsdale, S. W.; Lindahl, P. W.; Miinck, E. J. Biol. Chem. 1987, 262, 14289. (b) Harder, S. R.; Lu. W.-P.; Feinberg, B. A,; Ragsdale, S. W. Biochemistry 1989, 28, 9080. (9) Lu, W.-P.; Harder, S. R.; Ragsdale, S. W. J. Biol. Chem. 1990, 265, 3124. Publishers, Inc.: New York, 1988. 421. act as substrates. Methyl tetrahydrofolate is synthesized by a two-electron reduction of C02 to formate catalyzed by formate dehydrogenase, followed by a four-electron reduction of formate to CH3-THF catalyzed by a series of THF-dependent enzymes. In reaction 4 (Figure l), the methyl group of CH,-THF is then enzymatically transferred to a corrinoid p r ~ t e i n , ~ ? ~ generating a protein-bound methylcobamide. The subsequent steps 5 and 6 involve nonenzymatic methyl transfer9 to form a methyl-CODH intermediate and binding of CO at a metal site and methyl mi- gration at that site to afford a~etyl-CODH.~-~~ The order of methyl and CO binding in Figure 1 is arbitrary inasmuch as the occurrence of these processes may well be rand~m,~J* but the net outcome is the formation of the presumed acetyl intermediate. Finally, acetyl-CODH binds CoASH, apparently in the vicinity of the metal-containing site,I2 followed by reaction 7 of the acyl and thiol groups to yield acetyl-coA. When the complexity of Ct CODH (M, 148 000, aj3 subunits, 1 Zn, 2 Ni, - 12 Fe/S) and its reactions are considered, the extent of characterization since its purification to homogeneity in 198313 is remarkable. There remain for clarification, however, a number of fundamental chemical aspects. Two of these, the nature of the active site and the occurrence of reactions 5-7, are of principal concern here. While the active site of CODH is represented in Figure 1 as a single nickel center, this may be an oversimplification. In fact, (IO) Pezacka, E.; Wood, H. G. J. Biol. Chem. 1986,262, 1609. (b) Hu, S-1.; Drake, H. L.; Wood, H. G. J. Bacteriol. 1982, 149, 440. (11) Lu, W.-P.; Ragsdale, S. W. J. Biol. Chem. 1991, 266, 3554. (12) (a) Shanmugasundaram, T.; Kumar, G. K.; Wood, H. G. Biochem- istry 1988, 27, 6499. (b) Ragsdale, S. W.; Wood, H. G. J. Biol. Chem. 1985, zy 260. 3970. ---. -- -- (13) Ragsdale, S. W.; Clark, J. E.; Ljungdahl, L. G.; Lundie, L. L.; Drake, H. L. J. Biol. Chem. 1983, 258, 2364. (14) (a) Ragsdale, S. W.; Ljungdahl, L. G.; DerVartanian, D. V. Biochem. Biophys. Res. Commun. 1983,115, 658. (b) Ragsdale, S. W.; Wood, H. G.; Antholine, W. E. Proc. Natl. Acad. Sci. U.S.A. 1985, 82, 681 1. (c) Lindahl, P. A.; Miinck, E.; Ragsdale, S. W. J. Biol. Chem. 1990, 265, 3873. (d) Lindahl, P. A.; Ragsdale, S. W.; Miinck, E. J. Biol. Chem. 1990,265, 3880. (e) Fan, C.-L.; Gorst, C. M.; Ragsdale, S. W.; Hoffman, B. M. Biochemistry 1991, 30, 431. (15) Cramer, S. P.; Eidsness, M. K.; Pan, W.-H.; Morton, T. A.; Ragsdalc, S. W.; DerVartanian, D. V.; Ljungdahl, L. G.; Scott, R. A. Inorg. Chem. 1987, 26, 2477. 0002-7863/91/1513-8485$02.50/0 0 1991 American Chemical Society