Molecular Heme−Cyanide−Copper Bridged Assemblies:  Linkage Isomerism, Trends in ν_CN Values, and Relation to the Heme-<i>a</i>₃/Cu_B Site in Cyanide-Inhibited Heme−Copper Oxidases

Abstract

Bovine heart cytochrome c oxidase and related heme copper oxidases are inhibited by cyanide, which binds at the binuclear heme-a(3)/Cu(B) site where dioxygen is reduced to water. To determine the mode of cyanide binding, heme-based binuclear complexes containing iron-cyanide-copper bridges in different oxidation states have been prepared by the reaction of [(py)(OEP)Fe(CN)] with Cu(II,I) precursors and structurally characterized by X-ray methods. Structures of two precursor complexes and two binuclear Cu(I)-CN-Cu(I) species are reported. The assembly [(py)(OEP)Fe-CN-Cu(Npy(3))](2+) has a nearly linear Fe(III)-CN-Cu(II) bridge containing low-spin Fe(III). The assemblies [(OEP)Fe-NC-Cu(MeNpy(2))](+) and [(OEP-CH(2)CN)Fe-NC-Cu(Npy(3))](+) exhibit the high-spin bridges Fe(III)-NC-Cu(I) and Fe(II)-NC-Cu(I), respectively. These are the first title bridges in these oxidation states. Bridge atom sequences are obtained from structural refinements of both linkage isomers; those for the reduced bridges are consistent with the soft-acid nature of Cu(I). Cyanide stretching frequencies respond to metal oxidation state and bridge geometry and, using data for solution and solid states, fall into the following ranges: Fe(III)-CN-Cu(II), 2120-2184 cm(-)(1) (11 examples); Fe(III)-NC-Cu(I), 2072-2100 cm(-)(1) (2 examples); Fe(II)-NC-Cu(I), 2099-2107 cm(-)(1) (1 example). These data are compared with nu(CN) values for the enzymes in different oxidation states. A nonlinear Fe(III)-CN-Cu(II) bridge (Cu-N-C = 150-160 degrees ) is consistent with the 2146-2152 cm(-)(1) range found for the fully oxidized enzymes. Bands that can be assigned with some certainty as Fe-CN vibrations in partially and fully reduced enzymes do not appear to correspond to Fe(III)-NC-Cu(I) and Fe(II)-NC-Cu(I) bridges but rather to Fe(II)-CN modes. The current work complements and extends our previous investigation (Scott and Holm, J. Am. Chem. Soc. 1994, 116, 11357) of linear and nonlinear Fe(III)-CN-Cu(II) bridges and is part of an investigation directed at providing a molecular basis of cyanide toxicity. (MeNpy(2) = bis(2-(2-pyridylethyl))methylamine; Npy(3) = tris(2-pyridylmethyl)amine; OEP = octaethylporphyrinate(2-), OEP-CH(2)CN = N-(cyanomethyl)octaethylporphyrinate(1-).)