Models of the Cytochromes. Redox Properties and Thermodynamic Stabilities of Complexes of “Hindered” Iron(III) and Iron(II) Tetraphenylporphyrinates with Substituted Pyridines and Imidazoles

Abstract

The Fe III /Fe II and Fe II /Fe I reduction potentials of a series of model hemes have been measured by cyclic voltammetry in dimethylformamide at 25°C as a function of the concentration of added axial ligands. The six porphyrinate ligands utilized were tetraphenylporphyrin (TPP), tetramesitylporphyrin (TMP), and a series of "hindered" tetraphenylporphyrins having substituents (OCH 3 , F, Cl, Br) on both ortho positions of each of the four phenyl rings. The perchlorato salts of the iron(III) porphyrinates were utilized for the titrations. The axial ligands utilized were N-methylimidazole, 2-methylimidazole, and pyridines of basicities ranging in pK a (PyH + ) from 9.7 to 1.1. From the electrochemical titration, the equilibrium constants (log 2 and some log 1 ) of each iron porphyrinate with each ligand were determined. The values of log 2 for the iron(III) complexes decrease in the order Br > Cl > CH 3 > OCH 3 > H > F, while those for iron(II) decrease in the slightly modified order Br > Cl > CH 3 > F > OCH 3 > H. Rather than electronegativity or electron-donating/withdrawing characteristics, these results appear to follow primarily the physical size of the ortho substituents: The iron porphyrinates with the largest ortho substituents have the largest equilibrium constants. The hindered (TPP)Fe II complexes are usually, but not always, more stable than the corresponding hindered (TPP)Fe III complexes. For both (TPP)Fe III and the hindered (TPP)Fe III complexes, the slope of the correlation of log 2 III with the pK a of the conjugate acid of the pyridine ligand is 1.0. The equilibrium constants for hindered (TPP)Fe II complexes, however, have virtually no dependence upon the base strength of the axial pyridines, while those for (TPP)Fe II has a slight sensitivity, with a slope of 0.15. In contrast to common belief, 2-methylimidazole readily forms bis complexes with some iron(II) tetraphenylporphyrinates ((TMP)Fe II , ((2,6-Cl 2 )TPP)Fe II , and ((2,6-Br 2 ) 4 (TPP)Fe II ), although it does not with (TPP)-Fe II and its (2,6-F 2 ) 4 -and (2,6-(OCH 3 ) 2 ) 4 -counterparts. N-Methylimidazole is unique among the axial ligands of this study, in that the equilibrium constants for binding to both Fe(III) and Fe(II) are virtually identical for all porphyrinates studied.

Synthesis and characterization of a novel series of meso (nitrophenyl) and meso (carboxyphenyl) substituted porphyrins

“…As expected, the compounds containing the metal centre show two extra peaks at less negative potentials than that observed for reduction of the free base porphyrins. These peaks were assigned to the successive reduction of the iron (III)-iron(II) and iron (II)-iron (I) couples in the porphyrin complex 32,33 . However, the cyclic voltammograms are significantly changed in morphology and potential magnitude as the number of nitro groups is increased in the macrocycle.…”

Covalent heme attachment in Synechocystis hemoglobin is required to prevent ferrous heme dissociation

“…Since heme affinity (and thus protein stability) would increase with this tighter heme coordination, it is odd that the His117-heme vinyl bond would be necessary to stabilize the protein in the ferric oxidation state. Furthermore, small molecule model-heme studies affirm that bis-histidyl heme coordination may be tighter in the ferric than the ferrous oxidation state (Nesset et al 1996;Safo et al 1997). If this chemical principle holds true in SynHb, the protein should be more susceptible to heme loss and subsequent unfolding in the ferrous oxidation state compared to the ferric.…”

Electrochemical and NMR spectroscopic studies of distal pocket mutants of nitrophorin 2: Stability, structure, and dynamics of axial ligand complexes

“…Although carboxylate groups near the heme are one factor that helps to stabilize the Fe(III) state (12,25), another may be heme ruffling (19). It has been argued that for low-spin ferrihemes ruffling of the heme should disfavor reduction from Fe(III) to Fe(II), and hence ruffled hemes have more negative reduction potentials than planar hemes (19,26,27). This is probably because low-spin Fe(II) strongly disfavors a ruffled heme core (26,28).…”