Setting an Upper Limit on the Myoglobin Iron(IV)Hydroxide pK_a: Insight into Axial Ligand Tuning in Heme Protein Catalysis

Abstract

To provide insight into the iron(IV)hydroxide pKa of histidine ligated heme proteins, we have probed the active site of myoglobin compound II over the pH range of 3.9–9.5, using EXAFS, Mössbauer, and resonance Raman spectroscopies. We find no indication of ferryl protonation over this pH range, allowing us to set an upper limit of 2.7 on the iron(IV)hydroxide pKa in myoglobin. Together with the recent determination of an iron(IV)hydroxide pKa ∼ 12 in the thiolate-ligated heme enzyme cytochrome P450, this result provides insight into Nature’s ability to tune catalytic function through its choice of axial ligand.

Carbon Nitride Nanosheet-Supported Porphyrin: A New Biomimetic Catalyst for Highly Efficient Bioanalysis

“…Moreover, the relative integral peak area of pyridinic/ amino N dropped in comparison with that in Figure 3A, probably a consequence from the conversion of some pyridinic nitrogens into Co II −N after the formation of CoPPIX@C 3 N 4 . 39 This interaction could be verified by contrasting Co 2p 3/2 and Co 2p 1/2 peaks of CoPPIX with those of CoPPIX@C 3 N 4 . The former dual doublets occurred at 779.4/781.0 and 794.5/795.4 eV, respectively ( Figure 3C), and the latter moved to higher binding energies at 782.3/783.9 and 796.0/797.6 eV ( Figure 3D), which could be ascribed to the site affinity of positively charged Co II to N with high local electronegativity.…”

Mn(V)(O) versus Cr(V)(O) Porphyrinoid Complexes: Structural Characterization and Implications for Basicity Controlling H-Atom Abstraction

“…A 9 line signal centered at g = 1.987 is observed, consistent with a Cr V ( d 1 , S = ½) ion with hyperfine coupling to four equivalent pyrrole nitrogen atoms ( 14 N, I = 1). The satellite signals at high and low fields are due to hyperfine splitting from 53 Cr (9.5% abundant, I = 3/2).…”

“…In heme enzymes, the Cytochrome P450s are among the most powerful H-atom abstractors, utilizing Compound I ((Fe IV (O)(porph •+ )(cys)) for strong C-H cleavage. 1 The large driving force presented for H-atom abstraction by P450 can be related to the bond dissociation free energy (BDFE) of the O-H bond of Compound II (Fe IV (OH)(porph)(cys)), formed after H-atom transfer (HAT). The O-H BDFE can be further dissected into electron (E°) and proton (pK a ) affinities (or basicity), and evidence indicates that it is the elevated basicity of the Fe IV =O unit in Cpd-II (pK a ~ 12) that provides an advantage in driving force for HAT.…”

Proton-Coupled Electron Transfer in Organic Synthesis: Fundamentals, Applications, and Opportunities

“…Moreover, the axial ligation of the metal oxo in iron heme proteins has been demonstrated to have a profound effect on the pK a of the Fe IV oxo form of the enzyme [49] as well as the Fe-O bond strength observed in model systems [50].…”