Coordination of N-Donor Ligands by the Monomeric Ferric Porphyrin N-Acetylmicroperoxidase-8

Abstract

The monomeric ferric hemepeptide from cytochrome c, N-acetylmicroperoxidase-8 (NAcMP8), retains the proximal His ligand and has a coordinated water molecule in the second axial site. It provides an opportunity for quantitatively studying in aqueous solution the coordination chemistry of an iron porphyrin with a single accessible coordination site. An examination of the dependence of the spectrophotometrically determined equilibrium constants for coordination of imidazole and cyanide as a function of pH provides a procedure for correcting conditional equilibrium constants for the ionization of coordinated H2O in NAcMP8 and protonation of the entering ligand, L. An examination of the coordination by NAcMP8 of L = primary amines and imidazoles (25 °C, μ = 0.1 M) and pyridines (as a function of temperature, μ = 0.1 M) has shown that the process of binding L to NAcMP8 may be complex. With some ligands such as pyridines and some primary amines there is evidence for formation of an outer-sphere complex before displacement of H2O occurs. In some cases, a third process occurs at high concentrations of L which may entail substitution of the proximal His ligand. Pyridines and imidazoles fall into different classes in their basicity−affinity for Fe(III) relationships; primary amines fall into two distinctive classes, with one class having a higher affinity for Fe(III) than expected from basicity alone. It is suggested that neutral or cationic functional groups in the side chain of these ligands provide a second site of attachment to the iron porphyrin by hydrogen bonding. A compensating effect between ΔH and ΔS values for coordination of pyridines to NAcMP8 is demonstrated; hence log K values, rather than the individual thermodynamics parameters, were used to explore the possible influence of the electronic structure of the ligands on the magnitude of their affinity for Fe(III). Log K for coordination of pyridines and imidazoles correlates linearly, and statistically meaningfully, with the energies of the frontier orbitals of σ and π symmetry (determined by ab initio or semiempirical molecular orbital methods at the RHF level of theory using, respectively, the 6-31G* split-valence polarized basis set and the PM3 model), which have large amplitude on the donor N atom. There is only a weak correlation between log K and the energy of the frontier σ orbital for primary amines. These observations suggest that both σ bonding and π bonding between planar aromatic ligands and Fe(III) play a significant role in determining the magnitude of the binding constant of these ligands to a ferric porphyrin.

Disproportionation of hydroxylamine by water-soluble iron(III) porphyrinate compounds

“…The formation of [Fe II (Porph)(H 2 NR)] or [Fe II (Porph)-(H 2 NR) 2 ] by autoreduction of porphyrinates with alkyl or aryl amines has also been reported previously [29]. In addition, the coordination of amines to microperoxidases has been thoroughly studied [30], and a binding constant K 1 = 8 Â 10 2 M À1 was obtained for coordination of HA in N-AcMP8. Only primary amines exhibited a redox reactivity toward microperoxidases [31], while NH 3 or imidazole were inert toward the iron(III) hemepeptide.…”

“…Time evolution leads to the formation of an intermediate of lower absorbance, red shifted from the original compound (k max = 405 nm). Both results point to a Fe III (Porph)(L)(L 0 ) complex.Bis-coordination of amines to microperoxidases, requiring the displacement of the proximal histidine, has been reported[30]. This is not the case for the reaction with HA in our reaction conditions, as1 H NMR signals of coordinated histidine were only slightly modified in the spectra recorded as a function of time (Supplementary information).3-Disproportionation mediated by [NHOH]:To account for the free-radical formation evidenced by the methylmetacrilate assay with [Fe III (TEPyP)] 5+ , the comparatively higher redox potential of [Fe III (TEPyP)] 5+ plays an essential role as it changes the scenario leading to an easy reduction of [Fe III (TEPyP)(HA) 2 ] 5+ by excess HA, with the concomitant formation of [Fe II (TEPyP)(HA) 2 ] 4+ and a radical nitrogen containing species, [NHOH] Á(Fig.…”

Covalently attached metalloporphyrins in LBL self-assembled redox polyelectrolyte thin films

“…On the other hand, the binding of primary amines to Fe(III) porphyrins has been carefully studied. It was demonstrated that there is a linear dependence of the affinity constant and the pK a of the conjugated acid of the primary amine [30]. In our case, the increase of ip for oxygen reduction correlates with a higher number of active redox centers, suggesting that the inclusion of ammonia as axial ligand promotes the required geometry to bind oxygen.…”

Could Redox‐Switched Binding of a Redox‐Active Ligand to a Copper(II) Centre Drive a Conformational Proton Pump Gate? A Synthetic Model Study

“…In the light of the present study, the facts that one histidine ligand to Cu B is labile and that during the enzyme cycle the tyrosine ± histidine ligand to Cu B is oxidised with a hydroxide ancillary ligand simultaneously produced [6,9,12] become most intriguing. Argument based upon the mixing of s/p electrons inherent within an imidazole [46] and the inter-ring conjugation anticipated for the tyrosine-histidine cofactor suggests its redox-state should strongly modulate its metal binding properties (Figure 8 B). The most recent evidence is that there indeed is electronic delocalisation between the rings of a histidine ± tyrosyl radical, [47] and we have shown that such inter-ring delocalisation between a ligand donor and its radical pendant can significantly alter the reactivity of a (organo-) metal centre.…”