The dramatic effect of N-methylimidazole on trans axial ligand binding to ferric heme: experiment and theory

Abstract

The presence of histidine or its mimic methylimidazole as the axial ligand on ferric heme dramatically weakens the opposite ferric–ligand bond.

Water binding to FeIIIhemes studied in a cooled ion trap: characterization of a strong ‘weak’ ligand

“…The complete calculated spectrum is shown in Figure S3A of ESI and displays the most intense bands close to 370 nm in the known intense experimental Soret region. The calculated spectrum of the free heme [PP-Fe III ] + is also represented in Figure 5b, together with the experimental spectrum of [PP-Fe III −N2] + , which we deem as closest to free [PP-Fe III ] + , owing to the very weak interaction of N2 with Fe III 4,27 .…”

“…This binding energy is important and is several times higher than that of O2 and CO to ferric heme, however inferior to that of NO (-24.9 kcal.mol -1 ) 5 . Therefore, in normal conditions, ferric heme shall not bind O2 nor 27 , even with the ligation occurring through a  donation from the lone pairs to Fe(3dz 2 ). Therefore water ferric heme occupies a striking intermediate case as…”

Heme ligation in the gas phase

“…The situation is however different for ferric complexes. Figure 7 shows an overview of the calculated energies of the spin states for free and ligated ferrous porphyrins ( Figure 7a) [30] and ferric porphyrins ( Figure 7b) [55], relative either to [Fe II P] or to [Fe III P] + . [Fe II P-Im] was positioned with respect to five coordinate [Fe II P] using the binding energy of imidazole to [Fe II P] calculated by Liao et al [45] equal to 15 kcal/mol.…”

“…In turn, a six-coordinate ferric heme with NO exhibits a binding energy, E=-3.65 ± 0.17 kcal/mol, strikingly lower by a factor of 6 relatively to five coordinate [Fe III NO] + . This value is obtained from van't Hoff temperature dependent measurements while studying the equilibrium of doubly protonated microperoxydase 11 (MP11), [Fe III MP11 2H] 3+ , with NO [55]. These low values are also paralleled in six-coordinate ferrous porphyrins, although in solution equilibria According to their calculations, the six-coordinate complex is only weakly bound, (E~5 kcal/mol), though showing all attributes of a strong bond: a short Fe-NO bond (1.6 Å), a high Fe-N stretching force constant -twice as high in the ferrous complex (blue profile) as compared to the ferric complex (red profile) (4.82 / 2.26 mdyn/Å), supported by experimental measurements.…”

“…The -donor effect is not specific to this compound N-methyl imidazole, and was observed in the ligation of the doubly protonated microperoxydase, [MP11+2H] 3+ (schemed in ref [55]) with O2 , CO and NO in 6C. The binding energy derived from the van't Hoff measurements and temperature corrections indicates a similar effect in the ratio of binding energies: = -0.69 ± 0.14 kcal/mol ( [MP11 2H-O2] 3+ ) as compared to the five coordinate heme value E=-2.26 ± 0.26 kcal/mol ([Fe III Heme-O2] + ) (see Table 4).…”