Iron-protoporphyrin dimethyl ester

When hemin (1) is treated with gaseous hydrogen chloride in anhydrous methanol/pyridine in the presence of iron(II) sulfate, protoporphyrin dimethyl ester (2), the metal-free ligand of hemin. is produced in almost quantitative yield. This compound is quite sensitive to oxygen... 

See also Iron hemoproteins excited-state relaxation, 173,175f Fe(II) protoporphyrin dimethyl ester... 

Killday etal. (1988) also provided evidence for internal autoreduction of ferric nitrosyl heme complexes, as previously proposed by Giddings (1977). Heating of chlorohemin( iron-III) dimethyl ester in dimethyl sulfoxide solution with imidazole and NO produced a product with an infrared spectra identical to that of nitrosyl iron(ll) protoporphyrin dimethyl ester prepared by dithionite reduction. Both spectra clearly showed the characteristic nitrosyl stretch at 1663 and 1665 cm. They thus proposed a mechanism for formation of cured meat pigment which includes internal autoreduction of NOMMb via globin imidazole residues. A second mole of nitrite is proposed to bind to the heat-denatured protein, possibly at a charged histidine residue generated in the previous autoreduction step. 

The positions of the narrow bands obtained at low temperatures with protoporphyrin dimethyl ester, were measured by comparison with an iron arc. The narrower band with a center near X 53,630, broke up into three components of frequency 18,462, 18,648, 18,909 cms.-1. The wider band (center at approx. X 5000) yielded six components 19,488, 19,668, 19,887, 20,107, 20,328, 20,544 cms.-1. It is interesting that the frequency differences in the first group are 186 and 260 cms.-1 and in the second 180, 219, 220, 221, 226 cms.-1. This suggests that the components in each group represent vibrational bands having a common value for the change in the vibrational quantum number. 

Protoporphyrin and its derivatives, because of their labile vinyl substituents, are susceptible to acid-catalyzed hydration. For this reason aqueous solutions should be avoided in the preparation of protoporphyrin dimethyl ester from protohemin, and subsequent reinsertion of the iron. Thus the direct esterification of protohemin under basic conditions appears to be the method of choice. More stable porphyrins such as H2oep are most conveniently prepared by the direct insertion of iron(lll) ion using the iron(III) chloride method5 the resultant Fe(IIl) (oep)Cl can be separated directly from the reaction medium as shining purple crystals. However, this method fails to give successful results with protoporphyrin derivatives. In general, the iron (II) sulfate method is the mildest and should be used for all prophyrins unless one is certain that the more rapid alternatives [boiling DMF with iron(II) chloride, or preferably the more stable iron(II) perchlorate] will have no ill effect on the peripheral substituents. 

The bispyridine haeme iron(II) compounds are low-spin 5 = 0 complexes and give only a single quadrupole split spectrum [1]. The bis-adducts of iron(II) and iron(III) protoporphyrin, a, /9, y, d-tetraphenylporphyrin, and protoporphyrin dimethyl ester with bases such as imidazole and pyridine are also low-spin [2]. The quadrupole splittings at 80 K were found to be... 

Taking protoporphyrin-IX (19) as the inexpensive commercially available starting material for porphyrin manipulations, the common substituent reactions are shown in Scheme 8. Protoporphyrin-IX is usually obtained simply by demetallation of hemin, the most efficient route (which provides the dimethyl ester, ready for chromatographic purification) involving treatment with iron(II) sulfate in methanol containing HC1 gas. 

Figure 14, Proton magnetic resonance spectrum at 100 MHz of fx oxo bis(protoporphyrin IX dimethyl ester iron(lIl)) in CDCI3 at 35°C...

Younathan, J., K.S. Wood, and T.J. Meyer (1992). Electrocatalytic reduction of nitrite and nitrosyl by iron(III) protoporphyrin-IX dimethyl ester immobilized in an electropolymerized film. Inorg. Chem. 31, 3280-3285. 

CfljHAoFeNgOeS, Iron(III) protoporphyrin IX dimethyl ester p-nitro-benzenethiolate, 42B, 377... 

Dimethyl protoporphyrinato(2-)iron(IIl), either as the chloride or the p-oxo dimer, is fairly soluble in chloroform and dichloromethane. The iron complex is much more stable toward light than the parent protoporphyrin but is still susceptible to acid-catalyzed hydration. The ester can be hydrolyzed to yield pure protohemin by using the alcoholic-KOH procedure.1,2 The optical spectra of these and other iron porphyrins have been reviewed recently.7... 

---