Heme protein models

All native NiR enzymes are believed to undergo a ferric nitrite-to-nitrosyl transformation, as in Eqs. (4.17)-(4.19) , but this may not be the case with other heme proteins. Doyle first reported that the reaction of ferrous hemoglobin (Hb) with nitrite was zero order in protein , but first order in nitrite and protons a similar dependence has been reported for the reaction of ferrous Mb with nitrite . This implies that the reductive dehydration is dependent on the reaction of Fe with HONO, or its equivalent as NO+, as in Equation (4.22)-(4.24), and 

Liu and coworkers utilized Hb adsorbed on colloidal gold nanoparticles in carbon paste electrode (CPE) to investigate the reduction of nitrite at pH 4. (One criticism of this work is that, at this low pH, aqueous Hb is denatured. 

Similar results were reported by Fan et al. in their voltammetric studies of nitrite reduction by Hb contained in DNA film electrodes at pH 4. These films showed well-defined Fe V couple at —0.36 V SCE, Eq. (4.26), and upon addition of nitrite two new cathodic peaks were observed. Also, when the lower scan potential was limited to —0.5 V, the Fe / peak current decreased linearly due to formation of stable Hb-Fe NO complex, as previously seen for Mb. Pre-electrolysis followed by linear scan voltammetric sweeps showed that at H-0.3 V the predominant species is met-Hb, at —0.5 V the Hb-NO complex is the predominates species, and at —0.9 V the Hb-Fe predominates, apparently due to NO depletion in the electroactive layer. 

Many additional reports have mentioned nitrite reduction by Mb 11, 

Methodology EVotein pH Fe /Fe (V) pH NOJ red. (V) Detection range (mM) Detection limit (mM) References 

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These minimalistic peptide scaffolds potentially provide a biologically relevant laboratory in which to explore the details of heme-peptide interactions and, with development, perhaps approach the observed range of natural heme protein fimction. These heme-peptide systems are more complex than typical small molecule bioinorganic porphyrin model compoimds, and yet are seemingly not as enigmatic as even the smallest natural heme proteins. Thus, in the continuum of heme protein model complexes these heme-peptide systems lie closer to, but certainly not at, the small molecule limit which allows for the effects of single amino acid changes to be directly elucidated. 

Lombardi A, Nastri F, Pavone V (2001) Peptide-based heme-protein models. Chem Rev 101 3165-3189... 

Traylor TG, Popovitz-Biro R (1988) Hydrogen bonding to the proximal imidazole in heme protein model compounds effects upon oxygen binding and peroxidase activity. J Am Chem Soc 110 239-243... 

The four-coordinate sqnare planar iron(n) porphyrins discussed above are not only of great valne in heme protein model chemistry, but also in chemical applications, since they undergo a wealth of ligand addition reactions. For example it has been shown that TPPFe complexes are active catalysts for important carbon transfer reactions in organic chemistry and are found to catalyze the stereoselective cyclopropanation of aUcenes, olefin formation from diazoalkanes, and the efficient and selective olefination of aldehydes and other carbonyl compounds. The active species in these carbon transfer reactions are presumably iron porphyrin carbene complexes. " It was also found that ferrous hemin anchored to Ti02 thin films reduce organic halides, which can pose serious health problems and are of considerable environmental concern because of their prevalence in groundwater. ... 

Becanse of their relevance in heme protein model chentistry, many studies have focused on the addition of... 

The main distortions that can occur upon CO binding are distortion of the porphyrin ring, such as ruffling, and/or expansion of the porphyrin core, but no significant tilting or bending of the Fe-CO bond. This finding is also supported by 3 C CP/MAS studies of heme protein models with axially... 

Zhang, Y., Mao, J.H., Oldfield, E. 57Fe Mossbauer isomer shifts of heme protein model systems Electronic structure calculations. J. Am. Chem. Soc. 2002,124, 7829-39. 

Peptide-based heme-protein models 01CRV3165. 

Perhaps the most obvious approach to the synthesis of heme protein models is to reproduce the local environment of the heme active site by covalently attaching various peptide fragments to a suitable porphyrin. If the peptide fragments contain suitable amino acids (e.g. histidine, methionine), reproduction of the coordination sphere of the heme protein may be possible. 

One of the initial examples of the strapped porphyrin approach to heme protein models was the cyclophane porphyrin 193 of Diekmann et al. . In this example steric... 

A further refinement to the production of heme protein models was the synthesis of doubly-strapped models containing different straps. As models for hemoglobin or myoglobin, incorporation of a nitrogen base into one strap would simulate the proximal face of the natural system while the steric encumbrance provided by the second strap would mimic the distal, oxygen-binding face. 

In this context, the reaction of azanone with isolated iron porph5nins seemed to be a relevant study to be carried out. The first experiments involved the reaction of common, previously described HNO donors such as trioxodinitrate (AS) and tol-uenesulfohydroxamic acid (a PA derivative, TSHA), with several model porphyrins, including the water soluble anionic meso-tetrakis(4-sulfonatophenyl)porphynnate [Fe(III)TPPS] , the cationic meso-tetrakis-N-ethyl pyridinium-2-yl porph3me [Fe(III) TEPyP], as well as the pentacoordinated heme-protein model... 

Genherg, L. Heisel, F. McLendon, G. Miller, R. J. D., Vibrational energy relaxation processes in heme proteins Model systems of vibrational energy dispersion in disordered systems. J. Phys. Chem. 1987, 91, 5521-5524. 

For monomeric host porphyrin framework, we may start from natural porphyrins such as protoporphyrin IX and its derivatives. In earlier times, the 3- and 8-vinyl and 13- and 17-propionates of protoporphyrin IX were subjected to simple chemical mc ifications like reduction, addition and condensation. The first chemical modification for synthesis of heme protein models reported by Lautch et al. is condensation of an oligopeptide with the two propionates. In order to mimic the proximity of the heme, terminal His or Cys of oligopeptide linked to the 13- and 17-propionates of heme can coordinate to the heme iron as axial ligands. 

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