Heme protein mimics

Dendritic derivatives of these macrocycles can be placed in the wider context of studies on metalloporphyrins with sterically hindered faces which have been designed in attempts to mimic the properties of heme proteins and chlorophylls, and there are suggestions that steric isolation of the metalloporphyrin nucleus is important in certain biological functions, The redox properties of metalloporphyrins are well-documented they are dominated by two, reversible one-electron transfers involving both the metal and the ligand. The first dendritic porphyrins of general structure 47 and their Zn complexes were reported by Inoue et al. who... 

This overall sequence of reactions is important because it mimics the natural process of heme rupture during catabolism of waste heme proteins. A blood corpuscle serves, on average, a useful life of about 120 days, and heme systems which perform more dangerous functions, such as cytochrome P450 (which activates molecular oxygen and subsequently hydroxylates hydrocarbons), survive for much shorter periods. In response to an unknown... 

Diederich et al.11921 reported the divergent synthesis of dendrimers possessing porphyrin cores with the aim of modeling redox potentials of electroactive chromophores via environmental polarity modification. The dendrimers thus can be considered as electron-transfer protein mimics for such proteins as cytochrome c oxidation potentials for cytochrome c in aqueous solution are known to be 300-400 mV more positive than those reported for similarly ligated heme mimics lacking hydrophobic peptide encapsulation J193a ... 

Model Compounds Very few ferrous complexes having non-porphyrin ligands react with dioxygen to form stable adducts. Unlike the pseudo-heme model complexes, all of the adducts prepared so far appear to be peroxo rather than superoxo species. To mimic the protein fragment on the non-heme proteins multidentate... 

Metallopeptide models refer to systems that are mostly unstructured in solntion in the absence of metal ions. It is applicable to design of metal-binding sites whose conserved residues appear mostly in a single peptide that is often much shorter than the whole protein. Designing metalloproteins using only the peptide with the consensus sequence, often called a motif, represents the minimalist approach in its purest sense. These motifs typically contain His, Cys, or both residues. In addition, metalloporphyrin-containing peptides have also been made to mimic basic features in heme proteins. 

These structural characteristics mean that the dendrimer porphyrin can be used to mimic the function of the heme protein - its ability to bind to oxygen. A dendrimer porphyrin with an Fe(II) ion can stably trap oxygen via coordination with imidazole ligands. The oxygen was reversibly trapped within the dendrimer, and it can be released when the oxygen in the surrounding solvent was removed. The dendrimer sphere shields the porphyrin part from the outer environment. Therefore, side effects such as irreversible oxidation of the porphyrin by water and dimerization of the oxygen-bound porphyrins can be suppressed. 

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 order to mimic the biological functions of heme proteins, one of the challenging targets is to realize... 

One strategy to mimic the heme proteins is to embed the iron(II) porphyrins in a polymer. Bell et al. incorporated iron-5,10,15,20-tetraphenylporphyrin into films of a... 

Syntheses of porphyrins and metalloporphyrins have been widely investigated over the last three decades to provide models which mimic functions of heme proteins, heme enzymes and supramolecular assembly of chlorophyll in green plants and photosynthesis bacteria. Results on the syntheses and structure of biomimetic porphyrins up to 1985 have been reviewed by Morgan and Dolphin. ... 

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. 

The critical discovery [195] was that, under mild conditions, triphosgene can be used to convert the four amino groups of 4.0-tetrakis(o-aminophenyl)porphyrin (4.0-TAPP) to isocyanato groups. This generates the useful new intermediate, a,a,a,a-tetrakis(o-isocyanatophenyl)porphyrin (4.0-TIPP), which can be derivatized with an almost unlimited range of functional groups, giving the freedom to prepare sophisticated superstructures that may more accurately mimic natural heme-protein structures. 

Synthetic models of myoglobin and hemoglobin are complex molecules that mimic the stereochemical properties of the protein active center [24] and have oxygen affinities similar to those measured for the protein [25-27]. The first heme model that reversibly binds oxygen (i.e. the picket-fence-oxygen complex Fe(TpivPP)(l,2-Melm)(02), shown in Fig. 3.3) was obtained in the early nine-teen-seventies by Collman and coworkers (TpivPP = tetrapivalami-nophenyl porphyrin 2-meIm = 2-methylimidazole) [18]. Research on synthetic models of the protein has led to a deeper understand-... 

Some pyridine-containing ligands of this type have been used to mimic the protein environment in non-heme iron metal proteins. The ligands L (10 and 11) tend to bind strongly to five positions of the coordination sphere leaving the sixth position available to bind unidentate ligands X [FeLX]w+. 

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