Dendrimers with porphyrin cores: Synthetic models for globular heme proteins

Dendritic iron porphyrins were synthesized as functional mimics of globular electron-transfer heme proteins. The cascade molecules 1 . Zn-3 . Zn of first to third generation were obtained starting from the (meso-diarylporphyrin) zinc 6 . Zn which contains four carboxylate arms for attachment of the poly(ether-amide) dendritic branches by peptide-coupling methodology (Scheme 1). Generation 3 compound 3 . Zn with 108 methyl-carboxylate end groups has a molecular weight of 19054 D, and computer modeling suggests that its structure is globular and densely-packed, measuring ca. 4 nm in diameter and, therefore, similar in dimensions to the electron-transfer protein cytochrome-c. Starting from the generation 1 poly(carboxylic acid) 11 . Zn and the generation 2 analog 12 . Zn the dendritic Zn-II porphyrins 4 . Zn and 5 . Zn, respectively, were obtained by esterification with triethyleneglycol monomethyl ether (Schemes 3 and 4). Demetallation followed by insertion of Fe-II and in situ oxidation afforded the water-soluble dendritic iron porphyrins 4 . FeCl and 5 . FeCl. The electrochemical behavior of esters 1 . Zn-3 . Zn in organic solvents changed smoothly with increasing dendritic generation (Table 1). Progressing from 1 . Zn to 3 . Zn in THF, the first porphyrin-centered oxidation and reduction potentials become more negative by 320 and 210 mV, respectively. These changes were attributed to strong microenvironmental effects imposed on the electroactive core by the densely packed dendritic surroundings. The electrochemical properties of 4 . FeCl and 5 . FeCl were investigated by cyclic voltammetry in both CH2Cl2 and H2O (Tables 2 and 3). Progressing from 4 . FeCl to 5 . FeCl in CH2Cl2, the redox potential of the biologically relevant Fe-III/Fe-II couple remained virtually unchanged, whereas in aqueous solution, 5 . FeCl exhibited a potential 420 mV more positive than did 4 . FeCl. The large difference between these potentials in H2O was attributed to differences in solvation of the core electrophore. Whereas the relatively open dendritic branches in 4 . FeCl do not impede access of bulk solvent to the central core, the densely packed dendritic superstructure of 5 . FeCl significantly reduces contact between the heme and external solvent. As a result, the more charged Fe-III state is destabilized relative to Fe-II, and the redox potential is strongly shifted to a more positive value.