Synthesis of dendritic metalloporphyrins with distal H-bond donors as model systems for hemoglobin

We report the synthesis of the first- (G1) and second-generation (G2) dendritic Fe-II porphyrins 1 (.) Fe-4 (.) Fe (G1) and 6-Fe (G2) bearing distal H-bond donors ideally positioned for stabilization of Fe-II-O-2 adducts by H-bonding (Fig. 1). A first approach towards the construction of these novel biomimetic systems failed unexpectedly: the Suzuki cross-coupling between appropriately functionalized Zn-II porphyrins and ortho-ethynylated aryl derivatives, serving as anchors for the distal H-bond donor moieties, was unsuccessful (Schemes 1, 3, and 5), presumably due to steric hindrance resulting from unfavorable coordination of the ethynyl residue to the I'd species in the catalytic cycle (Scheme 6). The target molecules were finally prepared by a route in which the ortho-ethynylated meso-aryl ring is introduced during porphyrin construction in a mixed condensation involving the two dipyrrylmethanes 33 and 34, and aldehyde 36 (Schemes 7 and 8). Following attachment of the dendrons (Scheme H), the distal H-bond donors were introduced by Sonogashira cross-coupling (Scheme 12), and subsequent metallation afforded the dendritic Fell porphyrins 1 (.) Fe-6 (.) Fe. H-1-NMR Spectroscopy proved the location of the H-bond donor moiety atop the porphyrin surface, and X-ray crystal-structure analysis of model system 45 (Fig. 2) revealed that this moiety would not sterically interfere with gas binding. With 1,2-dimethyl-1H-imidazole (DiMeIm) as ligand, the dendritic Fe-II porphyrins formed five-coordinate high-spin complexes (Figs. 3 and 4) and addition of CO led reversibly to the corresponding stable six-coordinate gas complexes (Fig. 6). Oxygenation, however, did not result in defined Fe-II-O-2 complexes as rapid decomposition to Fe-III species took place immediately, even in the case of the G2 dendrimer 6 (.) Fe(DiMeIm) (Fig. 7). In contrast, stable gas adducts are formed between dendritic Co-II porphyrins and O-2 in the presence of DiMeIm as axial ligand, as revealed by electron paramagnetic resonance (EPR). The possible stabilization of these complexes through H-bonding involving the distal ligand is currently under investigation in multidimensional and multifrequency pulse EPR experiments.