Probing the interactions between sterically demanding ferrihemes and histidine analogues. I. 2-D NMR studies of nonplanar ferriheme/bis(N-/2-methylimidazole) complexes; II. Synthesis of a trans-disubstituted tetraarylporphyrin with a bulky group near each potential axial ligation site

摘要

In a hemoprotein, histidine and other aromatic amines that ligate to the heme may encounter steric interactions from the following: (1) the peptide chains that form the pocket; or (2) the porphyrin ring that may have been distorted by the protein matrix or a distal ligand. Models that mimic these steric interactions need to be synthesized and studied in detail. The results of two research projects---both dealing with porphyrins that interact sterically with the axially ligated aromatic amines--are presented in this dissertation. In the first part, variable-temperature 2-D NMR studies of nonplanar ferriheme complexes are presented. Hemes are surprisingly flexible, and a significantly distorted conformation is accessible by the forces exerted by surrounding proteins and ligands. Iron(III) octaethyltetraphenylporphyrin ([Fe(III)OETPP]⁺) is a saddled macrocycle that could serve as a model for distorted hemes. Two low-spin [Fe(III)OETPP]⁺ complexes, one with two N-methylimidazole (N-MeIm) molecules as the axial ligands and the other with two 2-methylimidazole (2-MeImH), have been made, and their NMR spectra recorded as a function of temperature. Spectral assignment for the bis(N-MeIm) complex has been made through 2-D techniques. The NOESY spectra indicate that at about -40°C, the ring inversion halts while the axial ligand dissociation remains prevalent. The spectra of the bis(2-MeImH) complex at -85°C indicate that the dominant internal dynamics consists of ring inversion and a concerted rotation of the axial ligands. In the second part, the synthesis of a porphyrin with two sterically large groups near the potential sites of axial ligation is presented. In a bis(aromatic amine)/iron(III) complex of the alphabeta-atropisomer of 5,15-di-p-tolyl-10,20-bis[2,3-[(((hydrotris(3,5-dimethylpyrazolyl)borato)oxomolybdenio)dioxy]phenyl]porphyrin (1), the axial ligands are expected to be rotationally fixed. The synthesis of 1 is described. The corresponding trans -ditolylbis(dimethoxyphenyl)porphyrin (2) was synthesized from p-tolualdehyde and 2,3- dimethoxyphenyldipyrromethane in acidified aqueous sodium dodecyl sulfate in 16-25% yield. The demethylation of 2 and the subsequent reaction with HB(3,5-Me₂Pyz)₃(OCH₂CH₂O) afforded 1, characterized with FAB-MS (cation detection mode). The product most likely consists entirely of the alphabeta-atropisomer because of the steric constraint during the formation.