CORE SIZE AND FLEXIBILITY OF METALLOHYDROPORPHYRIN MACROCYCLES - IMPLICATIONS FOR F430 COORDINATION CHEMISTRY

We have used molecular mechanics calculations to investigate the effect of macrocycle reduction on core-hole size and flexibility of a series of metallo(hydro)porphyrin molecules. Macrocycle reduction at beta-pyrrole positions results in an increase in core size, whereas reduction at methine positions results in a decrease in core size. The tetrapyrroles are found to become significantly more flexible (susceptibile to S4 ruffling) only when reduction occurs at methine positions. These results are used to explain the unique ligand-binding ability of the nickel-tetrapyrrole F430 cofactor of the S-methyl coenzyme M reductase enzyme of methanogenic bacteria. Molecular mechanics also predicts the increased axial-ligand affinity of the native F430 isomer compared to the 12,13-diepimer, as a result of the increase in macrocycle torsional strain in the 4-coordinate native isomer.