General Structural Features that Modulate Ligand Affinity

There are many ways in which ligand affinity may be perturbed (Figure 4.25). It is convenient to divide these into two groups, referred to as distal and proximal effects. 163 Proximal effects are associated with the stereochemistry of the metalloporphyrinato moiety and the coordination of the axial base, and thus their influence on O2 and CO affinity is indirect. Distal effects pertain to noncovalent interactions of the metal-porphyrinato skeleton and the sixth ligand (02 , CO, etc.) with neighboring solvent molecules, with substituents, such as pickets or caps, on the porphyrin, and with the surrounding protein chain. The distal groups that hover over the Orbinding site engender the most important

distal effects. For convenience, the effects of crystal packing and the protein matrix on porphyrin conformation will be discussed among the proximal effects, although as nonbonded interactions they properly are distal effects. To a first approximation, the effects of substituents on the porphyrin ring, as transmitted through bonds to the metal center, do not perturb the ligand binding properties as much as do distal effects. 170 Thus substituents, such as vinyl and propionic-acid groups on protoporphyrin IX and o-pivalamidophenyl pickets, are ignored; one porphyrin is much like another. At the end of this subsection
the various ways ligand affinity may be modulated will be summarized in an augmented version of Figure 4.3.