“…While the core of each protein is mainly hydrophobic, the outer surface ranges in polarity from hydrophilic to amphiphilic to lipophilic. 10.3.1.1 Early Heme-Peptide Models: Porphyrin as Template Studies on natural proteins have shown that the protein environment modulates the specific function in a hierarchical manner [87]: the primary coordination sphere (i.e., the presence of one or both axial ligands, and their type and donor properties) controls the intrinsic reactivity of the metal center. Factors such as the local dielectric constant, hydrophobicity, hydrogen bonding, and steric interactions between the primary sphere and its immediate surroundings (i.e., the second coordination sphere) contribute to the next level of control.…”