Second sphere control of spin state: Differential tuning of axial ligand bonds in ferric porphyrin complexes by hydrogen bonding

• Hydrogen bonding can weaken as well as strengthen FeIII–OH bonds.
• A weak (FeIII)–OH bond (due to hydrogen bonding) stabilizes a low spin state.
• A stronger Fe(III)–OH (due to hydrogen bonding) stabilizes high spin state.
• Hemoglobin and peroxidases likely follow the same principle.

An iron porphyrin with a pre-organized hydrogen bonding (H-Bonding) distal architecture is utilized to avoid the inherent loss of entropy associated with H-Bonding from solvent (water) and mimic the behavior of metallo-enzyme active sites attributed to H-Bonding interactions of active site with the 2nd sphere residues. Resonance Raman (rR) data on these iron porphyrin complexes indicate that H-Bonding to an axial ligand like hydroxide can result in both stronger or weaker Fe(III)–OH bond relative to iron porphyrin complexes. The 6-coordinate (6C) complexes bearing water derived axial ligands, trans to imidazole or thiolate axial ligand with H-Bonding stabilize a low spin (LS) ground state (GS) when a complex without H-Bonding stabilizes a high spin (HS) ground state. DFT calculations reproduce the trend in the experimental data and provide a mechanism of how H-Bonding can indeed lead to stronger metal ligand bonds when the axial ligand donates an H-Bond and lead to weaker metal ligand bonds when the axial ligand accepts an H-Bond. The experimental and computational results explain how a weak Fe(III)–OH bond (due to H-Bonding) can lead to the stabilization of low spin ground state in synthetic mimics and in enzymes containing iron porphyrin active sites. H-Bonding to a water ligand bound to a reduced ferrous active site can only strengthen the Fe(II)–OH2 bond and thus exclusion of water and hydrophilic residues from distal sites of O2 binding/activating heme proteins is necessary to avoid inhibition of O2 binding by water. These results help demonstrate the predominant role played by H-Bonding and subtle changes in its orientation in determining the geometric and electronic structure of iron porphyrin based active sites in nature.

2nd sphere H-Bonding interaction to Fe(III)–OH species can lead to both weakening and strengthening of the Fe–OH bond. The stronger Fe–O bond results in high spin ground state whereas weaker Fe–O bond results in low spin ground state.Figure optionsDownload as PowerPoint slide