Secondary-Sphere Hydrogen Bonds Regulating Spin-Redox Interplay in Hemes

Area of Science:

• Bioinorganic Chemistry
• Computational Chemistry
• Biophysical Chemistry

Background:

• Hydrogen bonding (H-bonding) is crucial for metalloprotein function, influencing substrate binding and active-site geometry.
• In heme enzymes, H-bonding networks modulate iron's redox potentials and spin states, impacting catalytic efficiency.
• The precise molecular origins of H-bonding effects on heme electronic structure and redox properties require further exploration.

Purpose of the Study:

• To investigate the influence of secondary-sphere H-bonding interactions on the geometry, spin state, and redox properties of iron(III) porphyrin complexes.
• To elucidate the molecular mechanisms by which H-bonding regulates heme electronic structure and redox behavior.
• To provide fundamental insights into enzymatic regulation through H-bonding.

Main Methods:

• Synthesis and characterization of iron(III) porphyrin-phenoxide and iron(III)-chloro complexes.
• Spectroscopic analysis (e.g., UV-Vis, EPR) to determine spin states and structural parameters.
• Electrochemical studies (e.g., cyclic voltammetry) to probe redox potentials.
• Computational modeling (e.g., DFT calculations) to support experimental findings.

Main Results:

• Secondary-sphere H-bonding elongated the axial Fe─O bond and contracted the porphyrin core in iron(III) porphyrin-phenoxide complexes.
• H-bonding stabilized the intermediate-spin (S = 3/2) state, while its absence favored the high-spin (S = 5/2) state.
• Electrochemical studies showed positive shifts in Fe(III)/Fe(II) redox potentials and 1e- oxidation upon H-bonding, indicating redox noninnocence.

Conclusions:

• Secondary-sphere H-bonding significantly influences the geometry, spin state, and redox properties of heme iron centers.
• H-bonding acts as a key regulator of redox noninnocence in heme systems.
• These findings offer fundamental insights into the role of H-bonding in enzymatic catalysis and regulation.