Probing the Mechanism for 2,4'-Dihydroxyacetophenone Dioxygenase Using Biomimetic Iron Complexes

Area of Science:

• Bioinorganic Chemistry
• Organometallic Chemistry
• Enzyme Mimicry

Background:

• Nonheme iron enzymes play crucial roles in biological oxidation reactions.
• Understanding enzyme mechanisms often involves synthesizing model complexes.
• 2,4'-dihydroacetophenone dioxygenase (DAD) is a nonheme enzyme with an unknown substrate binding mode.

Purpose of the Study:

• To synthesize and characterize iron complexes that model the enzyme-substrate adduct and ferric forms of DAD.
• To investigate the coordination chemistry and electronic properties of these model complexes.
• To elucidate the substrate binding state and catalytic mechanism of DAD.

Main Methods:

• Synthesis and characterization of three iron complexes: [Fe(T1Et4iPrIP)(2-OH-AP)(OTf)](OTf) (2), [Fe(T1Et4iPrIP)(2-O-AP)](OTf) (3), and [Fe(T1Et4iPrIP)(DMF)3](OTf)3 (4).
• X-ray crystallography to determine the structures of complexes 2-4.
• UV-vis spectroscopy and TD-DFT calculations to analyze electronic properties.
• Stoichiometric and catalytic oxidation studies in the presence of O2.

Main Results:

• Complexes 2 and 3 serve as models for the DAD enzyme-substrate adduct, while complex 4 models the ferric DAD.
• X-ray crystallography revealed tridentate binding of the T1Et4iPrIP ligand in all complexes.
• Complex 2's UV-vis spectrum closely matched the DAD-substrate spectrum, suggesting protonated substrate binding.
• Complexes 2 and 3 exhibited catalytic oxidation of substrate mimics with O2.
• Complex 4 was reduced to complex 2 in the presence of 2-hydroxyacetophenone.

Conclusions:

• The substrate for DAD likely binds in a protonated form, as suggested by complex 2.
• The synthesized iron complexes provide valuable insights into the structure and function of DAD.
• The catalytic activity of complexes 2 and 3 demonstrates the potential of these models to mimic DAD's oxidative capabilities.