Structurally Modelling the 2-His-1-Carboxylate Facial Triad with a Bulky N,N,O Phenolate Ligand

Area of Science:

• Coordination Chemistry
• Bioinorganic Chemistry
• Organometallic Chemistry

Background:

• The 2-His-1-carboxylate facial triad (2H1C) is crucial in the active sites of various metalloenzymes.
• Developing synthetic models of these triads is essential for understanding enzyme mechanisms.
• Existing models often lack the precise coordination environment or stability required for accurate biomimicry.

Purpose of the Study:

• To synthesize and characterize a bulky, tripodal N,N,O ligand, Im^Ph2 NNO^tBu (L), designed to mimic the 2H1C.
• To explore the coordination chemistry of this ligand with non-heme metals like iron and zinc.
• To investigate the structural and electronic properties of the resulting metal complexes for biomimetic applications.

Main Methods:

• Ligand synthesis and characterization.
• Coordination of the ligand with MCl₂ (M = Fe, Zn) to form metal complexes.
• X-ray crystallography to determine complex structures.
• Solution studies in various solvents.
• Synthesis of a zinc thiolate complex for isopenicillin N synthase (IPNS) biomimicry.
• Cyclic voltammetry and Density Functional Theory (DFT) calculations for electrochemical analysis.

Main Results:

• High-yield synthesis of isostructural, tetrahedral non-heme complexes [Fe(L)(Cl)] and [Zn(L)(Cl)].
• Tridentate N,N,O ligand coordination confirmed in solid-state and solution.
• Formation of a tetrahedral zinc thiolate complex [Zn(L)(SPh)] relevant to IPNS.
• Redox non-innocence of the ligand observed, with distinct electrochemical oxidation pathways for iron and zinc complexes.

Conclusions:

• The Im^Ph2 NNO^tBu ligand provides access to well-defined mononuclear, monoligated, N,N,O-bound metal complexes.
• This ligand enables more accurate structural modeling of the 2H1C environment.
• The developed complexes serve as valuable tools for studying the mechanisms of 2H1C-containing enzymes.