Dynamic metal-binding scaffolds accelerate kinetics : flexible thianthrene versus rigid anthracene scaffolds

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2023-12

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The effect of structural dynamics regarding enzymatic catalysis is prevalently studied within biochemistry and biology literature. It has been shown that dynamics is not only generally important for proper function, but can be intimately linked to catalysis. Interestingly, analogous research concerning small-molecule chemistry is lacking, particularly concerning homogeneous transition metal-mediated reactions. Transition metal complexes are integral for the advancement of industrial methods (catalysis) and biology (drug discovery and sensing). Research efforts to design novel complexes or improve existing ones tend to focus on the electronic qualities of the metal center and overall steric profile. These important qualities are modulated by associated ligand design and synthesis. Perhaps molecular flexibility is an overlooked feature pertaining to nominally rigid transition metal complexes because of the accompanied synthetic challenge to incorporate it in a controlled manner. In this vein, we have adopted a scaffold-based approach to controllably integrate structural dynamics without disturbing the electronic properties of the metal complexes. Namely, analogous complexes featuring flexible thianthrene and rigid anthracene scaffolds were synthesized, providing a framework to study the effect of dynamics on the reactivity of a metal-mediated ligand substitution, biomimetic hydride transfer and hydrolysis catalysis. A more flexible, thianthrene-based Mn tricarbonyl complex performed a ligand substitution reaction at an approximate 5x greater rate than the anthracene congener. A similar rate enhancement was observed concerning a biomimetic hydride transfer reaction performed with analogous [Fe]-hydrogenase functional model complexes. Finally, a pair of thianthrene and anthracene-scaffolded Zn complexes exhibited variable reactivity regarding hydrolysis catalysis with an ester substrate. We have demonstrated that structural dynamics can affect and even improve the kinetics of homogeneous metal-based reactions and thus should be a critical factor pertaining to ligand design.

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