Mechanochemical Activation of Small Molecules

Mechanochemistry is a process in which chemical reactions are driven by mechanical stress; however, up to date only polymers were shown to undergo covalent mechanochemical transformations. The most common mechanochemical transformation is cleavage of chemical bonds leading to scission of the polymer main chain. In the last 20 years, a series of mechanophores, molecules that when incorporated into the center of polymer chains are capable of undergoing selective and productive mechanochemical reactions have been developed. Mechanophores undergo organic transformations such as isomerizations, ring-opening reactions and bond-specific scissions.¹ However, mechanophores are only activated if they are covalently bound to a polymer, inhibiting their use for small molecule syntheses. Importantly, mechanochemical transformations could be very useful in the synthesis of important molecules such as natural products and drugs, as the mechanical force changes the energy potential of different chemical processes, directing the reaction to different products from the ones obtained by classical thermal, electro and photochemistry. Here, we present an approach to use dynamic covalent chemistry to reversibly bind small molecules and induce their mechanochemical activation.

We synthesized boronic acid terminated polymers, capable of binding 1,2-diols reversibly through trans-esterification reactions. Mechanochemically stable polymers (Mwlim) with a boronic acid end group (P) and a small molecule (M₁-M₂) containing two 1,2-diols, bind to form a mechanochemically sensitive polymer chain with a mechanophore at its center (P-M₁-M₂-P, Mw>Mlim). Under solvodynamic shear, the small molecule breaks into two moieties (M₁ and M₂) and they can be released by a trans-esterification reaction with another 1,2-diol molecule or hydrolysis (Scheme 1).

Scheme 1: General reaction

1. Jun Li, Jeffrey S. Moore, Chem. Res., 2015, 48, 2181-2190