M.Sc Thesis

M.Sc StudentAgami Iris
SubjectMechanochemical Activation of Small Molecules
DepartmentDepartment of Chemistry
Supervisor ASSOCIATE PROF. Charles E. Diesendruck
Full Thesis textFull thesis text - English Version


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, the development of mechanophores, molecules that undergo selective and productive mechanochemical reactions, demonstrated the potential of mechanochemistry for organic synthesis. Incorporated into the center of polymer chains, mechanophores are capable of undergoing isomerizations, ring-opening reactions and bond-specific scissions. Recent research has demonstrated the utilization of mechanochemistry to instigate productive chemical processes in mechanophores that cannot be achieved by thermal, photo or electrochemistry such as a retro-Staudinger cycloaddion, C-C bond activation and additional retro-cycloadditions that do not follow Woodward Hoffman rules. However, these reactions occurred only if the small molecules are covalently bound to a polymer, overwise small molecules just move in relation to each other, , inhibiting their use for small molecule syntheses.

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. In this research, we present an approach to use dynamic covalent chemistry to reversibly bind small molecules by a polymer catalyst, induce their mechanochemical activation. This process reassembles the enzyme activity on a substrate, pointing towards catalytic mechanochemistry.

We synthesized boronic acid terminated polymers, capable of binding 1,2- or 1,3-diols reversibly through trans-esterification reactions. This covalent dynamic bond, while weak chemically, is quite strong mechanochemically, and therefore, after connectivity, mechanical stress could activate a different covalent bond. Mechanochemically stable polymers (molecular weight (Mw) below limiting molecular weight (Mlim)) 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 small molecule at its center (P-M1-M2-P, Mw > Mlim). Under solvodynamic shear, the small molecule breaks into two moieties (M1 and M2). These moieties can be released from the polymer by a trans-esterification reaction with another 1,2-diol molecule or hydrolysis (Scheme 1).

Scheme 1: General reaction