FUEL-DRIVEN SYNTHESIS OF DYNAMIC COVALENT CATALYSTS

In this thesis, I focus my attention on applying different ratchet mechanisms to the synthesis of a molecule, thus filling the gap between non-equilibrium self-assembly and molecular machines. In the second chapter, an energy ratchet mechanism is exploited for the synthesis of an hydrazone bond between an aldehyde and an hydrazide bearing a TACN·Zn(II) unit. In the presence of ATP hydrazone-bond formation is accelerated and the composition at thermodynamic equilibrium is shifted towards the product. Enzymatic hydrolysis of ATP installs a kinetically stable state at which hydrazone is present at a higher concentration compared to the composition at thermodynamic equilibrium in the presence of the degradation products of ATP. Initial thermodynamic equilibrium is restored by heating the sample. It is shown that the kinetic state has an enhanced catalytic activity in the hydrolysis of HPNPP, an RNA model compound. In the third chapter, the discovery that TACN*Zn(II) compounds can hydrolyse phosphodiester bonds at higher temperatures allowed us to explore the possibility of making the same system presented in Chapter 2 autonomous. At 70 °C, the formation of hydrazone was favoured both kinetically and thermodynamically by the presence of ADP in the solution. Hydrolysis of ADP into AMP+Pi catalysed by hydrazone push the system in a state far from equilibrium in which its concentration is higher than the thermodynamic. Since the cycle is performed at high temperature equilibration of hydrazone occurs spontaneously. In the fourth chapter, light is used to form a dimer starting from a TACN*Zn(II)-functionalized styryl pyrene which can react through [2+2] cycloaddition. Reaction passes first through the formation of a cis- isomer that dimerizes. Although this kind of reaction is well known to be reversible, in this case, it occurs only at concentrations below 200uM. The dimer has a CAC which is 30 times lower than the cac of the trans-isomer and 200 times the cac of the cis-isomer. When irradiation is performed in a range of concentrations where styryl pyrene molecule doesn’t aggregate but the dimer does, the multivalent properties of the dimer-aggregate can be exploited to have an increased catalytic activity towards HPNPP hydrolysis.