An Approach to Thermodynamically Controlled Supramolecular Assembly in Water


Supramolecular chemistry focuses on the formation of multi-molecular complexes held together by non-covalent interactions. One prominent sub-field of study within supramolecular chemistry is the use of thermodynamic favorability to drive the self-assembly of complex structures, such as rotaxanes. Rotaxanes are a type of supramolecular complex in which a linear ‘guest’ molecule with bulky ends is threaded through a large ring-shaped ‘host’ molecule. Rotaxanes are important for several reasons such as their use as molecular shuttles and synthetic dye stabilizers. Many rotaxane synthesis techniques rely solely on the thermodynamic favorability of non-covalent interactions such as π-rich and π-poor aromatic unit interactions. A recent study created a synthesis method that used reversible carbonyl condensation chemistry to form the linear guest molecule within the host macrocycle much like assembling a ship piece by piece within a bottle.1 Then they used an irreversible dehydration step to remove the formation reversibility and ‘trap’ the guest molecule within the host molecule, creating a stable rotaxane. This research project examined whether rotaxanes could be formed in water through the addition of sodium bisulfite to augment the method used in the previous study. This project tested the premise that the hydrophilicity of the water combined with the favorable non-covalent interactions would then drive rotaxane formation. It was theorized that this addition should increase the yield of rotaxane formation while simultaneously decreasing the complexity of the process. However, modified experiments focused on guest molecule formation in water produced much lower product yields than expected. Additional experimentation determined the cause for this drop in yield to be an unexpected reaction between the sodium bisulfite and the unadded bulky end groups of the guest molecule. This sodium bisulfite reaction was irreversible in the presence of aqueous base and thus removed much of the sodium bisulfite and the bulky end molecules from the reaction. Several attempted bypass reactions prove ineffective. Due to the overactivity of sodium bisulfite, future experiments could focus on testing other possible water solubilizing agents such as amino acids in imine formation reactions.



Rotaxane Formation, Thermodynamic Favorability, 5,5-dimethyl-1,3-cyclohexanedione, Sodium Bisulfite, Methyl 4-Formylbenzoate, Supramolecular Chemistry