UC Riverside

The field of molecular recognition illustrates the ability of synthetic receptors to act as hosts for important target molecules. These hosts are capable of binding guests in a manner akin to larger biological systems. Synthetic receptors are ideal molecules for observing host:guest interactions as they possess tunable structures that can be tailored to the desired target. As the differences in many biological targets are relatively small, the use of an array-based system allows for greater discrimination of these slight variations. This approach uses multiple variably functionalized receptors that act as a “chemical nose” for target molecules in a variety of optical sensing applications. This array-based system enables the receptors to sense a broader range of relevant biomacromolecules. The differential sensing of these small molecules can be measured via fluorescence outputs which are deconvoluted using Principal Component Analysis and other statistical methods. The use of water soluble deep cavitands allows for greater scope and tunability of their recognition abilities compared to other macrocyclic receptors. Much previous work has investigated deep cavitands with a negatively charged upper rim, so new structures that incorporate a positive charge were synthesized as a direct comparison of functionality. The diversification of functional groups at the upper rim broadens the scope of target molecules that the cavitands can sense, while the derivatization of the lower rim allows for increased solubility as well as secondary effects of the binding interactions. Deep cavitand hosts exhibit this selective target recognition by utilizing a self-folding deep pocket that provides a defined cavity for binding. This work has highlighted the importance of the synthetic variation of the receptors for sensing specific targets. The novel cationic cavitands remain neutral at the upper rim and only experience charge interactions at the lower rim of the structure. These positively charged receptors have provided an array-based system that is capable of enantioselective sensing of pheromone guests which have small differences in their structures that the array-based system was still able to discriminate between. Additionally, the discrimination of anions with the cationic cavitands showed a strong preference for iodide, despite large concentrations of competitive ions in solution. This secondary interaction at the lower rim of the cavitand structure causes a conformational change in the binding pocket of the cavitand, which influences the affinity of the bound guest for the cavitand. From the success with negatively charged guests, the sensing of phosphosugars has been investigated, and preliminary results show discrimination of fructose-6-phosphate and glucose-6-phosphate using the cavitand array.