Synthesis and Study of a Water-soluble Macrocycle

Rotaxanes are a class of mechanically interlocked molecules with various potential applications, such as stimuli-responsive molecular switches, drug delivery systems, and artificial muscles. In spite of their potential biological applications, this type of mechanically interlocked system is currently available almost exclusively in organic solvent systems; it is not yet available in aqueous solution. Being able to dissolve it in water would allow for the greater possibility of integrating biological molecules into the rotaxane architecture without losing their native biological structure and function. Therefore, the motivation of this project is to synthesize a [2]rotaxane by assembling them completely in water. This requires both the guest and the macrocycle to be individually soluble in water. The specific focus of this project is to develop a water-soluble macrocycle by functionalizing a diallyl derivative of 1,5-dihydroxynaphthalene[38]crown-10 (DNP38C10) to obtain the ammonium salt of the macrocyclic host. Then, the water-soluble host was self-assembled with a water-soluble guest, obtaining the desired [2]pseudorotaxane ([2]rotaxane without sterically-bulky stoppers). By studying the [2]pseudorotaxane using UV-visible spectroscopy, NMR, and ITC, there is evidence that the water-soluble host and the water-soluble guest bind and form the [2]pseudorotaxane, mainly due to - interactions and hydrophobic interactions. In the future, a water-soluble [2]rotaxane can be obtained upon addition of a water-soluble stopper to the [2]pseudorotaxane, which can lead to further studies of its properties and applications. When successfully functionalized with biological molecules, water-soluble [2]rotaxanes are expected to have promising biocompatibility and wide-ranging applications as mechanically interlocked molecules.