Host-guest Supramolecular Interactions Of EPR Probes With Water-soluble Pillar[n]arenes

Objective:Research on host-guest interaction is one of the key scientific topics in supramolecular chemistry.Pillar[n]arenes are a class of shining mycrocyclic hosts which were first synthesized in 2008.They have been widely used in supramolecular chemistry because of their unique rigid pillar architecture,versatile functionality,and interesting host-guest properties.The research on the host-guest interaction of pillar[n]arenes is valuable for further understanding of their self-assembly systems,and also helpful to expand their applications.At present,various methods such as NMR,UV,FL and ITC have been commonly used to study the interaction.Although these methods have been well established,they still have limitations in detection sensitivity and interpretation of molecular dynamics.In recent years,electron paramagnetic resonance(EPR)has been widely used in the field of host-guest interaction to study the structures and dynamics of stable radicals since EPR has the high sensitivity to changes in the surrounding environment of the radicals.In this thesis,we for the first time demonstrate that EPR probes can form the host-guest interaction with pillar[n]arenes.One aim in this thesis is to explore the interaction between water-soluble pillar[6]arene and nitroxide EPR probes,with the purpose of increasing the stability of radicals,revealing the forces between them,and further expanding the biomedical application of paramagnetic probes.The other aim is to optimize the structures of nitrone EPR probes,in order to improve their spin-trapping properties,and then study their potential supramolecular interactions.Methods:(1)EPR was used to study the interaction between 4-amino-2,2,6,6-tetramethylpiperidine-1-oxyl radicals(4-AT)and water-soluble pillar[6]arene(WP6)at room temperature under aerobic,anaerobic conditions,at low temperature,and at different p Hs.The redox properties and stability of 4-AT upon complexation with WP6 were studied by EPR.(2)DETP,GTP,NTMTP,QAHOTP were synthesized to study the substituent effect on the interaction between WP6 and TEMPOs by room-temperature and low-temperature EPR.(3)New BMPO-based spin traps FMPO and HMPO were obtained by introduction of F substituent as H-bond receptor and hydroxyl group as H-bond receptor/donor at 3-position of pyrroline ring respectively.The spin-trapping of superoxide,hydroxyl radical,and carbon-centered radicals by FMPO and HMPO were studied by EPR.Results:(1)Strong host-guest interaction between WP6 and 4-AT exists with the binding constant of 4.1×10³M^-1.The molecular rotation of 4-AT in the complex is3.7-fold faster than that of free 4-AT at low temperature.Moreover,the stability of4-AT towards ascorbic acid was increased in the presence of WP6.(2)The electrostatic interaction and cationic···?effect were clarified as the key forces between NTMTP/QAHOTP and pillararenes.(3)FMPO and HMPO exhibit good spin-trapping properties for different oxygen-centered radicals such as O₂^·-and HO^·,and carbon-centered radicals.Their superoxide spin adducts do not decompose spontaneously to the hydroxyl spin adducts or any paramagnetic byproducts.Superoxide spin adduct of HMPO-A is relatively persistent with half-lifetime of 8.2min,comparable to the value of superoxide spin adduct of EMPO.Conclusion:(1)Host-guest interaction between WP6 and 4-AT improved the redox stability of 4-AT.This work first studied the host-guest interaction between pillar[n]arenes and paramagnetic compounds,and explored their biomedical application.(2)The key force between different TEMPOs with 4-site substituents and WP6 is electrostatic interaction.The steric hindrance also has obvious effect on the interaction.Moreover,there exists cationic···?interaction between the radicals with the quaternary ammonium group and pillar[n]arene,and the length of linker directly influences the complexing site and strength.(3)FMPO and HMPO are easily prepared and exist as solids which are stable in solution.Various spin adducts show unique EPR features,enabling their specific detection.Future research can be directed to design new cyclic nitrones by balancing H-bonding,steric and inductive effects.