Recognition Of Bioactive Choline Derivatives With Oligourea-based Receptors

Bioactive choline derivatives are important biomolecules with trimethylammonium group and play a crucial role in biological organism.This dissertation details monomolecular polyurea receptors and the molecule cage based on anion coordination self-assembly for the selective recognition and sensing of this kind of biomolecules.This may be of great significance in understanding of the effect mechanism of protein and medicine design with modulating corresponding biological function.There are totally four parts.The first chapter summarizes all kinds of artificial molecular receptors including monomolecular polyurea receptors and the molecule cage based on metal coordination and anion coordination self-assembly,at the same time,the purpose and topic significance of this article were introduced in this chaper.Chapter 2-4 present details of this study with the main results as the following:1.Chirality sensing of choline derivatives by a triple anion helicate cageChirality sensing of choline derivatives was achieved by a self-assembled,racemic triple anion helicate cage which exhibits induced circular dichroism(ICD)upon encapsulation of a chiral guest.~1H NMR spectra revealed the trimethylammonium head of the choline derivatives can be encapsulated in the aromatic box of triple anion helicate cage.The crystal structure show?G1 was included in the aromatic box of triple anion helicate cage through electrostatic and cation????interactions which could be further confirmed by the 2DNMR spectra and ESI-MS.The CD spectra demonstrated each pair of enantiomers induced perfect mirror imaged spectra.The DFT and crystal experiments reaveled the helicities induced by the R,S enantiomers of G1-G3 are assigned as M and P respectively,however,that induced by G4-G7 are in the contrary.The ICD allowed determination of absolute configurations,ee values and association constants of chiral choline analogues.Moreover,the dynamic assembly/disassembly property of the host molecule enabled readily switching the ICD signals OFF/ON by alternatively adding acid/base.2.Chirality recognition of choline derivatives by a homochiral triple anion helicate cageBy introducing chiral auxiliaries into the urea ligand to synthesis ligand R-L~2 and S-L~2,the chiral ligand R-L~2 and S-L~2 can form homochiral triple helicate cage R-Cage and S-Cage,when coordinated with phosphate ions.The homochiral triple helicate cage can detect chiral choline derivatives by ~1H NMR and CD spectra.The formation of the homochiral triple helicate cage was supported by the CD spectra and ESI-MS.~1H NMR spectra revealed the homochiral triple helicate cage can encapsulate the trimethylammonium head of the guest.The appearance of disparate peak patterns of trimethylammonium group in R-G and S-G can provide quick method to determine the absolute configurations and ee value of guest.The CD spectra demonstrated R-G and S-G can enlarge the intense CD signal of homochiral triple helicate cage,but the direction was in the contrary,which could be used to detect the absolute configurations of guest.3.Selective recognition of choline phosphate with tripodal hexaurea receptorsTwo tripodal hexa-urea receptors have been developed by the terminal aromatic groups functionalized(nitrophenyl and naphthyl;L~3 and L~4).As revealed by the crystal structures,the guest is efficiently encapsulated within the cavity of the tripodal hosts.This binding is favored by a“dual-site”mode,i.e.the phosphate tail of choline phosphate is coordinated by the urea groups and the trimethylammonium head is bound by a“composite aromatic box”through cation????interactions and hydrogen bonding.Moreover,NMR spectroscopy,ESI-MS spectrometry and fluorescence studies(for L~4)demonstrate the selective binding and sensing of choline phosphate over other competing species such as ADP,ATP and choline.