Proline-Based Receptors For Chiral Recognition And Self-Assemble Of Hemicyanine Dye Recognition

Chiral recognition of important biological molecules such as sugar and amino acids and drugs e.g.Dopa is of great significance.Although many advances have been made,designing of highly effictive chiral recognition receptors remains a challenge.Proline,a natural amino acid,has a folded rigid structure formed by pyrrole ring,representing a potential chiral skeleton.It can be derived by at least two different groups respectively at its N-and C-termini.We proposed use proline residue as a structural framework to construct receptors by introducting the binding groups at the N-and Ctermini for chiral recognition of important biomolecules.In this dissertation,a series of chiral recognition receptors were designed and synthesized,by introducing phenylboronic acid and phenyl aldehyde groups at the Nand C-termini of proline residue.They are successfully implementation of chiral recognition of L-/D-dopa.In addition,boronic acid modified hemicyanine dye as a selective probe for NADH and NAD+were developed for use in solutions and in cells.The thesis consists of four chapters.In charpter 1,some of the biological important small molecules were briefly introduced at first.This was followed by the basic knowledge and mechanism of boronic acid to bind diol was summarized,together with the research based on boronic acid receptors applied for sensing of biological molecules and molecular recognition.Later,properties and applications of proline and cyanine dyes were described briefly,The objectives of this thesis were given.In chapter 2,choosing L-/D-Dopa as model chiral species,proline based chiral receptors L-/D-1,L-/D-2,L-3 and L-4 were designed and synthesized for chiral recognition of L-/D-Dopa via dynamic covalent bonds.1-4 differ in the positions of the boronic acid and aldehyde groups on the phenyl rings at the N-and C-termini of the proline residue.Only stereo structure matching of L-/D-Dopa could produce the recognition with absorption and CD spectra responses as a result of the formation of borate and imine.It was found that receptor L-1 exhibited chiral recognition of D-Dopa,which receptor L-2 preferred to L-Dopa.This supported the feasibility of using proline folded skeleton for designing of chiral recognition receptors.Chapter 3 presents a new strategy to balance the weak covalent interactions of the two binding groups introducted in the proline framework by introducing F atoms into the phenylrings leading to optional chiral recognition of L-/D-Dopa.The derivatives of L-1,F-labled chiral receptors F-L-1,F-L-2 and FF-L-3 were synthesized,in attempt to employ the strong electron-withdrawing F atoms to turn the binding with dopamine and to use the simpler 19F NMR to evaluate the chiral recognition.The unbalanced interactions of receptor L-1 with D-Dopa in terms of the phenylboronic acid/cis-diol and phenylaldehyde/anime could be improved by introducing a fluorine atom into the phenylaldehyde moiety.F-L-1 therefor exhibits the best chiral recognition,whereas larger differences of the interactions of the two binding groups in L-1 and F-L-2 with DDopa lead to poor chiral recognition,neither in receptor FF-L-3 that exhibit to strong interactions of the two binding groups.It appear that balanced moderate interactions of the two binding groups afforded for dopamine result in optional chiral recognition.Chapter 4 developes a sensing strategy to develop probe for selective recognition of NAD+and NADH.Hemicyanine dye Hcy-BA formed aggregates of size ca.100 nm,resulting for ?-? stacking and hydrophobic interactions in 0.05 M PBS buffer of pH 7.4.Owing to the difference in the charges of NAD+and NADH and their boronates of HcyBA,thereby the boronate complexes of Hcy-BA/NAD+and Hcy-BA/NADH exhibit different absorption and fluorescence response.Upon binding NADH,the aggregates are enlarged leading to dramatical colour change visible to the naked eyes.However,in the presence of NAD+,the Hcy-BA aggregates disassembled due to the electrostatic repulsion and the fluorescence intensity increases.This result in good selectivity for NAD+and NADH.