Studies On Design, Synthesis And Molecular Recognition Of Chiral Unsymmetrical Urea, Cholic Acid And Heteroaromatic Molecular Tweezers

The study on molecular recognition of artificial receptors is one of the frontiers in bioorganic chemistry. In this dissertation, the efforts were focused on design and synthesis of chiral tmsymmetrical urea, cholic acid and heteroaromatic molecular tweezers and their molecular recognition as well as enantioselective recognition. A series of useful and creative results have been obtained.Three new types of chiral molecular tweezers containing unsymmetrically disubstituted urea unit, four new types of chiral molecular tweezers based on steroid cholic acid and one type of heteroaromatic molecular tweezers involving multiple hydrogen-bonding site have been designed and synthesized. Among them the chiral unsymmetrical urea, cholic acid molecular tweezers have been designed and synthesized for the first time. The synthetic methods of the target compounds have been systematically investigated. A series of convenient and efficient reactions have been developed. Especially, instead of using toxic phosgene, the triphosgene was employed in the synthetic process of some receptors, which provides a convenient. safe and efficient method for the preparation of chiral unsymmetrical urea. All these cleft-type receptors possess different size of clefts, different recognition sites, different rigidity and flexibility and different chiral centers. Their structures were confirmed by IR, 1HNMR, MS and element analyses.Molecular recognition properties of the molecular tweezers synthesized for anion, neutral molecules and chiral molecules were examined by UV-visible spectra titration. The association constants (IgKa) and Gibbs free energy changes (- A Go)were determined. The 1HNMR spectra and computer-aided molecular modeling were used to elucidate further the recognition abilities. The results show that 1 : 1 inclusion complexes are formed for the most of molecular tweezers with guests examined. The chiral molecular tweezers containing unsymmetrical urea unit show good selective recognition for Cl-, Br-, I- and the association constants can reach to 104 M-1. The chiral tweezers derived from steroid cholic acid are favorable for complexation with D-amino acid methyl esters. The enantioselectivities KD/KL of some receptors are more than 9. The drive forces of molecular recognition mainly come from non-covalent forces between host and guest, such as hydrogen bond, π -π stacking, van der Waals interaction etc. At the same time, the rigidity and flexibility of receptors, micro-environmental effects of different cleft structures, the size/shape-matching relationship between host and guest also play crucial roles in the selective molecular binding process of molecular tweezers.