Studies On Design, Synthesis Of Azo, Cholic Acid And Heteroaromatic Molecular Clefts Using Microwave Irradiation And Molecular Recognition

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 new types of chiral and achiral azoamide hosts,bowl-shaped steroid cholic acid methyl esters with one chiral arm under microwave irradiation and heteroaromatic molecular tweezers under microwave irradiation in solid state and their molecular recognition as well as enantioselective recognition. A series of useful and creative results have been obtained.Three new typical molecular clefts containing azo, heteroaromatic and cholest unit have been designed and synthesized. Among them the chiral azoamide hosts were 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, during the preparation of heteroaromatic molecular clefts, we used microwave irradiation in solid state so that steps were shortened and yields were enhanced, and a new ecofrindly synthesis method was realized. 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, 'HNMR, MS and element analyses.Molecular recognition properties of the molecular clefts synthesized for 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 clefts with guests examined. The chiral molecular tweezers containing azo unit show excellent selective recognition ability forp-nitroaniline, and the association constants can attend to 5000 M-1. The steroid cholic acid methyl ester molecular clefts with one chiral arm are favorable for complexation with D-amino acid methyl esters. The enantioselectivities KD/KL of some hosts are more than 89. The drive forces of molecular recognition mainly come from non-covalent forces between host and guest , such as hydrogen bond , 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 cleft.