Novel Fluorescent Cyclodextrin: Design, Synthesis, Fluorescent Properties And Molecular Recognition

Cyclodextrins (CDs) have the ability to accommodate various small organic molecules in aqueous solution by its hydrophobic cavity. This great interest makes CDs, especially modified CDs deeply involved in the area of fluorescent molecular sensing, which plays an important role in biomedical field.Fluorophore can be attached to CDs to form fluorescence sensors. By using fluorescence technology, we can interrogate the properties of the cyclodextrins-guest complex. But the most common mechanism that fluorophore being expelled by guest from CD cavity is not satisfactory in some area. Reported papers generally focus on molecular recognition, but the fluorescence changes caused by the differentiation between self-inclusion structures are often overlooked. So in this thesis we mainly carried out research in this respect. In the past decade the construction of chemical sensors by using cooperative recognition systems, such as CD moiety as building block combining additional recognition sites has attracted much attention. This approach is an efficient way to expand the scope of guest molecules. Based on this point, we have also tried to carry out some research work on it.In this paper, various types of fluorophores and side chains were connected toβ-cyclodextrin. Their conformation, fluorescence, and interaction with guests were investigated by NMR, ICD, UV, fluorescence and other technologies. Some fluorescent CDs with wonderful sensing ability were found. Novel sensing mechanism was obtained by deeper insight into structure-conformation-fluorescence relationship.This thesis is made up by five parts:In chapter one, we give a brief introduction to the basic theory of fluorescence and fluorescent sensing mechanism. The subsequent section is detail introduction of sensing mechanism that will come across in this paper. Then several typical examples of fluorescence change upon complexation between fluorescence CDs and guests are shown within the area of fluorescent CD sensors. At the last of this chapter, the design strategies of this thesis are outlined. In chapter two, three isomeric fluorescentβ-cyclodextrins bearing 2-,3- and 4-(2-aminoethyl)amino-N-butylbenzamide respectively (CD1-CD3) have been synthesized. The conformations of these fluorescent CDs have been investigated by 2D NMR and induced circular dichromism. It is confirmed that the ortho-isomer CD1 takes a butyl-included conformation while the other two isomers CD2 and CD3 display a phenyl-included conformation respectively. The three fluorescent CDs 1-3 exhibited totally different self- and guest-inclusion fluorescence behavior. In the presence of adamantane carboxylate sodium (ADA) or deoxycholate sodium (DCA), the fluorescence intensity of CD1 showed an over one fold enhancement, while CD2 exhibited dramatic fluorescence quenching. Interestingly, the fluorescent responds of CD3 towards two guests respectively were highly distinguishable. The fluorescence intensity of CD3 only showed slight increase upon the addition of ADA, but the addition of DCA led to a large decrease in fluorescence intensity. The investigations have been further carried out by 2D NMR, induced circular dichromism and fluorescence spectroscopy to explore the relationships between the conformations and the fluorescence characteristics of CDs 1-3 in the absence and presence of guest molecules. Based on above investigations, the origins for the different fluorescence behaviors have been proposed.In chapter three, based on the distinguishable fluorescent spectra of ADA and DCA by CD3, a series of adamantine analogues and bile salts were tested as guests by CD3. We developed CD3 as an excellent bile salts sensor. Furthermore, we found that some hydrophilic small carboxylic acids also been recognized by CD3. With the aid of 2D NOESY NMR and induced circular dichromism, we revealed that the carboxylic acid guests could be induced into CD cavity staying together with fluorophore to enhance emission intensity.In chapter four, four fluorescent CDs 4-7 containing polyamine side chains were synthesized. The recognition of metal ions by these CD compounds has been tested, among various transition and alkali earth metal ions, only ferric ion can strongly quench fluorescence. They could act as wonderful colorimetric sensor for [Fe(SCN)6]3-. And by changing solvent and UV spectra, the origin of sensing capability of these CD compounds towards to Fe3+ has been revealed.In chapter five, three similar CD compounds bearing piperazine as main control unit in side chain were synthesized. Comparing with other two compounds, CD9 exhibited different fluorescence behavior relative to solution pH value. The deeper study on the conformation of CD9 in different pH solution has revealed the relationship of structure-conformation-fluorescence of CD9. It was found that the fluorescent intensity of CD9 can vary with the change of its conformation which depends on solution pH value. This conformation-controling pH-sensing mechanism is different from that for general pH sensor.