New N-Amido(Thio)Urea-Based Neutral Anion Receptors

Molecular recognition is one of the subjects receiving continuous interests in supramolecular chemistry. Since anions play a fundamental role in disclosing the essence of biological processes, anion recognition and sensing by synthetic receptors has received increasing recent attention. Especially, the development of neutral receptors based on hydrogen bonding has become a must for receptors of excellent anion-recognition ability. Selectivity and sensitivity are the key parameter in evaluating anion receptors, several strategies have been developed to improve anion-recognition ability of neutral receptors by incorporating more binding sites in a suitable arrangement, increasing the acidity of the hydrogen bonding donors, cooperating with electrostatic interactions, and utilizing allosteric interaction. In this thesis, a series of neutral anion receptors were designed and synthesized, employing the N-amido(thio)urea as an efficient binding site. Interactions of the binding moiety and anions were investigated in order to explore promising new approaches for improving anion-recognition ability of the neutral receptors.The dissertation consists of five chapters summarized as the following.Chapter 1 presents a general introduction to supramolecular chemistry relating to the researches in the development of neutral anion receptors based on hydrogen bond. Emphases were focused on the challenges existing in the design of neutral receptors, and the strategy resolving these problems. The objectives of this dissertation were proposed.Chapter 2 describes the syntheses and characterization of ca. 30 receptors designed in this thesis for anion recognition, including N-aliphaticamido-N'-(substituted)phenyl (thio)urea, poly-(N-amido-N'-phenyl)thiourea, N-(isonicotinamido)-N'-(substitutedphenyl)thioureas, and N-(2-(hydroxyl)benzylimino)-N'-phenylurea. The equipments, materials and methods involved in this dissertation are also described. Chapter 3 reports the anion binding of N-aliphaticamido-N-(substituted)phenyl (thio)urea. The N-amidothiourea binding site was employed on the basis of our previous work that showed a substantially enhanced anion binding affinity compared to the traditional N-phenylthiourea binding site. It was found that when the the acidity of thioureido -NH protons in N-aliphaticamido-N-phenylthioureas was lower than that in N-benzamido-N'-phenylthioureas, yet the anion binding ability was stronger. Protic solvent competition in MeCN by MeOH and ¹H NMR titrations in CD_CN supported the hydrogen bond interaction of the receptor with anion. The substituent of the N '-phenyl ring and of the N-amido group exist different influence on anion biding, the former remarkably influencing anion binding, while the latter affecting more to the absorption spectra of the receptor upon anion binding. Polymerizable N-amidothiourea-based receptors were polymerized and were fixated on the surface of glass. Contact angle measurements were used to understand interactions of anion and poly-N-amidothiourea-based receptors. Two new approaches were attempted to increase selectivity in anion binding, to properly decrease the acidity of thioureido -NH protons in a receptor with suitable structure, and to apply the molecular imprinting technology.Chapter 4 presents the design of N-(isonicotinamido)-N'-(substituted-phenyl) thioureas as simple neutral anion receptors capable of binding anion in aqueous solutions. A pyridine terminal was chosen to improve water solubility of the receptor molecules. These receptors showed substantial anion-binding ability in MeCN solution with binding constants of 10⁷ L mol^-1 order of magnitude. Significantly is that they showed sensitive response to anions such as CH₃CO₂^- in aqueous solutions with binding constants of 10³ L mol^-1 order of magnitude. The hydrogen bonding interaction between the receptor and anion was proved by ¹H NMR titration in CD₃CN, with no deprotonation occurring. The pyridine ring was shown to correspond to a phenyl ring bearing an electron withdrawing para-substituent of Hammett constant 0.75, which implied that the amido -NH is acidic enough to afford the capability of anion binding in aqueous solutions. Although this seems to point to the critical role of the acidity of the amido -NH proton, we showed that it was instead the less polar hydrophobic microenvironment afforded by the approaching of two aromatic rings in these receptors driven by hydrophobic interaction that promoted the anion binding in aqueous solutions. A new approach was provided for designing neutral receptors based on hydrogen bonding for anion binding in aqueous solutions by taking into account the receptor molecular conformation.Chapter 5 reports a homotropic allosteric receptor, N-(2-(hydroxyl)benzylimino)-N'-phenylurea, highly selective and sensitive for F^-. A moderate color change from colorless to yellow and a drastic fluorescence enhancement of c.a. 300 fold were observed when F^- is added to the receptor solution in MeCN, whereas other anion led to no color change and tiny fluorescence enhancement of less than 20 fold. The receptor bears three distinct hydrogen bonding groups, one phenolic -OH and two ureido NHs, which bind stepwise to F^-. Binding of the first F^- had a consequence of that of the subsequent interaction of the second F^-. The first F^- binding to the receptor's phenolic -OH resulted in the deprotonation and a conformation change in the receptor that reinforced its next binding to F^-. Differing from the stepwise binding to F^-, the receptor bound other anions such as CH₃CO₂^- and H₂PO₄^- in a single step via -OH and ureido -NH protons in a 1:1 stoichiometry. Since the acidity of the ureido -NH protons were known lower than that of the thioureido -NH protons, the anion binding ability of urea-based receptor should have been lower than those thiourea-based. The observed opposite thus suggested that it was the stepwise allosteric interactions that afforded both high selectivity and sensitivity for F^-. The study was expected to be of help for the design and development of highly selective and sensitive anion receptors.The main innovations of this dissertation were summarized and the prospection of the future work was discussed at the end.