Design And Synthesis Of Thiourea-Based Receptors For Anion Sensing

It is known that anions are of significant importance in chemical,biological, environmental and pharmacological science.With the inherent difficulties of addressing anions characterized by larger sizes(larger than cations in general),a greater varied shapes and pH dependence,design of anion receptors remains a challenging subject.Inspired by the anion hosts in biological systems which selectively recognize their guests through cooperation of multiple hydrogen binding,chemists have been extensively using hydrogen-binding groups as binding sites in artificial anion receptors,of which thiourea capable of forming double hydrogen bonds with anions received special attention.In this dissertation,we employ thiourea as a binding site and charge transfer(CT) chromophores or excited-state intramolecular proton transfer(ESIPT) fluorephores as signaling subunit to construct a series of anion receptors.Sensing mechanisms of these receptors were investigated by UV-Vis absorption spectroscopy,fluorescence spectroscopy,IR,MS,NMR,and X-ray diffraction.The dissertation consists of five chapters.In chapter 1,research progress of synthetic chromogenic and fluorogenic anion receptors were briefly reviewed,based on the main design principles for anion sensing.Chapter 2 describes synthetic details and characterizations of ca.30 compounds. These compounds are N-substitutedanilino(thio)ureas,N-benzylthioureas, diphenylthioureas,N,N'-bis(benzamido) thioureas,naphthamidothioureas, o-hydroxynaphthamidothioureas,and o-methoxynaphthamidothioureas.Equipments, materials,and methods involved in this dissertation are reported.Chapter 3 reports N-anilino-N'-phenythioureas as a new family of thiourea-based efficient anion receptors superior to classical N-alkyl(aryl)thioureas.It is shown that the N-anilino -NH proton is required to be acidic enough,i.e.the N-phenyl substituent is not less electron-withdrawing than m-Cl.Changes due to anion binding in the absorption spectra of these N-anilinothioureas are much more substantial than those of N-alkyl(aryl)thioureas and anion binding constants in acetonitrile,at 10⁶-10⁷ mol^-1 L order of magnitude for AcO^- for example,are much higher despite a similar acidity of the thioureido -NH protons.Crystal structure and IH NMR data show that the N-aniline chromophore is electronically decoupled from the thiourea anion binding site by the N-N bond and an intramolecular hydrogen bond exists in acetonitrile between the N-anilino -NH nitrogen atom and the other thioureido -NH proton. Conformation changes in the N-anilinothioureas upon anion binding was assumed to occur that leads to a much higher increment in the electron donating ability in the N-aniline chromophore that the CT is enhanced or switched on,compared to not switching on of a CT in the case of N-phenylthioureas.The anion binding constant shows a stronger dependence on the N-phenyl than N'-phenyl substituent,opposite to that observed with N-benzamidothioureas,and the CT band position of the anion binding complex depends much more on the N-phenyl substituent than that of the anion binding complexes of N-benzamidothioureas.The study opens a new way of extending structural diversity of the thiourea-based anion receptors and organocatalysts.Chapter 4 reports a series of N,N'-bis(substituted-benzamido)thioureas(BiTUs) which were designed as anion receptors based on their double hydrogen bonding interaction with anions.NMR and X-ray crystal structural analyses revealed that in these receptor molecules the benzamido moiety serving as a spectral signal reporter and the thiourea moiety anion binding site were decoupled by the twisted N-N single bond and the two thioureido and amido NH protons experienced differed electronic environment.Yet the absorption spectra of BiTUs in acetonitrile in the presence of anions such as AcO^-,F^-,and H₂PO₄^- underwent substantial changes by the appearance of a new band at ca.325nm which is red-shifted by ca.60nm and of a clear isosbestic point at 270nm.This suggests that anion binding leads to the communication between thiourea binding site and benzamido signal reporter via probably a conformational change around the N-N bond.The new band energies were found correlating linearly with the Hammer constant of the substituent with a slope of-0.361eV,indicative of the charge transfer character of the absorption band. The binding constants for AcO- and F- of BiTUs were obtained at not less than 107 M^-1 orders of magnitude that are much higher than those of the corresponding N, N'-bisarylthioureas.It is suggested that anion binding to the thiourea moiety in BiTUs switches on charge transfer in the anion-receptor binding complex which reinforces anion binding and therefore results in a dramatically enhanced binding affinity of the receptors.The symmetric N,N'-bis(benzamido)thioureas are therefore defined as allosteric receptors with higher anion binding constants.Chapter 5 describes a neutral N-amidothiourea based ESIPT anion receptor bearing an o-hydroxynaphthamide fluorephore and a thiourea binding site, 32-NSATU,and its fluorescent response toward anions.IR and NMR experiments showed that,compared with 12-NSATU beating o-hydroxyl substituent at a-position rather thanβ-position in 32-NSATU,the intramolecular hydrogen bond(IHB) OH…O=C in 32-NSATU was weaker than that in 12-NSATU.It was found that 32-NSATU only exhibited normal emission in aprotic solvents because of its poor IHB,whereas 12-NSATU emits ESIPT fluorescence at 441nm.Upon addition of anions such as F^-,AcO^- and H₂PO₄^-,a new emission band at 535nm of ESIPT was observed with 32-NSATU in acetonitrile increased intensely at the expense of the normal emission at 400nm.NMR titrations by anions showed that 32-NSATU bound anions through double hydrogen bonds with thioureido NHs.Because of high anion binding affinity and the formation of hydrogen binding network in the receptor-anion complex,32-NSATU rearranged its structure that the IHB of OH…O=C is strengthened after anion binding,leading to ESIPT and its fluorescence.This rational was supported by the inhibition of ESIPT when F^- or AcO^- concentration was more than 2 equivalence of 32-NSATU.The mechanism of anion induced excited-state intramolecular proton transfer is thus proposed,that shows a promising potential for constructing ratiometric fluorescent anion receptors.