| BackgroundOrganic fluorophores have attracted great interest from both academia and industry due to their potential applications in many fields, such as chemistry, materials science, biology, and medicine.Most of organic dyes have good luminescent properties in dilute solution, but in aggregate state, especially when in crystalline state, the fluorescence becomes weakened or quenched. This phenomenon is called "aggregation induced quenching"(ACQ). The ACQ effect have greatly limited their scope of practical applications, such as organic light-emitting diodes, chemosensors/biosensors etc. the ACQ effect has been a thorny obstruct that must be overcome.The development of efficient luminescent materials is a topic of great current interest. In2001, Tang discovered such a system, in which luminogen aggregation played a constructive, instead of a destructive, role in the light-emitting process:a series of silole molecules were found to be non-luminescent in the solution state but emissive in the aggregated state (as nanoparticle suspensions in poor solvents or as thin films in the solid state). They coined the term "aggregation-induced emission"(AIE) for this novel phenomenon, because the non-luminescent silole molecules were induced to emit by aggregate formation. The novel AIE effect is exactly opposite to the notorious ACQ effect discussed above. The phenomenon is of academic value. In last decade, The AIE luminogens have already shown practical applications in OLEDs, chem-sensors, and bio-probes, due to their efficient preparation and unique properties. However, until now, the studies of utilizing AIE dyes as FL sensors mainly concentrate on TPE derivatives and silole derivatives, so that developing new AIE-active sensory materials would be very rewarding work. Multi-component reaction (MCRs) is an ideal reaction mode which is consistent with the concept of green chemistry, It has attracted in-creased attention in synthetic chemistry for their distinct advantages such as such as atom economy, simplified workup procedures, great efficiency, high overall yields, and structure diversity and complexity of products. We have recently reported an efficient new five-component reaction (5CR) with raw material acquire, simple operation, moderate reaction characteristics Therefore, our group utilizes Multicomponent reactions (MCRs) to synthesis of the nitrogen heterocycles compound, Importantly, the5CR products pentasubstituted tetrahydropyrimidines show unusual characteristics of aggregation-induced emission enhancement (AIEE) and high fluorescence quantum yield. On one hand, In this thesis a new series of structure diversity, AIE-active pentasubstituted tetrahydropyrimidines derivatives have been directly synthesized via five-component reaction (5CR) under mild conditions, and study their optical properties, On the other hand we find that the AIE-active pentasubstituted tetrahydropyrimidines derivatives can apply as pH sensor and metal ion probes. This thesis is divided into five chapters (literature review, Convenient synthesis of C-6unsubstituted tetrahydropyrimidine-4,5-dicarboxylates via five-component Reactions, the optical properties of C-6unsubstituted tetrahydropyrimidine-4,5-dicarboxylates, detection copper ion and pH detection. The content of this thesis is divided into three parts (synthesis of pentasubstituted tetrahydropyrimidines derivatives via MCRs, optical properties and their applications).Part1Convenient Synthesis of C-6UnsubstitutedTetrahydropyrimidine-4,5-dicarboxylates via Five-component Reactions and Its Optical PropertiesObjection:We synthetize structure diversity pentasubstituted tetrahydropyrimidines derivatives via five-component reaction, and study their optical properties and explore their applications.Methods(1) Our group utilize Multicomponent reactions (MCRs) with atom economy, high efficiency, structural diversity and complexity of compounds to synthesis of pentasubstituted tetrahydropyrimidines derivatives.Results:(1) We have synthetized22compounds(2) Structural characterization by ESI-MS、1H and13C NMR(3) Assay the absorption spectra of the compound in solution and suspension by UV-visible spectrophotometry(4) Measure the excitation and emission spectra of the compound in solution, and suspension by steady-state fluorescenceConclusion(1) We have developed efficient and simple five component reactions (5CRs) of but-2-ynedioates, primary amines, primary amines, formaldehyde and aromatic aldehydes using urea as a catalyst, AcOH as an additive and methanol as solvent for the synthesis of C-2substituted tetrahydropyrimidine-4,5-dicarboxylates. The5CRs proceeded smoothly at room temperature to afford target products in40%-60%yields.(2) we found that6exhibit important AIEE properties because they show practically no emission in solution (ΦF,'0) but strong emission in aggregates withΦF,a up to93%(6bb)。 a library of6with high fluorescence efficiency could be built fast and efficiently by taking the5CR advantages of mild reaction conditions, readily available reactants, operational simplicity and potential ability in building structure diversity products.Part2The Optical Properties of C-6Unsubstituted Tetrahydropyrimidine-4,5-dicarboxylates6aaObjection:Pentasubstituted tetrahydropyrimidines not only exhibit important AIEE properties but also unusual size-independent emission (SIE) characteristics, as well as two kinds of fluorescent aggregates, bf-and gf-aggregates in different conditions. Therefore, In this part of the experiment, we will measure the optical properties of pentasubstituted tetrahydropyrimidines derivatives under different solvents, temperature, concentration, culture fluorescence isomer crystal and parse the crystal structure to understand molecules stacking mode, and explore the luminescence mechanism of the compound.Methods(1) Assay the absorption spectra of the compound in solution and suspension by UV-visible spectrophotometry(2) Measure the excitation and emission spectra of the compound in solution, and suspension, as well as different forms (powder, thin film, crystal) by steady-state fluorescence(3) The single crystal structure of the compound was determined by X-ray diffraction method(4) Diamond software parsing the molecular stacking mode and intermolecular forces in the single crystal structureResults:(1) The solvent, temperature, and concentration have a significant effect on the formation of the blue-green crystals。 We found that a slower crystallization rate (at higher temperatures or lower concentrations) favored the formation of bf-crystals. In contrast contrast, a faster rate (at lower temperatures or higher concentrations) favored the formation of gf-crystals. At the same time, We found that the particles that formed first under the studied conditions were the gf-forms. However, they could transform to the bf-forms by increasing ultrasonic time at higher temperatures. This means that the gf-particles are the kinetically favored form and the bf-particles are the thermodynamically favored form.(2) When the volume fraction of water (fw) in ethanol increased to80%, at the same time, the emission intensity was enhanced dramatically. This indicates the formation of J-aggregate. Compound6aa in ethanol is practically no emissive because the50-fold enlarged emission spectrum of6aa in ethanol is a noisy signal line.However, the ΦF value of6aa increases to0.52, as the fw, value is up to95%. The emission spectra of6aa in crystals and in powder (gently ground crystals) possess the same λem.max value as that in suspensions, which indicates that6aa in bf-aggregates shows SIE characteristics.(3) the processes of preparing the pure bf-aggregates, pure gf-aggregates as well as bf-and gf-aggregate mixtures of6aa under different aggregation conditions are practically the processes that alter the ratio of R/S-S/R and R/R-S/S stacking modes. In other words, the MSMs of6aa in crystals and suspensions could be tuned by changing the aggregation conditions.(4) According to the experimental results mentioned above, the AIEE property of6may result from their special structure and/-aggregation. Since the three phenyls of6are not conjugated with each other and connected to a non-aromatic central ring via C-C or C-N single bonds, they could rotate freely in monomer (in solution), which deactivates the corresponding excited states. This makes6non-emissive in solution. The strong fluorescence emission of6in aggregates should be attributed to its asymmetric stereo molecule structure efficiently preventing π-π stacking as well as J-aggregation restricting intramolecular rotation and forming intermolecular charge transfer states.(5) The non-emission of the surface molecules in the bf-and gf-crystalline aggregates may result from the high flexible and asymmetric stereo structure of6aa.ConclusionThe AIEE of6and the SIE characteristics of6aa may be attributed to i) the high flexible structures (the three phenyls of6are not conjugated with each other and connected to the non-aromatic tetrahydropyrimidine ring via single bonds); ii) the asymmetric stereostructure (the three phenyls adjacently are connected to the chiral tetrahydropyrimidine ring and are perpendicular from each other); and iii) J-aggregation. Part3Applications of C-6Unsubstituted Tetrahydropyrimidine-4,5-dicarboxylatesObjection:(1) Copper ion (Cu2+) is an essential trace element for many biological processes and systems, the detection of copper ion concentration has important clinical significance. Therefore, it is of great significance to develop high selective fluorescent enhancement chemosensors for Cu2+. We measured the fluorescence intensity of the5CR product with response to the concentration of copper ions, we found that6bh, one of these racemates, dimethyl2-(4-hydroxy-3-methoxyphenyl)-1,3-diphenyl-1,2,3,6-tetrahydropyrimidine-4,5-dicarboxylate(6bh, TPD-OH), can be a sensitive and selective fluorescent probe for Cu2+.(2) many important physiological processes of cell and organelle are closely related with pH value. in normal physiological conditions The concentration of H+is40nmol/L in the extracellular fluid and the rate of change is0.1-0.2pH unit in general, Strong alkaline and acid leads to heart, lung disease or neurological diseases, seriously it even has life-threatening, so we can use a variety of fluorescence parameters (such as fluorescence intensity, fluorescence lifetime) changes to measure the pH value, it can not only be used for fluorescence microscopy study,but also can detect the changes of intracellular pH in real-time it has attracted widespread attention. we found that one of these racemates, Dimethyl1,2,3,6-tetrahydro-2-(4-hydroxy)-1,3-diphenylpyrimidine-4,5-dicarboxylate,6bj, can be a sensitive and selective fluorescent probe for pH.Methods(1) Determination the changes of the absorption spectra, excitation spectra and emission spectra of6bh in the presence of other metal ions and in the different concentration of Cu2+by UV-visible spectrophotometry and steady-state fluorescence, study the sensitivity and selectivity of6bh for Cu2+, and explore the possible mechanism.(2) Determination the changes of the excitation spectra and emission spectra of6bj in different pH value, study the fluorescence intensity via the pH value and developt a new kind of pH fluorescence probe.Results:(1) The emission spectra of6bh (30μM) in the absence or in the presence of other metal ions (300μM)(Ag+, Ca2+, Co2+, Cu2+, Mn2+, Ni2+, Zn2+, Eu3+, Gd3+, Pr3+, Mg2+, Ce3+and Fe3+) indicate that only Cu2+caused a significant fluorescence enhancement and others showed no influence (Ag+and Ca2+) or a fluorescence quenching (all determined metals except Cu+, Ag+and Ca2+) on the emission spectra of6bh. Fe3+almost turned off the fluorescence of6bh in aggregates. When the concentration of Cu2+was decreased to30μM, the fluorescence intensity of6bh in aggregate also increased significantly(2) The fluorescence intensity at maximum emission wavelength (471nm) of6bh(30μM) in ethanol-water mixture (fw,=99%) in the absence of metal ion and in the presence of Cu2+, other transition metal ions or Cu2+with another transition metal ion are shown in Figure3b. It can be seen:(i) the influences of other metal ions at100μM of concentration on the fluorescence intensity of6bh were almost the same as that at300μM;(ii) the sensitivity of6bh to Cu2+is not influenced significantly by these commonly coexistent ions, which shows the interaction of Cu2+with6bh is competitive in the presence of other transition metal ions with high concentration. These proved that6bh is a high sensitive and selective probe for Cu2+.(3) The phenolic hydroxyl of6bj and6bh exists an acidic dissociation equilibrium in aqueous solutions. The phenolic hydroxyl of6bj and6bh exists a acidic dissociation equilibrium in aqueous solutions. When the pH increased higher than12, it almost no fluorescence, the amount of the neutral form in the equilibrium will increase but that of the anion form will decrease with the decrease of pH Since neutral form is not soluble but anion form is well soluble in aqueous solution, when the pH is4or5, the fluorescence intensity remained unchanged, the fluorescence intensity is20times than pH at11, under the irradiation of ultraviolet light we can easily discriminate the two forms. When the pH value is4, the fluorescence intensity reaches the maximum, the compound6bh formed large aggregates. It shows that compound6bj has sensitive to pHConclusion(1) A novel fluorescence enhancement probe for Cu2+,6bh, has been developed. The probe possesses high sensitivity and selectivity for Cu2+. Moreover, a good linear relationship between the fluorescence intensity of6bb. and the concentration of Cu2+ranges from0-60μM. Therefore,6bh can be used for the quantitative analysis of Cu2+in environmental water samples. An interesting phenomenon is that in addition to the fluorescence enhancement, the particle sizes of6bh become smaller upon increasing the concentrations of Cu2+, which is expected to result from the coordination-induced intermolecular hydrogen-bond dissociation. Considering the high selectivity and sensitivity to Cu2+, the interesting phenomenon of Cu2+-induced fluorescence enhancement with size-decrease, the special molecular stacking mode and no cytotoxicity,6bh is expected to be useful for practical applications, new probe design and theoretical research.(2)6bj is a phenol-moiety-containing compound that shows aggregation at pH values smaller than12to result in a high FL intensity with a pKa of10.5. Its cell cytotoxicity is smaller higher than6bh, so we can modify the structure of6bj and developt it as the pH probe with low cytotoxicity. |
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