Rational Design, Preparation And Investigations On Pyridine Contained Tetraazamacrocyclic Fluorescent Sensors

As one essential part of supramolecular chemistry, molecular recognition can be utilized to sense ions or neutral molecules. Sensors are able to transform the information of the targets (e.g. acid, concentration, viscosity, chemical or biological types) into physical signals that can be measured by analytical instruments. Small-molecule fluorescent probes emit in the region of UV-visible-near IR, and they respond to various concentrations of the targets sensitively. Fluorescent sensors outweigh traditional techniques in high selectivity, ON-OFF controllability, naked-eye visibility and biological compatibility. Besides, fluorescent measurements are non-invasive and able to detect the targets in situ, and therefore now develop prosperously.As common receptors, polyamine compounds have attracted worldwide attention due to the characteristics in both coordination and biological chemistry. Besides, when fluorophores are appended to this type of compounds, the products thus formed are able to meet the requirements of fluorescent sensors. Thus far, the most accessed polyamines are compounds based on tetraazamacrocycles. However, the dynamic process of forming metal complexes is relatively slow, which promote us to seek more suitable receptors. The introduction of a pyridine ring in the macrocycle lacking of conjugate system is expected to increase the stereochemical rigidity of its metal complexes, which is often associated with the increase of their thermodynamic stability. Moreover, the pyridine may also assist to functionalize the original macrocycle by means of providing a suitable coordinating site and thus facilitates the molecular recognition process toward specific targets.The dissertation describes the design, synthesis of fluorescent sensors for various ions and molecules based on pyridine contained tetraazamacrocycle L1. The performance of the sensors has been improved by modifying different fluophores to the mother ring, and the sensing mechanisms have also been thoroughly investigated and discussed. The details of the dissertation consist of the following content:(1) A fluorescent sensor composed of a naphthalene functionalized tetraazamacrocycle ligand (A) and Zn2+has been designed and prepared, which can be utilized for selective and ratiometric sensing of pyrophosphate (PPi) over other phosphate-containing anions in aqueous solution at physiological pH. Notably, the water soluble A itself also exhibits selective enhanced fluorescent response to Zn2+and this process eventually fulfils the synergic Zn2+c oordination-altered strategy. Above0.2μM PPi can be discerned using A-Zn2+(indicated by fluorescence speatra). Furthermore, the ratiometric sensing of A-Zn2+towards PPi performed well even in blood serum milieu. Finally, the sensor A-Zn2+was successfully employed to monitor a real-time assay of inorganic pyrophosphatase (PPase) by means of ratiometric fluorescent measurements for the first time.(2) A Zn2+tetraazamacrocycle complex (E) bearing three naphthalene moieties has been prepared. Complex E recognizes, binds and causes hydrolytic damage to DNA, and shows considerable cytotoxicity against human cervical (HeLa), breast (MCF-7) and lung (NCI-H157) cancer cell lines. Although ruthenium and osmium complexes have been thoroughly studied in the anticancer drug design, zinc complexes that function have seldom been referred. The lack of caspase-3activation after treatment with E in cancer cells combined with intricate DNA binding mode indicate that the mechanism of apoptotic induction may differ from that of cisplatin, which deserves further scrutiny and may provide grounds for establishing new structure-pharmacological activity relationships for the type of DNA-targeting complexes as novel antitumor drugs.(3) A tetraazamacrocycle fluorescent sensor (G) with a dansyl pendant arm has been designed and prepared, which can be utilized for selective and ratiometric sensing of Hg2+and bovine serum albumin (BSA) with two different responding modes in aqueous solution at physiological pH (50mM Tris-HCl, pH7.6). Above0.5ppb Hg2+can be discerned by coordinating with G (indicated by fluorescence speatra) and the emission color changes enable G to be applied to a fast Hg2+test paper assay. Sensor G has also been demonstrated to be easily cell-penetrable and applicable for Hg2+imaging in living cells. Imaging of BSA in the gel using SDS-PAGE (sodium dodecyl sulfate polyacrylamide gel electrophoresis) stained in the medium containing G verified that the binding of G and BSA was successful in the presence of nonprotein substances. The linear range of G towards BSA utilizing ratiometric fluorescent calibration via noncovalent interaction in solution is0-100μg mL-1with the detecting limit of1μg mL-1(indicated by fluorescence speatra), which has been successfully employed to determine the albumin concentration in blood serum by means of ratiometric fluorescent measurements for the first time. Finally, sensor G behaves as a fluorescent molecular switch composed of triple logic gates upon chemical inputs of Hg2+and BSA, which potentially provides intelligent diagnostics for Hg2+contaminated serum on the nanoscale.