Design And Synthesis Of In-Tab Complexes As Luminescent Probes For Biological Sensing

4-(Trimethyammonio)benzenethiolate (Tab) is a zwitterionic thiolate that shows affinity for a variety of metal ions to afford a class of novel coordination compounds. In the last few years, a main thrust in our group is to explore the reactivity of such a ligand toward designable molecular assemblies, and the subsequent application of these assemblies as advanced materials, biological model compounds and catalysts. On the other hand, the application of organic small molecules and coordination compounds as biological probes are emerging. These studies have offered both theoretical and realistic basis for the detection of DNA sequences. In view of such trend, we hypothesize that metal-Tab compounds may provide a unique opportunity as DNA sensors ascribed to their structural characteristics including water solubility, stability and tunable molecular skeleton.In this thesis, we report In(III)-based compounds integrating aromaticity and cationic function of-NMe3+ via the facile assembly of TabHPF6 and a planar chelator Phen or Dpphen with the central In3+ ion, and explore their synthetic reactivities. We also examine their biological application as fluorescent probes. These work are briefly summarized as follows:(1) We report coordination compounds [In(Tab)2(Phen)2](PF6)3 (2), [In(Tab)2(Phen)2·In(Tab)4(Phen)](OAc)6 (3) and [In(Tab)4(Phen)](OAc)3 (4), which formed via a counterintuitive solid-state pathway. Within 2-4, the Tab-to-Phen ratios are reversely related to the TabHPF6-to-Phen ratios employed as starting materials. Such a unique reactivity exerts a sharp contrast to the solution state reaction wherein [In(Tab)4](OAc)3 (1) or 4 is formed at low or high material concentration, respectively. Further reaction of a bulkier ancillary ligand Dpphen in the solid state generated [In(Tab)2(Dpphen)2](PF6)3 (5) exclusively. Compounds 1-5 are characterized by single crystal X-ray diffraction, IR spectra, UV-Vis spectra, elemental analyses, 1H NMR and electrospray ionization (ESI) mass spectra.(2) Compounds 2,4 and 5 are designed to interact with two different fluorophore carboxyfluorescein (FAM)-labeled DNAs (probe DNAs, delineated as P-DNAs) through electrostatic,?-stacking and hydrogen-bonding interactions, forming P-DNA@2, P-DNA@4 and P-DNA@5 hybrids, and quench the fluorescence of FAM via a photo-induced electron transfer process. The resulting hybrids thus formed can be examined as sensory platforms for target HIV-1 ds-DNA sequence with detection limits as low as 1.4 nM (2),1.7 nM (4) and 1.2 nM (5), and Sudan Ebolavirus RNA sequence with 1.0 nM (2),0.37 nM (4) and 0.81 nM (5), respectively.(3) Compounds 2,4 and 5 have strong affinity toward both ss-DNA, ds-DNA and G-quadruplex with the binding constants ranging from 106 to 107 M-1 through UV absorption titration and fluorescence titration experiments. Circular dichroism (CD) results indicate that 5 can induce human telomere sequence 22AG and G2T1 to form anti-patallel structures. Besides, they have strong ability in combining G-quadruplex such as 22AG(K+), 22AG(Na+), c-kit2(K+) and G2T1(Na+), and can stabilize their structures by forming complexes.