In Situ Formed Nucleic Acid-mimicking Coordination Polymer And Its Applications As A Biosensing System

Investigations of synthesizing functionalized Metal(Au, Ag, Cu)-SR coordination polymers for biochemical detection is a hotspot because of their special physical and chemical properties which are formed mainly through metal-metal interaction and metal-ligand interaction. Because of the strong electron-releasing property and high polarizability, SH-containing compounds attracted researchers' attention by using various ligands. As reported, metal-SR complexes can be easily synthesized through reducing Au(III) to Au(?) by SH-containing amino acids, organic compounds and small molecular compounds ligands such as cysteine(Cys), Phenylethylthiol(HS-C2H4Ph), and glutathione(GSH). Metal-SR coordination polymers are important in many applications, e.g. used as therapeutic medicine and sensing ensemble. A lot of work have been done by using metal-SR coordination polymers as precursors to synthesize functional metal- nanoclusters. While indeed, only a few strategies used metal-SR coordination polymers for biochemical sensing so far. In this report, we synthesized a special Au(?)-CoA coordination polymer utilizing CoA ligand for the first time by a rapid, simple and green way. The unique structure of Au(?)-CoA coordination polymer combined both the advantages of metal-SR coordination polymers and RNA, and with which we developed a fluorescence turn on strategy for sensitive and facile detection of HAT and citrate synthase activity.1. The reaction starts by mixing CoA with HAu Cl4, and Au(III) is reduced to Au(?) by CoA. Then the thiol moiety of CoA interacts with Au(?) to form thiol-Au(?) bond while aurophilic interaction occurs between the two adjacent Au(?) ions, consequently leading to the formation of Au(?)-CoA coordination polymer with-Au(?)-thiol- repeat units. Unlike the conventional coordination polymers, this CoA-functionalized coordination polymer is a chain with multiple adenine nucleotide residues, which is structurally similar to poly-A RNA, except the Au(?)-thiol linkage of the coordination polymer is used instead of the ribose-phosphate backbone of RNA chain. Some characterization experiments have been done including UV-vis spectroscopy, DLS and XPS experiments to verify the formation of Au(?)-CoA coordination polymer. In addition, PAGE experiments and fluorescent experiments were done after mixing Au(?)-CoA coordination polymers with RNA special dye SGII, the results revealed the RNA-mimicking property of the Au(?)-CoA coordination polymer. The special properties of Au(?)-CoA coordination polymer provided us a fluorescence analysis platform for biochemical detection of CoA.2. A new method by in situ formed nucleic acid-mimicking coordination polymer for label-free fluorescent activity assay of histone acetyltransferases was designed. HAT(p300)-catalyzed substrate acetylation produces CoA together with formation of CoA-Au(?) CPN, resulting in fluorescence signal-on with SGII staining. HAT(p300) can be sensitively detected with a wide linear range from 0.5 to 100 nM and a low detection limit of 0.2 n M. The potency of this assay was further proved by characterizing HATs inhibitors. The proposed assay is simple, single-step, antibody-free, and low-cost, which is promising for HATs-targeted epigenetic research and drug discovery.3. Another fluorescence strategy based on Au(?)-CoA coordination polymer was proposed for label-free detection of citrate synthase. Citrate synthase catalyzes the conversion of Ac-CoA and oxaloacetate into citrate and CoA. CoA interacts with HAu Cl4 to form RNA-mimicking Au(?)-CoA coordination polymers. After being combined with SGII, a fluorescence turn on signal was then detected. The detection linearity of citrate synthase ranges from 0.0033 to 0.264 U with a detection limit of 0.00165 U. Unlike those typical and labeled sensors, our assay is simple, free of antibody and sensitive with low detection limit. The method we used for citrate synthase also can be used for its inhibitor screening.