The Applications Of Biomacromolecule-templated Gold And Silver Nanoclusters In Drug And Biomolecule Analysis

Noble metal nanoclusters (NCs), espacially biomacromolecule-templated gold and silver nanoclusters (AuNCs and AgNCs), are of special interest in various applications including chemistry and biology, due to their excellent photophysical properties and good biocompability. As a new topic of luminescent sensors or probes, they have been widely uesd in the detection of heavy metal ions, anions, biothiols. proteins, nucleic acids and single nucleotide polymorphism. Quantitive determination of drugs and some small molecules, releated to diseases, is difficult by using NCs as probes in the asssys. because they can not directly interact with the NCs and change the fluorescence of the NCs. To solve those problems, we take advantage of oligonucleotide (DNA)-protected AgNCs and bovine serum albumin (BSA)-templated AuNCs as label-free, fluorescent probes. The main work we have done are shown as follows:1. DNA-templated silver nanoclusters as label-free fluorescent probes for detection of bleomycin (BLM). Based on the fact that the metal core of DNA-AgNCs was easily oxidized, resulting in the change of the luminescent properties of AgNCs, we developed a label-free, sensitive method for detection of BLM. The equal-molar-ratio mixture of BLM and Fe-2+. can reduce O2disovling in solution into oxidative active radical, which can cause the oxidation of the metal core of AgNCs, forming a non-fluorescent DNA-AgNCs. There is a good linear relationship between the quenching efficiency and the concentration of BLM over the range of100～400nmol/L. The limit of detection of BLM is54nmol/L. This method can be used to moniter other targets which can change the redox state of the metal core of NCs and help us understand the origin of the luminescence of NCs.2. BSA-templated gold nanoclusters as label-free fluorescent probes for detection of H2O2and uric acid. The thiol groups in BSA molecule not only play an important role in the synthesis and protection of NCs, but also have an influence on the fluorescence of NCs through the Au-S bond. We found H2O2can block the ligand-to-metal charge transfer process by breaking the the Au-S bond and changed the local microenvironment of NCs. We further used this H2O2-sensitive BSA-AuNCs to detect H2O2generated by the uricase-dependened cstalytic oxidation of uric acid (UA), finally indirectly quantify the amount of UA. This strategy can quantatively detect H2O2and UA in the range of10μmol/L～2mmol/L and10μmol/L-800μmol/L, respectively.3. A "turn off-on" fluorescent Cu2+-mediated probe for detection of clioquinol (CQ) based on gold nanoclusters. Besides the protection of the NCs from aggregation and being quenched by the solvent molecules, the BSA molecule also endues NCs with plenty of functional groups to chelate with metal ions. Cu2+can interact with the amines or carboxyls of some amino-acid residues in the surface of BSA-AuNCs and induce the excited state of the AuNCs to non-radiationally lose its energy through intersystem crossing (ISC) process. CQ can block the ISC process and retrieve the fluorescence of the BSA-AuNCs through forming more stable complex with Cu2+. CQ could be determinated in the linear range of1μmol/L to11μmol/L, with the correlation coefficient0.9960and the limit of detection around0.63μmol/L. The developed method can be able to detect CQ in real samples and be used for the detection of other molecules only if they can chelate with Cu2+.In summary, we have successfully developed methods for the deteciton of drugs and some disease-related small molecules, by using biomacromolecule-templeated fluorescent nable metal NCs, although those targets can not directly interact with NCs. We introduce many specific chemical reactions or coordations into the analytical assay using NCs. Upon making use of the dependence of the fluorescence on the properties of the metal core and the ligand shell, some general and universal detection strategies were developed.