Intrinsic Interactions Between Noble Metal Nanoparticles and Biomolecules: Fundamental Study and Analytical Applications

The focus of this dissertation is to explore the intrinsic interactions between noble metal nanoparticles (NMNPs) and biomolecules for various analytical applications. Biomolecules with amine groups and nitrogen atoms on cyclic rings could have strong noncovalent interactions with NMNPs. By displacing the charged capping agents on NMNPs, surface adsorption of biomolecules could significantly affect the stability of NMNPs. By utilizing the change of stability of NMNPs upon adsorption of biomolecules, four analytical applications have been developed in this dissertation. Firstly, a critical coagulation concentration (CCC)-based salt titration was developed to enable visual quantification in NMNP-based colorimetric detection (Chapter 2 and 3). Visual quantification using this CCC-based salt titration has been demonstrated in melamine and DNA detection, with a sensitivity and reliability comparable or higher than that using an absorbance reader. With no need for any analytical equipment, this visual quantification method is highly suitable for use in low resource settings. Secondly, a CCC-based colorimetric assay was developed for studying the interaction strengths between NMNPs and oligonucleotides/nucleotides (Chapter 4). This assay has been used to determine the interaction strengths between various NMNPs and DNA/RNA oligonucleotides/nucleotides. The results showed that the interaction strengths of 15 nt DNA homo-oligonucleotides with silver nanoparticles (AgNPs) ranks as A\u3eC\u3eT while that with gold nanoparticles (AuNPs) ranks as A\u3eT\u3eC. Interaction strengths of DNA monophosphate and triple phosphate nucleotides with AuNPs ranks as G\u3eT\u3eA\u3eC while interaction strengths of RNA monophosphate nucleotides with AuNPs ranks as on AgNPs of G\u3eU\u3eA\u3eC. Thirdly, a colorimetric method was developed for determining the interaction strengths between NMNPs and nucleobases/nucleosides (Chapter 5). This assay has been used to determine the interaction strengths between AgNPs and various DNA/RNA nucleobases/nucleosides. Interaction strengths with AgNPs ranks as A\u3eU\u3eT\u3eC\u3eG for nucleobases, G\u3eA\u3eT\u3eC for DNA nucleosides, and A\u3eG\u3eU\u3eC for RNA nucleosides. Lastly, a NMNP-bases method was developed to determine the net electric charges of antibiotics (Chapter 6). This method has been demonstrated with vancomycin. The charge of vancomycin at near neutral pH determined with this method was comparable to that reported in the literature. With a high sensitivity and general applicability, this NNMP-based method could be an appealing alternative for existing charge determination methods