Bioconjugation of triosmium carbonyl clusters
Tan, Yu Qian
Date of Issue2017-01-12
School of Physical and Mathematical Sciences
Nanyang Technological University
This thesis describes the conjugation of triosmium carbonyl clusters to biomolecules, in particular, nucleosides and oligopeptides. Several different approaches were employed for this conjugation, including the copper-catalyzed 1,3-dipolar azide-alkyne cycloaddition (CuAAC) reaction. Various triosmium carbonyl clusters were successfully conjugated to nucleosides, and the conjugation was also extended to hexaosmium carbonyl clusters. The effect of bioconjugation on the biological activity of the cluster was examined, with several clusters showing promising anti-proliferative activity. The CuAAC reaction was also utilized for the labelling of oligopeptides with osmium carbonyl clusters for TEM imaging. Oligopeptides were successfully conjugated to functionalized disubstituted phosphine clusters via simultaneous biorthogonal reactions. These oligopeptide-cluster conjugates underwent stereochemical changes upon protonation, and the effect of these changes on the structure and conformation of the oligopeptide were investigated. Cluster protonation was also investigated for development into SERS-based intracellular pH sensors.