Synthesis and Characterization of Photolabile Ruthenium Polypyridyl Crosslinkers with Applications in Soft Materials and Biology

Since its discovery in 1844, ruthenium has solidified its position as the most widely used transition metal in catalysis and excited state chemistry. Its lower toxicity and relatively low price (compared to other platinum group metals) have enabled many applications of ruthenium coordination compounds. In this dissertation I discuss ruthenium polypyridyl complexes that undergo photoinduced ligand exchange, and how this unique property can be harnessed to develop next-generation smart materials and responsive chemical biology tools. Ru(LL)2X22+ complexes, where LL is a bidentate aromatic heterocycle such as 2,2’-bipyridine, 1,10-phenanthroline, or 2,2’-biquinoline, and X is a pyridine-, nitrile-, sulfur-, or imidazole-based monodentate ligand, have the unique capability to undergo ligand exchange under visible light irradiation. We have harnessed this property to develop a series of visible-light-sensitive photodegradable crosslinkers by choosing X ligands that contain reactive moieties such as alkynes (for copper-mediated azide-alkyne cycloaddition (CuAAC)) or aldehydes (for Schiff base reaction with hydrazines). Ru(bpy)2(3-ethynylpyridine)2 (RuBEP) has been used in CuAAC reactions to circularize azide-terminated oligonucleotides important for gene regulation or transcriptome analysis. Ru(bpy)2 (3-pyridinaldehyde) 2 (RuAldehyde) alternately employed aldehydes to react with hydrazine-modified hyaluronic acid (HA-HYD). The resulting hydrogel was cytocompatible, efficiently degraded with visible light, and well adapted for the storage and delivery of active enzymes via lysine-mediated crosslinking into the hydrogel matrix. Finally, Ru(biq)2(5-hexynenitrile)2 and Ru(bpy) 2(5-hexynenitrile)2 were developed as crosslinkers to form PEG-based hydrogel, which was subsequently degraded using two different colors of visible light, orange and blue