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Abstract: The antibacterial activity of aminoglycosides stems from their high affinity binding to the 16S rRNA in bacteria resulting in inhibition of protein synthesis. Used to treat acute bacterial infections these antibiotics have limited applications due to their high dosage requirements and the emergence of resistant strains. We have synthesized and characterized the Cu(II) derivatives of six aminoglycosides. Kanamycin A, tobramycin and neamine exhibit preferential and tight binding to Cu(II) whereas neomycin B, kanamycin B and paromomycin don't bind as tightly. Frozen solution EPR and UV-visible spectroscopy suggest a change in geometry around the Cu(II) but the stabilities of the complexes in water differ. These copper derivatives efficiently cleave plasmid DNA at micromolar concentrations (hydrolytic) and at nanomolar concentrations in the presence of co-reactants such as hydrogen peroxide or ascorbic acid (oxidative or radical mediated). Hydrolysis is multi turnover and exhibits Michelis-Menten kinetics with enzyme-like behavior whereas oxidative cleavage is highly specific with C-4' H abstraction resulting in characteristic base propenal and nucleotide base products. Freeze-trapped EPR samples show the presence of radical species, and room temperature trapping by 2, 2'- dimethyl pyroline oxide confirms the presence of hydroxyl radicals in reactions containing hydrogen peroxide. Spin integration of EPR spectra of frozen samples obtained by mixing the complexes treated co-reactant shows the presence of a diamagnetic species in equilibrium with a paramagnetic species. The hydroxyl radical generated is not diffusible in the presence of substrate, which suggests that it may be copper based and is generated in close proximity to the substrate. This controlled formation of hydroxyl radicals may explain the high specificity exhibited by these complexes. Hammerhead ribozymes are selectively hydrolyzed in the presence of divalent ions with Mg2+ being the metal ion of choice in vivo. The mechanism of hammerhead cleavage has been a subject of extensive research for the past two decades and a model that conforms to all results is yet to emerge. Our studies with complex ions such as cobalt hexaammine and fac-triamminetriaquochromium(III) establish that Mg2+ must interact with the hammerhead in the catalytic site via outer sphere coordination of its bound water molecules. There are essentially two sets of sites, one structural and one catalytic. The structural site needs to be occupied for activity and corresponds to the high affinity site. Complex ions in the catalytic site and divalent ions in the structural site result in a slow but active hammerhead ribozyme suggesting that the complex ions are not inhibitory, contrary to what was suggested previously.