| Abstract | Biochemical studies: Transition metal-ion misregulation, in conjunction with oxidative stress and peptide aggregation, has been implicated in multiple neurodegenerative diseases. In Alzheimers disease, for example, copper(II) and zinc(II) ions abnormally accumulate in regions of the brain that contain #946;-amyloid plaques and display increased levels of oxidative injury. In this work, we examined the potential of L1 and L2 to serve as neurotherapeutic agents for the treatment of AD. Collectively, these studies showed that (i) L1 and L2 were capable of preventing and reversing metal-induced amyloid formation; (ii) the antioxidant capacity of L1 was enhanced dramatically upon conversion to a pyridol ring and; (iii) L2 was capable of preventing cellular death, induced by oxidative stress. Overall, our accomplishments revealed that L1 and L2 have therapeutic potential for the treatment of neurodegenerative disorders and animal studies are currently underway.^ ^Inorganic studies: Given the enhanced antioxidant activity observed for L2, we were curious to know whether this behavior would be reduced by a change in the position of the hydroxyl group from p- to m-substituted. Thus, L3 was produced and the radical reducing capacity was measured using the DPPH assay. From this study, we determined that the radical-scavenging capability of L2 was approximately equivalent to L3. We then set out to explore the chemical properties of a series of nickel(II), copper(II), and zinc(II) complexes derived from L1-L3, in order to understand how the electron-donating nature of the L1 was altered in response to p- and m-hydroxylation. The structural, electronic, and electrochemical properties of these complexes were studied using X-ray crystallography, spectroscopy (UV-visible and NMR), and cyclic voltammetry.^ ^The data collected from this series of experiments revealed that (i) hydroxylation enhanced the amount of ?-electronic charge density in the aromatic system; (ii) p-hydroxylation induces a larger electron-donating effect than m-hydroxylation; and (iii) the Lewis-basicity of the ligands increases across the series L2 L3 L1. |
