Silvia Pérez García

BIO-RELATED COPPER-MEDIATED OXIDATIVE PROCESSES

The present minireview deals with the use of the oxidative properties of copper(II/I) coordination compounds for valuable applications, namely the selective conversion of alcohols into aldehydes (or ketones), the cleavage of DNA strands (anti-cancer drugs), and the prevention of the formation of copper/amyloid plaques in Alzheimers disease (AD). The concise report is therefore organized in three clearly defined parts: i) the design and preparation of simple copper(II) (and copper(I)) coordination compounds, mimicking the enzymatic activity of galactose oxidase, to mediate the selective oxidation of alcoholic substrates; ii) the generation of copper-containing chemical nucleases for the development of effective anti-cancer agents; iii) the current state of the art regarding the elucidation of the copper-based biological mechanisms (involving β-amyloid) that govern neural degeneration in AD.

Dual role of Cu2+ ions on the aggregation and degradation of soluble Aβ oligomers and protofibrils investigated by fluorescence spectroscopy and AFM

The neuropathological character of copper(II) ions (Cu(2+)) upon interaction with soluble human amyloid-β(1-42) that subsequently generates senile plaques and/or reactive oxygen species (ROS) is considered as one of the very important features of Alzheimers disease. The present study carried out by using fluorescence spectroscopy and atomic-force microscopy (AFM) indeed confirms the dual role played by Cu(2+), namely as mediator of protein aggregation and as generator of ROS leading to irreversible protein alteration, which most likely involve two distinct copper-binding sites. The AFM investigations clearly evidence the copper-induced aggregation of Aβ oligomers and protofibrils, while comparative fluorescence measurements with copper and zinc reveals the crucial involvement of redox-active copper in the generation of Aβ-cross-linked structures.