A new water-soluble Cu(II) chelator that retrieves Cu from Cu(amyloid-β) species, stops associated ROS production and prevents Cu(II)-induced Aβ aggregation (Conference Paper)

摘要

The synthesis of the H_2L~(2-) ligand (N,N'-Bis[(5-sulfonato-2-hydroxy)benzyl]-N,N′-dimethyl-ethane-1,2-diamine) and characterizations of the corresponding Cu(II) complex [Cu(L)(H _2O)]~(2-) (1) by X-ray diffraction, EPR, UV-Visible and potentiometry are described. At pH 7.4, the affinity of Cu(II) for this ligand is approximately 4 × 10~(14) M~(- 1). Coordination of redox active metal ions such as copper or iron to the amyloid-β (Aβ) peptide has been linked to deleterious processes encountered in the etiology of Alzheimer disease (AD), such as Aβ aggregation and reactive oxygen species (ROS) production. In this context, the ability of the H_2L ~(2-) to extract Cu(II) from Cu(Aβ) species where Aβ is the peptide involved in AD, is reported as well as its capacity to redox silence the Cu(Aβ) induced ROS formation and to prevent Cu(II)-induced Aβ aggregation. Such water soluble sulfonato-derivatives of Cu(II) chelators are very interesting counterparts for in vitro study of chelators' properties required to attend further biological applications as therapeutic tools against AD.