Aβ(4-16) belongs to the ATCUN type peptides and therefore forms stable square planar complexes with Cu(II) ions at pH values above pH 5 (scheme 1A and spectroscopic data SI Figure .2). For ATCUN complexes, the Cu(II)/Cu(III) reaction is predicted to occur. Depending on the amino acid sequence, the Cu(II)/Cu(III) process is usually nearly electrochemically reversible (both oxidation and reduction peak are present, and ∆Ep is close to 59/n mV at 25 °C) as described for GGH-Cu(II), or quasi-reversible (both oxidation and reduction peak are present, and ∆Ep value is higher than 59 mV at 25 °C) for BAH-Cu(II). However, no reduction signal was observed (Figure A) for the Aβ(4-16)-Cu(II) complex in all pHs when 0.1 Vs -1 was applied. The absense of the Cu(III)/Cu(II) peak in the Aβ(4-16)-Cu(II) complex results from the presence of redox active tyrosine in the peptide sequence, which is quenching the Cu(III)/Cu(II) process. As was shown in a previous publication, replacing Tyr by Phe (a non redox active amino acid) resulted in the presence of a Cu(III)/Cu(II) peak for the Aβ-Cu(II) complex. For this reason, we not only investigated the Aβ(4-16)-Cu(II) complex but also oxidation of tyrosine in the peptide (Figure B). Tyrosine oxidation is visible in CVs recorded for the complex, Aβ and for the tyrosine amino acid itself. Oxidation of tyrosine in the Aβ sequence is an irreversible process due to the formation of a thermodynamically unstable tyrosyl radical. Therefore on registered CV only anodic peak is present (Figure ). For both the complex and the peptide itself the anodic signal shifted toward less positive potentials as the pH increased, which indicates that a proton exchange occurs in the process. The ratio of number of electrons and protons exchanged was estimated from the Ep,ox vs pH plots (Figure ). The oxidation potential for Aβ (4-16) and tyrosine shows a shift of 54 ± 2 and 63 ± 2 mV per pH unit, respectively, indicating a one-electron and one-proton process according to the Nernst equation. In contrast, the slope of 33 ± 1 mV per pH unit obtained for the Aβ(4 16)-Cu(II) complex indicates the transfer of two electrons and one proton (Figure ). It is likely that the shift in Cu(II)/Cu(III) oxidation potential (which in itself should not be pH dependent) is related to the deprotonation of not only tyrosine but also other amino acids in the peptide sequence, which changes the electrostatic environment around the metal centre and therefore facilitates the oxidation process on the electrode. This phenomena was observed by us earlier for other Cu-peptide complexes. The CVs also show a strong background from the broad oxidation of His which is centred outside the measured electrochemical window (Eox ~1.10 V, vs. Ag/AgCl. ) Similar studies, aiming to explain the influence of tyrosine on the oxidation process of copper(II) ions, were conducted by Tsai and Weber for tripeptide complex YGG-Cu(II). These authors proposed an electrochemical-chemical (EC) mechanism. Therefore, based on their article, an initial suggestion for a possible mechanism for Aβ(4-16)-Cu(II), where most likely in the first electrochemical step, tyrosine is deprotonated and oxidised to the radical (Y • ) and Cu(II) ions are oxidised to the Cu(III), could be: