Metal-Induced Amide Deprotonation and Binding Typical for Cu(II), Not Possible for Zn(II) and Fe(II)

Amide groups of the peptide backbone are very weak acids. In fact, their deprotonation in water solution is not a phenomenon usually observed in the measuring range of a glass electrode unless the proton is displaced by a metal such as Cu(II) or Ni(II). Other metals are not usually expected to deprotonate and bind to amide nitrogens, although, lately, some controversies have started to arise in the literature, suggesting that Zn(II) and Fe(II) may be capable of doing so. In order to clarify this phenomenon, we chose to study simple metal−peptide systems with Ala-to-Pro mutations, which excluded further amides from binding. A comparison of the metalbinding modes of Ac-AAAHAAA-NH2, Ac-AAPHAAA-NH2, and Ac-AAPHPAA-NH2 complexes with Cu(II), Zn(II), and Fe(II) is a simple and elegant way of showing that neither Zn(II) nor Fe(II) is able to deprotonate and bind to amide nitrogens.