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Full equilibria picture in aqueous binary and ternary systems involving copper(II), 1-methylimidazole-containing
hydrazonic ligands and the 103-112 human prion protein fragment
Journal: Inorganic Chemistry Manuscript ID Draft
Manuscript Type: Article Date Submitted by the
Author: n/a
Complete List of Authors: Cukierman, Daphne; Pontificia Universidade Catolica do Rio de Janeiro, Department of Chemistry
Bodnár, Nikolett; University of Debrecen, Department of Inorganic and Analytical Chemistry
Diniz, Renata; Universidade Federal de Minas Gerais
Nagy, Lajos; University of Debrecen, Department of Applied Chemistry Kállay, Csilla; University of Debrecen, Department of Inorganic and Analytical Chemistry
Rey, Nicolás; Pontificia Universidade Catolica do Rio de Janeiro,
ACS Paragon Plus Environment Submitted to Inorganic Chemistry
1
Full equilibria picture in aqueous binary and ternary systems involving copper(II), 1-methylimidazole-containing hydrazonic ligands
and the 103-112 human prion protein fragment
Daphne S. Cukierman1#, Nikolett Bodnár2#, Renata Diniz3, Lajos Nagy4, Csilla Kállay2*, Nicolás A. Rey1*
1 Department of Chemistry, Pontifical Catholic University of Rio de Janeiro, Rio de Janeiro, 22451-900, Brazil
2Department of Inorganic and Analytical Chemistry, University of Debrecen, Debrecen, 4032, Hungary
3 Department of Chemistry, ICEx, Federal University of Minas Gerais, Belo Horizonte, 31270-901, Brazil
4 Department of Applied Chemistry, University of Debrecen, Debrecen 4032, Hungary
*Joint corresponding authors:
Dr. Csilla Kállay – kallay.csilla@science.unideb.hu – (+36 52 512-900) Prof. Nicolás A. Rey – nicoarey@puc-rio.br – (+55 21) 3527-1813
# These authors contributed equally to the manuscript.
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2 Abstract
In the present work, we describe two novel 1-methylimidazole N-acylhydyrazonic ligands and their interaction with copper(II) ions in solution. Binary systems constituted by each of these hydrazones and the metal were studied by potentiometric titrations. The magnitude of their affinities for zinc(II) was also determined for the sake of comparison.
Additionally, a full evaluation of the copper(II) chelation profile of the new ligands in ternary systems containing a human prion protein fragment was performed. Mixed-ligand complexes comprising the HuPrP103-112 fragment, copper(II) ions and an N-acylhydrazone were characterized by potentiometry, UV-Vis and CD. Some of these species were also identified by ESI-MS, and unequivocally assigned through their isotopic distribution pattern. As far as we know, this is the first report concerning the stability of ternary complexes involving a hydrazonic metal-protein interaction modulator, copper and a peptide. The N-acylhydrazones’ ability in preventing this peptide’s oxidation was examined as well. Both ligands are able to partially prevent the formation of the doubly- oxidized product, a process catalyzed by copper(II) ions. Oxidative stress is considered an important hallmark of neurodegenerative diseases, as prion-related spongiform encephalopathies. In this context, an active intervention on the deleterious copper- catalyzed methionine oxidation could represent an interesting therapeutic approach.
Keywords:
N-acylhydrazones; copper; PrP fragment; ternary complexes; potentiometry; oxidation.
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