Solution and solid state study of copper(II) ternary complexes containing amino acids of interest for brain biochemistry – 2: Homocysteine with aspartate, glutamate or methionine Luciana Dornelas Pinto a , Pedro A.L. Puppin a , Vanessa M. Behring a , Odivaldo Cambraia Alves b , Nicolás A. Rey a , Judith Felcman a,⇑ a Department of Chemistry, Pontifícia Universidade Católica do Rio de Janeiro (PUC-Rio), Rio de Janeiro, Brazil b Institute of Chemistry, Universidade Federal Fluminense (UFF), Rio de Janeiro, Brazil article info Article history: Received 1 September 2010 Received in revised form 30 December 2011 Accepted 15 January 2012 Available online 2 February 2012 Keywords: Homocysteine Amyloid b-peptide Copper(II)-complexes Ternary systems abstract Alzheimer’s disease is characterized by the loss of synapses and by the presence of extra-cellular amyloid b-peptide (Ab) plaques, and it has been associated to copper metabolism. The plasma of patients with Alzheimer’s disease presents higher levels of the amino acid homocysteine (hCys). In this study, three new ternary complexes of copper(II) with homocysteine and three amino acids of Ab (aspartate, glutamate or methionine) were studied both in solution (pH-potentiometry and UV–Vis) and in the solid state (CHNS, AAS, TGA, EPR, and FT-IR). Molar conductance and electrochemical (CV) measurements were carried out as well. The binary complex [Cu(hCys) 2 ] was also synthesized and char- acterized. For the ternary complexes, the values of the stability constants (log b equal to 25.62 for CuAsphCys, 23.53 for CuGluhCys, and 18.61 for CuMethCys) are similar to those of the cysteine-containing ternary complexes CuAspCys and CuGluCys, recently reported by us, indicating a related N 2 OS coordination. The results found in the solid state are in agreement with the data found in solution studies whereby methionine, aspartic, and glutamic acids coordinate to copper(II) ion through the nitrogen atom of the amino group and one oxygen atom of the a-carboxylate group, and homocysteine coordinates through nitrogen and sulfur atoms. EPR data suggest that, in solution, the complexes are in a distorted tetrahedral geometry. Ó 2012 Elsevier B.V. All rights reserved. 1. Introduction Due to the advances in medicine, human life expectancy has in- creased in the last decades and, therefore, concerns with neurode- generative diseases became greater than ever. Alzheimer’s disease (AD) accounts for more than 70% of all cases of dementia [1]. AD is characterized by the presence of amyloid b-peptide (Ab) plaques [2,3] and loss of synapses. The Ab1–42 peptide is the predominant species found in the deposits of neuritic (senile) plaques [4]. In the last few years, various studies have been providing evidence that metal ions are critically involved in the pathogenesis of major neu- rological diseases. Zn(II), Cu(II), and Fe(III) are present along with Ab in the senile plaques in Alzheimer’s disease, where Al(III) is also detected [5,6]. The toxicity of Ab plaques is related to the produc- tion of hydrogen peroxide [7], and studies show that the presence of copper ions potentiates the toxicity of the plaques [7–9]. In the plasma of patients with Alzheimer’s disease, augmented levels of homocysteine (2-amino-4-mercaptobutyric acid, hCys) were found [10,11]. Homocysteine is an endogenous sulfur-con- taining amino acid produced metabolically by the demethylation of methionine. Homocysteine is involved in several biochemical processes and is a constituent of many proteins, which are good complexing agents. However, in spite of its beneficial functions, a plasma hCys concentration of more than 15 lM is described as hyperhomocysteinemia, a condition associated to inherited disor- ders in the metabolism of the main enzymes of hCys or to nutri- tional deficiencies of the vitamin cofactors B 6 and B 12 [12]. The determination of hCys in biological fluids (especially plas- ma) is very important because hyperhomocysteinemia has been associated with several conditions, such as coronary artery and cerebrovascular diseases, neural tube defects, mental disorders [12], and is a risk factor for the development of AD [13]. Studies reported that a major risk factor for vascular disease is related to elevated levels of hCys in plasma [13,14], and that people with cardiovascular risk factors have an increased risk of developing AD [13–17]. 0020-1693/$ - see front matter Ó 2012 Elsevier B.V. All rights reserved. doi:10.1016/j.ica.2012.01.025 ⇑ Corresponding author. Tel.: +55 21 35271329; fax: +55 21 35271637. E-mail address: felcman@puc-rio.br (J. Felcman). Inorganica Chimica Acta 386 (2012) 60–67 Contents lists available at SciVerse ScienceDirect Inorganica Chimica Acta journal homepage: www.elsevier.com/locate/ica