Copper(II) complexes with b-cyclodextrin–homocarnosine conjugates and their antioxidant activity Francesco Bellia a , Diego La Mendola b , Giuseppe Maccarrone a , Placido Mineo a , Daniele Vitalini c , Emilio Scamporrino a , Salvatore Sortino a , Graziella Vecchio a , Enrico Rizzarelli a,b, * a Dipartimento di Scienze Chimiche, Universita ` di Catania Viale A. Doria, 6, Catania CT 95125, Italy b Istituto di Biostrutture e Bioimmagini-CNR-Unita ` Organizzativa di Supporto di Catania Viale A. Doria, 6, Catania 95125, Italy c Istituto di Chimica e Tecnologia dei Polimeri, CNR-Sezione di Catania, Catania, Viale A. Doria, 6, Catania 95125, Italy Received 20 June 2006; accepted 6 July 2006 Available online 22 July 2006 Dedicated to Professor Vincenzo Balzani. Abstract Copper(II) complexes of the b-cyclodextrin (b-CD) functionalized with homocarnosine (HC) in the primary (CDHC6) and secondary rim (CDHC3) were characterized by means of different spectroscopic techniques such as UV–Vis absorption, circular dichroism, electron paramagnetic resonance and electron-spray mass spectrometry. Taken together, all the spectroscopic parameters indicate the formation of different copper(II) complex species at various pH values. In the CDHC3 copper(II) complex species, a direct involvement of the sec- ondary hydroxyl group 2 of functionalized b-CD’s ring has been pointed out. The antioxidant activity of the copper(II) complexes of the two derivatives was determined through pulse radiolysis measurements. The results obtained provide direct evidence for a high catalytic activity of both complexes towards the dismutation of the superoxide anion radical. It is also demonstrated that the complex formation is not detrimental to the excellent scavenger activity exhibited by the ligands alone towards hydroxyl radicals. These copper complexes then represent very intriguing antioxidant agents against well known toxic reactive oxygen species. Ó 2006 Elsevier B.V. All rights reserved. Keywords: Copper(II) complexes; Antioxidant activity; Cyclodextrin derivatives 1. Introduction Homocarnosine (c-aminobutyryl-L-histidine) is a dipep- tide related to a group of natural histidine-containing mol- ecules of which carnosine (b-alanyl-L-histidine) is the archetype [1,2]. These dipeptides are present in consider- able amounts in several vertebrate tissues including skeletal muscle, the eye, the olfactory system and the brain [3–6]. Their specific biological function is not yet known, how- ever, different hypotheses have been postulated: as being neurotransmitters, metal ion-chelating, having buffering effect, or as being antioxidants and antiglycating agents [7–13]. Homocarnosine is present in the human brain in greater amounts than in other mammals such as rats or mice (0.3–1.6 mM, with higher levels in subcortical gray matter), and its concentration is three to six times higher in adults than in infants [14]. It has been suggested as being a precursor for the neurotransmitter GABA hence serving as an important inhibitory neuromodulator in the human neocortex [15]. Homocarnosine can bind zinc in vivo and so modulate synaptic transmission directly by altering the availability of endogenous zinc as well as carnosine [7]. These peptides 0020-1693/$ - see front matter Ó 2006 Elsevier B.V. All rights reserved. doi:10.1016/j.ica.2006.07.028 * Corresponding author. Address: Dipartimento di Scienze Chimiche, Universita ` di Catania Viale A. Doria, 6, Catania CT 95125, Italy. Tel.: +39 0957385070; fax: +39 095337678. E-mail address: erizzarelli@unict.it (E. Rizzarelli). www.elsevier.com/locate/ica Inorganica Chimica Acta 360 (2007) 945–954