When ring makes the difference: coordination properties of Cu2+/Cu+ complexes with sulfur-pendant polyazamacrocycles for radiopharmaceutical applications. (6th May 2022)

• Record Type: Journal Article
• Authors: Tosato, Marianna; Pelosato, Matteo; Franchi, Sara; Isse, Abdirisak Ahmed; May, Nóra Veronica; Zanoni, Giordano; Mancin, Fabrizio; Pastore, Paolo; Badocco, Denis; Asti, Mattia; Di Marco, Valerio
• Is Part Of: New journal of chemistry. Volume 46:Number 21(2022)
• Page Start: 10012
• Page End: 10025
• Publication Date: 2022-05-06
• Subjects: Chemistry -- Periodicals; Chimie -- Périodiques; 540
• DOI: 10.1039/d2nj01032a
• Languages: English
• ISSNs: 1144-0546

Abstract

Abstract : The Cu 2+/+ complexes formed by sulfur-containing polyazamacrocycles were studied in aqueous solution using potentiometry, UV-Vis, NMR, EPR, and cyclic voltammetry. Abstract : Three polyazamacrocyclic ligands, i.e. 1, 5, 9-tris[2-(methylsulfanyl)ethyl]-1, 5, 9-triazacyclododecane (TACD3S), 1, 4, 7, 10-tetrakis[2-(methylsulfanyl)ethyl]-1, 4, 7, 10-tetrazacyclotridecane (TRI4S) and 1, 4, 8, 11-tetrakis[2-(methylsulfanyl)ethyl]-1, 4, 8, 11-tetrazacyclotetradecane (TE4S), were considered as potential chelators for the medically relevant copper radioisotopes. The ligands have been synthesized through facile, single-step reactions, and their acidity constants have been measured in aqueous solution at 25 °C. The kinetic, thermodynamic, electrochemical and structural properties of their Cu 2+ and Cu + complexes were investigated in aqueous solution at 25 °C using spectroscopic (UV-Visible, EPR, NMR) and electrochemical techniques (pH-potentiometric titrations, cyclic voltammetry and electrolysis). TACD3S was demonstrated to be unable to stabilize Cu 2+, whereas for TRI4S and TE4S the formation of stable monocupric (CuL 2+ ) and monocuprous (CuL + ) complexes was detected. TRI4S coordinates Cu 2+ via a [4N] and a [4N]S array of donor atoms while with TE4S only the latter geometry exists. The thermodynamic stability and the kinetic inertness of the copper complexes formed by TACD3S, TRI4S and TE4S were compared with those previously reported for 1, 4, 7, 10-tetrakis-[2-(methylsulfanyl)ethyl]-1, 4, 7, 10-tetrazacyclododecane (DO4S) to unravel the influence of the ring size and the nitrogen donor array on the copper chelation properties of these sulfur-rich macrocycles. The copresence of four nitrogen atoms is an essential feature to allow effective copper coordination when a 12-member ring is employed, as the Cu 2+ –DO4S complexes were far more stable than those of Cu 2+ –TACD3S. Furthermore, the larger ring size of TRI4S and TE4S, when compared to DO4S, progressively increases the rate of the Cu 2+ complexation reactions but decreases the thermodynamic stability of the Cu 2+ complexes. Despite this, the ability of TRI4S and TE4S to stably accommodate both copper oxidation states makes them very attractive for application in nuclear medicine as they could avoid the demetallation after the biologically triggered Cu 2+ /Cu + reduction.