Synthesis, Characterization, and Cu²⁺ Coordination Studies of a 3-Hydroxy-4-pyridinone Aza Scorpiand Derivative

The synthesis, acid-base behavior, and Cu²⁺ coordination chemistry of a new ligand (L1) consisting of an azamacrocyclic core appended with a lateral chain containing a 3-hydroxy-2-methyl-4(1H)-pyridinone group have been studied by potentiometry, cyclic voltammetry, and NMR and UV-vis spectroscopy. UV-vis and NMR studies showed that phenolate group was protonated at the highest pH values [log K = 9.72(1)]. Potentiometric studies point out the formation of Cu²⁺ complexes of 1:2, 2:2, 4:3, 1:1, and 2:1 Cu²⁺/L1 stoichiometries. UV-vis analysis and electrochemical studies evidence the implication of the pyridinone moieties in the metal coordination of the 1:2 Cu²⁺/L1 complexes. L1 shows a stronger chelating ability than the reference chelating ligand deferiprone. While L1 shows no cytotoxicity in HeLa and ARPE-19 human cell lines (3.1-25.0 μg/mL), it has significant antioxidant activity, as denoted by TEAC assays at physiological pH. The addition of Cu²⁺ diminishes the antioxidant activity because of its coordination to the pyridinone moiety phenolic group.