The dioxygen reactivity of as eries of TMPA-based copper(I) complexes (TMPA = tris(2-pyridylmethyl)amine), with and without secondary-coordination-sphere hydrogenbonding moieties,w as studied at À135 8 8Ci n2 -methyltetrahydrofuran (MeTHF). Kinetic stabilization of the H-bonded [( ðX 1 ÞðX 2 Þ TMPA)Cu II (O 2 C À )] + cupric superoxide species was achieved, and they were characterized by resonance Raman (rR) spectroscopy. The structures and physical properties of [( ðX 1 ÞðX 2 Þ TMPA)Cu II (N 3 À )] + azido analogues were compared, and the O 2 C À reactivity of ligand-Cu I complexes when an Hbonding moiety is replaced by amethyl group was contrasted. Ad rastic enhancement in the reactivity of the cupric superoxide towards phenolic substrates as well as oxidation of substrates possessing moderate C À Hb ond-dissociation energies is observed, correlating with the number and strength of the H-bonding groups.Oxidation and oxygenation reactions are vital for biological and synthetic processes. [1][2][3][4][5][6][7][8][9] In biology,s ome copper-containing metalloenzymes are capable of performing these reactions. [2,10] Forexample,galactose oxidase (GO) is responsible for the oxidation of primary alcohols to aldehydes (Figure 1A); monooxygenases such as peptidylglycine a-hydroxylating monooxygenase (PHM), dopamine b-monooxygenase (DbM), and lytic polysaccharide monooxygenases (LMPOs) catalytically hydroxylate organic substrates containing strong (85-100 kcal mol À1 )C ÀHb ond dissociation energies (BDEs) using dioxygen ( Figure 1B). [2,[10][11][12] These reactions are important for biosynthesis of human prohormones and neurotransmitters in the former,a nd breaking down polysaccharides in the latter. Acupric superoxide species (that is,Cu II À O 2 C À ,formed from the reaction of copper(I) and dioxygen) is postulated to be involved in the catalytic cycles of each of these enzymes. [11] In GO,t his complex abstracts ah ydrogen atom from anearby Tyrresidue,thereby forming the catalytically active intermediate responsible for substrate oxidation.While the exact nature of the reactive intermediate in LPMOs is still widely debated, [12][13][14] ac onsensus in the literature for PHM and DbMi sthat acupric superoxide is responsible for the initial hydrogen-atom transfer (HAT) from ac arbon substrate. [11] Thus,t he study of synthetic cupric superoxide model complexes to further understand their structures, physical-spectroscopic properties,a nd correlated reactivity toward the hydroxylation of substrates containing strong CÀ Hb onds is of considerable interest in catalysis.Ty pically,t hese primary copper-dioxygen superoxide model species [11,15,16] are difficult to study due to their tendency to form secondary Cu 2 -O 2 adducts (that is, m-1,2peroxo-dicopper(II), side-on peroxodicopper(II), or bis-moxodicopper(III) complexes) in solution. Researchers have been able to prevent the formation of 2:1C u:O 2 adducts through ligand design;the addition of as econdary coordination sphere of sterically bulky groups [17][18][19][20][21...

In this report, we investigate the physical and chemical properties of monocopper Cu(I) superoxo and Cu(II) peroxo and hydroperoxo complexes. These are prepared by cryoreduction/annealing of the parent [LCu I (O 2 )] + Cu(I) dioxygen adducts with the tripodal, N 4 -coordinating, tetradentate ligands L = PV tmpa, DMM tmpa, TMG 3 tren and are best described as [LCu II (O 2•− )] + Cu(II) complexes that possess end-on (η 1 -O 2 •− ) superoxo coordination. Cryogenic γ-irradiation (77 K) of the EPRsilent parent complexes generates mobile electrons from the solvent that reduce the [LCu II (O 2•− )] + within the frozen matrix, trapping the reduced form fixed in the structure of the parent complex. Cryoannealing, namely progressively raising the temperature of a frozen sample in stages and then cooling back to low temperature at each stage for examination, tracks the reduced product as it relaxes its structure and undergoes chemical transformations. We employ EPR and ENDOR (electron−nuclear double resonance) as powerful spectroscopic tools for examining the properties of the states that form. Surprisingly, the primary products of reduction of the Cu(II) superoxo species are metastable cuprous superoxo [LCu I (O 2•− )] + complexes. During annealing to higher temperatures this state first undergoes internal electron transfer (IET) to form the end-on Cu(II) peroxo state, which is then protonated to form Cu(II)−OOH species. This is the first time these methods, which have been used to determine key details of metalloenzyme catalytic cycles and are a powerful tools for tracking PCET reactions, have been applied to copper coordination compounds.

Theauthors declare no conflict of interest. Figure 5. Second-order rate constants for the reaction of [( ðXÞ2 TMPA)Cu II (O 2 C À )] + with p-methoxyphenol (X = NH 2 ,PV).Figure 6. Reactivity of [( ðPVÞ2 TMPA)Cu II (O 2 C À )] + with substrates containing weak to moderate CÀHBDEs.

Copper complexes are promising candidates for anticancer drugs, because of their redox properties and the ability to generate ROS (reactive oxygen species) in the cellular media. Most of the reported complexes with anticancer properties are based on Cu(II), which must be reduced to Cu(I) to exert the therapeutic action. Here, we report on the synthesis and characterization of two novel copper(I) complexes, a mononuclear complex [Cu(L1)2](ClO4) (1) and a binuclear helicate [Cu2(L2)2](ClO4)2 (2) (L1=2‐ethoxy‐1,10‐phenanthroline, L2=1,2‐bis((1,10‐phenanthrolin‐2‐yl)oxy)ethane), which were designed to be structurally comparable, in order to evaluate the effect of nuclearity on the artificial nuclease activity. The activity of helicate (2) was higher than that of the monometallic (1), and the DNA cleavage mechanism is through the generation of hydroxyl radical in a Fenton‐like reaction, which occurs after oxidation of Cu(I) by O2. Also, helicate (2) showed a higher cytotoxic effect against different cancer cells lines, while both complexes are more active than cisplatin.