Multinuclear Copper Complexes Research Articles

Metalloglycosidase Mimics: Oxidative Cleavage of Saccharides Promoted by Multinuclear Copper Complexes under Physiological Conditions.

Degradation of saccharides is relevant to the design of catalytic therapeutics, the production of biofuels, inhibition of biofilms, as well as other applications in chemical biology. Herein, we report the design of multinuclear Cu complexes that enable cleavage of saccharides under physiological conditions. Reactivity studies with para-nitrophenyl (pNP)-conjugated carbohydrates show that dinuclear Cu complexes exhibit a synergistic effect and promote faster and more robust cleavage of saccharide substrates, relative to the mononuclear Cu complex, while no further enhancement is observed for the tetranuclear Cu complex. The use of scavengers for reactive oxygen species confirms that saccharide cleavage is promoted by the formation of superoxide and hydroxyl radicals through CuII/I redox chemistry, similar to that observed for native copper-containing lytic polysaccharide monooxygenases (LMPOs). Differences in selectivity for di- and tetranuclear Cu complexes are modest. However, these are the first reported small multinuclear Cu complexes that show selectivity and reactivity against mono- and disaccharide substrates and form a basis for further development of metalloglycosidases for applications in chemical biology.

New copper(II) salicylaldimine derivatives for mild oxidation of cyclohexane

Two new salicylaldiminato-copper(II) complexes, [ $$\hbox {Cu}(\mathbf{L}^{\mathbf{1}})_{2}$$ ] (1) and [ $$\hbox {Cu}(\mathbf{L}^{\mathbf{2}})_{2}$$ ] (2) (where $$\mathbf{HL}^{\mathbf{1}}=4$$ -tert-Butyl-2-[(thiophen-2-ylmethylimino)-methyl]-phenol and $$\mathbf{HL}^{2} = 2,4$$ -Di-tert-butyl-6-[(thiophen-2-ylmethylimino)-methyl]-phenol), endowed with a pendant thiophenyl moiety, were synthesized and characterized using standard spectroscopic techniques (FT-IR, UV-Vis, MS) and elemental analysis. Complexes 1 and 2 were unequivocally characterized by single crystal X-ray crystallography, which confirmed bidentate bis-chelation of the deprotonated - $$\mathbf{L}^{\mathbf{1}}$$ and - $$\mathbf{L}^{\mathbf{2}}$$ ligands to the copper (II) centres via the phenoxo and imine atoms forming square planar complexes. The copper(II)-hydroperoxo derivatives of 1 and 2 ([ $$(\mathbf{L}^{\mathbf{1}})_{2}\hbox {Cu}^\mathrm{II}\hbox {-OOH}$$ ] (3) and [ $$(\mathbf{L}^{\mathbf{2}})_{2}\hbox {Cu}^\mathrm{II}\hbox {-OOH}$$ ] (4)) were also synthesized and the formation of the active intermediate in solution studied. Complexes 1 and 2 were tested as catalyst precursors in cyclohexane oxidation under mild reaction conditions using hydrogen peroxide ( $$\hbox {H}_{2} \hbox {O}_{2}$$ ) as a terminal oxidant, and were found to catalyse oxidation of the substrate with yields comparable to similar mononuclear and even multinuclear copper complexes. Synopsis Synthesis, characterisation, and molecular structure of salicylaldiminato-copper(II) complexes, and their catalytic evaluation in the oxidation of cyclohexane employing hydrogen peroxide as a terminal oxidant have been studied. The complexes catalysed conversion of cyclohexane with appreciable yields.

(Invited) In Situ XAFS Spectroscopy at Bio-Inspired Multicopper Catalysts for Oxygen Reduction Reaction

Platinum metal group (PMG) catalysts are used for oxygen reduction reaction (ORR) at cathodes in state-ofthe-art polymer electrolyte fuel cells (PEFCs). Since the PMG catalysts contain expensive rare metals, they should be replaced with rare-metal-free catalysts for widespread PEFCs. Recently, electrocatalysts synthesized from carbon and transition metal complexes have been studied [1,2]. It is known that ORR catalysts with multi-nuclear-active sites have high ORR activity [3]. It is also known that natural ORR catalysts such as laccases have a multinuclear copper complex as an active center and show high ORR activity [4], suggesting that laccase-inspired artificial ORR catalysts prepared from carbon and a multinuclear copper complex would show high ORR activity. In the present work, we incorporated a trinuclear copper complex ([Cu3(trz)3(μ3-OH)]Cl2·6H2O) [5] into graphene nanosheets to synthesize laccase-inspired electrocatalysts for ORR, where grapheme nanosheets worked as an electrical conductive material and the trinuclear copper complex with a triangle core imitated the active center of laccases. The trinuclear copper complex was prepared from copper chloride and 1,2,4-triazole according to the literature [5]. This copper complex and graphene oxide (GO) were mixed and then reduced in two methods. The first method is heat treatment at high temperature for a short time. The second method is electrochemical reduction on a glassy carbon (GC) electrode (-1.1 V vs. Ag|AgCl, 300 s). We carried out powdery X-ray diffraction (XRD) analysis, X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma atomic emission spectroscopy (ICP-AES) to characterize the catalysts. In situX-ray absorption fine structure (XAFS) spectroscopy was also carried out to estimate the molecular structure during ORR. For electrochemical measurements of the catalysts, the powdery catalyst was suspended in an ethanol-Nafion mixture to make ink containing the catalyst. The catalyst ink was put on a GC electrode and dried under the air at room temperature. Linear Sweep Voltammetry (LSV) was carried out under a saturated O2atmosphere using a rotary disk electrode to obtain current-potential curves. Britton-Robinson buffered solutions were used as electrolyte solutions. The heat reduction improved ORR activity. The catalyst obtained after the heat treatment showed higher ORR activity than that obtained after the electrochemical reduction. This result indicated that the two reduction methods might give different structures of ORR active sites. XPS spectra of the catalyst before and after the heat treatment were recorded to obtain information on structural changes. A peak originating from C-O was observed before the heat treatment. It disappeared after the heat treatment. This result indicated that GO was reduced to rGO by the heat treatment. The Cu2p spectra showed that CuII was also reduced to CuI. A new peak was observed in N1s spectra after the heat treatment. This peak might be attributed to new configuration that triazole rings were incorporated into graphene nanoshheets. In situ XAFS spectra clarified that the multi-copper arrangement was partially kept even after heat reduction and contributed to the higher ORR activity than other copper catalysts. References. [1] K. Kamiya, K. Hashimoto, S. Nakanishi, Chem. Commun., 2012, 48, 10213–10215. [2] T. Taniguchi, et al., Part. Part. Syst. Charact., 2013, 30, 1063-1070. [3] M. Thorum, J. Yadav, A. Gewirth, Angew. Chem. Int. Ed., 2009, 48, 165–167. [4] N. Mano, V. Soukharev, A. Heller, J. Phys. Chem. B, 2006, 110, 11180–11187. [5] T. Yamada, G. Maruta, S. Takeda, Chem. Commun., 2011, 47, 653–655

Copper-Based Electrocatalysts with Multinuclear Catalytic Sites for Oxygen Reduction Reaction

The oxygen reduction reaction (ORR) to water is catalyzed at cathodes in polymer electrolyte fuel cells (PEFCs). For widespread applications of PEFCs, low-cost cathode materials with high catalytic activity and durability are highly desirable. Since natural ORR catalysts such as multi-copper oxidases catalyze the ORR with almost no overpotential (ca. 20 mV)[1]and the enzymatic ORR occurs at a multinuclear copper complex, mimicking enzymatic active sites would allow us to develop non-precious metal-based ORR electrocatalysts for practical applications. Herein we report our research progress in synthetic and mechanistic studies on copper-based electrocatalysts for the ORR.[3,4]Our findings suggest that the design and synthesis of multinuclear copper cores might be a key to develop highly efficient and durable copper-based electrocatalysts for the ORR. References. [1] N. Mano, V. Soukharev, A. Heller, J. Phys. Chem. B, 110, 11180 (2006). [2] M.S. Thorum, J. Yadav, A.A. Gewirth, Ang. Chem. Int. Ed., 48, 165 (2008). [3] M. Kato et al., Phys. Chem. Chem. Phys., 17, 8638-8641 (2015). [4] M. Kato, N. Oyaizu, K. Shimazu, I. Yagi, J. Phys. Chem. C, in press. DOI: 10.1021/acs.jpcc.5b11663

ChemInform Abstract: Efficient and Environmentally Friendly Glaser Coupling of Terminal Alkynes Catalyzed by Multinuclear Copper Complexes under Base‐Free Conditions.

Abstract1,3‐Diynes are prepared by the title coupling using a dinuclear copper complex (COP) as catalyst in high yields.

(Invited) Tri-Copper-Incorporated Carbon Catalyst for Oxygen Reduction Reaction

Platinum metal group (PMG) catalysts are used for oxygen reduction reaction (ORR) at cathodes in state-of-the-art polymer electrolyte fuel cells (PEFCs). Since the PMG catalysts contain expensive rare metals, they should be replaced with rare-metal-free catalysts for widespread PEFCs. Recently, electrocatalysts synthesized from carbon and transition metal complexes have been studied [1,2]. It is known that ORR catalysts with multi-nuclear-active sites have high ORR activity [3]. It is also known that natural ORR catalysts such as laccases have a multinuclear copper complex as an active center and show high ORR activity [4], suggesting that laccase-inspired artificial ORR catalysts prepared from carbon and a multi-nuclear copper complex would show high ORR activity. In the present work, we incorporated a trinuclear copper complex ([Cu3(trz)3(μ3-OH)]Cl2·6H2O) [5] into graphene nanosheets to synthesize laccase-inspired electrocatalysts for ORR, where grapheme nanosheets worked as an electrical conductive material and the trinuclear copper complex with a triangle core imitated the active center of laccases. The trinuclear copper complex was prepared from copper chloride and 1,2,4-triazole according to the literature [5]. This copper complex and graphene oxide (GO) were mixed and then reduced in two methods. The first method is heat treatment at high temperature for a short time. The second method is electrochemical reduction on a glassy carbon (GC) electrode (-1.1 V vs. Ag|AgCl, 300 s). We carried out powdery X-ray diffraction (XRD) analysis, X-ray photoelectron spectroscopy (XPS) and inductively coupled plasma atomic emission spectroscopy (ICP-AES) to characterize the catalysts. X-ray absorption fine structure (XAFS) spectroscopy was also carried out to estimate the molecular structure. For electrochemical measurements of the catalysts, the powdery catalyst was suspended in an ethanol-Nafion mixture to make ink containing the catalyst. The catalyst ink was put on a GC electrode and dried under the air at room temperature. Linear Sweep Voltammetry (LSV) was carried out under a saturated O2atmosphere using a rotary disk electrode to obtain current-potential curves. Britton-Robinson buffered solutions were used as electrolyte solutions. The heat or electrochemical reduction improved ORR activity. The catalyst obtained after the heat treatment showed higher ORR activity than that obtained after the electrochemical reduction. This result indicated that the two reduction methods might give different structures of ORR active sites. XPS spectra of the catalyst before and after the heat treatment were recorded to obtain information on structural changes. A peak originating from C-O was observed before the heat treatment. It disappeared after the heat treatment. This result indicated that GO was reduced to rGO by the heat treatment. The Cu2p spectra showed that CuII was also reduced to CuI. A new peak was observed in N1s spectra after the heat treatment. This peak might be attributed to new configuration that triazole rings were incorporated into graphene nanoshheets. References. [1] K. Kamiya, K. Hashimoto, S. Nakanishi, Chem. Commun., 2012, 48, 10213–10215. [2] T. Taniguchi, et al., Part. Part. Syst. Charact., 2013, 30, 1063-1070. [3] M. Thorum, J. Yadav, A. Gewirth, Angew. Chem. Int. Ed., 2009, 48, 165–167. [4] N. Mano, V. Soukharev, A. Heller, J. Phys. Chem. B, 2006, 110, 11180–11187. [5] T. Yamada, G. Maruta, S. Takeda, Chem. Commun., 2011, 47, 653–655

Efficient and environmentally friendly Glaser coupling of terminal alkynes catalyzed by multinuclear copper complexes under base-free conditions

An efficient catalytic system with multinuclear copper complexes as catalysts has been developed for the aerobic Glaser coupling reaction, which adopts environmentally friendly water as the solvent at room temperature under base-free condition.

Non-Precious Metal Catalysts for the Oxygen Reduction Reaction

We report on our efforts to characterize the active site of Fe-based non-precious metal (NPM) catalysts for the oxygen reduction reaction (ORR). Acid leaching using aqua regia significantly decreases the amount of Fe present in the catalyst material to levels below 1 wt% with the lowest Fe content observed at 0.34 wt%. However, no change in the ORR onset is observed following catalyst treatment with acid when tested in acidic media. This indicates that some Fe centers are buried within the carbon material making then inaccessible to the acid treatment. These remaining Fe sites are accessible to oxygen and are catalytically active to the ORR. To further remove Fe from NPM ORR catalysts we exposed them to chlorine gas at high temperature (600- 1000 °C). Through this treatment Fe content as low as 0.16 wt% is achieved. After the demetalation with chlorine gas the ORR onset is seen to shift to more negative potentials by as much as 250 mV when tested in acidic media. Remetalation by exposure to FeCl3 results in partial recovery of ORR activity. We also summarize our efforts examining multinuclear copper complexes inspired by laccase, a class of blue copper oxidases that efficiently mediate the four-electron four-proton reduction of dioxygen to water.(1) We first prepare Cu complexes of 2,2'-dipicolylamine (DPA) and test its electrocatalytic activity towards the ORR. To investigate the effect of multinuclearity on the ORR, we connect two DPA units together with a flexible linker and installed a third metal-binding pocket in the ligand framework (Figure 1). The ORR onset potentials and the diffusion-limited current densities of [Cu(1)]2+ are comparable to that of [Cu(TPA)(H2O)]2+ previously reported by our group. However, the electron transfer rate between [Cu(1)]2+ and carbon electrode surface is low, indicating that more intimate coupling to the electrode may be required for efficient ORR. Covalently linking two [Cu(DPA)]2+ cores together results in ORR activities no better than [Cu(1)]2+ alone. This study highlights the viability of Cu complexes of DPA to mimic the T3-site of laccase and serves as a guide for designing future laccase models. The relationship between inter-site flexibility and cooperativity is long recognized; it is insufficient to simply connect reactive Cu sites. To ensure cooperativity comparable to that of metalloproteins, future catalysts will require more sophisticated designs. Reference 1. E. C. M. Tse, D. Schilter, D. L. Gray, T. B. Rauchfuss and A. A. Gewirth, Inorg. Chem., 53, 8505 (2014). Figure 1

(Invited) Deprotonation of a Multi-Nuclear Copper Complex for High Oxygen Reduction Reaction Activity Investigated By in Situ X-Ray Absorption Fine Structure Spectroscopy

The oxygen reduction reaction (ORR) occurs at the cathode in polymer electrolyte fuel cells (PEFCs) and its sluggish kinetics is one of the limiting factors for widespread applications of PEFCs. Although ORR catalysts have been extensively studied, platinum-based ORR catalysts with a high overpotential (>200 mV) are used even in the present state-of-the-art PEFCs. In nature enzymatic oxygen reduction is known to occur at low overpotentials: multi-copper oxidases such as laccase catalyze ORR with an overpotential of ca. 20 mV on electrode surfaces and have been employed in enzymatic fuel cells [1-2]. These enzymes, however, are fragile and their footnotes are large, making them unsuitable for use in practical PEFCs. It is highly desirable to design and develop artificial ORR catalysts with electrocatalytic properties similar to those of the enzymes [3]. Here, we present our resent studies on in situ X-ray absorption fine structure (XAFS) spectroscopy of a dinuclear copper complex of 3,5-diamiono-1,2,4-triazole, Cu-Hdatrz [4,5], supported on a carbon black under catalytic and non-catalytic conditions to gain insights into designing highly active copper-based catalysts. It is known that the Cu-Hdatrz catalyst shows high ORR activity in basic solution [5]. Our in situ XAFS measurements in neutral and basic solutions revealed that the electron transfer from a CuI species to O2 was faster under basic conditions than that under the neutral condition and deprotonation from the triazole ligand might cause the coordination geometrical changes under a basic condition, suggesting that the deprotonated structure of the CuIactive species may be a key to understand the high ORR activity of Cu-Hdatrz or to design multinuclear copper-triazole catalysts with low overpotentials. Acknowledgements This work was supported by New Energy, Industrial Technology Development Organization (NEDO). XAFS experiments were performed under the approval of the Photon Factory Program Advisory Committee (Proposal No. 2010G200 and 2013G173) References [1] N. Mano, V. Soukharev, A. Heller, J. Phys. Chem. B, 110, 11180 (2006) [2] M.S. Thorum, C.A. Anderson, J.J. Hatch, A.S. Campbell, N.M. Marshall, S.C. Zimmerman, Y. Liu, A.A. Gewirth, J. Phys. Chem. Lett, 1, 2251 (2010) [3] C.H. Kjargaard, J. Rossmeisi, J.K. Norskov, Inorg. Chem., 49, 3567 (2010) [4] E. Aznar, S. Ferrer, J. Borras, F. Lloret, M. Liu-Gonzalez, H. Rodriguez-Prieto, S. Garcia-Granda, Eur. J. Inorg. Chem., 2006, 5115 (2006) [5] M.S. Thorum, J. Yadav, A.A. Gewirth, Ang. Chem. Int. Ed., 48, 165 (2008)

Synthesis of Multinuclear Copper Complexes Bridged by Diquinolylamidinates and Their Application to Copper-Catalyzed Coupling of Terminal Alkynes and Aryl, Allyl, and Benzyl Halides

A dinuclear copper complex containing N,N′-diquinolylformamidinate and a tetranuclear copper complex containing N,N′-diquinolylacetamidinate were synthesized. The structure of complexes was confirmed by X-ray analysis, showing that copper atoms were bridged by amidinates and hydroxo or oxo ligands. The multinuclear copper complexes were effective for the coupling reactions of terminal alkynes and aryl, allyl, and benzyl halides.

Bio-inspired multinuclear copper complexes covalently immobilized on reduced graphene oxide as efficient electrocatalysts for the oxygen reduction reaction.

Inspired by the multicopper active site of laccase, which efficiently catalyzes the oxygen reduction reaction (ORR), herein we report a novel bio-inspired ORR catalyst composed of a multinuclear copper complex that was immobilized on the surface of reduced graphene oxide (rGO) via the covalently grafted triazole-dipyridine (TADPy) dinucleating ligand. This rGO-TADPyCu catalyst exhibited high ORR activity and superior long-term stability compared to Pt/C in alkaline media.

Organic–Inorganic Hybrids Constructed from Mixed-Valence Multinuclear Copper Complexes and Templated by Keggin Polyoxometalates

Five organic–inorganic hybrids containing mixed–valence multinuclear copper complexes and Keggin polyoxometalates, [CuI5CuII3(ptz)8(H2O)][HSiW12O40] (1), [CuI10CuII2(ptz)8(Cl)3][PW12O40] (2), [CuI2CuII4(ptz)6(OH)(H2O)2][PW12O40]·2H2O (3), CuI2CuII5(ptz)6(OH)2SiW12O40·6H2O (4), and [CuI2CuII5(ptz)6][PMoV3MoVI9O40]·8H2O (5) (ptz = 5-(2-pyridyl)-tetrazole), were hydrothermally synthesized and structurally characterized. Compound 1 exhibits a three-dimensional (3D) network that features unprecedented double chains consisting of tetranuclear Cu clusters. Compound 2 displays a 3D network that has unusual Cl-centered hexanuclear Cu clusters and Cl-bridged tetranuclear Cu units. Compound 3 shows a 3D supramolecular network extended by two-dimensional (2D) grid-like sheets which are composed of mixed-valence multinuclear copper chains and PW12 polyanions. Isostructural compounds 4 and 5 exhibit a 3D network consisting of 2D ladder-like copper–ptz layers and SiW12 (PMo12 in 5) polyanions. The roles of copper ions with different oxidation states and ptz ligands with different coordination modes in the construction of the copper–ptz frameworks are discussed. Their electrochemical properties were investigated as well.

ChemInform Abstract: Efficacy of C—N Coupling Reactions with a New Multinuclear Copper Complex Catalyst and Its Dissociation into Mononuclear Species.

AbstractA new air‐stable copper(I)‐pyridazine/rhenate hybrid complex is prepared and its activity is explored in C—N coupling.

Efficacy of C–N Coupling Reactions with a New Multinuclear Copper Complex Catalyst and Its Dissociation into Mononuclear Species

AbstractA new tetranuclear copper(I)–pyridazine (pda)/rhenate hybrid has been synthesized under hydrothermal conditions and structurally characterized by X‐ray crystallography. The activity of this catalyst, as well as its dissociation into mononuclear species, was investigated in homogeneous C–N arylation reactions. A variety of N‐arylamides and ‐azoles were synthesized in good to excellent yields, revealing the effect of polynuclear versus mononuclear Cu complexation in this type of coupling reaction.

Characterization and catalytic kinetics studies of N-cetyl-O-sulfate chitosan multinuclear copper complex as an artificial hydrolase

A novel multinuclear Cu(II) complex of N-cetyl-O-sulfate-chitosan (NCOS) was prepared and structurally characterized by X-ray photoelectron spectroscopy (XPS) and Infrared radiation (IR) spectroscopy. The capability of chelated copper ions to coordinate with the novel ligand was improved 55% over native chitosan. As artificial multinuclear phosphodiesterase, NCOS-Cu(II) complex was adopted to study its catalytic kinetics on hydrolysis of bis(4-nitriphenyl)phosphate (BNPP) in the heterogeneous system. The initial rate of BNPP hydrolysis catalyzed by NCOS-Cu(II) was 7 × 104 times higher than that of spontaneous BNPP hydrolysis. The behavior of BNPP catalytic hydrolysis fits Michaelis–Menten kinetics with kcat of 2.3 × 10−5 s−1, the maximum velocity (Vmax) of 2.3 × 10−9 mol L−1 s−1 and the Michaelis constant (KM) of 2.9 × 10−4 M, respectively. The metal-hydroxyl catalytic mechanism has been proposed.

Oxidative DNA Cleavage Promoted by Multinuclear Copper Complexes: Activity Dependence on the Complex Structure

Polynuclear copper complexes with two or three Cu(BPA) (BPA, bis(2-pyridylmethyl)amine) motifs, [Cu2(mTPXA)Cl4]3 H2O (1), [Cu2(pTPXA)Cl4]3 H2O (2), [Cu3(HPTAB)Cl5]Cl3 H2O (3) (mTPXA = N,N,N',N'-tetra-(2-pyridylmethyl)-m-xylylene diamine; pTPXA = N,N, N',N'-tetra-(2-pyridylmethyl)-p-xylylenediamine; HPTAB = N,N,N',N',N'',N''-hexakis(2-pyridylmethyl)-1,3,5-tris-(aminomethyl)benzene) have been synthesized and characterized. The crystal structures of compounds 2 and 3 showed each Cu(BPA) motif had a 4+1 square-pyramidal coordination environment with one chloride occupying the apical position and three N atoms from the same BPA moiety together with another Cl atom forming the basal plane. Fluorescence and circular dichroism (CD) spectroscopy studies indicated that the DNA binding followed an order of 3>2>1 in the compounds. These complexes cleave plasmid pUC19 DNA by using an oxidative mechanism with mercaptopropionic acid (MPA) as the reductant under aerobic conditions. Dinuclear Cu2+ complexes 1 and 2 showed much higher cleavage efficiency than their mononuclear analogue [Cu(bpa)Cl2] at the same [Cu2+] concentration, suggesting a synergistic effect of the Cu2+ centers. Moreover, the meta-dicopper centers in complex 1 facilitated the formation of linear DNA. Interestingly, the additional copper center to the meta-dicopper motif in complex 3 decreased the cleavage efficacy of meta-dicopper motif in complex 1, although it is able to cleave DNA to the linear form at higher [Cu2+] concentrations. Therefore, the higher DNA binding ability of complex 3 did not lead to higher cleavage efficiency. These findings have been correlated to the DNA binding mode and the ability of the Cu2+ complexes to activate oxygen (O2). This work is a good example of the rational design of multinuclear Cu2+ artificial nuclease and the activity of which can be manipulated by the geometry and the number of metal centers.

Targeted Guanine Oxidation by a Dinuclear Copper(II) Complex at Single Stranded/Double Stranded DNA Junctions

A dinuclear copper(II) complex [Cu(II)2(PD'O-)(H2O)2](ClO4)3 (5) with terminal Cu(II)-H(2)O moieties and a Cu...Cu distance of 4.13 A (X-ray structure) has been synthesized and characterized by EPR spectroscopy (ferromagnetic coupling observed) and cyclic voltammetry. Dizinc(II) and mononuclear copper(II) analogues [Zn(II)2(PD'O-)(H2O)2]3+ (7) and [Cu(II)(mPD'OH)(H2O)]2+ (6), respectively, have also been synthesized and structurally characterized. Reacting 5/MPA/O(2) (MPA = 3-mercaptopropionic acid) with DNA leads to a highly specific oxidation of guanine (G) at a junction between single- and double-stranded DNA. Mass spectrometric analysis of the major products indicates a gain of +18 and +34 amu relative to initial DNA strands. The most efficient reaction requires G at the first and second unpaired positions of each strand extending from the junction. Less reaction is observed for analogous targets in which the G cluster is farther from the junction or contains less than four Gs. Consistent with our previous systems, the multinuclear copper center is required for selective reaction; mononuclear complex 6 is not effective. Hydrogen peroxide as a substitute for MPA/O2 also does not lead to activity. Structural analysis of a [Cu(II)2(PD'O-)(G)]3+ complex (8) and dizinc analogue [Zn(II)(2)(PD'O-)(G)](ClO4)3 (9) (G = guanosine) reveals coordination of the G O6 and N7 atoms with the two copper (or zinc) centers and suggests that copper-G coordination likely plays a role in recognition of the DNA target. The Cu2-O2 intermediate responsible for guanine oxidation appears to be different from that responsible for direct-strand scission induced by other multinuclear copper complexes; the likely course of reaction is discussed.