Redox-inactive Metal Ions Research Articles

Redox-inactive metal ions promoted the catalytic reactivity of non-heme manganese complexes towards oxygen atom transfer.

Redox-inactive metal ions can modulate the reactivity of redox-active metal ions in a variety of biological and chemical oxidations. Many synthetic models have been developed to help address the elusive roles of these redox-inactive metal ions. Using a non-heme manganese(II) complex as the model, the influence of redox-inactive metal ions as a Lewis acid on its catalytic efficiency in oxygen atom transfer was investigated. In the absence of redox-inactive metal ions, the manganese(II) catalyst is very sluggish, for example, in cyclooctene epoxidation, providing only 9.9% conversion with 4.1% yield of epoxide. However, addition of 2 equiv. of Al(3+) to the manganese(II) catalyst sharply improves the epoxidation, providing up to 97.8% conversion with 91.4% yield of epoxide. EPR studies of the manganese(II) catalyst in the presence of an oxidant reveal a 16-line hyperfine structure centered at g = 2.0, clearly indicating the formation of a mixed valent di-μ-oxo-bridged diamond core, Mn(III)-(μ-O)2-Mn(IV). The presence of a Lewis acid like Al(3+) causes the dissociation of this diamond Mn(III)-(μ-O)2-Mn(IV) core to form monomeric manganese(iv) species which is responsible for improved epoxidation efficiency. This promotional effect has also been observed in other manganese complexes bearing various non-heme ligands. The findings presented here have provided a promising strategy to explore the catalytic reactivity of some di-μ-oxo-bridged complexes by adding non-redox metal ions to in situ dissociate those dimeric cores and may also provide clues to understand the mechanism of methane monooxygenase which has a similar diiron diamond core as the intermediate.

Redox-inactive metal ions modulate the reactivity and oxygen release of mononuclear non-haem iron(III)-peroxo complexes.

Redox-inactive metal ions that function as Lewis acids play pivotal roles in modulating the reactivity of oxygen-containing metal complexes and metalloenzymes, such as the oxygen-evolving complex in photosystem II and its small-molecule mimics. Here we report the synthesis and characterization of non-haem iron(III)-peroxo complexes that bind redox-inactive metal ions, (TMC)Fe(III)-(μ,η(2):η(2)-O2)-M(n+) (M(n+) = Sr(2+), Ca(2+), Zn(2+), Lu(3+), Y(3+) and Sc(3+); TMC, 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane). We demonstrate that the Ca(2+) and Sr(2+) complexes showed similar electrochemical properties and reactivities in one-electron oxidation or reduction reactions. However, the properties and reactivities of complexes formed with stronger Lewis acidities were found to be markedly different. Complexes that contain Ca(2+) or Sr(2+) ions were oxidized by an electron acceptor to release O2, whereas the release of O2 did not occur for complexes that bind stronger Lewis acids. We discuss these results in the light of the functional role of the Ca(2+) ion in the oxidation of water to dioxygen by the oxygen-evolving complex.

Spectroscopic capture and reactivity of a low-spin cobalt(IV)-oxo complex stabilized by binding redox-inactive metal ions.

High-valent cobalt-oxo intermediates are proposed as reactive intermediates in a number of cobalt-complex-mediated oxidation reactions. Herein we report the spectroscopic capture of low-spin (S=1/2) Co(IV)-oxo species in the presence of redox-inactive metal ions, such as Sc(3+), Ce(3+), Y(3+), and Zn(2+), and the investigation of their reactivity in C-H bond activation and sulfoxidation reactions. Theoretical calculations predict that the binding of Lewis acidic metal ions to the cobalt-oxo core increases the electrophilicity of the oxygen atom, resulting in the redox tautomerism of a highly unstable [(TAML)Co(III)(O˙)](2-) species to a more stable [(TAML)Co(IV)(O)(M(n+))] core. The present report supports the proposed role of the redox-inactive metal ions in facilitating the formation of high-valent metal-oxo cores as a necessary step for oxygen evolution in chemistry and biology.

Tuning Reactivity and Mechanism in Oxidation Reactions by Mononuclear Nonheme Iron(IV)-Oxo Complexes

Mononuclear nonheme iron enzymes generate high-valent iron(IV)-oxo intermediates that effect metabolically important oxidative transformations in the catalytic cycle of dioxygen activation. In 2003, researchers first spectroscopically characterized a mononuclear nonheme iron(IV)-oxo intermediate in the reaction of taurine: α-ketogultarate dioxygenase (TauD). This nonheme iron enzyme with an iron active center was coordinated to a 2-His-1- carboxylate facial triad motif. In the same year, researchers obtained the first crystal structure of a mononuclear nonheme iron(IV)-oxo complex bearing a macrocyclic supporting ligand, [(TMC)Fe(IV)(O)](2+) (TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecene), in studies that mimicked the biological enzymes. With these breakthrough results, many other studies have examined mononuclear nonheme iron(IV)-oxo intermediates trapped in enzymatic reactions or synthesized in biomimetic reactions. Over the past decade, researchers in the fields of biological, bioinorganic, and oxidation chemistry have extensively investigated the structure, spectroscopy, and reactivity of nonheme iron(IV)-oxo species, leading to a wealth of information from these enzymatic and biomimetic studies. This Account summarizes the reactivity and mechanisms of synthetic mononuclear nonheme iron(IV)-oxo complexes in oxidation reactions and examines factors that modulate their reactivities and change their reaction mechanisms. We focus on several reactions including the oxidation of organic and inorganic compounds, electron transfer, and oxygen atom exchange with water by synthetic mononuclear nonheme iron(IV)-oxo complexes. In addition, we recently observed that the C-H bond activation by nonheme iron(IV)-oxo and other nonheme metal(IV)-oxo complexes does not follow the H-atom abstraction/oxygen-rebound mechanism, which has been well-established in heme systems. The structural and electronic effects of supporting ligands on the oxidizing power of iron(IV)-oxo complexes are significant in these reactions. However, the difference in spin states between nonheme iron(IV)-oxo complexes with an octahedral geometry (with an S = 1 intermediate-spin state) or a trigonal bipyramidal (TBP) geometry (with an S = 2 high-spin state) does not lead to a significant change in reactivity in biomimetic systems. Thus, the importance of the high-spin state of iron(IV)-oxo species in nonheme iron enzymes remains unexplained. We also discuss how the axial and equatorial ligands and binding of redox-inactive metal ions and protons to the iron-oxo moiety influence the reactivities of the nonheme iron(IV)-oxo complexes. We emphasize how these changes can enhance the oxidizing power of nonheme metal(IV)-oxo complexes in oxygen atom transfer and electron-transfer reactions remarkably. This Account demonstrates great advancements in the understanding of the chemistry of mononuclear nonheme iron(IV)-oxo intermediates within the last 10 years.

Modulation of Quinone PCET Reaction by Ca2+ Ion Captured by Calix[4]quinone in Water

Calix[4]arene-triacid-monoquinone (CTAQ), a quinone-containing water-soluble ionophore, was utilized to investigate how proton-coupled electron transfer (PCET) reactions of quinones were influenced by redox-inactive metal ions in aqueous environment. This ionophoric quinone derivative captured a Ca(2+) ion that drastically altered the voltammetric behavior of quinone, showing a characteristic response to pH and unique redox wave separation. Spectroelectrochemistry verified significant stabilization of the semiquinone, and electrocatalytic currents were observed in the presence of Ca(2+)-free CTAQ. Using digital simulation of cyclic voltammograms to clarify how the thermodynamic properties of quinones were altered, a simple scheme was proposed that successfully accounted for all the observations. The change induced by Ca(2+) complexation was explained on the basis of the combined effects of the electrostatic influence of the captured metal ion and hydrogen bonding of water molecules with the support of DFT calculation.

Lewis-Acid-Promoted Stoichiometric and Catalytic Oxidations by Manganese Complexes Having Cross-Bridged Cyclam Ligand: A Comprehensive Study

Redox-inactive metal ions have been recognized to be able to participate in redox metal-ion-mediated biological and chemical oxidative events; however, their roles are still elusive. This work presents how the redox-inactive metal ions affect the oxidative reactivity of a well-investigated manganese(II) with its corresponding manganese(IV) complexes having cross-bridged cyclam ligand. In dry acetone, the presence of these metal ions can greatly accelerate stoichiometric oxidations of triphenylphosphine and sulfides by the manganese(IV) complexes through electron transfer or catalytic sulfoxidations by the corresponding manganese(II) complexes with PhIO. Significantly, the rate enhancements are highly Lewis-acid strength dependent on added metal ions. These metal ions like Al(3+) can also promote the thermodynamic driving force of the Mn(IV)-OH moiety to facilitate its hydrogen abstraction from ethylbenzene having a BDE(CH) value of 85 kcal/mol, while it is experimentally limited to 80 kcal/mol for Mn(IV)-OH alone. Adding Al(3+) may also improve the manganese(II)-catalyzed olefin epoxidation with PhIO. However, compared with those in electron transfer, improvements in hydrogen abstraction and electron transfer are minor. The existence of the interaction between Lewis acid and the manganese(IV) species was evidenced by the blue shift of the characteristic absorbance of the manganese(IV) species from 554 to 537 nm and by converting its EPR signal at g = 2.01 into a hyperfine 6-line signal upon adding Al(3+) (I = 5/2). Cyclic voltammograms of the manganese(IV) complexes reveal that adding Lewis acid would substantially shift its potential to the positive direction, thus enhancing its oxidizing capability.

Redox Inactive Metal Ion Promoted CH Activation of Benzene to Phenol with PdII(bpym): Demonstrating New Strategies in Catalyst Designs

Al in: A new strategy was introduced to modify the electronics and steric hindrance of the Pd(II) ion in order to change its reactivity towards benzene hydroxylation. In trifluoroacetic acid, free Pd(II) ions provide dominantly biphenyl, with phenol as minor product. Ligation of bpym to the Pd(II) ion results in its deactivation with regard to benzene functionalization. The addition of the redox inactive Al(III) ion to the Pd(II)(bpym) complex recovers its catalytic activity, and alters the reactivity of Pd(II) ion from benzene coupling to hydroxylation.

A Mononuclear Non-Heme Manganese(IV)–Oxo Complex Binding Redox-Inactive Metal Ions

Redox-inactive metal ions play pivotal roles in regulating the reactivities of high-valent metal-oxo species in a variety of enzymatic and chemical reactions. A mononuclear non-heme Mn(IV)-oxo complex bearing a pentadentate N5 ligand has been synthesized and used in the synthesis of a Mn(IV)-oxo complex binding scandium ions. The Mn(IV)-oxo complexes were characterized with various spectroscopic methods. The reactivities of the Mn(IV)-oxo complex are markedly influenced by binding of Sc(3+) ions in oxidation reactions, such as a ~2200-fold increase in the rate of oxidation of thioanisole (i.e., oxygen atom transfer) but a ~180-fold decrease in the rate of C-H bond activation of 1,4-cyclohexadiene (i.e., hydrogen atom transfer). The present results provide the first example of a non-heme Mn(IV)-oxo complex binding redox-inactive metal ions that shows a contrasting effect of the redox-inactive metal ions on the reactivities of metal-oxo species in the oxygen atom transfer and hydrogen atom transfer reactions.

A Mononuclear Nonheme Iron(III)-Peroxo Complex Binding Redox-Inactive Metal Ions.

Redox-inactive metal ions that function as Lewis acids play pivotal roles in modulating reactivities of oxygen-containing metal complexes in a variety of biological and biomimetic reactions, including dioxygen activation/formation and functionalization of organic substrates. Mononuclear nonheme iron(III)-peroxo species are invoked as active oxygen intermediates in the catalytic cycles of dioxygen activation by nonheme iron enzymes and their biomimetic compounds. Here, we report mononuclear nonheme iron(III)-peroxo complexes binding redox-inactive metal ions, [(TMC)FeIII(O2)]+-M3+ (M3+ = Sc3+ and Y3+; TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane), which are characterized spectroscopically as a 'side-on' iron(III)-peroxo complex binding a redox-inactive metal ion, (TMC)FeIII-(μ,η2:η2-O2)-M3+ (2-M). While an iron(III)-peroxo complex, [(TMC)FeIII(O2)]+, does not react with electron donors (e.g., ferrocene), one-electron reduction of the iron(III)-peroxo complexes binding redox-inactive metal ions occurs readily upon addition of electron donors, resulting in the generation of an iron(IV)-oxo complex, [(TMC)FeIV(O)]2+ (4), via heterolytic O-O bond cleavage of the peroxide ligand. The rates of the conversion of 2-M to 4 are found to depend on the Lewis acidity of the redox-inactive metal ions and the oxidation potential of the electron donors. We have also determined the fundamental electron-transfer properties of 2-M, such as the reduction potential and the reorganization energy in electron-transfer reaction. Based on the results presented herein, we have proposed a mechanism for the reactions of 2-M and electron donors; the reduction of 2-M to the reduced species, (TMC)FeII-(O2)-M3+ (2'-M), is the rate-determining step, followed by heterolytic O-O bond cleavage of the reduced species to form 4. The present results provide a biomimetic example demonstrating that redox-inactive metal ions bound to an iron(III)-peroxo intermediate play a significant role in activating the peroxide O-O bond to form a high-valent iron(IV)-oxo species.

Heterobimetallic Complexes with MIII-(μ-OH)-MII Cores (MIII = Fe, Mn, Ga; MII = Ca, Sr, and Ba): Structural, Kinetic, and Redox Properties.

The effects of redox-inactive metal ions on dioxygen activation were explored using a new FeII complex containing a tripodal ligand with 3 sulfonamido groups. This iron complex exhibited a faster initial rate for the reduction of O2 than its MnII analog. Increases in initial rates were also observed in the presence of group 2 metal ions for both the FeII and MnII complexes, which followed the trend NMe4+ < BaII < CaII = SrII. These studies led to the isolation of heterobimetallic complexes containing FeIII-(μ-OH)-MII cores (MII = Ca, Sr, and Ba) and one with a [SrII(OH)MnIII]+ motif. The analogous [CaII(OH)GaIII]+ complex was also prepared and its solid state molecular structure is nearly identical to that of the [CaII(OH)FeIII]+ system. Nuclear magnetic resonance studies indicated that the diamagnetic [CaII(OH)GaIII]+ complex retained its structure in solution. Electrochemical measurements on the heterobimetallic systems revealed similar one-electron reduction potentials for the [CaII(OH)FeIII]+ and [SrII(OH)FeIII]+ complexes, which were more positive than the potential observed for [BaII(OH)FeIII]+. Similar results were obtained for the heterobimetallic MnII complexes. These findings suggest that Lewis acidity is not the only factor to consider when evaluating the effects of group 2 ions on redox processes, including those within the oxygen-evolving complex of Photosystem II.

Radical-Scavenging Reactions of Ascorbic Acid and Its Analogue in the Presence of a Redox-Inactive Metal Ion

Radical-Scavenging Reactions of Ascorbic Acid and Its Analogue in the Presence of a Redox-Inactive Metal Ion

Mechanisms of metal ion-coupled electron transfer

Redox inactive metal ions acting as Lewis acids can control electron transfer from electron donors (D) to electron acceptors (A) by binding to radical anions of electron acceptors which act as Lewis bases. Such electron transfer is defined as metal ion-coupled electron transfer (MCET). Mechanisms of metal ion-coupled electron transfer are classified mainly into two pathways, i.e., metal ion binding to electron acceptors followed by electron transfer (MB/ET) and electron transfer followed by metal ion binding to the resulting radical anions of electron acceptors (ET/MB). In the former case, electron transfer and the stronger binding of metal ions to the radical anions occur in a concerted manner. Examples are shown in each case to clarify the factors to control MCET reactions in both thermal and photoinduced electron-transfer reactions including back electron-transfer reactions.

Structure and dissociation characteristics of metal chloride anion clusters containing redox-active metal ions studied by laser desorption and electrospray ionization mass spectrometry and ab initio calculations

Copper chloride anion clusters with both copper oxidation states can be made by laser desorption of CuCl(2) crystals. We have used this method to study the dissociation characteristics of such cluster ions. The stability and the structure of the observed complexes were probed by ab initio calculations. These calculations show that many of these complexes are bridged structures. Thus, for the Cu(2)Cl(4) dimer anion, formally [ClCu-Cl-CuCl(2)](-) , with putative mixed copper oxidation states, the two copper ions become equivalent through bridging. Such bridging does not occur when redox inactive metal ions are present as in [ClCu-Cl-CaCl(2)](-) . By observing the dissociation characteristics of a variety of metal chloride cluster anions produced from binary mixtures, the following Cl(-) affinity order is obtained: FeCl(3) > CuCl > CaCl(2) > FeCl(2) > AgCl ≈ CuCl(2) ≈ ZnCl(2) > LiCl. Ab initio calculations on the Cl(-) affinity of selected chlorides confirm this order as do Cl(-) affinity estimates from the experimentally known vertical electron detachment energies of the superhalogens CaCl(3)(-) and LiCl(2)(-) . An equimolar mixture of CuCl(2) and FeCl(3) produces an intense cluster ion, which, from (65)Cu labeling experiments, is best described as FeCl(4)(-)···Cu(+)···(-)Cl(4) Fe, a Cu(+) bound superhalogen FeCl(4)(-) dimer. The Cu(+) ion can be replaced by the redox inactive alkali cations and by Ag(+) but these metal ion bound FeCl(4)(-) dimers show an entirely different fragmentation behavior which is attributed to the absence of bridging. Electrospray ionization (ESI) of CuCl(2) produces an extended series of (CuCl(2))(n) Cl(-) anions (n = 1-11) and so in ESI very limited reduction of Cu(2+) takes place. The (CuCl(2))(n) Cl(-) anions show an abundant dissociation via loss of neutral Cu(2)Cl(4) which according to our ab initio calculations is 9 kcal/mol more stable than two CuCl(2).

Crystal structure of a metal ion-bound oxoiron(IV) complex and implications for biological electron transfer

Critical biological electron-transfer processes involving high-valent oxometal chemistry occur widely, for example in haem proteins [oxoiron(IV); Fe(IV)(O)] and in photosystem II. Photosystem II involves Ca(2+) as well as high-valent oxomanganese cluster species. However, there is no example of an interaction between metal ions and oxoiron(IV) complexes. Here, we report new findings concerning the binding of the redox-inactive metal ions Ca(2+) and Sc(3+) to a non-haem oxoiron(IV) complex, [(TMC)Fe(IV)(O)](2+) (TMC = 1,4,8,11-tetramethyl-1,4,8,11-tetraazacyclotetradecane). As determined by X-ray diffraction analysis, an oxo-Sc(3+) interaction leads to a structural distortion of the oxoiron(IV) moiety. More importantly, this interaction facilitates a two-electron reduction by ferrocene, whereas only a one-electron reduction process occurs without the metal ions. This control of redox behaviour provides valuable mechanistic insights into oxometal redox chemistry, and suggests a possible key role that an auxiliary Lewis acid metal ion could play in nature, as in photosystem II.

Electrochemistry and Spectroelectrochemistry of β,β′-Fused Quinoxalinoporphyrins and Related Extended Bis-porphyrins with Co(III), Co(II), and Co(I) Central Metal Ions

A series of cobalt(II) and cobalt(III) porphyrins with fused quinoxaline rings at one or more beta,beta'-pyrrolic units of the macrocycle were synthesized and characterized as to their electrochemical properties in nonaqueous media. Their UV-visible spectra were also measured before and during oxidation or reduction in a thin-layer cell. The investigated quinoxalinoporphyrins are represented as (PQ)Co, (QPQ)CoCl, (PQ(2))CoCl, Co(P)-TA-(P)Co, and Co(PQ)-(QP)Co, where PQ = the dianion of 5,10,15,20-tetrakis(3,5-di-tert-butylphenyl)-quinoxalino[2,3-b']porphyrin, QPQ = the dianion of the corresponding linear bisquinoxalino[2,3-b':12,13-b'']porphyrin, PQ(2) = the dianion of the corresponding corner bisquinoxalino[2,3-b':7,8-b'']porphyrin, and (P)-TA-(P) = the tetraanion of the bis-porphyrin with 5,10,15,20-tetrakis(3,5-di-tert-butylphenyl)porphyrins fused at opposite ends of tetraazaanthracene. (P)Co and (P)CoCl were also characterized where P = the dianion of 5,10,15,20-tetrakis(3,5-di-tert-butylphenyl)porphyrin. Each compound could be cycled between their Co(III), Co(II), and Co(I) forms under the application of a given oxidizing or reducing potential, although a one-electron reduction of the Co(II) quinoxalinoporphyrins led to a product with mixed Co(I) and porphyrin pi-anion radical character followed by generation of a pure Co(I) pi-anion radical species at more negative potentials. The effect of the position and number of quinoxaline groups on the redox potentials and mechanisms of each electron transfer were elucidated, and comparisons made to structurally similar compounds containing both redox active and redox inactive central metal ions. Surprisingly, the position and number of quinoxaline groups on the macrocycle has little or no effect on the redox potentials for the Co(II) --> Co(III) or Co(III) --> Co(II) processes, but this is not the case for other electron transfer reactions where significant differences are seen between the examined compounds. Significant interactions are also observed between the two porphyrin macrocycles of the laterally bridged dicobalt(II) bis-porphyrin dyad Co(P)-TA-(P)Co in its singly and doubly reduced form, but only weak interactions are seen between the two Co(PQ) units of the single bond biquinolalinyl-bridged dicobalt(II) bis-porphyrin dyad Co(PQ)-(QP)Co.

Tuning the Photophysical Behavior of Luminescent Cyclam Derivatives by Cation Binding and Excited State Redox Potential

The emission from two photoactive 14-membered macrocyclic ligands, 6-((naphthalen-1-ylmethyl)-amino)-trans-6,13-dimethyl-13-amino-1,4,8,11-tetraaza-cyclotetradecane (L1) and 6-((anthracen-9-ylmethyl)-amino)-trans-6,13-dimethyl-13-amino-1,4,8,11-tetraaza-cyclotetradecane (L2) is strongly quenched by a photoinduced electron transfer (PET) mechanism involving amine lone pairs as electron donors. Time-correlated single photon counting (TCSPC), multiplex transient grating (TG), and fluorescence upconversion (FU) measurements were performed to characterize this quenching mechanism. Upon complexation with the redox inactive metal ion, Zn(II), the emission of the ligands is dramatically altered, with a significant increase in the fluorescence quantum yields due to coordination-induced deactivation of the macrocyclic amine lone pair electron donors. For [ZnL2]2+, the substituted exocyclic amine nitrogen, which is not coordinated to the metal ion, does not quench the fluorescence due to an inductive effect of the proximal divalent metal ion that raises the ionization potential. However, for [ZnL1]2+, the naphthalene chromophore is a sufficiently strong excited-state oxidant for PET quenching to occur.

Zinc(II) Protects Against Metal-Mediated Free Radical Induced Damage: Studies on Single and Double-Strand DNA Breakage

M13 DNA was used as a source for single and double-stranded DNA. Free radical-induced damage to single and double stranded DNA was caused by ascorbate/iron and ascorbate/copper oxidative systems. The degree of breakage was estimated by running samples on an agarose gel and staining with ethidium bromide, followed by photographic analysis. DNA breakage was dependent on time and concentration of iron or copper ions. Zinc ions protected against damage caused by iron/ascorbate both to single-stranded and double-stranded DNA. In contrast, in the copper/ascorbate system zinc ions protected only against the double-stranded DNA (replicative form of M13) breakage, and not against copper-mediated single-stranded DNA breakages. It seemed to amplify the efficiency of breakage. The protection provided to the replicative form in the copper/ascorbate system is much less effective than the protection to DNA in the iron/ascorbate system. These results support the notion that redox-inactive metal ions, that compete for iron or copper binding sites, could provide protection against transition metal-mediated and free radical-induced damage.

Protection Against Free Radical-Induced and Transition Metal-Mediated Damage: The Use of “Pull” and “Push” Mechanisms

Free radicals have been incriminated in a variety of injurious processes including the toxicity of the herbicide paraquat and the damage following ischemia and reperfusion of different organs. Based on the assumption that iron and copper could serve as mediators for the transformation of relatively low reactive species (such as superoxide radicals, hydrogen peroxide, ascorbate, and others) to the highly reactive species, in the site-specific metal-mediated mechanism, two new modes for intervention have been tried out. The first is the introduction of specific chelators that "pull" out redox-active and available metals, and by this reduce the apparent damage. Desferrioxamine was shown to protect bacterial cells and mammals against the poisonous effects of paraquat. Using the retrogradly perfused isolated rat heart, we have demonstrated that the chelator neocuproine, which effectively binds both iron and copper provides a major protection against hydrogen peroxide-induced cardiac damage and against ischemia/reperfusion-induced arrhythmias. Likewise, TPEN a heavy metal chelator, provides almost total (greater than 90%) protection against ischemia/reperfusion-induced arrhythmias. The other mode of intervention is the use of redox-inactive metal ions that could compete for the binding sites of iron and copper, and by this "push" these metal ions out, lead to their displacement, and divert the site of free radical attack. Applying Zn(II) complexes provided a marked protection against metal mediated free radical-induced damage in the copper-mediated paraquat toxicity to E. coli, and in the arrhythmias induced by ischemia and reperfusion. It is proposed that the complex zinc-desferrioxamine would be the ultimate protector being effective by both the "pull" and "push" mechanisms.