Increasing the electron donation in a dinucleating ligand family: molecular and electronic structures in a series of CoIICoII complexes.

We have developed a family of dinucleating ligands with varying terminal donors to generate dinuclear peroxo and high-valent complexes and to correlate their stabilities and reactivities with their molecular and electronic structures as a function of the terminal donors. It appears that the electron-donating ability of the terminal donors is an important handle for controlling these stabilities and reactivities. Here, we present the synthesis of a new dinucleating ligand with potentially strong donating terminal imidazole donors. As CoII ions are sensitive to variations in donor strength in terms of coordination number, magnetism, UV-Vis-NIR spectra, redox potentials, we probe the electron donation ability of this new ligand in CoIICoII complexes in comparison to the parent CoIICoII complexes with terminal pyridine donors and we synthesize the analogous CoIICoII complexes with terminal 6-methylpyridines and methoxy-substituted pyridines. The molecular structures show indeed strong variations in coordination numbers and bond lengths. These differences in the molecular structures are reflected in the magnetic properties and in the d-d transitions demonstrating that the molecular structures remain intact upon dissolution. The redox potentials are analyzed with respect to the electron donation ability and are the only handle to observe an effect of the methoxy-substituted pyridines. All data taken together show the following order of electron donating ability for the terminal donors: 6-methylpyridines ≪ pyridines < methoxy-substituted pyridines ≪ imidazoles.

Generation and Reactivity of µ-1,2-Peroxo CuIICuII and Bis-µ-oxo CuIIICuIII Species and Catalytic Hydroxylation of Benzene to Phenol with Hydrogen Peroxide.

Tetradentate-N4 ligands stabilize dinuclear {CuII(µ-1,2-peroxo)CuII} and {CuIII(µ-O)2CuIII} species, and CuII complexes of these ligands were reported to catalyze the oxidation of benzene with H2O2. Here, we report {CuII(µ-1,2-peroxo)CuII} and {CuIII(µ-O)2CuIII} intermediates of dinucleating bis(tetradentate-N4) ligands depending on the absence or presence of 6-methyl substituents on the terminal pyridine donors, respectively, generated either from {CuICuI} precursors with O2 or from {CuIICuII} precursors with H2O2 and NEt3. Both intermediates are not stable even at low temperatures, but they show no electrophilic HAT reactivity with DHA. Catalytic investigations on the hydroxylation of benzene with excess H2O2 between 30 and 50 °C indicate that both radical-based and {Cu2On}-based mechanisms depend strongly on the catalytic conditions. In the presence of a radical scavenger, TONs of ∼920/∼720 have been achieved without/with the 6-methyl group of the ligand. Although {CuII(µ-OH)CuII} reacts with excess H2O2 at -40 °C to {CuII(OOH)}2 species, these are only stable for seconds at 20 °C and cannot account for catalytic oxidations over a period of 24 h at 30-50 °C.

Direct and remote control of electronic structures and redox potentials in µ-oxo diferric complexes.

Non-heme diiron enzymes activate O2 for the oxidation of substrates in the form of peroxo FeIII2 or high-valent FeIV2 intermediates. We have developed a dinucleating bis(tetradentate) ligand system that stabilizes peroxo and hydroperoxo FeIII2 complexes with terminal 6-methylpyridine donors, while the peroxo FeIII2 intermediate is reactive with terminal pyridine donors presumably via conversion to a fluent high-valent FeIV2 intermediate. We present here a derivative with electron-donating methoxy substituents at the pyridine donors and its diferric complexes with an {FeIIIX(µ-O)FeIIIX} (X- = Cl-, OAc-, and OH-) or an {FeIII(µ-O)(µ-OAc)FeIII} core. The complex-induced oxidation of EtOH with H2O2 provides µ-OAc-, and in acetone, the complex with mixed OH-/OAc- exogenous donors is obtained. Both reactivities indicate a reactive fluent peroxo FeIII2 intermediate. The coupling constant J and the LMCT transitions are insensitive to the nature of the directly bound ligands X- and reflect mainly the electronic structure of the central {FeIII(µ-O)FeIII} core, while Mössbauer spectroscopy and d-d transitions probe the local FeIII sites. The remote methoxy substituents decrease the potential for the oxidation to FeIV by ∼100 mV, while directly bound OH- in {FeIII(OH)(µ-O)FeIII(OH)} with a short 1.91 Å FeIII-OOH bond decreases the potential by 590 mV compared to {FeIII(OAc)(µ-O)FeIII(OAc)} with a 2.01 Å FeIII-OOAc bond. Interestingly, this FeIII-OH bond is even shorter (1.87 Å) in the mixed OH-/OAc- complex but the potential is the mean value of the potentials of the OH-/OH- and OAc-/OAc- complexes, thus reflecting the electron density of the central {FeIII(µ-O)FeIII} core and not of the local FeIII-OH unit.

Reactivities and Electronic Structures of µ-1,2-Peroxo and µ-1,2-Superoxo CoIIICoIII Complexes: Electrophilic Reactivity and O2 Release Induced by Oxidation.

Peroxo complexes are key intermediates in water oxidation catalysis (WOC). Cobalt plays an important role in WOC, either as oxides CoOx or as {CoIII(µ-1,2-peroxo)CoIII} complexes, which are the oldest peroxo complexes known. The oxidation of {CoIII(µ-1,2-peroxo)CoIII} complexes had usually been described to form {CoIII(µ-1,2-superoxo)CoIII} complexes; however, recently the formation of {CoIV(µ-1,2-peroxo)CoIII} species were suggested. Using a bis(tetradentate) dinucleating ligand, we present here the synthesis and characterization of {CoIII(µ-1,2-peroxo)(µ-OH)CoIII} and {CoIII(µ-OH)2CoIII} complexes. Oxidation of {CoIII(µ-1,2-peroxo)(µ-OH)CoIII} at -40 °C in CH3CN provides the stable {CoIII(µ-1,2-superoxo)(µ-OH)CoIII} species and activates electrophilic reactivity. Moreover, {CoIII(µ-1,2-peroxo)(µ-OH)CoIII} catalyzes water oxidation, not molecularly but rather via CoOx films. While {CoIII(µ-1,2-peroxo)(µ-OH)CoIII} can be reversibly deprotonated with DBU at -40 °C in CH3CN, {CoIII(µ-1,2-superoxo)(µ-OH)CoIII} undergoes irreversible conversions upon reaction with bases to a new intermediate that is also the decay product of {CoIII(µ-1,2-superoxo)(µ-OH)CoIII} in aqueous solution at pH > 2. Based on a combination of experimental methods, the new intermediate is proposed to have a {CoII(µ-OH)CoIII} core formed by the release of O2 from {CoIII(µ-1,2-superoxo)(µ-OH)CoIII} confirmed by a 100% yield of O2 upon photocatalytic oxidation of {CoIII(µ-1,2-peroxo)(µ-OH)CoIII}. This release of O2 by oxidation of a peroxo intermediate corresponds to the last step in molecular WOC.

Generation of a µ-1,2-hydroperoxo FeIIIFeIII and a µ-1,2-peroxo FeIVFeIII Complex.

µ-1,2-Peroxo-diferric intermediates (P) of non-heme diiron enzymes are proposed to convert upon protonation either to high-valent active species or to activated P' intermediates via hydroperoxo-diferric intermediates. Protonation of synthetic µ-1,2-peroxo model complexes occurred at the µ-oxo and not at the µ-1,2-peroxo bridge. Here we report a stable µ-1,2-peroxo complex {FeIII(µ-O)(µ-1,2-O2)FeIII} using a dinucleating ligand and study its reactivity. The reversible oxidation and protonation of the µ-1,2-peroxo-diferric complex provide µ-1,2-peroxo FeIVFeIII and µ-1,2-hydroperoxo-diferric species, respectively. Neither the oxidation nor the protonation induces a strong electrophilic reactivity. Hence, the observed intramolecular C-H hydroxylation of preorganized methyl groups of the parent µ-1,2-peroxo-diferric complex should occur via conversion to a more electrophilic high-valent species. The thorough characterization of these species provides structure-spectroscopy correlations allowing insights into the formation and reactivities of hydroperoxo intermediates in diiron enzymes and their conversion to activated P' or high-valent intermediates.

Evaluation of the binding mode of a cytotoxic dinuclear nickel complex to two neighboring phosphates of the DNA backbone.

A family of dinuclear complexes based on 2,7-disubstituted 1,8-naphthalenediol-ligands has been designed to bind covalently to two neighboring phosphate diester groups in the backbone of DNA. The dinuclear CuII and NiII complexes bind to DNA resulting in the inhibition of DNA synthesis in PCR experiments and in a cytotoxicity that is stronger for human cancer cells than for human stem cells of the same proliferation rate. These experiments support but cannot prove that the dinuclear complexes bind as intended to two neighboring phosphate ester groups of the DNA backbone. Here, we evaluate the potential binding mode of the cytotoxic dinuclear NiII complex using simple phosphate diester models (dimethyl phosphate and diphenyl phosphate). Depending on the reaction conditions, the phosphate diesters bind to the NiII ions in a bridging or in a terminal coordination mode. The latter occurs by substitution of two coordinated acetates by the phosphate diesters. This reaction has been followed by NMR spectroscopy, which demonstrates that the substitution of acetate by phosphate is thermodynamically strongly favored, while the exchange with excess phosphate is fast on the NMR time scale. The molecular structure of the NiII complex with two coordinated diphenyl phosphates served as a model for the computational evaluation of the binding to the DNA backbone. This combined experimental and computational study suggests a monodentate coordination mode of the DNA phosphate diesters to the NiII ions that is assisted by hydrogen bonds with water ligands.

Rational Design of a Confacial Pentaoctahedron: Anisotropic Exchange in a Linear ZnII FeIII FeIII FeIII ZnII Complex.

The first confacial pentaoctahedron comprised of transition metal ions namely ZnII FeIII A FeIII B FeIII A ZnII has been synthesized by using a dinucleating nonadentate ligand. The face-sharing bridging mode enforces short ZnII ⋅⋅⋅FeIII A and FeIII A ⋅⋅⋅FeIII B distances of 2.83 and 2.72 Å, respectively. Ab-initio CASSCF/NEVPT2 calculations provide significant negative zero-field splittings for FeIII A and FeIII B with |DA |>|DB | with the main component along the C3 axis. Hence, a spin-Hamiltonian comprised of anisotropic exchange, zero-field, and Zeeman term was employed. This allowed by following the boundary conditions from the theoretical results the simulation in a theory-guided parameter determination with Jxy =+0.37, Jz =-0.32, DA =-1.21, EA =-0.24, DB =-0.35, and EB =-0.01 cm-1 supported by simulations of high-field magnetic Mössbauer spectra recorded at 2 K. The weak but ferromagnetic FeIII A FeIII B interaction arises from the small bridging angle of 84.8° being at the switch from anti- to ferromagnetic for the face-sharing bridging mode.

Catalytic H2O2 Activation by a Diiron Complex for Methanol Oxidation.

In nature, C-H bond oxidation of CH4 involves a peroxo intermediate that decays to the high-valent active species of either a "closed" {FeIV(µ-O)2FeIV} core or an "open" {FeIV(O)(µ-O)FeIV(O)} core. To mimic and to obtain more mechanistic insight in this reaction mode, we have investigated the reactivity of the bioinspired diiron complex [(susan){Fe(OH)(µ-O)Fe(OH)}]2+ [susan = 4,7-dimethyl-1,1,10,10-tetrakis(2-pyridylmethyl)-1,4,7,10-tetraazadecane], which catalyzes CH3OH oxidation with H2O2 to HCHO and HCO2H. The kinetics is faster in the presence of a proton. 18O-labeling experiments show that the active species, generated by a decay of the initially formed peroxo intermediate [(susan){FeIII(µ-O)(µ-O2)FeIII}]2+, contains one reactive oxygen atom from the µ-oxo and another from the µ-peroxo bridge of its peroxo precursor. Considering an FeIVFeIV active species, a "closed" {FeIV(µ-O)2FeIV} core explains the observed labeling results, while a scrambling of the terminal and bridging oxo ligands is required to account for an "open" {FeIV(O)(µ-O)FeIV(O)} core.

Stronger Cytotoxicity for Cancer Cells Than for Fast Proliferating Human Stem Cells by Rationally Designed Dinuclear Complexes.

Cytostatic metallo-drugs mostly bind to the nucleobases of DNA. A new family of dinuclear transition metal complexes was rationally designed to selectively target the phosphate diesters of the DNA backbone by covalent bonding. The synthesis and characterization of the first dinuclear NiII2 complex of this family are presented, and its DNA binding and interference with DNA synthesis in polymerase chain reaction (PCR) are investigated and compared to those of the analogous CuII2 complex. The NiII2 complex also binds to DNA but forms fewer intermolecular DNA cross-links, while it interferes with DNA synthesis in PCR at lower concentrations than CuII2. To simulate possible competing phosphate-based ligands in vivo, these effects have been studied for both complexes with 100-200-fold excesses of phosphate and ATP, which provided no disturbance. The cytotoxicity of both complexes has been studied for human cancer cells and human stem cells with similar rates of proliferation. CuII2 shows the lowest IC50 values and a remarkable preference for killing the cancer cells. Three different assays show that the CuII2 complex induces apoptosis in cancer cells. These results are discussed to gain insight into the mechanisms of action and demonstrate the potential of this family of dinuclear complexes as anticancer drugs acting by a new binding target.

Proof of Phosphate Diester Binding Ability of Cytotoxic DNA-Binding Complexes.

We have rationally designed a family of dinuclear transition-metal complexes to bind two neighboring phosphate diester groups of DNA. The two metal ions are positioned at the distance of two neighboring phosphate diesters in DNA of 6-7 Å by a 1,8-naphthalenediol backbone. Two sterically demanding dipicolylamine pendant arms in the 2 and 7 positions stabilize coordination of the metal ions and prevent coordination to the less exposed nucleobases of DNA. Although the dinuclear NiII2 and CuII2 bind to DNA, inhibit DNA synthesis, and preferentially kill human cancer cells over fast proliferating human stem cells, the DNA binding mode was elusive. Here, we prove the principle phosphate diester binding ability of this family of dinuclear complexes by a new dinuclear NiII2 complex with dibenzimidazolamine pendant arms. The distance of the oxygen atoms of the coordinated phosphate diesters of 6.5 Å confirms the initial design and binding ability to two neighboring phosphate diesters of the DNA backbone. Moreover, the facile exchange of coordinated acetates by phosphate diesters indicates a preferential binding to phosphate diesters.

Rational Improvement of Single-Molecule Magnets by Enforcing Ferromagnetic Interactions.

The anisotropy barrier of polynuclear single-molecule magnets is expected to be higher with less tunneling the better stabilized the spin ground state is so that less MS mixing in the ground state and with excited spin states occur. We have realized this experimentally in two structurally related heptanuclear SMMs: the triplesalen-based [MnIII 6 CrIII ]3+ and the triplesalalen-based *[MnIII 6 CrIII ]3+ . The ligand system triplesalen was developed to enforce ferromagnetic interactions by the spin-polarization mechanism. However, we found weak antiferromagnetic couplings, that we assigned to an inefficient spin-polarization by a heteroradialene formation. To prevent this heteroradialene formation, the triplesalalen ligand H6 talalen t Bu 2 was designed. Here, we present the building block [(talalen t Bu 2 )MnIII 3 ]3+ and its application for the assembly of [{(talalen t Bu 2 )MnIII 3 }2 {CrIII (CN)6 }]3+ (=*[MnIII 6 CrIII ]3+ ). Both the trinuclear and heptanuclear complexes are SMMs. The comparison to the related triplesalen complex [(feld t Bu 2 )MnIII 3 ]3+ proves the absence of heteroradialene character and the enforcement of ferromagnetic MnIII -MnIII interactions in the (talalen t Bu 2 )6- complexes. This results in an increase of the barrier for spin reversal Ueff from 25 K in the triplesalen-based [MnIII 6 CrIII ]3+ SMMs to 37 K in the triplesalalen-based *[MnIII 6 CrIII ]3+ SMM proving the success of our concept. Based on this study, the next step in the rational improvement of our SMMs is discussed.

Two Unsupported Terminal Hydroxido Ligands in a µ-Oxo-Bridged Ferric Dimer: Protonation and Kinetic Lability Studies.

The dinuclear complex [(susan){FeIII(OH)(µ-O)FeIII(OH)}](ClO4)2 (Fe2(OH)2(ClO4)2; susan = 4,7-dimethyl-1,1,10,10-tetra(2-pyridylmethyl)-1,4,7,10-tetraazadecane) with two unsupported terminal hydroxido ligands and for comparison the fluorido-substituted complex [(susan){FeIIIF(µ-O)FeIIIF}](ClO4)2 (Fe2F2(ClO4)2) have been synthesized and characterized in the solid state as well in acetonitrile (CH3CN) and water (H2O) solutions. The Fe-OH bonds are strongly modulated by intermolecular hydrogen bonds (1.85 and 1.90 Å). UV-vis-near-IR (NIR) and Mössbauer spectroscopies prove that Fe2F22+ and Fe2(OH)22+ retain their structural integrity in a CH3CN solution. The OH- ligand induces a weaker ligand field than the F- ligand because of stronger π donation. This increased electron donation shifts the potential for the irreversible oxidation by 610 mV cathodically from 1.40 V in Fe2F22+ to 0.79 V versus Fc+/Fc in Fe2(OH)22+. Protonation/deprotonation studies in CH3CN and aqueous solutions of Fe2(OH)22+ provide two reversible acid-base equilibria. UV-vis-NIR, Mössbauer, and cryo electrospray ionization mass spectrometry experiments show conservation of the mono(µ-oxo) bridging motif, while the terminal OH- ligands are protonated to H2O. Titration experiments in aqueous solution at room temperature provide the p Ka values as p K1 = 4.9 and p K2 = 6.8. Kinetic studies by temperature- and pressure-dependent 17O NMR spectrometry revealed for the first time the water-exchange parameters [ kex298 = (3.9 ± 0.2) × 105 s-1, Δ H⧧ = 39.6 ± 0.2 kJ mol-1, Δ S⧧ = -5.1 ± 1 J mol-1 K-1, and Δ V⧧ = +3.0 ± 0.2 cm3 mol-1] and the underlying Id mechanism for a {FeIII(OH2)(µ-O)FeIII(OH2)} core. The same studies suggest that in solution the monoprotonated {FeIII(OH)(µ-O)FeIII(OH2)} complex has µ-O and µ-O2H3 bridges between the two Fe centers.

Reversible Carboxylate Shift in a µ-Oxo Diferric Complex in Solution by Acid-/Base-Addition.

A reversible carboxylate shift has been observed in a µ-oxo diferric complex in solution by UV-vis-NIR and FTIR spectroscopy triggered by the addition of a base or an acid. A terminal acetate decoordinates upon the addition of a proton, resulting in a shift of the remaining terminal acetato to a µ-η1:η1 bridge. The addition of a base restores the original structure containing only terminal acetates. The implications for metalloenzymes with carboxylate-bridged nonheme diiron active sites are discussed.

Suppression of Magnetic Quantum Tunneling in a Chiral Single-Molecule Magnet by Ferromagnetic Interactions.

Single-molecule magnets (SMMs) retain a magnetization without applied magnetic field for a decent time due to an energy barrier U for spin-reversal. Despite the success to increase U, the difficult to control magnetic quantum tunneling often leads to a decreased effective barrier Ueff and a fast relaxation. Here, we demonstrate the influence of the exchange coupling on the tunneling probability in two heptanuclear SMMs hosting the same spin-system with the same high spin ground state St = 21/2. A chirality-induced symmetry reduction leads to a switch of the MnIII-MnIII exchange from antiferromagnetic in the achiral SMM [MnIII6CrIII]3+ to ferromagnetic in the new chiral SMM RR[MnIII6CrIII]3+. Multispin Hamiltonian analysis by full-matrix diagonalization demonstrates that the ferromagnetic interactions in RR[MnIII6CrIII]3+ enforce a well-defined St = 21/2 ground state with substantially less mixing of MS substates in contrast to [MnIII6CrIII]3+ and no tunneling pathways below the top of the energy barrier. This is experimentally verified as Ueff is smaller than the calculated energy barrier U in [MnIII6CrIII]3+ due to tunneling pathways, whereas Ueff equals U in RR[MnIII6CrIII]3+ demonstrating the absence of quantum tunneling.

A Mixed-Valence Fluorido-Bridged FeIIFeIII Complex.

The reaction of the new dinucleating ligand susan6-Me with Fe(BF4)2·6H2O results in formation of the homovalent FeIIFeII complex [(susan6-Me){FeII(µ-F)2FeII}]2+ and the mixed-valence FeIIFeIII complex [(susan6-Me){FeIIF(µ-F)FeIIIF}]2+ depending on the absence or presence of dioxygen, respectively. Complex [(susan6-Me){FeIIF(µ-F)FeIIIF}]2+ is the first molecular mixed-valence complex with a fluorido bridge. The short FeIII-µ-F bond of 1.87 Å causes a large reorganization energy, resulting in a localized class II system with an intervalence charge-transfer band of high energy at 10000 cm-1.

Design and synthesis of a dinucleating ligand system with varying terminal donor functions that provides no bridging donor and its application to the synthesis of a series of Fe(III)-µ-O-Fe(III) complexes.

Based on a rational ligand design for stabilizing high-valent {Fe(µ-O)2Fe} cores, a new family of dinucleating bis(tetradentate) ligands with varying terminal donor functions has been developed: redox-inert biomimetic carboxylates in H4julia, pyridines in susan, and phenolates in H4hilde(Me2). Based on a retrosynthetic analysis, the ligands were synthesized and used for the preparation of their diferric complexes [(julia){Fe(OH2)(µ-O)Fe(OH2)}]·6H2O, [(julia){Fe(OH2)(µ-O)Fe(OH2)}]·7H2O, [(julia){Fe(DMSO)(µ-O)Fe(DMSO)}]·3DMSO, [(hilde(Me2)){Fe(µ-O)Fe}]·CH2Cl2, [(hilde(Me2)){FeCl}2]·2CH2Cl2, [(susan){FeCl(µ-O)FeCl}]Cl2·2H2O, [(susan){FeCl(µ-O)FeCl0.75(OCH3)0.25}](ClO4)2·0.5MeOH, and [(susan){FeCl(µ-O)FeCl}](ClO4)2·0.5EtOH, which were characterized by single-crystal X-ray diffraction, FTIR, UV-Vis-NIR, Mössbauer, magnetic, and electrochemical measurements. The strongly electron-donating phenolates afford five-coordination, while the carboxylates and pyridines lead to six-coordination. The analysis of the ligand conformations demonstrates a strong flexibility of the ligand backbone in the complexes. The different hydrogen-bonding in the secondary coordination sphere of [(julia){Fe(OH2)(µ-O)Fe(OH2)}] influences the C-O, C[double bond, length as m-dash]O, and Fe-O bond lengths and is reflected in the FTIR spectra. The physical properties of the central {Fe(µ-O)Fe} core (d-d, µ-oxo → Fe(III) CT, νas(Fe-O-Fe), J) are governed by the differences in terminal ligands - Fe(III) bonds: strongly covalent π-donation with phenolates, less covalent π-donation with carboxylates, and π-acceptation with pyridines. Thus, [(susan){FeCl(µ-O)FeCl}](2+) is oxidized at 1.48 V vs. Fc(+)/Fc, which is shifted to 1.14 V vs. Fc(+)/Fc by methanolate substitution, while [(julia){Fe(OH2)(µ-O)Fe(OH2)}] is oxidized ≤1 V vs. Fc(+)/Fc. [(hilde(Me2)){Fe(µ-O)Fe}] is oxidized at 0.36 V vs. Fc(+)/Fc to a phenoxyl radical. The catalytic oxidation of cyclohexane with TONs up to 39.5 and 27.0 for [(susan){FeCl(µ-O)FeCl}](2+) and [(hilde(Me2)){Fe(µ-O)Fe}], respectively, indicates the potential to form oxidizing intermediates.

Enhancing the ferromagnetic coupling in extended phloroglucinol complexes by increasing the metal SOMO-ligand overlap: synthesis and characterization of a trinuclear Co(II)(3) triplesalophen complex.

The triplesalophen complex [(baron(Me))Co(II)(3)] has been synthesized and characterized. The low-spin Co(II) ions possess an (2)A2 ground state with the magnetic orbitals of dyz type. These are well oriented for a strong π overlap with the bridging phloroglucinol, which results in the strongest ferromagnetic interactions by the spin-polarization mechanism for a 3d phloroglucinol complex.

Rational design of a cytotoxic dinuclear Cu2 complex that binds by molecular recognition at two neighboring phosphates of the DNA backbone.

The mechanism of the cytotoxic function of cisplatin and related anticancer drugs is based on their binding to the nucleobases of DNA. The development of new classes of anticancer drugs requires establishing other binding modes. Therefore, we performed a rational design for complexes that target two neighboring phosphates of the DNA backbone by molecular recognition resulting in a family of dinuclear complexes based on 2,7-disubstituted 1,8-naphthalenediol. This rigid backbone preorganizes the two metal ions for molecular recognition at the distance of two neighboring phosphates in DNA of 6-7 Å. Additionally, bulky chelating pendant arms in the 2,7-position impede nucleobase complexation by steric hindrance. We successfully synthesized the Cu(II)2 complex of the designed family of dinuclear complexes and studied its binding to dsDNA by independent ensemble and single-molecule methods like gel electrophoresis, precipitation, and titration experiments followed by UV-vis spectroscopy, atomic force microscopy (AFM), as well as optical tweezers (OT) and magnetic tweezers (MT) DNA stretching. The observed irreversible binding of our dinuclear Cu(II)2 complex to dsDNA leads to a blocking of DNA synthesis as studied by polymerase chain reactions and cytotoxicity for human cancer cells.

Aromatic versus heteroradialene character in extended thiophloroglucinol ligands and their trinuclear nickel(II) complexes.

Extended phloroglucinol ligands and complexes are best described as nonaromatic heteroradialenes. Herein, the electronic structures of extended thiophloroglucinol ligands and their Ni(II) 3 complexes are evaluated by comparison to their phloroglucinol analogs by means of NMR, FTIR, UV/Vis, and structural parameters. To provide a full set of compounds for this comparison of S versus O substitution, a new triplesalen ligand, its Ni(II) 3 complex, and a new thiophloroglucinol were synthesized. (1) H and (15) N NMR chemical shifts and coupling constants prove that the thiophloroglucinol ligands exist as the N-protonated and not the O-protonated tautomer. (13) C and (15) N NMR chemical shifts and structural parameters further demonstrated that the extended thiophloroglucinol ligands must be described with a predominant thione-enamine (heteroradialene) character despite the participation of a CS double bond. In the Ni(II) 3 complexes, this heteroradialene character is reduced but still predominant.

Switching from antiferromagnetic to ferromagnetic coupling in heptanuclear [M(t)6M(c)](n+) complexes by going from an achiral to a chiral triplesalen ligand.

The chiral triplesalen ligand H6chand(RR) has been used to synthesize the chiral heptanuclear complexes [{(chand(RR))Mn(III)3}2{Fe(II)(CN)6}](ClO4)2 ((RR)[Mn(III)6Fe(II)](ClO4)2) and [{(chand(RR))Fe(III)3}2{Fe(II)(CN)6}](ClO4)2 ((RR)[Fe(III)6Fe(II)](ClO4)2), which have been characterized by single-crystal X-ray diffraction, mass spectrometry, elemental analysis, FT-IR, Mössbauer, and UV-vis spectroscopies, electrochemistry, as well as DC and AC magnetic susceptibility measurements. The half-wave potential of the Fe(III)/Fe(II) couple in (RR)[Mn(III)6Fe(II)](2+) and (RR)[Fe(III)6Fe(II)](2+) is E1/2 = +0.21 and +0.75 V vs. Fc(+)/Fc, respectively, which (i) corresponds to a strong stabilization of the reduced Fe(II) species compared to the redox couple of free [Fe(II/III)(CN)6](4-/3-) and (ii) indicates a significant difference of the electronic coupling with the {(chand(RR))M(t)}(3+) units (M(t) = Mn(III), Fe(III)). Analysis of the DC magnetic data (µeffvs. T, VTVH) of both complexes by a full-matrix diagonalization of the spin-Hamiltonian including isotropic exchange, zero-field splitting with full consideration of the relative orientation of the D tensors and Zeeman interactions reveals ferromagnetic interactions of JMn-Mn = +0.17 ± 0.02 cm(-1) with DMn = -3.4 ± 0.3 cm(-1) for (RR)[Mn(III)6Fe(II)](2+) and JFe-Fe = +0.235 ± 0.005 cm(-1) with DFe = 0 for (RR)[Fe(III)6Fe(II)](2+). The comparison of the molecular structures of (RR)[Mn(III)6Fe(II)](2+) and (RR)[Fe(III)6Fe(II)](2+) with those of the heptanuclear complexes [M(t)6M(c)](n+) using the achiral triplesalen ligand (talen(t-Bu2))(6-) reveals significant differences in the ligand folding, smaller C-C bond distances in the central phloroglucinol ring and larger HOMA values. This indicates more aromatic character and less heteroradialene contribution in (RR)[Mn(III)6Fe(II)](2+) and (RR)[Fe(III)6Fe(II)](2+), which explains the switching from antiferromagnetic coupling in [M(t)6M(c)](n+) to ferromagnetic coupling in (RR)[M(t)6M(c)](n+) by a stronger contribution of the spin-polarization mechanism. This establishes a magnetostructural correlation between the structural parameters describing the aromaticity of the central phloroglucinol unit and the observed exchange couplings JMn-Mn.