We report the characterization and solution chemistry of a series of Fe(II) complexes based on the pentadentate ligands N4Py (1,1-di(pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)methanamine), MeN4Py (1,1-di(pyridin-2-yl)-N,N-bis(pyridin-2-ylmethyl)ethanamine), and the tetradentate ligand Bn-N3Py (N-benzyl-1,1-di(pyridin-2-yl)-N-(pyridin-2-ylmethyl)methanamine) ligands, i.e., [Fe(N4Py)(CH(3)CN)](ClO(4))(2) (1), [Fe(MeN4Py)(CH(3)CN)](ClO(4))(2) (2), and [Fe(Bn-N3Py)(CH(3)CN)(2)](ClO(4))(2) (3), respectively. Complexes 2 and 3 are characterized by X-ray crystallography, which indicates that they are low-spin Fe(II) complexes in the solid state. The solution properties of 1-3 are investigated using (1)H NMR, UV/vis absorption, and resonance Raman spectroscopies, cyclic voltammetry, and ESI-MS. These data confirm that in acetonitrile the complexes retain their solid-state structure, but in water immediate ligand exchange of the CH(3)CN ligand(s) for hydroxide or aqua ligands occurs with full dissociation of the polypyridyl ligand at low (<3) and high (>9) pH. pH jumping experiments confirm that over at least several minutes the ligand dissociation observed is fully reversible for complexes 1 and 2. In the pH range between 5 and 8, complexes 1 and 2 show an equilibrium between two different species. Furthermore, the aquated complexes show a spin equilibrium between low- and high-spin states with the equilibrium favoring the high-spin state for 1 but favoring the low-spin state for 2. Complex 3 forms only one species over the pH range 4-8, outside of which ligand dissociation occurs. The speciation analysis and the observation of an equilibrium between spin states in aqueous solution is proposed to be the origin of the effectiveness of complex 1 in cleaving DNA in water with (3)O(2) as terminal oxidant.

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Covalently linking two single strand DNA cleaving agents resulted in a new biomimetic binuclear iron complex capable of effecting oxidative double strand DNA cleavage.

Catalytic alkane oxidation with high selectivity using peracids and an (N4Py)Fe complex is presented and the role of [(N4Py)Fe(IV)=O]2+ species, molecular oxygen and hydroxyl radicals in the catalysis is discussed.

We are developing all-synthetic model cofactor-protein complexes in order to define the parameters controlling non-natural cofactor activity. The long-term objective is to establish the theoretical and practical basis for designing novel enzymes. A non-heme pentadentate ligand (N4Py) is being developed as a template for the site-specific attachment of a designed four-helix bundle. Previously, we attached two unprotected peptides via CH(2)Cl handles to N4Py. In the presence of hydrogen peroxide, the iron(II) complex of this ligand (2a) generates an Fe(III)OOH intermediate (3a) that can oxidize a wide variety of organic compounds. Here, we describe the synthesis of 27, a N4Py derivative in which four three-carbon spacers have been introduced, and show that four copies of an unprotected, single-cysteine peptide can be coupled via a thioether linkage to the ligand. In addition, a divergent synthesis route to tetrabromide ligand 1b has also been developed, providing the opportunity to prepare alternative pentadentate ligands efficiently by four cross-coupling reactions on a single molecule. Also, two of the four bromides of 1b can be selectively addressed by magnesium-bromide exchange.

Supplementary Information Syntheses of intermediate and ligands (P2, P3) ESI-MS data for Fe(II) complexes of ligands 4a-c generated in situ (P3) DNA cleavage with Fe(II)-N4Py complexes in the presence of DTT • Time profile of DNA cleavage (P3) • Rates of single-strand DNA cleavage (P4-P7) DNA cleavage with Fe(II)-N4Py complexes in the absence of DTT • Time profile of DNA cleavage (P8) • Rates of single-strand DNA cleavage (P9) k obs of all Fe(II)-N4Py complexes (P10) DNA cleavage with Fe(II)-BLM (P10, P11) DNA cleavage with iron salts (P11-P13) Mechanistic investigation of Fe(II)-1 (P13, P14) NMR spectra of intermediate and ligands (P15-P20)

The cytotoxicity of the anti-tumor drug BLM is believed to be related to the ability of the corresponding iron complex (Fe-BLM) to engage in oxidative double-strand DNA cleavage. The iron complex of the ligand N4Py (Fe-N4Py; N4Py = N,N-bis(2-pyridyl)-N-bis(2-pyridyl)methylamine) has proven to be a particularly valuable spectroscopic and functional model for Fe-BLM. It is also a very active oxidative DNA-cleaving agent. However, like all other synthetic Fe-BLM mimics, it gives only single-strand DNA cleavage. Since double-strand DNA cleavage requires the delivery of two oxidizing equivalents to the DNA, it was envisaged that multinuclear iron complexes might be capable of effecting double-strand cleavage. For this purpose, a series of ditopic and tritopic N4Py-derived ligands has been synthesized and the corresponding iron complexes have been evaluated for their efficacy in the oxidative cleavage of supercoiled pUC18 plasmid DNA. The dinuclear iron complexes showed significantly enhanced double-strand cleavage activity compared to mononuclear Fe-N4Py, which was relatively independent of the structure of the linking moiety. Covalent attachment of a 9-aminoacridine intercalator to a dinuclear complex did not give rise to improved double-strand DNA cleavage. The most efficient oxidative double-strand cleavage agents proved to be the trinuclear iron complexes. This is presumably the result of increased probability of the simultaneous delivery of two oxidizing equivalents to the DNA.

Anti‐Push: Der axiale Thiolatligand stabilisiert High‐Spin‐FeIII‐OOR‐Spezies (siehe Bild), wie man sie auch in Superoxid‐Reduktasen findet. Die Situation steht im Gegensatz zum „Push‐Effekt“, der in strukturell ähnlichen Low‐Spin‐FeIII‐OOR‐Systemen, einschließlich Cytochrom P450, auftritt und die O‐O‐Bindungsspaltung fördert. Diese Ergebnisse zeigen, wie sehr ähnliche aktive Zentren in Enzymen zwei sehr unterschiedliche Funktionen haben können.