University of Groningen Ligand Exchange and Spin State Equilibria of Fe-II ( N 4 Py ) and Related Complexes in Aqueous

We report the characterization and solution chemistry of a series of Fe complexes based on the pentadentate ligands N4Py (1,1-di(pyridin-2-yl)-N,N-bis(pyridin-2ylmethyl)methanamine), MeN4Py (1,1-di(pyridin-2-yl)-N,Nbis(pyridin-2-ylmethyl)ethanamine), and the tetradentate ligand Bn-N3Py (N-benzyl-1,1-di(pyridin-2-yl)-N-(pyridin-2ylmethyl)methanamine) ligands, i.e., [Fe(N4Py)(CH3CN)](ClO4)2 (1), [Fe(MeN4Py)(CH3CN)](ClO4)2 (2), and [Fe(Bn-N3Py)(CH3CN)2](ClO4)2 (3), respectively. Complexes 2 and 3 are characterized by X-ray crystallography, which indicates that they are low-spin Fe complexes in the solid state. The solution properties of 1−3 are investigated using 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 CH3CN 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 lowand 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 O2 as terminal oxidant. ■ INTRODUCTION Bleomycins (BLMs) are a class of glycopeptide antibiotics isolated from Streptomyces verticillus and are used in the clinical treatment of head, neck, and testicular cancers. The iron complex of bleomycin (Fe-BLM) is capable of effecting efficient cleavage of DNA and catalyzes oxidation of a number of organic substrates with O2 or H2O2, 3 respectively. The mechanism by which O2 is activated by nonheme iron systems, such as Fe-BLM, has received much attention recently. Many structural and functional model complexes for metallobleomycins have been developed in particular as synthetic DNA cleaving agents. Our group, together with Que and coworkers, has developed the pentadentate ligand 1,1-di(pyridin-2yl)-N,N-bis(pyridin-2-ylmethyl)methanamine) (N4Py) as a structural and functional model for the metal binding domain of the BLM. The Fe complex [Fe(N4Py)(CH3CN)](ClO4)2 (1) has been characterized and shown to be active both in organic functional group oxidative transformations with various terminal oxidants and in the oxidative cleavage of DNA with O2. 7b,10 To date, mechanistic studies of complex 1 and related complexes have focused either on their chemistry and catalytic activity in nonaqueous solvents, where the terminal oxidant employed is H2O2, 7a,9 peracids, or iodosylbenzenes, or on the cleavage of DNA in water with O2. 10 The activity of 1 in generating the active oxidant species with O2 that are capable of achieving DNA cleavage is remarkable, and the reaction of 1 with O2 is proposed to lead ultimately to formation of a low-spin Fe−OOH species. The Fe−OOH species is considered to be the precursor for the active species that is Received: August 27, 2011 Published: December 23, 2011 Article