Mixed-valence Iron Complexes Research Articles

Effect of a Substitute in a Ligand and a Counterion on the Properties of a Heptanuclear Mixed-Valence Iron Complex

Effect of a Substitute in a Ligand and a Counterion on the Properties of a Heptanuclear Mixed-Valence Iron Complex

Valence Delocalization and Metal-Metal Bonding in Carbon-Bridged Mixed-Valence Iron Complexes.

The carbide ligand in the iron-molybdenum cofactor (FeMoco) in nitrogenase bridges iron atoms in different oxidation states, yet it is difficult to discern its ability to mediate magnetic exchange interactions due to the structural complexity of the cofactor. Here, we describe two mixed-valent diiron complexes with C-based ketenylidene bridging ligands, and compare the carbon bridges with the more familiar sulfur bridges. The ground state of the [Fe2 (μ-CCO)2 ]+ complex with two carbon bridges (4) is S= , and it is valence delocalized on the Mössbauer timescale with a small thermal barrier for electron hopping that stems from the low Fe-C force constant. In contrast, one-electron reduction of the [Fe2 (μ-CCO)] complex with one carbon bridge (2) affords a mixed-valence species with a high-spin ground state (S= ), and the Fe-Fe distance contracts by 1 Å. Spectroscopic, magnetic, and computational studies of the latter reveal an Fe-Fe bonding interaction that leads to complete valence delocalization. Analysis of near-IR intervalence charge transfer transitions in 5 indicates a very large double exchange constant (B) in the range of 780-965 cm-1 . These results show that carbon bridges are extremely effective at stabilizing valence delocalized ground states in mixed-valent iron dimers.

Synthesis, characterization and magnetic properties of mixed-valence iron complexes with 2-pyridyl oximes

Two new mixed-valence iron complexes with 2-pyridyl oximes, [Fe(mpko)3Fe(H2O)2(NO3)](NO3)·2H2O (1) (mpko− = methyl(2-pyridyl)ketone oximate) and [{Fe(dpko)3}2Fe](ClO4)·4H2O (2) (dpko− = bis(2-pyridyl)ketone oximate), have been prepared by reaction of FeIII with mpkoH in methanol (1) and FeII with dpkoH in methanol/water (2). Dinuclear FeII(low-spin)FeIII(high-spin) and trinuclear FeII(low-spin)FeIII(high-spin)FeII(low-spin) cations are present in the crystal structure of 1 and 2, respectively. Intermolecular hydrogen bonds in 1 lead to weak antiferromagnetic interactions between pairs of neighboring FeIII centers, which allows observation of single-ion zero-field splitting effects.

Divalent metal ions modulated strong frustrated M(II)-Fe(III)3O (M = Fe, Mn, Mg) chains with metamagnetism only in a mixed valence iron complex.

Linking magnetically frustrated triangular FeO units by divalent metal ions (M(II) = Fe(II) for 1, Mn(II) for 2) gives isostructural 1D spin chains. Strong antiferromagnetic interactions were found in these complexes with significant frustrations but very interesting ferrimagnetic like transition and metamagnetism were found in mixed valence 1. By comparing the magnetic behaviours with isostructural complex 3 (with M(II) = Mg(II)), it is proposed that the spins of Fe(II) ions and Mn(II) ions have ferromagnetic and antiferromagnetic contributions respectively.

Long range charge transfer in trimetallic mixed-valence iron complexes mediated by redox non-innocent cyanoacetylide ligands

The reaction of Fe(C≡CC≡N)(dppe)Cp (1) with one-half equivalent of [trans-Fe(N≡CMe)2(dppx)2][BF4]2 (dppx = dppe ([2][BF4]2) or dppm ([3][BF4]2)) affords trimetallic [trans-Fe{N≡CC≡CFe(dppe)Cp}2(dppx)2][BF4]2 (dppx = dppe [4][BF4]2; dppx = dppm [5][BF4]2). Both [4][BF4]2 and [5][BF4]2 undergo three, one-electron oxidation processes, arising from sequential oxidation of the two terminal Fe(C≡CR)(dppe)Cp moieties and finally the central Fe(N≡CR)2(dppx)2 fragment. The redox products [4](n+) and [5](n+) (n = 3, 4) have been characterised by UV-vis-NIR and IR spectroelectrochemistry. The shifts in the characteristic ν(C≡CC≡N) bands upon oxidation demonstrate not only the localised electronic structure of the trications, but also the redox non-innocence of the cyanoacetylide ligands. The trimetallic [formally Fe(II/II/III) mixed-valence] complexes [4](3+) and [5](3+) feature two distinct IVCT transitions, one associated with charge transfer from the central 18-electron {Fe(N≡CR)2(dppx)2}(2+) to terminal {Fe(C≡CR)(dppe)Cp}(+) moiety, and a lower energy transition involving charge transfer between the terminal Fe fragments which are separated by the redox active 9-atom, 10-bond -C≡C-C≡N{Fe(dppx)2}N≡C-C≡C- bridge. The tetracationic complexes [4](4+) and [5](4+) generated by a further stepwise oxidation exhibit a single {Fe(N≡CR)2(dppx)2}(2+)→{Fe(C≡CR)(dppe)Cp}(+) IVCT transition.

Spectroscopic studies of oxo-centered, carboxylate-bridged, trinuclear mixed-valence iron (ІІІ, ІІІ, ІІ) complexes with aromatic hydroxycarboxylic acids

New type of oxo-centered, carboxylate-bridged, trinuclear, mixed-valence iron complexes of the general formula [Fe3O(OOCR)3(OOCR*)3L3] (where R=C13H27 or C15H31 and R*=C6H4(OH), (R′); C6H5CH(OH), (R″) or (C6H5)2C(OH), (R‴) and L=Methanol) were synthesized by the reaction of [Fe3O(OOCCH3)6(H2O)3] with straight chain carboxylic acids and aromatic hydroxycarboxylic acids. These were characterized by elemental analyses, spectral (electronic, infrared, Mössbauer, FAB mass and powder XRD) studies, conductance and magnetic susceptibility measurements. Infrared spectra suggested bidentate and bridging mode of coordination of both the carboxylate and hydroxycarboxylate anions along with Fe3O vibrations in the complexes. Mössbauer parameters indicated the presence of high-spin Fe(ІІ) (S=2) and high-spin Fe(ІІІ) (S=5/2) centers in the complexes, confirming the valence-localized type of species. An intervalence-transfer band observed at 13,690–13,850cm−1 range in the room-temperature electronic spectra of the complexes also suggested the complexes containing iron in mixed-valence state. Trinuclear nature of the complexes was confirmed by their FAB mass spectra. Magnetic moment values displayed octahedral geometry around each iron in the complexes and a net anti-ferromagnetic exchange coupling via μ-oxo atom related to mixed-valence pairs. A plausible structure for these complexes has been established on the basis of spectra and magnetic moment data.

Mixed-Valence Heptanuclear Iron Complexes with Ferromagnetic Interaction

Three new Prussian blue analogues, heptanuclear mixed-valence iron complexes of the type [Fe(II)(CN)(6){Fe(III)(1(-2H))}(6)]Cl(2)·nH(2)O, were synthesized and structurally and spectrally characterized, and their magnetic properties were investigated (1(-2H) corresponds to doubly deprotoned Schiff-base pentadentate ligands 1a, N,N'-bis(2-hydroxybenzylidene)-1,5-diamino-3-azapentane, 1b, N,N'-bis(3-ethoxy-2-hydroxybenzylidene)-1,7-diamino-4-azaheptane, or 1c, N,N'-bis(3-methoxy-2-hydroxybenzylidene)-1,6-diamino-3-azahexane). These compounds were formed by assembling the [Fe(CN)(6)](4-) building block with mononuclear complexes of the [Fe(1(-2H))Cl] type. X-ray structure analysis revealed that the complexes adopt a star-like architecture: the Fe(II) ion lies at the very center, and on its octahedral nodes the Fe(III) sites are coordinated in the Fe(II)-C≡N-Fe(III) manner. The Schiff-base pentadentate ligand moiety 1(-2H) coordinates a single Fe(III) center in two complexes 3b and 3c. Ligands 1a(-2H) in the complex cation of 3a adopt an unusual coordination mode: three donor atoms of the same ligand (one O and two N) coordinate one Fe(III), whereas the remaining N' and O' donor atoms coordinate the neighboring Fe(III) center creating the {Fe(ON(2))(N'O')N″} chromophore involving two 1a(-2H) ligand moieties. Moreover, three Fe(III) centers are interconnected with three 1a(-2H) ligands in such a manner that two {Fe(III)(3)(1a(-2H))(3)} units form two intramolecular rings. Magnetic investigation of the heptanuclear complexes revealed the high-spin state of all six Fe(III) coordination sites (s = 5/2), while the very central Fe(II) site is in the low-spin state (s = 0). At low temperature, the ferromagnetic exchange interactions stay evident for all three complexes. Mössbauer spectra of compounds 3a and 3b revealed a presence of two different doublets for both compounds: the major doublet is related to six Fe(III) high-spin coordination sites and the minor doublet refers to the low-spin very central Fe(II).

Synthesis and spectral characterization of trinuclear, oxo-centered, carboxylate-bridged, mixed-valence iron complexes with Schiff bases

Some novel trinuclear, oxo-centered, carboxylate-bridged, mixed-valence iron complexes of the general formula [Fe3O(OOCR)3(SB)3L3] (where R=C13H27, C15H31 or C17H35, HSB=Schiff bases and L=Ethanol) have been synthesized by the stepwise substitutions of acetate ions from μ3-oxo-hexa(acetato)tri(aqua)iron(II)diiron(III), first with straight chain carboxylic acids and then with Schiff bases. The complexes were characterized by elemental analyses, molecular weight determinations and spectral (electronic, infrared, FAB mass, Mössbauer and powder XRD) studies. Molar conductance measurements indicated the complexes to be non-electrolytes in nitrobenzene. Bridging nature of carboxylate and Schiff base anions in the complexes was established by their infrared spectra. Mössbauer spectroscopic studies indicated two quadrupole-split doublets due to Fe(II) and Fe(III) ions at 80, 200 and 295K, confirming the complexes are mixed-valence species. This was also supported by the observed electronic spectra of the complexes. Magnetic susceptibility measurements displayed octahedral geometry around iron in mixed-valence state and a net antiferromagnetic exchange coupling via μ-oxo atom. Trinuclear nature of the complexes was confirmed by their molecular weight determination and FAB mass spectra. A plausible structure for these complexes has been established on the basis of spectral and magnetic moment data.

Spin crossover in a heptanuclear mixed-valence iron complex

The complex [Fe(II){(CN)Fe(III)L(5)}(6)]Cl(2) consists of a mixed-valence heptanuclear cyanide-bridged unit formed of a Schiff-base pentadentate ligand L(5) and it shows a spin crossover of the peripheral Fe(III) centres.

Pressure effects and Mössbauer spectroscopic studies on a 3D mixed-valence iron spin-crossover complex with NiAs topology

A three-dimensional mixed-valence iron complex with NiAs-type topology, [(Fe(III)(3)O)Fe(II)(TA)(6)(H(2)O)(3)].(ClO(4))(2)(NO(3))(EtOH)(H(2)O)(2) (1, HTA = tetrazole-1H-acetic acid), shows spin-crossover behavior that was characterized via variable-temperature crystal structures, Mössbauer spectra and magnetic susceptibilities, the pressure effects on the transition behavior were also studied.

Variable temperature Mössbauer spectroscopic studies of oxo-centered trinuclear mixed-valence iron succinate, mesaconate and isophthalate complexes

Three new oxo-centered trinuclear mixed-valence iron complexes, iron succinate, iron mesaconate and iron isophthalate have been prepared. Temperature dependent valence delocalization processes were observed for all the complexes on variable temperature Mossbauer spectroscopic studies. Two clear quadrupole split doublets attributed to high-spin Fe(III) and high-spin Fe(II) states were existed for the complexes at liquid nitrogen temperature. At room temperature a nearly averaged singlet peak was observed for mesaconate complex and averaged doublet peaks were observed for succinate and isophthalate complexes with IS values 0.68 and 0.68 mms−1 and QS values 0.44 and 0.48 mms−1 respectively.

Electronic properties of mixed valence iron(II,III) dinuclear complexes with carboxylate bridges

Mixed valence dinuclear iron(II,III) complexes of the type [Fe 2L 2(H 2O) 4](NO 3)(H 2O) 3, where L is the dianion of a Schiff base ligand derived from α-amino acids (glycine and l-isoleucine) and 5-bromosalicylaldehyde, have been prepared and characterised using different spectroscopic methods, magnetic susceptibility, conductivity, and electrochemical measurements. The mixed valence iron complexes can be described as hexacoordinated species, in which the metal ion is surrounded by water molecules, the salicylidenimine ligand and two bridging carboxylate groups. The presence of bromine as a substituent in the salicylaldehyde ring stabilises the mixed valence species.

Pressure-induced charge-transfer phase transition in a mixed-valence iron complex

We have investigated the hydrostatic pressure effect on the charge-transfer (CT) phase transition in (n-C5H11)4N[FeIIFeIII(dto)3]. The system shows a pressure-induced CT phase transition. The CT phase transition appears discontinuously at around the pressure P=0.5 GPa and the transition temperature increases linearly with increasing the pressure above 0.5 GPa.The present investigation reveals that the CT phase transition of the system is a phenomenon where the spin and the charge states are strongly correlated with the lattice.

Pressure-induced charge-transfer phase transition in a mixed-valence iron complex

Abstract We have investigated the hydrostatic pressure effect on the charge-transfer (CT) phase transition in ( n -C 5 H 11 ) 4 N[Fe II Fe III (dto) 3 ]. The system shows a pressure-induced CT phase transition. The CT phase transition appears discontinuously at around the pressure P =0.5 GPa and the transition temperature increases linearly with increasing the pressure above 0.5 GPa.The present investigation reveals that the CT phase transition of the system is a phenomenon where the spin and the charge states are strongly correlated with the lattice.

Coordination algorithms control molecular architecture: [CuI4(L2)4]4+ grid complex versus [MII2(L2)2X4]y+ side-by-side complexes (M=Mn, Co, Ni, Zn; X=solvent or anion) and [FeII(L2)3][Cl3FeIIIOFeIIICl3

The synthesis and characterisation of a pyridazine-containing two-armed grid ligand L2 (prepared from one equivalent of 3,6-diformylpyridazine and two equivalents of p-anisidine) and the resulting transition metal (Zn, Cu, Ni, Co, Fe, Mn) complexes (1-9) are reported. Single-crystal X-ray structure determinations revealed that the copper(I) complex had self-assembled as a [2 x 2] grid, [Cu(I) (4)(L2)(4)][PF(6)](4).(CH(3)CN)(H(2)O)(CH(3)CH(2)OCH(2)CH(3))(0.25) (2.(CH(3)CN)(H(2)O)(CH(3)CH(2)OCH(2)CH(3))(0.25)), whereas the [Zn(2)(L2)(2)(CH(3)CN)(2)(H(2)O)(2)][ClO(4)](4).CH(3)CN (1.CH(3)CN), [Ni(II) (2)(L2)(2)(CH(3)CN)(4)][BF(4)](4).(CH(3)CH(2)OCH(2)CH(3))(0.25) (5 a.(CH(3)CH(2)OCH(2)CH(3))(0.25)) and [Co(II) (2)(L2)(2)(H(2)O)(2)(CH(3)CN)(2)][ClO(4)](4).(H(2)O)(CH(3)CN)(0.5) (6 a.(H(2)O)(CH(3)CN)(0.5)) complexes adopt a side-by-side architecture; iron(II) forms a monometallic cation binding three L2 ligands, [Fe(II)(L2)(3)][Fe(III)Cl(3)OCl(3)Fe(III)].CH(3)CN (7.CH(3)CN). A more soluble salt of the cation of 7, the diamagnetic complex [Fe(II)(L2)(3)][BF(4)](2).2 H(2)O (8), was prepared, as well as two derivatives of 2, [Cu(I) (2)(L2)(2)(NCS)(2)].H(2)O (3) and [Cu(I) (2)(L2)(NCS)(2)] (4). The manganese complex, [Mn(II) (2)(L2)(2)Cl(4)].3 H(2)O (9), was not structurally characterised, but is proposed to adopt a side-by-side architecture. Variable temperature magnetic susceptibility studies yielded small negative J values for the side-by-side complexes: J=-21.6 cm(-1) and g=2.17 for S=1 dinickel(II) complex [Ni(II) (2)(L2)(2)(H(2)O)(4)][BF(4)](4) (5 b) (fraction monomer 0.02); J=-7.6 cm(-1) and g=2.44 for S= 3/2 dicobalt(II) complex [Co(II) (2)(L2)(2)(H(2)O)(4)][ClO(4)](4) (6 b) (fraction monomer 0.02); J=-3.2 cm(-1) and g=1.95 for S= 5/2 dimanganese(II) complex 9 (fraction monomer 0.02). The double salt, mixed valent iron complex 7.H(2)O gave J=-75 cm(-1) and g=1.81 for the S= 5/2 diiron(III) anion (fraction monomer=0.025). These parameters are lower than normal for Fe(III)OFe(III) species because of fitting of superimposed monomer and dimer susceptibilities arising from trace impurities. The iron(II) centre in 7.H(2)O is low spin and hence diamagnetic, a fact confirmed by the preparation and characterisation of the simple diamagnetic iron(II) complex 8. Mössbauer measurements at 77 K confirmed that there are two iron sites in 7.H(2)O, a low-spin iron(II) site and a high-spin diiron(III) site. A full electrochemical investigation was undertaken for complexes 1, 2, 5 b, 6 b and 8 and this showed that multiple redox processes are a feature of all of them.

Pressure Effect on Charge-Transfer Phase Transition in a Mixed-Valence Iron Complex, (n-C3H7)4N[FeIIFeIII(dto)3] (dto = C2O2S2)

We have investigated the hydrostatic pressure effect on the charge-transfer phase transition between Fe II and Fe III in a mixed-valence iron complex, ( n -C 3 H 7 ) 4 N[Fe II Fe III (dto) 3 ] (dto...

Study on the Molecular Magnetism in Mixed Valence Iron Complexes, M[Fe II Fe III (mto) 3 ](M=( n -C n H 2n+1 ) 4 N, mto=monothiooxalato (C 2 O 3 S))

We have synthesized and investigated the physical properties of a new mixed valence iron complex, ( n -C 3 H 7 ) 4 N[Fe II Fe III (mto) 3 ] (mto=C 2 O 3 S). This complex behaves as a ferrimagnet with T N =38 K and θ= m 117 K. From the analysis of the Mössbauer spectrum of ( n -C 3 H 7 ) 4 N[Fe II Fe III (mto) 3 ] at 298 K, the spin state of Fe II was determined to be the high spin state (S=2), but it was difficult to determine the spin state of Fe III . So that, in order to elucidate the spin state of Fe III , we have investigated ESR spectra, and confirmed the coexistence of high spin state (S=5/2) and low spin state (S=1/2) for the Fe III sites. Moreover, we have synthesized ( n -C 4 H 9 ) 4 N[Fe II Fe III (mto) 3 ]. This complex shows the ferrimagnetic phase transition at 41 K, and Weiss constant is m 76 K. In our previous paper, we have reported that mixed-valence complex ( n -C 3 H 7 ) 4 N[Fe II Fe III (dto) 3 ] (dto=C 2 O 2 S 2 ) shows a new type of phase transition connected with charge transfer phase transition and spin-crossover transition around 120 K. In the title complexes, the charge transfer phase transition was not observed. mixed valence complex charge transfer phase transition monothiooxalato

Electron transfer in a trinuclear oxo-centred mixed-valence iron complex, in solid and solution statesDedicated to Professor Dieter Sellmann on the occasion of his 60th birthday.

Complexes [FeIII2MIIOL3] (M = Fe, Co, Ni, Cu; 2, 3, 4, 5) have been synthesised in which L2− is a pentadentate ligand designed to coordinate all three metal atoms in the central cluster and to inhibit dissociation and solvent exchange processes. Crystal structures for 2, 4 and 5 show threefold symmetry, attributed to rotational disorder. Magnetisation data for 2 indicate strong superexchange between basis oxidation states Fe(3+, 3+, 2+). Comparisons of IR spectra across the series of complexes confirm the non-threefold symmetry of the mixed-valence cluster on the vibrational time scale, both in the solid state and in solution. Proton NMR spectra in solution at room temperature do not distinguish the three iron sites, suggesting that pseudo-rotation by thermal electron transfer also operates. Cyclic voltammetry and spectroelectrochemical measurements show that the mixed-valence iron complex 2 can be oxidised reversibly to give the tri-iron(III) complex [Fe3OL3]+ and reduced reversibly and quasireversibly to give respectively [Fe3OL3]− and tri-iron(II) [Fe3OL3]2−, E0 = 85, −635, −1230 mV (versus Fc+/0) in dichloromethane (T = 298 K, 0.1 M [n-Bu4N][PF6]). Mossbauer spectra of 2 indicate significant valence delocalisation even at low temperature (4.2 K) with estimated valences Fe(2.9+, 2.9+, 2.2+) in the solid state. At higher temperatures no lifetime broadening is observed but additional Mossbauer absorptions are consistent with increasing proportions of trimer molecules with greater delocalisation, i.e. Fe(2.75+, 2.75+, 2.5+). In frozen solution (THF) the spectra indicate increasing proportions of molecules fully valence-delocalised on the Mossbauer time scale. The data are accounted for with a model which places the complex at the Robin–Day class III/II borderline. It combines strong superexchange with significant double exchange even at the lowest temperatures, while at higher temperatures in solution complete valence delocalisation occurs through intramolecular electron transfer at rates intermediate between the IR and NMR time scales.

Multi-Temperature Crystallographic Studies of Mixed-Valence Polynuclear Complexes; Valence Trapping Process in the Trinuclear Oxo-Bridged Iron Compound, [Fe3O(O2CC(CH3)3)6(C5H5N)3

Single-crystal X-ray diffraction data have been collected on five different crystals at 12 different temperatures (10, 28, 35, 60, 85, 100, 118, 135, 160, 200, 240, 295 K) on a trinuclear, oxo-bridged, mixed-valence iron complex, Fe3O(O2CC(CH3)3)6(C5H5N)3, using both synchrotron and conventional radiation sources. The present study for the first time provides structural information for an oxo-bridged trinuclear compound below the boiling point of nitrogen (77 K). The use of very low-temperature crystallographic data is crucial for understanding the physical properties of the complex. No change of space group is observed in the whole temperature range, although a reversible broadening of the Bragg peaks is observed around 85 K. The structure has ordering processes involving the tert-butyl groups, and above 85 K, four tert-butyl groups become disordered. Around 150 K, a fifth tert-butyl becomes disordered, whereas the last tert-butyl is ordered at all temperatures. Very significant temperature-dependent changes in the Fe-ligand bond lengths are observed which are interpreted as being due to dynamic disorder caused by intramolecular electron transfer (ET) between the metal sites. The ET process is significantly affected by changes in the molecular potential energy surface (PES) caused by the dynamic behavior of the tert-butyls. The dynamic disorder of the Fe3O core resulting from the ET process is examined through analysis of the atomic displacement parameters. The ET process involves only two of the three iron sites, with the third site appearing to be valence-trapped at all temperatures. The trapping of this iron site at all temperatures appears to be related to the asymmetry caused by the different dynamic behaviors of the tert-butyls. At very low temperatures (<10 K), the system becomes valence-trapped and consists of a single configuration without disorder. Boltzmann population models are used to estimate the energy difference between the two lowest-lying minima on the PES (ΔE < 100 cm-1) and between two disordered configurations of each of the tert-butyls (ΔE = 217, 212, 255, 359, and 345 cm-1).

Metabolic, metallic, and mitotic sources of oxidative stress in Alzheimer disease.

Cell bodies of neurons at risk of death in Alzheimer disease (AD) have increased lipid peroxidation, nitration, free carbonyls, and nucleic acid oxidation. These oxidative changes are uniform among neurons and are seen whether or not the neurons display neurofibrillary tangles and, in fact, are actually reduced in the latter case. In consideration of this localization of damage, in this review, we provide a summary of recent work demonstrating some key abnormalities that may initiate and promote neuronal oxidative damage. First, mitochondrial abnormalities might be the source of reactive oxygen species yielding perikaryal oxidative damage. The common 5-kb deletion mitochondrial (mt)DNA subtype was greatly increased in the AD cases, but only in neurons at risk. The importance of such mitochondrial abnormalities to oxidative stress was indicated by a high correlation coefficient between the extent of the mtDNA increase and RNA oxidative damage (r2 = 0.87). Nonetheless, because mitochondria in AD do not show striking oxidative damage, as one would expect if they were the direct producer of free radical species, we suspected that abnormal mitochondria supply a key reactant that, once in the cytoplasm, releases radicals. One such reactant, hydrogen peroxide, (H2O2), abundant in mitochondria, can react with iron via the Fenton reaction to produce.OH. To demonstrate this directly using a modified cytochemical technique that relies on the formation of mixed valence iron complexes, we found that redox-active iron is associated with vulnerable neurons. Interestingly, removal of iron was completely affected by using deferroxamine, after which iron could be rebound to re-establish lesion-dependent catalytic redox reactivity. Characterization of the iron-binding site suggests that binding is dependent on available histidine residues and on protein conformation. Taken together with our previous studies showing abnormalities in the iron homeostatic system including heme oxygenase, iron regulatory proteins 1 and 2, ceruloplasmin, and dimethylargininase, our results indicate that iron misregulation could play an important role in the pathogenesis of AD and therefore chelation therapy may be a useful therapeutic approach. Finally, we wanted to determine the proximal cause of mitochondrial abnormalities. One interesting mechanisms involves re-entry into the cell cycle, at which point organellokinesis and proliferation results in increased mitochondria. Supporting this, we have considerable in vivo and in vitro evidence for mitotic disturbances in AD and its relationship with the pathogenesis of AD.