John R. Pilbrow

Copper-mediated Amyloid-β Toxicity Is Associated with an Intermolecular Histidine Bridge

Amyloid-β peptide (Aβ) is pivotal to the pathogenesis of Alzheimer disease. Here we report the formation of a toxic Aβ-Cu2+ complex formed via a histidine-bridged dimer, as observed at Cu2+/peptide ratios of >0.6:1 by EPR spectroscopy. The toxicity of the Aβ-Cu2+ complex to cultured primary cortical neurons was attenuated when either the π -or τ-nitrogen of the imidazole side chains of His were methylated, thereby inhibiting formation of the His bridge. Toxicity did not correlate with the ability to form amyloid or perturb the acyl-chain region of a lipid membrane as measured by diphenyl-1,3,5-hexatriene anisotropy, but did correlate with lipid peroxidation and dityrosine formation. 31P magic angle spinning solid-state NMR showed that Aβ and Aβ-Cu2+ complexes interacted at the surface of a lipid membrane. These findings indicate that the generation of the Aβ toxic species is modulated by the Cu2+ concentration and the ability to form an intermolecular His bridge.

Recent developments in the studies of molecular oxygen adducts of cobalt (II) compounds and related systems

A. Introduction 296 B. Measurement of equilibrium constants of oxygen uptake 301 C. Structures of molecular oxygen complexes of cobalt(H) compounds 302 D. Electronic structures of molecular oxygen complexes 306 E. ESR studies of molecular oxygen complexes of cobalt(H) compounds and relatedsystems.. 312 (i) ESR theory for molecular oxygen adducts of cobalt(H) compounds and relatedsystems. 313 F. ESR studies of superoxide and other oxygen radical species . . _ _ _ _ . _ . _ _ . _ _ _ _ _ 322 G. Oxygenation of iron(H) and cobalt(E) protein compounds 325 (i) Hemoglobin 325 (ii) Coboglobin 329 (iii) Vitamin B,,,(Cbl”) 336 H. Oxygenation of metallo-porphyrins with some control of facial regions . _ . . _ . . _ . 338 (i) Role of iron porphyrinic materials in artificial blood 345 (ii) Polymer bound compounds capable of binding oxygen 345 I. Oxygenation of cobalt(H) porphyrins 349 I. Oxygenation of cobalt(H) Sehiff-base chelates. 351 K. Oxygenation of macrocyclic cobalt(H) chelates 356 L. Formation of molecular oxygen complexes on zeolites and cation exchanges ..... 357 M. Activation of molecular oxygen 357 (i) Role of cobalt(E) compounds in catalytic oxidation processes 357 (ii) Catalysis of electrochemical reduction of molecular oxygen . _ _ _ . _ _ _ . _ . . _ . 361

Spectroscopy of Naphthalene Diimides and Their Anion Radicals

Naphthalene diimides 1–4 having different N,N-disubstitution undergo single electron reduction processes either chemically or electrochemically to yield the corresponding radical anion in high yield. This study concentrates on 1, bearing pentyl side chains connected through the diimide nitrogens, and compares the results obtained against those bearing isopropyl, propargyl, and phenylalanyl side chains. Compound 1 exhibits mirror image absorption and fluorescence in the near-UV region in CH2Cl2 and dimethylformamide that is typical of monomeric N,N-dialkyl-substituted naphthalene diimides. In toluene, excimer-like emission is observed, which suggests ground-state complexes involving 1 are formed. X-Ray crystallography has been used to characterize 1 in the solid state. Cyclic voltammetry enables the reversible potentials for [NDI]0/– and [NDI]−/2– type processes to be measured. Bulk one-electron reduction of 1–4 is characterized by dramatic changes in the absorption and emission spectra. Additionally, highly structured EPR (electron paramagnetic resonance) signals from dimethylformamide solutions of the radical anions of 1–3 have been obtained and are consistent with coupling between the unpaired electron and the naphthalene diimide nitrogens and hydrogens and the NCH hydrogens of the appropriate side chains. The overall structure of the EPR spectrum is substituent-dependent. These changes in spectroscopic output upon an electronic input may be described as a simple ‘on/off’ switching mechanism with which to apply a ‘bottom-up’ approach to molecular device manufacture.

Physico-chemical probes of intercalation

A large number of drugs, particularly those with planar chromophores, bind to DNA and consequently interfere with its role as a template in replication and transcription. Many of them form a strong, but reversible, non-covalent complex with the DNA by intercalating between adjacent base-pairs. These drugs are powerful probes of nucleic acid structure and function, and a number of them are clinically useful chemotherapeutic agents. The process of intercalation is considered so crucial that the possible formation of an intercalated complex has been proposed for practically every drug known to bind to DNA (Gale et al., 1981). It is expedient, therefore, when investigating the mode of binding of new drugs at the molecular level to determine at an early stage whether or not intercalaction occurs. In the past, the evidence for classifying a particular drug as an intercalator was often inadequate. Many drugs were tentatively identified as intercalators well before the advent of current methodologies. Even now, some of the tests taken as diagnostic for intercalaction are not strictly adequate. In this review, we examine some of the most commonly employed physico-chetnical probes for intercalation, in order to determine which of them are sufficient and unambiguous.

Free-radical involvement in the drying and oxidation of victorian brown coal

Abstract The technique of electron spin resonance spectroscopy has been used to study the changes in free-radical nature and content of brown coals as a result of vacuum drying the coal at various temperatures, and exposing the dried coal to either air at room temperature or oxygen at 105 °C. Free-radical concentrations increased during the vacuum-drying process and this is thought to be a result of organic functional group breakdown. Free-radical concentrations in dry coals following air or oxygen exposure have been found to vary with exposure time. The observations can be explained in terms of free-radical involvement in the oxidation process.

Effective g values for S = 3/2 and S = 5/2

The EPR spectra due to S = 3/2 and S = 5/2 ions frequently exhibit highly anisotropic g values which arise from transitions within Kramers doublets in the low Zeeman field limit. Methods by which such effective g values are calculated have been reviewed, and errors and anomalies in the published literature clarified. A new, simpler method applicable to S = 3/2 ions has been described and is based on the expansion to third order of the exact eigenvalue formulas which hold along principal axes. The spectrum of cobalt pyridine chloride powder is simulated to illustrate the importance of determining g factors correctly and also to show that the transition probability must be multiplied by g −1 because EPR is a field-swept technique.

Electron Spin Resonance of Copper (II) Citrate Chelates

Electron spin resonance (ESR), paramagnetic susceptibility, and polarographic measurements have been made of copper (II) citrate chelates over a wide range of pH. The signal observed at pH 4 is typical of that found for copper (II) in a distorted octahedral environment. With increasing pH the signal becomes less intense and is replaced by a much broader spin resonance observable at relatively high concentrations of copper (II) and in frozen solutions. At pHs of about 11, a third signal is observed. The broad signal has been interpreted in terms of dipole—dipole coupling of copper (II) ions arising from dimer formation. Measurements show that the paramagnetic susceptibility is independent of pH. Solution of the spin Hamiltonian including the dipole—dipole interaction has made possible calculation of the line shape for the dimer signal. The calculations have led to a value of 3.1 A as the distance between the copper (II) dipoles and to the conclusion that each copper (II) ion is in a | 3z2—r2〉 ground state...

Heptanuclear iron(III) triethanolamine clusters exhibiting ‘millennium dome’-like topologies and an octanuclear analogue with ground spin states of S = 5/2 and 0, respectively

The synthesis and structural determination of the tripodal triethanolamine (teaH3) based octanuclear cluster [FeIII8O3(O2CCH2CH3)6(tea)(teaH)3(F)3]·0.5MeOH·0.5H2O (1) is reported. The octanuclear core in 1 has only been observed once before in the analogous teaH3 based [Fe8O3(O2CPh)9(tea)(teaH)3]·MeCN cluster and, as observed in that case, magnetic susceptibility measurements on 1 indicate a ground spin state of S = 0. Reaction of the trinuclear complex [FeIII3O(O2CCMe3)6(H2O)3](O2CCMe3) with the tripodal ligands 1-[N,N-bis(2-hydroxyethyl)-amino]-2-propanol (bheapH3) and triethanolamine (teaH3) gives [FeIII7O3(O2CCMe3)9(bheapH)3(H2O)3] (2) and [FeIII7O3(O2CCMe3)9(teaH)3(H2O)3] (3), respectively. The cores in 2 and 3 are dome-like in topology, an architecture unseen in any heptanuclear clusters reported to date. Magnetisation and susceptibility measurements show that clusters 2 and 3 exhibit ground spin states of S = 5/2. Low temperature EPR measurements confirm these ground spin states and yield zero-field splitting parameters of D = 0.28 cm−1 and E/D of 0.21 (for 3).

Systematic study of spin crossover and structure in [Co(terpyRX)2](Y)2 systems (terpyRX = 4'-alkoxy-2,2':6',2''-terpyridine, X = 4, 8, 12, Y = BF4(-), ClO4(-), PF6(-), BPh4(-)).

A family of spin crossover cobalt(II) complexes of the type [Co(terpyRX)(2)](Y)(2) x nH(2)O (X = 4, 8, 12 and Y = BF(4)(-), ClO(4)(-), PF(6)(-), BPh(4)(-)) has been synthesized, whereby the alkyl chain length, RX, and counteranion, Y, have been systematically varied. The structural (single crystal X-ray diffraction) and electronic (magnetic susceptibility, electron paramagnetic resonance (EPR)) properties have been investigated within this family of compounds. Single crystal X-ray diffraction analysis of [Co(terpyR8)(2)](ClO(4))(2), [Co(terpyR8)(2)](BF(4))(2) x H(2)O, and [Co(terpyR4)(2)](PF(6))(2) x 3 H(2)O, at 123 K, revealed compressed octahedral low spin Co(II) environments and showed varying extents of disorder in the alkyl tail portions of the terpyRX ligands. The magnetic and EPR studies were focused on the BF(4)(-) family and, for polycrystalline solid samples, revealed that the spin transition onset temperature (from low to high spin) decreased as the alkyl chain lengthened. EPR studies of polycrystalline powder samples confirmed these results, showing signals only due to the low spin state at the temperatures seen in magnetic measurements. Further to this, simultaneous simulation of the EPR spectra of frozen solutions of [Co(terpyR8)(2)](BF(4))(2) x H(2)O, recorded at S-, X-, and Q-band frequencies, allowed accurate determination of the g and A values of the low spin ground state. The temperature dependence of the polycrystalline powder EPR spectra of this and the R4 and R12 complexes is explained in terms of Jahn-Teller effects using the warped Mexican hat potential energy surface model perturbed by the low symmetry of the ligands. While well recognized in Cu(II) systems, this is one of the few times this approach has been used for Co(II).

Lineshapes in frequency-swept and field-swept epr for spin 12

Abstract Application of the well-known formula S(B, ν) = CηQ 0 V ij 2 f([ν − ν 0 ] 2 , σ ν ) which describes the net absorption of microwave radiation between two states, i and j, leads to a number of valuable new insights for magnetic-field-swept EPR. Here C is a constant which depends on the experimental conditions, |Vij|2 the square of the transition matrix element, Q0 the unloaded cavity Q factor, η the sample filling factor, σv, the linewidth (in frequency units), and f the lineshape function. The above equation describes both frequency-swept EPR, where ν0 is fixed and ν is varied, and field-swept EPR detected at a constant microwave frequency (ν = νc where ν0 is the proper field-dependent variable. The Aasa and Vanngard 1/g factor (J. Magn. Reson. 19, 308 (1975)) is required whenever the above equation is written in terms of field variables as has been a common practice for field-swept EPR. Linewidth anisotropy in field-swept EPR is found to arise in some cases simply as a consequence of the g anisotropy; true tinewidth anisotropy is a property of σν. Asymmetric field-swept lineshapes are predicted for g-strain broadening; i.e., when σν, depends linearly upon the magnetic field. Implications of these ideas for powder spectral simulations are described.