Octahedral (cis-cyclam)iron(III) complexes with O,N-coordinated o-iminosemiquinonate(1-) pi radicals and o-imidophenolate(2-) anions

Three octahedral complexes containing a (cis-cyclam)iron(III) moiety and an O,N-coordinated o-iminobenzosemiquinonate pi radical anion have been synthesized and characterized by X-ray crystallography at 100 K: [Fe(cis-cyclam)(L(1-3)(ISQ))](PF(6))(2) (1-3), where (L(1-3)(ISQ)) represents the monoanionic pi radicals derived from one-electron oxidations of the respective dianion of o-imidophenolate(2-), L(1), 2-imido-4,6-di-tert-butylphenolate(2-), L(2), and N-phenyl-2-imido-4,6-di-tert-butylphenolate(2-), L(3). Compounds 1-3 possess an S(t) = 0 ground state, which is attained via strong intramolecular antiferromagnetic exchange coupling between a low-spin central ferric ion (S(Fe) = 1/2) and an o-imino-benzosemiquinonate(1-) pi radical (S(rad) = 1/2). Zero-field M?ssbauer spectra of 1-3 at 80 K confirm the low-spin ferric electron configuration: isomer shift delta = 0.26 mm s(-1) and quadrupole splitting DeltaE(Q) = 1.96 mm s(-1) for 1, 0.28 and 1.93 for 2, and 0.33 and 1.88 for 3. All three complexes undergo a reversible, one-electron reduction of the coordinated o-imino-benzosemiquinonate ligand, yielding an [Fe(III)(cis-cyclam)(L(1-3)(IP))](+) monocation. The monocations of 1 and 2 display very similar rhombic signals in the X-band EPR spectra (g = 2.15, 2.12, and 1.97), indicative of low-spin ferric species. In contast, the monocation of 3 contains a high-spin ferric center (S(Fe) = 5/2) as is deduced from its M?ssbauer and EPR spectra.     

Thermolysis and Chemiluminescence of Monocyclic 1,2,4-Trioxan-5-ones

The 3,6-substituted 1,2,4-trioxan-5-ones 11 – 14 , on heating to 170–200°, underwent unimolecular thermolysis to generate electronically excited singlet ketones with an efficiency of ca. 0.2%. The chemiluminescence quantum yields (?oS_CL) depended on the nature of the 6-substitutents and increased linearly with temperature. The Arrhenius activation energies were obtained by measuring the rate of decay of luminescence and determined as 22.9, 30.4, 35.6, and 34.2 kcal/mol for 11 – 14 , respectively. Step analysis of the chemiluminescence of 14 afforded an average activation energy of 44.3 kcal/mol. This latter result is explicable in terms of two decomposition paths, higher and lower in energy, leading to excited and ‘dark’ products, respectively. The thermolysis of trioxanones 12 – 14 lacking a H-atom at the 6-position is interpreted as involving successive rupture of the peroxide bond, excision of ketone at the 3-substituted end, and loss of CO₂, to finally produce ketone originating from the 6-position (see Scheme 4).     

Factors influencing the autoxidation of fatty acids: effect of olefin geometry of the nonconjugated diene

Autoxidations of cis,cis, cis,trans, and trans,trans nonconjugated octadecadienoates and pentadecadienes were carried out in the presence of alpha-tocopherol to investigate the effect of olefin geometry on this oxidation process and provide insight into the factors that influence the autoxidation of fatty acids. We have found that as the trans character of the diene increases, the amount of O(2) trapping at the central (bis-allylic) position of the pentadienyl radical also increases. In addition, the rate constant for beta-fragmentation (k(beta) approximately 10(6) s(-1)) of the bis-allylic peroxyl radical decreased on going from the cis,cis to the trans,trans diene. We have also found that for the cis,trans nonconjugated dienes, there is a preference for trapping of the pentadienyl radical by O(2) at the transoid end, generating the cis,trans conjugated hydroperoxide as the major product.     

Fluxional processes in diamagnetic and paramagnetic allyl dicarbonyl and 2-methylallyl dicarbonyl molybdenum histidinato complexes as revealed by spectroscopic data and density functional calculations

This work describes a detailed study on the structure and dynamics of pseudooctahedral low-valent complexes of the type [Mo(His-N(epsilon)-R)(eta-2-R'-allyl)(CO)(2)] (His=N(delta),N,O-L-histidinate; R=H, R'=H (1); R=C(2)H(4)CO(2)Me, R'=H (2); R=H, R'=Me (3); R=C(2)H(4)CO(2)Me, R'=Me (4)). These diamagnetic 18-electron complexes were comprehensively characterized spectroscopically and by X-ray crystallography. In the solid state, the (substituted) allyl ligand is in an endo position in all compounds, but it is trans to the His-N(delta) atom in 1 and 2, whereas it is trans to the carboxylate O atom for the 2-Me-allyl compounds 3 and 4. In solution, both isomers are present in a solvent-dependent equilibrium. The third isomer (allyl trans to His-NH(2)) is not spectroscopically observed in solution. This is in agreement with the results from density functional (DFT) computations (BPW 91 functional) for 1 and 3, which predict a considerably higher energy (+6.3 and +5.9 kJ mol(-1), respectively) for this isomer. A likely path for isomerization is calculated, which is consistent with the activation energy determined by variable temperature NMR measurements. At least for 3, the preferred path involves several intermediates and a rotation of the 2-Me-allyl ligand. For the paramagnetic 17-electron congeners, DFT predicts the exo isomer of 3(+) with the 2-Me-allyl ligand trans to the carboxylate O atom to be by far the most stable isomer. For 1(+), an endo-exo equilibrium between the isomers with the allyl ligand trans to the carboxylate O atom is suggested. These suggestions are confirmed by EPR spectroscopy on the electrochemically generated species, which show signals for one- (4) and two- (2) metal-containing compounds. The appearance of the EPR spectra may be rationalized by inspection of the SOMOs from DFT calculations of the species in question. The notion of a metal-centered oxidation is also substantiated by IR spectroelectrochemistry and by UV/Vis spectra of the 17-electron complexes. Upon depleting the metal of electron density, the stretching vibrations of the carbonyl ligands shift more than 100 cm(-1) to higher wavenumbers, and the carbonyl vibration of the metal-coordinated carboxylate shifts by about 50 cm(-1). A color change from yellow to green upon oxidation is observed visually and quantified by the appearance of a new band at 622 nm (2(+)) and 546 nm (4(+)), respectively.     

Tuning the electronic structure of octahedral iron complexes [FeL(X)] (L = 1-alkyl-4,7-bis(4-tert-butyl-2-mercaptobenzyl)-1,4,7-triazacyclononane,X = Cl,CH(3)O,CN, NO). The S = 1/2 <==>3/2 Spin equilibrium of [FeL(Pr)(NO)

Two new pentadentate, pendent arm macrocyclic ligands of the type 1-alkyl-4,7-bis(4-tert-butyl-2-mercaptobenzyl)-1,4,7-triazacyclononane where alkyl represents an isopropyl, (L(Pr))(2-), or an ethyl group, (L(Et))(2-), have been synthesized. It is shown that they bind strongly to ferric ions generating six-coordinate species of the type [Fe(L(alk))X]. The ground state of these complexes is governed by the nature of the sixth ligand, X: [Fe(III)(L(Et))Cl] (2) possesses an S = 5/2 ground state as do [Fe(III)(L(Et))(OCH(3))] (3) and [Fe(III)(L(Pr))(OCH(3))] (4). In contrast, the cyano complexes [Fe(III)(L(Et))(CN)] (5) and [Fe(III)(L(Pr))(CN)] (6) are low spin ferric species (S = 1/2). The octahedral [FeNO](7) nitrosyl complex [Fe(L(Pr))(NO)] (7) displays spin equilibrium behavior S = 1/2<==>S = (3)/(2) in the solid state. Complexes [Zn(L(Pr))] (1), 4.CH(3)OH, 5.0.5toluene.CH(2)Cl(2), and 7.2.5CH(2)Cl(2) have been structurally characterized by low-temperature (100 K) X-ray crystallography. All iron complexes have been carefully studied by zero- and applied-field M?ssbauer spectroscopy. In addition, Sellmann's complexes [Fe(pyS(4))(NO)](0/1+) and [Fe(pyS(4))X] (X = PR(3), CO, SR(2)) have been studied by EPR and M?ssbauer spectroscopies and DFT calculations (pyS(4) = 2,6-bis(2-mercaptophenylthiomethyl)pyridine(2-)). It is concluded that the electronic structure of 7 with an S = 1/2 ground state is low spin ferrous (S(Fe) = 0) with a coordinated neutral NO radical (Fe(II)-NO) whereas the S = 3/2 state corresponds to a high spin ferric (S(Fe) = 5/2) antiferromagnetically coupled to an NO(-) anion (S = 1). The S = 1/2<==>S = 3/2 equilibrium is then that of valence tautomers rather than that of a simple high spin<==>low spin crossover.     

Assay development and high-throughput screening of caspases in microfluidic format

Caspase proteases are familiar targets in drug discovery. A common format for screening to identify caspase inhibitors employs fluorogenic or colorimetric tetra-peptide substrates in 96, 384, or 1536 -well microtiter plates. The primary motivation for increasing the number of wells per plate is to reduce the reagent cost per test and increase the throughput of HTS operations. There are significant challenges, however, to moving into or beyond the 1536-well format, such as submicroliter liquid handling, liquid evaporation, increased surface area-to-volume ratios, and the potential for artifacts and interference from small air-borne particles such as lint. Therefore, HTS scientists remain keenly interested in technologies that offer alternatives to the ever-shrinking microtiter plate well. Microfluidic assay technology represents an attractive option that, in theory, consumes only subnanoliter volumes of reagents per test. We have successfully employed a microfluidic assay technology in fluorogenic screening assays for several caspase isoforms utilizing the Caliper Technologies Labchip platform. Caspase-3 is used as a representative case to describe microfluidic assay development and initial high-throughput screening results. In addition, microfluidic screening and plate-based screening are compared in terms of reagent consumption, data quality, and ease of operation.     

Targeted ferromagnetic coupling in a trinuclear copperII complex: analysis of the St = 3/2 spin ground state

The trinuclear Cu(II) complex [(talen)Cu(II)(3)] (1) using the new triplesalen ligand H(6)talen has been synthesized and structurally characterized. The three Cu(II) ions are bridged in a m-phenylene linkage by the phloroglucinol backbone of the ligand. This m-phenylene bridging mode results in ferromagnetic couplings with an S(t) = (3)/(2) spin ground state, which has been analyzed by means of EPR spectroscopy and DFT calculations. The EPR spectrum exhibits an unprecedented pattern of 10 hyperfine lines due to the coupling of three Cu(II) ions (I = (3)/(2)). Resonances around g = 4 in both perpendicular and parallel mode EPR spectra demonstrate a zero-field splitting of D approximately 74 x 10(-4) cm(-1) arising from anisotropic/antisymmetric exchange interactions. The DFT calculations show an alteration in the sign of the spin densities of the central benzene ring corroborating the spin-polarization mechanism as origin for the ferromagnetic coupling.     

Nanocrystalline iron oxide aerogels as mesoporous magnetic architectures

We have developed crystalline nanoarchitectures of iron oxide that exhibit superparamagnetic behavior while still retaining the desirable bicontinuous pore-solid networks and monolithic nature of an aerogel. Iron oxide aerogels are initially produced in an X-ray-amorphous, high-surface-area form, by adapting recently established sol-gel methods using Fe(III) salts and epoxide-based proton scavengers. Controlled temperature/atmosphere treatments convert the as-prepared iron oxide aerogels into nanocrystalline forms with the inverse spinel structure. As a function of the bathing gas, treatment temperature, and treatment history, these nanocrystalline forms can be reversibly tuned to predominantly exhibit either Fe(3)O(4) (magnetite) or gamma-Fe(2)O(3) (maghemite) phases, as verified by electron microscopy, X-ray and electron diffraction, microprobe Raman spectroscopy, and magnetic analysis. Peak deconvolution of the Raman-active Fe-O bands yields valuable information on the local structure and vacancy content of the various aerogel forms, and facilitates the differentiation of Fe(3)O(4) and gamma-Fe(2)O(3) components, which are difficult to assign using only diffraction methods. These nanocrystalline, magnetic forms retain the inherent characteristics of aerogels, including high surface area (>140 m(2) g(-1)), through-connected porosity concentrated in the mesopore size range (2-50 nm), and nanoscale particle sizes (7-18 nm). On the basis of this synthetic and processing protocol, we produce multifunctional nanostructured materials with effective control of the pore-solid architecture, the nanocrystalline phase, and subsequent magnetic properties.     

Molecular and electronic structure of four- and five-coordinate cobalt complexes containing two o-phenylenediamine- or two o-aminophenol-type ligands at various oxidation levels: an experimental, density functional, and correlated ab initio study

The bidentate ligands N-phenyl-o-phenylenediamine, H(2)((2)L(N)IP), or its analogue 2-(2-trifluoromethyl)anilino-4,6-di-tert-butylphenol, ((4)L(N)IP), react with [Co(II)(CH(3)CO(2))(2)]4H(2)O and triethylamine in acetonitrile in the presence of air yielding the square-planar, four-coordinate species [Co((2)L(N))(2)] (1) and [Co((4)L(O))(2)] (4) with an S=1/2 ground state. The corresponding nickel complexes [Ni((4)L(O))(2)] (8) and its cobaltocene reduced form [Co(III)(Cp)(2)][Ni((4)L(O))(2)] (9) have also been synthesized. The five-coordinate species [Co((2)L(N))(2)(tBu-py)] (2) (S=1/2) and its one-electron oxidized forms [Co((2)L(N))(2)(tBu-py)](O(2)CCH(3)) (2 a) or [Co((2)L(N))(2)I] (3) with diamagnetic ground states (S=0) have been prepared, as has the species [Co((4)L(O))(2)(CH(2)CN)] (7). The one-electron reduced form of 4, namely [Co(Cp)(2)][Co((4)L(O))(2)] (5) has been generated through the reduction of 4 with [Co(Cp)(2)]. Complexes 1, 2, 2 a, 3, 4, 5, 7, 8, and 9 have been characterized by X-ray crystallography (100 K). The ligands are non-innocent and may exist as catecholate-like dianions ((2)L(N)IP)(2-), ((4)L(N)IP)(2-) or pi-radical semiquinonate monoanions ((2)L(N)ISQ)(*) (-), ((4)L(N)ISQ)(*) (-) or as neutral benzoquinones ((2) L(N)IBQ)(0), ((4) L(N)IBQ)(0); the spectroscopic oxidation states of the central metal ions vary accordingly. Electronic absorption, magnetic circular dichroism, and EPR spectroscopy, as well as variable temperature magnetic susceptibility measurements have been used to experimentally determine the electronic structures of these complexes. Density functional theoretical (DFT) and correlated ab initio calculation have been performed on the neutral and monoanionic species [Co((1)L(N))(2)](0,-) in order to understand the structural and spectroscopic properties of complexes. It is shown that the corresponding nickel complexes 8 and 9 contain a low-spin nickel(II) ion regardless of the oxidation level of the ligand, whereas for the corresponding cobalt complexes the situation is more complicated. Spectroscopic oxidation states describing a d(6) (Co(III)) or d(7) (Co(II)) electron configuration cannot be unambiguously assigned.