NO* release from MbFe(II)NO and HbFe(II)NO after oxidation by peroxynitrite

In this work, we showed that the reaction of peroxynitrite with MbFe(II)NO, in analogy to the corresponding reaction with HbFe(II)NO (Herold, S. Inorg. Chem. 2004, 43, 3783-3785), proceeds in two steps via the formation of MbFe(III)NO, from which NO* dissociates to produce iron(III)myoglobin (Mb = myoglobin; Hb = hemoglobin). The second-order rate constants for the first steps are on the order of 10(4) and 10(3) M(-1) s(-1), for the reaction of peroxynitrite with MbFe(II)NO and HbFe(II)NO, respectively. For both proteins, we found that the values of the second-order rate constants increase with decreasing pH, an observation that suggests that HOONO is the species responsible for oxidation of the iron center. Nevertheless, it cannot be excluded that the pH-dependence arises from different conformations taken up by the proteins at different pH values. In the presence of 1.2 mM CO2, the values of the second-order rate constants are larger, on the order of 10(5) and 10(4) M(-1) s(-1), for the reaction of peroxynitrite with MbFe(II)NO and HbFe(II)NO, respectively. The pH-dependence of the values for the reaction with MbFe(II)NO suggests that ONOOCO2- or the radicals produced from its decay (CO3*-/NO2*) are responsible for the oxidation of MbFe(II)NO to MbFe(III)NO. In the presence of large amounts of nitrite (in the tens and hundreds of millimoles range), we observed a slight acceleration of the rate of oxidation of HbFe(II)NO by peroxynitrite. A catalytic rate constant of 40 +/- 2 M(-1) s(-1) was determined at pH 7.0. Preliminary studies of the reaction between nitrite and HbFe(II)NO showed that this compound also can oxidize the iron center, albeit at a significantly slower rate. At pH 7.0, we obtained an approximate second-order rate constant of 3 x 10(-3) M(-1) s(-1).     

Isothiazolo[5,4‐d]isoxazole S,S‐dioxides and pyrazolo [3,4‐d]‐isothiazole S,S‐dioxides through cycloaddition reaction on 3‐benzylaminoisothiazole S,S‐dioxides

By reacting 4,5‐unsubstituted isothiazole dioxides with diazoalkanes and nitrile oxides bicyclic pyrazolo[3,4‐d]isothiazole and isothiazolo[5,4‐d]isoxazole S,S‐dioxides were obtained in good yield through a regioselective cycloaddition reaction. Through cycloaddition reaction of 3‐benzylamino‐4‐bromo‐isothiazole S,S‐dioxide labile cycloadducts were formed that underwent in situ dehydrobromination affording the corresponding aromatized compounds.     

Tuning anisotropy barriers in a family of tetrairon(III) single-molecule magnets with an S = 5 ground state

Tetrairon(III) Single-Molecule Magnets (SMMs) with a propeller-like structure exhibit tuneable magnetic anisotropy barriers in both height and shape. The clusters [Fe4(L1)2(dpm)6] (1), [Fe4(L2)2(dpm)6] (2), [Fe4(L3)2(dpm)6].Et2O (3.Et2O), and [Fe4(OEt)3(L4)(dpm)6] (4) have been prepared by reaction of [Fe4(OMe)6(dpm)6] (5) with tripodal ligands R-C(CH2OH)3 (H3L1, R = Me; H3L2, R = CH2Br; H3L3, R = Ph; H3L4, R = tBu; Hdpm = dipivaloylmethane). The iron(III) ions exhibit a centered-triangular topology and are linked by six alkoxo bridges, which propagate antiferromagnetic interactions resulting in an S = 5 ground spin state. Single crystals of 4 reproducibly contain at least two geometric isomers. From high-frequency EPR studies, the axial zero-field splitting parameter (D) is invariably negative, as found in 5 (D = -0.21 cm(-1)) and amounts to -0.445 cm(-1) in 1, -0.432 cm(-1) in 2, -0.42 cm(-1) in 3.Et2O, and -0.27 cm(-1) in 4 (dominant isomer). The anisotropy barrier Ueff determined by AC magnetic susceptibility measurements is Ueff/kB = 17.0 K in 1, 16.6 K in 2, 15.6 K in 3.Et2O, 5.95 K in 4, and 3.5 K in 5. Both |D| and U(eff) are found to increase with increasing helical pitch of the Fe(O2Fe)3 core. The fourth-order longitudinal anisotropy parameter B4(0), which affects the shape of the anisotropy barrier, concomitantly changes from positive in 1 ("compressed parabola") to negative in 5 ("stretched parabola"). With the aid of spin Hamiltonian calculations the observed trends have been attributed to fine modulation of single-ion anisotropies induced by a change of helical pitch.     

Water, solute, and segmental dynamics in polysaccharide hydrogels

Polysaccharide hydrogels have found several applications in the food industry, in biomedicine, and cosmetics. The study of polysaccharide hydrogels offers a challenging scenario of intrinsic heterogeneities in the crosslinking density and large time and space ranges that characterize a number of dynamic processes entailing segmental motions, water diffusion, and small-molecule diffusion. The understanding of such complex features is essential because of the extensive use of polysaccharidic moieties in the food industry, biomedical devices, and cosmetics. The study of phenomena occurring at the nanoscale to the mesoscale requires the combination of investigative tools to probe different time and distance scales and the structural characterization of the networks by established methodologies such as swelling and elastic modulus measurements. Elastic and quasielastic neutron scattering, and fluorescence recovery after photobleaching are emerging methodologies in this field. In this feature article we focus, somewhat arbitrarily, on these new approaches because other techniques, such as low-resolution proton NMR relaxometry and rheology, have been already described thoroughly in the literature. Case examples of polysaccharide hydrogels studied by neutron scattering and fluorescence recovery are presented here as contributions to the comprehension of the dynamic behavior of physical and chemical hydrogels based on polysaccharides. Quasielastic incoherent neutron scattering experiment on a Sephadex hydrogel sample at different temperatures.     

Steepest Descent on Real Flag Manifolds

Real flag manifolds are the isotropy orbits of noncompact symmetricspaces G/K. Any such manifold M is acted on transitively bythe (noncompact) Lie group G, and it is embedded in euclideanspace as a taut submanifold. The aim of this paper is to showthat the gradient flow of any height function is a one-parametersubgroup of G, where the gradient is defined with respect toa suitable homogeneous metric s on M; this generalizes the Kählermetric on adjoint orbits (the so-called complex flag manifolds).2000 Mathematics Subject Classification 53C30, 53C35.     

Study of aromatic nucleophilic substitution with amines on nitrothiophenes in room-temperature ionic liquids: are the different effects on the behavior of para-like and ortho-like isomers on going from conventional solvents to room-temperature ionic liquids related to solvation effects?

The kinetics of the nucleophilic aromatic substitution of some 2-L-5-nitrothiophenes (para-like isomers) with three different amines (pyrrolidine, piperidine, and morpholine) were studied in three room-temperature ionic liquids ([bmim][BF4], [bmim][PF6], and [bm(2)im][BF4], where bmim = 1-butyl-3-methylimidazolium and bm(2)im = 1-butyl-2,3-dimethylimidazolium). To calculate thermodynamic parameters, a useful instrument to gain information concerning reagent-solvent interactions, the reaction was carried out over the temperature range 293-313 K. The reaction occurs faster in ionic liquids than in conventional solvents (methanol, benzene), a dependence of rate constants on amine concentration similar to that observed in methanol, suggesting a parallel behavior. The above reaction also was studied with 2-bromo-3-nitrothiophene, an ortho-like derivative able to give peculiar intramolecular interactions in the transition state, which are strongly affected by the reaction medium.     

Formation and relaxation of excited states in solution: a new time dependent polarizable continuum model based on time dependent density functional theory

In this paper a novel approach to study the formation and relaxation of excited states in solution is presented within the integral equation formalism version of the polarizable continuum model. Such an approach uses the excited state relaxed density matrix to correct the time dependent density functional theory excitation energies and it introduces a state-specific solvent response, which can be further generalized within a time dependent formalism. This generalization is based on the use of a complex dielectric permittivity as a function of the frequency, epsilonomega. The approach is here presented in its theoretical formulation and applied to the various steps involved in the formation and relaxation of electronic excited states in solvated molecules. In particular, vertical excitations (and emissions), as well as time dependent Stokes shift and complete relaxation from vertical excited states back to ground state, can be obtained as different applications of the same theory. Numerical results on two molecular systems are reported to better illustrate the features of the model.     

Determination of perfluorooctanoic acid and perfluorooctanesulfonate in human tissues by liquid chromatography/single quadrupole mass spectrometry

A method is described that permits the measurement of the levels of perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) in human liver, kidney, adipose tissue, brain, basal ganglia, hypophysis, thyroid, gonads, pancreas, lung, skeletal muscle and blood, even in subjects not occupationally exposed to these compounds. The purification of samples involved the use of trifunctional (tC18) and strong anion-exchange (SAX) solid-phase extraction cartridges, and the analysis utilized a high-performance liquid chromatograph coupled to a single quadrupole mass spectrometer (LC/MS). The analyses were conducted on a mixed-bed reversed-phase column by gradient runs using 3 mM ammonium acetate/methanol mixtures at different proportions as the mobile phase. The detector was used in electrospray negative ion mode by recording simultaneously the ions m/z 413.0 (PFOA) and 499.0 (PFOS). Perfluorononanoic acid (PFNA), added to the samples before the purification, was used as the internal standard (ion monitored = m/z 463.6). The recovery rates of the extraction procedure ranged from 79.6 to 95.6% (CV% 1.7-7.4%) for PFOA, from 79.7 to 100.8% (CV% = 1.2-7.1) for PFOS, and from 89.1 to 102.3% (CV% = 0.9-5.2 %) for PFNA. The calibration curves were linear up to at least 400 ng of analytes per gram of tissue. The detection limits (signal-to-noise ratio = 3) were 0.1 ng/g for both PFOA and PFOS measured in all tissues except adipose tissue, where the limits were about 0.2 ng/g. The content of analytes in tissues varied from 0.3 to 3.8 ng/g (respectively: basal ganglia and lung) for PFOA, and from 1.0 to 13.6 ng/g (respectively: skeletal muscle and liver) for the linear isomer of PFOS. The method is suitable to evaluate the content of PFOA and PFOS in different tissues taken from the general population exposed to very low concentrations of these pollutants.     

Pulse radiolysis studies of the reactions of CO3*- and NO2* with nitrosyl(II)myoglobin and nitrosyl(II)hemoglobin

The reactions of carbonate radical anion [CO3*-, systematic name: trioxidocarbonate*1-] with nitrosyl(II)hemoglobin (HbFe(II)NO) and nitrosyl(II)myoglobin (MbFe(II)NO) were studied by pulse radiolysis in N2O-saturated 0.25 M sodium bicarbonate solutions at pH 10.0 and room temperature. The reactions proceed in two steps: outer-sphere oxidation of the nitrosyliron(II) proteins to their corresponding nitrosyliron(III) forms and subsequent dissociation of NO*. The second-order rate constants measured for the first reaction steps were (4.3 +/- 0.2) x 10(8) and (1.5 +/- 0.3) x 10(8) M(-1) s(-1), for MbFe(II)NO and HbFe(II)NO, respectively. The reactions between nitrogen dioxide and MbFe(II)NO or HbFe(II)NO were studied by pulse radiolysis in N2O-saturated 0.1 M phosphate buffer pH 7.4 containing 5 mM nitrite. Also for the reactions of this oxidant with the nitrosyliron(II) forms of Mb and Hb a two-step reaction was observed: oxidation of the iron was followed by dissociation of NO*. The second-order rate constants measured for the first reaction steps were (2.9 +/- 0.3) x 10(7) and (1.8 +/- 0.3) x 10(7) M(-1) s(-1), for MbFe(II)NO and HbFe(II)NO, respectively. Both radicals appear to be able to oxidize the iron(II) centers of the proteins directly. Only for the reactions with HbFe(II)NO it cannot be excluded that, in a parallel reaction, CO3*- and NO2* first react with amino acid(s) of the globin, which then oxidize the nitrosyliron(II) center.     

Solvation of coumarin 153 in supercritical fluoroform

We present a study of local density augmentation around an attractive solute (i.e., giving rise to more attractive interaction with the solvent than solvent-solvent interactions) in supercritical fluoroform. This work is based on molecular dynamics simulations of coumarin 153 in supercritical fluoroform at densities both above and below the critical density, ranging from dilute gas-like to liquid-like, at a reduced temperature (T/T(c)) of 1.03. We focused on studying the structure of the solvation shell and the variation of the solute electronic absorption and emission shifts with density. Quantum calculations at the density functional theory (DFT) level were run on the solute in the ground state, and time-dependent DFT calculations were performed in the solute excited state in order to determine the solute-solvent potential parameters. The results obtained for the Stokes shift are in agreement with the experimental measurements. To evaluate local density augmentation from simulations, we used two different definitions, one based on the solvation number and the other derived from solvatochromic shifts. In the former case, the agreement with experimental results is good, while, in the latter case, better agreement is achieved by perturbatively including the induced-dipole contribution to the solvation energy.