Biomedical subjects

Joshua Telser

Publications and source records attributed to Joshua Telser.

27 records · Page 2Linked to original sources

PubMed2003

High-frequency and -field EPR spectroscopy of tris(2,4-pentanedionato)manganese(III): investigation of solid-state versus solution Jahn-Teller effects.

High-frequency and -field electron paramagnetic resonance (HFEPR) spectroscopy of a classical coordination complex, Mn(acac)(3) (Hacac = 2,4-pentanedione), has been performed on both solid powder and frozen solution (in CH(2)Cl(2)/toluene, 3:2 v/v) samples. Parallel mode detection X-band EPR spectra exhibiting resolved (55)Mn hyperfine coupling were additionally obtained for frozen solutions. Magnetic susceptibility and field-dependent magnetization measurements were also made on powder samples. Analysis of the entire EPR data set for the frozen solution allowed extraction of the relevant spin Hamiltonian parameters: D = -4.52(2); |E| = 0.25(2) cm(-1); g(iso) = 1.99(1). The somewhat lower quality solid-state HFEPR data and the magnetic measurements confirmed these parameters. These parameters are compared to those for other complexes of Mn(III) and to previous studies on Mn(acac)(3) using X-ray crystallography, solution electronic absorption spectroscopy, and powder magnetic susceptibility. Crystal structures have been reported for Mn(acac)(3) and show tetragonal distortion, as expected for this Jahn-Teller ion (Mn(3+), 3d(4)). However, in one case, the molecule exhibits axial compression and, in another, axial elongation. The current HFEPR studies clearly show the negative sign of D, which corresponds to an axial (tetragonal) elongation in frozen solution. The correspondence among solution and solid-state HFEPR data, solid-state magnetic measurements, and an HFEPR study by others on a related complex indicates that the form of Mn(acac)(3) studied here exhibits axial elongation in all cases. Such tetragonal elongation has been found for Mn(3+) and Cr(2+) complexes with homoleptic pseudooctahedral geometry as well as for Mn(3+) in square pyramidal geometry. This taken together with the results obtained here for Mn(acac)(3) in frozen solution indicates that axial elongation could be considered the "natural" form of Jahn-Teller distortion for octahedral high-spin 3d(4) ions. The previous electronic absorption data together with current HFEPR and magnetic data allow estimation of ligand-field parameters for Mn(acac)(3).

Journal Article↗

PubMed2003

Direct observation of fine structure transitions in a paramagnetic nickel(II) complex using far-infrared magnetic spectroscopy: a new method for studying high-spin transition metal complexes.

Novel far-infrared (FIR) absorption spectroscopy in conjunction with multiple, fixed external magnetic fields (FIR magnetic spectroscopy, FIRMS) has been used to investigate pseudotetrahedral complexes with the formula M(PPh(3))(2)Cl(2) (M = Ni, Zn; Ph = C(6)H(5)). Crystal structures have been reported for the Ni complex; we report the structure of the Zn complex. Transmission spectra at 5 K of Ni(PPh(3))(2)Cl(2) (S = 1) at zero magnetic field exhibit absorption bands at 11.41, 15.28, and 23.0 cm(-1). The two lower frequency bands show great sensitivity to external magnetic field, and their field dependence is as expected for electron spin transitions allowing precise determination of the following parameters: |D| = 13.35(1) cm(-1), |E| = 1.93(1) cm(-1), g(x,y) = 2.20(1), g(z) = 2.00(1). Corresponding spectra of Zn(PPh(3))(2)Cl(2) (S = 0) exhibit bands only at >20 cm(-1), which show no field dependence. FIRMS is a promising technique for direct investigation of the electronic structure of high-spin transition metal complexes.

Journal Article↗

PubMed2003

High frequency and field EPR spectroscopy of Mn(III) complexes in frozen solutions.

We have performed high-frequency and -field electron paramagnetic resonance (HFEPR) experiments on two complexes of high-spin Mn(III) (3d(4),S=2): mesotetrasulfonato-porphyrinatomanganese(III) (Mn(TSP)) and [(R,R)-(-)-N,N(')-bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediaminomanganese(III)] (Mn(salen)). The main aim of this work was to qualitatively and quantitatively characterize the conditions suitable for HFEPR of high-spin transition metal complexes in frozen solutions, and compare them with experiments performed on solid samples. Mn(TSP) is a porphyrin complex soluble in water, in contrast to most metalloporphyrins. Mn(salen), often referred to as Jacobsen's catalyst, is a complex widely used in organic synthesis for alkene epoxidation, and is soluble in organic solvents. High-quality HFEPR signals were observed for solid state Mn(TSP), as has been previously shown for many Mn(III) complexes. The present study is, however, the first to report high-quality HFEPR spectra of a Mn(III) complex in frozen aqueous solution. Analysis of the data yielded the following spin Hamiltonian parameters: S=2; D=-3.16+/-0.02 cm(-1), E=0, and isotropic g=2.00(2). No X-band EPR signals were observed for Mn(TSP), which is a consequence of this being a rigorously axial spin system. Mn(salen), in contrast, did not give good quality HFEPR spectra in the solid state, but high-quality HFEPR spectra were recorded in frozen organic solutions. Analysis of the data yielded the following spin Hamiltonian parameters: S=2; D=-2.47+/-0.02 cm(-1), |E|=0.17+/-0.01 cm(-1), and isotropic g=2.00(2). These values differ from those reported using X-band parallel mode EPR [J. Am. Chem. Soc. 123 (2001) 5710], as discussed in the text. Therefore, a comparison between HFEPR and parallel-mode X-band spectroscopy is made. Finally, the concentration sensitivity aspect of HFEPR spectroscopy is also discussed.

Electron Spin Resonance Spectroscopy↗

PubMed2002

EPR spectra from "EPR-silent" species: high-frequency and high-field EPR spectroscopy of pseudotetrahedral complexes of nickel(II).

High-frequency and high-field electron paramagnetic resonance (HFEPR) spectroscopy (using frequencies of approximately 90-550 GHz and fields up to approximately 15 T) has been used to probe the non-Kramers, S = 1, Ni(2+) ion in a series of pseudotetrahedral complexes of general formula NiL(2)X(2), where L = PPh(3) (Ph = phenyl) and X = Cl, Br, and I. Analysis based on full-matrix solutions to the spin Hamiltonian for an S = 1 system gave zero-field splitting parameters: D = +13.20(5) cm(-1), /E/ = 1.85(5) cm(-1), g(x) = g(y) = g(z) = 2.20(5) for Ni(PPh(3))(2)Cl(2). These values are in good agreement with those obtained by powder magnetic susceptibility and field-dependent magnetization measurements and with earlier, single-crystal magnetic susceptibility measurements. For Ni(PPh(3))(2)Br(2), HFEPR suggested /D/ = 4.5(5) cm(-1), /E/ = 1.5(5) cm(-1), g(x) = g(y) = 2.2(1), and g(z) = 2.0(1), which are in agreement with concurrent magnetic measurements, but do not agree with previous single-crystal work. The previous studies were performed on a minor crystal form, while the present study was performed on the major form, and apparently the electronic parameters differ greatly between the two. HFEPR of Ni(PPh(3))(2)I(2) was unsuccessful; however, magnetic susceptibility measurements indicated /D/ = 27.9(1) cm(-1), /E/ = 4.7(1), g(x) = 1.95(5), g(y) = 2.00(5), and g(z) = 2.11(5). This magnitude of the zero-field splitting ( approximately 840 GHz) is too large for successful detection of resonances, even for current HFEPR spectrometers. The electronic structure of these complexes is discussed in terms of their molecular structure and previous electronic absorption spectroscopic studies. This analysis, which involved fitting of experimental data to ligand-field parameters, shows that the halo ligands act as strong pi-donors, while the triphenylphosphane ligands are pi-acceptors.

Electron Spin Resonance Spectroscopy↗

PubMed2002

EPR study of substrate binding to the Mn(II) active site of the bacterial antibiotic resistance enzyme FosA: a better way to examine Mn(II).

FosA is a manganese metalloglutathione transferase that confers resistance to the broad-spectrum antibiotic fosfomycin, (1R,2S)-epoxypropylphosphonic acid. The reaction catalyzed by FosA involves the attack by glutathione on fosfomycin to yield the product 1-(S-glutathionyl)-2-hydroxypropylphosphonic acid. The enzyme is a dimer of 16 kDa subunits, each of which harbors one mononuclear Mn(II) site. The coordination environment of the Mn(II) in the FosA x Mn(2+) complex is composed of a glutamate and two histidine ligands and three water molecules. Here we report EPR spectroscopic studies on FosA, in which EPR spectra were obtained at 35 GHz and 2 K using dispersion-detection rapid-passage techniques. This approach provides an absorption envelope line shape, in contrast to the conventional (slow-passage) derivative line shape, and is a more reliable way to collect spectra from Mn(II) centers with large zero-field splitting. We obtain excellent spectra of FosA bound with substrate, substrate analogue phosphate ion, and product, whereas these states cannot be studied by X-band, slow-passage methods. Simulation of the EPR spectra shows that binding of substrate or analogue causes a profound change in the electronic parameters of the Mn(II) ion. The axial zero-field splitting changes from [D] = 0.06 cm(-1) for substrate-free enzyme to 0.23 cm(-1) for fosfomycin-bound enzyme, 0.28 (1) cm(-1) for FosA with phosphate, and 0.27 (1) cm(-1) with product. Such a large zero-field splitting is uncommon for Mn(II). A simple ligand field analysis of this change indicates that binding of the phosphonate/phosphate group of substrate or analogue changes the electronic energy levels of the Mn(II) 3d orbitals by several thousand cm(-1), indicative of a significant change in the Mn(II) coordination sphere. Comparison with related enzymes (glyoxalase I and MnSOD) suggests that the change in the coordination environment on substrate binding may correspond to loss of the glutamate ligand.

Anti-Bacterial Agents↗

PubMed2002

17O ENDOR detection of a solvent-derived Ni-(OH(x))-Fe bridge that is lost upon activation of the hydrogenase from Desulfovibrio gigas.

Crystallographic studies of the hydrogenases (Hases) from Desulfovibrio gigas (Dg) and Desulfovibrio vulgaris Miyazaki (DvM) have revealed heterodinuclear nickel-iron active centers in both enzymes. The structures, which represent the as-isolated (unready) Ni-A (S = (1)/(2)) enzyme state, disclose a nonprotein ligand (labeled as X) bridging the two metals. The bridging atom was suggested to be an oxygenic (O(2)(-) or OH(-)) species in Dg Hase and an inorganic sulfide in DvM Hase. To determine the nature and chemical characteristics of the Ni-X-Fe bridging ligand in Dg Hase, we have performed 35 GHz CW (17)O ENDOR measurements on the Ni-A form of the enzyme, exchanged into H(2)(17)O, on the active Ni-C (S = (1)/(2)) form prepared by H(2)-reduction of Ni-A in H(2)(17)O, and also on Ni-A formed by reoxidation of Ni-C in H(2)(17)O. In the native state of the protein (Ni-A), the bridging ligand does not exchange with the H(2)(17)O solvent. However, after a reduction/reoxidation cycle (Ni-A --> Ni-C --> Ni-A), an (17)O label is introduced at the active site, as seen by ENDOR. Detailed analysis of a 2-D field-frequency plot of ENDOR spectra taken across the EPR envelope of Ni-A((17)O) shows that the incorporated (17)O has a roughly axial hyperfine tensor, A((17)O) approximately [5, 7, 20] MHz, discloses its orientation relative to the g tensor, and also yields an estimate of the quadrupole tensor. The substantial isotropic component (a(iso)((17)O) approximately 11 MHz) of the hyperfine interaction indicates that a solvent-derived (17)O is indeed a ligand to Ni and thus that the bridging ligand X in the Ni-A state of Dg Hase is indeed an oxygenic (O(2)(-) or OH(-)) species; comparison with earlier EPR results by others indicates that the same holds for Ni-B. The small (57)Fe hyperfine coupling seen previously for Ni-A (A((57)Fe) approximately 0.9 MHz) is now shown to persist in Ni-C, A((57)Fe) approximately 0.8 MHz. However, the (17)O signal is lost upon reductive activation to the Ni-C state; reoxidation to Ni-A leads to the reappearance of the signal. Consideration of the electronic structure of the EPR-active states of the dinuclear center leads us to suggest that the oxygenic bridge in Ni-A(B) is lost in Ni-C and is re-formed from solvent upon reoxidation to Ni-A. This implies that the reductive activation to Ni-C opens Ni/Fe coordination sites which may play a central role in the enzyme's activity.

Binding Sites↗

PubMed2002

High-frequency and -field electron paramagnetic resonance of high-spin manganese(III) in tetrapyrrole complexes.

High-field and -frequency electron paramagnetic resonance (HFEPR) spectroscopy has been used to study three complexes of high spin Manganese(III), 3d4, S = 2. The complexes studied were tetraphenylporphyrinatomanganese(III) chloride (MnTPPCI), phthalocyanatomanganese(III) chloride (MnPcCl), and (8,12-diethyl-2,3,7,13,17,18-hexamethylcorrolato)manganese(III) (MnCor). We demonstrate the ability to obtain both field-oriented (single-crystal like) spectra and true powder pattern HFEPR spectra of solid samples. The latter are obtained by immobilizing the powder, either in an n-eicosane mull or KBr pellet. We can also obtain frozen solution HFEPR spectra with good signal-to-noise, and yielding the expected true powder pattern. Frozen solution spectra are described for MnTPPCl in 2:3 (v/v) toluene/CH2Cl2 solution and for MnCor in neat pyridine (py) solution. All of the HFEPR spectra have been fully analyzed using spectral simulation software and a complete set of spin Hamiltonian parameters has been determined for each complex in each medium. Both porphyrinic complexes (MnTPPCl and MnPcCl) are rigorously axial systems, with similar axial zero-field splitting (zfs): D approximately -2.3 cm(-1), and g values quite close to 2.00. In contrast, the corrole complex, MnCor, exhibits slightly larger magnitude, rhombic zfs: D approximtely -2.6 cm(-1), absolute value(E) approximately 0.015 cm(-1), also with g values quite close to 2.00. These results are discussed in terms of the molecular structures of these complexes and their electronic structure. We propose that there is a significant mixing of the triplet (S = 1) excited state with the quintet (S= 2) ground state in Mn(III) complexes with porphyrinic ligands, which is even more pronounced for corroles.

Bromides↗

PubMed1999

High-Frequency and -Field Electron Paramagnetic Resonance of High-Spin Manganese(III) in Porphyrinic Complexes.

High-field and -frequency electron paramagnetic resonance (HFEPR) spectroscopy has been used to study two complexes of high-spin manganese(III), d(4), S = 2. The complexes studied were (tetraphenylporphyrinato)manganese(III) chloride and (phthalocyanato)manganese(III) chloride. Our previous HFEPR study (Goldberg, D. P.; Telser, J.; Krzystek, J.; Montalban, A. G.; Brunel, L.-C.; Barrett, A. G. M.; Hoffman, B. M. J. Am. Chem. Soc. 1997, 119, 8722-8723) included results on the porphyrin complex; however, we were unable to obtain true powder pattern HFEPR spectra, as the crystallites oriented in the intense external magnetic field. In this work we are now able to immobilize the powder, either in an n-eicosane mull or KBr pellet and obtain true powder pattern spectra. These spectra have been fully analyzed using spectral simulation software, and a complete set of spin Hamiltonian parameters has been determined for each complex. Both complexes are rigorously axial systems, with relatively low magnitude zero-field splitting: D approximately -2.3 cm(-)(1) and g values quite close to 2.00. Prior to this work, no experimental nor theoretical data exist for the metal-based electronic energy levels in Mn(III) complexes of porphyrinic ligands. This lack of information is in contrast to other transition metal complexes and is likely due to the dominance of ligand-based transitions in the absorption spectra of Mn(III) complexes of this type. We have therefore made use of theoretical values for the electronic energy levels of (phthalocyanato)copper(II), which electronically resembles these Mn(III) complexes. This analogy works surprisingly well in terms of the agreement between the calculated and experimentally determined EPR parameters. These results show a significant mixing of the triplet (S = 1) excited state with the quintet (S = 2) ground state in Mn(III) complexes with porphyrinic ligands. This is in agreement with the experimental observation of lower spin ground states in other metalloporphyrinic complexes, such as those of Fe(II) with S = 1.

Journal Article↗

PubMed1999

Investigation of the Unusual Electronic Structure of Pyrococcus furiosus 4Fe Ferredoxin by EPR Spectroscopy of Protein Reduced at Ambient and Cryogenic Temperatures.

The hyperthermophilic archaeon Pyrococcus furiosus contains a novel ferredoxin (Pf-Fd) in which, in the native 4Fe form, three of the Fe ions are coordinated to the protein by cysteinyl thiolato ligands, but the fourth Fe is coordinated by an aspartyl carboxylato ligand ([Fe(4)S(4)(cys)(3)(asp)](2)(-)(,3)(-)). Chemical reduction at ambient temperature of the oxidized 4Fe form (Pf-Fd 4Fe-ox, S = 0 ground state, with the cluster core indicated by [Fe(4)S(4)](2+)(ox)) produces a reduced 4Fe form (Pf-Fd 4Fe-red, with the cluster core indicated by [Fe(4)S(4)](+)(red)). Pf-Fd 4Fe-red, [Fe(4)S(4)](+)(red) core, in frozen solution exhibits S = (1)/(2) and (3)/(2) electronic states that are not in thermal equilibrium. The two spin states thus represent alternate ground states of the reduced cluster (cluster cores indicated by [Fe(4)S(4)](+)(red1) and [Fe(4)S(4)](+)(red2), respectively), rather than a ground and excited spin state. Low-temperature (77 K) reduction of 4Fe-ox in frozen solution by gamma-irradiation produces in high yield the reduced state of the cluster that is trapped in the structure of the oxidized parent cluster, and thus has a cluster core denoted by [Fe(4)S(4)](+)(ox). The [Fe(4)S(4)](+)(ox) form also exhibits non thermally converting S = (3)/(2) and (1)/(2) components in the same proportion as seen for [Fe(4)S(4)](+)(red). The EPR signal of the S = (3)/(2) component that results from cryoreduction ([Fe(4)S(4)](+)(ox2)) is indistinguishable, within experimental variability, from that seen in the ambient-temperature, chemically reduced protein ([Fe(4)S(4)](+)(red2)), and the signals of the two S = (1)/(2) components ([Fe(4)S(4)](+)(ox1) and [Fe(4)S(4)](+)(red1), respectively) closely resemble each other, although they are not identical. Previous NMR studies at ambient temperature showed evidence for only one species in fluid solution for both Pf-Fd 4Fe-ox and 4Fe-red. Taken together, the NMR and EPR results indicate that fluid solutions of either oxidized or reduced Pf-Fd contain only one conformer, but that frozen solutions of each contain two distinct conformers, with each one of the pair of oxidized protein forms having a corresponding reduced form. A shift in the coordination mode of the aspartyl carboxylato ligand is proposed to account for this conformational flexibility.

Journal Article↗