Mn(dca)2(pym)2 and Mn(dca)2(pym)(H2O) {dca = dicyanamide; pym = pyrimidine}: New coordination polymers exhibiting 1- and 2-D topologies

Two new coordination polymers comprised of Mn(2+), N(CN)(2)(-) (dicyanamide, herein denoted dca) and pyrimidine (pym) have been synthesized and structurally and magnetically characterized. Mn(dca)(2)(pym)(2), , crystallizes in the orthorhombic space group Pbcn and forms trans bi-bridged Mn-(micro(1,5)-dca)(2)-Mn ribbons that extend along the b-axis of the unit cell. Two terminally bonded pym ligands are trans-coordinated to the Mn center. Adjacent chains interdigitate in an undulating fashion presumably due to a templating effect imposed by the pym ligands where N-atoms of consecutive pym rings stack parallel to the chain axis. Mn(dca)(2)(pym)(H(2)O), , which crystallizes in the monoclinic space group P2(1)/c, has a unique interdigitated 2D network that consists of double-bridged [Mn(2)(dca)(2)(pym)(2)(H(2)O)(2)](2+)"dimers" that are connected via single-bridging dca ligands. Each MnN(5)O octahedron is comprised of a coordinated H(2)O, a monodentate pym ligand, and four micro(1,5)-bridging dca anions. The magnetic data for were fitted to a uniform antiferromagnetic chain model which yielded J/k(B) = -0.34(1) K. In contrast, is best described as an alternating chain owing to the presence of both single- and double-bridging dca anions; a least-squares fit afforded J(a) = -0.43(1) and J(b) = -0.20(2) K, respectively. A transition to long-range magnetic ordering was observed for below approximately 2.4 K in addition to a field-induced spin flop transition at 15.6 kOe (1.7 K).     

cis-trans photoisomerization in [Ru(DIP)2(MeOH)2][OTf]2: synthesis, NMR, X-ray structure of the trans-isomer and photophysical properties

The first trans-ruthenium complex trans-[Ru(DIP)2(MeOH)2][OTf]2 (1b, where DIP = 4,7-diphenyl-1,10-phenanthroline) incorporating a pi-extended ligand was prepared via two methods: either photolysis of cis-[Ru(DIP)2(OTf)2] in MeOH-Et(2)O or via crystallization from MeOH-Et(2)O in direct sunlight. The X-ray molecular structure of is reported and confirmed the trans geometry of the title compound. The cis-trans isomerization process was monitored by 1H-NMR and showed that 1b reverts back to cis-[Ru(DIP)2(MeOH)2][OTf]2 (1a) in methanol-d4 after 15 h at 55 degrees C or several days at room temperature. The absorption spectra recorded in MeOH showed a bathochromic shift of the MLCT band of the trans-isomer 1b relative to that of the cis complex 1a. Interestingly at 77 K the emission spectrum of 1b is red shifted compared to the cis analog 1a. A rational explanation in terms of the energy of the excited states in the cis- and trans-isomers is proposed to explain this behavior.     

Intramolecular electron transfer within a covalent, fixed-distance donor-acceptor molecule in an ionic liquid

Intramolecular photoinduced charge separation and recombination within the donor-acceptor molecule 4-(N-pyrrolidino)naphthalene-1,8-imide-pyromellitimide, 5ANI-PI, are studied using ultrafast transient absorption spectroscopy in the room-temperature ionic liquid, 1-ethyl-3-methylimidazolium bis(trifluoromethanesulfonyl)amide [EMIM][Tf2N]. The rate constants of both photoinduced charge separation and charge recombination for 5ANI-PI in [EMIM][Tf2N] are comparable to those observed in pyridine, which has a static dielectric constant similar to that of [EMIM][Tf2N] but a viscosity that is nearly 2 orders of magnitude lower than that of [EMIM][Tf2N]. The electron-transfer dynamics of 5ANI-PI in [EMIM][Tf2N] are compared to those in pyridine as a function of temperature and are discussed in the context of recently reported ionic liquid solvation studies.     

Intralaboratory validation of cell-free translation assay for detecting ricin toxin biological activity

A cell-free translation (CFT) assay for determining ricin biological activity was validated. The statistical data from the validation study showed a high level of precision within and between runs of the assay. The assay was specific for determining ricin biological activity in food-based matrixes and discriminated ricin from other ribosome-inactivating proteins. The mean bias (relative error) between measured ricin concentrations of 3 validation samples and their nominal concentrations was 1.1, 6.6, and 20.3%, while the coefficient of variation (CV) was 14.1, 7.7, and 13.5%, respectively, demonstrating good precision, accuracy, and linearity. The CVs of ricin concentrations in 2 ricin-containing samples calculated from a dilution series were <5 and <12%, respectively, demonstrating very good parallelism. The analyte stability of ricin-containing samples stored for 1 month either at 4 or -20 degrees C, the stability of ricin stock solutions, and the results of assays executed by different analysts and using different luminometers were evaluated. The statistical validation data confirmed that the 4-parameter logistic equation, y = (a - d)/[1 + (x/c)b] + d, provided an accurate representation of a sigmoidal relationship between the measured response and the observed ricin concentration for the CFT assay.     

Racemization of secondary alcohols catalyzed by cyclopentadienylruthenium complexes: evidence for an alkoxide pathway by fast beta-hydride elimination-readdition

The racemization of sec-alcohols catalyzed by pentaphenylcyclopentadienyl-ruthenium complex 3a has been investigated. The mechanism involves ruthenium-alkoxide intermediates: reaction of tert-butoxide ruthenium complex 4 with a series of sec-alcohols with different electronic properties gave ruthenium complexes bearing a secondary alkoxide as a ligand. The characterization of these alkoxide complexes by NMR spectroscopy together with a study of the reaction using in situ IR spectroscopy is consistent with a mechanism in which the alkoxide substitution step and the beta-hydride elimination step occur without CO dissociation. The alkoxide substitution reaction is proposed to begin with hydrogen bonding of the incoming alcohol to the active ruthenium-alkoxide intermediate. Subsequent alkoxide exchange can occur via two pathways: i) an associative pathway involving a eta3-CpRu intermediate; or ii) a dissociative pathway within the solvent cage. Racemization at room temperature of a 1:1 mixture of (S)-1-phenylethanol and (S)-1-phenyl-[D4]-ethanol gave only rac-1-phenylethanol, and rac-1-phenyl-[D4]-ethanol, providing strong support for a mechanism in which the substrate stays coordinated to the metal center throughout the racemization, and does not leave the coordination sphere. Furthermore, racemization of a sec-alcohol bearing a ketone moiety within the same molecule does not result in any reduction of the original ketone, which rules out a mechanism where the intermediate ketone is trapped within the solvent cage. These results are consistent with a mechanism where eta3-Ph(5)C(5)-ruthenium intermediates are involved. Competitive racemization on nondeuterated and alpha-deuterated alpha-phenylethanols was used to determine the kinetic isotope effect kH/kD for the ruthenium-catalyzed racemization. The kinetic isotope effect kH/kD for p- X-C(6)H(4)CH(OH)CH(3) was 1.08, 1.27 and 1.45 for X=OMe, H, and CF3, respectively.     

Mass spectrometric evidence for different complexes of peptides and proteins with arsenic(III), arsenic(V), copper(II), and zinc(II) species

Trivalent and pentavalent arsenic were incubated with sulfur-containing amino acid, peptide and protein solutions both as organic compounds (phenylarsine oxide, phenylarsonic acid, dimethylarsinic acid, monomethylarsonic acid) and as inorganic compounds (arsenite, As(III), and arsenate, As(V)). After incubation of phenylarsine oxide solutions with cysteine and glutathione the mass spectra showed a covalent bond between arsenic and sulfur, which was stable at both acidic and neutral pH values. The mass spectra were dominated by monovalent ions at m/z 272 for cysteine samples and at m/z 458 for glutathione samples. Based on these masses the ionic structures could be ascribed to either fragment ions of the covalent arsenic-sulfur complexes or to other arsenic-bonding sites presumably at the amino group. Interestingly, under the same conditions no interactions of inorganic arsenite or arsenate could be measured. In the presence of added Cu(2+) ions all mass signals caused by a reaction of phenylarsine oxide with glutathione disappeared. In these mass spectra only the oxidised form of glutathione (GSSG) was found because of the redox activity of Cu(II). For the model protein lysozyme, no interactions with arsenic could be detected, whereas definite Cu- and Zn-lysozyme complexes with a stoichiometry of 1:1 and 2:1 for Zn(2+) ions and Cu(2+) ions, respectively, were observed. In contrast, for thioredoxin a bonding of As that depended on the concentration of the disulfide-reducing agent tris(2-carboxyethyl) phosphine was demonstrated.For three different phenylarsonic acids and for dimethylarsinic acid that all contain pentavalent arsenic, complexes with glutathione appeared in the mass spectra, which can be attributed to non-covalent interactions or to a covalent bond caused by an additive reaction.The optimisation of the experimental conditions necessary for the mass spectrometric analysis of the interactions of the arsenic species with peptides and proteins is described and the obtained mass spectra that provide information on the kinds of bonds are discussed.     

Coupled affinity-hydrophobic monolithic column for on-line removal of immunoglobulin G, preconcentration of low abundance proteins and separation by capillary zone electrophoresis

A butyl methacrylate-co-ethylene dimethacrylate (BuMA-co-EDMA) monolith was synthesized by UV initiated polymerization at the inlet end of a 75 microm I.D. fused silica capillary that had been previously coated with a protein compatible polymer, poly(vinyl)alcohol. The monolith was used for on-line preconcentration of proteins followed by capillary electrophoresis (CE) separation. For the analysis of standard proteins (cytochrome c, lysozyme and trypsinogen A) this system proved reproducible. The run-to-run %RSD values for migration time and corrected peak area were less than 5%, which is typical of CE. As measured by frontal analysis using lysozyme as solute, saturation of a 1cm monolith was reached after loading 48 ng of protein. Finally, the BuMA-co-EDMA monolithic preconcentrator was coupled to a protein G monolithic column via a zero dead volume union. The coupled system was used for on-line removal of IgG, preconcentration of standard proteins and CE separation. This system could be a valuable sample preparation tool for the analysis of low abundance proteins in complex samples such as human serum, in which high abundance proteins, e.g., human serum albumin (HSA) and immunoglobulin G (IgG), hinder identification and quantification of low abundance proteins.     

Tumor selectivity at short times following systemic administration of a liposomal temoporfin formulation in a murine tumor model

Meso-tetra(hydroxyphenyl)chlorin (mTHPC) (INN: Temoporfin) is one of the most potent photodynamically active substances in clinical use. Treatment protocols for Temoporfin-mediated photodynamic therapy often rely on drug-light intervals of several days in order for the photosensitizer to accumulate within the target tissue, though tumor selectivity is limited. Here, the mTHPC localization was studied at 2-8 h following systemic administration of a liposomal Temoporfin formulation (0.15 mg kg(-1) b.w.) in HT29 human colon adenocarcinoma in NMRI nu/nu mice. Photosensitizer distribution within tumor and internal organs was investigated by means of high performance liquid chromatography following chemical extraction, as well as in situ fluorescence imaging and point-monitoring fluorescence spectroscopy. For tumor tissue, the Temoporfin concentrations at 4 h (0.16+/-0.024 ng mg(-1)) and 8 h (0.18+/-0.064 ng mg(-1)) were significantly higher than at 2 h (0.08+/-0.026 ng mg(-1)). The average tumor-to-muscle and the tumor-to-skin selectivity were 6.6 and 2, respectively, and did not vary significantly with time after photosensitizer injection. In plasma, the Temoporfin concentration was low (0.07+/-0.07 ng mg(-1)) and showed no significant variation with time. Our results indicate a rapid biodistribution and clearance from the bloodstream. Within the same type of organ, data from both fluorescence methods generally exhibited a significant correlation with the extraction results.     

Controlling electron transfer dynamics in donor-bridge-acceptor molecules by increasing unpaired spin density on the bridge

A t-butylphenylnitroxide (BPNO*) stable radical is attached to an electron donor-bridge-acceptor (D-B-A) system having well-defined distances between the components: MeOAn-6ANI-Ph(BPNO*)-NI, where MeOAn=p-methoxyaniline, 6ANI=4-(N-piperidinyl)naphthalene-1,8-dicarboximide, Ph=phenyl, and NI=naphthalene-1,8:4,5-bis(dicarboximide). MeOAn-6ANI, BPNO*, and NI are attached to the 1, 3, and 5 positions of the Ph bridge, respectively. Time-resolved optical and EPR spectroscopy show that BPNO* influences the spin dynamics of the photogenerated triradical states 2,4(MeOAn+*-6ANI-Ph(BPNO*)-NI-*), resulting in slower charge recombination within the triradical, as compared to the corresponding biradical lacking BPNO*. The observed spin-spin exchange interaction between the photogenerated radicals MeOAn+* and NI-* is not altered by the presence of BPNO*. However, the increased spin density on the bridge greatly increases radical pair (RP) intersystem crossing from the photogenerated singlet RP to the triplet RP. Rapid formation of the triplet RP makes it possible to observe a biexponential decay of the total RP population with components of tau=740 ps (0.75) and 104 ns (0.25). Kinetic modeling shows that the faster decay rate is due to rapid establishment of an equilibrium between the triplet RP and the neutral triplet state resulting from charge recombination, whereas the slower rate monitors recombination of the singlet RP to ground state.