Characterization of currently marketed heparin products: analysis of molecular weight and heparinase-I digest patterns

We evaluated polyacrylamide gel electrophoresis (PAGE) and size exclusion chromatography coupled with multi-angle laser light scattering (SEC-MALLS) approaches to determine weight-average molecular weight (M _w) and polydispersity (PD) of heparins. A set of unfractionated heparin sodium (UFH) and low-molecular-weight heparin (LMWH) samples obtained from nine manufacturers which supply the US market were assessed. For SEC-MALLS, we measured values for water content, refractive index increment (dn/dc), and the second virial coefficient (A ₂) for each sample prior to molecular weight assessment. For UFH, a mean ± standard deviation value for M _w of 16,773 ± 797 was observed with a range of 15,620 to 18,363 (n = 20, run in triplicate). For LMWHs by SEC-MALLS, we measured mean M _w values for dalteparin, tinzaparin, and enoxaparin of 6,717 ± 71 (n = 4), 6,670 ± 417 (n = 3), and 3,959 ± 145 (n = 3), respectively. PAGE analysis of the same UFH, dalteparin, tinzaparin, and enoxaparin samples showed values of 16,135 ± 643 (n = 20), 5,845 ± 45 (n = 4), 6,049 ± 95 (n = 3), and 4,772 ± 69 (n = 3), respectively. These orthogonal measurements are the first M _w results obtained with a large heparin sample set on product being marketed after the heparin crisis of 2008 changed the level of scrutiny of this drug class. In this study, we compare our new data set to samples analyzed over 10 years earlier. In addition, we found that the PAGE analysis of heparinase digested UFH and neat LMWH samples yield characteristic patterns that provide a facile approach for identification and assessment of drug quality and uniformity.     

Probing stepwise reaction of NNP-ligand copper(I) complex with elemental sulfur by using N-heterocyclic carbene as a trapper

The dinuclear NNP-ligand copper(I) complex [o-N═CH(C(4)H(3)N)-PPh(2)C(6)H(4)](2)Cu(2) (1) has been synthesized by the reaction of (CuMes)(4) (Mes = 2,4,6-Me(3)C(6)H(2)) with N-((1H-pyrrol-2-yl)-methylene)-2-(diphenylphosphino)benzenamine under an elimination of MesH. Further reaction of 1 with an excess of S(8) produced a mononuclear Cu(II) complex [o-N═CH(C(4)H(3)N)-P(S)Ph(2)C(6)H(4)](2)Cu (5) and CuS. CuS was identified by Raman spectroscopy and 1 and 5 were clearly confirmed by X-ray crystallography. The N-heterocyclic carbene was employed to react with 1 to give a mononuclear [o-N═CH(C(4)H(3)N)-PPh(2)C(6)H(4)]Cu{C[N(iPr)CMe](2)} (2). The reactions of 2 were carried out with (1)/(8), (2)/(8), and (5)/(8) equiv of S(8), leading to compounds [o-N═CH(C(4)H(3)N)-P(S)Ph(2)C(6)H(4)]Cu{C[N(iPr)CMe](2)} (3), [o-N═CH(C(4)H(3)N)-P(S)Ph(2)C(6)H(4)]Cu (4), and 5 respectively, in which CuS was generated in the third reaction and S═C[N(iPr)CMe](2) in the latter two reactions. The clean confirmation of 2-4 demonstrates a stepwise reaction process of 1 with S(8) to 5 and CuS and the N-heterocyclic carbene acts well as a trapping agent.     

K3B6O10Cl: a new structure analogous to perovskite with a large second harmonic generation response and deep UV absorption edge

Introduction of the Cl(-) anion in the borate systems generates a new perovskite-like phase, K(3)B(6)O(10)Cl, which exhibits a large second harmonic response, about four times that of KH(2)PO(4) (KDP), and is transparent from the deep UV (180 nm) to middle-IR region. K(3)B(6)O(10)Cl crystallizes in the noncentrosymmetric and rhombohedral space group R3m. The structure consists of the A-site hexaborate [B(6)O(10)] groups and the BX(3) Cl-centered octahedral [ClK(6)] groups linked together through vertices to form the perovskite framework represented by ABX(3).     

Studies of the isomerization and photophysical properties of a novel 2,2':6',2'-terpyridine-based ligand and its complexes

A novel 2,2':6',2'-terpyridine-based ligand L and its complexes [ML(2)](ClO(4))(2)·CH(2)Cl(2) (M = Cd 1, Zn 2, Cu 4, Mn 5), [CoL(2)](ClO(4))(2)3, CdLI(2)6 and CdL(SCN)(2)7 were synthesized and fully characterized. The crystal structures of 1-6 were solved by single crystal X-ray diffraction analysis. The linear absorption and emission properties, and third-order nonlinear optical (NLO) properties of all the complexes were systematically investigated. The equilibrium of the trans- and cis- isomers of L was studied both experimentally and theoretically. The configurations and photophysical properties of the complexes display a large dependence on the choice of metal ions and anions.     

Synthesis, crystal structures, photophysical properties, and bioimaging of living cells of bis-β-diketonate phenothiazine ligands and its cyclic dinuclear complexes

Two bis-β-diketones, RCOCH(2)CO-EPTZ-COCH(2)COR (EPTZ = 10-ethylphenothiazine; R = C(6)H(5) for H(2)L(1) and CF(3) for H(2)L(2)) and their cyclic dinuclear Zn(II), Cd(II), Ni(II), Mn(II), Cu(II), Co(II) complexes have been synthesized and fully characterized. Their crystal structures were determined by single crystal X-ray diffraction analysis. Their photophysical properties have been further investigated both experimentally and theoretically. The results revealed that significant enhancement of two-photon absorption cross section values were obtained for the cyclic dinuclear Zn(II) and Cd(II) complexes compared with their free ligands. Additionally, confocal microscopy and two-photon microscopy fluorescent imaging of MCF-7 cells labeled with two ligands and Zn(II) complexes reveal their potential applications as a biological fluorescent probe.     

Effects of inherent/enhanced solid acidity and morphology of diatomite templates on the synthesis and porosity of hierarchically porous carbon

The inherent or enhanced solid acidity of raw or activated diatomite is found to have significant effects on the synthesis of hierarchically porous diatomite-templated carbon with high surface area and special porous structure. The solid acidity makes raw/activated diatomite a catalyst for the generation of porous carbon, and the porous parameters of the carbon products are strongly dependent on the solid acidity of diatomite templates. The morphology of diatomite also dramatically affects the textural structure of porous carbon. Two types of macroporous structures in the carbon product, the partially solid pillars and the ordered hollow tubes, derive from the replication of the central and the edge pores of diatom shell, respectively. The hierarchically porous carbon shows good capability for the adsorption of solvent naphtha and H(2), enabling potential applications in adsorption and gas storage.     

First-principle investigation of magnetic coupling mechanism in hypothesized a-site-ordered perovskite YMn₃Sc₄O₁₂

We have systematically investigated the electronic and magnetic properties of hypothesized A‐site‐ordered perovskite YMn₃Sc₄O₁₂ using first‐principle calculation based on the density functional theory. Our calculated results predict that YMn₃Sc₄O₁₂ is both thermodynamically and mechanically stable and its ground state is antiferromagnetic insulator. The Mn³⁺ is in the high‐spin state. More importantly, by comparison to YMn₃Al₄O₁₂, we point out that the empty Sc 3d orbital provides the Mn? O? Sc? O? Mn superexchange interaction, which is similar to its isostructural perovskite CaCu₃Ti₄O₁₂, and enhances the antiferromagnetic interaction between Mn ions. From these calculations, we can clearly see that the empty 3d orbital plays an important role to realize superexchange interaction. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011