Synthesis and Characterization of Fumarate Copolyesters for Use in Bioresorbable Bone Cement Compositions

Unsaturated amorphous copolyesters of varied composition were prepared by transesterification copolymerization of diethyl fumarate, and two diols, 1,2‐propanediol and 2‐methyl‐1,3‐propanediol. The copolyesters were characterized by IR, ¹H‐ and ¹³C‐NMR, GPC, DSC, and TGA. The glass transition is changing with composition from 0°C to 19°C as the content of 1,2‐propanediol residue in the copolyester increases. The copolyester structure and composition have an impact on the compressive strength and hydrolytic stability of the composites prepared by crosslinking the fumarate double bonds with N‐vinyl pyrrolidone in the presence of inorganic filler, calcium sulfate dihydrate, with the addition of a radical initiator, benzoyl peroxide, at ambient temperatures.     

Oxidative modification of native protein residues using cerium(IV) ammonium nitrate

A new protein modification strategy has been developed that is based on an oxidative coupling reaction that targets electron-rich amino acids. This strategy relies on cerium(IV) ammonium nitrate (CAN) as an oxidation reagent and results in the coupling of tyrosine and tryptophan residues to phenylene diamine and anisidine derivatives. The methodology was first identified and characterized on peptides and small molecules, and was subsequently adapted for protein modification by determining appropriate buffer conditions. Using the optimized procedure, native and introduced solvent-accessible residues on proteins were selectively modified with polyethylene glycol (PEG) and small peptides. This unprecedented bioconjugation strategy targets these under-utilized amino acids with excellent chemoselectivity and affords good-to-high yields using low concentrations of the oxidant and coupling partners, short reaction times, and mild conditions.     

Chirality and Polarity in the f‐Block Borates M4[B16O26(OH)4(H2O)3Cl4] (M=Sm,Eu, Gd,Pu, Am,Cm, and Cf)

The reactions of trivalent lanthanides and actinides with molten boric acid in high chloride concentrations result in the formation of M₄[B₁₆O₂₆(OH)₄(H₂O)₃Cl₄] (M=Sm, Eu, Gd, Pu, Am, Cm, Cf). This cubic structure type is remarkably complex and displays both chirality and polarity. The polymeric borate network forms helical features that are linked via two different types of nine‐coordinate f‐element environments. The f–f transitions are unusually intense and result in dark coloration of these compounds with actinides.     

In‐house and synchrotron X‐ray diffraction studies of 2‐phenyl‐1,10‐phenanthroline,protonated salts,complexes with gold(III) and copper(II), and an orthometallation product with palladium(II)

Different salts of the 2‐phenyl‐1,10‐phenanthrolin‐1‐ium cation, (pnpH)⁺, are obtained by reacting 2‐phenyl‐1,10‐phenanthroline (pnp), C₁₈H₁₂N₂, (I), with a variety of anions, such as hexafluoridophosphate, C₁₈H₁₃N₂⁺·PF₆⁻, (II), trifluoromethanesulfonate, C₁₈H₁₃N₂⁺·CF₃SO₃⁻, (III), tetrachloridoaurate, (C₁₈H₁₃N₂)[AuCl₄], (IV), and bromide (as the dihydrate), C₁₈H₁₃N₂⁺·Br⁻·2H₂O, (V). Compound (I) crystallizes with Z′ = 2, with both independent molecules adopting a coplanar conformation. In (II)–(IV), a hydrogen bond exists between the cation and anion, while one of the lattice water molecules serves as a hydrogen‐bonded bridge between the cation and anion in (V). Reaction of (I) with HAuCl₄ gives the salt complex (IV); however, reaction with KAuCl₄ produces the monodentate complex trichlorido(2‐phenyl‐1,10‐phenanthroline‐κN¹⁰)gold(III), [AuCl₃(C₁₈H₁₂N₂)], (VI). Dichlorido(2‐phenyl‐1,10‐phenanthroline‐κ²N,N′)copper(II), [CuCl₂(C₁₈H₁₂N₂)], (VII), results from the reaction of CuCl₂·2H₂O and (I), in which the Cu^II center adopts a tetrahedrally distorted square‐planar geometry. The pendent phenyl ring twists to a bisecting position relative to the phenanthroline plane. The square‐planar Pd^II complex, bromido[2‐(phenanthrolin‐2‐yl)phenyl‐κ³C¹,N,N′]palladium(II), [PdBr(C₁₈H₁₁N₂)], (VIII), is obtained from the reaction of (I) with [PdCl₂(cycloocta‐1,5‐diene)], followed by addition of bromine. A coplanar geometry for the pendent ring is adopted as a result of the tridentate bonding motif.     

An equivariant tensor product on Mackey functors

For all subgroups H of a cyclic p-group G we define norm functors that build a G-Mackey functor from an H-Mackey functor. We give an explicit construction of these functors in terms of generators and relations based solely on the intrinsic, algebraic properties of Mackey functors and Tambara functors. We use these norm functors to define a monoidal structure on the category of Mackey functors where Tambara functors are the commutative ring objects.     

Conditioning saliva for use in a microfluidic biosensor

This report details an approach to saliva conditioning for compatibility of raw patient samples with microfluidic immunoassay components, principally biosensor surfaces susceptible to fouling. Stimulated whole human saliva spiked with a small molecule analyte (phenytoin, 252 Da) was first depleted of cells, debris and high molecular weight glycoproteins (mucins) using membrane filtration. This process significantly reduced but did not eliminate fouling of biosensor surfaces exposed to the sample. An H-filter, which separates solutes from mixed samples based on their diffusion in laminar flow, was used to extract the analyte from the remaining large molecular weight species in the filtered saliva sample. Patient samples treated in this way retained 23% of the analyte with 97% and 92% reduction in glycoproteins and proteins, respectively, and resulted in 3.6 times less surface fouling than either untreated or filtered saliva alone. These sample conditioning steps will enable the use of fouling-sensitive detection techniques in future studies using clinical saliva samples.     

Investigation of the copper binding site and the role of histidine as a ligand in riboflavin binding protein

Riboflavin Binding Protein (RBP) binds copper in a 1:1 molar ratio, forming a distinct well-ordered type II site. The nature of this site has been examined using X-ray absorption and pulsed electron paramagnetic resonance (EPR) spectroscopies, revealing a four coordinate oxygen/nitrogen rich environment. On the basis of analysis of the Cambridge Structural Database, the average protein bound copper-ligand bond length of 1.96 A, obtained by extended x-ray absorption fine structure (EXAFS), is consistent with four coordinate Cu(I) and Cu(II) models that utilize mixed oxygen and nitrogen ligand distributions. These data suggest a Cu-O 3N coordination state for copper bound to RBP. While pulsed EPR studies including hyperfine sublevel correlation spectroscopy and electron nuclear double resonance show clear spectroscopic evidence for a histidine bound to the copper, inclusion of a histidine in the EXAFS simulation did not lead to any significant improvement in the fit.     

Molecular dynamics simulation of the forces between colloidal nanoparticles in n-decane solvent

Molecular dynamics is utilized to simulate solvation forces between two nanoparticles immersed in liquid n-decane. Three types of solvophilic nanoparticles are investigated with sizes in the 1-6 nm range: small and large amorphous spheres and crystalline cubes. We find that the solvation forces are negligible for the small spheres, which have diameters comparable to the end-to-end distance of all-trans decane, and we attribute this to the inability of the small spheres to induce decane ordering in the interparticle gap. The cubic nanoparticles (and to a lesser extent, the large spheres) are able to induce the formation of solidlike, n-decane layers in their gap for certain nanoparticle separations, and the transition between layered and disordered structures leads to solvation forces that oscillate between repulsion and attraction as the nanoparticle separation is varied. We find that the Derjaguin approximation [B. V. Derjaguin, Kolloid-Z. 69, 155 (1934)] is not effective at describing the dependence of the solvation forces on nanoparticle size and shape-contrasting results from a previous study involving these nanoparticles in Lennard-Jones solvent [Y. Qin and K. A. Fichthorn, J. Chem. Phys. 119, 9745 (2003)]. In particular, we find that for decane, the magnitude of the repulsive solvation forces is sensitive to nanoparticle size and shape, a phenomenon we attribute to the size and rigid-rod structure of n-decane, which makes its ordering in the interparticle gap sensitive to the size and the surface roughness of the nanoparticles.     

Infrared spectroscopy of anionic hydrated fluorobenzenes

We investigate the structural motifs of anionic hydrated fluorobenzenes by infrared photodissociation spectroscopy and density functional theory. Our calculations show that all fluorobenzene anions under investigation are strongly distorted from the neutral planar molecular geometries. In the anions, different F atoms are no longer equivalent, providing structurally different binding sites for water molecules and giving rise to a multitude of low-lying isomers. The absorption bands for hexa- and pentafluorobenzene show that only one isomer for the respective monohydrate complexes is populated in our experiment. For C6F6.-H2O, we can assign these bands to an isomer where water forms a weak double ionic hydrogen bond with two F atoms in the ion, in accord with the results of Bowen et al. [J. Chem. Phys. 127, 014312 (2007), following paper.] The spectroscopic motif of the binary complexes changes slightly with decreasing fluorination of the aromatic anion. For dihydrated hexafluorobenzene anions, several isomers are populated in our experiments, some of which may be due to hydrogen bonding between water molecules.     

Cored anion-exchange chromatography media for antibody flow-through purification

Agarose-based anion-exchangers (e.g. quaternary amine, Q) have been widely used in monoclonal antibody flow-through purification to remove trace levels of impurities. Such media are often packed in a large column and the operation is usually robust but with limited throughput due to the compressibility of agarose and consequentially low bed permeability. In order to address this limitation, cored Q beads consisting of a rigid core and a thin agarose gel coating were developed and evaluated for protein flow-through chromatography. Using laboratory-scale columns it was found that, the cored beads indeed provide significantly enhanced rigidity and flow permeability relative to conventional homogeneous agarose resins. Depending on the structure and size of the cored beads, the permeability was 2-4-fold higher than that of a commonly used commercial agarose resin. Good virus and host cell protein clearance was achieved with the cored Q beads even at increased flow velocities. In addition, the impermeable core allows for more efficient use of buffers without loss of useful capacity in polishing applications. Process analyses based upon the experimental data demonstrated that the enhanced permeability achieved with the cored beads can significantly improve process throughput and economics.