Patient-centric Comparability Assessment of Biopharmaceuticals.

The comparability assessment of a biological product after implementing a manufacturing process change should involve a risk-based approach. Process changes may occur at any stage of the product lifecycle: early development, clinical manufacture for pivotal trials, or post-approval. The risk of the change to impact product quality varies.

Iron-promoted ortho- and/or ipso-hydroxylation of benzoic acids with H(2)O(2).

Regioselective hydroxylation of aromatic acids with hydrogen peroxide proceeds readily in the presence of iron(II) complexes with tetradentate aminopyridine ligands [Fe(II)(BPMEN)(CH(3)CN)(2)](ClO(4))(2) (1) and [Fe(II)(TPA)(CH(3)CN)(2)](OTf)(2) (2), where BPMEN=N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)-1,2-ethylenediamine, TPA=tris-(2-pyridylmethyl)amine. Two cis-sites, which are occupied by labile acetonitrile molecules in 1 and 2, are available for coordination of H(2)O(2) and substituted benzoic acids. The hydroxylation of the aromatic ring occurs exclusively in the vicinity of the anchoring carboxylate functional group: ortho-hydroxylation affords salicylates, whereas ipso-hydroxylation with concomitant decarboxylation yields phenolates.

Electrode chemistry yields a nanoparticle-based NMR sensor for calcium.

Magnetic nanoparticles (NPs) have been used to obtain NMR-based sensors for analytes ranging from small molecules to viruses by the conjugation of biomolecules (antibodies, proteins, oligonucleotides) to the surface of NPs. In the presence of an analyte, the NPs form clusters that alter the relaxation time of the surrounding water protons. Here, we show that an organic molecule that binds calcium ions of nonbiological origin, rather than a biomolecule, can be employed to modify the surface of a magnetic NP.

Single-coil, multisample, proton relaxation method for magnetic relaxation switch assays.

Nanoparticle based magnetic relaxation switch (MRSw) biosensors offer the opportunity to develop magnetic resonance based in vitro diagnostics. Critical attributes for point of care in vitro diagnostic products include simple instrumentation and ease of use. To this end, high-resolution biexponential analysis was used to permit measurement and assignment of two samples with a single radio frequency detection coil.

Multiparameter magnetic relaxation switch assays.

Magnetic nanoparticles (NPs) can serve as magnetic relaxation switches (MRSw's), switching from a dispersed to a clustered state, or the reverse, due to the presence of molecular targets, with changes in the spin-spin relaxation time of water (T2). Biotinylated NP probes reacted with an avidin molecular target to form stable NP clusters, which permitted several NMR parameters to be measured as a function of cluster size. Associated with avidin-induced NP cluster formation was an increase in the spin-spin relation rate (1/T2), while the spin-lattice relaxation rate (1/T1)was unaffected.

Synthesis and catalytic properties in olefin epoxidation of novel iron(II) complexes with pyridine-containing macrocycles bearing an aminopropyl pendant arm.

Three novel iron(II) complexes with pyridine-containing macrocycles bearing an aminopropyl pendant arm were synthesized and characterized. Crystal structures of two of the complexes revealed high-spin iron(II) centers coordinated to the five ligand nitrogen atoms with no coordination of either the solvent molecules or anions, resulting in an unusual square-pyramidal geometry. Related tetradentate ligand CRH formed a low-spin iron(II) complex (meso form was structurally characterized) with a planar arrangement of the four nitrogen atoms from the macrocycle and two axial acetonitrile molecules.

Ortho-hydroxylation of benzoic acids with hydrogen peroxide at a non-heme iron center.

The iron-assisted hydroxylation of benzoic acid to salicylic acid by 1/H2O2 has been achieved in good yield under mild conditions (where is [Fe(II)(BPMEN)(CH3CN)2](ClO4)2 and BPMEN =N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)ethane-1,2-diamine); the product of this reaction is a novel mononuclear iron(III) complex with a chelating salicylate.

Dioxygen binding to complexes with Fe(II)2(mu-OH)2 cores: steric control of activation barriers and O2-adduct formation.

A series of complexes with [Fe(II)(2)(mu-OH)(2)] cores has been synthesized with N3 and N4 ligands and structurally characterized to serve as models for nonheme diiron(II) sites in enzymes that bind and activate O(2). These complexes react with O(2) in solution via bimolecular rate-limiting steps that differ in rate by 10(3)-fold, depending on ligand denticity and steric hindrance near the diiron center. Low-temperature trapping of a (mu-oxo)(mu-1,2-peroxo)diiron(III) intermediate after O(2) binding requires sufficient steric hindrance around the diiron center and the loss of a proton (presumably that of a hydroxo bridge or a yet unobserved hydroperoxo intermediate).

Reactivity of a (mu-oxo)(mu-hydroxo)diiron(III) diamond core with water, urea, substituted ureas, and acetamide.

A series of iron(III) complexes of the tetradentate ligand BPMEN (N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)ethane-1,2-diamine) were prepared and structurally characterized. Complex [Fe(2)(mu-O)(mu-OH)(BPMEN)(2)](ClO(4))(3) (1) contains a (mu-oxo)(mu-hydroxo)diiron(III) diamond core. Complex [Fe(BPMEN)(urea)(OEt)](ClO(4))(2) (2) is a rare example of a mononuclear non-heme iron(III) alkoxide complex.

Polymerization of propyl malolactonate in the presence of Candida rugosa lipase.

To gain better insight into mechanistic features of enzyme-catalyzed malolactonate polymerization, reactions with propyl malolactonate were analyzed while varying enzyme concentration, reaction media composition, and reaction temperature. Monomer conversion and product molecular weights were characterized by (1)H NMR and MALDI-TOF MS, respectively. A high extent of thermal polymerization of propyl malolactonate was observed, while the polymer chain length in all reactions was controlled by the elimination of alpha-hydrogen from propyl malolactonate with formation of a new initiator and the new chains.