Modeling features of the non-heme diiron cores in O2-activating enzymes through the synthesis, characterization, and oxidation of 1,8-naphthyridine-based complexes

Multidentate naphthyridine-based ligands were used to prepare a series of diiron(II) complexes. The compound [Fe(2)(BPMAN)(mu-O(2)CPh)(2)](OTf)(2) (1), where BPMAN = 2,7-bis[bis(2-pyridylmethyl)aminomethyl]-1,8-naphthyridine, exhibits two reversible oxidation waves with E(1/2) values at +310 and +733 mV vs Cp(2)Fe(+)/Cp(2)Fe, as revealed by cyclic voltammetry. Reaction with O(2) or H(2)O(2) affords a product with optical and M?ssbauer properties that are characteristic of a (mu-oxo)diiron(III) species. The complexes [Fe(2)(BPMAN)(mu-OH)(mu-O(2)CAr(Tol))](OTf)(2) (2) and [Fe(2)(BPMAN)(mu-OMe)(mu-O(2)CAr(Tol))](OTf)(2) (3) were synthesized, where Ar(Tol)CO(2)(-) is the sterically hindered ligand 2,6-di(p-tolyl)benzoate. Compound 2 has a reversible redox wave at +11 mV, and both 2 and 3 react with O(2), via a mixed-valent Fe(II)Fe(III) intermediate, to give final products that are also consistent with (mu-oxo)diiron(III) species. The paddle-wheel compound [Fe(2)(BBAN)(mu-O(2)CAr(Tol))(3)](OTf) (4), where BBAN = 2,7-bis(N,N-dibenzylaminomethyl)-1,8-naphthyridine, reacts with dioxygen to yield benzaldehyde via oxidative N-dealkylation of a benzyl group on BBAN, an internal substrate. In the presence of bis(4-methylbenzyl)amine, the reaction also produces p-tolualdehyde, revealing oxidation of an external substrate. A structurally related compound, [Fe(2)(BEAN)(mu-O(2)CAr(Tol))(3)](OTf) (5), where BEAN = 2,7-bis(N,N-diethylaminomethyl)-1,8-naphthyridine, does not undergo N-dealkylation, nor does it facilitate the oxidation of bis(4-methylbenzyl)amine. The contrast in reactivity of 4 and 5 is attributed to a difference in accessibility of the substrate to the diiron centers of the two compounds. The M?ssbauer spectroscopic properties of the diiron(II) complexes were also investigated.     

The estimation and use of measurement uncertainty for a drug substance test procedure validated according to USP <1225>

The vision for metrology at the United States Pharmacopeia (USP) is for international recognition, harmonization, and official acceptance of all USP reference standards that are based on sound, scientific, metrological principles, such as measurement uncertainty (MU). Pharmaceutical testing laboratories will need to estimate the MU for their test procedures. This paper demonstrates how to estimate MU for a test procedure validated following the requirements in USP General Chapter <1225>, Validation of Compendial Procedures. The test procedure determines the assay and impurities for a pharmaceutical drug substance. Pharmaceutical manufacturing companies are required to test the drug substance used in their drug products. In this example, a new test procedure was developed and validated following the requirements in USP <1225>. The MU was estimated using the data from the test procedure validation. The MU estimate determined that the test procedure was fit for use with one determination, avoiding the expense of duplicate determinations. The MU estimate was used to set up decision rules for comparing test data to the assay and impurity specifications. The information from the MU estimate was used to monitor the routine use of the test procedure using control charts that assess accuracy and precision of each run based upon actual test procedure performance capability.     

First order optimality conditions for mathematical programs with semidefinite cone complementarity constraints

In this paper we consider a mathematical program with semidefinite cone complementarity constraints (SDCMPCC). Such a problem is a matrix analogue of the mathematical program with (vector) complementarity constraints (MPCC) and includes MPCC as a special case. We first derive explicit formulas for the proximal and limiting normal cone of the graph of the normal cone to the positive semidefinite cone. Using these formulas and classical nonsmooth first order necessary optimality conditions we derive explicit expressions for the strong-, Mordukhovich- and Clarke- (S-, M- and C-)stationary conditions. Moreover we give constraint qualifications under which a local solution of SDCMPCC is a S-, M- and C-stationary point. Moreover we show that applying these results to MPCC produces new and weaker necessary optimality conditions.     

The Phase-Transfer Catalyzed Synthesis of Bis(4-Aryloxy-3-Nitrophenyl) Sulfones

Ten bis(4-aryloxy-3-nitrophenyl) sulfones were synthesized via a phase-transfer catalyzed, nucleophilic displacement reaction involving phenoxides and bis(4-chloro-3-nitrophenyl) sulfone.     

13C NMR quantification of mono and diacylglycerols obtained through the solvent‐free lipase‐catalyzed esterification of saturated fatty acids

In the present investigation, we studied the enzymatic synthesis of monoacylglycerols (MAG) and diacylglycerols (DAG) via the esterification of saturated fatty acids (stearic, palmitic and an industrial residue containing 87% palmitic acid) and glycerol in a solvent‐free system. Three immobilized lipases (Lipozyme RM IM, Lipozyme TL IM and Novozym 435) and different reaction conditions were evaluated. Under the optimal reaction conditions, esterifications catalyzed by Lipozyme RM IM resulted in a mixture of MAG and DAG at high conversion rates for all of the substrates. In addition, except for the reaction of industrial residue at atmospheric pressure, all of these products met the World Health Organization and European Union directives for acylglycerol mixtures for use in food applications. The products were quantified by ¹³C NMR, with the aid of an external reference signal which was generated from a sealed coaxial tube filled with acetonitrile‐d3. After calibrating the area of this signal using the classical external reference method, the same coaxial tube was used repeatedly to quantify the reaction products. Copyright © 2012 John Wiley & Sons, Ltd.     

Conformational landscapes of bimesogenic compounds and their implications for the formation of modulated nematic phases

ABSTRACT

The twist-bend phase (N_TB) is most commonly observed in materials with a gross-bent shape: dimers; bent-cores; bent-oligomers. We had suggested previously that the bend-angle of such systems effectively dictates the relative thermal stability of the N_TB phase. However, our earlier paper relied on the use of a single energy-minimum conformer and so failed to capture any information about flexibility and conformational distribution. In the present work, we revisit our hypothesis and examine a second set of dimers with varying linking groups and spacer composition. We have improved on our earlier work by studying the conformational landscape of each material, allowing average bend-angles to be determined as well as the conformer distribution. We observe that the stability of the N_TB phase exhibits a strong dependence not only on the Boltzmann-weighted average bend-angle (rather than just a static conformer), but also on the distribution of conformers. To a lesser extent, the flexibility of the spacer appears important. Ultimately, this work satisfies both theoretical treatments and our initial experimental study and demonstrates the importance of molecular bend to the N_TB phase.     

A class of solvable coupled nonlinear oscillators with amplitude independent frequencies

Existence of amplitude independent frequencies of oscillation is an unusual property for a nonlinear oscillator. We find that a class of N coupled nonlinear Liénard type oscillators exhibit this interesting property. We show that a specific subset can be explicitly solved from which we demonstrate the existence of periodic and quasiperiodic solutions. Another set of N coupled nonlinear oscillators, possessing the amplitude independent nature of frequencies, is almost integrable in the sense that the system can be reduced to a single nonautonomous first order scalar differential equation which can be easily integrated numerically.