Development of an accelerated low-pH reversed-phase liquid chromatography column stability test

The important experimental design criteria for an accelerated low-pH RPLC column stability test are discussed. The influence of method variables on the amount and rate of retention-loss and the final optimized parameters for the accelerated low-pH RPLC stability test are presented. The retention-loss curves for selected C8 and C18 stationary phases are compared. These studies indicate that ligand chain length, functionality and bonding density play an important role in determining the low-pH stability of a stationary phase. Additionally, elemental analysis data are used to infer the mechanism responsible for the observed retention-loss under low-pH conditions.     

Radial limits of interpolating Blaschke products

It is shown that if (_n) is a sequence of distinct points on the unit circle, then, for a sequence (a_n) of points in the closed unit disk, there exists an interpolating Blaschke product B with B*(_n)=a_n for all n if and only if (a_n) is bounded away from zero. This complements results of Cargo, Carroll, Colwell, Belna and Piranian on prescribing radial limits for Blaschke products.Mathematics Subject Classification (2000): 30D50Revised version: 1 June 2004Acknowledgment The authors thank the Mathematisches Forschungsinstitut Oberwolfach for the support and for the kind hospitality they always receive. The work presented here is part of their 2002–2004 project Inner functions. The first author also thanks Universität Bern where she spent her sabbatical, as well as Université de Metz, where she was professeur invité for one month. The second author presented this work in May 2004 at the fourth congress of the European network Analysis and Operators in Dalfsen, the Netherlands. He gratefully acknowledges the support he received from the European communitys human potential program, contract HPRN-CT-2000-00116.     

Rational design of alkylene-linked bis-pyridiniumaldoximes as improved acetylcholinesterase reactivators

To improve the potency of 2-pralidoxime (2-PAM) for treating organophosphate poisoning, we dimerized 2-PAM and its analogs according to Wilson's pioneering work and the 3D structure of human acetylcholinesterase (hAChE) inactivated by isoflurophate. 1,7-Heptylene-bis-N,N'-syn-2-pyridiniumaldoxime, the most potent of the alkylene-linked dimeric reactivators, was readily synthesized using bistriflate and is 100 times more potent than 2-PAM in reactivating hAChE poisoned by isoflurophate. Experimental and computational studies confirm that 2-PAM in its biologically active form adopts the syn-I configuration. Further, they suggest that the improved performance of dimeric oximes is conferred by two-site binding with one oxime pointing toward the diisopropyl ester at the catalytic site of hAChE and the other anchored at the peripheral site. This type of binding may induce a conformational change in the acyl pocket loop which modulates the catalytic site via a domino effect.     

The dipyrrolide ligand as a template for the spontaneous formation of a tetranuclear iron(II) complex

The meso-disubstituted dipyrrolide ligand (L) has promoted the formation of a unique tetranuclear iron(II) compound that contains both diazaferrocenyl and distorted-tetrahedral iron centres.     

4-Fluorinated L-lysine analogs as selective i-NOS inhibitors: methodology for introducing fluorine into the lysine side chain

In the literature, the introduction of fluorine into bioactive molecules has been known to enhance the biological activity relative to the parent molecule. Described in this article is the synthesis of 4R-fluoro-L-NIL (12) and 4,4-difluoro-L-NIL (23) as part of our iNOS program. Both 12 and 23 were found to be selective iNOS inhibitors as shown in Table 2 below. Secondarily, methodology to synthesize orthogonally protected 4-fluoro-L-lysine and 4,4-difluoro-L-lysine has been developed.     

Correlation of Dative Bond Length and Donor Proton Affinity in Adducts of SO3: A Good Predictor for HCCCN-SO3

The rotational spectrum of HCCCN-SO₃ has been observed using Fourier transform microwave spectroscopy. The vibrationally averaged structure is that of a symmetric top, with the HCCCN axis along the C₃ axis of the SO₃, and the nitrogen end near the sulfur. The N-S bond length is 2.567(13) Å, which is slightly shorter than the sum of the van der Waals radii. The NSO angle is 91.7(4)°, indicating a small but distinct distortion of the SO₃ from planarity, and the N-S interaction can be described as a chemical bond in an early stage of its formation. The N-S bond lengths in a series of SO₃ adducts with amines, nitriles, and pyridine are shown to correlate well with the proton affinities of the bases. In addition, for the bases considered here, the proton affinities vary in a regular manner with the ionization energies corresponding to removal of a lone pair electron. Thus, the trend in proton affinities follows the variation in energy gap between donor and acceptor orbitals in these complexes, accounting for the utility of the proton affinity in correlating aspects of structure and bonding across the series.     

Silicon-directed selective gamma substitution of an α,β-unsaturated ester

Ethyl 3-methyl-2-trimethylsilyl-3-butenoate ($\text{3}$) undergoes reaction selectively at carbon 4, upon treatment with a Lewis acid and carbonyl compounds, acetals/ketals, acid chlorides, and chloromethyl phenyl sulfide. This overall conversion represents a highly selective gamma substitution on an α,β-unsaturated ester.     

Solving binary cutting stock problems by column generation and branch-and-bound

We present an algorithm for the binary cutting stock problem that employs both column generation and branch-and-bound to obtain optimal integer solutions. We formulate a branching rule that can be incorporated into the subproblem to allow column generation at any node in the branch-and-bound tree. Implementation details and computational experience are discussed.This research was supported by NSF and AFOSR grant DDM-9115768     

Synthesis of olivanic acid analogues: a facile route to 3-(2-pyrimidinylthio-) substituted derivatives

3-(2-Pyrimidinylthio-) substituted olivanic acid analogues, with and without a C-6 hydroxyethyl substituent, have been synthesised in high yield using an intramolecular Wittig reaction followed by deprotection to afford zwitterions with high antibacterial activity.