Towards Diastereomeric Pure Salts with Antisolvent Methods

Chiral molecules, especially enantiomers and diastereomers of purity > 99 %, present a significant market share within the chemical, pharmaceutical, and flavor industries. Antisolvent precipitations, both batch and semicontinuous operations to serve the current trends in flow chemistry were demonstrated to be environmentally benign and efficient tools in achieving high optical purities. Although salts are known to be insoluble in supercritical CO₂, instabilities of the nascent salts were detected and applied for increasing efficiency. Diastereomeric excess values of the crystalline products exceeded 99 % in maximum of three consecutive steps both by repeated resolution with half molar equivalent of the amine to the acid and by direct recrystallization of the salts.     

Analysis of Modified Nucleotide Aptamer Library Generated by Thermophilic DNA Polymerases

One of the pivotal steps in aptamer selection is the amplification of target-specific oligonucleotides by thermophilic DNA polymerases; it can be a challenging task if nucleic acids possessing modified nucleotides are to be amplified. Hence, the identification of compatible DNA polymerase and modified nucleotide pairs is necessary for effective selection of aptamers with unnatural nucleotides. We present an in-depth study of using 5-indolyl-AA-dUTP (TAdUTP) to generate oligonucleotide libraries for aptamer selection. We found that, among the eight studied DNA polymerases, only Vent(exo-) and KOD XL are capable of adapting TAdUTP, and that replacing dTTP did not have a significant effect on the productivity of KOD XL. We demonstrated that water-in-oil emulsion PCR is suitable for the generation of aptamer libraries of modified nucleotides. Finally, high-throughput sequence analysis showed that neither the error rate nor the PCR bias was significantly affected by using TAdUTP. In summary, we propose that KOD XL and TAdUTP could be effectively used for aptamer selection without distorting the sequence space of random oligonucleotide libraries.     

Modeling heterogeneous bacterial populations exposed to antibiotics: The logistic‐dynamics case

In typical in vitro tests for clinical use or development of antibiotics, samples from a bacterial population are exposed to an antibiotic at various concentrations. The resulting data can then be used to build a mathematical model suitable for dosing regimen design or for further development. For bacterial populations that include resistant subpopulations—an issue that has reached alarming proportions—building such a model is challenging. In prior work, we developed a related modeling framework for such heterogeneous bacterial populations following linear dynamics when exposed to an antibiotic. We extend this framework to the case of logistic dynamics, common among strongly resistant bacterial strains. Explicit formulas are developed that can be easily used in parameter estimation and subsequent dosing regimen design under realistic pharmacokinetic conditions. A case study using experimental data from the effect of an antibiotic on a gram‐negative bacterial population exemplifies the usefulness of the proposed approach. © 2015 American Institute of Chemical Engineers AIChE J, 61: 2385–2393, 2015     

Product design: Formulation of a screen-printable sintering-type conductive paste

Due to the complexity of the screen-printing operation and the rheological behaviors of the screen-printable paste, such a paste is usually formulated by trial-and-error. In this report, a systematic procedure, based on heuristics and mechanistic models, for the design of a screen-printable paste is developed. The procedure is demonstrated by a case study of the formulation of a conductive paste of copper particles.     

DPP-4 Cleaves α/β-Peptide Bonds: Substrate Specificity and Half-Lives

The incorporation of β-amino acids into a peptide sequence has gained particular attention as β- and α/β-peptides have shown remarkable proteolytic stability, even after a single homologation at the scissile bond. Several peptidases have been shown to cleave such bonds with high specificity but at a much slower rate compared to α-peptide bonds. In this study, a series of analogs of dipeptidyl peptidase-4 (DPP-4) substrate inhibitors were synthesized in order to investigate whether β-amino acid homologation at the scissile bond could be a valid approach to improving peptide stability towards DPP-4 degradation. DPP-4 cleaved the α/β-peptide bond after the N-terminal penultimate Pro with a broad specificity and retained full activity regardless of the β³-amino acid side chain and peptide length. Significantly improved half-lives were observed for β³Ile-containing peptides. Replacing the penultimate Pro with a conformationally constrained Pro mimetic led to proteolytic resistance. DPP-4 cleavage of α/β-peptide bonds with a broad promiscuity represents a new insight into the stability of peptide analogs containing β-amino acids as such analogs were thought to be stable towards enzymatic degradation.     

Effect of compatibilization in injection‐molded polycarbonate and liquid crystalline polymer blend

The effect of compatibilizing polycarbonate (PC) and LC5000, a thermotropic liquid crystalline polymer consisting of 80/20% of hydroxybenzoic acid and poly(terephthalate) with a laboratory synthesized compatibilizer was studied. The compatibilizer was synthesized by transesterification of PC and LC5000 with the aid of a catalyst. The effect of compatibilization was investigated by studying the mechanical and morphological properties of injection‐molded plaques with different thicknesses. Substantial improvement was observed in the mechanical properties after compatibilization. Significant enhancement in the fibrillation was also observed in the samples after addition of compatibilizer. The surface finish of the compatibilized samples was smooth and homogenous as compared to the uncompatibilized samples. The skin‐core phenomenon in the tensile fractured surfaces was less obvious in the former samples, indicating better adhesion and homogeneity. These morphological studies showed that the mechanical properties enhancement lay in improved fibrillation and interfacial adhesion between the dispersed and major phases. © 2002 Wiley Periodicals, Inc. J Appl Polym Sci 84: 568–575, 2002; DOI 10.1002/app.10308     

Trans isomeric octadecenoic acids are related inversely to arachidonic acid and DHA and positively related to mead acid in umbilical vessel wall lipids

Long-chain PUFA play an important role in early human neurodevelopment. Significant inverse correlations were reported between values of trans isomeric and long-chain PUFA in plasma lipids of preterm infants and children aged 1–15 yr as well as in venous cord blood lipids of full-term infants. Here we report FA compositional data of cord blood vessel wall lipids in 308 healthy, full-term infants (gestational age: 39.7±1.2 wk, birth weight: 3528±429 g, mean±SD). The median (interquartile range) of the sum of 18-carbon trans FA was 0.22 (0.13)% w/w in umbilical artery and 0.16 (0.10)% w/w in umbilical vein lipids. Nonparametric correlation analysis showed significant inverse correlations between the sum of 18-carbon trans FA and both arachidonic acid and DHA in artery (r=−0.38, P<0.01, and r=−0.20, P<0.01) and vein (r=−0.36, P<0.01, and −0.17, P<0.01) wall lipids. In addition, the sum of 18-carbon trans FA was significantly positively correlated to Mead acid, a general indicator of EFA deficiency, in both artery (r=+0.35, P<0.01) and vein (r=+0.31, P<0.01) wall lipids. The present results obtained in a large group of full-term infants suggest that maternal trans FA intake is inversely associated with long-chain PUFA status of the infant at birth.