Monitoring of amoxicilline and ceftazidime in the microdialysate of diabetic foot and serum by capillary electrophoresis with contactless conductivity detection

Determination of the broad-spectrum antibiotics amoxicilline (AMX) and ceftazidime (CTZ) in blood serum and microdialysates of the subcutaneous tissue of the lower limbs is performed using CE with contactless conductivity detection (C⁴D). Baseline separation of AMX is achieved in 0.5 M acetic acid as the background electrolyte and separation of CTZ in 3.2 M acetic acid with addition of 13% v/v methanol. The CE-C⁴D determination is performed in a 25 µm capillary with suppression of the EOF using INST-coating on an effective length of 18 cm and the attained migration time is 4.2 min for AMX and 4.4 min for CTZ. The analysis was performed using 20 µl of serum and 15 µl of microdialysate, treated by the addition of acetonitrile in a ratio of 1/3 v/v and the sample is injected into the capillary using the large volume sample stacking technique. The LOQ attained in the microdialysate is 148 ng/ml for AMX and 339 ng/ml for CTZ, and in serum 143 ng/ml for AMX and 318 ng/ml for CTZ. The CE-C⁴D method is employed for monitoring the passage of AMX and CTZ from the blood circulatory system into the subcutaneous tissue at the sites of diabetic ulceration in patients suffering from diabetic foot syndrome and also for measuring the pharmacokinetics following intravenous application of bolus antibiotic doses.     

Isometric artifacts from polymerase chain reaction-massively parallel sequencing analysis of short tandem repeat loci: An emerging issue from a new technology?

The recent introduction of polymerase chain reaction (PCR)-massively parallel sequencing (MPS) technologies in forensics has changed the approach to allelic short tandem repeat (STR) typing because sequencing cloned PCR fragments enables alleles with identical molecular weights to be distinguished based on their nucleotide sequences. Therefore, because PCR fidelity mainly depends on template integrity, new technical issues could arise in the interpretation of the results obtained from the degraded samples. In this work, a set of DNA samples degraded in vitro was used to investigate whether PCR-MPS could generate “isometric drop-ins” (IDIs; i.e., molecular products having the same length as the original allele but with a different nucleotide sequence within the repeated units). The Precision ID GlobalFiler NGS STR panel kit was used to analyze 0.5 and 1 ng of mock samples in duplicate tests (for a total of 16 PCR-MPS analyses). As expected, several well-known PCR artifacts (such as allelic dropout, stutters above the threshold) were scored; 95 IDIs with an average occurrence of 5.9 IDIs per test (min: 1, max: 11) were scored as well. In total, IDIs represented one of the most frequent artifacts. The coverage of these IDIs reached up to 981 reads (median: 239 reads), and the ratios with the coverage of the original allele ranged from 0.069 to 7.285 (median: 0.221). In addition, approximately 5.2% of the IDIs showed coverage higher than that of the original allele. Molecular analysis of these artifacts showed that they were generated in 96.8% of cases through a single nucleotide change event, with the C > T transition being the most frequent (85.7%). Thus, in a forensic evaluation of evidence, IDIs may represent an actual issue, particularly when DNA mixtures need to be interpreted because they could mislead the operator regarding the number of contributors. Overall, the molecular features of the IDIs described in this work, as well as the performance of duplicate tests, may be useful tools for managing this new class of artifacts otherwise not detected by capillary electrophoresis technology.     

Covalent anionic copolymer coatings with tunable electroosmotic flow for optimization of capillary electrophoretic separations

We present a method for finely adjustable electroosmotic flow (EOF) velocity in cathodic direction for the optimization of separations in capillary electrophoresis. To this end, we use surface modification of the separation fused silica capillary by the covalently attached copolymer of acrylamide (AM) and 2-acrylamido-2-methyl-1-propanesulfonate (AMPS), that is, poly(AM-co-AMPS) or PAMAMPS. Coatings were formed by the in-capillary polymerization of a mixture of the neutral AM and anionic AMPS monomers premixed in various ratios in order to control the charge density of the copolymer. EOF mobility varies in the 0 to ∼40 × 10⁻⁹ m² V⁻¹ s⁻¹ interval for PAMAMPS coatings ranging from 0 to 60 mol.% of charged AMPS monomer. For EOF in PAMAMPS-treated capillaries, we observed (i) a negligible dependence on pH in the 2–10 interval, (ii) a minor variance among background electrolytes (BGEs) in function of their components and (iii) its standard decrease with increasing ionic strength of the BGE. Interest in variable cathodic EOF was demonstrated by the amelioration of separation of two kinds of isomeric anionic analytes, that is, monosaccharides phosphates and helquat enantiomers, in counter-EOF mode.     

Iron-modified zeolite BETA: efficient catalyst in methyllaurate, 2-hexyl-1,3-dioxolane, 4-methyl-2-propyltetrahydro-2H-pyran-4-ol and 4-methyl-2-phenyl-tetrahydro-2H-pyran-4-ol synthesis

Research on Chemical Intermediates - Several types of modified zeolite BETA38 with different iron loading were prepared. Prepared materials were characterized using different techniques (XRD, XRF,...     

Crosslinking Super Yellow to produce super OLEDs: Crosslinking with azides enables improved performance

An increasing number of organic light-emitting diodes (OLEDs) is nowadays based on the use of polymers as the emissive material. For this material class in particular, solution-processing of the OLEDs has gained traction in both research and industry. However, in order to access multilayer material systems, orthogonal solvents must be used to prevent dissolution of previously prepared layers. The use of crosslinkers can facilitate this production method by reducing the number of orthogonal solvents needed since insoluble networks are generated. In this work, a novel bisazide crosslinker is employed to insolubilize Super Yellow, a polyphenylene-vinylene emitter. This allows the use of an additional poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine electron blocking layer (EBL) from the same solvent. Devices including the blocking layer show improved efficacies compared to reference devices without the additional EBL, while also maintaining the emission spectrum. Using the upscalable technique of doctor blading, OLEDs were fabricated which showed a particularly noticeable effect of the blocking layer with a nearly twofold increase in luminance and a 56% increase in current efficacy.     

Simplified,interpretable graph convolutional neural networks for small molecule activity prediction

Journal of Computer-Aided Molecular Design - We here present a streamlined, explainable graph convolutional neural network (gCNN) architecture for small molecule activity prediction. We first...     

4-Phosphoryl Pyrazolones for Highly Selective Lithium Separation from Alkali Metal Ions

Effective receptors for the separation of Li⁺ from a mixture with other alkali metal ions under mild conditions remains an important challenge that could benefit from new approaches. In this study, it is demonstrated that the 4-phosphoryl pyrazolones, H L ²-H L ⁴, in the presence of the typical industrial organophosphorus co-ligands tributylphosphine oxide (TBPO), tributylphosphate (TBP) and trioctylphosphine oxide (TOPO), are able to selectively recognise and extract lithium ions from aqueous solution. Structural investigations in solution as well as in the solid state reveal the existence of a series of multinuclear Li⁺ complexes that include dimers (TBPO, TBP) as well as rarely observed trimers (TOPO) and represent the first clear evidence for the synergistic role of the co-ligands in the extraction process. Our findings are supported by detailed NMR, MS and extraction studies. Liquid-liquid extraction in the presence of TOPO revealed an unprecedented high Li⁺ extraction efficiency (78 %) for H L ⁴ compared to the use of the industrially employed acylpyrazolone H L ¹ (15 %) and benzoyl-1,1,1-trifluoroacetone (52 %) extractants. In addition, a high selectivity for Li⁺ over Na⁺, K⁺ and Cs⁺ under mild conditions (pH ∼8.2) confirms that H L ²-H L ⁴ represent a new class of ligands that are very effective extractants for use in lithium separation.     

Exploring the Reactivity of B-Connected Carboranylphosphines in Frustrated Lewis Pair Chemistry: A New Frame for a Classic System

The primary phosphines MesPH₂ and tBuPH₂ react with 9-iodo-m-carborane yielding B9-connected secondary carboranylphosphines 1,7-H₂C₂B₁₀H₉-9-PHR (R=2,4,6-Me₃C₆H₂ (Mes; 1 a ), tBu ( 1 b )). Addition of tris(pentafluorophenyl)borane (BCF) to 1 a , b resulted in the zwitterionic compounds 1,7-H₂C₂B₁₀H₉-9-PHR(p-C₆F₄)BF(C₆F₅)₂ ( 2 a , b ) through nucleophilic para substitution of a C₆F₅ ring followed by fluoride transfer to boron. Further reaction with Me₂SiHCl prompted a H−F exchange yielding the zwitterionic compounds 1,7-H₂C₂B₁₀H₉-9-PHR(p-C₆F₄)BH(C₆F₅)₂ ( 3 a , b ). The reaction of 2 a , b with one equivalent of R'MgBr (R’=Me, Ph) gave the extremely water-sensitive frustrated Lewis pairs 1,7-H₂C₂B₁₀H₉-9-PR(p-C₆F₄)B(C₆F₅)₂ ( 4 a , b ). Hydrolysis of the B−C₆F₄ bond in 4 a , b gave the first tertiary B-carboranyl phosphines with three distinct substituents, 1,7-H₂C₂B₁₀H₉-9-PR(p-C₆F₄H) ( 5 a , b ). Deprotonation of the zwitterionic compounds 2 a , b and 3 a , b formed anionic phosphines [1,7-H₂C₂B₁₀H₉-9-PR(p-C₆F₄)BX(C₆F₅)₂]⁻[DMSOH]⁺ (R=Mes, X=F ( 6 a ), R=tBu, X=F ( 6 b ); R=Mes, X=H ( 7 a ), R=tBu, X=H ( 7 b )). Reaction of 2 a , b with an excess of Grignard reagents resulted in the addition of R’ at the boron atom yielding the anions [1,7-H₂C₂B₁₀H₉-9-PR(p-C₆F₄)BR’(C₆F₅)₂]⁻ (R=Mes, R’=Me ( 8 a ), R=tBu, R’=Me ( 8 b ); R=Mes, R’=Ph ( 9 a ), R=tBu, R’=Ph ( 9 b )) with [MgBr(Et₂O)_n]⁺ as counterion. The ability of the zwitterionic compounds 3 a , b to hydrogenate imines as well as the Brønsted acidity of 3 a were investigated.     

Radical Reactivity of the Biradical [⋅P(μ-NTer)2P⋅] and Isolation of a Persistent Phosphorus-Cantered Monoradical [⋅P(μ-NTer)2P-Et]

The activation of C−Br bonds in various bromoalkanes by the biradical [⋅P(μ-NTer)₂P⋅] ( 1 ) (Ter=2,6-bis-(2,4,6-trimethylphenyl)-phenyl) is reported, yielding trans-addition products of the type [Br−P(μ-NTer)₂P−R] ( 2 ), so-called 1,3-substituted cyclo-1,3-diphospha-2,4-diazanes. This addition reaction, which represents a new easy approach to asymmetrically substituted cyclo-1,3-diphospha-2,4-diazanes, was investigated mechanistically by different spectroscopic methods (NMR, EPR, IR, Raman); the results suggested a stepwise radical reaction mechanism, as evidenced by the in-situ detection of the phosphorus-centered monoradical [⋅P(μ-NTer)₂P-R].< To provide further evidence for the radical mechanism, [⋅P(μ-NTer)₂P-Et] ( 3Et ⋅) was synthesized directly by reduction of the bromoethane addition product [Br-P(μ-NTer)₂P-Et] ( 2 a ) with magnesium, resulting in the formation of the persistent phosphorus-centered monoradical [⋅P(μ-NTer)₂P-Et], which could be isolated and fully characterized, including single-crystal X-ray diffraction. Comparison of the EPR spectrum of the radical intermediate in the addition reaction with that of the synthesized new [⋅P(μ-NTer)₂P-Et] radical clearly proves the existence of radicals over the course of the reaction of biradical [⋅P(μ-NTer)₂P⋅] ( 1 ) with bromoethane. Extensive DFT and coupled cluster calculations corroborate the experimental data for a radical mechanism in the reaction of biradical [⋅P(μ-NTer)₂P⋅] with EtBr. In the field of hetero-cyclobutane-1,3-diyls, the demonstration of a stepwise radical reaction represents a new aspect and closes the gap between P-centered biradicals and P-centered monoradicals in terms of radical reactivity.     

An Anionic Amido-Substituted Seven-Vertex Siliconoid Cluster

The silanide [Si₄{N(SiMe₃)Dipp}₃]⁻ ( 1 ) transforms into the anionic siliconoid cluster [Si₇{N(SiMe₃)Dipp}₃]⁻ ( 2 ) with four unsubstituted silicon atoms as a contact ion pair with [K([18]crown-6)] in C₆D₆ at room temperature within five weeks. Anion 2 was investigated by natural population analysis and visualization of intrinsic atomic orbitals. Magnetically induced current-density calculations of 2 revealed two distinct strong diatropic vortices that sum up in one direction and create a strongly shielded apical silicon atom in 2 .