Facile N9-Alkylation of Xanthine Derivatives and Their Use as Precursors for N-Heterocyclic Carbene Complexes

The xanthine-derivatives 1,3,7-trimethylxanthine, 1,3-dimethyl-7-benzylxanthine and 1,3-dimethyl-7-(4-chlorobenzyl)xanthine are readily ethylated at N9 using the cheap alkylating agents ethyl tosylate or diethyl sulfate. The resulting xanthinium tosylate or ethyl sulfate salts can be converted into the corresponding PF6- and chloride salts. The reaction of these xanthinium salts with silver(I) oxide results in the formation of different silver(I) carbene-complexes. In the presence of ammonia, ammine complexes [Ag(NHC)(NH3)]PF6 are formed, whilst with Et2NH, the bis(carbene) salts [Ag(NHC)2]PF6 were isolated. Using the xanthinium chloride salts neutral silver(I) carbenes [Ag(NHC)Cl] were prepared. These silver complexes were used in a variety of transmetallation reactions to give the corresponding gold(I), ruthenium(II) as well as rhodium(I) and rhodium(III) complexes. The compounds were characterized by various spectroscopic methods as well as X-ray diffraction.

Development and validation of a method for the simultaneous analysis of fatty acid ethyl esters, ethyl sulfate and ethyl glucuronide in neonatal meconium: application in two cases of alcohol consumption during pregnancy

Alcohol consumption during pregnancy constitutes one of the leading preventable causes of birth defects and neurodevelopmental disorders in the exposed children. Fatty acid ethyl esters (FAEEs), ethyl glucuronide (EtG) and ethyl sulfate (EtS) have been studied as potential biomarkers of alcohol consumption. However, most analytical approaches proposed for their analysis in meconium samples consist of separated extraction procedures requiring the use of two meconium aliquots, which is costly in terms of both time and materials. Therefore, the aim of this study was to develop and validate a method for the simultaneous extraction of 9 FAEEs, EtG and EtS from one meconium aliquot. The sample was homogenized using methanol, and then FAEEs were extracted with hexane while EtG and EtS were isolated using acetonitrile. Then, extracts were applied to solid-phase extraction columns and analysed by gas chromatography mass spectrometry (FAEEs) and liquid chromatography tandem mass spectrometry (EtG and EtS). Calibration curves were linear with r values greater than 0.99. The LODs ranged from 0.8 to 7.5 ng/g for FAEEs and were 0.2 ng/g and 0.8 ng/g for EtS and EtG, respectively. LOQs ranged from 5 to 25 ng/g for FAEEs and were 1 ng/g and 2.5 ng/g for EtS and EtG, respectively. Accuracies and precisions were between 93.8 and 107% and between 3.5 and 9.7%, respectively. The recovery values ranged from 89.1 to 109%. The method proved to be sensitive, specific, simple and fast and allowed for the reduction of the amount of organic solvent used for extraction compared to other published data while higher recoveries were obtained. The method was used for analysis of meconium samples in two cases of mothers who were consuming alcohol during pregnancy.

Ethanol Biomarker Testing and Challenges: Lessons Learned From a College of American Pathologists Proficiency Testing Survey

Context.— Clinical and forensic testing for ethanol biomarkers including ethyl glucuronide (EtG) and ethyl sulfate (EtS) is used to discern alcohol use from abstinence. These markers can be key in major decisions including transplant eligibility or retaining licensure after alcohol misuse. Accuracy, precision, and recognition of the implications of reporting cutoffs are all essential for correct interpretation. Objective.— To evaluate trends in testing for EtG and EtS, including how laboratories perform testing and how comparable participant results are. Design.— The study examined the College of American Pathologists' ethanol biomarker proficiency testing survey from 2013 to 2019. Trends in methodology, reporting cutoffs, and participant performance were evaluated for qualitative and quantitative EtG testing and for quantitative EtS testing. Results.— There was little consensus in reporting cutoffs, which ranged from 10 to 1000 ng/mL for EtG and 10 to 1500 ng/mL for EtS. Although median EtG and EtS compared well with target concentrations, individual participants' results varied widely. For quantitative enzyme immunoassay, accuracy and precision were best in EtG challenges less than 1500 ng/mL. For EtG or EtS by mass spectrometry, overall accuracy was good over a wide concentration range, but variability between participants was high. Approximately 10% (409 of 4059) of results were unacceptable, which for mass spectrometry corresponded to more than 35% above or below the group mean. Conclusions.— Although many participants performed well, there was insufficient consensus in reporting cutoffs and a consistent fraction of laboratories failed to achieve survey standards. Guidelines for assay performance and reporting could greatly benefit laboratories and end users.

Silica Nanoparticles Reinforced Ionogel as Nonvolatile and Stretchable Conductors

Ionogels combine the advantages of being conductive, stretchable, transparent and nonvolatile, which makes them suitable to be applied as conductors for flexible electronic devices. In this paper, a series of ionogels based on 1-ethyl-3-methylimidazolium ethyl-sulfate ([C2mim][EtSO4]) and polyacrylic networks were prepared. Silica nanoparticles (SNPs) were dispersed into the ionogel matrix to enhance its mechanical properties. The thermal, mechanical and electrical properties of the ionogels with various contents of crosslinking agents and SNPs were studied. The results show that a small amount of SNP doping just increases the breaking strain/stress and the nonvolatility of ionogels, as well as maintaining adequate conductivity and a high degree of transparency. Furthermore, the experimental results demonstrate that SNP-reinforced ionogels can be applied as conductors for dielectric elastomer actuators and stretchable wires, as well as for signal transmission.

Abnormally High Blood Acetaldehyde Concentrations Suggest a Potential of Postmortem Ethanol Generation

Ethanol is one of the most commonly used and abused substances worldwide. Identifying whether the source of ethanol detected in corpses is antemortem ingestion or postmortem generation is especially important for determining the cause of death, which remains a vibrant field of research. During the synthesis of ethanol in the putrefaction process of corpses, other small molecules such as acetaldehyde and n-propanol could also be produced. According to our prospective statistical analysis based on authentic samples from forensic cases, it is rational to suspect ethanol generation after death when the concentration of acetaldehyde detected in blood exceeds 0.014 g/dL. Through in vitro simulation experiments, in addition to confirming that ethyl glucuronide and ethyl sulfate are the reliable biomarkers of antemortem ingestion of ethanol, we propose that acetaldehyde is far more sensitive than n-propanol as a potential marker in the blood of corpses for postmortem ethanol formation.