Search

Herein, we introduce an electrochemically assisted generation of nitryl radicals from ferric nitrate under mild reaction conditions using a simple setup with inexpensive graphite and stainless-steel electrodes. The mechanism of the reaction is supported by detailed spectroscopic and experimental studies. Powered by electricity and driven by electrons, the synthetic diversity of this reaction has been demonstrated through the development of highly efficient nitration protocols of various unsaturated hydrocarbons. In addition to a broad application area, these protocols are easy to scale for decagram quantities, and exhibit exceptional substrate generality and functional-group compatibility., Angewandte Chemie. International Edition, 62 (28), ISSN:1433-7851, ISSN:1521-3773, ISSN:0570-0833

We report a mild and operationally simple trifluoroacylation strategy of olefines, that utilizes trifluoroacetic anhydride as a low‐cost and readily available reagent. This light‐mediated process is fundamentally different from conventional methodologies and occurs through a trifluoroacyl radical mechanism promoted by a photocatalyst, which triggers a C−O bond fragmentation. Mechanistic studies (kinetic isotope effects, spectroelectrochemistry, optical spectroscopy, theoretical investigations) highlight the evidence of a fleeting CF3CO radical under photoredox conditions. The trifluoroacyl radical can be stabilized under CO atmosphere, delivering the trifluoroacetylation product with higher chemical efficiency. Furthermore, the method can be turned into a trifluoromethylation protocol by simply changing the reaction parameters. Beyond simple alkenes, this method allows for chemo‐ and regioselective functionalization of small‐molecule drugs and common pharmacophores., The trifluoroacyl radical is generated by C−O bond fragmentation of trifluoroacetic anhydride under photoredox conditions and undergoes olefinic C−H bond trifluoroacetylation in a mechanistically unique fashion. The protocol is operationally simple, scalable, and enables the late‐stage diversification of complex biorelevant molecules delivering the corresponding α,β‐unsaturated trifluoromethyl ketones in one step.

The outstanding impact of fluorine atom in drug discovery cannot be overestimated. Substantially, the incorporation of the gem-difluoro (CF2) group into organic frameworks is highly sought due to the influence of this unit on physicochemical and pharmacological properties of molecules. Yet, introduction of CF2 moiety into organic structures is a step-intensive preparation, and known approaches are often limited to certain classes of molecules. Development of strategies for a rapid incorporation of gem-difluoro synthon that utilizes inexpensive commercial reagents is highly desirable. In the context of divergency and applicability of such reagents, switchable synthesis can be beneficial to access a wide range of fluorinated compounds. Herein we report a mild and operationally simple protocols to access various gem-difluoro compounds that employs chlorodifloroacetic anhydride (CDFAA) as a low cost and versatile fluoroalkylating reagent. Detailed mechanistic investigations revealed that electron-transfer photocatalysis triggers mesolytic cleavage of a C−Cl bond generating a gem-difluoro carboxy radical. In the presence of alkene molecule, this radical species acts as an efficient and unique bifunctional reagent that, under solvent-controlled reaction conditions, delivers a wide range of gem-difluorinated γ-lactams, γ-lactones, as well as promotes oxy-perfluoroalkylation. These protocols are flow and batch scalable, possess excellent chemo- and regioselectivity, and can be used for the late-stage diversification of biorelevant molecules.

ContextMethod-specific reference intervals (RIs) determine utility of IGF-I as a biomarker in GH-related diseases. Differences between populations might affect applicability of RIs.ObjectiveTo compare population-specific RIs derived from IGF-I routine testing in laboratories in the United States and Europe using the same assay.Design and settingUncensored routine IGF-I testing results generated over 5 years in 4 accredited laboratories (US, n = 778 173 males/710 752 females; Europe, n = 23 220 males/40 183 females).Main outcome measuresConstruction of RIs by indirect statistical methods designed to use routine testing data (modified Hoffmann approach). Comparison to published RIs, between the US and Europe, and between regions in the United States with lower and higher mean body mass indexes (BMIs).ResultsLower limits (LLs) of RIs calculated from all routine data sets do not differ from the published LLs. The same is true for upper limits (ULs) calculated from European routine data. ULs derived from US routine data are significantly higher (children, 10-18 years [mean, %]: boys + 149.3 ng/mL [+34.6%]; girls + 94.9 ng/mL [+19.8%]); adults (19-95 years: males + 45 ng/mL [+20.3%]; and females + 29.7 ng/mL [+13.8%]). Average IGF-I is higher in samples from Colorado (lower mean BMI) compared with Alabama (P ConclusionsWe provide evidence that in large datasets from the same population, direct sampling and the indirect Hoffmann approach provide comparable RIs. Although LLs are comparable between Europe and the United States, the UL is significantly higher in the United States. We suggest use of adapted RIs for the United States.

Die vorliegende Arbeit beschreibt die Synthese und Charakterisierung eines hypervalenten Iodreagenzes, das die direkte und selektive Nitrooxylierung enolisierbarer Carbonylverbindungen und damit Zugang zu einer Breite organischer Salpetersäureester erlaubt. Das Reagenz ist unter konventionellen Laborbedingungen stabil, leicht handzuhaben und erlaubt den Transfer der Nitrooxygruppe unter milden Bedingungen. Die Aktivierung des Reagenzes durch Brønstedt‐ und Lewis‐Säuren wurde im Rahmen der Darstellung nitrooxylierter β‐Ketoester, 1,3‐Diketone sowie Malonate gezeigt, während ein photoredoxkatalytischer Aktivierungsmodus den Zugang zu nitrooxylierten Oxindolen erlaubt. Im Rahmen der Arbeit wurde der Mechanismus unter Verwendung von Pulsradiolyse, Fluoreszenzspektroskopie und UV‐Vis‐Spektroelektrochemie untersucht. Hierbei zeigte sich ein einzigartiger SET‐induzierter konzertierter Reaktionsverlauf, der nicht auf der Bildung des freien Nitratradikals beruht. ISSN:1521-3757 ISSN:0044-8249

Herein, the synthesis and characterization of a hypervalent‐iodine‐based reagent that enables a direct and selective nitrooxylation of enolizable C−H bonds to access a broad array of organic nitrate esters is reported. This compound is bench stable, easy‐to‐handle, and delivers the nitrooxy (‐ONO2) group under mild reaction conditions. Activation of the reagent by Brønsted and Lewis acids was demonstrated in the synthesis of nitrooxylated β‐keto esters, 1,3‐diketones, and malonates, while its activity under photoredox catalysis was shown in the synthesis of nitrooxylated oxindoles. Detailed mechanistic studies including pulse radiolysis, Stern–Volmer quenching studies, and UV/Vis spectroelectrochemistry reveal a unique single‐electron‐transfer (SET)‐induced concerted mechanistic pathway not reliant upon generation of the nitrate radical. ISSN:1433-7851 ISSN:1521-3773 ISSN:0570-0833

Patient-based real-time quality control (PBRTQC) is a laboratory tool for monitoring the performance of the testing process. It includes well-established procedures like Bull’s algorithm, average of nomals, moving median, moving average (MA) and exponentially (weighted) MAs. Following the setup and optimization processes, a key step prior to the routine implementation of PBRTQC is the verification and documentation of the performance of the PBRTQC as part of the laboratory quality system. This verification process should provide a realistic representation of the performance of the PBRTQC in the environment it is being implemented in, to allow proper risk assessment by laboratory practitioners. This document focuses on the recommendation on performance verification of PBRTQC prior to implementation.

For many years the concept of patient-based quality control (QC) has been discussed and implemented in hematology laboratories; however, the techniques have not been widely implemented in clinical chemistry. This is mainly because of the complexity of this form of QC, as it needs to be optimized for each population and often for each analyte. However, the clear advantages of this form of QC, together with the ongoing realization of the shortcomings of “conventional” QC, have driven a need to provide guidance to laboratories to assist in deploying patient-based QC. This overview describes the components of a patient-based QC system (calculation algorithm, block size, truncation limits, control limits) and the relationship of these to the analyte being controlled. We also discuss the need for patient-based QC system optimization using patient data from the individual testing laboratory to reliably detect systematic errors while ensuring that there are few false alarms. The term patient-based real-time quality control covers many activities that use data from patient samples to detect analytical errors. These activities include the monitoring of patient population parameters such as the mean or median analyte value or using single within-patient changes such as the delta check. In this report, we will restrict the discussion to population-based parameters. This overview is intended to serve as a guide for the implementation of a patient-based QC system. The report does not cover the clinical evaluation of the population.

This article discusses the mathematical models of the individual structures and modes of operation of a double-circuit solar collector with thermo siphon circulation. To perform this task, we considered a new design of a flat solar collector with thermo siphon circulation, in which the heat transfer coefficient was increased by eliminating additional partitions between the panel and thermal insulation. The efficiency of the solar collector is achieved due to the presence of the metering tank and the heat pump in the tank, where the condenser and evaporator are made in the form of a “spiral in a spiral” type heat exchanger, and the heat exchanger pipelines are placed one above the other, which allows increasing the area and intensity of heat exchange. The result of this work is a theoretical and mathematical analysis of the unsteady thermal regime of flat solar collectors on the modes of operation under consideration. Based on the results of the analysis, it is possible to optimize individual structural elements, as well as to predict the thermal regime and select alternative solutions for the design of flat solar collectors and the choice of operating modes.

Background High interest in chronic heart failure (CHF) is accounted for by its high incidence, poor prognosis, growing number of hospital admissions due to the heart failure relapse, and inadequate treatment. These facts necessitate a search for new pharmacological agents for the CHF correction. Herbal medicinal products appear to be very promising as they have a noticeable therapeutic effect and tend to be more harmless in comparison to the most of synthesized medications. Purpose Our aim was to study the composition of the Primula veris L. solid herbal extract (PVSHE) and its effects on the myocardial contractile function in animals with experimental CHF. Study design The study design involved the identification of the raw material composition of the P. veris L. extract. For the experimental part of our research, we used the model of CHF to elucidate the cardioprotective properties of PVSHE. Methods The active extract constituents were isolated by thin-layer chromatography and column chromatography; the extract components were identified by high-performance liquid chromatography, ultraviolet spectroscopy (UVS), and nuclear magnetic resonance spectroscopy (NMRS). To model CHF, L-isoproterenol at a dose of 2.5 mg/kg was intraperitoneally injected to the experimental rats twice a day for 21 days. Cardiac output was assessed with the loading test, adrenoreactivity test, and maximum isometric loading test; CHF markers adrenomedullin and copeptin were detected in blood plasma with ELISA kit for adrenomedullin and copeptin (Coud-Clone Corp., USA). Results P. veris L. solid herbal extract contains flavonoid aglycons (apigenin, quercetine, kaemferol), flavonoid glycosides (cinarozid, rutin, hyperozid), as well as polymethoxylated flavonoids acting as chemotaxonomic markers for the genus Primula (8-methoxy-flavone; 3′,4′methylenedioxy-5′-methoxyflavone). The substance 3′,4′methylenedioxy-5′-methoxyflavone has been isolated from the primrose herb for the first time. We showed that the PVSHE has a cardioprotective effect when it was administered at a dose of 30 mg/kg in the experimental CHF, as evidenced by a lower number of animal death, lower level of CHF markers in the blood plasma of the experimental animals, the higher increase in rate of myocardial contraction and relaxation, the higher level of left ventricular pressure (LVP) and of maximum intensity of structural performance (MISP), as compared to the control group. Conclusion P. veris L. solid herbal extract contains flavonoid aglycons, flavonoid glycosides, and polymethoxylated flavonoids. The herbal agent increases the myocardial contractility in experimental CHF.

Demonstrated herein is the construction of trifluoromethylated quaternary carbon centers by an asymmetric radical transformation. Enantioenriched trifluoromethylated oxindoles were accessed using a hypervalent iodine-based trifluoromethyl transfer reagent in combination with a magnesium Lewis acid catalyst and PyBOX-type ligands to achieve up to 99 % ee and excellent chemical yields. Mechanistic studies were performed by experimental and computational methods and suggest a single-electron transfer induced SN2-type mechanism. This example is thereby the first report on the construction of enantioenriched trifluoromethylated carbon centers using hypervalent iodine-based reagents proceeding through such a reaction pathway. ISSN:1433-7851 ISSN:1521-3773 ISSN:0570-0833

In the research herein, we have considered the thermal and hydraulic analysis of transfer media motion mode in the flat solar collector. We have substantiated the thermal and hydraulic parameters of the flat plate solar collector. Heat absorbing flat solar collector tubes hydraulic analysis has shown, that using the heat transfer standard size there might be located the pipeline, the length of which 2.5 times more than of the collector's body, sufficiently increasing at that insolation time on the transfer media.

Background: IGF-I is the most widely used biomarker for management of GH related diseases. Reproducible assays and method-specific reference intervals (RIs) are crucial determinants of its clinical utility. Assay validation and RIs based on >15,000 subjects were published for the IDS iSYS IGF-I assay (J Clin Endocrinol Metab 2014). We now analyzed distribution of IGF-I results obtained in routine samples analyzed by accredited laboratories in the US and Europe, all using the IDS iSYS assay. Methods: All results from routine IGF-I measurements during the past 5 years in 4 laboratories were included (US lab n=778,173 males/710,752 females; European labs (Germany/Belgium, n=23,220 males/40,183 females). Assay performance across laboratories was confirmed through proficiency testing schemes and exchange of patient samples. We constructed RIs adjusted for age/sex from European and US cohorts separately using a modified Hoffmann approach (Am J Clin Pathol 2015), and compared to the originally published RIs (n=6697 males/8317 females, adults from Europe). A subset of US samples was used to compare IGF-I between regions with lower (Colorado) and higher (Alabama) mean body mass index (BMI). Results: Lower limits (LLs) of RIs calculated from routine results are superimposable to LLs from the original publication for all ages and sexes, regardless whether IGF-I results were from Europe or the US. For groups with sufficient n, upper limits (ULs) of RIs calculated from European routine data were also not statistically different from the originally published central 95%. However, a striking difference exists in calculated ULs from data of European and US origin: For ages 10-18 years, calculated UL on average was 149.3 ng/mL (34.6%) higher in boys and 94.9 ng/mL (19.8%) in girls from the US. In adults (19-95 years), calculated UL on average was 45 ng/mL (20.3%) higher in males and 29.7 ng/mL (13.8%) in females from the US. Within the US, mean IGF-I was significantly higher in samples from Colorado (lower mean BMI) than in Alabama (p

Background Geenius HIV 1/2 Supplemental Assay (Geenius; Bio-Rad Laboratories) is the only Food and Drug Administration-approved HIV-1/HIV-2 antibody differentiation test for the second step in the HIV laboratory testing algorithm. We characterized the occurrence of true HIV-1 and HIV-2 infections as well as false results in 6 US clinical laboratories using Geenius. Methods We examined routine HIV testing outcome data from the time the laboratories began using the algorithm with Geenius until September 30, 2017. We calculated the positive predictive value for Geenius HIV-1 and HIV-2 reactivity separately. Results Of 5,046,684 specimens tested, 41,791 had reactive antigen/antibody test results. Most specimens with reactive antigen/antibody results were HIV-1 antibody-positive established infections (n = 32,421), 1,865 of which also had indeterminate HIV-2 bands present. Ninety-three specimens were HIV-2 antibody positive or untypable for HIV-1/HIV-2 antibody. Acute HIV-1 infections were found in 528 specimens; 881 specimens lacked the nucleic acid test to determine the possibility of acute HIV-1 infection. False-positive antigen/antibody test results were present in 7505 specimens. Few specimens (n = 363) had false-positive antigen/antibody results with indeterminate Geenius and negative HIV-1 nucleic acid test results. The positive predictive values of Geenius reactivity were 99.4% for HIV-1 and 4.3% for HIV-2. Conclusions Routine testing using the laboratory testing algorithm with Geenius resulted in most specimens resolving as HIV negative or HIV-1 positive. The occurrence of indeterminate HIV-2 bands with a Geenius final assay interpretation of HIV-1 positive was more common than true HIV-2 infections. Reporting indeterminate HIV-2 results in this situation may cause confusion with interpreting HIV infection status.

Reference intervals are a vital part of the information supplied by clinical laboratories to support interpretation of numerical pathology results such as are produced in clinical chemistry and hematology laboratories. The traditional method for establishing reference intervals, known as the direct approach, is based on collecting samples from members of a preselected reference population, making the measurements and then determining the intervals. An alternative approach is to perform analysis of results generated as part of routine pathology testing and using appropriate statistical techniques to determine reference intervals. This is known as the indirect approach. This paper from a working group of the International Federation of Clinical Chemistry (IFCC) Committee on Reference Intervals and Decision Limits (C-RIDL) aims to summarize current thinking on indirect approaches to reference intervals. The indirect approach has some major potential advantages compared with direct methods. The processes are faster, cheaper and do not involve patient inconvenience, discomfort or the risks associated with generating new patient health information. Indirect methods also use the same preanalytical and analytical techniques used for patient management and can provide very large numbers for assessment. Limitations to the indirect methods include possible effects of diseased subpopulations on the derived interval. The IFCC C-RIDL aims to encourage the use of indirect methods to establish and verify reference intervals, to promote publication of such intervals with clear explanation of the process used and also to support the development of improved statistical techniques for these studies.