Pure Form Research Articles

Analytical method development and validation for simultaneous estimation of Bempedoic acid and Ezetimibe in pure and its pharmaceutical dosage form by RP-HPLC.

A simple, accurate and precise method was developed for the simultaneous estimation of the bempedoic acid and ezetimibe in pure and tablet dosage form. The developed method was validated as per International Conference on Harmonization guidelines. The chromatographic separation was achieved isocratically on a Waters- C18, 250 × 4.6mm, 5μm column. Mobile phase containing K2HPO4-methanol in the ratio 60:40 in buffer at pH 4.3 was pumped through column at a flow rate of 1.0ml/min. The temperature was maintained at 25°C. The optimized wavelength selected was 242 nm. The separation of bempedoic acid and ezetimibe showed retention times of 3.090 and 4.268 min respectively. The RSD values of the bempedoic acid and ezetimibe were 0.34 and 0.08 respectively. The accuracy of method was determined at three levels (50,100 and 150%). The percentage recovery was obtained as 100.0 and 100.0% for bempedoic acid and ezetimibe, respectively. The limits of determination and quantitation obtained from regression equations of bempedoic acid and ezetimibe were 1.065, 3.550 and 0.203, 0.677, respectively. The regression equation of bempedoic acid is y = 20,795x + 24,168, and it is y = 6,885.7x + 11,000 for ezetimibe. The retention times were decreased and the run time was decreased, so that the method developed is simple and economical that can be adopted for regular quality control tests in industry.

Amphoteric SnO2 nanoparticles via pH-controlled continuous flow solvothermal synthesis

Amphoteric oxides can be challenging to produce in phase pure form due to their sensitivity to the pH of the reaction mixture. The high-pressure, high-temperature reaction conditions of hydrothermal processes make the pH difficult to control. Here we report a simple approach to obtain nanoparticles of amphoteric oxides, where cheap metal nitrate precursors are reacted in alcohol (2-propanol) water mixtures (25 vol%:75 vol%) to maintain a neutral pH under solvothermal conditions. Phase pure SnO2 nanoparticles were synthesized in a continuous flow solvothermal reactor at 250 °C, 300 °C, 350 °C and 400 °C with sizes ranging from 3 nm to 7 nm. The nanoparticles were characterized using powder X-ray diffraction, transmission electron microscopy, energy dispersive X-ray spectroscopy, Raman spectroscopy, 119Sn MAS NMR spectroscopy, Brunauer-Emmett-Teller nitrogen adsorption, UV–VIS, and as anode material in CR2032 Li-ion battery cells. To demonstrate generality, amphoteric oxides ZnO, Bi2O3, Cr2O3 and γ-AlOOH were also synthesized.

Simultaneous Determination of Pyridoxine HCl, Isoniazid, Trimethoprim and Sulfamethoxazole by Double Divisor Ratio Spectra Derivative Spectroscopic Method

Tuberculosis could be regarded as a serious and enduring menace to global health. A significant hurdle in tuberculosis treatment lies in drug resistance, including the emergence of multiple drug resistance. A regulatory agency has recently endorsed the fixed-dose combination of pyridoxine HCl, isoniazid, trimethoprim, and sulfamethoxazole as a robust therapy for cases of tuberculosis resistant to multiple drugs. Therefore, a successful attempt was made to develop and validate a novel spectroscopic method, i.e., double deviation ratio spectra derivative spectroscopic method, for the simultaneous determination of pyridoxine HCl, Isoniazid, trimethoprim, and sulfamethoxazole in their pure form. The optimized divisor concentration in the developed method was found to be a mixture of 6 μg/mL of sulfamethoxazole and 16 μg/mL of pyridoxine HCl for the determination of isoniazid and trimethoprim in the same quaternary mixture. Similarly, the optimized divisor concentration for the determination of sulfamethoxazole and pyridoxine HCl was found to be a mixture of isoniazid and trimethoprim with concentrations of 10 and 12 μg/mL, respectively. With the developed method, the linearity for pyridoxine HCl, isoniazid, trimethoprim, and sulfamethoxazole was found to be in the range of 8 to 40 μg/mL, 10 to 30 μg/mL, 12 to 36 μg/mL, and 4 to 12 μg/mL, respectively. The results of the accuracy study, in terms of percentage recovery, were found to be 99.92 ± 0.978, 100.04 ± 1.731, 99.87 ± 1.811, and 98.83 ± 0.922 for the simultaneous determination of pyridoxine HCl, isoniazid, trimethoprim, and sulfamethoxazole, respectively, using the developed method. The developed method has been successfully validated as per the ICH guidelines.

Plasma-Activated Tap Water with Oxidative Potential Has an Inactivating Effect on Microbiological Contaminants in Aqueous Suspensions.

Plasma-activated water (PAW) generated from tap water has gained attention as a disinfectant when used directly in its pure form. Little is known about the application of PAW for bacterial inactivation in aqueous environments because its use in fluids results in dilutions. We investigated the effect of PAW in aqueous suspensions simulating such dilutions, and we focused on the minimal addition of PAW volumes to bacterial aqueous suspensions still resulting in high inactivation rates. The antimicrobial effect was highly dependent on the activation of PAW. An increase in activation power from 90 to 100 W resulted in a greater microbial reduction with an identical 10 min activation time. The susceptibility to PAW dilutions was analyzed in detail regarding nine Gram-negative species out of Enterobacterales and other waterborne microorganisms as well as four Gram-positive species present in two different matrices, in saline and in tap water, at high concentrations simulating massive contamination situations. For this purpose, the PAW activation setting of 90 W and 30 min was defined in order to be able to differentiate the limitations of inactivation in individual bacterial species. The Gram-negatives in saline demonstrated susceptibility when one volume unit of PAW was added. However, twice the PAW volume was necessary for inactivation when bacteria were present in tap water. Gram-positive microorganisms were more robust, indicated by prolonged contact times before inactivation. Our results indicate that PAW can be used for bacterial decontamination processes in aqueous environments when added in surplus. Optimized activation settings such as electric power to generate PAW and the contact times to the samples increase the effect of the inactivation a wide range of bacteria, regardless of their resistance profiles.

ReqNet and ReqSim: A Network and Semantic Similarity Dataset of Requirements from the Tree Structure of System Requirement Specifications

Abstract Systems are developed as a solution to the problem space defined by their requirements. The requirements are acquired during the elicitation process. The creative nature of the elicitation process, proprietary nature of requirements, the need of extensive preprocessing and the diverse techniques for analysis restricts the development of a requirement dataset. There exists no standard method to create a requirement dataset. Thus, we devise a semi-formal method to create a multi-purpose requirement dataset that harnesses human knowledge in the system requirement specification documents (SyRSDs) to facilitate the deployment of modern computing algorithms. Our dataset has three forms. (1) ReqList, a list of requirements from 86 distinct systems with their document structure in pure text form. The 12701 requirements are ready to leverage natural language processing techniques and unsupervised machine learning techniques. (2) ReqNet, a large network of requirements consisting of 17375 nodes to deploy graph-theoretic algorithms for requirement engineering. ReqNet portrays small-world network characteristics with an average distance of 9.5619 links. (3) ReqSim, a dataset consisting of 10933 pairs of requirements annotated with their similarity scores. ReqSim enables sentence-level supervised learning tasks to exploit the semantics of requirements. The similarity scores are coherent with human knowledge. Our dataset is grounded by the tree structure of SyRSDs. We devise a method to extract a tree from the SyRSDs. The tree structure resonates with the hierarchical nature of the requirement allocation process. The ReqList, ReqNet and ReqSim dataset is available at https://github.com/ChandanKSahu/ReqList_ReqNet_ReqSim.

In-depth metabolite characterization of seaweed-based plant biostimulants: Insights into bioactive components

Biostimulants derived from Kappaphycus alvarezii are renowned for sustainable agricultural enhancement, yet the exploration of numerous other tropical algae remains uncharted. This study aimed to unravel the metabolite diversity, bioactivities, and potential plant biostimulant properties of extracts derived from Kappaphycus alvarezii (KAE), Gracilaria debilis (GDE), and Sargassum cinctum (SCE). Two-year field trials showcased a significant boost in maize grain yields, indicating the biostimulant potential of each extract.Application of 7.5 % seaweed extract concentration substantially increased grain yields by 32 %, 29 %, and 31 % over the control for KAE, GDE, and SCE in the first-year trial and by 31 %, 28 %, and 32 % in the second year. Even a lower concentration of 2.5 % resulted in an increase in grain yield over the control. High-resolution chromatographic techniques coupled with tandem mass spectrometry (MS/MS) revealed 198, 202, and 191 compounds in KAE, GDE, and SCE, respectively. GC–MS profiling further unveiled 23, 21, and 12 metabolites, respectively. The extracts from red and brown seaweeds harbored distinct metabolites with low similarities to each other. These extracts contained a spectrum of compounds, including glycerol, glycine, valine, ellagic acid, cromakalim, genistein, 1,4-β-d-glucan, polyamines, n1-acetylspermine, mannose, propionic acid, benzoic acid, glycine, coumaric acid, hydroxycinnamic acids, and resveratrol. These compounds, known for their potent bio-stimulatory properties in various crops when applied exogenously in pure forms. This study transcends the conventional understanding of seaweed extract efficacy by shedding light on lesser-known metabolites which might have potential biostimulant roles. In contrast to the well-established components traditionally associated with seaweed extracts, this exploration highlights the need to test the biological activities of several other overlooked compounds spanning diverse classes.

Exploring the electrocatalytic performance of silicene and single atom doped silicene for HER, OER and ORR activity using density functional theory

The transition towards hydrogen energy is paramount due to its potential to mitigate environmental pollution caused by fossil fuels. The greener and cleaner way of producing and utilizing hydrogen is through water electrolysis and hydrogen fuel cell where the sluggish reaction kinetics bottlenecks the widescale implementation. Hence, in this study, density functional theory (DFT) is utilized to study the HER, OER and ORR performance of pristine and doped silicene sheets where the dopants (B, C, N, Al and P) are introduced as single atom. The thermodynamical stability for pristine and doped sheets are confirmed with ADMP study and the cohesive energy for all the sheets are found to be around -4.2 eV per atom which validates their stability. The hydrogen evolution reaction (HER) performance of all the sheets is studied and the N doped silicene exhibits better catalytic property with a lowest overpotential of 70 mV and the C doped silicene shown good HER performance with an overpotential of 180 mV. In case of oxygen evolution reaction (OER) and oxygen reduction reaction (ORR), the pristine silicene is found to behave better in the ORR performance while the C doped silicene has the lowest overpotential compared with the other sheets. The variation in the catalytic performance is studied with the reactivity parameters which implies that the nucleophilic nature of the material enhances the HER performance. Furthermore, the results suggest that C doped silicene can be utilized as a bifunctional catalyst for the HER and OER performance. This study suggests that the silicene in the pure form as well as with dopant can be a good electrocatalyst for the water splitting and fuel cell application.

Carbon-based Flame Retardants for Polymers: A Bottom-up Review.

This state-of-the-art review is geared toward elucidating the molecular understanding of the carbon-based flame-retardant mechanisms for polymers via holistic characterization combining detailed analytical assessments and computational material science. The use of carbon-based flame retardants, which include graphite, graphene, carbon nanotubes (CNTs), carbon dots (CDs), and fullerenes, in their pure and functionalized forms are initially reviewed to evaluate their flame retardancy performance and to determine their elevation of the flammability resistance on various types of polymers. The early transition metal carbides such as MXenes, regarded as next-generation carbon-based flame retardants, are discussed with respect to their superior flame retardancy and multifunctional applications. At the core of this review is the utilization of cutting-edge molecular dynamics (MD) simulations which sets a precedence of an alternative bottom-up approach to fill the knowledge gap through insights into the thermal resisting process of the carbon-based flame retardants, such as the formation of carbonaceous char and intermediate chemical reactions offered by the unique carbon bonding arrangements and microscopic in-situ architectures. Combining MD simulations with detailed experimental assessments and characterization, a more targeted development as well as a systematic material synthesis framework can be realized for the future development of advanced flame-retardant polymers.

Synthesis and Inclusion Properties of a β-Cyclodextrin Heptaphosphoramidate.

In this study, we report a novel per-6-substituted β-cyclodextrin (4) featuring seven phosphoramidate moieties as an innovative host for inclusion. This structurally well-defined host has remarkable water solubility and was isolated in pure form. Analytical techniques such as NMR and ITC were used to probe the molecular interactions with different drug molecules. Our investigations revealed that host 4 can form 2:1 inclusion complexes with various drugs. Further studies showed that the inclusions of drugs by β-CD host (4) are mostly enthalpy driven, highlighting the potential roles played by the phosphoramidate functionalities of the host. Comparatively, a per-O2, O3-acetylated analog (6) of compound 4 was also obtained, which also shows unusual water solubility but diminished inclusion capability.

The Application of Cathodoluminescence (CL) for the Characterization of Blue Pigments

The combined application of Cathodoluminescence (CL) with Scanning Electron Microscopy (SEM) on paintings and painted surfaces has the potential to identify both organic and inorganic pigments on a micrometre or even nanometre scale. Additionally, the combination with Energy-Dispersive Spectrometry (EDS) allows for a more holistic, elemental, and mineralogical characterization of pigments. In addressing the need for the creation of a robust, open access database of characteristic CL spectra of pigments, a large project has been undertaken, focusing primarily on common organic and inorganic pigments. The present paper focuses on the CL characterization of 10 significant blue pigments in pure powder form: cerulean blue, Egyptian blue, Han blue, indigo, lapis lazuli, Maya blue, phthalo blue, vivianite, ultramarine blue, and zirconium blue. The CL spectra present characteristic bands for most of the pigments, allowing their secure identification, especially when combining the results with the EDS analyses. The effect of binding media and of the mixture of different pigments was also studied, via the analysis of mixtures of pigments with oil painted over canvas. Overall, both the binding medium and the mixture of pigments do not appear to create significant differences in the occurring spectra, thus allowing the identification of individual pigments. EDS and RAMAN spectra are included in order to facilitate comparison with other databases.

Diastereo-Divergent Synthesis of Ring A-lactones Derived From Cholesterol and Diosgenin. A Convenient Solution for an Old Problem. NMR and X-Ray Characterization

A convenient protocol for the synthesis of A-ring lactones derived from cholesterol was developed. A lactone reduction-lactol separation-reoxidation sequence, applied to the inseparable mixture of diastereomeric lactones allows the production of multigram amounts of each lactone in pure form. The same sequence applied to A-ring lactones derived from diosgenin produced similar results. A detailed NMR characterization of all the obtained lactones is also provided. X-ray diffraction corroborated the structure of the obtained compounds.

Iron Oxyhydroxide Transformation in a Flooded Rice Paddy Field and the Effect of Adsorbed Phosphate.

The mobility and bioavailability of phosphate in paddy soils are closely coupled to redox-driven Fe-mineral dynamics. However, the role of phosphate during Fe-mineral dissolution and transformations in soils remains unclear. Here, we investigated the transformations of ferrihydrite and lepidocrocite and the effects of phosphate pre-adsorbed to ferrihydrite during a 16-week field incubation in a flooded sandy rice paddy soil in Thailand. For the deployment of the synthetic Fe-minerals in the soil, the minerals were contained in mesh bags either in pure form or after mixing with soil material. In the latter case, the Fe-minerals were labeled with 57Fe to allow the tracing of minerals in the soil matrix with 57Fe Mössbauer spectroscopy. Porewater geochemical conditions were monitored, and changes in the Fe-mineral composition were analyzed using 57Fe Mössbauer spectroscopy and/or X-ray diffraction analysis. Reductive dissolution of ferrihydrite and lepidocrocite played a minor role in the pure mineral mesh bags, while in the 57Fe-mineral-soil mixes more than half of the minerals was dissolved. The pure ferrihydrite was transformed largely to goethite (82-85%), while ferrihydrite mixed with soil only resulted in 32% of all remaining 57Fe present as goethite after 16 weeks. In contrast, lepidocrocite was only transformed to 12% goethite when not mixed with soil, but 31% of all remaining 57Fe was found in goethite when it was mixed with soil. Adsorbed phosphate strongly hindered ferrihydrite transformation to other minerals, regardless of whether it was mixed with soil. Our results clearly demonstrate the influence of the complex soil matrix on Fe-mineral transformations in soils under field conditions and how phosphate can impact Fe oxyhydroxide dynamics under Fe reducing soil conditions.

Influence of heterochirality on the structure, dynamics, biological properties of cyclic(PFPF) tetrapeptides obtained by solvent-free ball mill mechanosynthesis

Cyclic tetrapeptides c(Pro-Phe-Pro-Phe) obtained by the mechanosynthetic method using a ball mill were isolated in a pure stereochemical form as a homochiral system (all L-amino acids, sample A) and as a heterochiral system with D configuration at one of the stereogenic centers of Phe (sample B). The structure and stereochemistry of both samples were determined by X-ray diffraction studies of single crystals. In DMSO and acetonitrile, sample A exists as an equimolar mixture of two conformers, while only one is monitored for sample B. The conformational space and energetic preferences for possible conformers were calculated using DFT methods. The distinctly different conformational flexibility of the two samples was experimentally proven by Variable Temperature (VT) and 2D EXSY NMR measurements. Both samples were docked to histone deacetylase HDAC8. Cytotoxic studies proved that none of the tested cyclic peptide is toxic.

Characterization of a novel TFG variant causing autosomal recessive pure hereditary spastic paraplegia.

TFG mutations have previously been implicated in autosomal recessive hereditary spastic paraplegia (HSP), also known as SPG57. This study aimed to investigate the clinical and molecular features of TFG mutations in a Taiwanese HSP cohort. Genetic analysis of TFG was conducted in 242 unrelated Taiwanese HSP patients using a targeted resequencing panel covering the entire coding regions of TFG. Functional assays were performed using an in vitro cell model to assess the impact of TFG variants on protein function. Additionally, other representative TFG mutant proteins were examined to understand the broader implications of TFG mutations in HSP. The study identified a novel homozygous TFG c.177A>C (p.(Lys59Asn)) variant in a family with adolescent-onset, pure form HSP. Functional analysis revealed that the Lys59Asn TFG variant, similar to other HSP-associated TFG mutants, exhibited a low affinity between TFG monomers and abnormal assembly of TFG homo-oligomers. These structural alterations led to aberrant intracellular distribution, compromising TFG's protein secretion function and resulting in decreased cellular viability. These findings confirm that the homozygous TFG c.177A>C (p.(Lys59Asn)) variant is a novel cause of SPG57. The study expands our understanding of the clinical and mutational spectrum of TFG-associated diseases, highlighting the functional defects associated with this specific TFG variant. Overall, this research contributes to the broader comprehension of the genetic and molecular mechanisms underlying HSP.

Structural Basis for Recognition of the FLAG-tag by Anti-FLAG M2

The FLAG-tag/anti-FLAG system is a widely used biochemical tool for protein detection and purification. Anti-FLAG M2 is the most popular antibody against the FLAG-tag, due to its ease of use, versatility, and availability in pure form or as bead conjugate. M2 binds N-terminal, C-terminal and internal FLAG-tags and binding is calcium-independent, but the molecular basis for the FLAG-tag specificity and recognition remains unresolved.Here we present an atomic resolution (1.17 Å) structure of the FLAG peptide in complex with the Fab of anti-FLAG M2, revealing key binding determinants. Five of the eight FLAG peptide residues form direct interactions with paratope residues. The FLAG peptide adopts a 310 helix conformation in complex with the Fab. These structural insights allowed us to rationally introduce point mutations on both the peptide and antibody side. We tested these by surface plasmon resonance, leading us to propose a shorter yet equally binding version of the FLAG-tag for the M2 antibody.

The electrical and dielectric features of Al/YbFeO3/p-Si/Al and Al/YbFe0.90Co0.10O3/p-Si/Al structures with interfacial perovskite-oxide layer depending on bias voltage and frequency

In this investigation, thin films of YbFeO3, both in its pure form and doped with 10% Co, were fabricated on a p-Si substrate at 500 °C through the radio-frequency magnetron sputtering method. Examination via Scanning Electron Microscopy demonstrated a porous texture for the pure sample, contrasting with a smooth and crack-free surface post-Co doping. Analysis via X-ray photoelectron spectroscopy unveiled Yb’s 3 + oxidation state, alongside the presence of lattice oxygen, oxygen vacancies, and adsorbed oxygen evident in Gaussian fitting curves. Photoluminescence spectroscopy revealed an augmented emission intensity, likely attributed to increased defect initiation in the Co-doped specimen. Moreover, Raman spectroscopy was employed to identify vibration modes in the examined samples, demonstrating shifts in Raman peaks indicative of Co substitution and subsequent distortion in the crystal structure of YbFeO3. Electrical assessments were conducted at room temperature (300 K) under ambient conditions, employing voltage and frequency as variables. Capacitance–voltage measurements illustrated the emergence of an accumulation, with depletion and inversion regions manifesting at different frequencies based on the applied voltage, attributed to the YbFeO3 interfacial layer at the Al and p-Si interface. The conductance-voltage characteristics indicated that the structure exhibited maximum conductance in the accumulation region. Series resistance for these configurations was deduced from capacitance-conductance-voltage measurements, indicating a dependence on both bias voltage and frequency. The doping process led to a reduction in capacitance and series resistance, accompanied by an increase in conductance values. After obtaining corrected capacitance and conductance parameters, it became evident that series resistance significantly influences both parameters. Interface state density (Nss), determined through the Hill-Coleman relation demonstrated a decreasing trend with increasing frequency. The pure sample exhibited higher interface state density compared to the Co-doped sample at each frequency, highlighting that the 10% Co-doped YbFeO3 thin film enhances the quality of the metal–semiconductor interface properties compared to the pure contact.

Tacrolimus and Cyclosporin Pharmacotherapy, Detection Methods, Cytochrome P450 Enzymes after Heart Transplantation.

Advances in organ transplantation were made after the discovery of the pure form of cyclosporine by Dr Jean Borel in the 1970s. In fact, in clinical practice achieving a delicate balance in circulating immunosuppressive necessitate focus on the difficult task of posttransplant therapeutic drug monitoring. The purpose of this study was to determine the pharmacologic properties of cyclosporine- tacrolimus, detection methods, and the effects on the activity of cytochrome P450 enzymes when prescribing the most efficient treatments in forms of polypharmacy for the recipients of heart transplantation. Scientific literature on the interactions of tacrolimus and cyclosporine with human cytochrome P450 enzymes was searched using PUBMED.Gov (https://pubmed.ncbi.nlm.nih.gov/), Web of Science, and Scopus. Prescription immunosuppressive drugs based on polypharmacy accompanied by induction agents could result in hidden neurotoxicity and nephrotoxicity. A literature search shows that cyclosporine prescription with antihypertensives drugs needs close monitoring. Co-administration of tacrolimus and diltiazem or verapamil needs a decrease in the tacrolimus dose by 20-50%. Vigilant attention to the lowest possible statin dose is needed when coadministered with fluvastatin or pravastatin. Polypharmacy based on ticlopidine, clopidogrel, and cyclosporine or tacrolimus needs monitoring of immunosuppressive drug levels for several months. A prescription with clotrimazole or fluconazole needs close monitoring, and itraconazole or ketoconazole needs to reduce the initial dose by 50%. Combination with nefazodone needs to be avoided, and alternative drugs such as sertraline or citalopram could be prescribed in addition to further monitoring consideration. In prescription with phenytoin, the bound and free phenytoin levels need close monitoring. Polypharmacy based on tacrolimus or cyclosporine needs vigilant therapeutic drug monitoring due to the cytochrome P450 enzymes associated with biochemical variables in metabolic pathways. Further attention to polypharmacy should be given to circulate drugs that could hide pharmacokinetics interactions associated with infections, malignancies, chronic kidney disease, and rejection after organ transplantation.

Validation of RP-HPLC-PDA method for determination of five Antidiabetic drugs in Pharmaceutical Formulations

A gradient reverse phase technique can be considered as a good method for separation and quantification of drugs. High-performance liquid chromatography was developed and verified for the determination of five antidiabetic drugs “Metformin, Glipizide, Repaglinide, Acarbose and Glimepiride” in pure form and in their pharmaceutical formulations within 21.8 minutes. Separation was carried out using the C18 column (150 mm×4.6 mm, 5 μm) with a mobile phase consisting of two solutions (A and B). PDA detection was set at 240 nm and temperature 30C. The retention time of metformin, glipizide, repaglinide, acarbose and glimepiride was detected at 2.12, 10.37, 12.49, 19.8, 21.8 min. respectively. Also, limits of detection were reported to be 0.0025, 0.0016, 0.005, 0.003, 0.002 mg/ml and limits of quantification as 0.0078,0.005, 0.017, 0.0091, 0.006 mg/ml. This analytical method, according to ICH standards, can also be relevant and beneficial for pharmaceutical and quality control studies.

Post-Ugi Acid-Catalyzed Fragmentation and Trapping: An Unprecedented Approach towards Novel Bis(indolyl)acetamides

AbstractAn unprecedented post-Ugi Brønsted acid catalyzed fragmentation followed by in situ trapping of the alkylideneindolenine intermediate by indole nucleophiles was developed to furnish novel bis(indolyl)acetamides. The amide fragment formed during this acid-catalyzed fragmentation of the Ugi adduct was also isolated and characterized. The carboxylic acid and amine components of the Ugi reaction were carefully chosen to permit a simple water wash for the removal of the amide fragment to obtain the desired bis(indolyl)acetamides in a pure form.

Proof in Administrative Law: the German Perspective

German administrative law is characterized by the idea that the authorities and, in the case of a lawsuit, the administrative judges have sovereignty over the investigation of the facts ‐ the so-called principle of ex officio inquiry (Section 1). In the relationship between the official and judicial investigation of the facts, it is striking that the judicial duty to investigate is not limited by the official duty to clarify the facts. This shift in the direction of a judicial right of final decision, also with regard to the factual basis of administrative decisions, derived from the German Constitution (Article 19(4) Grundgesetz) can probably only be explained by the historical background of National Socialist despotism. The article reveals that the instruments of evidence collection (Section 2), the consideration of evidence (Section 3), the evidential standard (Section 4) and the burden of proof (Section 5) are based on the principle of ex officio inquiry. This principle is based on the assumption that only a perceivable set of facts can be established. Therefore, practice and sectoral administrative laws show that in areas where obtaining knowledge is particularly difficult, the principle of ex officio investigation and the law of evidence based on it must be modified and, in particular, strong participation of the parties in obtaining the facts must be made possible. At the same time, the German law of evidence is based on theories and instruments of civil procedural law, which is characterized by the principle of production of evidence. Against this background, the article aims to illustrate that, contrary to the first impression, German administrative law does not implement the principle of official investigation in its pure form, but it is understood in a refined open and area-specific manner.