Site-to-site peptide transport on a molecular platform using a small-molecule robotic arm

Peptides attached to a cysteine hydrazide ‘transporter module’ are transported selectively in either direction between two chemically similar sites on a molecular platform, enabled by the discovery of new operating methods for a molecular transporter that functions through ratcheting. Substrate repositioning is achieved using a small-molecule robotic arm controlled by a protonation-mediated rotary switch and attachment/release dynamic covalent chemistry. A polar solvent mixtures were found to favour Z to E isomerization of the doubly-protonated switch, transporting cargo in one direction (arbitrarily defined as ‘forward’) in up to 85% yield, while polar solvent mixtures were unexpectedly found to favour E to Z isomerization enabling transport in the reverse (‘backward’) direction in >98% yield. Transport of the substrates proceeded in a matter of hours (compared to 6 days even for simple cargoes with the original system) without the peptides at any time dissociating from the machine nor exchanging with others in the bulk. Under the new operating conditions, key intermediates of the switch are sufficiently stabilized within the macrocycle formed between switch, arm, substrate and platform that they can be identified and structurally characterized by ¹H NMR. The size of the peptide cargo has no significant effect on the rate or efficiency of transport in either direction. The new operating conditions allow detailed physical organic chemistry of the ratcheted transport mechanism to be uncovered, improve efficiency, and enable the transport of more complex cargoes than was previously possible.

Peptides are transported in either direction between chemically similar sites on a molecular platform, substrate repositioning is achieved using a cysteine hydrazide transporter module and a small-molecule robotic arm controlled by a rotary switch.     

Combined application of INAA and PIXE for studying the regional aerosol composition in Southern Africa

As part of the SAFARI-92 biomass buming experiment, aerosol collections were carried out with several size-fractionating sampling devices at a number of sites in Southern Africa. One of the samplers used at all ground-based sites was a stacked filter unit (SFU). The SFU samples were analyzed by both INAA and PIXE analysis. The present paper gives an intercomparison of the analytical results obtained in order to assess the accuracy and to check the quality assurance of the analytical procedures. Twenty-one common elements were determined by both INAA and PIXE. Concentrations of 13 elements (i.e., Na, Mg, Al, Cl, K, Ca, Ti, V, Cr, Mn, Fe, Zn and Br) were generally measured with sufficient precision in both techniques for performing the intercomparison. The INAA and PIXE data were compared in terms of PIXE/INAA concentration ratios on a sample by sample basis for the coarse and fine size fraction separately. the atmospheric concentrations for K, Mn and Fe agreed within 5–10%, the agreement between the data for the other common elements was typically better than 15%. Possible explanations for lower than 1.0 ratios for Cl, Br and Na are presented. The common elements were classified into groups according to their detectability and sensitivity in each technique.     

Ketalizations of aryl ω-(2-imidazolyl)alkyl ketones by glycerol and 3-mercapto-1,2-propanediol. synthesis and characterization of cis- and trans-{2-aryl-2-[ω-(2-imidazolyl)alkyl](1,3-dioxolan-4-yl and 1,3-oxathiolan-5-yl)}methanols

Aryl 2-[(2-imidazolyl)ethyl or 3-(2-imidazolyl)propyl]ketones were ketalized by glycerol or 3-mercapto-1,2-propanediol in boiling benzene in the presence of 4-toluenesulfonic acid to provide the title compounds. The aryl substituents are 4-chloro-, 4-bromo-, 4-fluoro-, or 2,4-dichlorophenyl. While aryl (2-imidazolyl)methyl ketones condensed with glycerol to form cis- and trans-{2-aryl-2-[(2-imidazolyl)methyl]-4-(hydroxymethyl)}-1,3-dioxolanes, related condensations with 3-mercapto-1,2-propanediol, under similar, or even more stringent reaction conditions, produced no 1,3-oxathiolane analogs, with the starting ketones being recovered. Separation and structure determination of these racemic cis and trans isomeric products are described. The structure of these stereoisomers was established by means of ¹H and ¹³C nmr correlation and nOe experiments. Selective methylation of the N-unsubstituted 2-imidazolyl alcohols with one equivalent sodium hydride and methyl iodide provided the corresponding N-methyl alcohols in excellent yields. With excess benzoyl chloride, N-unsubstituted 2-imidazolyl alcohols were initially converted to O, N-dibenzoates from which the N-benzoyl group was easily cleaved by ammonium hydroxide in ethanol to provide benzoate esters.     

Cerium Oxide Nanorods Synthesized by Dalbergia sissoo Extract for Antioxidant,Cytotoxicity, and Photocatalytic Applications

In this study, cerium oxide nanorods (CeO₂-NRs) were synthesized by using the phytochemicals present in the Dalbergia sissoo extract. The physiochemical characteristics of the as-prepared CeO₂-NRs were investigated by using ultraviolet-visible spectroscopy (UV-VIS), scanning electron microscopy (SEM), Fourier transform infrared spectroscopy (FTIR), and X-ray diffraction analysis (XRD). The SEM and UV-VIS analyses revealed that the acquired nanomaterials possessed a rod-like morphology while the XRD results further confirmed that the synthesized NRs exhibited a cubic crystal lattice system. The antioxidant capacity of the synthesized CeO₂-NRs was investigated by using several in vitro biochemical assays. It was observed that the synthesized NRs exhibited better antioxidant potential in comparison to the industrial antioxidant of the butylated hydroxyanisole (BHA) in 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. The biochemical assays, including lipid peroxidation (LPO), total antioxidant capacity (TAC), and catalase activity (CAT), were also performed in the human lymphocytes incubated with the CeO₂-NRs to investigate the impact of the NRs on these oxidative biomarkers. Enhanced reductive capabilities were observed in all the assays, revealing that the NRs possess excellent antioxidant properties. Moreover, the cytotoxic potential of the CeO₂-NRs was also investigated with the MTT assay. The CeO₂-NRs were found to effectively kill off the cancerous cells (MCF-7 human breast cancer cell line), further indicating that the synthesized NRs exhibit anticancer potential as well. One of the major applications studied for the prepared CeO₂-NRs was performing the statistical optimization of the photocatalytic degradation reaction of the methyl orange (MO) dye. The reaction was optimized by using the technique of response surface methodology (RSM). This advanced approach facilitates the development of the predictive model on the basis of central composite design (CCD) for this degradation reaction. The maximum degradation of 99.31% was achieved at the experimental optimized conditions, which corresponded rather well with the predicted percentage degradation values of 99.58%. These results indicate that the developed predictive model can effectively explain the performed experimental reaction. To conclude, the CeO₂-NRs exhibited excellent results for multiple applications.     

Recent Updates on the Functional Impact of Kahweol and Cafestol on Cancer

Kahweol and cafestol are two diterpenes extracted from Coffea arabica beans that have distinct biological activities. Recent research describes their potential activities, which include anti-inflammatory, anti-diabetic, and anti-cancer properties, among others. The two diterpenes have been shown to have anticancer effects in various in vitro and in vivo cancer models. This review aims to shed light on the recent developments regarding the potential effects of kahweol and cafestol on various cancers. A systematic literature search through Google Scholar and PubMed was performed between February and May 2022 to collect updates about the potential effects of cafestol and kahweol on different cancers in in vitro and in vivo models. The search terms “Kahweol and Cancer” and “Cafestol and Cancer” were used in this literature review as keywords; the findings demonstrated that kahweol and cafestol exhibit diverse effects on different cancers in in vitro and in vivo models, showing pro-apoptotic, cytotoxic, anti-proliferative, and anti-migratory properties. In conclusion, the diterpenes kahweol and cafestol display significant anticancer effects, while remarkably unaffecting normal cells. Our results show that both kahweol and cafestol exert their actions on various cancers via inducing apoptosis and inhibiting cell growth. Additionally, kahweol acts by inhibiting cell migration.     

Performance evaluation of praseodymium doped fiber amplifiers

Optical Review - In this paper, we report the performance evaluation of praseodymium doped fiber amplifier (PDFA) operating in 1.25–1.35 μm band of wavelengths based on...     

Kinetic spectrophotometric methods for the determination of alfuzosin hydrochloride in bulk and pharmaceutical formulations

Simple and sensitive kinetic spectrophotometric methods were established for the determination of alfuzosin hydrochloride in bulk and in its pharmaceutical preparations using alkaline potassium permanganate as an oxidizing agent. The methods involve determination of alfuzosin HCl by kinetic studies of its oxidation at room temperature for a fixed time of 15 min. The absorbance of the colored manganate ions was measured at 610 nm. Alternatively, the decrease in the absorbance of permanganate upon addition of the studied drug was also measured at 525 nm. The absorbance-concentration plots in both procedures were rectilinear over the range of 2.0–30.0 μg/mL. The different experimental parameters affecting the development were carefully studied and optimized. The determination of alfuzosin HCl by the fixed concentration and initial rate methods is also feasible with the calibration equations obtained but the fixed time method has been found to be more applicable. Both procedures were applied to the determination of alfuzosin HCl in formulations. The results obtained were in good agreement with those obtained using reference methods.     

Determination of trace amounts of chromium (VI) by flow injection analysis with chemiluminescence detection

A new sensitive chemiluminescence (CL) method combined with continuous flow injection analysis is described for the determination of Cr(VI). Strong CL signals were generated by Cr(VI)-catalysed oxidation of gallic acid in the presence of potassium permanganate and hydrogen peroxide. Effects of reagent concentrations, temperature, pH, flow rates, mixing coil length and mixing flow sequences on the chemiluminescence intensity were studied. Under the optimised experimental conditions, the relationship between the logarithm of concentration (log?C) of Cr(VI) and the logarithm of intensity (log?I) is linear over the range of 2?×?10^?11 – 5?×?10^?4?mol?L^?1, with the detection limit (3σ) of 4?×?10^?12?mol?L^?1. Relative standard deviation of ten measurements of 1?×?10^?9?mol?L^?1 Cr(VI) is 1.7%. This flow injection analysis (FIA) system proved to be able to analyse up to 40 samples h^?1. Effects of various interferences possibly present in the water samples were investigated. Most cations and anions, as well as organic compounds, did not interfere with the determination of Cr(VI) in water samples. The experimental results obtained for chromium in reference materials were also in good agreement with the certified values.     

Phenylpropanoids from Tanacetum baltistanicum with Nematocidal and Insecticidal Activities

Chemistry of Natural Compounds - One new and seven known secondary metabolites 1–8 were isolated, and the nematocidal and insecticidal activities of major compounds from Tanacetum...     

Deciphering the Role of Filamin B Calponin-Homology Domain in Causing the Larsen Syndrome,Boomerang Dysplasia,and Atelosteogenesis Type I Spectrum Disorders via a Computational Approach

Filamins (FLN) are a family of actin-binding proteins involved in regulating the cytoskeleton and signaling phenomenon by developing a network with F-actin and FLN-binding partners. The FLN family comprises three conserved isoforms in mammals: FLNA, FLNB, and FLNC. FLNB is a multidomain monomer protein with domains containing an actin-binding N-terminal domain (ABD 1–242), encompassing two calponin-homology domains (assigned CH1 and CH2). Primary variants in FLNB mostly occur in the domain (CH2) and surrounding the hinge-1 region. The four autosomal dominant disorders that are associated with FLNB variants are Larsen syndrome, atelosteogenesis type I (AOI), atelosteogenesis type III (AOIII), and boomerang dysplasia (BD). Despite the intense clustering of FLNB variants contributing to the LS-AO-BD disorders, the genotype-phenotype correlation is still enigmatic. In silico prediction tools and molecular dynamics simulation (MDS) approaches have offered the potential for variant classification and pathogenicity predictions. We retrieved 285 FLNB missense variants from the UniProt, ClinVar, and HGMD databases in the current study. Of these, five and 39 variants were located in the CH1 and CH2 domains, respectively. These variants were subjected to various pathogenicity and stability prediction tools, evolutionary and conservation analyses, and biophysical and physicochemical properties analyses. Molecular dynamics simulation (MDS) was performed on the three candidate variants in the CH2 domain (W148R, F161C, and L171R) that were predicted to be the most pathogenic. The MDS analysis results showed that these three variants are highly compact compared to the native protein, suggesting that they could affect the protein on the structural and functional levels. The computational approach demonstrates the differences between the FLNB mutants and the wild type in a structural and functional context. Our findings expand our knowledge on the genotype-phenotype correlation in FLNB-related LS-AO-BD disorders on the molecular level, which may pave the way for optimizing drug therapy by integrating precision medicine.