The control of stereo-, regio-, and chemo-selectivity in transition-metal-catalyzed coupling reactions is a key topic in organic synthesis. Several methods for controlling selectivity have been reported thus far. On the other hand, the reduction of the catalyst loading in the reaction is one of the most important issues in organic synthesis from the standpoint of green sustainable chemistry. As another advantage of reducing the catalyst loading, the expression of the reaction selectivity and the substituent effect caused by the reduction of the catalyst loading to the parts-par-million (ppm) level in various catalytic reactions is presented herein.

The KcsA is a prokaryotic potassium-oriented channel, which is sourced from the Streptomyces lividans soil bacteria. From extensive studies that have been carried over the KcsA potassium channel, it has been proved that various factors enable the gating and shuttling of the potassium ions into and out of the cells. Some of the factors include the different concentration of protons in the inside and outside membrane. The other factor is the existence of the selectivity filter equipped in the exit of channel pore, which enables the movement of the K⁺ ions. Not only are potassium ions present in the channel but also sodium ions. Potassium and sodium ions are the ions that are essential in the conductivity of a cell because of their charge. An intuitive idea about why K⁺ ions are at least 10,000 times more permeant than Na⁺ ions is presented in various entities. The hypothesis is that the selectivity ratio is probably related to the successive entry of Na⁺ ions, based on the premise that the ratio seems to be relevant to unpredictable quantities caused by Brownian corrosion of ions.

Viral infections inflict many serious human diseases, being responsible for remarkably high mortality rates. In this sense, both the academy and the pharmaceutical industry are continuously searching for new compounds with antiviral activity, and in addition, face the challenge of developing greener and more efficient methods to synthesize these compounds. This becomes even more important with drugs possessing stereogenic centers as highly enantioselective processes are required. In this minireview, the advances achieved to improve synthetic routes efficiency and sustainability of important commercially antiviral chiral drugs are discussed, highlighting the use of organocatalytic methods.

The Julia-Kocienski olefination reaction has become over past 30 years since its discovery one of the key C-C connective methods that is used in the late-stage natural product synthesis. The reaction proceeds under mild reaction conditions, with wide substrate scope and functional group tolerance, and with high (E) selectivity. In this review, we discuss the reaction from a mechanistic point of view and disclose key features that play an important role in reaction selectivity. Finally, the mechanistic aspects of the newly developed modification of the Julia-Kocienski reaction, which allows the formation of both (E) and (Z) olefins, from the same reaction partners, are discussed.

Autism spectrum disorders (ASD) is a heterogeneous group of neurodevelopmental disorders characterized by food selectivity in a significant portion of the population. The nature of this selectivity remains unclear, with hypotheses suggesting associations with sensory disorders or stereotypical and repetitive patterns of activity and interests. This study aimed to determine the prevalence and nature of food selectivity traits in individuals with ASD compared to the neurotypical population. The study involved 219 participants, with 115 diagnosed with autism and 92 without. 12 children undergoing diagnosis were excluded from the analyses. Findings revealed that food selectivity traits are more common in individuals with ASD, with differences in preferences mainly involving structure, color, taste, and serving method. Children with ASD had more food selectivity traits than those without, and certain food characteristics could alter intake as they grow. Selectivity occurred for both sensory and stereotypical reasons, but stereotypical features significantly differentiated neurotypical individuals from those with ASD.

Recently, ice with the stacking disorder structure, consisting of random sequences of cubic ice (Ic) and hexagonal ice (Ih) layers, is reported to be more stable than pure Ih/Ic. While, due to a much lower free energy barrier of heterogeneous nucleation, in practice, the freezing process of water is usually controlled by heterogeneous nucleation which is triggered by an external medium. Herein, molecular dynamic simulations were carried out to explore the polymorph dependence of ice on the lattice structure of substrates. It turns out that, during the nucleation stage, the polymorph of ice nuclei can be severely altered by the graphene substrate, on which the Ih was found to occupy an absolute majority in new-formed ice. This can be attributed to the structure similarity between graphene and basal face of Ih. Besides the nucleation stage, our results suggest that the substrate can not affect the polymorph of ice which is far from the graphene surface. The polymorph selectivity of graphene to Ih will diminish with the growth of ice layer.

The transforming growth factor-β (TGF-β), in which overexpression have been associated with various diseases, has become an attractive molecular target for the treatment of cancers. Three series of 3-substituted-4-(quinoxalin-6-yl) pyrazoles 14a–h, 15a–h, 16a–h, 22a, 22b, 22d, 23a, 23b, 23d, 24b, and 24d were synthesized and evaluated for their activin receptor-like kinase 5 (ALK5) and p38α mitogen activated protein (MAP) kinase inhibitory activity in an enzymatic assays. Among these compounds, the most active compound 16f inhibited ALK5 phosphorylation with an IC₅₀ value of 0.28 µM, with 98% inhibition at 10 µM. Compound 16f also had good selectivity index of >35 against p38α MAP kinase, with 9.0-fold more selective than clinical candidate, compound 3 (LY-2157299). Molecular docking study was performed to identify the mechanism of action of the synthesized compounds and their good binding interactions were observed. ADMET prediction of good active compounds showed that these ones possess good pharmacokinetics and drug-likeness behavior.

We recently screened a series of new aziridines β-D-galactopyranoside derivatives for selective anticancer activity and identified 2-methyl-2,3-[N-(4-methylbenzenesulfonyl)imino]propyl 2,3-di-O-benzyl-4,6-O-(S)-benzylidene-β-D-galactopyranoside (AzGalp) as the most promising compound. In this article, we explore possible mechanisms involved in the cytotoxicity of this aziridine and evaluate its selective anticancer activity using cancer cells and normal cells from a variety of tissues. Our data show that AzGalp induces DNA damage (detected with the comet assay). Cells deficient in the DNA repair pathway nucleotide excision repair (NER) were hypersensitive to the cytotoxicity of this compound. These results suggest that AzGalp induces bulky DNA adducts, and that cancer cells lacking a functional NER pathway may be particularly vulnerable to the anticancer effects of this aziridine. Several experiments revealed that neither the generation of oxidative stress nor the inhibition of glycolysis played a significant role in the cytotoxicity of AzGalp. The combinations of AzGalp with either oxaliplatin or 5-fluorouracil slightly improved the ability of both anticancer drugs to selectively kill cancer cells. AzGalp also displayed selective cytotoxicity against a panel of malignant cells versus normal cells; the highest selectivity was observed for two acute promyelocytic leukemia cell lines. Additional preclinical studies are necessary to evaluate the anticancer potential of AzGalp.

One important goal of research on heterogeneous catalysis for Fischer Tropsch synthesis (FTS) is to understand the connection linking catalyst morphology and its activity. Development of these effective catalysts highlights the potential for understanding the effectiveness of promoted supported catalysts and revealing their complex and dynamic effects in FTS. The metal-support interaction (MSI) is influenced by the physicochemical and textural features provided by the modified support and can directly influence the sizes of active metal crystallites, reactants and/or products mass transfer, dispersion, mechanical strength, stability and consequently the adsorption-desorption characteristics of the catalyst. Herein, this article explores the general strategies for modifying silica supports (achieved through doping, coating, or promoting the support or support precursor) and how these strategies can be manipulated to further alter catalyst performance and product selectivity by enhancing the amount of active metal species and improving the intrinsic turnover frequency (TOF). Furthermore, the review emphasises a new strategy (the inverse model of the silica support modification) aiming at overcoming the challenges posed by active metal coating or coverage, as well as pore blockages by promoters that occur during conventional preparation of promoted silica supported FT catalysts.

Histone deacetylase (HDAC) inhibitors are class of drugs used in the cancer treatment. Here, we developed a library of 19 analogues of Vorinostat, an HDAC inhibitor used in lymphomas treatment. In Vorinostat, we replaced the hydrophobic phenyl group with various tricyclic ‘caps’ possessing a central, eight-membered, heterocyclic ring, and investigated the HDAC activity and cytotoxic effect on the cancer and normal cell lines. We found that three out of the 19 compounds, based on dibenzo[b,f]azocin-6(5H)-one, 11,12-dihydrodibenzo[b,f]azocin-6(5H)-one and benzo[b]naphtho[2,3-f][1,5]diazocine-6,14(5H,13H)-dione scaffolds, showed better HDACs inhibition than the referenced Vorinostat. In leukemic cell line MV4-11 and in lymphoma cell line – Daudi three compounds showed lower IC50 values than Vorinostat. These compounds had higher activity and selectivity against MV4-11 and Daudi cell lines than reference Vorinostat. We also observed a strong correlation between HDACs inhibition and the cytotoxic effect. Cell lines derived from solid tumors: A549 (lung carcinoma) and MCF-7 (breast adenocarcinoma) as well as reference Balb/3T3 (normal murine fibroblasts) were less susceptible to compounds tested. Developed derivatives show superior properties than Vorinostat, thus they are applicable as selective agents for leukemia and lymphoma treatment.

In our continuous search for selective anticancer treatments, we have screened 65 extracts from 45 plants collected in several areas of Western Andalusia (Spain) for cytotoxic activity against lung cancer cells and lung normal cells. Active extracts were also tested against 11 cell lines from other tissues. An extract from the leaves of Tetraclinis articulata (Vahl) Mast. (Cupressaceae) showed a marked cytotoxicity (IC₅₀ = 0.37 ± 0.03 µg/mL) and selectivity (selectivity index = 378.3) against the lung cancer cells; cisplatin, 5-fluorouracil and an extract from the leaves of Taxus baccata L. (Taxaceae) were less cytotoxic and selective.

The Cu cocatalyst supported on the surface of TiO2 photocatalysts has demonstrated unique activity and selectivity in photocatalytic CO2 reduction. The valence state of copper significantly influences the catalytic process; however, due to the inherent instability of copper's valence states, the precise role of different valence states in CO2 reduction remains inadequately understood. In this study, CuOx/TiO2 catalysts were synthesized using an in-situ growth reduction method, and we investigated the impact of various valence copper species on CO2 photocatalytic reduction. Our results indicate that Cu+ and Cu0 serve as primary active sites, with the selectivity for CH4 and CO products during CO2 photoreduction being closely related to their respective ratios on the catalyst surface. The adsorption and activation mechanisms of CO on both Cu+ and Cu0 surfaces are identified as critical factors determining product selectivity in photocatalytic processes. Furthermore, it is confirmed that Cu+ primarily facilitates CH4 production while Cu0 is responsible for generating CO. This study provides valuable insights into developing highly selective photocatalysts.

This work focused on the solubility of ethane in three promising ionic liquids {1-Hexyl-3-methylimidazolium bis(trifluormethylsulfonyl) imide [HMIM][Tf2N], 1-Butyl-3-methyl-imidazolium dimethyl-phosphate [BMIM][DMP] and 1-Propyl-3- methylimidazolium bis(trifluoromethyl-sulfonyl)-imide [PMIM][Tf2N]}. The solubilities were measured at 303.15 K to 343.15 K and pressures up to 1.4 MPa using a gravimetric microbalance. The overall ranking of ethane solubility in the ionic liquids from highest to lowest is the following: [HMIM][Tf2N] > [PMIM][Tf2N] > [BMIM][DMP]. The Peng- Robinson equation of state was used to model the experimental data using three different mixing rules: van der Waals one, van der Waals two and Wong-Sandler mixing rules combined with the Non-Random Two-Liquid model. The average absolute deviations for the three mixing rules for the ionic liquids at the three temperatures were (4.39, 2.45 and 2.45) %, respectively. Henry’s Law constants for ethane in [BMIM] [DMP] were the highest (lowest solubility) amongst other ionic liquids studied in this work. The selectivity of CO2 over C2H6 was estimated at the three temperatures and the overall ranking of the selectivity was in the following order: [PMIM][Tf2N] > [BMIM][DMP] > [HMIM][Tf2N]> Selexol. Selexol, a widely used physical solvent in gas sweetening has better selectivity than the three ionic liquids studied. [PMIM][Tf2N], a promising solvent, has the highest selectivity among the three ILs studied, and would therefore be the best choice if in addition to carbon dioxide capture, ethane co-absorption was to be avoided. The enthalpy and entropy of solvation at infinite dilution were also estimated.

Phosphodiesterases (PDEs) hydrolyze cyclic nucleotides to modulate multiple signaling events in cells. PDEs are recognized to actively associate with cyclic nucleotide receptors (Protein Kinases, PK) in larger macromolecular assemblies referred to as signalosomes. Complexation of PDEs with PK generates an expanded active site which enhances PDE activity. This facilitates signalosome-associated PDEs to preferentially catalyze active hydrolysis of cyclic nucleotides bound to PK, and aid in signal termination. PDEs are important drug targets and current strategies for inhibitor discovery are based entirely on targeting conserved PDE catalytic domains. This often results in inhibitors with cross-reactivity amongst closely related PDEs and attendant unwanted side effects. Here, our approach targets PDE-PK complexes as they would occur in signalosomes, thereby offering greater specificity. Our developed fluorescence polarization assay has been adapted to identify inhibitors that block cyclic nucleotide pockets in PDE-PK complexes in one mode, and disrupt protein-protein interactions between PDEs and cyclic nucleotide activating protein kinases in a second mode. We tested this approach with three different systems: cAMP-specific PDE8-PKAR, cGMP-specific PDE5-PKG and dual-specificity RegA-RD complexes and ranked inhibitors according to their inhibition potency. Targeting PDE-PK complexes offers biochemical tools for describing the exquisite specificity of cyclic nucleotide signaling networks in cells.

A single dose of psilocybin, a psychedelic and serotonin 2A receptor (5-HT2AR) agonist, may be associated with antidepressant effects. The mechanism behind its antidepressive action is unknown but could be linked to increased synaptogenesis and down-regulation of cerebral 5-HT2AR. Here, we investigate if a single psychedelic dose of psilocybin changes synaptic vesicle protein 2A (SV2A) and 5-HT2AR density in the pig brain. Twenty-four awake pigs received either 0.08 mg/kg psilocybin or saline intravenously. Twelve pigs (n=6/intervention) were euthanized one day post-injection, while the remaining twelve pigs were euthanized seven days post-injection (n=6/intervention). We performed autoradiography on hippocampus and prefrontal cortex (PFC) sections with [3H]UCB-J (SV2A), [3H]MDL100907 (5-HT2AR antagonist) and [3H]Cimbi-36 (5-HT2AR agonist). One day post psilocybin injection, we observed 4.4% higher hippocampal SV2A density and lowered hippocampal and PFC 5-HT2AR density (-15.21% to -50.19%). These differences were statistically significant in the hippocampus for all radioligands and in PFC for [3H]Cimbi-36 only. Seven days post-intervention, there was still significantly higher SV2A density in hippocampus (+9.24%) and PFC (+6.1%) whereas there were no longer any differences in 5-HT2AR density. Our findings suggest that psilocybin’s antidepressive actions are linked to increased persistent synaptogenesis and possibly also to an acute decrease in 5-HT2AR density.

Random copolymers made of both (PIM-polyimide) and (6FDA-durene-PI) were prepared for the first time by a facile one-step polycondensation reaction. By combining the highly porous and contorted structure of PIM (polymers with intrinsic microporosity) and high thermomechanical properties of PI (polyimide), the membranes obtained from these random copolymers [(PIM-PI)x-(6FDA-durene-PI)y] showed high CO₂ permeability (> 1047 Barrer) with moderate CO₂/N₂ (> 16.5) and CO₂/CH₄ (> 18) selectivity, together with excellent thermal and mechanical properties. The membranes prepared from three different compositions of two comonomers (1:4, 1:6 and 1:10 of x:y), all showed similar morphological and physical properties, and gas separation performance, indicating ease of synthesis and practicability for large-scale production. The gas separation performance of these membranes at various pressure ranges (100–1500 torr) was also investigated.

This work describes the catalytic performances of attapulgite/ZSM-5 extrudate in comparison to conventional alumina-bound ZSM-5 extrudate in toluene methylation. The novel attapulgite/ZSM-5 extrudate is prepared by using natural clay attapulgite as binder which introduces mobile alkaline species and macropores to the extrudate. In contrast to alumina-bound extrudate, this novel extrudate shows significantly higher para-selectivity and stability. By using characterization techniques, including in-situ XRD, SEM, NH3 temperature programmed desorption (TPD), thermogravimetric analysis and n-hexane/cyclohexane physical adsorption, the catalytic performance improvement of attapulgite/ZSM-5 extrudate is correlated with the neutralization of Brønsted acid sites by mobile alkaline species during calcination and reaction process. Moreover, a higher para-selectivity was obtained over attapulgite-bound modified ZSM-5 extrudate. The strategy of extruding ZSM-5 catalysts with attapulgite as binder is facile and universal. Such method paves a new way for preparation of shaped toluene methylation catalyst with enhanced para-selectivity and stability.

Recent advances in synthetic membranes allow their use in fields as diverse as food and agriculture, biotechnology, industrial wastewater treatment, and potable water production. Among the newly developed technologies, nanofiltration for liquids and more particularly for desalination of seawater or saline aquifers are actively pursued. However, current solid-state membranes performance is limited, which calls for the development of novel formulations for membranes offering both high permeability (ion and water flux) and ion differentiation (selectivity), usually considered antagonist features. We report the development of hybrid nanoporous membranes made of solid-state polymeric carbonate track-etched (PCTE) thin films in which biological ion channels such as Gramicidin A (GA), alpha-hemolysin (α-HL), and outer-membrane protein F (OmpF) aquaporin are confined and graphene oxide (GO) conjugated cobalt ion selective binding peptide motifs (Copep) are adsorbed, referring as bioinspired and biomimetic approaches, respectively. These solid-state nanoporous membranes are attracting widespread attention since they offer scalability, mechanical robustness, selectivity, controlled pore dimension and shape, for water sustainability. The ion permeability, ion diffusion coefficient and selective ion recognition are evaluated via nanofiltration, cell diffusion kinetics, and UV-Visible absorption spectroscopy to gain insights into the role of key performance parameters including effective ion confinement in track-etched pores, rich surface chemistry, and peptide-induced channel for selective ion transport. These findings provide new avenues for artificial ion channels by synergistic combination of eco-friendly material design such as GO enabled by bio-molecular recognition chemistry.

In recent years, the class of metal-organic framework (MOF) materials emerged. These materials' unique properties can be assigned to their structure, containing inorganic nodes connected with organic linkers. Due to their porosity and flexibility, MOFs have become suitable for various energy-related applications, including gas storage, hydrogen production and heterogeneous catalysis, and photocatalysis. Using DFT+U calculations, we show that the substitution of metal centers in inorganic nodes and the strain engineering of UiO-66 alters the electronic and optical properties of this material. We show that applying mechanical strain on UiO-66 enables the control of absorption coefficient in the UV-Vis spectrum and the photocatalytic processes' selectivity when reactants for several photocatalytic processes are present. The presented findings could lead to general strategies for designing novel MOFs for sustainable energy conversion applications.

Autism spectrum disorder (ASD) involves social communication difficulties and repetitive behaviors, with a growing prevalence worldwide. Symptoms include cognitive impairments, gastrointestinal (GI) issues, feeding difficulties, and psychological problems. A significant concern in ASD is food selectivity, leading to nutrient deficiencies. Common GI issues in ASD, such as constipation and irritable bowel syndrome, stem from abnormal gut flora and immune system dysregulation. Sensory sensitivities and behavioral challenges exacerbate these problems, correlating with neurological symptom severity. Children with ASD also exhibit higher oxidative stress due to low antioxidant levels like glutathione. Therapeutic diets, including ketogenic, high-antioxidant, gluten-free, and casein-free, show potential in managing ASD symptoms like behavior, communication, GI issues, and oxidative stress, though the evidence is limited. Various studies have focused on different populations, but there is increasing concern about the impact on children. This review examines the effect of food selectivity, GI problems, and antioxidant deficiencies in ASD and revises the effectiveness of various therapeutic diets, highlighting the need for further research to confirm their long-term benefits.

This study investigates the process of multi-walled carbon nanotube (MWCNT) coatings to enhance the lamp heating temperature for solar thermal absorption applications. The primary focus is studying the effects of self-organized honeycomb structures of CNTs formed on silicon substrates on different cell area ratios (CAR). The drop-casting process developed honeycomb-structured MWCNT-coated absorbers with varying CAR values ranging from ~ 60% to 17%. The optical properties were investigated within the visible (400-800 nm) and near-infrared (934-1651nm) wavelength ranges. Although fully coated MWCNT absorbers showed the lowest reflectance, honeycomb structures with a ~ 17% CAR achieved high-temperature absorption. These structures maintained 8.4% reflectance at 550 nm while dramatically increasing infrared reflection to 80.5% at 1321 nm. The performance of solar thermal was assessed throughout a range of irradiance intensities, from 0.04 W/cm² to 0.39 W/cm². The honeycomb structure with a ~17% CAR value consistently performed better than other structures by reaching the highest absorption temperatures (ranging from 52.5°C to 285.5°C) across all measured intensities. A direct correlation was observed between the reflection ratio (visible: 550 nm / infrared: 1321 nm) and temperature absorption efficiency, where lower reflection ratios were associated with higher temperature absorption. This study highlights the significant potential for the large-scale production of cost-effective solar thermal absorbers through the application of optimized honeycomb-structured absorbers coated with MWCNTs. These contributions enhance solar energy efficiency for applications in water heating and purification, thereby promoting sustainable development.

In the frame of our diversity-oriented research on multitarget small molecule anticancer agents, utilizing convergent synthetic sequences terminated by Sonogashira coupling reactions, a preliminary selection of representative alkyne-tethered vindoline hybrids was synthesized. The novel hybrids with additional pharmacophoric fragments of well-documented anticancer agents, including FDA-approved tyrosine-kinase inhibitors (imatinib and erlotinib) or ferrocene or chalcone units, were evaluated for their antiproliferative activity on malignant cell lines MDA-MB-231 (triple negative breast cancer), A2780 (ovarian cancer), HeLa (human cervical cancer) and SH-SY5Y (neuroblastoma) as well as human embryonal lung fibroblast MRC-5 served as reference non-malignant cell line for the assessment of the therapeutic window of the tested hybrids. The biological assays identified a trimethoxyphenyl-containing chalcone-vindoline hybrid (36) as a promising lead compound exhibiting submicromolar activity on A2780 cells with a marked therapeutic window. These results suggest that ovarian cancer might be considered as a prioritized target of treatment with 36.

The theory of electron spin has been proposed for a century, but the study of quantum effects in biological molecules is still in its infancy. Chirality-induced spin selectivity (CISS) is a very modern theory that can explain many biochemical phenomena. In this paper, we propose a new theoretical model based on CISS theory and quantum chemistry theory, which can well explain the theoretical explanation of the chiral selectivity of chiral proteins. Moreover, this theory can predict the spin state of corresponding chiral molecules. Taking L-DOPA and AADC enzyme as examples, this theoretical model solves the theoretical explanation of AADC enzyme's chiral catalysis selectivity problem and successfully predicts the spin state of L-DOPA and D-DOPA's valence electrons.

Choanoflagellates are single-celled eukaryotes with complex signaling pathways. They are considered the closest non-metazoan ancestors to mammals and other metazoans, and form multicellular-like states called rosettes. The choanoflagellate Monosiga brevicollis contains over 150 PDZ domains, an important peptide-binding domain in all three domains of life (Archaea, Bacteria, and Eukarya). Therefore, an understanding of PDZ domain signaling pathways in choanoflagellates may provide insight into the origins of multicellularity. PDZ domains recognize the C-terminus of target proteins and regulate signaling and trafficking pathways, as well as cellular adhesion. Here, we developed a computational program, Domain Analysis and Motif Matcher (DAMM), that predicts target specificity in choanoflagellate PDZ domains by analyzing peptide-binding cleft sequence identity as compared to human PDZ domains. We used this program, protein biochemistry, fluorescence polarization, and structural analyses to characterize the specificity of A9UPE9_MONBE, a M. brevicollis PDZ domain-containing protein with no homology to any metazoan protein, finding that its PDZ domain is most similar to those of the DLG family. We then identified two endogenous sequences that bind A9UPE9 PDZ with <100 M affinity, a value commonly considered the threshold for cellular PDZ-peptide interactions. Taken together, this approach can be used to predict cellular targets of previously uncharacterized PDZ domains in choanoflagellates and other organisms. Our data contributes to investigations into choanoflagellate signaling and how it informs metazoan evolution.

In organic synthesis, due to their high electrophilicity and leaving group properties, halogens play pivotal roles in the activation and structural derivations of organic compounds. Recently, cyclizations induced by halogen groups that allow the production of diverse targets and the structural reorganization of organic molecules have attracted significant attention from synthetic chemists. Electrophilic halogen atoms activate unsaturated and saturated hydrocarbon moieties via the generation of halonium intermediates, followed by the attack of carbon-, nitrogen-, oxygen-, and sulfur-containing nucleophiles to give highly functionalized carbo- and heterocycles. Interestingly, new transformations of halogenated organic molecules that can control the formation and stereoselectivity of the products according to the difference in the size and number of halogen atoms have recently been discovered. These unique cyclizations may possibly be used as efficient synthetic strategies with future advances. In this review, innovative reactions controlled by halogen groups are discussed as a new concept in the field of organic synthesis.

The search for economical and sustainable sources of PUFAs within the framework of the circular economy is encouraged by their proven beneficial effects on health. The extraction of monkfish liver oil (MLO) for the synthesis of omega-3 ethyl esters was performed evaluating two blending systems and four green solvents. Moreover, the potential solubility of the MLO in green solvents was studied using the predictive simulation software COSMO-RS. The production of the ethyl esters was performed by one or two step reactions. Novozym 435, two resting cells (Aspergillus flavus and Rhizopus oryzae) obtained in our laboratory and mix of them were used as biocatalysts in a solvent-free system. The yields for Novozym 435, R. oryzae and A. flavus in the one-step esterification were 63%, 61% and 46%, respectively. The hydrolysis step in the two-step reaction led to 83%, 88% and 93% of free fatty acids (FFA) for Novozym 435, R. oryzae and A. flavus respectively. However, Novozym 435 showed the highest yield in the esterification step (85%) followed by R. oryzae (65%) and A. flavus (41%). Moreover, selectivity in front of polyunsaturated fatty acids of R. oryzae lipase was evidenced, since it did slightly esterified docosahexaenoic acid (DHA) in all the esterification reactions tested.

G protein-coupled receptors (GPCRs) play a key role in many cellular signaling mechanisms, and must select among multiple coupling possibilities in a ligand-specific manner in order to carry out a myriad of functions in diverse cellular contexts. Much has been learned about the molecular mechanisms of ligand-GPCR complexes from Molecular Dynamics (MD) simulations. However, to explore ligand-specific differences in the response of a GPCR to diverse ligands, as is required to understand ligand bias and functional selectivity, necessitates creating very large amounts of data from the needed large-scale simulations. This becomes a Big Data problem for the high dimensionality analysis of the accumulated trajectories. Here we describe a new machine learning (ML) approach to the problem that is based on transforming the analysis of GPCR function-related, ligand-specific differences encoded in the MD simulation trajectories into a representation recognizable by state-of-the-art deep learning object recognition technology. We illustrate this method by applying it to recognize the pharmacological classification of ligands bound to the 5-HT2A and D2 subtypes of class A GPCRs from the serotonin and dopamine families. The ML-based approach is shown to perform the classification task with high accuracy, and we identify the molecular determinants of the classifications in the context of GPCR structure and function. This study builds a framework for the efficient computational analysis of MD Big Data collected for the purpose of understanding ligand-specific GPCR activity.

Water quality monitoring was an important objective in the surroundings. In this study, we investigated the sensing characteristics of the arrayed flexible chloride sensor with XBee wireless sensing system. The sensitivity and linearity of the wireless chloride sensing devices were 91.6 mV/pCl and 0.988, respectively. The hysteresis voltages were 50.14 mV and 36.71 mV during the cycles of 1 M → 10⁻¹ M → 1 M → 10⁻³ M → 1 M and 1 M → 10⁻³ M → 1 M → 10⁻¹ M → 1 M, respectively. The selectivity coefficients of the ClO⁻ ion, ClO₄⁻ ion, NO₃⁻ ion and I⁻ ion for Cl⁻ ion were 5.0 × 10⁻², 1.0 × 10⁻¹, 5.9 × 10⁻³ and 5.6×10⁻¹, respectively. The sensing characteristics of real time measurement were investigated for dynamic microfluidic. The arrayed flexible chloride sensor was integrated with the microfluidic device, syringe pump and wireless sensing system. The sensitivity and linearity were 273.1 mV/pCl and 0.978 at 35 μL/min, respectively.

Polyphenols are well-known health promoting agents, but they have some limitations due to their spontaneous oxidation. This evidence has limited their use as drugs in the last years. In this field, several chemical modifications have been proposed to overcome these restrictions; among these, the esterification seems to be the preferred. Ester derivatives could be able to reduce the bioavailability problems connected to polyphenols. On the other hand, the presence of the esterase enzymes in the body guarantees the ester hydrolysis, which in turn frees the two molecules that make it up. Lipase-catalyzed esterifications afforded several derivatives of flavonoids glycosides, in green conditions. In this short note, pancreatic porcine lipase was firstly used as a cheap bio-catalyst, to synthesize oleoyl derivatives of quercetin in aglycone form. Results demonstrated how the enzyme acyl regioselective in position C-3, with high yields and easy purification processes

The real implementation of biogas reforming at industrial scale to obtain interesting products, like hydrogen or syngas, is a developing research field where multidisciplinary teams are continuously adding improvements and innovative technologies. Thus, these works can contribute to the proliferation of green technologies where circular economy and sustainability are present. To assess the sustainability of these processes, there are different tools like life cycle assessment (LCA), which implies a complete procedure where even small details count to consider a certain technology sustainable or not. The aim of this work was to review works where LCA is applied to different aspects of biogas reforming, especially focusing on the role of catalysts, which are essential to improve the efficiency of a certain process, but also present a strong influence on its environmental impact. As a conclusion, catalysts have an influence on LCA through the improvement on the catalytic performance and the impact of their production, whereas other aspects related to biogas or methane reforming could equally influence on their durability or reusability, with the subsequent effect on LCA. Further research about this subject is required in a continuously changing technology with plenty of possibilities.

The real-time monitoring of food freshness in refrigerators is of significant importance in detecting potential food spoiling and preventing serious health issues. One method that is commonly reported and has received substantial attention is the discrimination of food freshness by the tracking of volatile molecules. Nevertheless, the ambient environment of low temperature (normally below 4^oC) and high humidity (90% R.H.) as well as poor selectivity in sensing gas species remain the challenge. In this research, an integrated smart gas-tracking device is designed and fabricated. By applying pump voltage on the yttria-stabilized zirconia (YSZ) membrane, the oxygen concentration in the testing chamber can be manually tailored. Due to the working principle of the sensor following the mixed potential behavior, distinct differences in sensitivity and selectivity are observed for the sensor that operated at different oxygen concentrations. Typically, the sensor gives satisfactory selectivity to H₂S, NH₃, and C₂H₅OH at the oxygen concentrations of 10%, 30%, and 40%, respectively. In addition, an acceptable response/recovery rate (within 24 s) is also confirmed. Finally, a refrigerator prototype that includes the smart gas sensor is built, and satisfactory performance in discriminating food freshness status of fresh or semi-fresh is verified for the proposed refrigerator prototype. In conclusion, these aforementioned promising results suggest that the proposed integrated smart gas sensor could be a potential candidate for alarming food spoilage.

Some recent studies show that filters in convolutional neural networks (CNNs) have low color selectivity in datasets of natural scenes such as Imagenet. CNNs, bio-inspired in the visual cortex, are characterized by their hierarchical learning structure, which appears to gradually transform the representation space. Inspired by the direct connection between the LGN and V4, which allows V4 to handle low-level information closer to the trichromatic input in addition to processed information that comes from V2/V3, we propose the addition of a long skip connection (LSC) between the first and last blocks of the feature extraction stage to allow deeper parts of the network to receive information from shallower layers. This type of connection improves classification accuracy by combining simple-visual and complex-abstract features to create more color-selective ones. We have applied this strategy to classic CNN architectures and quantitatively and qualitatively analyzed the improvement in accuracy while focusing on color selectivity. The results show that, in general, skip connections improve accuracy, but LSC improves it even more and enhances the color selectivity of the original CNN architectures. As a side result, we propose a new color representation procedure for organizing and filtering feature maps, making their visualization more manageable.

A series of novel chiral nonmetallocene pincer-type rare earth metal dialkyl complexes bearing the chiral monoanionic tridentate C2-symmetric 1,3-bis(oxazolinymethylidene)isoindoline (BOXMI) ligand (BOXMI)Ln(CH2SiMe3)2 1-3 (1, Ln = Sc, yield = 57%; 2, Ln = Lu, yield = 55%; 3, Ln = Y, yield = 62%) have been prepared in moderate yields via the acid-base reaction between the BOXMI ligand and rare earth metal tri(trimethylsilylmethyl) complexes. The X-ray diffractions show that both of the complexes 1 and 2 contain one Boxmi ligand and two trimethylsilylmethyl ligands, adopting a distorted-trigonal-bipyramidal configuration. In the presence of cocatalyst such as borate and AlR3, these complexes 1-3 exhibit high activities up to 6.8 × 104 (g of polymer)/(molLn h) and high cis-1,4-selectivities up to 97%) in the polymerization of isoprene in toluene, yielding the cis-1,4-polyisoprenes with high molecular weights (Mn up to 710000 g/mol) and bimodal molecular weight distributions (Mw/Mn = 2.0-4.5).

Different dopamine receptor (DR) subtypes are involved in pathophysiological conditions such as Parkinson´s Disease (PD), schizophrenia and depression. While many DR-targeting drugs have been approved by the FDA, only a very small number is truly selective for one of the DR subtypes. Additionally, most of them show promiscuous activity at related G-protein coupled receptors, thus suffering from diverse side-effect profiles. Multiple studies have shown that combined in silico / in vitro approaches are a valuable contribution to drug discovery processes. They can also be applied to divulge the mechanisms behind ligand selectivity. In this study, novel DR ligands were investigated in vitro to assess binding affinities at different DR subtypes. Thus, nine D2R/D3R-selective ligands (micro- to nanomolar binding affinities, D3R-selective profile) were successfully identified. The most promising ligand exerted nanomolar D3R activity (KI = 2.3 nM) with 263.7-fold D2R/D3R selectivity. Subsequently, ligand selectivity was rationalized in silico based on ligand interaction with a secondary binding pocket, supporting selectivity data determined in vitro. The developed workflow and identified ligands could aid in the further understanding of structural motifs responsible for DR subtype selectivity, thus, benefitting drug development in D2R/D3R-associated pathologies like PD.

Controlling the selectivity of detonation initiation reaction of explosive is a Holy Grail, and it seems to be an “idiot's daydream”, by strengthening external electric field, to reduce the explosive sensitivity. The effects of external electric fields on the initiation reactions in NH2NO2∙∙∙NH3, a model system of the nitroamine explosive with alkaline additive, were investigated at the MP2/6-311++G(2d,p) and CCSD/6-311++G(2d,p) level. The concerted effect in the intermolecular hydrogen exchange is characterized by an index of the imaginary vibrations. Due to the weakened concerted effects by the electric field along the −x-direction opposite to the “reaction axis”, the dominant reaction changes from the hydrogen exchange to 1,3-intramolecular hydrogen transference with the increase of the field strengths. Furthermore, the stronger the field strengths, the higher the barrier heights become, indicating the lower sensitivities. Therefore, by strengthening the field strength and adjusting the orientation between the field and “reaction axis”, not only can the reaction selectivity be controlled, but also the sensitivity can be reduced, in particular under a super-strong field. Thus, a traditional concept, which the explosive is dangerous under the super-strong external electric field, is broken theoretically. Compared to the neutral medium, the low sensitivity of the explosive with alkaline can be achieved under the stronger field. Employing atoms in molecules, reduced density gradient and surface electrostatic potentials, the origin of the reaction selectivity and sensitivity change is revealed. This work provides a new idea to the technical improvement for adding the external electric field into the explosive system.

Precise monitoring of NOx concentrations in nitric oxide delivery systems is crucial to ensure the safety and well-being of patients undergoing inhaled nitric oxide (iNO) therapy for pulmonary arterial hypertension. Currently, NOx sensing in commercialized iNO instruments predominantly relies on chemiluminescence sensors, which not only drives up costs but also limits their portability. Herein, we developed solid state gas sensors utilizing Ni-based sensing materials for effectively tracking the level of NO and NO2 in NO delivery system. These sensors comprised of NiO-SE or (NiFe2O4+30 wt.% Fe2O3)-SE vs. Mn-based RE demonstrated high selectivity towards 100 ppm NO under the interference of 10 ppm NO2 or 3 ppm NO2 under the interference of 100 ppm NO, respectively. Meanwhile, excellent stability, repeatability, and humidity resistance were also verified for proposed sensors. Sensing mechanisms were thoroughly investigated through assessments of adsorption capabilities and electrochemical reactivity. It turns out that the superior electrochemical reactivity of NiO towards NO, alongside with the NO2 favorable adsorption characteristics of (NiFe2O4 + 30 wt.% Fe2O3), is the primary reason for the high selectivity to NOx. These findings indicate a bright future for the application of these NOx sensors in innovative iNO treatment technologies.

Opioid analgesics have been used for more than 5,000 years and remain the principal pain medications prescribed today. Although morphine is considered the gold standard for pain relief, this µ-opioid receptor (MOP)-selective agonist provides only moderate relief for many chronic pain conditions and promotes several unwanted effects that can adversely affect patient quality-of-life, prevent adherence to treatment or generate addiction. In addition to the lack of progress in the development of better analgesics, there have been no significant breakthroughs to date that have addressed side effects mentioned above. Fortunately, a better understanding of opioid pharmacology has restored hope for the development of better and safer pain medications. In this review, we describe how clinically approved opioids were initially characterized as biased ligands and what impact this approach could have on clinical practice. We also looked at the preclinical and clinical development of MOP biased agonists, with an emphasis on the oliceridine story, as the first specifically designed biased painkiller. Moreover, we explore the discrepancies between ligands with low intrinsic efficacy and those with biased properties. Finally, we examine the rationale behind biased ligand development during the opioid crisis era.

Peptide/Histidine Transporter PHT1 (SLC15A4) is expressed in lysosomal membranes of immune cells where it plays an important role in metabolic and inflammatory signaling. PHT1 is an H+-coupled/histidine symporter that can transport a broad range of oligopeptides, including a variety of bacterial-derived peptides. Moreover, it enables the scaffolding of various metabolic signaling molecules and interacts with key regulatory elements of the immune response. Therefore, it is not surprising that PHT1 is associated with the development of autoimmune diseases, such as systemic lupus erythematosus (SLE). Unfortunately, the pharmacological development of PHT1 has been hampered by the lack of appropriate transport assays. With the aim to address this shortcoming, a novel transport assay based on solid supported membrane-based electrophysiology (SSME) is presented. Key findings of the present SSME studies include the first recordings of electrophysiological properties, a pH dependence analysis, an assessment of PHT1 substrate selectivity, as well as the transport kinetics of the identified substrates. In contrast to previous works, PHT1 is studied its native lysosomal environment. Moreover, observed substrate selectivity is validated by molecular docking. Overall, this new SSME-based assay is expected to contribute to unlock the pharmacological potential of PHT1 and to deepen the understanding of its functional properties.

A fluorescent probe, N'-((3-methyl-5-oxo-1-phenyl-4, 5-dihydro-1H-pyrazol-4-yl) methylene)-2-oxo-2H-chromene-3-carbohydrazide (MPMC), was synthesized and characterized. Characterizations of the synthetic MPMC were conducted by proton nuclear magnetic resonance (1HNMR) spectroscopy and carbon-13 nuclear magnetic resonance spectroscopy (13C NMR). The fluorescence emission behaviors of probe MPMC towards diverse metal ions were detected and the probe exhibited high sensitivity and selectivity towards Cu2+ over other metal ions via quenching of its fluorescence. Furthermore, the existence of other metal actions made no difference on the fluorescence intensity of the MPMC-Cu2+ system apparently, that is, MPMC displayed a good anti-interference ability. Job’s plot of MPMC and copper ions indicated the detection limit was 15.16 nM (R2=0.9612) for the assayed actions, with a stoichiometric ratio of 1:1 for MPMC and Cu2+. Additionally, the color of MPMC probe solution changed from nearly colorless to yellow in the presence of Cu2+ in visible light, which the color change could be observed by the naked eye. Similarly, the color resolved bright yellow into blue in ultraviolet light. Also reusability studies indicated that MPMC probe was reusable. The pH effect of probe MPMC to Cu2+ had a broad range of pH detection 4.0 to 11.0. The response time of MPMC probe for determining Cu2+ was within 1 min. The recognition of Cu2+ by MPMC performed on pre-treated paper under sunlight and UV light both had a distinct colour change. Thus, the solid-state method for detecting Cu2+ with the naked-eye, was both economical and convenient.

The spatial and temporal variability in dietary preferences of juvenile three-spined stickleback Gasterosteus aculeatus, was studied across typical coastal habitats of Keret Archipelago, Kandalaksha Bay, the White Sea. Sampling of fish using beach seine was implemented in late July-early August and in late August, and zooplankton samples were collected to make a quantitative evaluation of abundance of potential prey items. Similarity Percentage (SIMPER) analysis implemented over the data obtained from stomach content analysis revealed five planktonic taxa mostly contributing to the diet of juvenile sticklebacks, of which copepod Temora longicornis was the most important prey item at marine sites, while Acartia longiremis prevailed in diet of fishes in marine lagoon. Calculation of selectivity index demonstrated that some taxa (e.g., A. longiremis) were always avoided by juvenile fishes, others (e.g. Microsetella norvegica) were firstly avoided and then selected in late August. Calculation of selectivity index was implemented per sample and per individual fish indicated that taxa like T. longicornis and were selected during the whole period of study, fishes demonstrated pronounced individual variation in prey selectivity. In general, data on selectivity indicated that despite juvenile sticklebacks feed on mostly available prey items, they can demonstrate taxonomic and size-specific prey selectivity.

Perhaps the greatest challenge in the graft copolymerization of acrylic acid onto starch initiated by Fenton’s is the selectivity of the grafting reaction. Low selectivity means that too much of unwanted homopolymer polyacrylic acid is produced. In this paper, it has been analyzed why with this reaction system, involving a water soluble monomer and indirect initiation, the graft selectivity is such a challenge. Several other grafting reactions, especially with monomers of low water solubility or when direct initiation is applied, show a better grafting performance. A scheme is presented based on reaction engineering principles, that supports an explanation of the observed differences. A more selective activation of starch is a factor, but perhaps even more important is a low monomer to starch ratio at the starting sites of graft reactions. Based on these insights, several methods to improve the graft selectivity are evaluated, with the help of literature data but mostly by experimental explorations in our laboratory. Most promising appears to be a dedicated dosage method, to add monomer in portions over time, tested in a batch reactor with gelatinized cassava starch. This way, both grafting percentage and graft selectivity could be improved. Such could not be realized with the more conventional dosage, which is to add all monomer before the start of the reaction. This can be considered a principal breaktrough. Still, more research and development would be needed to refine the method and to implement the idea also in a continuous reactor at larger scale.

The hetero Diels-Alder (HDA) reaction between the ambident heterodiene 3-methylene-2,4-chromandione (MCDO) and the non-symmetric methyl vinyl ether (MVE) is investigated within the Molecular Electron Density Theory (MEDT) at the B3LYP/6-311G(d,p) computational level. The aim of this study is to gain insight into the molecular mechanism and to elucidate the factors that control the selectivity found experimentally. DFT-based reactivity indices reveal that MCDO exhibits strong electrophilic character, while MVE displays a strong nucleophilic character. Meanwhile, Parr function explains the ortho regioselectivity of this HDA reaction. The highly polar nature of this HDA reaction, supported by the high global electron density transfer (GEDT) taking place at the transition state structures (TSs), accounts for the very low activation energy associated with the most favorable TS-4on. The ambident nature of MCDO allows the formation of two constitutional isomeric cycloadduct. In the case of MVE, the pseudocyclic selectivity is attained by a thermodynamic control. This polar HDA reaction displays an endo stereoselectivity and a complete ortho regioselectivity. A comparative Relative Interacting Atomic Energy (RIAE) analysis of the two diastereomeric TS-4on and TS-6on indicates a highly likeness between them, which explains the low pseudocyclic selectivity under kinetic control.