Equimolar Research Articles

Exposure to Secondhand Cannabis Smoke Among Children

The degree that in-home cannabis smoking can be detected in the urine of resident children is unclear. Test association of in-home cannabis smoking with urinary cannabinoids in children living at home. This cross-sectional study used baseline data from Project Fresh Air, a 2012-2016 randomized clinical trial to reduce fine particulate matter levels. Eligible participants were recruited from households in San Diego County, California, with children under age 14 years and an adult tobacco smoker in residence. Children's urine samples were analyzed in 2022. In-home cannabis smoking, measured by: parent or guardian report of in-home cannabis smoking; number of daily nonspecific smoking events computed via an air particle count algorithm; and number of daily cannabis smoking events ascertained by residualization, adjusting for air nicotine, tobacco smoking, and other air particle generating or ventilating activities. Levels of the cannabis biomarker Δ9-tetrahydrocannabinol (THC) and its major metabolites, 11-hydroxy-Δ9-tetrahydrocannabinol and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol. Biomarker molar equivalents were summed to represent total THC equivalents (TTE) in urine. Logistic regression assessed whether in-home smoking was associated with cannabis biomarker detection. For children with detectable urinary cannabinoids, linear regression assessed in-home smoking association with quantity of urinary TTE. A total of 275 children were included in analysis (mean [SD] age, 3.6 [3.6] years; 144 male [52.4%]; 38 Black [13.8%], 132 Hispanic [48.0%], and 52 White [18.9%]). Twenty-nine households (10.6%) reported in-home cannabis smoking in the past 7 days; 75 children [27.3%] had detectable urinary cannabinoids. Odds of detectable TTE in children's urine were significantly higher in households with reported in-home cannabis smoking than households without (odds ratio [OR], 5.0; 95% CI, 2.4-10.4) and with each additional ascertained daily cannabis smoking event (OR, 2.5; 95% CI, 1.6-3.9). Although the point estimate for TTE levels was higher among children with detectable urinary cannabinoids and exposure to more daily cannabis smoking events (increase per event, 35.68%; 95% CI, -7.12% to 98.21%), the difference was not statistically significant. In this cross-sectional study, in-home cannabis smoking was associated with significantly increased odds of child exposure to cannabis smoke, as assessed by urinary cannabinoid biomarkers. As young children spend most of their time at home, reducing in-home cannabis smoking could substantially reduce their exposure to the toxic and carcinogenic chemicals found in cannabis smoke.

Photocrosslinkable starch cinnamyl ethers as bioinspired bio-based polymers.

A novel starch-based ether bearing cinnamyl functionalities, conferring photo-crosslinking properties, is synthesised by reaction with cinnamyl chloride in the presence of sodium hydroxide. Natural yuca was selected as a sustainable source of starch. Three different molar equivalents of reagents are used, affording starch-cinnamyl ethers with different degrees of substitution, ranging from 0.09 to 1.24, as determined by liquid phase nuclear magnetic resonance (NMR). The double bonds in the cinnamyl moieties show reactivity towards photodimerization upon irradiation at 254 nm, affording a novel cross-linked bio-inspired polymer. The formation of the covalent ether linkage and the [2+2] cycloaddition of the cinnamyl units are confirmed by a combination of spectroscopic techniques, including solid state NMR. The materials are further characterized by gel permeation chromatography (GPC), thermogravimetric analysis (TGA), and X-ray diffraction analysis (XRD). Starch-cinnamyl ethers with a DS of 0.09 are water soluble, and suitable for the preparation of transparent films potentially exploitable for biodegradable packaging materials.

Biodiesel Production from Soybean Oil Using a Free-Enzyme and Whole-Cell Dual Lipase System as a Biocatalyst.

A dual lipase system has been developed to convert soybean oil into biodiesel through synergistic catalysis of Thermomyces lanuginosus lipase (TLL) and Yarrowia lipolytica lipase 2 (YLL) in this study. Pichia pastoris recombinant strains expressing lipases were successfully constructed, and the activities of TLL and YLL in the fermentation supernatant reached 23,142.71 ± 280.54 U/mL and 895.44 ± 27.31 U/mL, respectively. Immediately thereafter, free lipase was used to catalyze the preparation of biodiesel from soybean oil. After optimizing reaction conditions, 80 U/g oil TLL and 20 U/g oil YLL were used to catalyze the production of biodiesel, and a 95.56% biodiesel yield was obtained at 40°C, 40% moisture content (water/oil, w/w), and stepwise addition of five molar equivalents of methanol. Double lipase plasmids (tll gene and yll gene in different proportions) were constructed in vitro and introduced into P. pastoris to construct a recombinant strain with optimal activity. Under the reaction conditions of 40% moisture content, 8% whole-cell biocatalyst dosage, and stepwise addition of five molar equivalents of methanol, the biodiesel yield reached 95.35% after 24h at 40°C. These results show that synergistic catalysis is an effective strategy for biodiesel synthesis and can not only improve the biodiesel yield but also shorten the reaction time. This study provides a scientific basis for biodiesel production by multi-enzyme compounding, with potential industrial applications.

Ambidentate behavior of oximate in VO(OMe)2+ and VO2 + complexes with biacetylmonoxime 4-R-benzoylhydrazones: syntheses, structures, and properties

Reactions of bis(acetylacetonato)oxovanadium(IV), [VO(acac)2], with biacetylmonoxime 4-R-benzoylhydrazones (H2L1 (R = Me) and H2L2 (R = OMe), where 2Hs represent the dissociable oxime and amide protons) in 1:1 mole ratio in methanol result in complexes [VO(OMe)(MeOH)(L1)] (1) and [VO(μ-OMe)(L2)]2 (2). When reactions were performed in the presence of two molar equivalents of KOH, K[VO2(L1)]·MeOH (3) and K[VO2(L2)]·2MeOH (4) were obtained. The complexes have been characterized using elemental analysis and mass spectrometry along with magnetic, solution electrical conductivity, thermogravimetric, various spectroscopic (IR, UV-Vis, and 1H NMR), and cyclic voltammetric measurements. The molecular structures of H2L1 and complexes 1-4 were determined by single-crystal X-ray crystallographic studies. In both 1 and the dimethoxo bridged centrosymmetric 2, the metal centers are in distorted octahedral NO5 environment, where (L1/2)2− meridionally coordinate the respective metal centers through the amidate-O, imine-N, and oximate-O and form fused 5,6-membered chelate rings. In 3 and 4, the metal centers have distorted trigonal bipyramidal N2O3 coordination spheres, where the fused 5,5-membered chelate rings forming amidate-O, imine-N, and oximate-N donors (L1/2)2− occupy the axial-equatorial-axial positions. The physical properties of all four complexes are consistent with their molecular formulas and structures.

The role of TGFbeta signals in Lead (Pb)‐induced Cerebral Amyloid Angiopathy

AbstractBackgroundMounting evidence suggests that acute and past exposure to the environmental toxicant lead (Pb) results in longitudinal decline in cognitive function and brain atrophy. In animals, chronic Pb exposure can increase brain Aβ deposition. However, it remains unclear how Pb induces different natures of amyloid depositions and underlying mechanisms to contribute to the pathogenesis of AD and related dementia.MethodFemale APP/PS1 mice at 8 weeks old were administered with either 50 mg/kg Pb‐acetate (PbAc) (i.e., 27 mg Pb/kg) via oral gavage or an equivalent molar concentration of Na‐acetate (NaAc) once daily for additional 3 days or 8 weeks, in the presence or absence of an PAI‐1 inhibitor (12mg/kg). Parenchymal plaques and vascular amyloid deposition were quantitated by double staining with Thioflavin S and anti‐collagen IV antibody. Brain sections were also stained with anti‐NeuN (for neurons), anti‐myelin basic protein (for myelination) and anti‐rabbit FITC (for reactive astrocytes) antibodies. Assays for perivascular drainage as well as in vitro vascular binding with Aβ and microglial endocytosis were also performed.Result2‐month Pb exposure increased vascular Aβ deposits in neocortex of female APP/PS1 mice at the 4‐month of age by almost 300% (p<0.01). In contrast, Pb only increased parenchymal amyloid in the same brain areas by 86.7% (p<0.05). Demyelination, but not neuronal loss was observed in Pb‐treated AD mice that had significantly cognitive deficits detected by Y‐maze. Following Pb treatments, the ratios of Aβ1‐40/Aβ1‐42 in Pb‐treated groups increased to 0.58 ± 0.21 in the cortical parenchyma and 0.50 ± 0.10 in the brain vasculature, as compared to those in the control group (0.39 ± 0.09 and 0.11 ± 0.02). Additionally, TGF‐β1, Smad2, PAI‐1 and fibronectin were significantly induced in cerebrovasculature isolated from mice treated with 27 mg/kg of Pb for 3 days, accompanied by dramatic inhibition of perivascular drainage and vascular binding with Aβ1‐40. Furthermore, Pb exposure induced microglial TGF‐β1 and inhibited clearance of Aβ40 and LRP‐1 expression. Interestingly enough, all of these alterations induced by Pb exposure could be markedly ameliorated by a PAI‐1 inhibitor.ConclusionTGF‐β signals play distinct roles in Pb‐induced amyloid pathology.

Disilicon‐Mediated Carbon Monoxide Activation: From a 1,2,3‐Trisila‐ to 1,3‐Disilacyclopentadienes with Hypercoordinate λ4Si‐λ3C Double Bonds

AbstractThe facile reaction of the SiPh2‐bridged bis‐silylene (LSi:)2SiPh2 (L=PhC(NBut)2) with diphenylacetylene affords the unprecedented 1,2,3‐trisilacyclopentadiene (LSi)2(PhC)2SiPh2 1 with a hypercoordinate λ4Si−λ3Si double bond. Compound 1 is very oxophilic and consumes three molar equivalents of inert N2O to form the bicyclic oxygenation product 2 through O‐atom insertion in the Si=Si and Si−Si bonds. Strikingly, 1 can completely split the C≡O bonds of carbon monoxide under ambient conditions (1 atm, room temperature), yielding the 1,3‐disilacyclopentadiene 3, representing the first hypercoordinate example of a cyclosilene with a λ4Si‐λ3C double bond. Likewise, reaction of Xyl‐NC (Xyl=2,6‐dimethylphenyl), an isocyanide isoelectronic with CO, with 1 furnishes the related 1,3‐disilacyclopentadiene 4 but with an amidinato silylene pendent attached to the Si=C carbon ring atom.

Disilicon-Mediated Carbon Monoxide Activation: From a 1,2,3-Trisila- to 1,3-Disilacyclopentadienes with Hypercoordinate λ4Si-λ3C Double Bonds.

The facile reaction of the SiPh2-bridged bis-silylene (LSi:)2SiPh2 (L=PhC(NBut)2) with diphenylacetylene affords the unprecedented 1,2,3-trisilacyclopentadiene (LSi)2(PhC)2SiPh2 1 with a hypercoordinate λ4Si-λ3Si double bond. Compound 1 is very oxophilic and consumes three molar equivalents of inert N2O to form the bicyclic oxygenation product 2 through O-atom insertion in the Si=Si and Si-Si bonds. Strikingly, 1 can completely split the C≡O bonds of carbon monoxide under ambient conditions (1 atm, room temperature), yielding the 1,3-disilacyclopentadiene 3, representing the first hypercoordinate example of a cyclosilene with a λ4Si-λ3C double bond. Likewise, reaction of Xyl-NC (Xyl=2,6-dimethylphenyl), an isocyanide isoelectronic with CO, with 1 furnishes the related 1,3-disilacyclopentadiene 4 but with an amidinato silylene pendent attached to the Si=C carbon ring atom.

Synthesis and structural studies on zinc(II) macrocyclic and hetrocyclic complexes derived from schiff base and mixed ligands of 1,4-dihydroquinoxaline-2,3-dione, orthophenylene diamine and hydroquinone

In this study two new zinc(II) complexes involving oxygen and nitrogen donor sequences derived from 1,4-dihydroquinoxaline-2,3-dione (QXD), o-phenylenediamine (OPD) and hydroquinone (HQ) were synthesized through a template procedure. The structural elucidation of these complexes was carried out using measurement of molar conductance in 1x10-3 M solution of DMSO and various spectral techniques; 1H and 13C NMR, FT-IR, UV-VIS and AAS. The results showed that the zinc(II) ion coordinates with the Schiff base ligands in octahedral geometry, leading to the formation of stable macrocyclic and heterocyclic structures. The cyclic ligand (L) was found to coordinate as NNNN donor, through four imine nitrogen atoms which were formed up on condensation of the –NH2 groups on o-phenylenediamine with C=O group on quinoxaline dione in a 2:2 mole ratio, in the presence of one mole equivalent of ZnCl2 in ethanol medium. It also indicates the formation of a new mixed ligand zinc(II) complex with an OO OO O O coordination around zinc(II). The study contributes to the understanding of the coordination chemistry of zinc(II) with Schiff bases and provides insights into the development of novel zinc-based complex compounds. KEY WORDS: Macrocyclic and mixed ligand, 1,4-Dihydroquinoxaline-2,3-dione, o-Phenylenediamine, Hydroquinone Bull. Chem. Soc. Ethiop. 2025, 39(1), 49-64. DOI: https://dx.doi.org/10.4314/bcse.v39i1.4

Spectroscopic and biological studies of Pd(II) complexes of 5-(p-tolyl)-1,3,4-oxadiazole-2-thiol

Reactions of Na2PdCl4 with two equivalents of 5-(p-tolyl)-1,3,4-oxadiazole-2-thiol (MoxSH), afford complex of the type [Pd(MoxS)2] (1). Further reaction with equivalent mole of diphosphine ligand {Ph2P(CH2)nPPh2} ( where n = 1 dppm, 2 dppe, 3 dppp, 4 dppb, (CH2)n = dppf ) or two equivalents of triphenyl phosphine or triphenyl phosphine sulfide affords mixed-ligand complexes of the type [Pd(MoxS)2(Ph2P(CH2)nPPh2)] (2-6), [Pd(MoxS)2(PPh3)2] (7) and [Pd(MoxS)2(SPPh3)2](8). The prepared complexes were characterized using different physical and spectroscopic methods. The results indicated that the MoxS ligand behave as coordinate in a anion monodentate fashion sulfur atom to give a square planer around the metal ion. Preliminary anti-bacterial activity has been assessed against Escherichia coli, Staphylococcus aureus, and Bacillus subtilis bacteria. The prepared complexes show good activity in compared with standard drug. [Pd(MoxS)2(dppf)] (6) displays good activity (18, 22 and 20 mm) against certain tested microbes Escherichia coli, Staphylococcus aureus and Bacillus subtilis, respectively. KEY WORDS: Complexes, Palladium, Thione, Anti-bacteria, Phosphine Bull. Chem. Soc. Ethiop. 2025, 39(1), 79-90. DOI: https://dx.doi.org/10.4314/bcse.v39i1.6

Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of Ca2+ and Mg2+ in the formulation

Oligonucleotide therapeutics (ASOs and siRNAs) have been explored for modulation of gene expression in the central nervous system (CNS), with several drugs approved and many in clinical evaluation. Administration of highly concentrated oligonucleotides to the CNS can induce acute neurotoxicity. We demonstrate that delivery of concentrated oligonucleotides to the CSF in awake mice induces acute toxicity, observable within seconds of injection. Electroencephalography (EEG) and electromyography (EMG) in awake mice demonstrated seizures. Using ion chromatography, we show that siRNAs can tightly bind Ca2+ and Mg2+ up to molar equivalents of the phosphodiester (PO)/phosphorothioate (PS) bonds independently of the structure or phosphorothioate content. Optimization of the formulation by adding high concentrations (above biological levels) of divalent cations (Ca2+ alone, Mg2+ alone, or Ca2+ and Mg2+) prevents seizures with no impact on the distribution or efficacy of the oligonucleotide. The data here establishes the importance of adding Ca2+ and Mg2+ to the formulation for the safety of CNS administration of therapeutic oligonucleotides.

Synthesis, Crystal Structure, DFT Calculations, Bioactivity Study, and Docking Results of Bis‐Hydrazone Based on 1,2,4‐Triazol‐3‐Thione

AbstractThe new, unexpected bioactive bis‐hydrazone derivative (4) was obtained, in 74 % yield, by reacting two molar equivalents of pyrazole‐4‐carbaldehyde (1) with one molar equivalent of 2,5‐dihydrazineyl‐1,3,4‐thiadiazole (2). The compound was comprehensively characterized, including X‐ray single crystal, DFT calculations, and bioactivity assessments. Hirschfeld surface analysis confirmed the presence of hydrogen bonding interactions, particularly N−H⋅⋅⋅N and C−H⋅⋅⋅π interactions, which influence the overall crystal packing. The target bis‐hydrazone exhibited significant antimicrobial activity against multi‐drug‐resistant bacterial strains, with the largest activity against S.typhimurium with an inhibition zone of 17.1±0.6 mm and MIC 31.25 μg/mL. The compound also demonstrated significant cytotoxic effects on cancer cells, with a higher IC50 ratio of 134.43 μg/mL against the normal cell line Wi38 and the lowest IC50 value of 45.88 μg/mL against the cancer cell line Caco2. Molecular docking was carried out with estrogen receptor alpha (ERα) and sodium‐glucose transporter SGLT1, which are relevant to Mcf7 and Caco2 cancer cell lines, respectively. Docking suggests the presence of specific amino acids that may influence the binding affinity between the ligand and receptor active sites through residue overlaps in chains A for SGLT1 and B for Erα, offering the ligand as a promising anticancer consistent with the IC50 outcomes.

Lead Acetate Exposure and Cerebral Amyloid Accumulation: Mechanistic Evaluations in APP/PS1 Mice.

The role of environmental factors in Alzheimer's disease (AD) pathogenesis remains elusive. Mounting evidence suggests that acute and past exposure to the environmental toxicant lead (Pb) is associated with longitudinal decline in cognitive function, brain atrophy, and greater brain -amyloid () deposition. However, the nature of Pb-induced amyloid deposition and how it contributes to AD development remain unclear. This study investigates the role of Pb in the pathogenesis of cerebral amyloid angiopathy (CAA) and whether plasminogen activator inhibitor-1 (PAI-1) contributes to this process in the APP/PS1 mouse model. Female APP/PS1 mice at 8 wk of age were administered either Pb-acetate (PbAc) (i.e., ) or an equivalent molar concentration of sodium acetate (NaAc) via oral gavage once daily for 8 wk. Amyloid deposition and vascular amyloid were determined by immunostaining. In addition, perivascular drainage, vascular binding assay, and microglial endocytosis were examined to determine underlying mechanisms. Furthermore, magnetic resonance imaging demyelination imaging was performed invivo measure the level of demyelination. Finally, Y-maze and Morris water maze tests were assessed to evaluate the cognitive function of mice. APP/PS1 mice (an AD mice model) exposed to PbAc demonstrated more vascular amyloid deposition less neocortical myelination, and lower cognitive function, as well as greater vascular binding to , higher ratios, strikingly lower levels in the perivascular drainage, and microglial endocytosis. Importantly, exposure to a specific PAI-1 inhibitor, tiplaxtinin, which previously was reported to lower CAA pathology in mice, resulted in less CAA-related outcomes following PbAc exposure. Our findings suggest that PbAc induced CAA/AD pathogenesis via the PAI-1 signaling in the APP/PS1 mouse model, and the inhibition of PAI-1 could be a potential therapeutic target for PbAc-mediated CAA/AD disorders. https://doi.org/10.1289/EHP14384.

Preparation and Properties of Crosslinked Quaternized Chitosan-Based Hydrogel Films Ionically Bonded with Acetylsalicylic Acid for Biomedical Materials.

The aim of the current study is to develop chitosan-based biomaterials which can sustainably release acetylsalicylic acid while presenting significant biological activity. Herein, an innovative ionic bonding strategy between hydroxypropyl trimethyl ammonium chloride chitosan (HACC) and acetylsalicylic acid (AA) was proposed, skillfully utilizing the electrostatic attraction of the ionic bond to achieve the controlled release of drugs. Based on this point, six crosslinked N-[(2-hydroxy-3-trimethylammonium)propyl]chitosan acetylsalicylic acid salt (CHACAA) hydrogel films with varying acetylsalicylic acid contents were prepared by a crosslinking reaction. The results of 1H nuclear magnetic resonance spectroscopy (1H NMR) and scanning electron morphology (SEM) confirmed the crosslinked structure, while the obtained hydrogel films possessed favorable thermal stability, mechanical properties, and swelling ability. In addition, the drug release behavior of the hydrogel films was also investigated. As expected, the prepared hydrogel films demonstrated the capability for the sustainable release of acetylsalicylic acid due to ion pair attraction dynamics. Furthermore, the bioactivities of CHACAA-3 and CHACAA-4 hydrogel films with acetylsalicylic acid molar equivalents of 1.25 and 1.5 times those of HACC were particularly pronounced, which not only exhibited an excellent drug sustained-release ability and antibacterial effect, but also had a higher potential for binding and scavenging inflammatory factors, including NO and TNF-α. These findings suggest that CHACAA-3 and CHACAA-4 hydrogel films hold great potential for applications in wound dressing, tissue engineering scaffolds, and drug carriers.

Stability of a Multiresponsive Sulfonium Vinyl Sulfide Linker toward Nucleophilic/Radical Thiols, Reactive Nitrogen Species, and in Cells under Pro-inflammatory Stimulation.

Chemical linkages that respond to biological stimuli are important for many pharmaceutical and biotechnological applications, making it relevant to explore new variants with different responsivity profiles. This work explores the responsiveness of a TAT peptide-based sulfonium vinyl sulfide probe that responds to nucleophilic thiols, radical thiol species (RTS), and reactive nitrogen species (RNS). Under model conditions, response to nucleophilic thiols was very slow (hours/days), though fast with down to molar equivalents of either RTS or RNS (minutes). These reactions led to the traceless release of a methionine-containing peptide in the first two cases and to a hydroxy nitration adduct in the third case. Despite the sensitive nature of the probe, it remained stable for at least ∼2 h in the presence of cells during TAT-mediated trafficking, even under pro-inflammatory stimulation. The thiol-responsiveness is intermediate to that observed for disulfide linkers and conventional cysteine-maleimide linkers, presenting opportunities for biotechnological applications.

High Entropy Alloys as High Performance Catalysts for Electrolytic Water Splitting

Renewable energy driven electrolytic water splitting is a required technology for low-carbon hydrogen production to achieve the goal of net-zero CO2 emission by 2050. This technology also serves as a necessary energy storage route to resolve the intolerable intermittency and unreliability issues of renewable energies. The prevailing of this hydrogen production technology however is restricted by the high cost of electricity. Consequently, developments of cost–effective highly efficient and stable electrocatalysts to drive the electrolytic water splitting reactions are the key. In terms of catalyst developments, mono-component systems are first explored, followed by multi–component systems, taking advantages of possible positive synergy between constituent components. Recently, a new class of multi-component catalyst systems, entropy-stabilized materials, including alloys, oxides, sulfides, phosphides, etc., emerges and is demonstrated promising performances toward electrocatalysis. In light of the variable and flexible element compositions, entropy-stabilized materials provide infinite and enormous potentials for the design of promising electrocatalysts. The key is to maximize the synergy between constituent components. High entropy alloys (HEA), defined as alloys composed of five or more major metallic elements, have been under intensive and extensive development in past fifteen years for their extraordinary mechanical, magnetic, corrosion, and catalytic properties. Herein, an equi–molar FeCoNiCuMo HEA on nickel foam was developed as a breakthrough catalyst for electrocatalytic water splitting, in terms of both activity and stability, in pH-universal media and in severe industrial operation conditions. Furthermore, a new catalytic phenomenon is discovered. Two different catalytic mechanisms function simultaneously on different constituents of the catalyst, and the synergistic interactions between the two categorical domains leads to catalytic kinetics faster than the theoretical limit set by a single rate-limiting step, Tafel step of the Volmer-Tafel route. A new kinetic model is developed to predict a new theoretical lower limit of Tafel slopes of 15 mV/dec based on a synergistic interaction between the two categorical domains of the high entropy alloy catalyst. This new development proves that the theoretical lower limit of Tafel slope of 30 mV/dec posed for the Volmer-Tafel mechanism functioning on a single component catalyst can be further reduced to 15 mV/dec through synergistic interactions between two categorical domains of a multi-component catalyst. It is demonstrated that high entropy materials, composed of five or more atomically/molecularly well-mixed major components, are intrinsically promising candidates for realization of quantum leaps in catalytic performances of catalysts.

Magnesium(II) Porphyrazine with Thiophenylmethylene Groups-Synthesis, Electrochemical Characterization, UV-Visible Titration with Palladium Ions, and Density Functional Theory Calculations.

The presented studies aimed to evaluate the peripheral coordinating properties of a novel porphyrinoid family representative preceded by its synthesis for potential sensing purposes. Two synthetic pathways were employed to a obtain maleonitrile derivative, further used as a starting material in the cyclotetramerization reaction. In the first one, DAMN was used in sequential double-reductive alkylation with 2-thiophene-carboxyaldehyde and sodium borohydride. In the second, DAMN was used in a one-pot reaction with 2-thiophene-carboxyaldehyde in the presence of a 5-ethyl-2-methylpyridine borane complex in methanol and acetic acid. Following the Linstead approach, the cyclization reaction led to a novel symmetrical magnesium(II) octaaminoporphyrazine with methyl(2-thiophenylmethylene) substituents. The macrocycle's electrochemical properties were assessed by cyclic and differential pulse voltammetries revealing one reduction and two oxidation peak potentials. The additional spectroelectrochemical measurements showed formation of a cationic form of the macrocycle at an applied potential of 0.6 V. The coordinating properties due to the palladium ion of novel porphyrazines were measured with the use of titration combined with UV-vis spectrometry. The titration of Pd2+ revealed the good sensing activity of porphyrazine in the range of 0.1 to 5 palladium molar equivalents. In addition, Pd2+ ions coordination was also assessed by electrochemical studies, indicating the peak potential shift of 0.1 V in the presence of metal cations. DFT calculations showed the good agreement between theoretical and experimental data in the UV-vis and 1H NMR studies.

Real-time detection of enzymatically formed hydrogen sulfide by pathogenic variants of cystathionine beta-synthase using hemoglobin I of Lucina pectinata as a biosensor

Classical homocystinuria is a rare disease caused by mutations in cystathionine β-synthase (CBS) gene (OMIM 613381). CBS catalyzes the first step of the transsulfuration pathway that converts homocysteine (Hcy) into cystathionine (Cysta) via a number of co-substrates and mechanisms. Formation of Cysta by condensation of Hcy and cysteine (Cys) produces a molar equivalent of hydrogen sulfide (H2S). H2S plays important roles in cognitive and vascular functions. Clinically, patients with CBS deficiency present with vascular, ocular, neurological and skeletal impairments. Biochemically, CBS deficiency manifests with elevated Hcy and reduced concentration of Cysta in plasma and urine. A number of pathogenic variants of human CBS have been characterized by their residual enzymatic activity, but very few studies have examined H2S production by pathogenic CBS variants, possibly due to technical hurdles in H2S detection and quantification. We describe a method for the real-time, continuous quantification of H2S formed by wild-type and pathogenic variants of human recombinant CBS, as well as by fibroblast extracts from healthy controls and patients diagnosed with CBS deficiency. The method takes advantage of the specificity and high affinity of hemoglobin I of the clam Lucina pectinata toward H2S and is based on UV–visible spectrophotometry. Comparison with the gold-standard, end-point H2S quantification method employing monobromobimane, as well as correlations with CBS enzymatic activity determined by LC-MS/MS showed agreement and correlation, and permitted the direct, time-resolved determination of H2S production rates by purified human recombinant CBS and by CBS present in fibroblast extracts. Rates of H2S production were highest for wild-type CBS, and lower for pathogenic variants. This method enables the examination of structural determinants of CBS that are important for H2S production and its possible relevance to the clinical outcome of patients.

Efficient removal of p-nitrophenol from water by imidazolium ionic liquids functionalized cellulose microsphere

Removing p-nitrophenol (PNP) from water resources is crucial due to its significant threat to the environment and human health. Herein, imidazolium ionic liquids with short/long alkyl chain ([C2VIm]Br and [C8VIm]Br) modified cellulose microspheres (MCC-[C2VIm]Br and MCC-[C8VIm]Br) were synthesized by radiation method. To examine the impact of adsorbent hydrophilicity on adsorption performance, batch and column experiments were conducted for PNP adsorption. The MCC-[C2VIm]Br and MCC-[C8VIm]Br, with an equivalent molar import amount of ionic liquids, exhibited maximum adsorption capacities of 190.84 mg/g and 191.20 mg/g for PNP, respectively, and the adsorption equilibrium was reached within 30 min. Both adsorbents displayed exceptional reusability. Integrating the findings from XPS and FTIR analyses, and AgNO3 identification, the suggested adsorption mechanism posited that the adsorbents engaged with PNP through ion exchange, hydrogen bonds and π-π stacking. Remarkably, the hydrophobic MCC-[C8VIm]Br exhibited superior selectivity for PNP than the hydrophilic MCC-[C2VIm]Br, while had little effect on adsorption capacity and rate. MCC-[C8VIm]Br-2 with high grafting yield increased the adsorption capacity to 327.87 mg/g. Moreover, MCC-[C8VIm]Br-2 demonstrated efficient PNP removal from various real water samples, and column experiments illustrated its selective capture of PNP from groundwater. The promising adsorption performance indicates that MCC-[C8VIm]Br-2 holds potential for PNP removal from wastewater.

Preventing acute neurotoxicity of CNS therapeutic oligonucleotides with the addition of Ca2+ and Mg2+ in the formulation.

Oligonucleotide therapeutics (ASOs and siRNAs) have been explored for modulation of gene expression in the central nervous system (CNS), with several drugs approved and many in clinical evaluation. Administration of highly concentrated oligonucleotides to the CNS can induce acute neurotoxicity. We demonstrate that delivery of concentrated oligonucleotides to the CSF in awake mice induces acute toxicity, observable within seconds of injection. Electroencephalography (EEG) and electromyography (EMG) in awake mice demonstrated seizures. Using ion chromatography, we show that siRNAs can tightly bind Ca2+ and Mg2+ up to molar equivalents of the phosphodiester (PO)/phosphorothioate (PS) bonds independently of the structure or phosphorothioate content. Optimization of the formulation by adding high concentrations (above biological levels) of divalent cations (Ca2+ alone, Mg2+ alone, or Ca2+ and Mg2+) prevents seizures with no impact on the distribution or efficacy of the oligonucleotide. The data here establishes the importance of adding Ca2+ and Mg2+ to the formulation for the safety of CNS administration of therapeutic oligonucleotides.

Molecular-strain induced phosphinidene reactivity of a phosphanorcaradiene

Phosphanorcaradienes are an appealing class of phosphorus compounds that can serve as synthons of transient phosphinidenes. However, the synthesis of such species is a formidable task owing to their intrinsic high reactivity. Herein we report straightforward synthesis, characterization and reactivity studies of a phosphanorcaradiene, in which one of the benzene rings in the flanking fluorenyl substituents is intramolecularly dearomatized through attachment to the phosphorus atom. It is facilely obtained by the reduction of phosphorus(III) dichloride precursor with potassium graphite. Despite being thermally robust, it acts as a synthetic equivalent of a transient phosphinidene. It reacts with trimethylphosphine and isonitrile to yield phosphanylidene-phosphorane and 1-phospha-3-azaallene, respectively. When it is treated with one and two molar equivalents of azide, iminophosphane and bis(imino)phosphane are isolated, respectively. Moreover, it is capable of activating ethylene and alkyne to afford [1 + 2] cycloaddition products, as well as oxidative cleavage of Si–H and N–H bonds to yield secondary phosphines. All the reactions proceed smoothly at room temperature without the presence of transition metals. The driving force for these reactions is most likely the high ring-constraint of the three-membered PC2 ring and recovery of the aromaticity of the benzene ring.