1H NMR Spectroscopy Research Articles

Organometallic Ru(III) Catalysts for α-Alkylation of Carbonyl Compounds using Alcohols: Mechanistic Insights via Detection of Key Intermediates.

Three novel cyclometalated ruthenium complexes ([Ru.L(9)] [Ru.L(10)] and [Ru.L(11)]) featuring azo functionalities were synthesized and characterized using a variety of spectroscopic techniques, namely FT-IR, electronic absorption spectroscopy, and ESI-MS. Representative solid-state structures of the acquired complexes were determined through X-ray crystallography. These complexes were evidenced to be efficient catalysts for the synthesis of various α-alkylated compounds utilizing simple acetophenone derivatives with easily affordable and economically viable alcohols, which were isolated and characterized via 1H and 13C NMR spectroscopy. The optimum reaction conditions were found by employing toluene as solvent, potassium tert-butoxide as base at 115 oC temperature utilizing 0.8 mol% of catalyst [Ru.L(10)]. The yield of the desired compounds found to be in the range of 83 - 97%. Additionally, mass spectrometry provided insights into the in-situ generated ruthenium hydride and ruthenium alkoxy intermediates, shedding light on the catalytic mechanism.

Synthesis, crystal structures and antiproliferative activities of a new indole-containing dipyridylmethanone hydrazone Schiff base and its cadmium(II) complex.

In this study, we introduce a novel indole-containing pyridine-based Schiff base, (E)-2-({[bis(pyridin-2-yl)methylidene]hydrazin-1-ylidene}methyl)-1H-indole, C20H15N5 (2-DPHI), and its cadmium(II) complex poly[[2-({[bis(pyridin-2-yl)methylidene]hydrazin-1-ylidene}methyl)-1H-indole]di-μ-chlorido-cadmium(II)], [CdCl2(C20H15N5)]n (pCd2), as potential anticancer agents. The Schiff base was synthesized by reacting dipyridylmethanone hydrazone with indole-2-formaldehyde, while the cadmium complex was prepared by combining CdCl2 and 2-DPHI in methanol at room temperature. Both compounds were evaluated for their cytotoxicity against three human cancer cell lines (A375, A549 and HeLa) and a normal cell line (HFF-1). The ligand 2-DPHI exhibited notable antitumour activity, with an IC50 value of 12.22 µM against A375 and 15.17 µM against A549 after 48 h, while the pCd2 complex showed an even stronger inhibition of A375 cells, with an IC50 value of 4.88 µM, outperforming both 2-DPHI and CdCl2. Both compounds demonstrated lower toxicity towards normal cells compared to cancer cells. The structures of 2-DPHI and pCd2 were fully characterized using single-crystal X-ray diffraction, elemental analysis, high-resolution mass spectrometry and FT-IR, 1H NMR, 13C NMR and UV-Vis spectroscopy.

Evaluating the Impact of the Membrane Thickness on the Function of the Intramembrane Protease GlpG.

Cellular membranes exhibit a huge diversity of lipids and membrane proteins that differ in their properties and chemical structure. Cells organize these molecules into distinct membrane compartments characterized by specific lipid profiles and hydrophobic thicknesses of the respective domains. If a hydrophobic mismatch occurs between a membrane protein and the surrounding lipids, there can be functional consequences like reduced protein activity. This phenomenon has been extensively studied for single-pass transmembrane proteins, rhodopsin, and small polypeptides such as gramicidin. Here we investigate the E. coli rhomboid intramembrane protease GlpG as a model to systematically explore the impact of membrane thickness on GlpG activity. We used fully saturated dilauroylpohosphatidylcholine (DLPC) and dimyristoylphosphatidylcholine (DMPC) model lipids and altered membrane thickness by varying the cholesterol content. Physical membrane parameters were determined by 2H and 31P NMR spectroscopy and correlated with GlpG activity measurements in the respective host membranes. Differences in bulk and annular lipids as well as alterations in protein structure in the respective host membranes were determined using molecular dynamics simulations. Our findings indicate that GlpG can influence the membrane thickness in DLPC/cholesterol membranes but not in DMPC/cholesterol membranes. Moreover, we observe that GlpG protease activity is reduced in DLPC membranes at low cholesterol content, which was not observed for DMPC. While a change in GlpG activity can already be due to smallest differences in the lipid environment, potentially enabling allosteric regulation of intramembrane proteolysis, there is no overall correlation to cholesterol-mediated lipid bilayer organization and phase behavior. Additional factors such as the influence of cholesterol on membrane bending rigidity and curvature energy need to be considered. In conclusion, the functionality of α-helical membrane proteins such as GlpG relies not only on hydrophobic matching but also on other membrane properties, specific lipid interaction and the composition of the annular layer.

Synthesis, In Silico Prediction, and In Vitro Evaluation of Anti-tumor Activities of Novel 4'-Hydroxybiphenyl-4-carboxylic Acid Derivatives as EGFR Allosteric Site Inhibitors.

Allosteric inhibition of EGFR tyrosine kinase (TK) is currently among the most attractive approaches for designing and developing anti-cancer drugs to avoid chemoresistance exhibited by clinically approved ATP-competitive inhibitors. The current work aimed to synthesize new biphenyl-containing derivatives that were predicted to act as EGFR TK allosteric site inhibitors based on molecular docking studies. A new series of 4'-hydroxybiphenyl-4-carboxylic acid derivatives, including hydrazine-1-carbothioamide (S3-S6) and 1,2,4-triazole (S7-S10) derivatives, were synthesized and characterized using IR, 1HNMR, 13CNMR, and HR-mass spectroscopy. Compound S4 had a relatively high pharmacophore-fit score, indicating that it may have biological activity similar to the EGFR allosteric inhibitor reference, and it scored a relatively low ΔG against EGFR TK allosteric site, indicating a high likelihood of drug-receptor complex formation. Compound S4 was cytotoxic to the three cancer cell lines tested, particularly HCT-116 colorectal cancer cells, with an IC50 value comparable to Erlotinib. Compound S4 induced the intrinsic apoptotic pathway in HCT-116 cells by arresting them in the G2/M phase. All of the new derivatives, including S4, met the in silico requirements for EGFR allosteric inhibitory activity. Compound S4 is a promising EGFR tyrosine kinase allosteric inhibitor that warrants further research.

The Use of the Carbonyl Group (C-3) of Isatin for the Construction of Pyrazoline Moiety and the Study of its Antioxidant Activity

A series of novel pyrazoline derivatives 5-13 were synthesized in three steps from isatin, with yields ranging from 40 to 72% over the multistep procedure. The first step included the condensation of isatin with p-aminoacetophenone to afford the corresponding Schiff base 1 in a 75% yield. In the second step, the enolate form of Schiff base 1 was reacted with different aromatic aldehydes (benzaldehyde, p-nitrobenzaldehyde, and p-chlorobenzaldehyde) to give the title chalcone derivatives 2-4 in 60-72 yields. In the third step, pyrazoline derivatives 5-13 were synthesized via cycloaddition reactions between compounds 2-4 and hydrazine hydrate, phenyl hydrazine, or p-nitrophenyl hydrazine. The cycloaddition produced the target pyrazoline compounds in 40-72% isolated yields. All prepared compounds were characterized by FT-IR and 1H NMR spectroscopy. Some of the prepared compounds were tested for antioxidant properties.

Synthesis and Study Biological Activity of Some New Substituted Thiazolidin-4-one Derivatives

The microwave (MW) method was used to create a series of new thiazolidin-4-one derivatives containing benzothiazole and azo groups. Azoaldehyde derivative A was synthesized via the coupling reaction of 2-aminobenzothiazole diazonium ions and 2-hydroxybenzaldehyde. The resultant azoaldehyde A was then subjected to condensation reactions with the primary aromatic amines using the MW method to give azoimines derivatives S1-S5. Finally, compounds S1-S5 were reacted with α-mercaptoacetic acid by the MW method to generate the thiazolidin-4-one derivatives T1-T5. The novel-produced compounds T1-T5 were identified by FT-IR, 1H NMR, and 13C NMR spectroscopy. The DPPH was used to determine the antioxidant activity of the novel-produced compounds T1-T5. The obtained results for T1 and T5 were excellent as antioxidants in comparison with ascorbic acid, while in the antibacterial study, it was discovered that T2, T3, and T5 were found to be more successful than Gentamycin as a control drug against Staphylococcus aureus in an antibacterial investigation, while T3 was found to be more effective than the reference drug against Escherichia coli.

HSCCC Straightforward Fast Preparative Method for Isolation of Two Major Cytotoxic Withanolides from Athenaea fasciculata (Vell.) I.M.C. Rodrigues & Stehmann

Athenaea fasciculata belongs to the Solanaceae family and is a promising source of cytotoxic withanolides known as aurelianolides A and B. In the last years, the pharmacological studies of these aurelianolides on different leukemia cell lines have stimulated new studies on their potential as alternative candidates for new lead anticancer drugs. However, the obtention of these two pure compounds by traditional preparative is a costly and long time-consuming process, which is performed in several steps. This study aimed to propose a straightforward approach for isolating aurelianolides A and B using high-speed countercurrent chromatography (HSCCC). In this study, among 10 different solvent systems, the system composed of n-hexane/ethyl acetate/methanol/water 3:6:2:1 (v/v/v/v) was chosen for optimization. This HEMWat system was optimized to 4:8:2:4 (v/v/v/v) and chosen for HSCCC separation in a tail-to-head elution mode. After the HSCCC scale-up procedure, a withanolides mixture (200.0 mg) was separated within 160 min in a single-step purification process. In total, 78.9 mg of aurelianolide A (up to 95.0% purity) and 54.3 mg of aurelianolide B (up to 88.5% purity) was obtained by this fast sequential liquid–liquid partition process. The isolated withanolides were identified by 1H and 13C NMR spectroscopy (this method has proven to be faster and more efficient than classical procedures (CC and Prep-TLC)).

Preparation of Environmentally Friendly Anticorrosive Coatings with Aniline Trimer-Modified Waterborne Polyurethane

Eco-friendly waterborne coatings frequently exhibit poor corrosion resistance, high solvent content, and extended curing times, attributed to the excessive employment of hydrophilic groups and petroleum-derived polyols. In this work, aniline trimer (ACAT) and polyethylene glycol (PEG) were used as chain extenders. E-44 epoxy resin was subsequently utilized to modify the system and an aniline trimer-modified waterborne polyurethane (AT-WPU) dispersion was prepared and characterized. The chemical structure of the synthesized ACAT was characterized employing 1H NMR, ESI-MS, and FTIR spectroscopy. The structure and coating performance of the AT-WPU dispersion were investigated utilizing FTIR, particle size analysis, thermogravimetric analysis, DSC, TEM, SEM, and electrochemical corrosion testing. The results demonstrate that the aniline trimer-modified waterborne polyurethane dispersion was successfully synthesized. Additionally, the DSC analysis results and thermogravimetric graphs indicate that the glass transition temperature and thermal stability of the coatings increased with the addition of aniline trimer. As the aniline trimer content increased, the hardness and adhesion of the coatings were significantly enhanced. In the electrochemical corrosion assessment, the corrosion current density of AT-WPU-3 attained 7.245 × 10−9 A·cm−2, and the corrosion rate was as low as 0.08 μm·Y−1, indicating excellent corrosion resistance. The present study provides promising practical applications in the domain of metal material protection.

Extraction and In Vitro and In Vivo Antioxidant Activity Evaluation of Polyphenols from Lychee Pericarp

Background Finding a new promising plant antioxidant to combat or prevent cardiovascular disease remains a major challenge for researchers. Lychee pericarp, which includes a variety of polyphenols, is a prospective source of botanical antioxidants. Purpose In response to this issue, we assessed the effect of lychee bark extract on oxygen radical scavenging capacity and separate vascular protective ability in vivo. Methods In the current study, the lychee pericarp enrichment product (RLP) was obtained by optimizing an extraction method and separated using modern separation methods. The structure of the isolated compounds was assessed using 1H-NMR, 13C-NMR, and electrospray ionization-mass spectrometry, and the content of polyphenols obtained from the extract was quantified using the area normalization method. In addition, the capacity of RLP to scavenge oxygen radicals in vitro was assessed using the DPPH (1,1-diphenyl-2-picrylhydrazyl) and T-AOC (total antioxidant capacity) techniques. Furthermore, an isoprenaline hydrochloride (ISO)-induced rat model of acute myocardial ischemia was established, and four biochemical indicators were used to assess the effect of lychee bark extract on oxygen radical scavenging capacity and cardiovascular protective ability in vivo. Results RLP extraction produced 11 chemicals, 6 of which were structurally assessed. Quantitative analysis revealed that epicatechin, PC-C(epicatechin-(4β↓8,2β↓O↓7)-epicatechin-(4β↓8)-epicatechin), type A proanthocyanidin trimer, proanthocyanidin A2, and type B proanthocyanidin dimer were the most abundant polyphenols. The in vitro DPPH and T-AOC findings revealed that RLP exhibited strong free radical scavenging activity, approximately 1.5-fold that of vitamin C. The four biochemical indicators confirmed the antioxidant activity and cardiovascular protective ability of RLP in vivo. Conclusion RLP has good in vivo and in vitro antioxidant activity, confirming lychee pericarp as a prospective source of botanical antioxidants.

New Pd(II)-pincer type complexes as potential antitumor drugs: synthesis, nucleophilic substitution reactions, DNA/HSA interaction, molecular docking study and cytotoxic activity.

Two new complexes of Pd(II), [Pd(L1)Cl]Cl (Pd1) and [Pd(L2)Cl]Cl (Pd2), (where L1 = N2,N6-bis(5-methylthiazol-2-yl)pyridine-2,6-dicarboxamide and L2 = N2,N6-di(benzo[d]thiazol-2-yl)pyridine-2.6-dicarboxamide) were synthesized. Characterization of the complexes was performed using elemental analysis, IR, 1H NMR spectroscopy and MALDI-TOF mass spectrometry. The nucleophilic substitution reactions of complexes with L-Methionine (L-Met), L-Cysteine (L-Cys) and guanosine-5'-monophosphate (5'-GMP) were studied by stopped-flow method at physiological conditions (pH = 7.2 and 37 °C). Complex Pd1 was more reactive than Pd2 in all studied reactions, while the order of reactivity of the selected ligands was: L-Met > L-Cys > 5'-GMP. The interaction of complexes with calf thymus-DNA (CT-DNA) was studied by Uv-Vis absorption and fluorescence emission spectroscopy. Competitive binding studies with intercalative agent ethidium bromide (EB) and minor groove binder Hoechst 33258 were performed as well. Both complexes interacted with DNA through intercalation and minor groove binding, where the latter was preferred. Additionally, the interaction of Pd1 and Pd2 complexes with human serum albumin (HSA) was studied employing fluorescence quenching spectroscopy. The results indicate a moderate binding affinity of complexes, with slightly stronger binding of the Pd1. Fluorescence competition experiments with site-markers (eosin Y and ibuprofen) for HSA were used to locate the binding site of Pd1 to the HSA. Additionally, the interaction with DNA and HSA was studied by molecular docking and the revealed results were in good agreement with the experimentally obtained ones. Pd1 complex exhibited cytotoxicity toward human (HCT116) and mouse cell lines (CT26) of colorectal cancer, mouse (4T1) and human (MDA-MB468) breast cancer lines and non-cancerous mouse mesenchymal stem cells (mMSC). In addition, Pd1 complex demonstrated significant selectivity towards cancer cells over non-cancerous mMSC, indicating a high potential to eliminate malignant cells without affecting normal cells. It induced apoptosis in CT26 cells, effectively arrested the cell cycle in the S phase, and selectively down-regulated cyclin D and cyclin E. Moreover, it can alter the expression of cell cycle regulators by increasing p21 and decreasing p-AKT. These findings confirm its ability to disrupt key tumor cell survival signals and suggest that the Pd1 complex is a potent candidate for effective cancer treatment.

Selective Metal‐Coordinated Nanodrugs Based on Thiazine Moiety for Anticancer Therapeutics: Spectroscopic, Theoretical, and Molecular Docking Studies

ABSTRACTThe current study involved production, comprehensive structural analysis, and physicochemical characterizing of two distinctive complexes namely, Cu(TBH) and Zn(TBH); TBH donor ligand: N′‐(1‐(3,6‐dihydro‐4‐hydroxy‐2,6‐dioxo‐2H‐1,3‐thiazin‐5‐yl)ethylidene)‐2‐hydroxybenzohydrazide) using a wide range of analytical methods, including elemental analysis, UV–Vis, FT‐IR, and 1HNMR spectrometry, molar conductivity and magnetic susceptibility measurements, and thermal analysis. According to the findings, chelation can occur through O, N, and O donor atoms of monoanionic chelator for generating mono‐nuclear chelates with tetrahedral geometry for Cu (II) and octahedral geometry for Zn (II). The anticarcinogenic ability of TBH chelator and its coordinated compounds against human liver cancer (HepG‐2) was investigated. The Cu(TBH) complex was found to have selective and promising anticancer activity against a liver cancer cell line, with lower IC50 (liver carcinoma cell line) and higher IC50 (normal human cell line) values than other produced compounds and standard drugs. Utilizing DFT computations, the molecular structures of the TBH and its complexes were verified, offering a detailed understanding of their quantum chemical characteristics. A quantitative structure–activity relationship (QSAR) model, which illustrates the association between DFT‐computed descriptors and biological activities pIC50, was also created using multiple linear regression (MLR) on the synthesized compounds as anticancer medicines. Additionally, there are no issues with the produced compounds' oral bioavailability according to (ROF) Lipinski's rule of five. Furthermore, docking studies of the synthesized TBH chelator and its chelates with CDK2 kinase have been performed to validate the biological findings. According to our findings, the novel Cu(TBH) nanodrug exhibits considerable cytotoxic activity, prompting further study into its pharmacological profile and exploring its potential in drug development.

Bioisosteric Replacement in the Search for Biologically Active Compounds: Design, Synthesis and Anti-Inflammatory Activity of Novel [1,2,4]triazino[2,3-c]quinazolines

Background: Designing novel biologically active compounds with anti-inflammatory properties based on condensed quinazolines is a significant area of interest in modern medicinal chemistry. In the present study, we describe the development of promising new bioactive molecules through the bioisosteric replacement of a carbon atom with a sulfur atom in anti-inflammatory agents, specifically 3-methyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)butanoate. Methods: Design and synthetic studies have led to the series of previously unknown substituted 2-[((3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)methyl)thio]carboxylic acids and their esters. These compounds were synthesized by reacting 6-chloroalkyl-3-R-2H-[1,2,4]triazino[2,3-c]quinazolin-2-ones with sulfanylalkyl carboxylic acids and their functional derivatives. The purity and structure of the obtained compounds were confirmed using a set of physicochemical methods, including elemental analysis, HPLC-MS, and 1H NMR spectroscopy. Molecular modeling, predicted toxicity, drug-likeness, and pharmacokinetics data were used to select compounds for evaluation of their effects on acute aseptic inflammation (carrageenan-induced paw edema test) and on markers of the inflammatory process. Results: The compound 2-((1-(3-methyl-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazolin-6-yl)ethyl)thio)acetic acid (compound 2e) was identified as the most active anti-inflammatory agent (AA = 53.41%), demonstrating significant inhibition of both paw edema development and the generation of pro-inflammatory cytokines and mediators. Conclusions: Results from docking studies and analysis of “structure-affinity” correlations revealed that these compounds are promising candidates for further modification and detailed investigation of their anti-inflammatory activity

Dual inhibition of SGLT 1 and 2 alleviates intracellular sodium overload in uraemic cardiomyopathy

Abstract Background Chronic kidney disease (CKD) is a leading cause of mortality with the risk of developing cardiovascular disease higher than progression to kidney failure. The aetiology of uraemic cardiomyopathy is multifactorial and includes metabolic derangement. It was previously shown that elevated intracellular sodium (Nai) is causally linked to cardiac metabolic impairment and that targeting sodium homeostasis can reprogramme cardiac metabolism. Dual inhibition of sodium-glucose co-transporters (SGLT) 1 and 2 is an emerging therapy for CKD, however the impact on intracellular sodium and cardiac metabolism is yet to be elucidated. Purpose This study aimed to assess whether dual SGLT1/2 inhibitor sotagliflozin impacts cardiometabolic phenotype in CKD. Methods CKD was surgically induced by 5/6 nephrectomy in Wistar rats (n=46) for a period of 4 weeks, with chronic sotagliflozin treatment (5mg/kg) given for the last 3 weeks. Upon termination, hearts were Langendorff-perfused and studied using 31P and 23Na NMR spectroscopy (Sham n=7, CKD n=6, CKD+sotagliflozin n=5). To assess the cardiac-specific effect of the drug, acute sotagliflozin treatment (30mM) was delivered in the Langendorff perfusate to an additional group of CKD hearts (n=5). Furthermore, the effect of chronic sotagliflozin treatment on in vivo cardiac function (echocardiography n=23) and metabolic profile (1H NMR spectroscopy n=15) was assessed. Results CKD animals were characterized by significant renal dysfunction (2-fold increase in urea and creatinine vs sham, p<0.05), and HFpEF (EF(%) sham 82±2 vs CKD 80±1 p>0.05; diastolic dysfunction (E/A) sham 1.39±0.03 vs CKD 1.11±0.01, p=0.0018). Myocardial Nai was significantly elevated in CKD animals compared to sham controls (TQF 23Na 3.04±0.18 vs 2.01±0.32 arb units, p=0.03). Chronic sotagliflozin treatment didn’t impact renal or cardiac dysfunction. Neither chronic nor acute drug treatment impacted baseline CKD cardiac energetics (PCr/ATP sham 1.53±0.22, CKD 1.25±0.13, chronic 1.16±0.14, acute 1.18±0.13, p>0.05; ΔGATP (kJ/mol) sham -64±4, CKD -66±8, chronic -56±1, acute -59±3, p>0.05). However, both chronic and acute sotagliflozin treatment normalised the increased myocardial Nai (TQF 23Na chronic 2.17±0.12, acute 2.23±0.14 arb units, p>0.05 vs sham). Chronic drug dosing altered the systemic metabolic profile of CKD animals reducing the levels of circulating triglycerides and FFA (p<0.05) as well as altering metabolomic profile of liver, muscle and kidneys. Conclusion(s) We have shown that uraemic cardiomyopathy is characterised by HFpEF, elevated myocardial Nai and altered systemic metabolic profile. Both chronic and acute treatment with dual SGLT1/2 inhibitor sotagliflozin normalised myocardial Nai. The alleviation of Nai load could lead to improved cardiometabolic outcomes in CKD.

Serum metabolomics improve risk stratification for incident heart failure

Abstract Background The prediction and early detection of heart failure (HF) is vital to reduce its substantial impact on quality of life, survival and healthcare expenditure. Current incident HF risk stratification strategies achieve only modest performance. Moreover, state-of-the-art risk scores focus on commonly acknowledged clinical risk factors, thus necessitating the integration of heterogenous data sources and prioritizing individuals with obvious risk constellations. Purpose Here, we explored the predictive value of serum metabolomics (168 metabolites detected by proton nuclear magnetic resonance (1H-NMR) spectroscopy) for incident HF. Methods Leveraging data of n = 68,311 individuals and > 0.8 million person-years of follow-up from the UK Biobank (UKB) cohort, we (I) evaluated the association of individual metabolites with incident HF via fitting of per-metabolite COX proportional hazards models and (II) trained and validated elastic net (EN) models to predict incident HF using the serum metabolome. Discriminative performance was benchmarked against a comprehensive, well-validated clinical risk score (Pooled Cohort Equations to Prevent HF, PCP-HF). External validation was conducted in the independent FINRISK study. Results Several metabolites were independently associated with incident HF (90/168 adjusting for age and sex, 48/168 adjusting for PCP-HF). Performance-optimized risk models effectively retained key predictors representing highly correlated clusters (≈ 80 % feature reduction). The addition of metabolomics to PCP-HF improved predictive performance (Harrel’s C: 0.768 vs. 0.755, ΔC = 0.013 (95% confidence interval (CI) 0.004 – 0.022), continuous net reclassification improvement (NRI) = 0.287 (95% CI 0.200 – 0.367), relative integrated discrimination improvement (IDI): 17.47 % (95% CI 9.463 - 27.825)). Simplified models only including age, sex and metabolomics performed almost as well as the PCP-HF model (Harrel’s C: 0.745 vs. 0.755, ΔC = 0.010 (95% CI -0.004 - 0.027), continuous NRI: 0.097 (95% CI -0.025 - 0.217), relative IDI: 13.445 % (95% CI -10.608 - 41.454)). Risk and survival stratification was improved by integrating metabolomics. External validation within FINRISK revealed similar patterns using the original model coefficients. Conclusions Serum metabolomics improve the prediction of incident HF risk. Scores obtained from the combination of age, sex and metabolomics exhibit similar predictive power as clinical risk models. Offering serum metabolomics to a middle-aged cohort might significantly improve HF risk stratification, thus facilitating preventive efforts. Via a single blood draw, serum metabolomics displays a highly cost- and time-effective, standardizable, and scalable alternative to clinical risk scores involving physical measurements and history taking in addition to clinical chemistry.Relative performance (test split)ROC & DCA plots (test split)

Influence of pH on the Self‐Assembly Properties of Heterofunctional POEGMA‐Based Block Copolymers During RAFT‐PISA

ABSTRACTPOEGMA‐based block copolymers self‐assemblies with surface‐functionalized carboxylic acid or propargyl groups were synthesized by successive reversible addition‐fragmentation chain transfer (RAFT) polymerization of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) and RAFT‐mediated polymerization‐induced self‐assembly (RAFT‐PISA) in dispersion of 2‐(methacryloyloxy)‐N,N,N‐trimethylethanaminium hexafluorophosphate (METAPF6). The temperature responsive properties of the carboxylic acid–terminated POEGMA (POEGMACDP) and propargyl‐terminated POEGMA (POEGMACDPy) were studied in aqueous buffer solutions at pH 2.3 and 9.2. At pH 2.3, POEGMACDP aqueous solution exhibits a cloud point while no cloud point was observed at pH 9.2. POEGMACDPy shows a cloud point at both pH levels. The RAFT‐PISA in dispersion of METAPF6 at 75°C in either pH 2.3 or 9.2 buffer solution using POEGMACDP or POEGMACDPy as macro‐RAFT agents led to block copolymers, as confirmed by DOSY analysis. For POEGMACDP (DPn = 9), DPn,NMR,PMETAPF6 was 47 at pH 2.3 and 27 at pH 9.2 and for POEGMACDPy (DPn = 10), DPn,NMR,PMETAPF6 was 36 at pH 2.3 and 22 at pH 9.2, as shown by 1H NMR spectroscopy. Both in situ POEGMACDP‐b‐PMETAPF6 and POEGMACDPy‐b‐PMETAPF6 self‐assemblies in aqueous solutions exhibited an increase in Dh and PDI when the pH increased from 2.3 to 9.2, as measured by DLS at 20°C. TEM analyses revealed almost spherical self‐assemblies, unaffected by pH or chain‐end functionality.

Discovery of New Thiourea Derivatives as Potential SIRT Inhibitors

Objective: This study aimed to design and synthesize novel thiourea-based compounds targeting Sirtuins (SIRTs), a class of histone deacetylase enzymes implicated in various cellular processes, including cancer, and to evaluate their cytotoxic potential against colon cancer cells. Methods: Virtual modeling and molecular docking studies were conducted to design the compounds and assess their interaction with SIRT enzymes. Compounds showing acceptable docking scores were selected for organic synthesis. The final compounds (MA-1 to MA-6) were synthesized and characterized using FTIR, ¹H-NMR, and ¹³C-NMR spectroscopy. Cytotoxicity studies were performed on SW480 colon cancer cells to evaluate the biological activity of the synthesized compounds. Results: All synthesized compounds exhibited promising cytotoxicity against SW480 colon cancer cells, with MA-2 demonstrating a particularly strong effect. The half-maximal inhibition concentration (IC50) of the compounds was in the single-digit micromolar range, comparable to established SIRT inhibitors Selisistat and AGK2. Conclusion: The thiourea-based compounds synthesized in this study, especially MA-2, showed significant potential as SIRT inhibitors with cytotoxic activity against colon cancer cells. These results warrant further investigation into their therapeutic potential.

Effect of bacterial dissociation on lipopolysaccharide structure: A study of O-polysaccharide from the marine bacterium Pseudoalteromonas agarivorans KMM 232 (O-form)

The lipopolysaccharide (LPS) was obtained from a bacterium Pseudoalteromonas agarivorans KMM 232 (O-form) isolated from a seawater sample collected at a depth of 500 m. The O-polysaccharide (OPS) was isolated by mild acid degradation of the LPS and studied by chemical methods along with 1D and 2D 1H and 13C NMR spectroscopy, including 1H,1H COSY, 1H,1H TOCSY, 1H,1H ROESY and 1H,13C HSQC, and 1H,13C HMBC experiments. The following new structure of the OPS from P. agarivorans KMM 232 (O-form) containing 2-acetamido-2-deoxy-d-glucose (D-GlcNAc), d-glucose (D-Glc), d-glucuronic acid (D-GlcA), 4,6-O-[(R)-1-carboxyethylidene]-d-galactose [D-Galp4,6 (R-Pyr)] and two residues of d-galactose (D-Gal) was established:

Divalent transition metal complexes with mixed of β-enaminone and N,O-donor ligands: synthesis, characterization and biological assessment

This study extensively describes the synthesizing and characterizing of new β-enaminone complexes derived from dimedone and amines coordinated with transition metals Fe(II), Co(II), Ni(II), and Cu(II), also two ligand's metformin (Met) and 8-hydroxyquinoline (8-hq). These were determined via FT-IR, 1H-NMR, electron and mass spectroscopy, molar electrical conductivity, thermal analysis (TGA, DTA and DSC) and characterized by metal content determination (%), magnetic susceptibility and elemental analysis (C.H.N.) and SEM technique. The measurements indicate that the complexes have six coordination numbers, where the β-enaminone is coordinated as tetradentate ligand through the two nitrogen atoms and the two oxygen atoms beside metformin is coordinated through the two nitrogen atoms and 8-hydroxyquinoline is coordinated by oxygen and nitrogen atoms as bidentate ligands. The conductance suggests that all complexes have electrolytic behavior, being conductive in a ratio of (1:2). SEM results revealed the presence of nanostructures on sample surfaces. The biological activity of the prepared ligands and complexes are studied in different concentrations for four types of bacteria Staphylococcus aureus has (+G) and Escherichia coli, Pseudomonas aeruginosa, Klebsiella have (-G), well as, the influence of the fungus. The ligands have disparate effectiveness while complexes have high effectiveness inhibiting the bacteria and fungus. KEY WORDS: Mixed ligand systems, Dimedone, β-Enaminone ligands, Transition metals, Biological application Bull. Chem. Soc. Ethiop. 2025, 39(1), 65-78. DOI: https://dx.doi.org/10.4314/bcse.v39i1.5

Crystal structures and photophysical properties of mono- and dinuclear ZnII complexes flanked by triethylammonium

Two new zinc(II) complexes, triethylammonium dichlorido[2-(4-nitrophenyl)-4-phenylquinolin-8-olato]zinc(II), (C6H16N){Zn(C21H13N2O3)Cl2] (ZnOQ), and bis(triethylammonium) {2,2′-[1,4-phenylenebis(nitrilomethylidyne)]diphenolato}bis[dichloridozinc(II)], (C6H16N)2[Zn2(C20H14N2O2)Cl4] (ZnBS), were synthesized and their structures were determined using ESI–MS spectrometry, 1H NMR spectroscopy, and single-crystal X-ray diffraction. The results showed that the ligands 2-(4-nitrophenyl)-4-phenylquinolin-8-ol (HOQ) and N,N′-bis(2-hydroxybenzylidene)benzene-1,4-diamine (H2BS) were deprotonated by triethyl-amine, forming the counter-ion Et3NH+, which interacts via an N—H...O hydrogen bond with the ligand. The ZnII atoms have a distorted trigonal–pyramidal (ZnOQ) and distorted tetrahedral (ZnBS) geometries with a coordination number of four, coordinating with the ligands via N and O atoms. The N atoms coordinating with ZnII correspond to the heterocyclic nitrogen for the HOQ ligand, while for the H2BS ligand, it is the nitrogen of the imine (CH=N). The crystal packing of ZnOQ is characterized by C—H...π interactions, while that of ZnBS by C—H...Cl interactions. The emission spectra showed that ZnBS complex exhibits green fluorescence in the solid state with a small band-gap energy, and the ZnOQ complex does exhibit non-fluorescence.

Promising Anti-Inflammatory Properties of Ursolic Acid Isolated from Atylosia goensis.

Indigenous plants are plant species that are native to a specific region and have evolved naturally and adapted to local environmental conditions over a long period. This study aimed to explore the anti-arthritic effects of Atylosia goensis, an indigenous plant species in the Western Ghats of India. An ethanolic extract of Atylosia goensis was obtained using the Soxhlet extraction method, which revealed a diverse array of phytochemicals through liquid chromatography-mass spectroscopy (LC-MS). Key compounds, including fatty acids, sterols, and potential health-beneficial compounds, were identified, and one prominent phytoconstituent, ursolic acid, was spectroscopically characterized using 1H NMR, 13C NMR, and mass spectrometry. The research also examined the anti-inflammatory activity and in-vitro and in-vivo anti-arthritic activity of ethanolic extract. The ethanol extract exhibited notable inhibition of Cox-2, indicating potential anti-inflammatory effects. The in vivo anti-arthritic activity of ursolic acid was evaluated at different doses (200 and 400 mg/kg) over a 24-day period. Ursolic acid significantly reduced joint edema, particularly at higher doses, thereby emphasizing its anti-inflammatory properties. Biomarker analysis revealed dose-dependent attenuation of disease-associated biomarker levels, supporting the potential therapeutic efficacy of ursolic acid in arthritis management. Moreover, the hepatoprotective potential of ursolic acid was evident in biochemical parameters, including SGPT, SGOT, and ALP levels. Both doses of ursolic acid effectively mitigated liver dysfunction induced in the disease control group, demonstrating its protective role in liver health. Histopathological assessments corroborated these findings, indicating a reduction in inflammatory areas following ursolic acid treatment, especially at higher doses. This experimental work provides valuable information on the therapeutic potential of Atylosia goensis and ursolic acid, emphasizing their roles in anti-inflammatory and hepatoprotective applications. This study contributes to the understanding of plant-derived compounds for potential pharmaceutical use in the management of inflammatory and arthritic conditions.