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Gold nanoclusters (Au NCs) exhibit broad fluorescent spectra from visible to near-infrared regions and good enzyme-mimicking catalytic activities. Combined with excellent stability and exceptional biocompatibility, the Au NCs have been widely exploited in biomedicine such as biocatalysis and bioimaging. Especially, the long fluorescence lifetime and large Stokes shift attribute Au NCs to good probes for fluorescence sensing and biological detection. In this review, we systematically summarized the molecular structure and fluorescence properties of Au NCs and highlighted the advances in fluorescence sensing and biological detection. The Au NCs display high sensitivity and specificity in detecting iodine ions, metal ions, and reactive oxygen species, as well as certain diseases based on the fluorescence activities of Au NCs. We also proposed several points to improve the practicability and accelerate the clinical translation of the Au NCs. [ABSTRACT FROM AUTHOR]

We reported for the first time the generation of titanium (Ti) nanoparticles (NPs) in different liquids (deionized (DI) water and sodium dodecyl sulfate (SDS) solution) and at a range of temperatures (5 °C, 28 °C, 60 °C, and 80 °C) using continuous-wave high-power laser ablation in liquid (CWLAL). The CWLAL technique is a convenient and cost-effective way to generate NPs. The key outcomes of our investigation are the effects of temperature and the liquid mediums on the average size, generation rate, shape, surface charges, and crystallographic structure of the NPs. Generated NPs show consistent spherical shape regardless of liquid medium changes and temperature variation. SDS solution notably impacts NP size and generation rate with higher surface charges than DI water. For instance, at temperatures of 28 °C and 80 °C, the generation rates in SDS solution are 316 mg/hr and 309 mg/hr, with average NP sizes of 33 nm and 34 nm, respectively. In contrast, the generation rates in DI water are 96 mg/hr and 302 mg/hr, with NP sizes of 13 nm and 20 nm, respectively. The weaker crystallographic structure observed in NPs generated in SDS solution, compared to the more robust crystallographic structure of NPs synthesized in DI water. Liquid temperature plays a significant role in determining surface charges, average particle size, and molecular structure of NPs. The choice of the liquid medium and temperature can be critical for tailoring NP characteristics to specific applications. Ongoing work is being conducted to explore the possibilities of further progress in this area to generate efficient and customized NPs. [ABSTRACT FROM AUTHOR]

In this research work, we synthesized a Schiff base derivative, N,N-dimethyl-4-{[(4-nitrophenyl)imino]-methyl}aniline, denoted as (n1). The molecule (n1) was characterized using spectroscopic analyses, including FT-IR, NMR 1H, and 13C. Our compound (n1) is an unsaturated molecule, consisting of two benzylic rings connected by a methylimine bridge. The resulting system comprises seven alternating π bonds. At both ends of (n1) and in the para position, there are the N(CH3)2 group with a strong electron-donating effect and the NO2 group with a strong electron-accepting effect. The molecular structure of our compound prompted us to evaluate and study its properties in the field of NLO. The assessment of NLO properties is conducted by determining the Egap and employing density functional theory (DFT) quantum chemistry studies. The optical gap of (n1), measured using the Tauc method, is found to be 2.7 eV, serving as a reference value for the choice of the DFT functional in theoretical calculations. Quantum chemistry studies were carried out using Gaussian09 software, and the results were visualized with GaussView05. CAM-B3lyp functional was chosen for theoretical calculations due to its close agreement with experimental values. The studies confirm that (n1) exhibits significant NLO properties. Additionally, NBO (Natural Bond Orbital) analyses provide insight into the mechanism and trajectory of intramolecular charge transfer in (n1). [ABSTRACT FROM AUTHOR]

Six Schiff bases with general name 5-(diethylamino)-2-(((halophenyl)imino)methyl)phenol (where halo = 4-fluoro (H1), 2-fluoro (H2), 2-bromo (H3), 4-bromo (H4), 4-chloro (H5) and 3-chloro-4-fluoro (H6)) were prepared by the condensation reaction between 4-(diethylamino)salicylaldehyde and suitable halogenated aromatic amines. The six halogenated Schiff bases were elucidated using different spectroscopic techniques and the structure of H3 and H6 were confirmed using single-crystal X-ray crystallography. The bond lengths of C7–N1, C7–C8 and C8–C9 obtained from structural analysis for both compounds depicted their enol-tautomeric characteristic form. The Hirshfeld analysis revealed that H‧‧‧H intermolecular contacts contributed most towards the Hirshfeld surfaces of both H3 (47.6%) and H6 (39.9%). Quantum chemical calculation studies showed that H1 and H2 have the highest and lowest energy band gap (∆E = 3.80 eV for H1 and ∆E = 3.73 eV for H2), depicting H2 and H1 as the most and least chemically reactive respectively among all the compounds. α-Amylase and α-glucosidase assay were used to evaluate the antidiabetes prowess of the synthesized compounds. All the compounds exhibited lower IC50 values than acarbose (reference drug) in α-amylase assay experiments and H5 with lowest IC50 value of 63.54 μM could be suggested to have the highest α-amylase inhibitory potential among the test samples. For α-glucosidase assay, H1–H6 displayed good antidiabetic potential. However, none of the compounds outshined acarbose with H6 having highest α-glucosidase inhibitory potential when compared to others i.e., IC50 of H6 = 60.89 μM and IC50 of acarbose = 51.42 μM. We measured the antioxidant potential of H1–H6 exploring 2,2-diphenyl-1-picrylhydrazyl (DPPH), nitric oxide (NO) and ferric reducing ability power (FRAP) assays. The DPPH as well as NO radical scavenging assay showed that all the compounds exhibited excellent antioxidant results with some of the compounds surpassing catechin (reference drug). Compound H5 with IC50 values of 30.32 mM and 31.73 mM outshined catechin with IC50 values of 31.17 mM and 140.62 mM for DPPH and NO assays respectively. All the compounds fell within the threshold of Lipinski's Ro5 projecting them as orally bioavailable and less toxic future therapeutics. [ABSTRACT FROM AUTHOR]

Currently, graph-based molecular structure descriptors are frequently used in QSAR (Quantitative Structure-Activity Relationship) and QSPR (Quantitative Structure-Property Relationship) modeling of the properties of chemical compounds. Octane isomers have an important role in the testing of such relationships. In this study, we compute some well-known topological descriptors of the molecular graphs of isomeric octanes and their line graphs, both indices and coindices. Then we analyze the correlation coefficients between the physicochemical properties of the octane isomers and some well-known topological indices and their coindices of the molecular graphs and the line molecular graphs of the octane isomers, to find the particular topological descriptors that have the best predictive values. [ABSTRACT FROM AUTHOR]

The development of sequencing technology has promoted discovery of variants in the human genome. Identifying functions of these variants is important for us to link genotype to phenotype, and to diagnose diseases. However, it usually requires researchers to visit multiple databases. Here, we presented a one-stop webserver for variant function annotation tools (VCAT, https://biomed.nscc-gz.cn/zhaolab/VCAT/) that is the first one connecting variant to functions via the epigenome, protein, drug and RNA. VCAT is also the first one to make all annotations visualized in interactive charts or molecular structures. VCAT allows users to upload data in VCF format, and download results via a URL. Moreover, VCAT has annotated a huge number (1,262,041,068) of variants collected from dbSNP, 1000 Genomes projects, gnomAD, ICGC, TCGA, and HPRC Pangenome project. For these variants, users are able to searcher their functions, related diseases and drugs from VCAT. In summary, VCAT provides a one-stop webserver to explore the potential functions of human genomic variants including their relationship with diseases and drugs. [ABSTRACT FROM AUTHOR]

This research delves into a comprehensive investigation of a specific group of alkanes, with the primary objective of establishing meaningful associations between their inherent physical attributes and a set of graphical parameters ranging from topological indices to their associated graphical entropies. Though there are countless techniques to relate molecular structure and physical properties of chemical compounds, the pursuit has often been pricey and arduous. With a view to curb the expense and intense labour, this work focuses on attaining some of these properties using graphical interpretations and statistical interventions. Driven by this objective, we compute Sombor index, a recently developed topological tool and some of its variants for all structural isomers of alkanes with carbon range four to nine. Furthermore, our study employs multiple regression analysis to explore their connections with some physical attributes of alkanes while concurrently addressing the challenge posed by multicollinearity. We have adopted the technique of robust regression to scale down the impact of outliers in the dataset, while generating regression models. Further, the established results are justified with a 10-fold cross validation process and a comparison with the results obtained from different topological indices. The results of this research contribute a valuable insight to the fields of chemical informatics and structural analysis, offering an enhanced comprehension of the interplay between molecular structure and physical attributes within alkanes. [ABSTRACT FROM AUTHOR]

In this research, medications used for treating heart disease, specifically focusing on calcium channel blockers, were analyzed. A computer-based computing technique was used to simplify calculations and data analysis. Using MATLAB coding, we calculated their degree-based topological indices obtained from the M-polynomial. Various regression analyses were used to establish a relationship between these indices and the physicochemical features of the drugs. QSPR models were created to determine the effectiveness by correlating these indices with eight physicochemical features of the drugs. Confidence intervals were calculated at a 95% level for the intercept and slope in the linear regression models. The results indicate that the inverse sum indeg index (I) proved to be the most dependable indices for predicting boiling point, flashpoint, and enthalpy of vaporization. The symmetric division index (SDD) was effective in forecasting polarizability and molar refractivity, while the second modified Zagreb index ( m M 2 ) emerged as the best predictor for molar volume in linear, quadratic, and cubic regression models. Furthermore, the forgotten index (F) was identified as the top estimator for boiling point, flashpoint, enthalpy, and polar surface area in both quadratic and cubic regression models. Lastly, the SDD index, with a correlation coefficient of R = 1, is proposed as the most accurate estimator for the characteristics of polar surface area in quadratic, and cubic regression equations. Calculated feature values show a strong correlation with the actual values, indicating the indices' reliable predictive capabilities. [ABSTRACT FROM AUTHOR]

The global pandemic caused by the novel virus SARS-CoV-2 (Severe Acute Respiratory Syndrome CoronaVirus 2), also known as COVID-19, is now a serious public health concern that has affected people worldwide. The condition has become worse due to a lack of adequate treatment. To combat the pandemic, several drugs are being investigated. A topological index (or molecular descriptor) is a numerical parameter that correlates the molecular structure of a chemical compound to its various physico-chemical properties and plays a significant role in the development of QSPR/QSAR (quantitative structure–property relationship/quantitative structure-activity relationship) models. In this study, we evaluate the degree-based topological indices (namely, the Nirmala index, first and second inverse Nirmala indices, geometric-quadratic and quadratic-geometric indices) of nine antiviral drugs (namely, Molnupiravir, Remdesivir, Chloroquine, Ritonavir, Theaflavin, Arbidol, Hydroxychloroquine, Thalidomide and Lopinavir) used in the remedy of COVID-19 patients, with the help of their respective M-polynomials. Also, we calculate the neighborhood degree sum-based indices of Molnupiravir by using its neighborhood M-polynomial (that is, NM-polynomial). In addition, we execute the correlation analysis among the topological indices and physico-chemical properties of these antiviral drugs. Furthermore, we demonstrate the QSPR models for strong correlation through the linear, quadratic and cubic regression analysis to appraise the effectiveness of the topological indices. And, the squared correlation coefficients obtained from the performed curvilinear regression models are compared with those acquired in the previous studies. The obtained topological indices and established QSPR models which may be helpful to predict the pharmacokinetic properties of these antiviral drugs and in the discovery of new drugs related to the medication for the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

A general review of quantum molecular similarity structure and applications is presented. The backbone of the discussion corresponds to the general problem of the data structure associated with the mathematical representation of a molecular set. How to standardize, and how to compare it to any other problem. This computational track describes the exact isometric vectors of the similarity matrix in a Minkowskian space. The further aim is to construct a set of origin-shifted vectors forming the vertices of a molecular polyhedron. From here, one can calculate a set of statistical-like momenta, providing a set of scalars that describe in a compact form the attached molecular set. Finally, the definition of a quantum QSPR operator permits building up a system of equations that can be further employed to determine the unknown properties of molecules in the original set. This last achievement leads to a quantum QSPR algorithm comparable with the classical QSPR counterpart but described in molecular space, not parameter space. [ABSTRACT FROM AUTHOR]

Background: Many morphological and histological changes take place in aging skin. Topical tretinoin is the gold standard anti-aging agent used to reduce signs of aging through stimulation of epidermal growth and differentiation and inhibition of collagenase. Objective: The aim of this systematic review is to summarize studies evaluating the efficacy of tretinoin compared with other topical medications and cosmeceuticals in reducing the appearance of skin aging. Methods: A systematic review was conducted following the Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines. The literature search was conducted using the PubMed and Embase databases from conception to December 2023. Studies were included if they compared anti-aging outcomes of topical medications with those of topical tretinoin (also called all-trans retinoic acid and retinoic acid). Studies were excluded if they compared non-topical anti-aging treatments with tretinoin or were conducted on animal models. Results: The literature search resulted in 25 studies that met all inclusion and exclusion criteria. The most common study comparators to tretinoin included other forms of vitamin A. Outcomes were reported on the basis of visual reduction of aging signs, histological assessment of the epidermis and dermis, and protein expression. Although comparators to tretinoin had variable efficacy (greater in 7 studies, equivalent in 13 studies, and less in 3 studies), most studies found the comparator to be less irritating and better tolerated by patients than tretinoin. Discussion: Tretinoin is currently the gold standard therapy for the treatment of photoaging, but its poor tolerability often limits its use. Unfortunately, given that most studies comparing topical therapies with tretinoin are of poor quality and/or demonstrate bias, there is a lack of substantial evidence to support an alternative first-line therapy. However, given there are some data to support the efficacy of retinoid precursors, namely retinaldehyde, pro-retinal nanoparticles, and conjugated alpha-hydroxy acid and retinoid (AHA-ret), these agents can be considered a second-line option for anti-aging treatment in patients who cannot tolerate tretinoin. [ABSTRACT FROM AUTHOR]

Summary: Identifying dysregulated plasma proteins in osteoporosis (OP) progression offers insights into prevention and treatment. This study found 8 such proteins associated with OP, suggesting them as therapy targets. This discovery may cut drug development costs and improve personalized treatments. Purpose: This study aims to identify potential therapeutic targets for OP using summary data-based Mendelian randomization (SMR) and colocalization analysis methods. Furthermore, we seek to explore the biological significance and pharmacological value of these drug targets. Methods: To identify potential therapeutic targets for OP, we conducted SMR and colocalization analysis. Plasma protein (pQTL, exposure) data were sourced from the study by Ferkingstad et al. (n = 35,559). Summary statistics for bone mineral density (BMD, outcome) were obtained from the GWAS Catalog (n = 56,284). Additionally, we utilized enrichment analysis, protein–protein interaction (PPI) network analysis, drug prediction, and molecular docking to further analyze the biological significance and pharmacological value of these drug targets. Results: In the SMR analysis, while 20 proteins showed significance, only 8 potential drug targets (GCKR, ERBB3, CFHR1, GPN1, SDF2, VTN, BET1L, and SERPING1) received support from colocalization (PP.H4 > 0.8). These proteins are closely associated with immune function in terms of biological significance. Molecular docking also demonstrated favorable binding of drugs to proteins, consistent with existing structural data, further substantiating the pharmacological value of these targets. Conclusions: The study identified 8 potential drug targets for OP. These prospective targets are believed to have a higher chance of success in clinical trials, thus aiding in prioritizing OP drug development and reducing development costs. [ABSTRACT FROM AUTHOR]

Poly (ethylene glycol dimethacrylate-1,2-ethanedithiol) (P(EDGMA-EDT)) and poly (ethylene glycol dimethacrylate-3,6-dioxy-1,8-octanedithiol) (P(EDGMA-DODT)) are excellent solid polymer electrolytes synthesized experimentally. The coordination structure, redox properties, and modification design of P(EDGMA-EDT)-LiTFSI and P(EDGMA-DODT)-LiTFSI are investigated by density functional theory. The theoretical simulation of infrared spectra and the coordination structure information show that the ester carbonyl group in P(EDGMA-EDT) and the ester carbonyl group and ether oxygen in P(EDGMA-DODT) interact with Li+ ions. Li+ ion coordination numbers in these two electrolytes are 4 and 5; thioether and ester groups in polymers are their redox active sites, respectively. Modified sulfone oxide P(EDGMA-EDT)2-SO2 and P(EDGMA-DODT)2-SO2 cannot only maintain the reduction stability but also greatly improve the oxidation potential. LiPF6, LiDFBOP, and LiBF3Cl are good candidates for sulfone-based polymers. The electron-withdrawing groups (− 4Br, − 4Cl, − 4F, − NO2, and − CN) substitution can improve the oxidation potential of P(EDGMA-EDT) but have little effect on the oxidation potential of P(EDGMA-DODT) and reduce the reduction stability of both polymers. These findings provide theoretical guidance for the coordination structure as well as the molecular design of solid electrolytes containing ester groups and thioether. [ABSTRACT FROM AUTHOR]

Contamination of drug products and substances containing impurities is a significant concern in the pharmaceutical industry because it may impact the quality and safety of medicinal products. Special attention is required when mutagenic impurities are present in pharmaceuticals, as they may pose a risk of carcinogenicity to humans. Therefore, controlling potential mutagenic impurities in active pharmaceutical ingredients to an acceptable safety limit is mandatory to ensure patient safety. As per the International Council for Harmonization (ICH) M7 (R2)3 Guideline, mutagenic impurities are those compounds or materials that induce point mutations. In 2018, the sartan class of drugs was recalled due to the presence of N-nitrosamine impurities, which are potential mutagens. In addition to the primary impurities being detected, this class of products, especially losartan, irbesartan and valsartan, have been identified as having organic azido contaminants, which are again highly reactive toward DNA, leading to an increased risk of cancer. These azido impurities form during the preparation of the tetrazole moiety via the reaction of a nitrile intermediate with sodium azide. Given that this is a newly raised issue in the pharmaceutical world, it should be noteworthy to review the related literature. Thus, this review article critically accounts for (i) the toxicity of azido impurities and the proposed mechanism of mutagenicity, (ii) the regulatory perspective, and (iii) the sources and control strategies used during the preparation of drug substances and (iv) future perspectives. [ABSTRACT FROM AUTHOR]

Glycans, consisting of covalently linked sugar units, are a major class of biopolymers essential to all known living organisms. To better understand their biological functions and further applications in fields from biomedicine to materials science, detailed knowledge of their structure is essential. However, due to the extraordinary complexity and conformational flexibility of glycans, state-of-the-art glycan analysis methods often fail to provide structural information with atomic precision. Here, we combine electrospray deposition in ultra-high vacuum with non-contact atomic force microscopy and theoretical calculations to unravel the structure of β-cyclodextrin, a cyclic glucose oligomer, with atomic-scale detail. Our results, established on the single-molecule level, reveal the different adsorption geometries and conformations of β-cyclodextrin. The position of individual hydroxy groups and the location of the stabilizing intramolecular H-bonds are deduced from atomically resolved images, enabling the unambiguous assignment of the molecular structure and demonstrating the potential of the method for glycan analysis. Glycans are structurally complex biomolecules and very challenging to analyse. Here the authors show atomically resolved imaging of β-cyclodextrins with non-contact atomic force microscopy, revealing the structure of individual glycans with atomic detail. [ABSTRACT FROM AUTHOR]

Cancer is a major global health challenge, being the second leading cause of morbidity and mortality after cardiovascular disease. The growing economic burden and profound psychosocial impact on patients and their families make it urgent to find innovative and effective anticancer solutions. For this reason, interest in using natural compounds to develop new cancer treatments has grown. In this respect, antofine, an alkaloid class found in Apocynaceae, Lauraceae, and Moraceae family plants, exhibits promising biological properties, including anti-inflammatory, anticancer, antiviral, and antifungal activities. Several molecular mechanisms have been identified underlying antofine anti-cancerous effects, including the inhibition of nuclear factor κB (NF-κB) and AKT/mTOR signaling pathways, epigenetic inhibition of protein synthesis, ribosomal targeting, induction of apoptosis, inhibition of DNA synthesis, and cell cycle arrest. This study discusses the molecular structure, sources, photochemistry, and anticancer properties of antofine in relation to its structure–activity relationship and molecular targets. Then, examine in vitro and in vivo studies and analyze the mechanisms of action underpinning antofine efficacy against cancer cells. This review also discusses multidrug resistance in human cancer and the potential of antofine in this context. Safety and toxicity concerns are also addressed as well as current challenges in antofine research, including the need for clinical trials and bioavailability optimization. This review aims to provide comprehensive information for more effective natural compound-based cancer treatments. [ABSTRACT FROM AUTHOR]

To study an effective removal method of residual cephalosporin antibiotics in water, taking the ceftriaxone sodium (CFS) as a research object, the adsorption effects of the resins with different characteristic parameters for CFS were investigated in the pH range of 2.0–5.0. MTS9570, a sorbent containing sulfonic-phosphoric acid bi-functional group, was optimally selected and further to study the adsorption removal behavior to CFS in depth for the first time. Owning to the highest fitness of the pseudo-second-order and intra-particle diffusion (R2 > 0.99), two models can better describe the process of CFS onto MTS9570, indicating that the process is controlled by the chemi-sorption and intra-particle diffusion together. Compared with Freundlich and Temkin isotherm, Langmuir isotherm is the best fitness with highest R2 and lowest AIC values, indicating that there exists a monolayer adsorption on the surface of MTS9570 sorbent to CFS. ∆H < 0, ∆S > 0 and ∆G < 0, imply that the adsorption is an exothermic spontaneous process with increased randomness at the solid–liquid interface. The adsorption ability of MTS9570 after six adsorption–desorption cycles can still reach 90.13% of the initial adsorption capacity, indicating that the adsorbent has good reusability. Combining the above results with the bi-functional group of the adsorbent as well as the molecular structure of CFS, we speculate that the potential adsorption mechanism of MTS9570 to CFS may be mainly controlled by electrostatic interaction and supplemented by hydrogen bonding. [ABSTRACT FROM AUTHOR]

Alkalization changes the physicochemical, bioactive, and powder flow properties of cocoa powders, so it is an essential factor affecting the quality of cocoa products. This study investigated the relationship of the alkalization process with physicochemical properties such as color, pH, and bioactive properties such as total phenolic, flavonoid, and antioxidant capacity of cocoa powders. For this purpose, natural cocoa powders were alkalized using sodium hydroxide (NaOH) or potassium carbonate (K2CO3), or potassium hydroxide (KOH) solutions at their different concentrations. The browning index, darkness, and pH values increased while the total phenolic content, flavonoid, and antioxidant capacity decreased depending on the type of alkali used. FTIR spectra revealed changes in the stretching vibrations in the molecular structure of alkalized cocoa powders. Even though the alkalization process did not affect the microstructure of cocoa particles visibly, treatment with different alkali agents altered the thermal behavior, compressibility and caused a decrease in the powder flowability. [ABSTRACT FROM AUTHOR]

Biomedical network learning offers fresh prospects for expediting drug repositioning. However, traditional network architectures struggle to quantify the relationship between micro-scale drug spatial structures and corresponding macro-scale biomedical networks, limiting their ability to capture key pharmacological properties and complex biomedical information crucial for drug screening and therapeutic discovery. Moreover, challenges such as difficulty in capturing long-range dependencies hinder current network-based approaches. To address these limitations, we introduce the Spatial Hierarchical Network, modeling molecular 3D structures and biological associations into a unified network. We propose an end-to-end framework, SpHN-VDA, integrating spatial hierarchical information through triple attention mechanisms to enhance machine understanding of molecular functionality and improve the accuracy of virus-drug association identification. SpHN-VDA outperforms leading models across three datasets, particularly excelling in out-of-distribution and cold-start scenarios. It also exhibits enhanced robustness against data perturbation, ranging from 20% to 40%. It accurately identifies critical motifs for binding sites, even without protein residue annotations. Leveraging reliability of SpHN-VDA, we have identified 25 potential candidate drugs through gene expression analysis and CMap. Molecular docking experiments with the SARS-CoV-2 spike protein further corroborate the predictions. This research highlights the broad potential of SpHN-VDA to enhance drug repositioning and identify effective treatments for various diseases. The Spatial Hierarchical Network model enhances drug repositioning by quantifying and integrating 3D spatial network with biomedical network information and offers interpretations from biological relationships down to atomic interactions. [ABSTRACT FROM AUTHOR]

New Schiff base ligand: 4-methoxy salicaldhyde-2-2-phenyl-hydrazono acetaldehíyde prepared by facile method. The molecular structures characterized by elemental analysis and proton magnetic resonance spectra (1H-NMR spectra). This spectra at the chemical shifts (3.5–10.39 ppm) confirmed the types and the numbers of protons. The sharp melting point at the range 110–112 °C confirmed purity. New optically active metal (samarium, terbium and gadolinium) complexes of the Schiff base synthesized in a one pot reaction. Vibrational IR spectra confirmed functional groups. Scanning electron microscopy micrographs confirmed that the modified microstructure of the metal complexes differed in morphology than the ligand. Powder X-ray diffraction patterns confirmed good crystalline structure. The optically activity of the solid metal complexes confirmed from electronic absorption spectra. The UV absorbance band at the wavelength range 280–390 nm and the intense phosphorescence bands up to 830 nm enabled application in photo dynamic therapy for apoptosis cancer cells by conversion triplet oxygen in the tissues into reactive singlet oxygen. Low charge transfer energy: 2.59–2.61 eV, high molar extinction coefficients (ε) at the order of magnitude M− 1 cm− 1 and the intense phosphorescence bands reflected good photodynamic activity. The metal complexes are thermally stable. [ABSTRACT FROM AUTHOR]

Glycosphingolipids (GSL) are a highly heterogeneous class of lipids representing the majority of the sphingolipid category. GSL are fundamental constituents of cellular membranes that have key roles in various biological processes, such as cellular signaling, recognition, and adhesion. Understanding the structural complexity of GSL is pivotal for unraveling their functional significance in a biological context, specifically their crucial role in the pathophysiology of various diseases. Mass spectrometry (MS) has emerged as a versatile and indispensable tool for the structural elucidation of GSL enabling a deeper understanding of their complex molecular structures and their key roles in cellular dynamics and patholophysiology. Here, we provide a thorough overview of MS techniques tailored for the analysis of GSL, emphasizing their utility in probing GSL intricate structures to advance our understanding of the functional relevance of GSL in health and disease. The application of tandem MS using diverse fragmentation techniques, including novel ion activation methodologies, in studying glycan sequences, linkage positions, and fatty acid composition is extensively discussed. Finally, we address current challenges, such as the detection of low-abundance species and the interpretation of complex spectra, and offer insights into potential solutions and future directions by improving MS instrumentation for enhanced sensitivity and resolution, developing novel ionization techniques, or integrating MS with other analytical approaches for comprehensive GSL characterization. [ABSTRACT FROM AUTHOR]

Plant-pathogenic bacteria are one of the major constraints on agricultural yield. In order to selectively treat these bacteria, it is essential to understand the molecular structure of their cell membrane. Previous studies have focused on analyzing hydrolyzed fatty acids (FA) due to the complexity of bacterial membrane lipids. These studies have highlighted the occurrence of branched-chain fatty acids (BCFA) alongside normal-chain fatty acids (NCFA) in many bacteria. As several FA are bound in the intact phospholipids of the bacterial membrane, the presence of isomeric FA complicates lipid analysis. Furthermore, commercially available reference standards do not fully cover potential lipid isomers. To address this issue, we have developed a reversed-phase high-performance liquid chromatography (RP-HPLC) method with tandem mass spectrometry (MS/MS) to analyze the phospholipids of various plant-pathogenic bacteria with a focus on BCFA containing phospholipids. The study revealed the separation of three isomeric phosphatidylethanolamines (PE) depending on the number of bound BCFA to NCFA. The validation of the retention order was based on available reference standards in combination with the analysis of hydrolyzed fatty acids through gas chromatography with mass spectrometry (GC/MS) after fractionation. Additionally, the transferability of the retention order to other major lipid classes, such as phosphatidylglycerols (PG) and cardiolipins (CL), was thoroughly examined. Using the information regarding the retention behavior, the phospholipid profile of six plant-pathogenic bacteria was structurally elucidated. Furthermore, the developed LC–MS/MS method was used to classify the plant-pathogenic bacteria based on the number of bound BCFA in the phospholipidome. [ABSTRACT FROM AUTHOR]

Toluene solubles (TS) play a crucial role in mesophase pitch (MP), but their influence on the spinnability of MP and the properties of carbon fiber remains unclear. In this work, a solvent extraction method is employed to regulate the TS content in MP for improving its spinnability, and the MPs with different TS contents are prepared. The results show that TS, characterized as a small molecule (IOS = 0.337) with an alkyl side chain length index (Abs1460/Abs1380) of 2.012, can significantly improve the flowability of the system. Following comprehensive characterization, a unique molecular structure model is constructed. The removal of a portion of TS increases the regularity of the microcrystalline structure to a certain extent (d002 = 3.447 Å, Lc = 8.86 nm), further optimizing the spinning performance of compounded MPs with different TS contents, and improving the tensile strength and thermal conductivity of their carbon fibers. The compounded sample MP-TS-17, containing 17 wt% TS, shows superior spinning performance at a high rotary speed of 315 rpm, accompanying with an average and even diameter of 12.60 μm. The carbon fiber derived from MP-TS-17 perform an impressive tensile strength of 2.39 GPa and a high thermal conductivity of 612 W·m−1·K−1. Compared with the carbon fiber from the raw material MP, its mechanical strength and thermal conductivity are improved by 97.4% and 120%, respectively, demonstrating a promising approach for preparing high-performance petroleum-based mesophase pitch carbon fiber. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) is a global health concern caused by the bacterium Mycobacterium tuberculosis. This infectious disease primarily affects the lungs but can also impact other organs. Effective TB control involves early diagnosis, appropriate treatment with a combination of antibiotics, and public health measures to prevent transmission. However, ongoing challenges include drug-resistant strains and socioeconomic factors influencing its prevalence. Drugs such as isoniazid, pyrazinamide, ethambutol, ethionamide, linezolid, and levofloxacin are approved for the treatment of drug-susceptible tuberculosis. The properties and other activities of the drug, can be analyzed by modelling its chemical structure in terms of a molecular graph , by considering the atoms as the vertex set and the bonds between the two atoms as the edge set . A molecular descriptor or topological index of represents the corresponding chemical molecule as a numerical value. Domination is one of the key concepts in the molecular structure used to analyze the properties of atoms. In this article, the domination distance-based topological indices of the drugs isoniazid, pyrazinamide, ethambutol, ethionamide, linezolid, and levofloxacin are computed to conduct QSPR (Quantitative Structure–Property Relationship) analysis, exploring their physicochemical and ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) properties. Quadratic regression is then used in the QSPR analysis to examine the physicochemical and ADMET properties of these drugs. The results of this analysis indicate that the domination Schultz index and domination SM index are the indices most strongly correlated with the majority of the physicochemical and ADMET properties. The QSPR analysis can also be extended to analogs of these drugs and to other treatment drugs, such as rifampin and rifapentine, to further explore their properties. [ABSTRACT FROM AUTHOR]

S2P intramembrane metalloproteases regulate diverse signaling pathways across all three domains of life. However, the mechanism by which S2P metalloproteases engage substrates and catalyze peptide hydrolysis within lipid membranes has remained elusive. Here we determine the cryo-EM structure of the S2P family intramembrane metalloprotease SpoIVFB from Bacillus subtilis bound to its native substrate Pro-σK. The structure and accompanying biochemical data demonstrate that SpoIVFB positions Pro-σK at the enzyme active site through a β-sheet augmentation mechanism, and reveal key interactions between Pro-σK and the interdomain linker connecting SpoIVFB transmembrane and CBS domains. The cryo-EM structure and molecular dynamics simulation reveal a plausible path for water to access the membrane-buried active site of SpoIVFB, and suggest a possible role of membrane lipids in facilitating substrate capture. These results provide key insight into how S2P intramembrane metalloproteases capture and position substrates for hydrolytic proteolysis within the hydrophobic interior of a lipid membrane. How the S2P family of intramembrane metalloproteases engage substrates has remained unclear. Here, the authors reveal cryo-EM structures showing beta-sheet augmentation as a key factor in substrate binding, linking this mechanism to all four classes of intramembrane proteases. [ABSTRACT FROM AUTHOR]

Vorasidenib (VORANIGO®; Servier) is an orally administered, first-in-class, highly brain-penetrant dual inhibitor of mutant isocitrate dehydrogenase 1 and 2 (IDH1/2) enzymes being developed for use in IDH-mutant diffuse glioma. Vorasidenib received its first approval on 6 August 2024, in the USA, for the treatment of adult and pediatric patients aged 12 years and older with grade 2 astrocytoma or oligodendroglioma with a susceptible IDH1 or IDH2 mutation following surgery, including biopsy, sub-total resection, or gross total resection. Approval was based on results from the multinational phase III INDIGO trial, in which vorasidenib significantly improved progression-free survival and time to the next anticancer intervention relative to placebo. In the EU and other countries worldwide, regulatory review of vorasidenib in IDH-mutant glioma is currently underway. This article summarizes the milestones in the development of vorasidenib leading to this first approval for glioma. [ABSTRACT FROM AUTHOR]

Golidocitinib (高瑞哲®) is an oral, potent, selective Janus kinase 1 (JAK1) inhibitor being developed by Dizal (Jiangsu) Pharmaceutical Co., Ltd for the treatment of cancer, including peripheral T cell lymphoma (PTCL). In June 2024, golidocitinib received conditional approval in China for the treatment of adult patients with relapsed or refractory (r/r) PTCL who have received at least one line of systemic treatment. This article summarizes the milestones in the development of golidocitinib leading to this first approval for the treatment of adults with PTCL. [ABSTRACT FROM AUTHOR]

Biosensors stand at the forefront of innovation in critical fields such as medicine, food safety, and environmental monitoring, offering precise detection of specific biomarkers. Among these, polymer-based biosensors have emerged as powerful tools, evolving from inert materials to intricately tailored structures capable of precise molecular binding. Electrospinning, a prominent fabrication method, offers a cost-effective approach for developing diagnostic kits, pushing the boundaries of biosensors with exceptionally low analyte detection limits. However, the reliance on commercial polymers restricts the versatility of electrospun nanofibers due to the fixed properties and limited functionalization options of off-the-shelf materials. These constraints prevent the tailoring of nanofibers to meet specific or diverse needs, as their molecular structure and surface functionalities are not easily adjustable. A promising solution is integrating Controlled Radical Polymerization (CRP) with electrospinning. CRP provides precise control over polymer properties, enabling the creation of nanofibers with customized functionalities for various applications. This approach combines the benefits of electrospinning, such as high surface area-to-volume ratios, with the advanced capabilities of CRP to enhance the selectivity and sensitivity of biosensors. This review represents recent advancements in biosensors, covering acquisition, characterization, and applications, with a focal point on the role of functional polymers. Exploring biosensor architecture, electrospinning principles, controlled polymer synthesis, CRP techniques, and polymer topologies, the manuscript also discusses challenges and future prospects, including microfluidic integration, multi-detection capabilities, machine learning, and the development of wearable biosensors. [ABSTRACT FROM AUTHOR]

This paper investigates the significance of employing random subgraphs and analyzing the expected values of Zagreb ndices within chemical graphs. By examining smaller, representative subsets, we uncover valuable insights into the properties and characteristics of complex networks. The expected values of Zagreb indices serve as critical mathematical measures for quantifying the structural complexity of chemical graphs, providing essential information about connectivity and branching patterns within molecules. Our primary contribution includes deriving theoretical expressions for these indices and validating them through extensive computational experiments on fullerene graphs C 20 and C 60 . The results demonstrate that our theoretical predictions closely align with experimental findings, affirming the robustness of Zagreb indices in characterizing molecular structures. Additionally, our analysis of specific cases, such as complete graphs and complete bipartite graphs, is consistent with previous studies, further reinforcing our methodology. This research emphasizes the relevance of random subgraphs and expected values of Zagreb indices in advancing our understanding of molecular behavior and stability, with important implications for materials science and drug design. [ABSTRACT FROM AUTHOR]

The microphase-separated structures of block copolymers are inherently highly ordered local structures, commonly characterized by differences in domain width and curvature. By focusing on diblock copolymers, we propose local order parameters (LOPs) that accurately distinguish between adjacent microphase-separated structures on the phase diagram. We used the Molecular Assembly structure Learning package for Identifying Order parameters (MALIO) to evaluate the structure classification performance of 186 candidate LOPs. MALIO calculates the numerical values of all candidate LOPs for the input microphase-separated structures to create a dataset, and then performs supervised machine learning to select the best LOPs quickly and systematically. We evaluated the robustness of the selected LOPs in terms of classification accuracy against variations in miscibility and fraction of block. The minimum local area size required for LOPs to achieve their classification performances is closely related to the characteristic sizes of the microphase-separated structures. The proposed LOPs are potentially applicable over a large area on the phase diagram. [ABSTRACT FROM AUTHOR]

Highlights: Organic spacers in Ruddlesden–Popper (RP) perovskites play a vital role in tuning crystallization, charge transport and photovoltaic performance for RP perovskite solar cells (PSCs). Fundamental understanding of the functions of molecular structure of organic spacers is the prerequisite to design high-performance PSCs. This review proposes practical design strategies in seeking RP molecular structure to maximize its photovoltaic performance for PSCs. Layer-structured Ruddlesden–Popper (RP) perovskites (RPPs) with decent stability have captured the imagination of the photovoltaic research community and bring hope for boosting the development of perovskite solar cell (PSC) technology. However, two-dimensional (2D) or quasi-2D RP PSCs are encountered with some challenges of the large exciton binding energy, blocked charge transport and poor film quality, which restrict their photovoltaic performance. Fortunately, these issues can be readily resolved by rationally designing spacer cations of RPPs. This review mainly focuses on how to design the molecular structures of organic spacers and aims to endow RPPs with outstanding photovoltaic applications. We firstly elucidated the important roles of organic spacers in impacting crystallization kinetics, charge transporting ability and stability of RPPs. Then we brought three aspects to attention for designing organic spacers. Finally, we presented the specific molecular structure design strategies for organic spacers of RPPs aiming to improve photovoltaic performance of RP PSCs. These proposed strategies in this review will provide new avenues to develop novel organic spacers for RPPs and advance the development of RPP photovoltaic technology for future applications. [ABSTRACT FROM AUTHOR]

The DNA single-strand break (SSB) repair pathway is initiated by the multifunctional enzyme PARP-1, which recognizes the broken DNA ends by its two zinc-finger domains, Zn1 and Zn2. Despite a number of experiments performed with different DNA configurations and reduced fragments of PARP-1, many details of this interaction that is crucial to the correct initiation of the repair chain are still unclear. We performed Molecular Dynamics (MD) computer simulations of the interaction between the Zn1/Zn2 domains of PARP-1 and a DNA hairpin including a missing nucleotide to simulate the presence of an SSB, a construct used in recent experiments. The role of Zn1 and Zn2 interacting with the SSB ends is studied in detail, both independently and cooperatively. We also explored, PARP-1 operating as a dimer, with the two Zn-fingers coming from two separate copies of the enzyme. By an extensive set of all-atom molecular simulations employing state-of-the art force fields, assisted by empirical docking and free-energy calculations, we conclude that the particular conformation of the DNA hairpin can indeed spontaneously open up by thermal fluctuations, up to extremely kinked deformations. However, such extreme localized deformations are rarely observed in free, long DNA fragments. Protein side-loops make contact with the DNA hairpin grooves, and help Zn2 to penetrate deep in the SSB gap. In this way, Zn2 can interact with the nucleotides opposite to the missing base. Overall, Zn1 plays a secondary role: the crucial factor for the interaction is rather the relative arrangement of the Zn1/Zn2 couple, and their mutual orientation with respect to the 3 ′ and 5 ′ SSB end terminals. This helps to obtain an early interacting configuration, which ultimately leads to molecular PARP-1-DNA structures similar to those observed experimentally. Such findings represent an important step toward defining the detailed function of PARP-1 in the early stages of SSB recognition. [ABSTRACT FROM AUTHOR]

A method has been developed for the formation of hybrid membranes consisting of a hydrophilic microporous substrate and a hydrophobic nanofibrous polymer layer deposited by electrospinning. A track-etched poly(ethylene terephthalate) membrane has been used as the hydrophilic microporous substrate, onto the surface of which a thin layer of titanium is deposited by magnetron sputtering to provide the nanofibrous layer with adhesion. Simultaneously, this layer has been used as an electrode of a deposition collector for the electrospinning formation the nanofibrous coating. It has been shown that the application of this method for the preparation of polymer coatings using poly(vinylidene fluoride) as a starting material for the formation of nanofibers makes it possible to obtain a highly hydrophobic layer, the surface of which has an average water contact angle of 143.3 ± 1.3° depending on the deposition density. The morphological study of the nanofibrous coating has shown that its microstructure is typical of nonwoven materials. The nanofibers that form the porous system of this layer have a wide scatter of sizes. FTIR spectroscopic and X-ray diffraction investigations of the molecular structure of the nanofibrous layer have shown that the β-phase prevails in its structure, with this phase being characterized by the maximum dipole moment. It has been shown that the elaborated hybrid membranes ensure high separation selectivity of desalinating an aqueous 26.5 g/L sodium chloride solution by the membrane distillation method. In the studied regime of the membrane distillation, the salt rejection coefficient for membranes with nanofibrous layer densities of 20.7 ± 0.2–27.6 ± 0.2 g/m2 is 99.97−99.98%. It has been found that the use of a highly hydrophobic nanofibrous layer with a developed porous structure in combination with a hydrophilic microporous substrate makes it possible to increase the productivity of the membrane distillation process. The value of the maximum condensate flow through the membranes is, on average, 7.0 kg m2/h, and its value depends on the density of the deposited nanofibrous layer. [ABSTRACT FROM AUTHOR]

Context: Indandione-based materials are promising candidates for organic electronics, offering high electron mobility and tunable optoelectronic properties. In this study, we explore the optoelectronic and photovoltaic properties of indandione-based donor–acceptor (D-A) materials, specifically (R1) and (R2), by introducing malononitrile group acceptors into their molecular structure. These strong electron-withdrawing acceptors are designed to enhance charge transfer and overall material performance. The designed molecules (DM1–DM4) exhibit a low optical band gap of approximately 1.77 eV, significantly lower than the reference materials (R1 and R2) at around 2.24 eV in a solvent environment. Among the designed molecules, DM4 stands out with superior photovoltaic parameters, including a narrow optical band gap (1.77 eV), higher electron affinity (3.49 eV), an extended excited state lifetime (10.0 ns) owing to its low electron and hole reorganization energies (λe ~ 0.13 eV and λh ~ 0.24 eV), and improved short-circuit current density (Jsc) of ~ 15.73 mA/cm2. Notably, DM4 achieves a power conversion efficiency (PCE) of ~ 18.5%, making it an excellent candidate for device applications. Method: A comprehensive computational investigation was carried out on indandione-based D-A materials with malononitrile group acceptors (DM1–DM4) using density functional theory (DFT) and time-dependent DFT (TD-DFT) methods, as implemented in Gaussian 16 software. We examined the electronic and optical properties of the proposed molecules through frontier molecular orbital (FMO) analysis, UV–Vis absorption spectra, density of states (DOS), exciton binding energy (Eb), and transition density matrix (TDM) analysis, utilizing GaussView 6.0 and Multiwfn 3.8 software. The photovoltaic parameters and power conversion efficiency (PCE) were evaluated using the Scharber and Alharbi models. [ABSTRACT FROM AUTHOR]

Context: Alzheimer's disease (AD) is the leading cause of dementia around the world, totaling about 55 million cases, with an estimated growth to 74.7 million cases in 2030, which makes its treatment widely desired. Several studies and strategies are being developed considering the main theories regarding its origin since it is not yet fully understood. Among these strategies, the 5-HT6 receptor antagonism emerges as an auspicious and viable symptomatic treatment approach for AD. The 5-HT6 receptor belongs to the G protein-coupled receptor (GPCR) family and is closely implicated in memory loss processes. As a serotonin receptor, it plays an important role in cognitive function. Consequently, targeting this receptor presents a compelling therapeutic opportunity. By employing antagonists to block its activity, the 5-HT6 receptor's functions can be effectively modulated, leading to potential improvements in cognition and memory. Methods: Addressing this challenge, our research explored a promising avenue in drug discovery for AD, employing Artificial Neural Networks–Quantitative Structure-Activity Relationship (ANN-QSAR) models. These models have demonstrated great potential in predicting the biological activity of compounds based on their molecular structures. By harnessing the capabilities of machine learning and computational chemistry, we aimed to create a systematic approach for analyzing and forecasting the activity of potential drug candidates, thus streamlining the drug discovery process. We assembled a diverse set of compounds targeting this receptor and utilized density functional theory (DFT) calculations to extract essential molecular descriptors, effectively representing the structural features of the compounds. Subsequently, these molecular descriptors served as input for training the ANN-QSAR models alongside corresponding biological activity data, enabling us to predict the potential efficacy of novel compounds as 5-hydroxytryptamine receptor 6 (5-HT6) antagonists. Through extensive analysis and validation of ANN-QSAR models, we identified eight new promising compounds with therapeutic potential against AD. [ABSTRACT FROM AUTHOR]

The radiation-induced telomerization of tetrafluoroethylene in pentafluorochlorobenzene, pentafluorobromobenzene, and hexafluorobenzene has been studied. It has been shown that the process efficiency and the chain length of the resulting telomers depends on the binding energy of the substituent in the fluorinated benzene rings. An analysis of the IR spectra showed that changes in the molecular structure of telomers occurred under the influence of gamma radiation; these changes were expressed in the detachment of terminal benzene rings and the formation of terminal carboxyl groups. In addition, polymer chain degradation leading to the formation of telomers with a shorter chain length was observed. The hydrophobic properties of the samples of all irradiated telomers were preserved. [ABSTRACT FROM AUTHOR]

The aim of this study is to explain the consequences of the occurrence of enthalpy–entropy compensation (EEC) and isoequilibrium relationship during slow pyrolysis of cigarette butt filters (CBFs), consisting cellulose acetate (AC) as the main component. By using model-free and model-based kinetic methods and thermodynamic calculations, the complete reaction mechanism and extrathermodynamic issues about investigated process are completely resolved. It was established that compensation phenomenon where isoequilibrium temperature occurs is a consequence of formation of low-entropy molecular structure (cellulose II) and breaking of hydrogen bonds. Consequently, it was concluded that mechanisms which include a formation of low-entropy molecular structure and H-bonds breakage enter the changes in both enthalpy and entropy, which compensate each other. For the cellulose II generation, it was necessary to invest energy which represents use up energy. This "wasted" energy turns into work for creation of cellulose II molecular structures, whereby additional energy was provided from "local" decomposition reactions (which were identified in the established process mechanism) that arise from pyrolysis of starting material. Therefore, it was concluded that for "local reactions", a negative ΔS° value was identified, but for the global process, the entropy change retained a positive value. Considering thermodynamic effects manifested through compensation temperature found below glass transition temperature (Tg) in the undercooling conditions, it was concluded that small amounts of plasticizers affect reduction of free volume in the glassy state. Obtained results indicated a decrease in β-relaxation mode of cellulose acetate by an abatement of the polymer free volume. [ABSTRACT FROM AUTHOR]

The objective of this study was to explore the influence of different factors on the aggregation effect on hemoglobin (Hb) and enzymes during the preparation of Polyhemoglobin-Superoxide dismutase-Catalase-Carbonic anhydrase (PolyHb-SOD-CAT-CA). Several factors including temperatures, pH values, Glutaraldehyde (GDA) amounts and enzymes amounts were investigated systematically to study their effects on the enzymes recoveries and polymerization rates including the Superoxide dismutase (SOD), Catalase (CAT) and Carbonic anhydrase (CA), as well as their effects on the molecular weight distribution of PolyHb-SOD-CAT-CA. Then the oxygen affinity and methemoglobin (MetHb) contents of obtained PolyHb-SOD-CAT-CA were measured to evaluate the effects of enzyme crosslinking on the properties of Polyhemoglobin (PolyHb) moieties in the molecular structure of obtained PolyHb-SOD-CAT-CA conjugate. The results showed that the enzyme recoveries and polymerization rates could be decreased with the temperatures increasing and could be generally kept stable in the physiological pH conditions, but presented only slight changes among the investigated enzyme amounts ranges. Although the GDA concentration increasing could promote the enzyme polymerization rates, the enzyme recoveries decreased in whole. The polymerization rate and molecular size of PolyHb-SOD-CAT-CA conjugate increased with the elevation of temperature and the concentration of GDA. Lastly, the P50 values, Hill coefficients, and MetHb contents of PolyHb-SOD-CAT-CA conjugate with different enzyme crosslinking degrees exhibited no obvious differences with each other. In conclusion, the polymerization reactions between enzymes and Hb molecules could be remarkably affected by temperatures, pH values, and GDA amounts, and the enzyme crosslinking presented no obvious effects on the Hb properties, especially about the oxygen affinity and oxidation degrees. [ABSTRACT FROM AUTHOR]

A new Cd(II) derivative, [Cd(2-Hstp)(Hbipy)2] (1), was obtained hydrothermally by the combination of Cd(NO3)2·4H2O as metal salt, the flexible aromatic carboxylate, 2-sulfoterephthalic acid (2-stp), and the N-donor ancillary ligand, 4,4′-bipyridine (bipy), as organic linker. Single crystal X-ray diffraction analysis revealed the molecular structure of the complex, in which the Cd(II) atoms show a distorted octahedral geometry. In the asymmetric unit, both the carboxylate and the N-donor connector bridge pairs of cadmium ions; this ultimately leads to the formation of a set of undulated sheets formed by fused rings comprising six cadmium centers, two bipy, and four 2-stp ligands. Considering each complex as a node, the supramolecular structure can be seen as a 6-c uninodal net of the type pcu, with point symbol {412.63} and vertex symbol [4.4.4.4.4.4.4.4.4.4.4.4.*.*.*]. The Cd(II) derivative endowed the material with moderate luminescent properties. Finally, the molecular geometry of 1 has been studied by DFT computation applying the B3LYP/def2-SVP level of theory. [ABSTRACT FROM AUTHOR]

Using X-ray diffraction, IR spectroscopy, and quantum chemistry [B3LYP/6–311 + + G**, AIM], the molecular and supramolecular structures and association of 5-phenyl-1H-pyrrole-2-carbonyl azide were studied in detail. The motives for the formation of supramolecular and crystal structures have been established. A topological analysis of non-valent interactions in the crystal was carried out. A probable reason has been established for the relatively low sensitivity of 5-phenyl-1H-pyrrole-2-carbonyl azide to ionizing ultraviolet and X-ray radiation compared to other pyrrole-2-carbonyl azides. Indeed, the relative stability of the new pyrrolazide lies in the organization of associative dimeric structures, in the formation of which the nitrogen atoms of the azide fragment participate through hydrogen bonds. [ABSTRACT FROM AUTHOR]

A large data set of over 30 thousand organic compounds containing carbon, nitrogen, oxygen, fluorine, and hydrogen was collected, and the density of each compound was predicted by 1D descriptors derived from its molecular formula and 2D descriptors derived from its constitutional structural features. The 2D structural features are composed of Benson's groups, corrected groups, and 2D structural features of the whole molecular structures. All the descriptors were extracted by an in-house program in Java with a function to ensure that each atom (or bond) of molecules is represented by Benson's groups once for atom-based (or bond-based) descriptors. Partial least square (PLS) and random forest (RF) methods were used separately to build models to predict the density. Further, the variable selection of descriptors was performed by variable importance of RF. For partial least square, the combination of the models constructed by descriptors based on the atoms and the bonds achieved the best results in this paper: for the cross-validation of the training set, the Pearson correlation coefficient (R) = 0.9270, mean absolute error (MAE) = 0.0270 g·cm−3, and root mean squared error (RMSE) = 0.0426 g·cm−3; for the prediction of the test set, R = 0.9454, MAE = 0.0263 g·cm−3, and RMSE = 0.0375 g·cm−3. [ABSTRACT FROM AUTHOR]

Background: Modifying the mechanical properties of the solid phase of a porous material, in this study calcium-silicate-hydrate, is frequently possible by changing synthesis conditions, but changes in these conditions can also influence porosity, which in turn may affect the mechanical properties of the porous material. Experimental methods to decouple porosity from the viscoelastic properties of the porous material will aid in optimization of the structure of the solid phase to achieve the desired mechanical properties. Objective: Explore different nanoindentation techniques in order to determine the viscoelastic properties of the solid phase (without the affect of porosity) of a stiff porous material via experimental methods alone. Methods: Compacted pellets of calcium-silicate-hydrate were prepared with different porosity and subjected to three nanoindentation techniques to determine viscoelastic behavior and the influence of porosity: dynamic, stress relaxation, and creep. Results of the porosity and of the viscoelastic behavior measurements were analyzed with a reverse-micromechanics model to determine viscoelastic properties of the solid phase, which has not been achieved previously for calcium-silicate-hydrate. These methods can be used in development and refinement of materials to determine how changes in the solid phase (e.g. molecular structure) influence viscoelastic behavior while considering the effect of porosity. Results: Dynamic nanoindentation was found to be unreliable for the stiff material studied in this work. Normalized stress relaxation and creep data were found to be independent of porosity. Reverse micro-mechanics modeling allowed for characterization of the creep modulus that is consistent with other studies that used computational or synchrotron x-ray methods to characterize mechanical properties of the solid calcium-silicate-hydrate phase. Conclusion: Creep experiments provide more reliable data than dynamic or stress relaxation experiments. When the porosity is known, reverse-micromechanics modeling can be used determine the creep modulus of the solid phase and thus be used to predict creep modulus of a composite with an arbitrary porosity. If the porosity is not known, the viscoelastic properties of the solid phase can still be compared to each other using a normalized creep modulus that is independent of porosity. [ABSTRACT FROM AUTHOR]

The cultivated apple (Malus domestica Borkh.) is an economically important fruit crop in countries worldwide, including Bosnia and Herzegovina (BIH).The gene bank activities in BIH were initiated in the 1930s and continued until the war in the 1990s, when much of the documentation was lost. Since then, uncoordinated efforts were made to establish apple collections in different regions, but a comprehensive analysis of genetic resources was lacking. This prompted the current study where we present the first thorough overview of the national genetic resources of BIH apples. Thus, we analyzed 165 accessions in the apple gene bank at the Institute for Genetic Resources (IGR) established at Banja Luka using the 20 K apple Infinium® single nucleotide polymorphism (SNP) array. We combined the results with previously published data on the germplasm collections at Srebrenik and Goražde, genotyped using the Axiom® Apple 480 K SNP array. In total, 234 accessions were included in the study of which 220 were presumed to be local cultivars and 14 were known international reference cultivars. We identified numerous genotypic duplicates within and between collections and suggested preferred names to be used in the future. We found the BIH germplasm to have relatively few parent-offspring relationships, particularly among local cultivars, which might reflect the country's history and patterns of apple cultivar introduction. A number of cultivars unique to BIH and a weakly defined genetic group were identified via STRUCTURE analysis, representing interesting targets for future research and preservation efforts. [ABSTRACT FROM AUTHOR]

Single-molecule localization microscopy (SMLM) surpasses the diffraction limit by randomly switching fluorophores between fluorescent and dark states, precisely pinpointing the resulted isolated emission patterns, thereby reconstructing the super-resolution images based on the accumulated locations of thousands to millions of single molecules. This technique achieves a ten-fold improvement in resolution, unveiling the intricate details of molecular activities and structures in cells and tissues. Multicolor SMLM extends this capability by imaging distinct protein species labeled with various fluorescent probes, providing insights into structural intricacies and spatial relationships among different targets. This review explores recent advancements in multicolor SMLM, evaluates the strengths and limitations of each variant, and discusses the future prospects. [ABSTRACT FROM AUTHOR]

Dendrimers, distinguished by their mono-dispersed globular or spheroid macromolecular structures with repeated branches, exhibit unique and desirable characteristics that set them apart from other polymers. These characteristics include their nanoscopic size, precise control over molecular structure, low polydispersity index, water solubility, exceptional physicochemical stability, self-assembly capabilities, polyvalency, chemical stability, electrostatic interactions, solubility, and minimal cytotoxicity. Dendrimers are prepared from monomers using either divergent or convergent step-growth polymerization. Dendrimers have the ability to reduce the toxicity of medications while enhancing their effectiveness. This review will delve into various types of dendrimers such as poly (amidoamine) dendrimers, peptide dendrimers, smart dendrimers, polyethylene glycol dendrimers, poly (propylene imine) dendrimers, polyester dendrimers, Janus dendrimers, and etc. in the field of drug delivery and gene delivery systems that utilize them. Dendrimer-drug conjugates offer numerous benefits over conventional drug carriers, such as enhanced drug uptake by the tumor, reduced systemic toxicity issues, and increased antitumor activity of the administrated medications. To achieve this objective, the authors utilized the Science Direct, PubMed, and Scopus databases to acquire the information, evaluating references individually, extracting essential details, and assessing the quality of the included studies. [ABSTRACT FROM AUTHOR]

Reintroducing recycled plastics into production processes can lead to irreversible degradation and changes in their properties, thereby limiting their recycling potential to a finite number of loops. This study investigates the impact of process-induced degradation resulting from multiple reprocessing cycles on specific material properties and aims to establish structure–property relationships. Four different polyolefins, including two polypropylenes, high-density polyethylene, and low-density polyethylene, were selected for the study. The materials underwent extrusion, pelletizing, injection molding, and milling before being reintroduced into the reprocessing cycle. This sequence of processing steps was repeated six times on each material. Various characterization techniques, including high-temperature gel permeation chromatography, melt mass flow rate, parallel-plate rheology, differential scanning calorimetry, gas chromatography–mass spectrometry, and optical defect control system, were performed to evaluate the molecular structure, rheological behavior, thermal stability, and the resulting contaminants and defects after each reprocessing step. The reprocessing of polypropylene resulted in a gradual decrease in the average molecular weights accompanied by a shift to lower viscosities and higher melt mass flow rates, whereas the polyethylene grades showed the opposite trend with a less pronounced effect in high-density polyethylene. The volatile organic compounds rose in polypropylene and sank in polyethylene after reprocessing. Additionally, all four materials exhibited an increase in degradation-related defects based on optical defect analysis. [ABSTRACT FROM AUTHOR]

Nuclear receptors (NRs) play a crucial role as biological targets in drug discovery. However, determining which compounds can act as endocrine disruptors and modulate the function of NRs with a reduced amount of candidate drugs is a challenging task. Moreover, the computational methods for NR-binding activity prediction mostly focus on a single receptor at a time, which may limit their effectiveness. Hence, the transfer of learned knowledge among multiple NRs can improve the performance of molecular predictors and lead to the development of more effective drugs. In this research, we integrate graph neural networks (GNNs) and Transformers to introduce a few-shot GNN-Transformer, Meta-GTNRP to predict the binding activity of compounds using the combined information of different NRs and identify potential NR-modulators with limited data. The Meta-GTNRP model captures the local information in graph-structured data and preserves the global-semantic structure of molecular graph embeddings for NR-binding activity prediction. Furthermore, a few-shot meta-learning approach is proposed to optimize model parameters for different NR-binding tasks and leverage the complementarity among multiple NR-specific tasks to predict binding activity of compounds for each NR with just a few labeled molecules. Experiments with a compound database containing annotations on the binding activity for 11 NRs shows that Meta-GTNRP outperforms other graph-based approaches. The data and code are available at: https://github.com/ltorres97/Meta-GTNRP. Scientific contribution The proposed few-shot GNN-Transformer model, Meta-GTNRP captures the local structure of molecular graphs and preserves the global-semantic information of graph embeddings to predict the NR-binding activity of compounds with limited available data; A few-shot meta-learning framework adapts model parameters across NR-specific tasks for different NRs in a joint learning procedure to predict the binding activity of compounds for each NR with just a few labeled molecules in highly imbalanced data scenarios; Meta-GTNRP is a data-efficient approach that combines the strengths of GNNs and Transformers to predict the NR-binding properties of compounds through an optimized meta-learning procedure and deliver robust results valuable to identify potential NR-based drug candidates. [ABSTRACT FROM AUTHOR]

The P2X1 receptor is a trimeric ligand-gated ion channel that plays an important role in urogenital and immune functions, offering the potential for new drug treatments. However, progress in this area has been hindered by limited structural information and a lack of well-characterised tool compounds. In this study, we employ cryogenic electron microscopy (cryo-EM) to elucidate the structures of the P2X1 receptor in an ATP-bound desensitised state and an NF449-bound closed state. NF449, a potent P2X1 receptor antagonist, engages the receptor distinctively, while ATP, the endogenous ligand, binds in a manner consistent with other P2X receptors. To explore the molecular basis of receptor inhibition, activation, and ligand interactions, key residues involved in ligand and metal ion binding were mutated. Radioligand binding assays with [3H]-α,β-methylene ATP and intracellular calcium ion influx assays were used to evaluate the effects of these mutations. These experiments validate key ligand-receptor interactions and identify conserved and non-conserved residues critical for ligand binding or receptor modulation. This research expands our understanding of the P2X1 receptor structure at a molecular level and opens new avenues for in silico drug design targeting the P2X1 receptor. The P2X1 receptor is a promising target for the development of a non-hormonal male contraceptive. Here, researchers determined the atomic structure of the P2X1 receptor, revealing opportunities for developing drugs to target this receptor. [ABSTRACT FROM AUTHOR]

Organic semiconductors (OSCs) are featured by weak spin-orbit coupling due to their light chemical element composition, which enables them to maintain spin orientation for a long spin lifetime and show significant potential in room-temperature spin transport. Carrier mobility and spin lifetime are the two main factors of the spin transport performance of OSCs, however, their ambiguous mechanisms with molecular structure make the development of spintronic materials really stagnant. Herein, the effects of halogen substitution in bay-annulated indigo-based polymers on carrier mobility and spin relaxation have been systematically investigated. The enhanced carrier mobility with an undiminished spin lifetime contributes to a 3.7-fold increase in spin diffusion length and a record-high magnetoresistance of 8.7% at room temperature. By analyzing the spin-orbit coupling and hyperfine interaction, it was found that the distance of the substitution site from the conjugated center and the nitrogen atoms in the molecules play crucial roles in spin relaxation. Based on the above results, we proposed a molecular design strategy of halogen substitution far from conjugate center to enhance spin transport efficiency, presenting a promising avenue for advancing the field of organic spintronics. The spin transport mechanism remains unclear for organic semiconductors. Here, authors investigate the effect of halogen substitution in bay-annulated indigo-based polymers and reveal the distance of substitution site from conjugated center and nitrogen atoms play crucial roles in spin relaxation. [ABSTRACT FROM AUTHOR]

Heterocyclic compounds play a crucial role in the drug discovery process and development due to their significant presence and importance. Here, we report a comprehensive analysis of α-aminophosphonates containing pyridine (3a–g), prepared according to a clear-cut, uncomplicated procedure. The phosphonates are thoroughly characterized using various methods, such as elemental analysis, mass spectrometry, proton and carbon NMR, and FT-IR. The molecular docking interactions between the phosphonate and DRP-1 target protein observed that compound 3d had the top-ranked binding energy towards DRP-1 with a value equal to − 9.54 kcal/mol and this theoretically proves its inhibitory efficacy against DRP-1 arbitrated mitochondrial fission. Besides, the anticancer characteristics of compound 3d showed the best IC50 against HepG-2, MCF-7, and Caco-2 which confirmed our results towards suppressing DRP-1 protein (in-silico), and it elucidated no cytotoxic effects against human normal cell line (WI-38). Further, its pharmacokinetics were observed theoretically using ADMET. Moreover,compound 3d investigated the most potent antimicrobial ability against two pathological fungal strains, A. flavus and C. albicans, and four bacterial strains, E. coli, B. subtillis, S. aureus, and P. aregeunosa. Additionally, compound 3d clarified a powerful antioxidant scavenging activity against DPPH and ABTS free radicals (in-vitro). Furthermore, Density functional theory (DFT) was used to study the molecular structures of the synthesized compounds 3a–g, utilizing 6–311++G(d,p) as the basis set and to learn more about the molecules' reactive sites, the energies of the molecular electrostatic potential (MEP), the lowest unoccupied molecular orbital (LUMO), and the highest occupied molecular orbital (HOMO) were observed. Theoretically, FT-IR and Nuclear magnetic resonance (NMR) measurements are calculated for every compound under investigation to show how theory and experiment relate. It was found that there was an excellent agreement between the theoretical and experimental data. Conclusively, all novel synthesized phosphonates could be used as pharmaceutical agents against pathogenic microbial strains and as anticancer candidates by inhibiting DRP-1-mediated mitochondrial mitophagy. [ABSTRACT FROM AUTHOR]