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ABSTRACT Herein, pyrazinamide (L1) was used as a powerful ligand to promote a CuSO4‐catalyzed reaction between aryl halides and imidazole (HID) under mild conditions, generating various N‐arylation products in good to excellent yields. The findings indicate that CuSO4 was reduced and coordinated with L1 to form [CuIL1], which activated ArX to produce [ArCuIL1X] through oxidative addition. This intermediate subsequently underwent reductive elimination to form N‐arylation products, with [ArCuILID] being generated from a reaction between [ArCuIL1X] and HID. This method was successfully extended to the synthesis of 2‐phenylindole and pyrrolo[1,2‐a]quinoxaline under mild conditions. The method significantly enhances the efficiency and cost effectiveness of C‐N coupling reaction. [ABSTRACT FROM AUTHOR]

Oligo‐adenine (polyA) is primarily known for its critical role in mRNA stability, translational status, and gene regulation. Beyond its biological functions, extensive research has unveiled the diverse applications of polyA. In response to environmental stimuli, single polyA strands undergo distinctive structural transitions into diverse secondary configurations, which are reversible upon the introduction of appropriate counter‐triggers. In this review, we systematically summarize recent advances of noncanonical structures derived from polyA, including A‐motif duplex, A‐cyanuric acid triplex, A‐coralyne‐A duplex, and T ⋅ A‐T triplex. The structural characteristics and mechanisms underlying these conformations under specific external stimuli are addressed, followed by examples of their applications in stimuli‐responsive DNA hydrogels, supramolecular fibre assembly, molecular electronics and switches, biosensing and bioengineering, payloads encapsulation and release, and others. A detailed comparison of these polyA‐derived noncanonical structures is provided, highlighting their distinctive features. Furthermore, by integrating their stimuli‐responsiveness and conformational characteristics, advanced material development, such as pH‐cascaded DNA hydrogels and supramolecular fibres exhibiting dynamic structural transitions adapting environmental cues, are introduced. An outlook for future developments is also discussed. These polyA derived, stimuli‐responsive, noncanonical structures enrich the arsenal of DNA "toolbox", offering dynamic DNA frameworks for diverse future applications. [ABSTRACT FROM AUTHOR]

The phosphinito–phosphinous acid ligand (PAP) is a singular bidentate-like self-assembled ligand exhibiting dissymmetric but interchangeable electronic properties. This unusual structure has been used for the generation of active palladium hydride through alcohol oxidation. In this paper, we report the first theoretical highlight of the adaptative modulation ability of this ligand within a direct H-abstraction path for Pd and Pt catalyzed alcohol oxidation. A reaction forces study revealed rearrangements in the ligand self-assembling system triggered by a simple proton shift to promote the metal hydride generation via concerted six-center mechanism. We unveil here the peculiar behavior of the phosphinito–phosphinous acid ligand in this catalysis. [ABSTRACT FROM AUTHOR]

Lead halide perovskite solar cells (PSCs) have demonstrated power conversion efficiencies comparable to silicon‐based solar cells, yet their instability under environmental stressors, such as humidity, heat, and light, remains a significant barrier to commercialization. A primary cause of this instability is the uncoordinated lead ions (Pb2+), which accelerates the degradation of PSCs and pose environmental concerns due to potential lead leakage. Recently, the introduction of ligands into PSCs has shown promise in mitigating lead toxicity through effective passivation, primarily by forming hydrogen bonds (H‐bonds) between functional groups of the ligands and the perovskite structure. In this minireview, we explore the critical role of H‐bonds in stabilizing PSCs by enhancing the structural integrity of the perovskite layer and reducing lead leakage. Furthermore, we discuss the contribution of these ligands in defect passivation, hydrophobicity, self‐encapsulation, cross‐linking, and self‐healing mechanisms. These insights will highlight the multi‐functional capabilities of ligands in improving the long‐term stability and durability of PSCs, offering pathways to address current challenges in their commercialization. [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]

The development of photocatalysts must be meticulous, especially when they are designed to degrade hazardous dyes that cause mutagenesis and carcinogenesis. In this meticulous approach, Ni-based metal–organic frameworks with different ligands, including terephthalic acid (NTP), 2-aminoterephthalic acid (NATP), and their composite with g-C3N4 (NTP/GCN, and NATP/GCN) have been synthesized using hydrothermal method. Structural analysis by XRD and ATR-IR revealed synergistic properties due to robust chemical interactions between the NATP-MOFs and GCN systems. A flower-like morphology was observed for both NTP and NATP, while their composites showed mixed-particulate structures mimicking the morphology of GCN. Optical analyses indicated visible-light driven properties with modulated recombination resistance in the system. Among the synthesized bare and composite systems, NATP/GCN exhibited the highest photocatalytic degradation efficiency for the cationic rhodamine B dye (~ 93% in 120 min), while it was relatively less efficient for the anionic Congo red dye, (~ 64% in 120 min). The insights gained from the fundamental characterizations including Mott–Schottky, scavenger, and electrochemical impedance analysis revealed that the amino-groups in NATP/GCN composite offered the band edge potentials suitable for the effective generation of energetic radical species with the improved carrier delocalization, recombination resistance, and charge transfer properties in the composite system through Z-scheme formation. Parametric investigations by varying the concentration of catalyst, dye, and pH along with recycle studies, demonstrated the excellent stability of the developed composites for sustainable photocatalytic applications. [ABSTRACT FROM AUTHOR]

Multidentate bis‐NHCs ligands with various spacers are expected to combine the advantages of coordination chemistry and catalysis. These offer opportunities to construct various organometallic frameworks involving transition metals and main group elements. Therefore, developing a general procedure for synthesizing a variety of carbene salt precursors using a convenient technique is key in this context. The extended protocol of a solvent‐free approach for synthesizing various bridged bis‐imidazolium carbene salts, including tris and tetrakis‐imidazolium precursors, is reported here. This method can be performed in the laboratory, leading to high yields (80–95 %) and isolated as analytically pure, multigram, bench‐stable compounds. [ABSTRACT FROM AUTHOR]

Organometallic complexes, which include ligands such as carbon monoxide (CO), carbenes, alkyls, phenyls, p-bound alkynes, alkenes, cyclopentadienyls, and arenes, have been extensively utilized in fields like materials chemistry and catalysis. These complexes also offer opportunities for the development of new medications with unique modes of action. Specifically, we are interested in anticancer drugs that can enhance the effectiveness of platinum treatments, broaden their range of action, reduce adverse effects, and prevent resistance. The distinct physiochemical properties of organometallic complexes have made them valuable in homogeneous catalysis, including the production of lead compounds and therapeutic possibilities. Over the past 20 years, a small group of researchers worldwide has explored the medical applications of these compounds’ unique characteristics, such as their structural diversity, potential for ligand exchange, and redox and catalytic properties. The results have been remarkable, and it is anticipated that numerous other organometallic compounds will undergo clinical trials in the coming years in addition to those already underway. In this brief study, we outline the advantages that organometallic metal complexes have over coordination compounds and pure organic molecules. [ABSTRACT FROM AUTHOR]

In protein‐ligand docking, the score assigned to a protein‐ligand complex is approximate. Especially, the internal energy of the ligand is difficult to compute precisely using a molecular mechanics based force‐field, introducing significant noise in the rank‐ordering of ligands. We propose an open‐source protocol (https://github.com/UnixJunkie/MMO), using two quantum mechanics (QM) single point energy calculations, plus a Monte Carlo (Monte Carlo) based ligand minimization procedure in‐between, to estimate ligand strain after docking. The MC simulation uses the ANI‐2x (QM approximating) force field and is performed in the dihedral space. On some protein targets, using strain filtering after docking allows to significantly improve hit rates. We performed a structure‐based virtual screening campaign on nine protein targets from the Laboratoire d'Innovation Thérapeutique—PubChem assays dataset using Cambridge crystallographic data centre genetic optimization for ligand docking. Then, docked ligands were submitted to the strain estimation protocol and the impact on hit rate was analyzed. As for docking, the method does not always work. However, if sufficient active and inactive molecules are known for a given protein target, its efficiency can be evaluated. [ABSTRACT FROM AUTHOR]

Insights into the molecular mechanism and factors affecting nitrite‐to‐NO transformation at transition metal sites are essential for developing sustainable technologies relevant to NO‐based therapeutics, waste water treatment, and agriculture. A set of copper(II)–nitrite complexes 1–4 have been isolated employing tridentate pincer‐type ligands (quL, pyL, ClArOL−, PhOL−) featuring systematically varied donors. Although the X‐ray crystal structures of the copper(II)–nitrite cores in 1–4 are comparable, electrochemical studies on complexes 1–4 reveal that redox properties of these complexes differ due to the changes in the σ‐donor abilities of the phenolate/N‐heterocycle based donor sites. Reactivity of these nitrite complexes with oxygen‐atom‐transfer (OAT) reagent (e. g. triphenyl phosphine Ph3P) and H+/e− donor reagent (e. g. substituted phenols ArOH) show the reduction of nitrite to NO gas. Detailed kinetic investigations including kinetic isotope effect (KIE), Eyring analyses for determining the activation parameters unfold that reduction of nitrite at copper(II) by Ph3P or ArOH are influenced by the CuII/CuI redox potential. Finally, this study allows mechanism driven development of catalytic nitrite reduction by ArOH in the presence of 10 mol % copper complex (1). [ABSTRACT FROM AUTHOR]

Fluorescent molecules have enabled single-molecule detection of toxins, biomarkers, and pollutants under controlled conditions. Unfortunately, these fluorophores are typically organic molecules that degrade or become photobleached when applied to non-ideal systems. Noble metal nanoclusters, in particular gold nanoclusters (AuNCs), pose a solution to the problems of degradation and photobleaching. Despite the low fluorescence quantum yield of AuNCs without thiolated ligands, labeling these clusters with fluorescent ligands allows enhancement of the fluorescence intensity and manipulation of the emission wavelength. In this work, we explore the labeling of the bi-icosahedron Au25 (bi-Au25) nanocluster. The bi-Au25 nanocluster has unique stability and electrochemical properties making it an attractive, yet poorly studied, candidate for fluorescent labeling. In order to demonstrate its potential as a near-IR emitting nanocluster we synthesized and labeled the bi-Au25 with the novel fluorophore 6-(9-Anthryl)-5-hexyne-1-thiol, or simply anthracenethiol. Two common ligands used in the synthesis of bi-Au25 are hexanethiol and phenylethanethiol, and we spectroscopically verify the ability for the straight-chain alkane hexanethiol to block the labeling of bi-Au25, while the aromatic phenylethanethiol enables the labeling of the complex. These products are characterized with square wave voltammetry, UV-vis and fluorescence spectrophotometry, and NMR spectrometry. The fluorescently labeled bi-Au25 nanocluster demonstrates a 25x increase in NIR photoluminescence at ~ 810 nm when originally capped with phenylethanethiol, and not the long-chain alkanethiol. The quantum yield of this cluster has been improved from 0.0786% in the unlabeled cluster to 1.97% in the labeled product. [ABSTRACT FROM AUTHOR]

This computational study explores the copper (I) chloride catalyzed synthesis of (E)‐1‐(2,2‐dichloro‐1‐phenylvinyl)‐2‐phenyldiazene (2Cl‐VD) from readily available hydrazone derivative and carbon tetrachloride (CCl4). 2Cl‐VD has been extensively utilized to synthesize variety of heterocyclic organic compounds in mild conditions. The present computational investigations primarily focus on understanding the role of copper (I) and N1,N1,N2,N2‐tetramethylethane‐1,2‐diamine (TMEDA) in this reaction, TMEDA often being considered a proton scavenger by experimentalists. Considering TMEDA as a ligand significantly alters the energy barrier. In fact, it is only 8.3 kcal/mol higher compared to the ligand‐free (LF) route for the removal of a chlorine atom to form the radical ·CCl3 but the following steps are almost barrierless. This intermediate then participates in attacking the electrophilic carbon in the hydrazone. Crucially, the study reveals that the overall potential energy surface is thermodynamically favorable, and the theoretical turnover frequency (TOF) value is higher in the case of Cu(I)‐TMEDA complex catalyzed pathway. [ABSTRACT FROM AUTHOR]

In this study, new ligand was prepared by condensation reaction between Ibuprofen and 5-amino salicylic acid (IAS), this prepared ligand was used to prepare three complexes of triorgnotin(IV) salts to obtain the corresponding complexes. The ligand (IAS) and complexes were characterized by several techniques such as infrared spectroscopy, (tin, proton and carbon) magnetic resonance (1H, 13C, 119Sn NMR), elemental analyses. The antioxidant activity of the complexes was also studied. It was produced by two methods: DPPH and CUPRAC. The resulting complexes gave a higher rate of inhibition than the ligand due to the presence of the tin element in the complexes. Complex 1 (tri phenyltin-IAS) also shown greater antioxidant activity than the other compounds. [ABSTRACT FROM AUTHOR]

Platinum nanoclusters (PtNCs) are promising in catalysis due to their large specific surface area and unique physicochemical properties. Here, ultrasmall and uniform PtNCs are facilely synthesized with the mediation of amidine‐functionalized polyamines patched on mesoporous poly(divinylbenzene‐4‐vinylbenzyl chloride) beads. When each ligand patch has 14 amidines, ultrafine PtNCs (with the size as low as 1.1±0.1 nm) are formed as a result of several factors: deprotonated amidines (carbenes) strongly passivate on Pt atoms, amidines act as co‐stabilizers along with weak polyamine ligands, and PtNCs are confined to discrete ligand patches. When one ligand patch contains 9.3 amidines, the resulting PtNCs (1.7±0.3 nm) reach the highest turnover frequency of 536 h−1 for the catalytic reduction of 4‐nitrophenol in a batch reaction. This catalyst remains rather stable in a continuous flow test as a 4‐nitrophenol conversion of over 95 % is still achieved after running consecutively for 10 h. [ABSTRACT FROM AUTHOR]

Patient specific treatments for different cancers are currently being actively addressed through nuclear medicine. More recently, the identification of biomarker namely; prostate-specific membrane antigen (PSMA) expressed on the prostate cancer cell surface has been considered as a turning point in prostate cancer management using radiopharmaceuticals. In this treatment method, apart from radionuclide, organic ligands that target PSMA constitute an essential component. PSMA-11 and PSMA-617 are two important ligands that form the radiopharmaceuticals, [68Ga]Ga-PSMA-11, [177Lu]Lu-PSMA-617, which are currently powering the prostate cancer management, especially metastatic castration resistant prostate cancer (mCRPC) in most part of the world. Identification of efficient synthetic routes towards these highly expensive ligands is an important prerequisite to make this treatment modality more popular. In this account, the synthetic challenges that we circumvent during the solution phase synthesis of PSMA-11 and PSMA-617, through different chemical synthetic routes are demonstrated. Post-synthesis, both the ligands, PSMA-11 and PSMA-617 were successfully radiolabelled using 68Ga, and 177Lu, respectively, to generate corresponding labelled products [68Ga]Ga-PSMA-11, and [177Lu]Lu-PSMA-617, in good radiochemical purity. [ABSTRACT FROM AUTHOR]

Abstract 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 $$\:{10}^{6}$$ M− 1 cm− 1 and the intense phosphorescence bands reflected good photodynamic activity. The metal complexes are thermally stable.

Abstract The development of photocatalysts must be meticulous, especially when they are designed to degrade hazardous dyes that cause mutagenesis and carcinogenesis. In this meticulous approach, Ni-based metal–organic frameworks with different ligands, including terephthalic acid (NTP), 2-aminoterephthalic acid (NATP), and their composite with g-C3N4 (NTP/GCN, and NATP/GCN) have been synthesized using hydrothermal method. Structural analysis by XRD and ATR-IR revealed synergistic properties due to robust chemical interactions between the NATP-MOFs and GCN systems. A flower-like morphology was observed for both NTP and NATP, while their composites showed mixed-particulate structures mimicking the morphology of GCN. Optical analyses indicated visible-light driven properties with modulated recombination resistance in the system. Among the synthesized bare and composite systems, NATP/GCN exhibited the highest photocatalytic degradation efficiency for the cationic rhodamine B dye (~ 93% in 120 min), while it was relatively less efficient for the anionic Congo red dye, (~ 64% in 120 min). The insights gained from the fundamental characterizations including Mott–Schottky, scavenger, and electrochemical impedance analysis revealed that the amino-groups in NATP/GCN composite offered the band edge potentials suitable for the effective generation of energetic radical species with the improved carrier delocalization, recombination resistance, and charge transfer properties in the composite system through Z-scheme formation. Parametric investigations by varying the concentration of catalyst, dye, and pH along with recycle studies, demonstrated the excellent stability of the developed composites for sustainable photocatalytic applications.

By combining tandem asymmetric gold catalysis and subsequent stereoconvergent hydrolysis of enol ester in a one-pot process, hydroxylated propargylic esters are converted into chiral β-oxygenated ketones with mostly good enantiomeric ratios and in largely good to excellent yields. The product chiral center is formed via stereoselective cyclization of a hydroxylated allenyl ester intermediate, which is enabled by asymmetric gold-ligand cooperation.

[Display omitted] Cesium lead halide perovskite nanocrystals (IPNCs) exhibit excellent optoelectronic properties but are susceptible to degradation in practical environments due to their ionic surface and unstable ligand capping. Here, we propose a post-synthesis surface passivation strategy for CsPbX 3 (X = Br, I) IPNCs by employing combined zinc halide and zinc phenylbutyrate (Zn(PA) 2) as surface ligands. ZnBr 2 fills surface halide vacancies on IPNCs, resulting in high photoluminescence efficiency, whereas Zn(PA) 2 stabilizes IPNCs by substituting surface ammonium ligands. Additionally, the −PA capping endows IPNCs with high solubility in polystyrene (PS), enabling the direct fabrication of highly efficient and uniform IPNCs-PS color conversion films through in situ polymerization of the IPNC-styrene solution. The resulting IPNCs-PS films displayed significantly enhanced stability, retaining excellent PL persistence after 1000 h of photoaging. This novel ligand and modification method presents a promising strategy for improving the efficiency and stability of IPNCs, facilitating their potential applications in display backlight and other optoelectronic applications. [ABSTRACT FROM AUTHOR]

Abstract Background The TetR family of transcriptional regulators (TFRs), serving as crucial regulators of diverse cellular processes, undergo conformational changes induced by small-molecule ligands, which either inhibit or activate them to modulate target gene expression. Some ligands of TFRs in actinomycetes and their regulatory effects have been identified and studied; however, regulatory mechanisms of the TetR family in the lincomycin-producing Streptomyces lincolnensis remain poorly understood. Results In this study, we found that AbrT (SLCG_1979), a TetR family regulator, plays a pivotal role in regulating lincomycin production and morphological development in S. lincolnensis. Deletion of abrT gene resulted in increased lincomycin A (Lin-A) production, but delayed mycelium formation and sporulation on solid media. AbrT directly or indirectly repressed the expression of lincomycin biosynthetic (lin) cluster genes and activated that of the morphological developmental genes amfC, whiB, and ftsZ. We demonstrated that AbrT bound to two motifs (5′-CGCGTACTCGTA-3′ and 5′-CGTACGATAGCT-3′) present in the bidirectional promoter between abrT and SLCG_1980 genes. This consequently repressed abrT itself and its adjacent gene SLCG_1980 that encodes an arabinose efflux permease. D-arabinose, not naturally occurring as L-arabinose, was identified as the effector molecule of AbrT, reducing its binding affinity to abrT-SLCG_1980 intergenic region. Furthermore, based on functional analysis of the AbrT homologue in Saccharopolyspora erythraea, we inferred that the TetR family regulator AbrT may play an important role in regulating secondary metabolism in actinomycetes. Conclusions AbrT functions as a regulator for governing lincomycin production and morphological development of S. lincolnensis. Our findings demonstrated that D-arabinose acts as a ligand of AbrT to mediate the regulation of lincomycin biosynthesis in S. lincolnensis. Our findings provide novel insights into ligand-mediated regulation in antibiotic biosynthesis.

Abstract Background Colorectal cancer (CRC) is ranked as the third most commonly diagnosed cancer and the third cause of cancer related deaths. CRC is greatly attributed to genetic and epigenetic mutations and immune dysregulation. Tumor aberrant expression of Toll-like Receptors (TLRs) can contribute to tumorigenesis. Recent studies suggested that microRNAs act as direct ligands of TLRs altering their expression and signaling pathways. Aim To prove our concept that specific miRNA mimics may act as antagonists of their specific toll like receptors inhibiting their expression that could limit the release of pro-inflammatory and pro-tumorigenic cytokines leading to apoptosis of tumor cells. Methods From public microarray databases, we retrieved TLRs and miRNAs related to CRC followed by in silico docking of the selected miRNA ligands into the TLRs. Clinical validation after co-immunoprecipitation of TLRs and their interacting miRNA ligands was done. Expression of TLRs 1, 7,8 was determined by ELISA while miRNAs was measured by RT-qPCR. In addition, microRNA mimics of the down regulated miRNAs were transfected into human CRC cell lines. Results Our data demonstrate that TLRs 1, 7, 8 are up regulated in CRC compared to controls. Further, three miRNAs (-122, -29b and -15b) are relatively downregulated, while 4 miRNAs (-202, miRNA-98, -21 and -let7i) are upregulated in CRC patients compared to those with benign tumor and healthy controls. Transfection of down regulated miRNA mimics into CRC cell lines resulted in a significant reduction of the number and viability of cells as well as down regulating the expression of TLRs 1, 7 and 8 with ultimate reduction of downstream effector IL6 protein, suggesting that these miRNAs are negative regulators of carcinogenesis. Conclusion MicroRNAs could act as antagonistic ligands of TLRs limiting the inflammatory tumor microenvironment.

Abstract Several different signaling pathways that regulate cell proliferation and differentiation are initiated by binding of ligands to cell-surface and membrane-bound enzyme-linked receptors, such as receptor tyrosine kinases and serine-threonine kinases. They prompt phosphorylation of tyrosine and serine-threonine residues and initiate downstream signaling pathways and priming of intracellular molecules that convey the signal in the cytoplasm and nucleus, with transcriptional activation of specific genes enriching cell growth and survival-related cascades. These cell processes are rhythmically driven by molecular clockworks endowed in every cell type and when deregulated play a crucial role in cancer onset and progression. Growth factors and their matching receptor-dependent signaling are frequently overexpressed and/or dysregulated in many cancer types. In this review we focus on the interplay between biological clocks and Growth Factor Receptor-dependent signaling in the context of carcinogenesis.

Abstract Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes. Encapsulating α-emitting radionuclides within nanoparticles can help overcome many of these challenges. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are a biodegradable and biocompatible delivery platform that has been used for drug delivery. In this study, PLGA nanoparticles are utilized for encapsulation and retention of actinium-225 ([225Ac]Ac3+). Encapsulation of [225Ac]Ac3+ within PLGA nanoparticles (Zave = 155.3 nm) was achieved by adapting a double-emulsion solvent evaporation method. The encapsulation efficiency was affected by both the solvent conditions and the chelation of [225Ac]Ac3+. Chelation of [225Ac]Ac3+ to a lipophilic 2,9-bis-lactam-1,10-phenanthroline ligand ([225Ac]AcBLPhen) significantly decreased its release (

As a class of semiconductor nanocrystals that exhibit high photoluminescence quantum yield (PLQY) at tunable wavelengths, perovskite nanocrystals (PNCs) are attractive candidates for optoelectronic and light‐emitting devices. However, attempts to optimize PNC integration into such applications suffer from PNC instability and loss of PL over time. Here, we describe the impact of organic and polymeric N‐oxides when used in conjunction with PNCs, whereby a significant increase in PNC quantum yield is observed in solution, and stable PL emission is obtained in polymeric nanocomposites. Specifically, when using aliphatic N‐oxides in ligand exchange with CsPbBr3 PNCs in solution, a substantial boost in PNC brightness is observed (~40% or more PLQY increase), followed by an alteration of the perovskite chemistry. When N‐oxide substituents are positioned pendent to a poly(n‐butyl methacrylate) backbone, the optically clear flexible nanocomposite films obtained have bright PL emission and maintain optical clarity for months. X‐ray diffraction is useful for characterizing the PNC crystalline structure following exposure to aliphatic N‐oxides, while electron microscopy (EM) and small‐angle X‐ray scattering (SAXS) measurements of the PNC‐polymer nanocomposites show this polymeric N‐oxide platform to cleanly disperse PNCs in flexible polymer films. [ABSTRACT FROM AUTHOR]

Secreted signaling peptides are central regulators of growth, development, and stress responses, but specific steps in the evolution of these peptides and their receptors are not well understood. Also, the molecular mechanisms of peptide-receptor binding are only known for a few examples, primarily owing to the limited availability of protein structural determination capabilities to few laboratories worldwide. Plants have evolved a multitude of secreted signaling peptides and corresponding transmembrane receptors. Stress-responsive SERINE RICH ENDOGENOUS PEPTIDES (SCOOPs) were recently identified. Bioactive SCOOPs are proteolytically processed by subtilases and are perceived by the leucine-rich repeat receptor kinase MALE DISCOVERER 1-INTERACTING RECEPTOR-LIKE KINASE 2 (MIK2) in the model plant Arabidopsis thaliana. How SCOOPs and MIK2 have (co)evolved, and how SCOOPs bind to MIK2 are unknown. Using in silico analysis of 350 plant genomes and subsequent functional testing, we revealed the conservation of MIK2 as SCOOP receptor within the plant order Brassicales. We then leveraged AI-based structural modeling and comparative genomics to identify two conserved putative SCOOP-MIK2 binding pockets across Brassicales MIK2 homologues predicted to interact with the "SxS" motif of otherwise sequence-divergent SCOOPs. Mutagenesis of both predicted binding pockets compromised SCOOP binding to MIK2, SCOOP-induced complex formation between MIK2 and its coreceptor BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1, and SCOOP-induced reactive oxygen species production, thus, confirming our in silico predictions. Collectively, in addition to revealing the elusive SCOOP-MIK2 binding mechanism, our analytic pipeline combining phylogenomics, AI-based structural predictions, and experimental biochemical and physiological validation provides a blueprint for the elucidation of peptide ligand-receptor perception mechanisms. [ABSTRACT FROM AUTHOR]

Background: The TetR family of transcriptional regulators (TFRs), serving as crucial regulators of diverse cellular processes, undergo conformational changes induced by small-molecule ligands, which either inhibit or activate them to modulate target gene expression. Some ligands of TFRs in actinomycetes and their regulatory effects have been identified and studied; however, regulatory mechanisms of the TetR family in the lincomycin-producing Streptomyces lincolnensis remain poorly understood. Results: In this study, we found that AbrT (SLCG_1979), a TetR family regulator, plays a pivotal role in regulating lincomycin production and morphological development in S. lincolnensis. Deletion of abrT gene resulted in increased lincomycin A (Lin-A) production, but delayed mycelium formation and sporulation on solid media. AbrT directly or indirectly repressed the expression of lincomycin biosynthetic (lin) cluster genes and activated that of the morphological developmental genes amfC, whiB, and ftsZ. We demonstrated that AbrT bound to two motifs (5′-CGCGTACTCGTA-3′ and 5′-CGTACGATAGCT-3′) present in the bidirectional promoter between abrT and SLCG_1980 genes. This consequently repressed abrT itself and its adjacent gene SLCG_1980 that encodes an arabinose efflux permease. D-arabinose, not naturally occurring as L-arabinose, was identified as the effector molecule of AbrT, reducing its binding affinity to abrT-SLCG_1980 intergenic region. Furthermore, based on functional analysis of the AbrT homologue in Saccharopolyspora erythraea, we inferred that the TetR family regulator AbrT may play an important role in regulating secondary metabolism in actinomycetes. Conclusions: AbrT functions as a regulator for governing lincomycin production and morphological development of S. lincolnensis. Our findings demonstrated that D-arabinose acts as a ligand of AbrT to mediate the regulation of lincomycin biosynthesis in S. lincolnensis. Our findings provide novel insights into ligand-mediated regulation in antibiotic biosynthesis. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) reported that of all the non-communicable diseases, cancer is considered the second cause of death worldwide. This has driven the big pharma companies to prioritise anticancer products in their pipeline. In addition, research has focused on exploration of new anticancer molecules and design of suitable dosage forms to achieve effective drug delivery to the tumour site. Nanotechnology is a valuable tool to build nano delivery systems with controlled and targeted drug release properties. Nanoparticles can be fabricated by robust, scalable and economic techniques using various polymers. Moreover, specific functional groups can be introduced to the surface of nanoparticles enabling targeting to a specific tissue; besides, they exhibit versatile drug release patterns according to the rate of polymer degradation. This review outlines the processes and advances in surface functionalisation of nanoparticles employed for treatment of breast cancer. The therapeutic molecules, the polymers used to fabricate nanoparticles, the techniques used to prepare the nanoparticles have been reviewed with a focus on the processes employed to functionalise these nanoparticles with suitable ligands to target different types of breast cancer. [ABSTRACT FROM AUTHOR]

A novel 1D coordination polymeric copper complex based on 4‐(4′‐nitrophenylhydrazono)‐5‐trifluoromethyl‐2,4‐dihydropyrazol‐3‐one was prepared and characterized spectroscopically and thermally and via X‐ray crystallographic investigation. The prepared copper‐based structure was proved to have a 1D coordination polymer. X‐ray studies showed that the polymeric copper complex was of octahedral geometry, the ligand acted as a bidentate ligand, and the nitro group attached to the ligand acted as a bridging group. The cytotoxic activities of the copper polymer were evaluated including against MCF‐7 cells (breast cancer cell line), HepG‐2 cells (hepatocellular carcinoma), and HCT‐116 cells (colon cancer cell line). The morphological alterations of the complex treated cells were investigated using an inverted microscope. The cell cycle and apoptosis were evaluated and reported. The copper polymer exhibited the best antitumor activity against HepG‐2 cells (35.22 ± 4.80 μM) while also causing a decline in the G2/M phase and a remarkable enhancement in the early apoptosis. [ABSTRACT FROM AUTHOR]

This study presents a comprehensive analysis of N-(9H-purin-6-yl) Benzamide (NPB) using a combination of Density Functional Theory (DFT) calculations and experimental techniques. The molecular configuration of NPB was optimized using DFT/B3LYP method employing the 6-311++G (d,p) basis set. The fundamental frequencies were calculated and assigned, which agree well with the experimental results. The UV-Vis spectroscopic analyses, HOMO-LUMO energy gap assessment, Molecular Electrostatic Potential calculation, and Mulliken charge analysis, Fukui function calculation and Natural bond orbital analysis were performed for the NPB molecule. The UV-Visible spectral analysis, which predicts the transition of bonding and anti-bonding π-electrons from the purine ring to the aromatic ring of the NPB molecule. A smaller energy gap in the HOMO-LUMO analysis reveals that the NPB molecule is more reactive and Mulliken atomic charge distribution analysis indicates that the carbon atoms are highly influenced by their substituents. Natural Bond Orbital (NBO) analysis was employed to investigate the bonding within the NPB molecule. The Fukui function analysis indicates that the biological activity of the NPB molecule. In order to analyze the structure of NPB molecule, the thermodynamic properties in the temperature range 100–1000 K were obtained by thermodynamic analysis software SHERMO calculator. The molecular docking analysis was carried out for antimalarial proteins (5ZNC, 2BMA, 7E27, 7E26) using auto-docking simulations. This computational method confirms the bioactivity and drug-likeness parameters of the NPB molecule. The molecular docking results predicts the formation of hydrogen bonds between the ligand (NPB) and the protein receptors. Based on these findings, this study establishes that the distinctive methodology applied to identify NPB molecule as a potential candidate for an antimalarial drug designing, which is suitable for in vivo and in vitro investigations. [ABSTRACT FROM AUTHOR]

Synthesis of PSMA-617, a peptide based ligand used in the preparation of nuclear medicine, 177Lu-PSMA-617, for the treatment of prostate cancer, is demonstrated in 6 steps, starting from appropriately protected amino acid building blocks. A solution phase Boc-strategy was adopted for the synthesis of peptide, wherein deprotection of carbamate group using HCl (g), was employed as the key step. The synthesis furnished PSMA-617 in purity >99.5 % as confirmed by HPLC analysis. ESI-MS and NMR analysis supported the structural integrity of the compound. The synthesized ligand was radiolabelled using 177Lu to generate the desired radiopharmaceutical, 177Lu-PSMA-617, in radiochemical purity >98 %, as revealed by radio HPLC and TLC analysis. This establishes its potential as a nuclear medicine for therapeutic application. [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome caused by a coronavirus is a recent viral infection. There is no scientific evidence or clinical trials to indicate that possible therapies have demonstrated results in suspected or confirmed patients. This work aims to perform a virtual screening of 1430 ligands through molecular docking and to evaluate the possible inhibitory capacity of these drugs about the Mpro protease of Covid-19. The selected drugs were registered with the FDA and available in the virtual drug library, widely used by the population. The simulation was performed using the MolAiCalD algorithm, with a Lamarckian genetic model (GA) combined with energy estimation based on rigid and flexible conformation grids. In addition, molecular dynamics studies were also performed to verify the stability of the receptor-ligand complexes formed through analyses of RMSD, RMSF, H–Bond, SASA, and MMGBSA. Compared to the binding energy of the synthetic redocking coupling (−6.8 kcal/mol/RMSD of 1.34 Å), which was considerably higher, it was then decided to analyze the parameters of only three ligands: ergotamine (−9.9 kcal/mol/RMSD of 2.0 Å), dihydroergotamine (−9.8 kcal/mol/RMSD of 1.46 Å) and olysio (−9.5 kcal/mol/RMSD of 1.5 Å). It can be stated that ergotamine showed the best interactions with the Mpro protease of Covid-19 in the in silico study, showing itself as a promising candidate for treating Covid-19. [ABSTRACT FROM AUTHOR]

Remarkable progress has characterized the field of electrocatalysis in recent decades, driven in part by an enhanced comprehension of catalyst structures and mechanisms at the nanoscale. Atomically precise metal nanoclusters, serving as exemplary models, significantly expand the range of accessible structures through diverse cores and ligands, creating an exceptional platform for the investigation of catalytic reactions. Notably, ligand‐protected Au nanoclusters (NCs) with precisely defined core numbers offer a distinct advantage in elucidating the correlation between their specific structures and the reaction mechanisms in electrocatalysis. The strategic modulation of the fine microstructures of Au NCs presents crucial opportunities for tailoring their electrocatalytic performance across various reactions. This review delves into the profound structural effects of Au NC cores and ligands in electrocatalysis, elucidating their underlying mechanisms. A detailed exploration of the fundamentals of Au NCs, considering core and ligand structures, follows. Subsequently, the interaction between the core and ligand structures of Au NCs and their impact on electrocatalytic performance in diverse reactions are examined. Concluding the discourse, challenges and personal prospects are presented to guide the rational design of efficient electrocatalysts and advance electrocatalytic reactions. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer (CRC) is ranked as the third most commonly diagnosed cancer and the third cause of cancer related deaths. CRC is greatly attributed to genetic and epigenetic mutations and immune dysregulation. Tumor aberrant expression of Toll-like Receptors (TLRs) can contribute to tumorigenesis. Recent studies suggested that microRNAs act as direct ligands of TLRs altering their expression and signaling pathways. Aim: To prove our concept that specific miRNA mimics may act as antagonists of their specific toll like receptors inhibiting their expression that could limit the release of pro-inflammatory and pro-tumorigenic cytokines leading to apoptosis of tumor cells. Methods: From public microarray databases, we retrieved TLRs and miRNAs related to CRC followed by in silico docking of the selected miRNA ligands into the TLRs. Clinical validation after co-immunoprecipitation of TLRs and their interacting miRNA ligands was done. Expression of TLRs 1, 7,8 was determined by ELISA while miRNAs was measured by RT-qPCR. In addition, microRNA mimics of the down regulated miRNAs were transfected into human CRC cell lines. Results: Our data demonstrate that TLRs 1, 7, 8 are up regulated in CRC compared to controls. Further, three miRNAs (-122, -29b and -15b) are relatively downregulated, while 4 miRNAs (-202, miRNA-98, -21 and -let7i) are upregulated in CRC patients compared to those with benign tumor and healthy controls. Transfection of down regulated miRNA mimics into CRC cell lines resulted in a significant reduction of the number and viability of cells as well as down regulating the expression of TLRs 1, 7 and 8 with ultimate reduction of downstream effector IL6 protein, suggesting that these miRNAs are negative regulators of carcinogenesis. Conclusion: MicroRNAs could act as antagonistic ligands of TLRs limiting the inflammatory tumor microenvironment. Key points: • Specific miRNAs were identified by in silico docking as signaling antagonists of 3 TLRs and were validated in clinical samples. • TLRs 1, 7, 8 were upregulated while their miRNAs (-122, -29b and -15b)were down regulated in CRC. • Transfection of downregulated miRNA mimics into CRC cell lines resulted in downregulation of TLRs that was associated with reduction in IL6 protein and tumor growth. • The present study proposed a novel approach that enables a reliable integration of Toll like receptors and miRNAs in CRC pathogenesis. [ABSTRACT FROM AUTHOR]

Strigolactones (SLs) are plant hormones with significant roles in plant growth, development and environmental interactions. SLs were first discovered to stimulate the germination of parasitic plants such as Striga and Orobanche, but they have now been revealed to regulate a variety of physiological processes in plants. Since their detection as germination stimulants, SLs have received a lot of attention for their several activities in controlling shoot branching, stress responses and symbiotic interactions with beneficial microorganisms. This review examines recent bioinformatics approaches to evaluating SLs and their receptors. By thoroughly exploring the significance of SLs in plant biology, this article highlights the potential for interdisciplinary research to fully use SLs in agriculture and other applications. [ABSTRACT FROM AUTHOR]

Novel 1-phenyl(1-thiophen-2-yl)-4-(diphenylphosphoryl)butane-1,3-diones were synthesized by the Claisen-type condensation of 1-(diphenylphosphoryl)propan-2-one with ethyl phenyl(thiophene-2-yl)carboxylates. The tautomeric equilibrium of diketone moiety of phosphine oxides was investigated by 1H and 13C{1H} NMR spectroscopy. Two species out of five possible tautomers (diketo and mono-enol) were observed in the solution of 1-phenyl(1-thiophen-2-yl)-4-(diphenylphosphoryl)butane-1,3-diones. The major tautomer was the mono-enol form with content 80–90%. Furthermore, the double bond position at C3 atom was determined by 13C{1H} NMR spectroscopy. [ABSTRACT FROM AUTHOR]

This study examined the formation of palladium (II) complex compounds with γ-glutamic acid amide in aqueous solutions and calculated the complex stability constants, also known as formation constants. After the complexes were separated from one another, each compound's structure and characteristics were studied individually. Based on data from NMR, IR, and UV spectroscopy it was established, that two ligand molecules coordinate in a monodentate manner along the donor nitrogen atoms of the amino group and in a bidentate manner along the nitrogen atoms of the amino group and oxygen. A planar square internal coordination sphere is formed in the trans- structure, respectively, in the complexes [Pd2Namine2Cl] ([PdL2Cl2]), [Pd2Namine2Ocarb] ([Pd(НL)2]). [ABSTRACT FROM AUTHOR]

This study presents the synthesis and electrocatalytic performance of the cobalt(III) complex [Co3(μ1,1,1‐O)(μ1,3‐CH3CO2)(L)3]2(DMF)3 (Cotri), featuring a double deprotonated (N,O)‐donor ligand (L2‐), where the protonated form of it (H2L) is 2,2′‐(hydrazine‐1,2‐diylidenebis(ethan‐1‐yl‐1‐ylidene))diphenol. The X‐ray structure reveals a trinuclear cobalt cluster formed with three cobalt(III) centers interlinking through oxido (μ1,1,1‐O) and acetato (μ1,3‐O2CCH3) bridges in coupling with bis‐congregator‐type chelating ligands. Cotri adopts cobalt centers of octahedral and trigonal bipyramidal coordination geometries and bears a dominant Co(2)...H(DMF) agostic interactions appraised by lattice dimethyl formamide (DMF) molecules. Further, Cotri shows promising heterogeneous electrocatalytic hydrogen evolution activity in 1 M KOH, with an overpotential of 441 mV to achieve 10 mA/cm2 current density. Tafel slope analysis suggests the Volmer–Heyrovsky step as the rate‐determining step. The number of active sites and TOF for Cotri were estimated at 4.010 × 10−8 mol and 0.2467 s−1, respectively, ensuring its excellent hydrogen generation activity. Stability assessments through controlled potential electrolysis (CPE) and cyclic voltammetry (CV) for multiple cycles addressed the transformation of Cotri to Co2O3 nanoparticles, which turned out to be a more active Co2O3 electrocatalyst. The morphology and particle size of the in situ developed Co2O3 active catalyst under the electrochemical conditions attributes to the superior hydrogen evolution activity. [ABSTRACT FROM AUTHOR]

In the present study, metal complexes of Mn(II), Ni(II), Co(II), Cu(II) and Hg(II) were synthesized using new Tetraazamacrocyclic Schiff Base (5E,8E,14E,17E)-6,8,15,17-tetramethyl-1,2,3,4,4a,7,9a,10,11,12,13,13a,16,18a-tetradecahydrodibenzo [b,i][1,4,8,11]tetraazacyclotetradecine (L) derived from 1,2-diamino cyclo hexane with the acetyl acetone. Compounds have been exanimated and confirmed by fourier-transform infrared (FT-IR), ultraviolet-visible (UV-visible), proton nuclear magnetic resonance (¹HNMR), carbon nuclear magnetic resonance (13CNMR), microelemental analyses (CHN), thermal analysis (TG), conductivity and magnetic susceptibility. The propose geometry for all complexes [MLCl2] structures were octahedral. Thermogravimetric of cobalt complex was carried out in two steps by fission into several small aggregates. [ABSTRACT FROM AUTHOR]

To fight against the present pandemic scenario of COVID-19 outbreak, medication with drugs and vaccines is extremely essential other than ventilation support. In this paper, we present a list of ligands which are expected to have the highest binding affinity with the S-glycoprotein of 2019-nCoV and thus can be used to make the drug for the novel coronavirus. Here, we implemented an architecture using 1D convolutional networks to predict drug–target interaction (DTI) values. The network was trained on the KIBA (Kinase Inhibitor Bioactivity) dataset. With this network, we predicted the KIBA scores (which gives a measure of binding affinity) of a list of ligands against the S-glycoprotein of 2019-nCoV. Based on these KIBA scores, we are proposing a list of ligands (33 top ligands based on best interactions) which have a high binding affinity with the S-glycoprotein of 2019-nCoV and thus can be used for the formation of drugs. [ABSTRACT FROM AUTHOR]

Several different signaling pathways that regulate cell proliferation and differentiation are initiated by binding of ligands to cell-surface and membrane-bound enzyme-linked receptors, such as receptor tyrosine kinases and serine-threonine kinases. They prompt phosphorylation of tyrosine and serine-threonine residues and initiate downstream signaling pathways and priming of intracellular molecules that convey the signal in the cytoplasm and nucleus, with transcriptional activation of specific genes enriching cell growth and survival-related cascades. These cell processes are rhythmically driven by molecular clockworks endowed in every cell type and when deregulated play a crucial role in cancer onset and progression. Growth factors and their matching receptor-dependent signaling are frequently overexpressed and/or dysregulated in many cancer types. In this review we focus on the interplay between biological clocks and Growth Factor Receptor-dependent signaling in the context of carcinogenesis. [ABSTRACT FROM AUTHOR]

Targeted alpha therapy (TAT) relies on chemical affinity or active targeting using radioimmunoconjugates as strategies to deliver α-emitting radionuclides to cancerous tissue. These strategies can be affected by transmetalation of the parent radionuclide by competing ions in vivo and the bond-breaking recoil energy of decay daughters. The retention of α-emitting radionuclides and the dose delivered to cancer cells are influenced by these processes. Encapsulating α-emitting radionuclides within nanoparticles can help overcome many of these challenges. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles are a biodegradable and biocompatible delivery platform that has been used for drug delivery. In this study, PLGA nanoparticles are utilized for encapsulation and retention of actinium-225 ([225Ac]Ac3+). Encapsulation of [225Ac]Ac3+ within PLGA nanoparticles (Zave = 155.3 nm) was achieved by adapting a double-emulsion solvent evaporation method. The encapsulation efficiency was affected by both the solvent conditions and the chelation of [225Ac]Ac3+. Chelation of [225Ac]Ac3+ to a lipophilic 2,9-bis-lactam-1,10-phenanthroline ligand ([225Ac]AcBLPhen) significantly decreased its release (< 2%) and that of its decay daughters (< 50%) from PLGA nanoparticles. PLGA nanoparticles encapsulating [225Ac]AcBLPhen significantly increased the delivery of [225Ac]Ac3+ to murine (E0771) and human (MCF-7 and MDA-MB-231) breast cancer cells with a concomitant increase in cell death over free [225Ac]Ac3+ in solution. These results demonstrate that PLGA nanoparticles have potential as radionuclide delivery platforms for TAT to advance precision radiotherapy for cancer. In addition, this technology offers an alternative use for ligands with poor aqueous solubility, low stability, or low affinity, allowing them to be repurposed for TAT by encapsulation within PLGA nanoparticles. [ABSTRACT FROM AUTHOR]

The opioid crisis in the United States is a significant public health issue, with a nearly threefold increase in opioid-related fatalities between 1999 and 2014. In response to this crisis, society has made numerous efforts to mitigate its impact. Recent advancements in understanding the structural intricacies of the κ opioid receptor (KOR) have improved our knowledge of how opioids interact with their receptors, triggering downstream signaling pathways that lead to pain relief. This review concentrates on the KOR, offering crucial structural insights into the binding mechanisms of both agonists and antagonists to the receptor. Through comparative analysis of the atomic details of the binding site, distinct interactions specific to agonists and antagonists have been identified. These insights not only enhance our understanding of ligand binding mechanisms but also shed light on potential pathways for developing new opioid analgesics with an improved risk-benefit profile. [ABSTRACT FROM AUTHOR]

The environmental factor aryl hydrocarbon receptor (AhR), a key protein connecting the external environmental signals (e.g., environmental endocrine disruptor TCDD) to internal cellular processes, is involved in the activation of peripheral macrophages and inflammatory response in human body. Thus, there is widespread interest in finding compounds to anti‐inflammatory response in macrophages by targeting human AhR. Here, ensemble docking based‐virtual screening was first used to screen a library (~200,000 compounds) against human AhR ligand binding domain (LBD) and 25 compounds were identified as potential inhibitors. Then, 9 out of the 25 ligands were found to down‐regulate the mRNA expression of CYP1A1 (a downstream gene of AhR signaling) in AhR overexpressing macrophages. The most potent compound AE‐411/41415610 was selected for further study and found to reduce both mRNA and protein expressions level of CYP1A1 in mouse peritoneal macrophage. Moreover, protein chip signal pathway analysis indicated that AE‐411/41415610 play a role in regulating JAK–STAT and AKT–mTOR pathways. In sum, the discovered hits with novel scaffolds provided a starting point for future design of more effective AhR‐targeted lead compounds to regulate CYP1A1 expression of inflammatory peritoneal macrophages. [ABSTRACT FROM AUTHOR]

Cancer is considered the world's deadliest disease, and its underlying pathology is intricate. Though cancer patients have had access to chemotherapeutics since aeons, the traditional treatments sometimes cause discomfort, have unwanted side effects, and are not site-specific. In this regard, several nanomaterials have lately been developed and explored specifically for use in cancer treatment ascribable to their unique optically active, magnetic, and electrical properties owing to nano-sized (1 to 100 nm) particles. Targeting, improved bioavailability, and low toxicity are vital reasons for nanomedicines becoming increasingly popular. Nanoparticles actively and passively target the cancer cells and kill them. Various ligands, including aptamers, biomolecules, peptides and/or antibodies have been in use for active targeting of cancer, while the cell characteristics, like leaky vasculature, angiogenesis etc., of cancer cells facilitate passive targeting. Focusing on nano oncology research investigations and clinical applications, this review traces the development and current state of targeted cancer therapy using nanomaterials. Also, this article furnishes account of challenges hindering the reach of these materials to clinical applications. [ABSTRACT FROM AUTHOR]

The optimization of photoluminescence (PL) spectral bandwidths in InP‐based colloidal quantum dots (QDs) faces limitations with traditional synthetic methods. This study introduces a novel approach utilizing light‐induced thiolate ligand detachment to selectively precipitate QDs within an ensemble, triggered by photons whose energy matches the red tail of the band‐edge absorption peak. We demonstrate that incorporating benzoquinone as an electron acceptor under inert conditions crucially enhances the efficiency of photoexcited hole‐induced ligand detachment. Through careful optimization of laser exposure conditions, we successfully narrowed the PL bandwidth of InP/ZnSe/ZnS QDs from 39 to 35 nm. Our findings offer significant insights into the development of high‐performance QD‐based displays, promising advancements in color purity. [ABSTRACT FROM AUTHOR]

The synthesis of a new tetracationic porphyrin derivative is described. Contrary to the best known derivatives in the literature, which are derived from 5,10,15,20-tetrakis-4-pyridylporphyrin (TPyP), in this procedure we start from 5,10,15,20-tetrakis-(4-carboxymethoxyphenyl)porphyrin (TPPCOOMe), obtained by the condensation reaction between pyrrole and 4-formylbenzoate. The reaction is carried out in refluxed xylene, avoiding the use of halogenated solvents. The final product, 5,10,15,20-tetrakis-(4-(3-carbamoyl-pyridyl)-methylphenyl)porphyrin bromide (P15p), exhibits four cationic portions that make it soluble in water and suitable for G4 stabilization. The choice to synthesize a derivative of TPPCOOMe is based on the idea of having a possible stabilizer that, unlike those obtained from TPyP, shows the cationic moieties farther from the porphyrin core and thus closer to the phosphate groups present on the G4 loops. [ABSTRACT FROM AUTHOR]

4-(tris(4-methyl-1H-pyrazol-1-yl)methyl)aniline was prepared in a 63% yield utilizing a C–F activation strategy from a mixture of 4-(trifluoromethyl)aniline, 4-methylpyrazole, and KOH in dimethylsulfoxide (DMSO). The identity of the product was confirmed by nuclear magnetic resonance spectroscopy, infrared spectroscopy, mass spectrometry, and single-crystal analysis. An analysis of crystals grown from the layering method (CH2Cl2/acetone/pentane) indicated two distinct polymorphs of the title compound. Moreover, density functional theory calculations utilizing the MN15L density functional and the def2-TZVP basis set indicated that 4-(tris(4-methyl-1H-pyrazol-1-yl)methyl)aniline forms with similar energetics to the previously reported unmethylated analog. [ABSTRACT FROM AUTHOR]

Two solvent models, COSMO (old parametrization) and COSMO2 (new parametrization) are compared for a set of protein–ligand complexes in quantum quasi-docking, which is two-stage docking: positioning of a ligand in a target protein and calculation of binding enthalpy of the protein–ligand system using the PM7 quantum-chemical semiempirical method. In quantum quasi-docking, a wide spectrum of unique low-energy minima of the protein–ligand system is first found while employing the classical force field. Then energies of all these minima are recalculated within one of the continual models using the modern PM7 method with allowance for the solvent, and the global energy minimum is determined among the recalculated energies. The solution of the quantum quasi-docking problem is the position of the ligand in the protein corresponding to the global minimum of the protein–ligand system energy calculated by the quantum-chemical method with allowance for the solvent. Effectiveness of quantum quasi-docking is defined by the value (below 2 Å) of the root-mean-square deviation of ligand atoms from one another in two positions, namely, the position of the ligand in the protein corresponding to the calculated global energy minimum and the experimentally found crystallized position of the ligand with the protein. Comparison is performed for ten protein–ligand test complexes with well-defined structures taken from the Protein Data Bank, for which the ligand–protein binding enthalpy is measured and the positioning of the ligand in the protein is successful in quasi-docking within both solvent models used. In both methods, PM7 + COSMO and PM7 + COSMO2, a high correlation coefficient of the experimental and calculated ligand–protein binding enthalpy is obtained for both calculation techniques. Allowance for moveability of protein atoms in calculations of binding enthalpy leads to an increase in its negative values and to a slight decrease in the correlation coefficient of the experimental and calculated values. The role of hydrogen bonds between protein and ligand atoms is revealed: their contribution to binding enthalpy ranges from 14 to 24% for different complexes. The results indicate the way of implementing quantum docking so that the global minimum of the protein–ligand system energy calculated by the quantum-chemical technique is immediately obtained using the global optimization procedure. [ABSTRACT FROM AUTHOR]