Chemical Review and Letters

Abstract This study reports the synthesis and biological evaluation of novel quinazoline derivatives as potential inhibitors of epidermal growth factor receptor (EGFR) for lung cancer therapy. A series of quinazoline derivatives (3a–3f) were synthesized through a three-step process involving Schiff base formation, N-benzylidene amide formation, and subsequent cyclization. The structures of the synthesized compounds were confirmed using FT-IR and ¹H-NMR spectroscopy. In vitro cytotoxicity assays were conducted on the A549 lung cancer cell line to evaluate the inhibitory activity of these compounds. Molecular docking studies were performed to investigate the binding interactions between the synthesized compounds and the EGFR active site.
Cytotoxicity assays revealed that several quinazoline derivatives exhibited significant inhibitory activity. Notably, Compound IIIa demonstrated the highest potency, surpassing the IC₅₀ value of erlotinib. Molecular docking studies showed that Compounds IIIa–IIIe exhibited higher binding affinities for EGFR compared to erlotinib, correlating with the experimental IC₅₀ values. Key interactions, including hydrogen bonds with ASP831 and hydrophobic contacts with Leu718, Leu764, and Met769, were identified.
The findings suggest that these synthesized quinazoline derivatives, particularly Compound IIIa, hold promise as potential EGFR inhibitors. The correlation between docking scores and experimental IC₅₀ values validates the predictive power of molecular docking in this context. Further studies are warranted to explore their biological mechanisms and systemic effects, aiming to translate these findings into clinical applications.

Abstract This work investigates the reaction mechanism of hydrogen atom abstraction from 3-hydroxybutanal (3HB) by the chlorine (Cl) radical under atmospheric conditions, a process relevant to the degradation of volatile organic compounds (VOCs). Density Functional Theory (DFT) calculations were carried out at the B3LYP/def2-SVP level to explore five possible abstraction pathways, each involving a distinct hydrogen site within the 3HB molecule. Vibrational frequency analyses confirmed the presence of five corresponding transition states (TS1–TS5). Rate constants for each pathway were computed using KiSThelP software across a temperature range of 278–400 K. The calculated rate constants are 2.5817 × 10¹, 1.6695 × 10-7, 8.3975 × 10², 1.1758 × 10-11, and 2.3056 × 10-10 cm³•molecule-1•s-1 for pathways 1 through 5, respectively. These results indicate that hydrogen abstraction at site 3 (pathway 3) is the most kinetically favorable. Thermodynamic analysis supports this conclusion, with the product from pathway 3 exhibiting the lowest Gibbs free energy and reaction enthalpy (–22.25 kcal/mol), confirming it as the most thermodynamically stable. All pathways are exothermic and exergonic. These findings provide detailed mechanistic insight into the atmospheric reactivity of 3HB and may be extended to other structurally related VOCs, contributing to a better understanding of atmospheric oxidation processes.

Abstract Benzimidazole is the central core for drug synthesis. Obtaining detailed information about its synthesis mechanism can help us to design new catalysts to increase synthesis yield. Our previous results showed that in the absence of any catalysts, the steps 1 and 3 in which nitrogen in phenylene diamine attack on the formic acid carbon have higher barrier energies; while, dehydration steps (steps 2 and 4) have less barrier energies. In this paper, graphene quantum dot is used as a catalyst for benzimidazole synthesis, and all elementary steps are in detail studied. Stabilization energy due to the interaction between two reactants (formic acid and phenylene diamine) in the absence and presence of graphene catalyst are -9.08 and -26.29 kcal·mol-1, respectively. This causes that the rate determining step (RDS) is reduced more when graphene is used as the catalyst. The RDS for benzimidazole synthesis in the absence and presence of catalyst are 36.05 and 27.88 kcal·mol-1, respectively. In addition to the RDS, all other transition structures in the presence of graphene have energies less than the total energies of isolated formic acid and phenylene diamine. Considering thermal, entropic, and solvation free energy corrections reduces the relative barrier energy by 2.18 kcal·mol⁻¹. These corrections include zero-point vibrational energy (ZPVE), thermal contributions (TS and H), and solvation free energy (ΔGsolv), which together provide a more accurate representation of the reaction energetics.

Abstract One of the poultry businesses that is developing in Indonesia is duck farming. Duck farming has a relatively smaller risk, so it has great potential for development. One solution that is being developed is the use of keratin contained in duck feathers as an adsorbent that can be used to reduce metal levels. This research aims to determine the optimum volume and adsorption capacity required in the manganese ion adsorption process. The optimum volume and manganese adsorption capacity were measured using Atomic Absorption Spectrophotometer (AAS) to determine the amount of manganese ions that were adsorbed with the duck feather keratin-Na2S2O5- HDPE composite adsorbent. Determination of the optimum volume is carried out with volume variations of 0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4, 1.6, 1.8, 2.0 liters, while determining Adsorption capacity was carried out using a 100 ppm manganese solution flowed at a speed of 0.2 liters/minute. The results of this research show that the optimum conditions for manganese ion adsorption occur at a volume of 1.2 liters of 82.248 mg/L and an adsorption capacity of 17.029 mg/g. The conclusion of this research is that HDPE duck feather composite can absorb mn metal ions, where the resulting adsorbent will have strong adsorption capacity and can bind metal ions.

Abstract This review article presents a comprehensive analysis of the synthesis, physicochemical properties, technological processes, and applications of vinyl esters of carboxylic acids. The study highlights the strategic importance of vinyl esters as key intermediates in organic synthesis and industrial polymer production. Special attention is devoted to catalytic vinylation reactions involving acetylene, alkynes, and vinyl acetate, using both homogeneous and heterogeneous catalytic systems based on transition metals such as ruthenium, palladium, cobalt, and iridium. The article also examines environmentally and economically viable approaches to synthesizing vinyl esters, including enzymatic and green catalytic methods. Additionally, the structural transformations, photochemical rearrangements, and decomposition pathways of vinyl esters are analyzed. The practical applications of vinyl esters in medicine, materials science, coatings, adhesives, and biodegradable polymers are critically reviewed, demonstrating their significance as sustainable alternatives in modern polymer and fine chemical industries.

Abstract Igand[4-(8-hydroxyquinolin-5-yl),diazenyl)benzoic acid] (HQDbA) is a novel heterocyclic azo dye that was created by reacting 4-amino benzoic acid with an ethanolic mixture of 8-hydroxy quinolines. We used spectroscopy to study its metal complexes with Cu(II), Cd(II), Hg(II), and Pd(II) ions. Azo ligands and their related metal complexes have been characterized using a range of spectral techniques, such as mass spectrometry, FT-IR, UV-vis, atomic absorption, molar conductance measurements, and C.H.N. elemental analysis. The Pd(II) ion in these complexes has a square planar shape, and the chelate type is 1:1 [M:L] chelates. Cu(II), Hg(II), and Cd(II) ions were proposed to have an octahedral geometry as 1:2 [M:L] chelates.. The di-ions of Pb, Pd, Hg, Cd, and Cu that form metal complexes are compared to the IV effects of the Pt(II) complex in biological screening. Based on the data, the chelate composition of "1:2" [M:L] for each of the Cd(II), Cu(II), and Hg(II) ions was established. The complexes have an octahedral shape. Additionally, these complexes have a chelates composition of (1:1)[M:L] and exhibit a square planar geometry for the Pd(II) ion. Considering that the Pt(II) complex's biological screening effect is assessed in connection with.

Abstract New complex compounds of platinum (II) with the biologically active ligand monoethanolamine (HL), featuring cis-, trans- [Pt(H2L)2Cl2], [Pt(H2L)2Br2] structures, as well as tetramine [Pt(H2L)4]Cl2 types, were synthesized under various conditions. Studies indicate that in all the synthesized complexes, monoethanolamine is coordinated monodentately to the nitrogen atom of the amino group, and deprotonation of the hydroxyl group of the ligand does not occur. It was determined that the composition and structure of the obtained complexes are strongly influenced by the nature of the initial platinum salts and the synthesis conditions. For instance, when cis-[Pt(NH3Cl)2] is used as the initial platinum (II) salt, its interaction with monoethanolamine under specific conditions results in the formation of a cis-complex with the composition [Pt(H2L)2Cl2]. In an alkaline medium, the reaction of PtCl2 with monoethanolamine in a 1:10 ratio produces tetramine-type complexes [Pt(H2L)4]Cl2. The structure of the resulting trans-complex [Pt(H2L)2Cl2] was confirmed through X-ray diffraction analysis. Biological testing revealed that complexes I-IV exhibit varying levels of antitumor activity.

Abstract The Schiff base ligand (Z)-2-((2-amino-3,5-dibromobenzylidene)amino)phenol, was synthesized through a condensation reaction between 2-amino-3,5-dibromobenzaldehyde and 2-aminophenol in a 1:1 molar ratio. The structure of the ligand was confirmed and characterized by using various spectroscopic techniques including FT-IR, UV-visible, ¹H and ¹³C-NMR spectroscopy, electron ionization mass spectrometry (EI-MS) and supported by DFT-optimized structures. The melting point of the compound was also determined. The metal complexes were synthesized by the reacting of Schiff base ligand with Ni(II), Mn(II), Cu(II) and Co(II) ions in 2:1 ligand-to-metal molar ratio. The resulting complexes have the general formulas [M(L)(C3H7NO2)] where M = Ni(II), Mn(II) and Cu(II) and [Co(L)2] for the cobalt complex, where C3H7NO2 represents 2-aminopropane-1,3-diol. The complexes were characterized by FT-IR, UV-visible, molar conductance, magnetic moment measurements and melting point. The low molar conductance values indicate a non-electrolytic nature, while magnetic moment data confirm a tetrahedral geometry around all metal centers Ni(II), Mn(II), Cu(II) and Co(II). Furthermore, Antibacterial activity was evaluated by inhibition zone measurement. The ligand and its complexes was tested against Staphylococcus aureus and Pseudomonas aeruginosa, as a result complexes Mn(II) and Cu(II) showed antibacterial activity . Finally, the DFT studies assisted to better understand of the electronics structure, reactivity and stability of ligands.

Abstract A series of new bis-macrocyclic diamide compounds were synthesized in good yields (85% for the oxythiobis intermediate and 45% for the final cyclized product) and structurally confirmed through FT-IR, ¹H/¹³C NMR, 2D NMR (COSY, HSQC), HRMS, and CHN analyses. Motivated by the existing gap in developing macrocyclic diamide receptors with both strong and selective anion affinity in competitive polar media, this work was guided by the hypothesis that linking two diamide macrocyclic units would enhance cooperative hydrogen bonding and improve anion recognition. The bis-macrocyclic framework exhibited significantly enhanced anion-binding ability, as demonstrated by ¹H NMR titration studies. Compound 5 showed strong and selective binding toward fluoride ions, accompanied by notable downfield shifts of the amide NH protons (Δδ = +0.37 ppm). UV–Vis measurements also revealed a measurable red shift from 278 to 284 nm upon fluoride addition, supporting complex formation through hydrogen bonding. The association constants followed the order F⁻ (Ka = 1.2 × 10³ M⁻¹) > H₂PO₄⁻ (6.8 × 10² M⁻¹) > HSO₄⁻ (4.2 × 10² M⁻¹) > Cl⁻ (2.8 × 10² M⁻¹) > Br⁻ (1.1 × 10² M⁻¹). The strong preference for fluoride confirms that recognition is dominated by cooperative hydrogen bonding rather than deprotonation. Overall, compound 5 demonstrates promising performance as an efficient and selective anion receptor, particularly for fluoride sensing applications.

Abstract Background: HDAC6 is distinctive among histone deacetylases (HDACs) due to its unique structural characteristics and catalytic domains. The targeted inhibition of HDAC6 offers more potential benefits than the pan HDAC inhibitors.
Objectives: Hence, this study aimed to perform a computational analysis of compounds designed to use isatin-hydrazone as a surface recognition group, to predict their ADMET characteristics, and to clarify their binding modes to HDAC6 and other HDACs through docking studies and molecular dynamics simulations.
Methods: The ADMET and drug-likeness properties of the designed compounds were predicted using ADMETlab 3.0. Molecular docking studies were performed with Autodock4Zn, integrated within Amdock v1.5.2, focusing on HDAC6, HDAC8, and HDAC2. Additionally, a molecular dynamics simulation spanning 100 nanoseconds was conducted using the Desmond package from the Schrödinger software suite, applying Newton's equations of motion to explore protein-ligand interactions at the atomic level.
Results: All designed compounds have shown a desirable physicochemical characteristic and have successfully met all the quantitative (QED = 0.504, compounds 9a and 9b) and qualitative criteria for drug-likeness. Their ADMET analysis has revealed a favorable absorption parameter (highest Caco2 permeability -4.95 log cm/s, 9b), distribution parameters, low-moderate plasma clearance, and a favorable toxicity profile. Regarding molecular docking, the designed compounds have shown a higher binding affinity (G) to HDAC6 than HDAC8 and HDAC2 (except compounds 9c and 10a), where compound 9a had the highest G (-7.91 Kcal/mol). Compounds 9c and 10a demonstrate a novel binding mode to HDAC2, coordinating Zn2+ through the isatin-hydrazone nucleus and contributing to its greater affinity to HDAC2 (G = -11.23 and -7.99 Kcal/mol, respectively). In molecular dynamics simulation, compounds 9a and 9c have shown a stable binding to HDAC6 and HDAC2, respectively, maintaining their coordination with Zn2+ throughout the simulation time.
Conclusion: Our findings have revealed that the newly designed compounds have proper ADMET, binding affinity, and selectivity to HDAC6, making them suitable candidates for further analysis. Remarkably, two compounds exhibited a novel binding to HDAC2, potentially paving the way for a new zinc-binding group.

Abstract 5-Fluorouracil (5-Fu) is an antimetabolite class of anticancer agents that induces apoptosis by inhibiting thymidylate acid biosynthesis. Drug Development of 5-fluorouracil is an effort to obtain higher activity and a specific target receptor compared with 5-fluorouracil as a first-line drug for breast cancer. 5-Fluorouracil derivatives (2-Cl-benzoyloxymethyl-5Fu, 3-NO2-benzoyloxymethyl-5Fu, 4-OCH3-benzoyloxymethyl-5Fu, 4-CF3-benzoyloxymethyl-5Fu, 3,4-Cl-benzoyloxymethyl-5Fu, and 4-NO2-benzoyloxymethyl-5Fu) were successfully synthesized and identified but have not been studied in silico and in vitro (cytotoxic activity, and immunocytochemistry (p53, telomerase, and apoptosis) in MCF7). The First step, in silico study, showed that 5-Fu derivatives had better binding affinity than 5-Fu. The second step was an in vitro study, which included cytotoxicity tests and immunocytochemistry. The cytotoxicity test showed that the best IC50 was 3-NO2-benzoyloxymethyl-5-Fu among other 5-Fu derivatives with 348,398 µM. The results of immunocytochemistry telomerase, p53, and apoptosis (double staining and flowcytometry) studies revealed that 4-NO2-benzoylooxymethyl-5-Fu, 4-CF3-benzoylooxymethyl-5-Fu, and 4-methoxybenzoylooxymethyl-5-Fu activity were better than other 5-Fu derivatives and 5-Fu as a lead compound. In general, the results showed that 5-Fluorouracil derivatives had a significant effect (in vitro and in silico study) compared with 5-Fluorouracil

Abstract The present study investigates the phytochemical composition, vitamin content, and bioactive properties of Cucurbita pepo leaves, alongside their application in the green synthesis of silver nanoparticles (AgNPs). Ethanolic and acetone extracts of Cucurbita pepo leaves were analyzed for their total phenolic and flavonoid content, revealing significant antioxidant and metal-chelating activities, with ethanol proving to be the superior solvent. Chromatographic and spectrophotometric analyses identified a diverse profile of phenolic compounds and vitamins, including ascorbic acid and α-tocopherol. The green synthesis of AgNPs was achieved using these extracts, with nanoparticles characterized by UV-Vis, SEM, EDX, and XRD techniques, confirming their stability and crystalline structure. The synthesized AgNPs exhibited promising antibacterial activity against both Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli) bacteria, outperforming the crude extracts. This study highlights Cucurbita pepo leaves as a rich source of natural antioxidants, vitamins, and bioactive compounds with potential applications in nanotechnology with antimicrobial therapies.

Abstract Herein, a tricoordinate Cu(I) complex was synthesized employing a neutral bidentate Schiff base (L4Cl), via the condensation of 4-chlorobenzaldehyde with 2,2-dimethylpropane-1,3-diamine, followed by complexation with copper(I) iodide. The structural features of the ligand and its corresponding complex were confirmed by FT-IR, 1H and 13C{1H} NMR spectroscopy, along with elemental (CHN) analysis. Moreover, the catalytic efficiency of the complex was evaluated in the one-pot synthesis of 1,2,3-triazoles, which are effective anticancer agents, via a three-component reaction involving phenylacetylene, sodium azide, and various benzyl bromides in aqueous medium. The optimized reaction conditions offer significant advantages, including shorter reaction times, high yields, reduced reaction temperature, and a simplified product isolation process. The efficient synthesis of triazoles using the Cu(I) complex highlights its potential as a promising catalyst for future advancements in drug development targeting malignant cells.

Abstract Colon Cancer and “BreastCancer" were considered as the almost types of solid tumor diagnosed in human It accounts for 16% of all kinds of cancer deaths globally this operation earlybiologicallybearing cyclic imides an effect components were Synthesized.The heterocyclic molecule known as Isatinbelongs toindolines, which are the most significanttypes of organic compounds. In medical chemistry, Isatin, Isatin analog and their Schiff bases have latelydrawn a greatattention. Isatin is shown to exhibitdifferentbiological activitiessuch as antiviral, antimicrobial, anti cancer, anti-inflammatory,analgesic, antioxidant as well as anticonvulsant activities. The isatinmoiety-containing BisSchiff basesare shownto own a broad spectrum of pharmacological activities.. The presentstudyprovideslatest information on the most commonly active isatinbis-Schiff bases, includingantimicrobial, anticancer, antiviral, anticonvulsant, anti-inflammatory in addition to analgesic activities.

In the current work,through an ultrasonic reaction, the complexes have been prepared so as to offer a fast, cost-effective and environmentally-friendly method.It was prepared from condensation of 2,5- diamino-phenol with Isatin in order to prepare the Schiff base compound namely [(E-2-((4-amino-2-hydroxyphenyl)imino)indol-3-one ] (3-HMIDI), followed by a reaction of the resultant compound (3-HMIDI) with Piperazin while the second ligand prepared from the condensation of 4-amino-3-hydroxybenzenesulfonamide with Isatin in order to prepare the Schiff base compound namely [Z-2-( (4-amino-2-hydroxyphenyl)-1-piperazin)1-yl methyl)indol-3-one ] (3-HDAB), followed by a reaction of the resultant compound (3-HDAB) with Piperazin.Variouscharacterization and analytical methods were usedsuch as (Mass , UV-Vis. spectroscopy in investigation of prepared ligands. Evaluation of a groupof Novel anticanceractivities of the prepared imides was done, and the results suggested that the majority of them had high anticancer activities.

Abstract The discharge of heavy metal ions, persistent organic pollutants, and radioactive species into industrial effluents and wastewater poses a critical threat to environmental sustainability and public health. Conventional sorbent materials are often hindered by limited sorption capacity, poor selectivity, and insufficient reusability, which significantly restrict their large-scale applicability. To address these challenges, increasing research efforts have focused on the design of modified sorbents through chemical functionalization, polymer incorporation, and nanomaterial integration. These strategies have yielded sorbents with enhanced sorption performance, accelerated kinetics, tailored selectivity, and improved regeneration potential. This review provides a comprehensive overview of the synthesis approaches for modified sorbents, including chelating agent functionalization, polymer matrix hybridization, and nanoparticle-assisted modification. A growing body of evidence demonstrates the superior performance of modified sorbents in removing toxic heavy metal ions (Pb²⁺, Cd²⁺, Hg²⁺), synthetic dyes, and organic pollutants from aqueous environments. Finally, the review highlights emerging challenges and future prospects, with particular emphasis on the development of multifunctional, environmentally benign, and intelligent (“smart”) sorbent materials. Their potential for industrial-scale implementation and sustainable environmental remediation is discussed as a promising direction for future research.

Abstract Structural, elastic, electronic and optical properties of the perovskite-type hydrides CaXH3 (X = Co, Rh) were investigated using the first-principles full-potential linearized augmented plane wave method based on density functional theory calculations. We have investigated formation energies, lattice parameters, bulk moduli, elastic constants, electronic structures, and optical properties.

Calculated negative formation energies point to their stability, and indicate that the most stable compound is CaRhH3. In addition, elastic properties and mechanical coefficients confirm that these compounds are stable.

The densities of states (DOS) in the compounds are not zero at the Fermi level reflecting their metallic behavior and the largest contributions to the partial DOS’es were observed to stem from the presence of the transition metal element. The hybridization reaction between X-d states and H-1s states is stronger than that between Ca-d states and H-1s states, which is an important feature for these hydrogen storage compounds.

Abstract The simultaneous incorporation of Fe²⁺ and Fe³⁺ ions using co-precipitation methods with variation in pH and temperature has modified the structural, optical, electronic, magnetic, and photocatalytic activity of TiO2 powder. The characterization of photocatalyst composites had been carried out using spectrophotometry Raman, XRD, SAA, DRS, XPS, and VSM. The higher the pH of the synthesis has caused a decrease in magnetic properties, TiO2 crystal composition, crystal size, and band gap, but increase surface area. Meanwhile, the higher temperature synthesis (110 oC) has caused a decrease in magnetic properties, TiO2 crystal composition, surface area, but increase crystal size, crystallinity, and band gap. Photocatalyst composites synthesized with higher pH and lower reaction temperature have shown greater photocatalytic activity.

Abstract In the present investigation, the preparation of 1-ethynylcyclopentan-1-ol was carried out via the enantioselective alkynylation of cyclopentanone using a Zn(OTf)₂/TBAF·3H₂O complex catalytic system. Тhe process was carried out in acetonitrile (MeCN) medium for 120 minutes at –10 °C. The molar ratio of acetylene to cyclopentanone was adjusted to 2:1, while the combined loading of the catalytic system Zn(OTf)2/TBAF·3H2O was maintained at 0.05 mol with respect to the starting materials. Furthermore, its subsequent oxidative homolytic dimerization and Sonogashira-type C–C cross-coupling reaction with benzyl chloride were explored. A comprehensive study was performed on various parameters affecting the formation process and the efficiency of acetylene alcohol derivatives, such as temperature regime, reaction time, catalytic composition and solvent polarity, stoichiometric ratios of reagents and substrates, as well as the identity and proportion of transient intermediates and side-products. Based on the acquired experimental data, the optimal conditions for the nucleophilic addition–coupling pathway were established, and the plausible reaction mechanisms were proposed. The obtained compounds were thoroughly characterized, and their equilibrium constants, molecular structures, purity levels, and chemical composition were verified using modern physicochemical analysis techniques.

Abstract Dental prostheses are an essential component of restorative dentistry, enhancing not only function but also aesthetics and oral health. Cobalt-chromium (Co-Cr) alloys are among the materials commonly used for dental frameworks, primarily due to their corrosion resistance and high mechanical strength. This study examined the effects of integrating molybdenum disulfide (MoS2) at different concentrations (0%wt, 6%et, and 8%wt) on the mechanical properties and corrosion resistance of Co-Cr dental alloys. It fabricated 90 specimens (30 per group) and assessed their compressive strength, hardness, and corrosion resistance. Incorporating MoS2 markedly improved the mechanical characteristics of the Co-Cr alloy. Compressive strength and hardness differed significantly across groups (p < 0.05). They were greatest in the 8%wt MoS2 group (141.3 MPa and 912.1 IU, respectively), followed by the 6%wt MoS₂ group (131 MPa and 693.6 IU), and smallest in the 0%wt MoS2 group (87.72 MPa and 595.3 IU). Corrosion resistance increased with the MoS2 concentration and was greatest in the 8%wt MoS2 group. The presence of Mo facilitated the development of a protective oxide layer, thereby reducing corrosion. Our findings indicate that incorporating MoS2 into Co-Cr dental alloys can improve mechanical strength, durability, and corrosion resistance. Such improvements may result in longer-lasting, more durable dental prostheses, benefiting both practitioners and patients. Future research should focus on the long-term clinical performance and biocompatibility of MoS2-enhanced Co-Cr alloys to confirm their use in dental prostheses.