Advanced Journal of Chemistry, Section A

Abstract This study aims to enhance the pozzolanic reactivity and cementitious performance of palm oil fuel ash (POFA) and fly ash (FA) nanoparticles as eco-friendly supplementary materials in nanostructured engineered cementitious composites (ECC), thereby reducing industrial boiler waste and contributing to sustainable construction practices. POFA and FA were dried and ground into nanoparticles using a ball mill with replacement levels of 0%, 5%, 10%, and 15%. Characterization was performed using XRF, XRD, and FTIR, while physical tests included slump flow, density, and compressive strength. XRF confirmed the cementitious and pozzolanic properties of POFA and FA, with POFA containing over 50% SiO₂+Al₂O₃+Fe₂O₃ and FA exceeding 70%. XRD showed average crystal sizes of 28.02 nm (POFA) and 16.46 nm (FA) with amorphous phases of 71.78% and 91.93%, respectively. FTIR revealed dominant Si–O–Si and Si–OH groups, indicating high silica content and pozzolanic reactivity. The slump flow decreased with higher POFA and FA content due to water absorption but remained within the high-performance concrete range (500–800 mm). Density values decreased yet stayed between normal and lightweight concrete limits. The compressive strength increased with higher nanoparticle content, reaching 46.34–72.73 MPa at 28 days, confirming improved hydration and mechanical performance

Abstract Environmental pollution is one of the most challenging issues for the sustainability of our planet, human health, and ecosystem integrity. Increasing evidence of the release of organic, inorganic, and emerging contaminants necessitates measures for more accurate, rapid, and inexpensive techniques for contamination detection. Although traditional analytical methodologies yield reliable results, they are often hampered by time-consuming sample preparation, high operational costs, and low applicability in the field. Recent developments in analytical science have provided a host of innovative technologies that can overcome these limitations. This review provides a thorough examination of emerging analytical techniques for the detection of pollutants in the environment, including nanomaterial-based sensors, surface-enhanced Raman spectroscopy (SERS), laser-induced breakdown spectroscopy (LIBS), and mass spectrometry-coupled hybrid systems GC–GC-MS and LC–MS/MS. Portable applications have also been developed by integrating microfluidic and lab-on-a-chip devices for convenient real-time analysis. Finally, the inclusion of machine learning (ML) and artificial intelligence (AI) algorithms has dramatically changed the data interpretation process to include predictive modeling and automated environmental monitoring. There is also an emphasis on environmentally friendly and sustainable analytical techniques, including miniaturized, solvent-free, and bioanalytical procedures, that conform to green chemistry guidelines. Despite these achievements, there are significant obstacles in terms of standardization, analytical performance, and scalability. The objectives of this review are to discuss the present advancements, address the identified limitations, and offer future research strategies on smart, integrated, and sustainable analytical methodologies for the rapid detection and management of environmental contaminants.

Abstract Quercetin is a natural flavonoid with strong antioxidant and therapeutic potential; yet, its practical use is hindered by poor aqueous solubility. To overcome this limitation, this study develops a functional carrier system based on a β-cyclodextrin metal–organic framework (β-CD-MOF) modified with cetyltrimethylammonium bromide (CTAB). In this design, CTAB acts as a surface-active modifier that improves the interaction between quercetin and the framework, while β-cyclodextrin provides hydrophobic cavities capable of accommodating bioactive molecules. Structural and morphological characterizations using FTIR, XRD, SEM, and PSA confirm the successful synthesis and modification of the material. In vitro release studies reveal a biphasic and controlled release profile, accompanied by a notable improvement in quercetin solubility compared to its free form. Overall, these findings demonstrate that CTAB-modified β-CD-MOF effectively encapsulates quercetin and enhances its dissolution behavior, highlighting its potential as a promising carrier system for hydrophobic compounds.

Abstract Despite advances in cancer therapy, severe side effects and drug resistance highlight the need for safer multi-target strategies. Targeting multiple receptor tyrosine kinases has emerged as a rational approach, and natural products, particularly xanthones from Garcinia mangostana, offer structurally diverse scaffolds with promising anticancer potential. This study presents an in vitro evaluation of three xanthones: 8-deoxygartanin (1), gartanin (2), and garcinone B (3) evaluated against epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor-2 (VEGFR-2/KDR). Among the tested compounds, 8-deoxygartanin (1) exhibited the strongest dual inhibitory activity, with 78% and 51% inhibition of VEGFR-2 and EGFR, respectively, at 10 µM. Molecular docking analysis indicated that compound (1) binds to the active pockets of both kinases primarily through hydrophobic interactions. Furthermore, molecular dynamics simulations confirmed the stability of compound (1)-protein complexes over 500 ns in an aqueous environment. Structure-activity relationship (SAR) analysis revealed that prenylation and the specific distribution of hydroxyl and methoxy groups significantly influenced potency and selectivity. Comparison with mangostin-type analogues further underscored the superior profile of compound (1). This study provides novel mechanistic insights into Garcinia-derived xanthones and highlights 8-deoxygartanin as a promising scaffold for the rational design of dual EGFR/KDR-targeting anticancer agents.

Abstract Aroyl hydrazones derived from 4,4,4-trifluoro-1-(3-furanyl)-1,3-butanedione represent a structurally distinctive and chemically significant class of organic compounds with considerable potential for application in various fields, including coordination chemistry, spectroscopy, and medicinal chemistry. These compounds exhibit versatile chelating behavior and are of great interest due to their pronounced biological activity. In the present study, a series of aroyl hydrazones was successfully synthesized via condensation of substituted acid hydrazides with the trifluoroacetyl moiety of the β-diketone precursor. Structural elucidation was carried out using Fourier-transform infrared (FTIR) spectroscopy, ¹H and ¹³C nuclear magnetic resonance (NMR) techniques, and theoretical methods based on density functional theory (DFT). Experimental data correlated well with DFT-optimized structures, confirming the predominance of the hydrazone tautomer. Theoretical calculations also provided HOMO-LUMO energy levels, dipole moments, molecular electrostatic potential (MEP) maps, and Mulliken charge distributions. Molecular docking studies revealed energetically favorable binding interactions with P. aeruginosa target proteins. Molecular docking of the H2L¹ ligand with the 1U1Z protein exhibited strong binding interactions (–11.6255 kcal/mol) via hydrogen bonds, π-π, and π-anion contacts, suggesting promising biological activity. Taken together, the findings of this study underline the potential applicability of these hydrazones as ligands for metal complexation and as promising bioactive compounds.

Abstract Triple-negative breast cancer (TNBC), which lacks ER, PR, and HER2 expression, remains challenging to treat due to the absence of targeted therapeutic options and frequent chemoresistance. Cyclosenegalin A, a cyclic heptapeptide, offers a compact β-turn scaffold amenable to selective receptor engagement but displays only moderate native activity. In this study, computational modeling, chemical synthesis, and cell-based evaluation were integrated to develop cyclosenegalin-derived peptides as anticancer candidates. A 29-member analog panel was sketched in ChemDraw, converted to 3D in Chem3D, and subjected to geometry and frequency optimization using Gaussian (DFT B3LYP/3-21G) to afford electronically stable conformers. Molecular docking with AutoDock Vina against ERα (PDB: 3ERT), PR (2OVH), EGFR kinase (2ITY), and the IκBα/NF-κB complex (1NFI) identified two multi-target leads, A14 and A21, which exhibited consistently lower predicted binding free energies and extensive hydrogen-bond and hydrophobic contact networks at key pocket residues. Both peptides were synthesized via Fmoc-based solid-phase assembly, macrocyclized under dilute conditions, purified by RP-HPLC to >95% purity, and structurally confirmed by ESI-MS (calcd/obs: A14, 757.89 Da / [M+H]⁺ 761–762; A21, 762.87 Da / [M+H]⁺ 762). Antiproliferative activity evaluated using the MTT assay against luminal T-47D and TNBC MDA-MB-231 cells showed that A21 was the most potent analog, with IC₅₀ values of 387.99 ± 10.2 µg/mL (T-47D) and 143.15 ± 6.4 µg/mL (MDA-MB-231), outperforming A14 (710.28 ± 12.4 µg/mL and 220.05 ± 8.6 µg/mL, respectively). Both peptides demonstrated preferential cytotoxicity toward the TNBC subtype, with A21 offering a favorable balance of potency and subtype selectivity. Collectively, these findings validate a docking-led design pipeline for cyclosenegalin-based cyclic peptides and identify A21 as a tractable lead for further optimization, mechanistic studies focused on EGFR/NF-κB pathway modulation, and future in vivo investigations.

Abstract A rapid, precise, and economical LC-MS/MS method was developed and validated for the quantification of vincristine. The method utilizes electrospray ionization in positive mode with multiple reaction monitoring (MRM) for a precursor-to-product ion transition of m/z 825.3 > 807.3. Effective chromatographic separation was achieved using a Thermo Hypurity C18 column (50 mm x 4.6 mm, 5 µm). The mobile phase consisted of 2 mM ammonium formate with 0.2% formic acid in acetonitrile at a ratio of 30:70 (v/v), pumped at a flow rate of 0.5 mL/min. The retention time (RT) for vincristine was 1.21 minutes and the total run time was 2.5 minutes. The method was validated according to ICH Q2(R1) guidelines, with the Limit of Detection (LOD) and Limit of Quantitation (LOQ) determined to be 3 ppm and 10 ppm, respectively, calculated using standard regression statistics. Linearity was established over a concentration range of 10– 150 ppm (y = 698.983 x − 2606.21; R² = 0.995734). Accuracy (mean % recovery) across LOQ, 50%, 100%, and 150% levels was within 91–106%, and precision (relative standard deviation [%RSD]) ranged from 1.2% to 3.1% (intraday and inter-day), meeting the acceptance criteria for routine analysis. The system suitability %RSD for the peak area was 2.27%, and the RSD for RT was 0.45%. The method was successfully applied to quantify vincristine loaded on drug-eluting stents (DES) and to evaluate in vitro release kinetics (DES extraction and release sample testing included in validation). This method is suitable for routine quality control and formulation development of vincristine-containing DES.

Abstract This study investigated the phytochemical composition and antitubercular potential of Cissus verticillata using an integrated gas chromatography mass spectroscopy (GC–MS), molecular docking, and ADMET approach. The authenticated hydroalcoholic extract showed a dark brown to greenish-brown appearance, a yield of 10.95%, near-neutral pH, and the absence of foreign matter, heavy metals, pesticide residues, and pathogenic microorganisms, confirming its suitability for pharmacological use. Preliminary phytochemical screening indicated a rich metabolite profile with strong presence of alkaloids, flavonoids, and phenolic compounds, along with moderate levels of saponins and tannins. GC–MS analysis identified 55 phytochemical constituents, with major compounds, including L-prolyl-L-valine (13.28%), 3,6-diisopropylpiperazin-2,5-dione (4.72%), hydrocinnamic acid (3.84%), and tyrosol (2.39%), supported by minor sterols, esters, and phenolics, which contribute to chemical diversity. Molecular docking against Mycobacterium tuberculosis MurG glycosyltransferase (PDB ID: 2WGE) revealed strong binding affinities for squalene (–8.3 kcal/mol), loliolide (–7.2 kcal/mol), quinic acid (–7.1 kcal/mol), and methyl-N-hydroxybenzenecarboximidate (–7.0 kcal/mol), surpassing or matching the native ligand. Key hydrophobic and hydrogen-bond interactions were observed with PHE404, HIS311, PRO280, and GLY403. The ADMET analysis highlighted loliolide, maltol, 5-hydroxymethylfurfural, and quinic acid as drug-like candidates with favorable solubility, absorption, low toxicity, and minimal environmental bioaccumulation. Collectively, these findings position Cissus verticillata is a promising source of antitubercular lead compounds, warranting further experimental validation.

Abstract This study aimed to evaluate the inhibitory effects of apremilast on activated coagulation factor XII (FXIIa) using chromogenic enzyme assays and to examine molecular interactions between apremilast and benzamidine with the target protein 6I63 (FXIIa) through in silico techniques including docking, structural analyses, and dynamic simulations. The interaction strength of these complexes, focusing on hydrogen bonds, Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), and Solvent Accessible Surface Area (SASA), was analyzed. Additionally, the selectivity of apremilast toward FXIIa over other related serine proteases (FIXa, FXa, FXIa, and plasma kallikrein) was determined using chromogenic assays. The findings indicated that apremilast has a significant inhibitory effect on FXIIa, while no notable effects were observed on the other proteases, suggesting selectivity for FXIIa. Furthermore, apremilast showed stronger binding affinity with 6I63 (−6.9 kcal/mol) compared to benzamidine (−5.3 kcal/mol), indicating a more stable and specific interaction. Apremilast induced greater compactness and stability of the complex, with lower RMSD and SASA values, whereas benzamidine favored a more flexible and less stable interaction. These results highlight distinct mechanisms by which each ligand interacts with FXIIa and provide insights into their therapeutic potential, suggesting apremilast could be effective in treating FXIIa-related diseases. In addition, ADME analysis revealed that benzamidine has better solubility, intestinal absorption, and excretion, while apremilast exhibits superior oral absorption and stronger inhibition of cytochrome P450 enzymes. Toxicity studies showed both compounds are mutagenic. Taken together, apremilast could serve as a lead compound for developing new therapeutic agents targeting FXIIa-related diseases.

Abstract Cardiometabolic diseases (CMDs), including type 2 diabetes, obesity, and cardiovascular disorders, share interlinked pathogenic mechanisms involving chronic inflammation, insulin resistance, oxidative stress, and endothelial dysfunction. Multi-target agents derived from natural compounds offer promising therapeutic avenues for CMD management. Lupeol, a pentacyclic triterpenoid, has demonstrated diverse bioactivities, yet its mechanistic relevance in CMDs has not been comprehensively elucidated.We aimed to elucidate the multitarget pharmacological potential of lupeol against CMDs through an integrated computational approach encompassing network pharmacology, computational docking, and dynamic simulation.Lupeol- and CMD-associated targets were retrieved from various databases and analyzed via protein–protein interaction (PPI) analysis via Cytoscape. Functional enrichment was performed using DAVID and Metascape. Drug-likeness and toxicity were assessed through SwissADME and ADMETlab 2.0. Binding affinities were evaluated using computational docking, followed by MD simulations and specific tissue expressions to validate complex stability. A total of 179 shared targets were identified, with STAT3, MAPK3, ESR1, EGFR, and CXCR4 emerging as key hub genes. GO and KEGG enrichment highlighted significant involvement in PI3K–Akt, MAPK, JAK–STAT, and AGE–RAGE regulatory pathways. Lupeol exhibited strong interaction energies (–9.08 to –6.08 kcal/mol) and stable interactions with major CMD targets. ADME-Tox profiling demonstrated its oral bioavailability, BBB permeability, and low toxicity risk. MD simulations showed stable protein–ligand conformations under near-physiological conditions. Collectively, these findings highlight lupeol as a promising multi-target lead compound for cardiometabolic disease management and provide a robust computational foundation for its future experimental and translational evaluation.

Abstract This study examines the corrosion inhibition efficacy of a novel quinazolinone derivative, 1'H-spiro[cyclohexane-1,2-quinazolin]-4'(3'H)-one (ZB5). The compound was characterized by ¹³C-NMR and ¹H-NMR spectroscopy, and its corrosion inhibition activity on mild steel (MS) was evaluated in a 1.0 M HCl solution using potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS). ZB5 demonstrated remarkable protection, with an inhibition efficiency of 82.83% at 10⁻³ M. Adsorption studies revealed that ZB5 follows the Langmuir isotherm model, confirming monolayer adsorption on the MS surface. Surface characterization by SEM/EDS, XRD, and FTIR confirmed the formation of a protective layer, while ICP-OES analysis provided information on elemental composition and ion release. Further density functional theory (DFT) calculations and Monte Carlo (MC) simulations established a strong correlation between the electronic structure of ZB5 and its adsorption behavior, thus confirming the experimental results. Overall, this work provides robust experimental and theoretical evidence for ZB5's strong corrosion-inhibiting capacity, highlighting its potential as an effective protective agent for mild steel in acidic environments.

Abstract Paper-based colorimetric sensors have been widely applied as cost-effective tools for on-site pesticide detection. The availability of inexpensive imaging technologies, such as smartphones, has enhanced the efficiency of detection methodologies. This work describes the development of an image analysis-assisted paper-based colorimetric aptasensor for malathion (MLT) detection. The sensing paper was fabricated by immobilizing a mixture of citrate-capped gold nanoparticles (cit-AuNPs) and thiolated DNA aptamer (Apt) onto Whatman filter paper. After a 3-minute reaction, the paper exhibited a visible color change in the presence of MLT due to cit-AuNP aggregation. Smartphone images of the sensing paper, captured before and after MLT addition, were processed using ImageJ software to obtain red, green, and blue (RGB) values, with the response expressed as ΔRGB. The aptasensor achieved a limit of detection (LOD) of 0.67 μM with a linear range of 100–1,000 μM. This paper-based colorimetric aptasensor provides a simple and rapid method for on-site MLT detection.

Abstract The development of high-performance proton exchange membranes (PEMs) is crucial for improving the efficiency and durability of fuel cells. In this study, sulfonated polystyrene (SPS) was reinforced with different loadings of MIL-101(Cr) (2.5, 5, and 7.5 wt%), a highly porous metal–organic framework (MOF) with a specific surface area of 1,811.06 m² g⁻¹, to fabricate nanocomposite membranes via a solution-casting method. The incorporation of MIL-101(Cr) significantly enhanced key physicochemical and electrochemical properties of the membranes. Water uptake increased from 38.2% to 48.6%, while the ion exchange capacity (IEC) reached up to 0.95 meq g⁻¹ with increasing MOF content. The composite membranes exhibited excellent oxidative stability, retaining more than 97% of their original weight after exposure to Fenton’s reagent at 80 °C. Electrochemical impedance spectroscopy (EIS) revealed that proton conductivity increased with MIL-101(Cr) loading, reaching a maximum value of 0.0914 S cm⁻¹ at 80 °C and 60% relative humidity for the membrane containing 7.5 wt% MIL-101(Cr). In addition, methanol permeability remained in the order of 10⁻⁷ cm² s⁻¹, leading to a markedly improved selectivity factor compared to the MOF-free membrane. These results demonstrate that MIL-101(Cr)-based SPS nanocomposite membranes exhibit a well-balanced combination of high proton conductivity, low methanol crossover, and excellent oxidative stability, highlighting their strong potential for application in next-generation proton exchange membrane fuel cells (PEMFCs) and direct methanol fuel cells (DMFCs).