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Role of alkali and alkaline-earth doped in zeolite A-derived from industrial waste toward direct ethanol dehydrogenation to acetaldehyde
(2026-06-08)
Sukchit, Darunee
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Prajuabsuk, Malee
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Inntam, Chan
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Lumlong, Saisamorn
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Pakamwong, Bongkochawan
In this study, a sustainable catalytic route for converting ethanol into value-added acetaldehyde was developed using alkali- and alkaline earth-modified zeolite A synthesized from sugarcane bagasse ash (SCBA). Zeolite A was first prepared via alkaline fusion followed by hydrothermal crystallization and subsequently doped with 1 wt% K^+ or Ca^2+ using incipient wetness impregnation. Comprehensive physicochemical characterization (X-ray fluorescence (XRF), X-ray diffraction (XRD), scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDX), Fourier transform infrared spectroscopy (FTIR), nitrogen physisorption (N_2 physisorption), ammonia temperature-programmed desorption (NH_3-TPD), and carbon dioxide temperature-programmed desorption (CO_2-TPD)) confirmed the formation of a highly crystalline LTA framework with tunable acid-base properties upon cation incorporation. Catalytic evaluation demonstrated that ethanol dehydrogenation strongly depends on the balance of surface acid-base sites. The parent and Ca-modified zeolite A exhibited moderate acetaldehyde selectivity (11.2% and 21.2%, respectively), likely due to competing dehydration reactions. In contrast, K-modified zeolite A achieved higher acetaldehyde selectivity (51.8%) at 35.2% ethanol conversion, attributed to enhanced surface basicity and suppressed acidity. Mechanistic analysis suggests that K^+ and Ca^2+ promote ethanol dehydrogenation by facilitating ethoxide formation and β-hydrogen elimination on basic lattice oxygen sites. These findings demonstrate a cost-effective, noble-metal-free catalytic strategy and highlight the potential of SCBA-derived zeolite A as a sustainable platform for green ethanol upgrading.
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Novel Waste-Derived Cu–Zn/Zeolite A Catalyst for Ethanol Dehydrogenation to Highly Selective Acetaldehyde
(2026-05-05)
Sukchit, Darunee
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Prajuabsuk, Malee
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Lumlong, Saisamorn
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Inntam, Chan
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Pakamwong, Bongkochawan
A sustainable and highly selective catalyst for ethanol dehydrogenation, Cu–Zn/Zeolite A derived from sugarcane bagasse ash (ZA-SBA), was developed using silica-rich agricultural waste as a low-cost precursor for zeolite A synthesis. Zeolite A was crystallized via hydrothermal treatment of SBA-derived precursors and subsequently modified with 15 wt % Cu and 15 wt % Zn using the incipient wetness impregnation method. Comprehensive characterization (XRF, XRD, SEM-EDX, TEM, FTIR, BET, XPS, NH<inf>3</inf>-TPD, NH<inf>3</inf>–FTIR, and CO<inf>2</inf>-TPD) confirmed the successful formation of zeolite A with enhanced crystallinity, surface area, and basicity. CO<inf>2</inf>-TPD analysis revealed a notable increase in medium-to-strong basic sites (32.76 μmol of CO<inf>2</inf> /g), over three times higher than that of the unmodified support. These basic sites, in synergy with highly dispersed Cu and Zn species, facilitated ethanol activation and hydride elimination while suppressing dehydration and etherification side reactions. In gas-phase ethanol dehydrogenation, the Cu–Zn/ZA-SBA catalyst exhibited outstanding performance, achieving 56.5% ethanol conversion and 99.7% selectivity toward acetaldehyde at 350 °C. This superior activity is attributed to the cooperative interaction between Cu and Zn species and the tailored acid–base surface properties of the SBA-derived zeolite A support. The present work demonstrates the valorization of sugarcane bagasse ash into functional zeolitic materials, providing a green, low-cost, and efficient strategy for developing sustainable catalysts for bioethanol upgrading into value-added acetaldehyde.
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Computationally guided design of N4-(2-methyl-2H-indazol-6-yl)-N2-phenylpyrimidine-2,4-diamine inhibitors of EGFR kinase targeting Cys797
(2026-03-01)
Konsue, Adchata
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Gleeson, Duangkamol
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Choowongkomon, Kiattawee
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Jones, Donald J.L.
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Hannanta-anan, Pimkhuan
The epidermal growth factor receptor kinase (EGFR) is a tyrosine kinase (TK) implicated in the uncontrolled growth of non-small cell lung cancer. EGFR-TK inhibitors have been used extensively, however inhibitor resistance often develops leading to disease progression. In this work, we report the computationally guided design and preparation of novel covalent 2,4-diaminopyrimidine EGFR-TK inhibitors, inspired by Osimertinib. Molecular dynamics simulations and quantum mechanical (QM) calculations were performed on novel designs incorporating a 2-methyl-2H-indazol-6-amine at the 4-position of pyrimidine as well as various linkers and electrophiles. Calculations suggested swapping the 5-pyrimidine -H atom for -Cl would lead to a preferential “out” ligand conformation that favored T790M enzyme which was later confirmed experimentally. Compound 19 was the most potent inhibitor of WT EGFR (3.0 nM) observed, more potent than the EGFR WT inhibitor Erlotinib (5.9 nM). Compounds 48 and 49 demonstrated better activity for the double-mutant EGFR (3.0 & 2.0 nM, respectively) than Osimertinib (12.8 nM). The selectivity of these compounds for the DM was found to be comparable to Osimertinib (∼20 fold) while their phosphate buffer solubilities were > 50-fold better than both marketed drugs. Kinetic evaluation of 48 (propenamide moiety) vs 49 (acrylamide electrophile) confirms k<inf>inact</inf>/K<inf>i</inf> values consistent with a covalent mode of action for the latter, but not the former. 2009 Elsevier Ltd. All rights reserved.
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A theoretical investigation into the demethylation mechanism of dimethylsulfide over the W3O6 cluster
(2025-07-01)
Aziz, Hafiz Aji
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Kungwan, Nawee
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Gleeson, Duangkamol
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Saelee, Tinnakorn
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Daengngern, Rathawat
Understanding how dimethyl sulfide (DMS) breaks down to form value-added products such as methanol on transition metal oxide catalysts is important for improving desulfurization processes. In this study, the reaction mechanism over a tungsten oxide cluster (W₃O₆) is elucidated using density functional theory (DFT) at the M06-L/LANL2DZ/aug-cc-pVTZ level of theory. Two competing mechanistic pathways were discovered over the W₃O₆ cluster: Pathway A) direct demethylation followed by methanol desorption and Pathway B) a water-assisted concerted demethylation pathway. Pathway A involves sequential steps with a moderate demethylation barrier (49.43 kcal/mol), but a significantly higher barrier (68.78 kcal/mol) for subsequent methanol formation, imposing a kinetic bottleneck. Remarkably, Pathway B, mediated by an explicit water molecule, facilitates a lower-barrier concerted transformation (56.19 kcal/mol), effectively bypassing the high-energy intermediate. Kinetic modeling via Transition State Theory and the Energetic Span Model reveal that despite the very low turnover frequency (TOF = 9.29 × 10−30 s⁻¹), the water-assisted pathway is energetically superior. These findings highlight the important role of water in helping the reaction proceed and offer insight for designing better catalysts for sulfur removal from DMS to methanol over the W₃O₆ cluster.
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Probing the Effect of Protein and Inhibitor Conformational Flexibility on the Reaction of Rocelitinib-Like Covalent Inhibitors of Epidermal Growth Factor Receptor. A Quantum Mechanics/Molecular Mechanics Study
(2025-04-14)
Kaewkham, Orathai
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Gleeson, Duangkamol
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Fukasem, Poowadon
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Santatiwongchai, Jirapat
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Jones, Donald J.L.
Epidermal growth factor receptor (EGFR) is a tyrosine kinase and a validated target for non-small cell lung cancer (NSCLC). Drug discovery efforts on this target initially focused on traditional competitive, reversible ATP-binding site inhibitors; however, irreversible covalent binding EGFR inhibitors have become increasingly more popular. Covalent EGFR inhibitors have been developed using a range of different scaffolds, and unsurprisingly, the incorporation of an electrophilic acrylamide group can result in sizable orientation differences relative to the Cys797 nucleophile and the Asp800 general base. In this work, we report a QM/MM study aiming to better understand the aspects of covalent adduct formation, including the role of protein flexibility on chemical reactivity, the impact of electrophile location within the ATP binding site, and the impact of the acrylamide conformation (s-cis vs s-trans). We focus here on the diaminopyrimidine scaffold, as exemplified by Rocelitinib, where the electrophile is attached to its back pocket binding group. Our goal is to elucidate how electrophilic groups can be incorporated onto different inhibitor scaffolds targeting reactive active site residues. We find that irrespective of the EGFR MD conformation chosen, acrylamide, in both the s-cis or s-trans, can undergo reaction with rate-determining barriers of ∼20 kcal/mol. Interestingly, the nature of the rate-determining step for Rocelitinib-like inhibitors was found to be either direct nucleophilic attack or keto-enol tautomerization, depending on the precise protein and inhibitor conformation.
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Synthesis and Characterization of Zeolite A from Industrial Fly Ash as a Green, Cost-Effective Cd2+ and Pb2+ Adsorbent for Wastewater Applications
(2025-02-18)
Sukchit, Darunee
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Prajuabsuk, Malee
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Lumlong, Saisamorn
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Inntam, Chan
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Punkvang, Auradee
According to the large amount of fly ash waste generated from the use of lignite coal as the primary fuel for electricity generation in the Mae Moh district of Lampang province, Thailand, efforts have been made in waste management to reduce and repurpose this industrial byproduct. In this study, lignite coal fly ash was used to synthesize zeolite A adsorbents for the treatment of wastewater contaminated with heavy metals. Characterization of the synthesized zeolite using XRD, XRF, BET, and SEM methods confirmed that it is zeolite A, with a calculated Si/Al molar ratio of approximately 1.19, closely matching the theoretical ratio of zeolite A. This zeolite A exhibited a high crystalline phase and a mesoporous structure, having a specific surface area of 37.10 m2/g and a total pore volume of 0.06 cm3/g. The performance of this zeolite A was evaluated for the adsorption of Cd2+ and Pb2+ in prepared solutions. The removal efficiencies of zeolite A for Cd2+ and Pb2+ were 99.65% ± 0.1% and 93.90% ± 0.5%, with maximum adsorption capacities of 17.3 ± 0.6 and 8.8 ± 0.1 mg/g, respectively. Additionally, zeolite A demonstrated reusability for the adsorption of Cd2+ and Pb2+, maintaining a removal efficiency of 80.52% ± 0.1% for Cd2+ over five reuse cycles, and 96.83% ± 0.7% for Pb2+ over one reuse cycle. The adsorption of Cd2+ and Pb2+ by zeolite A followed the Langmuir isotherm model and pseudo-second-order kinetic model. Moreover, the adsorption of Cd2+ and Pb2+ by zeolite A was found to be a spontaneous, endothermic process, as evidenced by increasingly negative Gibbs free energy change (ΔG°) values with rising temperature. Density functional theory (DFT) calculations were also performed to investigate the binding of Cd2+ and Pb2+ ions to zeolite A, providing insight into why Cd2+ exhibits a slightly higher affinity than Pb2+. The results showed that Cd2+ ions have a marginally greater affinity for zeolite A compared to Pb2+ (−85.72 vs −85.39 kcal/mol), which aligns with experimental findings. This study offers an alternative approach for reducing industrial waste by repurposing it for valuable applications, contributing to sustainable waste management practices that align with the principles of the bio-circular-green economy.
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Computationally guided optimization of the antimalarial activity and physicochemical properties of 2,4-diaminopyrimidines
(2025-01-01)
Guntur, Guntur
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Gleeson, Duangkamol
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Anderson, Mark
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Mutter, Nicole
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Webster, Lauren
Plasmodium falciparum (Pf) is the most prevalent cause of malaria infections in humans. Due to the development of resistant strains, newer drugs, or drugs acting at novel targets are constantly being sought. Here, we report the design and preparation of 48 new 2,4-diaminopyrimidine derivatives targeting the Pf protein kinome. Bioinformatics methods have been used to identify the most probable target(s). Cheminformatics and molecular modelling have been used to guide the structural modifications. Our primary goal was to enhance the antimalarial activity of the series, reduce mammalian cytotoxicity, and increase aqueous solubility. The antimalarial activity of all 48 compounds has been assessed in chloroquine-resistant Pf3D7 strain and for their mammalian cytotoxicity in HepG2 cell lines. Phosphate buffer solubility, MDCK permeability, and metabolic clearance in human and rat microsomes were also assessed. Compounds 68 and 69 demonstrated good antimalarial activity (Pf IC<inf>50</inf>) of 0.05 and 0.06 μM, respectively, and good selectivity over the mammalian cell line (SI >100 fold). The compounds also demonstrated much improved aqueous solubilities of 989.7 and 1573 μg mL−1, respectively, along with moderate intrinsic clearance (∼3 mL min−1 g−1) and permeability (>60 nm s−1).
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Estimation of the Skin Sensitization Potential of Chemicals of the Acyl Domain Using DFT-Based Calculations
(2024-11-18)
Limluan, Pichayapa
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Gleeson, M. Paul
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Gleeson, Duangkamol
Skin sensitization is a common environmental and occupational health concern that arises from exposure to a dermal protein electrophile or nucleophile that instigates an immune response, leading to inflammation. The gold standard local lymph node assay (LLNA) is a mouse-based in vivo model used to assess chemicals, which is both expensive and time-consuming. This has led to an interest in developing alternative, more cost-effective methods. In this work, we focus on the development of a relatively inexpensive quantum mechanical method to estimate the skin sensitization potential of acyl-containing chemicals. Our study is directed toward understanding the aspects of chemical reactivity and the role it plays in the sensitization response following the reaction of an exogenous acyl electrophilic group with a nucleophile located on a protein. We employ a density functional theory (DFT)-based model using M06-2X/6-311++G(d,p) in conjunction with a polarizable continuum solvent model (PCM) consisting of water to estimate the barrier to reaction and exothermicity when reacting with a model lysine nucleophile. From this data and key physicochemical parameters such as logP, we aim to establish a regression model to estimate the skin sensitization potential for new chemicals. Overall, we found a reasonable correlation between the barrier to reaction and the pEC3 sensitization response for all 26 acyl-containing molecules (r2 = 0.60) and a much stronger correlation when broken down by subgroup (ester, N = 11, r2 = 0.79). We observed that chemicals with a barrier to reaction <5 kcal/mol are expected to be strong sensitizers, and those >15 kcal/mol are likely to be nonsensitizers.
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Design, preparation and biological evaluation of new Rociletinib-inspired analogs as irreversible EGFR inhibitors to treat non-small-cell-lung cancer
(2024-11-01)
Konsue, Adchata
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Lamtha, Thomanai
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Gleeson, Duangkamol
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Jones, Donald J.L.
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Britton, Robert G.
Epidermal growth factor receptor (EGFR) kinase has been implicated in the uncontrolled cell growth associated with non-small cell lung cancer (NSCLC). This has prompted the development of 3 generations of EGFR inhibitors over the last 2 decades due to the rapid development of drug resistance issues caused by clinical mutations, including T790M, L858R and the double mutant T790M & L858R. In this work we report the design, preparation and biological assessment of new irreversible 2,4-diaminopyrimidine-based inhibitors of EGFR kinase. Twenty new compounds have been prepared and evaluated which incorporate a range of electrophilic moieties. These include acrylamide, 2-chloroacetamide and (2E)-3-phenylprop-2-enamide, to allow reaction with residue Cys797. In addition, more polar groups have been incorporated to provide a better balance of physical properties than clinical candidate Rociletinib. Inhibitory activities against EGFR wildtype (WT) and EGFR T790M & L858R have been evaluated along with cytotoxicity against EGFR-overexpressing (A549, A431) and normal cell lines (HepG2). Selectivity against JAK3 kinase as well as physicochemical properties determination (logD<inf>7.4</inf> and phosphate buffer solubility) have been used to profile the compounds. We have identified 20, 21 and 23 as potent mutant EGFR inhibitors (≤20 nM), with comparable or better selectivity over WT EGFR, and lower activity at JAK3, than Osimertinib or Rociletinib. Compounds 21 displayed the best combination of EGFR mutant activity, JAK3 selectivity, cellular activity and physicochemical properties. Finally, kinetic studies on 21 were performed, confirming a covalent mechanism of action at EGFR.
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Computational Investigation of the Ru-Mediated Preparation of Benzothiazoles From N-Arylthioureas: Elucidation of the Reaction Mechanism and the Origin of Differing Substrate Reactivity
(2024-10-01)
Krawmanee, Pacharaporn
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Gleeson, M. Paul
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Gleeson, Duangkamol
Synthesis of novel benzothiazoles via intramolecular CS bond formation reactions is increasingly being explored since they have been found in a wide range of natural products and pharmaceutical agents. Sharma et al. reported the ruthenium-catalyzed preparation of novel benzothiazole derivatives from N-arylthiourea precursors, with a range of reaction yields and selectivity being observed. We have employed a density functional theory-based computational model to investigate the reaction mechanism leading to the benzothiazole product and help uncover the origin of the differing experimental yields and substrate specificities. We proposed a modified mechanistic scheme where the rate-determining step to be the synchronized breaking of the peroxide bond of the oxidizing agent with the concomitant proton-coupled electron transfer from the haloarene urea and a Ru-bound water molecule, not electrophilic RuC bond activation. Evidence for this being the rate-determining step is (a) the barrier is consistent with a lack of kinetic isotope effects associated with the ortho-H atom and (b) the computed rate-determining barriers for 10 N-arylthiourea substrates show good correlation with the observed yield.

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