Abstract: 4-Dimethylamino-2’-hydroxy chalcone (DHC) 1 is an important natural compound that is nearly non-fluorescent in solution but highly fluorescent in its crystalline state. At room temperature, the weak fluorescence from DHC solution is exclusively from its keto tautomer, without notable contribution from its enol tautomer. By using low temperature fluorescence, the study found that the enol emission could be detected upon cooling with liquid N₂ in a protic solvent (e.g. EtOH). This led to observation of the fluorescence vibronic structure of enol tautomer, in addition to its enol emission λ_em ≈ 473 nm that is well separated from its keto tautomer emission (λ_em ≈ 600 nm). By freezing DHC in a solvent matrix, the study revealed the fluorescent characteristics of a single molecule in a rigid environment. Further comparison of DHC in a solvent matrix and crystalline state disclosed that the emission of crystalline DHC was primarily from the keto tautomer, along with some minor contribution from the enol tautomer, despite the tight packing environment in the crystalline state.

Abstract: Syzygium polyanthum (Indonesian bay leaf) is widely consumed as a culinary spice and is traditionally used for health related purposes, yet chemical standardization of region specific materials remains limited, particularly for nonpolar fractions that contain volatile and semivolatile constituents. This study aimed to generate a baseline chemical fingerprint of the n hexane fraction of S. polyanthum leaves collected in Paniki Bawah, Mapanget District, Manado, Indonesia. Dried leaf powder was macerated with 96% ethanol for six days with daily solvent renewal, the filtrate was concentrated under reduced pressure, redissolved in warm distilled water, and fractionated by liquid liquid partitioning to obtain the n hexane fraction. The fraction was analyzed by GC MS, and peak identities were assigned by spectral library matching. Twenty constituents were tentatively identified, dominated by fatty acids and fatty acid methyl esters, with additional aliphatic ketones and terpene related compounds. Major annotations included decanoic acid, dodecanoic acid, tetradecanoic acid, 2 undecanone, 2 tridecanone, nerolidol, and 6,10,14 trimethyl 2 pentadecanone. The clustering of multiple library hits at identical retention times suggests potential coelution; therefore, the reported profile is best interpreted as a qualitative screening fingerprint rather than definitive quantification. Overall, these findings provide a region specific reference for future marker selection, batch to batch comparison, and integration with targeted bioactivity assays to support quality control development for S. polyanthum based products.

Abstract: The compound Z-6-heneicosen-11-one, a possible pheromone component of the hickory tussock moth, Lophocampa caryae, and a known pheromone component of the Douglas fir tussock moth, Orgyia pseudotsugata, was synthesized by a new four step procedure with a 39% overall yield and a six-step procedure incorporating a protecting group with a 28% overall yield. This new synthesis is comparable to other similar syntheses for this molecule in the literature.

Abstract: LiAlH₄ reduction of tert-butyl (S)-butyl(1-((2-cycloheptylethyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate (1) gave imidazolidine 2, while treatment with LDA furnished the β-elimination product, cinnamamide 3. Both products were fully characterized. Reductive cyclization of N-alkylated-N-Boc-protected amino acid amides with LiAlH₄ may be a viable synthetic method for trisubstituted chiral imidazolidines.

Abstract: N-Alkyl urazoles are important heterocyclic compounds that serve as important precursors to potent N-alkyl 1,2,4-triazoline-3,5-dione electrophiles. Traditional methods for urazole synthesis have relied upon the use of toxic isocyanates. We have modified and optimized an overlooked and poorly-described literature method for the synthesis of urazoles that now avoids the use of isocyanates, limits the use of solvents, and provides urazoles without the need for purification steps. A variety of urazoles are afforded in good to high yields.

Abstract:

This study reports the convenient synthesis of a new series of sustainable heterocyclic compounds called 3-N-Substituted 5-aryl(hetaryl)-thieno[2,3-d]pyrimidin-4(3H)-ones, encompassing two biologically important pharmacophores namely thiophen and pyrimidine. A stepwise synthesis of 5-aryl(hetaryl)thieno[2,3-d]pyrimidine-4(3H)-ones with variable substituents at the N 3 position was proposed, which involves the synthesis of aromatic and heteroaromatic substituted 2-aminothiophenes, their condensation with N,N′-dimethylformamide dimethylacetal. Obtained 2-dimethylaminomethyleneamino-thiophenes condense with primary amines. This sequence of reactions leads to the production of new polyheteroconjugated systems with advantages like simple work up, easy separation of the products and chromatography-free purification. Structural elucidation was done by spectroscopic method and elemental analysis and have confirmed their molecular structure. The synthesized compounds were tested on their antibacteriial activity against Gram positive and Gram negative bacteria. Compound 6k showed notable antibacterial activity compared to the standard drug (Gentamicin) against S. aureus bacteria. Compounds 6e and 6k were evaluated for their antimicrobial potential via molecular docking against S. aureus Aminoglycoside Phosphotransferase and P. aeruginosa TrmD. Compound 6k exhibited superior binding affinity and an enhanced pharmacokinetic profile, positioning it as a promising lead for further optimization and development as an antimicrobial agent. However, as this study represents an initial screening, further in silico investigations are required for predicting antibacterial activity of target derivatives with calculated substituents. Overall, this work highlights the efficiency of a convenient approach for synthesizing 3-N-Substituted 5-aryl(hetaryl)-thieno[2,3-d]pyrimidin-4(3H)-ones and underscores their potential as promising scaffolds for the development of potent antibacterial agents.

Abstract:

Aiming at p53-reactivating compounds, a convergent scheme for the preparation of conjugates with the dispiro-indolinone-pyrrolidine-thioimidazolone and glutarimide moieties connected via a triazole-containing linker were proposed. Target conjugates were synthesized by azide-alkyne cycloaddition reactions between propargylthio-substituted dispiro-indolinone-pyrrolidine-imidazolones and an azido-glutarimide derivative. The starting compounds were available isothiocyanates, glycine, substituted benzaldehydes, chloroacetamide, and ethyl acrylate. The key azide-alkyne cycloaddition step was carried out using TBTA as a catalyst, achieving >70% product yields. The resulting bifunctional compounds contained a fragment of dispiroindolinone (p53-MDM2 interaction inhibitor) and glutarimide, an ubiquitin ligase ligand. The dispiroindolinone-glutarimide conjugate with 5-bromoisatine and 4-bromophenyl moieties showed a potential for p53 re-activation as determined by preferential cytotoxicity against HCT116 colon carcinoma cells (wild type53) compared to the isogenic HCT116p53^-/- subline.

Abstract: Over the last 20 years Deep-Eutectic-Solvents (DES) have been making a significant impact in the field of chemistry, with applications in nanotechnology, biomass transformation, electrochemistry pharmaceuticals and a host of other applications that includes catalysis. Considering the importance of chiral organocatalysis for the selective synthesis of drugs, pharmaceuticals and fragrances etc. DESs were quickly harnessed as the media for carrying out organocatalytic transformations. In this review, we discuss some of the most important examples from the literature that have made an impact in the field over the last 5 years. A more recent development has been the incorporation of DESs in structured and self-organized gel-like assemblies that are known as EutectoGels. These soft structures offer a more defined and compact environment that can influence stereoselectivity by pre-organizing the reactants in three-dimensional space, and potential control the types of transition states that can be formed.

Abstract: cycloaddition of isatin ketonitrone 1,3-dipoles, generated from the condensation of various substituted isatins and arylhydroxylamines, with coumarins. The pentacyclic products bearing four consecutive stereocenters, including two quaternary carbon stereocenters fused in one ring structure, were smoothly acquired in moderate to high yields (22-98%) with high regio- (α and exo type) and diastereoselectivities (>20:1 dr). The synthesized compounds (>45 examples) were well characterized through different spectroscopic techniques, such as single crystal XRD, FTIR, NMR, and mass spectral analysis.

Abstract: 9-Mesitylacridinium salts are widely recognized as efficient organic photoredox catalysts owing to their strong excited-state oxidizing power and stability under visible-light ir-radiation. In this study, a new mesityl acridinium derivative bearing a di-tert-butylphenyl substituent on the nitrogen atom was synthesized. The introduction of tert-butyl groups on the N-aryl moiety was primarily aimed at improving solubility and chemical stability of the acridinium salt. The target compound was obtained in high overall yield starting from a 9(10H)-acridinone precursor through a concise synthetic sequence. The synthesis consists of a copper-catalyzed C–N coupling reaction to install the aryl substituent on the nitrogen atom, followed by a Grignard reaction and subsequent acid treatment to afford the corresponding acridinium salt. All transformations proceeded smoothly, providing efficient access to the desired novel acridinium derivative. This work presents a practical example of structural modification of mesitylacridinium derivatives directed toward enhanced solubility and stability, and provides a useful synthetic plat-form for the preparation of structurally diverse acridinium salts.

Abstract: In this study we engineered bilayered electrospun scaffolds consisting of hydrophobic PDLLA and hydrophilic PVP layer which incorporate either native HA or semi-synthetic HA-Gly-OH at concentrations of 1% and 3% w/w. Generally, bilayer scaffolds electrospun on different days delaminated, while herein they maintained their integrity because electrospun on the same day. Sequential electrospinning enabled the bilayer structure, characterized via Scanning Electron Microscopy (SEM), Atomic Force Microscopy (AFM), and Young’s modulus measurements to assess morphology and mechanics. In vitro cytotoxicity and cell viability assays with fibroblast cells confirmed good biocompatibility for both the individual layers and bilayer system. Among the tested formulations, the bilayer PDLLA/PVP–HA-Gly-OH 1% showed the most promising performance, attributed to the synergistic effects of HA and Gly-OH in promoting adhesion and proliferation.

Abstract: 1,4-Dimethoxy-2,3-dinitrobenzene (1) reduction using sodium hydrosulfite gave 3,6-dimethoxybenzene-1,2-diamine (2) and 3,6-dimethoxy-2-nitroaniline (3) in 24% and 59% yield respectively. The nitroaniline 3 was acetylated with acetyl chloride to give N-(3,6-dimethoxy-2-nitrophenyl)acetamide (4) in 65% yield and with acetic anhydride to give N,N’-(3,6-dimethoxy-2-nitrophenyl)diacetamide (5) in 78% yield. Novel compounds 4 and 5 were characterized by FT-IR, 1H and 13C-NMR, and HRMS. The X-ray crystal structure of acetamide 4 is presented.

Abstract: Many medicines do not dissolve well in water, which can limit how quickly and effectively they work. One proven way to improve this is to attach a natural sugar molecule to the drug. In this study, we investigate paracetamol β-D-glucoside (C₁₄H₁₉NO₇), a modified form of paracetamol in which glucose is chemically linked to the drug through a β-glycosidic bond. This simple molecular change increases water solubility by 6–8 times compared to regular paracetamol, allowing faster dissolution and more flexible liquid formulations. The sugar–drug link is stable under normal body conditions but breaks apart under specific environments. At neutral pH (similar to blood), the compound remains highly stable, with a half-life exceeding 1000 hours at 25 ℃. Under acidic conditions similar to the stomach (pH 2, 37 ℃), it breaks down within minutes, releasing active paracetamol. Natural enzymes in the intestine and liver can also rapidly cleave the bond, enabling controlled and site-specific drug activation. Computer simulations confirm the proposed breakdown mechanism and support the experimental findings. Stability testing was performed under internationally recognised pharmaceutical guidelines (ICH, USP, FDA, EMA), showing predictable behaviour and acceptable impurity control. Formulation strategies such as protective coatings and temperature management suggest a projected shelf life of 2–3 years. Importantly, when the compound breaks down, it releases both paracetamol and a small amount of glucose. This creates a dual-action system that provides pain relief while also contributing mild energy support during illness. Paracetamol β-D-glucoside, therefore, represents a practical and scientifically validated approach to improving a widely used medicine.

Abstract: DNA-encoded chemical libraries (DECLs/DELs) enable the pooled synthesis and selection of millions to billions of DNA-barcoded small molecules, providing an efficient route to discover binders and early leads against diverse biological targets. As DEL-derived programs advance toward identifying clinical candidates, the asset surface of a DEL platform expands from a small set of optimized hits to include library designs, building-block combinations, DNA tags, selection data, and physical library stocks, thus creating new challenges in registration, traceability, and scalable ownership in transfer practices. Non-fungible tokens (NFTs) are unique blockchain-native tokens that can represent digital assets that can be coupled to smart contracts to enable traceable transactions and programmable rights management, which inspire proposals to tokenize intellectual-property (IP) assets such as patents. Here, we review (i) the scientific and commercial value of DEL in modern drug discovery, (ii) NFT/blockchain concepts, specifically in reported biomedical-IP and supply-chain use cases, and (iii) a conceptual architecture for NFT-enabled registration and controlled transfer of DEL libraries or sublibraries using on-chain identifiers with off-chain encrypted metadata and legal agreements.

Abstract: 1,2,4-Trisubstituted chiral homoallylic alcohols are valuable intermediates in natural product synthesis and complex molecular architectures; however, their asymmetric catalytic synthesis remains challenging due to the need for simultaneous and precise control of regioselectivity, diastereoselectivity, E/Z geometry, and enantioselectivity. Herein, we report a chiral transfer reaction based on a palladium-catalyzed three-component reaction of aldehydes, borylated allyl acetate, dimethylzinc for the efficient synthesis of 1,2,4-trisubstituted anti-(Z)-chiral homoallylic alcohol derivatives. Readily accessible borylated chiral homoallylic alcohols, prepared for example via Sharpless asymmetric epoxidation, serve as effective starting materials, allowing highly stereocontrolled formation of 1,2,4-trisubstituted anti-(Z)-chiral homoallylic alcohols.

Abstract: We present a modular building block strategy for synthesizing phosphonated polyaromatic systems as an alternative to the conventional late-stage phosphonation of prefabricated aromatic scaffolds, which often requires harsh conditions and has limited tolerance for functional groups. A monophosphonated biphenyl building block was obtained via nickel-catalyzed phosphonation of dibromobiphenyl at 170 °C for three hours. This synthesis is more economical and milder than typical high-temperature palladium systems. In parallel, a borated pyrene derivative was prepared by Suzuki-Miyaura borylation. The final palladium-catalyzed Suzuki cross-coupling reaction produced the target compound, octaethyl(pyrene-tetrakis(biphenyl))tetrakis(phosphonate), Et8-PyTPPE. Single crystal X-ray diffraction reveals a centrosymmetric molecule that crystallizes in the triclinic space group P–1, with the inversion center located at the central C–C bond of the pyrene core. The pyrene unit is essentially planar, while the biphenylphosphonate arms are highly twisted relative to the core and to each other. The crystal packing is dominated by weak intermolecular interactions, and no significant π–π stacking is observed. Hirshfeld surface analysis shows that H···H (60.5%) and C···H (22.5%) contacts predominate, while O···H interactions (14.4%) with phosphoryl oxygen atoms represent the most relevant directed contacts. From photophysical investigations, Et8-PyTPPE exhibits blue fluorescence (λem. = 452 nm) in solution and aggregation-induced red-shifted emission with nanosecond lifetimes in the solid state, confirming purely fluorescent behavior.

Abstract: This study investigates the synthesis of 1-hydroperoxyadamantane addressing discrep-ancies in prior literature. Our results demonstrate that previous authors were unable to obtain claimed compound under the conditions they described. We confirmed that 1-hydroperoxyadamantane can be synthesized in good yields via the reaction of 1,3-dehydroadamantane with concentrated hydrogen peroxide in DCM. Structure of 1-hydroperoxyadamantane was confirmed by SC XRD analysis. These findings clarify the conditions necessary for successful synthesis of this compound and highlight the im-portance of comprehensive analytical verification. The study also provides a very detailed, repeatedly verified method for synthesizing 1,3-dehydroadamantane and a description of the necessary laboratory equipment.

Abstract: An alkene-tethered enaminone was synthesized in four steps from bromoacetic acid and 3,3-dimethylallyl alcohol. The enaminone was fully characterized, including UV-Vis spectra. TBADT-catalyzed HAT of the alkene-tethered enaminone initiated a fragmentation that yielded the literature-known phenylacetone-derived enaminone.

Abstract: Phenazine derivatives are attractive organic chromophores due to their redox activity and photophysical properties, yet their application in photocatalytic hydrogenation reactions remains underexplored. In this work, a homogeneous phenazine-based photocatalytic system was developed and applied to the visible-light-driven hydrogenation of nitro compounds under mild conditions. The photocatalysts’ activity was evaluated using nitrobenzene as a model substrate in the presence of triethanolamine as a sacrificial hydrogen and electron donor. Reaction parameters including photocatalyst structure, solvent, hydrogen source, irradiation wavelength, and catalyst loading were systematically investigated. Under optimized conditions, nitrobenzene was converted to aniline with yields of up to 81% after 12 h of irradiation at ambient temperature. Kinetic studies revealed that prolonged irradiation does not enhance conversion and can lead to decreased yields due to the instability and reconversion of azo-type intermediates. Substrate scope investigations demonstrated higher reductive efficiency for nitroarenes bearing electron-withdrawing substituents, whereas aliphatic nitro compounds were only partially reduced, often yielding oxime or N–OH intermediates. UV–Vis, fluorescence, and EPR spectroscopy provided mechanistic insight and confirmed the involvement of radical species generated upon light irradiation. Overall, this study establishes phenazine-based photocatalysts as effective metal-free systems for the hydrogenation of nitroarenes under visible light and mild reaction conditions.

Abstract: Background. Late-stage metastatic cutaneous melanoma (MCM) and neuroblastoma (NB) are the most aggressive skin and childhood cancers with survival rate < 50%, mainly due to the emergence of resistance to available drugs, thus requiring urgent solution. Quaternary phosphonium salts (QPSs) can exhibit up to strong anticancer effects, regardless the developed resistances. Methods. Triphenyl (1) and diphenyl (3 and 4) phosphonium salts were synthesized, treating commercial triphenyl phosphine and synthesized 11-diphenylphosphanyl-undecan-1-ol (2) respectively, with benzyl bromide. Upon fully characterization, they were tested, for the first time, on MeTRAV (BRAF^V600D) and MeOV (BRAFV600E) vemurafenib (PLX)-resistant MCM cells, etoposide (ETO)-sensitive (HTLA 230) and multidrug resistant (MDR) (HTLA ER) NB cells, not tumorigenic human keratinocytes (HaCaT) and mouse embryonic fibroblasts (3T3), as well as red blood cells (RBCs). Results and Discussion. Viability of MeTRAV cells was decreased to 44.8% by admin-istration of 1 (100 µM), in intermediate-time (48h) treatments, while short-time exposure (24h) to 3 (≥ 75 µM) and 4 (≥ 50 µM) was sufficient to reduce their viability to 33.6 and 32.2%. Viability of MeOV was decreased under 50% with 5 µM concentrations of 1 and 25 µM of 3 and 4, while were exterminated (26.9, 20.6 and 21.8%) with higher concentrations after 48h exposure. Collectively, 1 was the better performant compound (IC₅₀ = 6.4 µM, 48h). Viability of HTLA ER cells was decreased under 50% upon 72h administrations of 1 at concentrations ≥ 50 µM, 48h (≥ 75 µM) and 72h (≥ 50 µM) of 3 and after 72h (≥ 75 µM) of 4, but 72-hours exposure and high concentrations of all compounds were necessary for their extermination (31.2, 28.7, 29.7%). Viability of HTLA 230 cells was not < 50% when 1 and 4 were administered for only 24h, while their viability was < 50% after administration of 3 at all-times exposure. At high concentrations all compounds exterminated cells (33.6, 25.3%, 1, 48-72h; 38.6, 30.2, 24.7%, 3, 24-72h; 33.2%, 4, 72h). The best performant compounds were 1 (IC₅₀ = 4.0 µM, HTLA 230) and 3 (IC₅₀ = 27.8 µM, HTLA ER) at 72h exposure. The cytotoxic effects of compound 4 on MeTRAV cells, when exposed to 24/48h treatments were comparable to those of PLX on same cells in 72h ones. 1, in shorter 48h treatments of PLX-R MeOV, was 2.5forl more cytotoxic than PLX in 72h ones. All compounds were no cytotoxic to 3T3 cells, at all time of exposure, low cytotoxic to HaCaT cells in 24 and 48h treatments and softly cytotoxic to RBCs in 24h ones. Conclusions. Compound 1 could be a promising platform to develop new intermediate-time therapies for PLX-R MeOV cells, while 4, to develop 24- and 48-hours treatments for PLX-R MeTRAV cells. Also, all compounds could be developed as new treatment options for both ETO-sensitive and MDR late-stage HR-NB cells, being all more effective than ETO by 1.2, 2.0, 1.3 times (HTLA 230) and 3.2, 4.7 and 3.2 times (HTLA ER). All compounds could be interesting to be developed as adjuvants in already existing anticancer cocktails to treat MCM and/or NB.