Organics

Understanding the factors that affect the detonation performance of high-energy molecules (HEMs) is crucial for the design of novel explosives and fuels with desirable characteristics. While molecular factors, such as the presence of specific functional groups that give organic molecules explosive properties, are key determinants of detonation characteristics, other factors like the geometry of molecules in crystal structures can also affect the high-energy properties of materials. Although it is known that slight deviations in the crystal structure geometry affect the sensitivity of nitroaromatic explosives, the influence of these variations on detonation performance remains unknown. In this study, we extracted different crystal structures of the same high-energy nitroaromatic molecules from the Cambridge Structural Database and calculated their detonation velocities and pressures using the Kamlet–Jacobs equations. Results indicated that different geometries of the same crystal structure can lead to non-negligible differences in detonation velocities and pressures. In the case of the 2,4,6-triamino-1,3,5-trinitrobenzene molecule, discrepancies in detonation pressures among different crystal structures were calculated to be 7.68%. Analysis of geometrical arrangements showed that these differences are mainly the consequence of diverse non-covalent bonding patterns that affect crystal densities. Full article

Quinolones represent one of the largest classes of synthetic antibiotics used in both human and veterinary medicine. Since the discovery of nalidixic acid, a substantial body of research has been carried out on quinolones, resulting in the synthesis of several quinolone derivatives with exceptional pharmacology. In addition to their antibacterial action, quinolones have a broad spectrum of diverse biological activities. In this regard, the present review examines the literature of recent years describing synthesis protocols, reactivity and biological properties, with particular emphasis on the antibacterial, antimalarial, antitrypanosomal, antileishmanial, antiviral and anticancer activities of this famous class of molecules. Finally, this review highlights the potential of quinolones as preferred pharmacophores in medicinal chemistry. The aim is to highlight the innovative aspects of the rational design of new therapeutic agents with this structural motif, in the face of emerging antibiotic resistance and the urgent need for new active molecules. Full article

Indole heterocycles have an established reactivity, and these compounds are H-bond donors via a peculiar non-basic NH. However, the indole core has been scarcely employed in organocatalysis, with only a few examples relevant to electrophilic halogenation reported. To expand the range of potential transformations achievable via indole catalysis, we have designed a set of new organic species incorporating an indole core, alongside three privelaged chiral moieties found in many known organocatalysts, namely a quaternary ammonium salt, a diamine and an amino-urea. Herein, we report an optimised synthetic route for the preparation of these potential catalytic species in an enantiomerically pure form. The syntheses are conceived to be modular and therefore will allow each of the three single organic catalysts to be expanded into families without alteration of the synthetic layout, therefore leading to a fast optimisation of new asymmetric procedures. Full article

This study describes the efficient synthesis of five dinitrochalcones (DNCHs) using an ultrasonic bath as an unconventional method to improve reaction yields and reduce reaction times. The Claisen–Schmidt condensation of nitroacetophenones and nitrobenzaldehydes was carried out in a cyclohexane–methanol solvent system under ultrasonic irradiation, achieving yields between 56% and 92%. The application of ultrasound not only accelerated the reaction but also improved the overall efficiency compared to conventional methods such as magnetic stirring. The synthesized compounds were characterized by NMR spectroscopy, which corroborated their structures. Therefore, it is confirmed that obtaining DNCHs with a nitro group in ortho by ultrasonic irradiation is an energetically efficient and environmentally friendly alternative. Full article

γ-amino butyric acid (GABA) is an inhibitory neurotransmitter whose deficiency has been associated with various neurological disorders. However, its low liposolubility limits its use as a supplement. Thus, multiple investigations have focused on searching for lipophilic GABA analogs that can modulate the activity of the GABA_B receptor, which could be associated with the etiology of some central nervous system disorders. The GABA analogs available on the market are Vigabatrin, Gabapentin as well as Pregabalin and Baclofen. In this work, we report on the synthesis of GABA analogs, taking the scaffold of GABA, Pregabalin, and Baclofen as a starting point. The analogs include structural features that could favor the affinity of the molecules for the GABA_B receptor, such as heterocyclic rings in the γ-position and alkyl or p-Cl-phenyl substituents (in analogy to Pregabalin and Baclofen, respectively). These analogs were synthesized by a sequence of reactions involving an N-alkylation, a 1,4-conjugated addition of dialkyl and diarylcuprates and a basic hydrolysis. Furthermore, a computational molecular docking over the GABA_B receptor was performed to evaluate the interaction of each compound in the Baclofen binding site. With this information, we evaluated our compounds as GABA_B agonists through a QSAR analysis. Finally, by means of molecular similarity analysis, and in silico ADME prediction, we support our three best compounds (8a–b, 8d) as potential GABA_B receptor agonists. Full article

A graft reaction of polyvinyl chloride (PVC) with furfural was conducted in a tetrahydrofuran solution. The resulting graft structure (FF-g-PVC) was characterized using UV spectroscopy, photoluminescence (PL), Fourier Transform Infrared (FTIR) spectroscopy, Raman spectroscopy, and proton nuclear magnetic resonance (¹H NMR) spectroscopy. The grafting efficiency was determined through ultraviolet spectrophotometry. Thermal stability analysis via thermogravimetric (TG) testing revealed that furfural was successfully grafted onto the PVC chain. In a nitrogen atmosphere, the temperature of the maximum weight loss rate during the first stage of pyrolysis increased from 296.3 °C to 301.7 °C, while the activation energy for the second stage increased from 199.4 kJ/mol to 294.4 kJ/mol, indicating enhanced stability and delayed degradation of the PVC. Additionally, microwave irradiation markedly improved the graft reaction, achieving a grafting rate of 57.76‰ compared to only 1.808‰ with water bath heating. The optimal conditions were found to be a PVC/FF/Zn ratio of 1:1:0.9, with microwave irradiation for 20 min at 40 °C. Full article

Six secondary amine derivatives derived from salicylaldehyde (SA) were successfully synthesized in good to excellent yields and evaluated for their biological activities. The synthesized compounds exhibited remarkable antioxidant properties, as determined by ABTS and phenanthroline assays. Notably, compound 2 demonstrated an IC₅₀ value of 5.14 ± 0.11 µM in the ABTS assay, approximately six to nine times lower than the standards BHT and BHA. In the phenanthroline assay, all compounds showed inhibition capacities five to ten times greater than BHT and comparable to BHA, with A_0.5 values ranging from 9.42 to 31.73 µM. Among these, compound 5 displayed the lowest A_0.5 value of 9.42 ± 1.02 µM. The anti-inflammatory activity, assessed through BSA denaturation, revealed that compounds 2 and 5 were the most promising, although their activity was moderate compared to the standard diclofenac. The insecticidal potential of the compounds was evaluated against the storage insect pest Tribolium castaneum. Among the tested derivatives, compounds 1 and 6 exhibited the highest efficacy, achieving maximum mortality rates of 73.31% and 76.67%, respectively, over a seven-day treatment period. Furthermore, the molecular geometry, electronic properties, and intramolecular interactions of all compounds were investigated using DFT calculations. Thermodynamic analyses of the antioxidant mechanisms suggested that the NH bond is the most likely site for free radical attacks. These findings underscore the significant biological potential of the synthesized salicylaldehyde-derived secondary amines. Full article

The commercial flame-retardant 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) was almost quantitatively converted in sodium [2-(2-hydroxyphenyl)phenyl]phosphinate Na[OH-Ph-Ph-PHO₂] and disodium 2-(2-phosphinatophenyl)benzen-1-olate Na₂[O-Ph-Ph-PHO₂] under mild reaction conditions and without the use of toxic reactants. The structure of Na[OH-Ph-Ph-PHO₂] was determined by means of single-crystal X-ray diffraction. The inter- and intramolecular Na-O interactions generate a stair-like framework where the sodium cations are five-coordinated and exhibit a highly distorted coordination sphere. The two compounds are characterized by appreciable blue luminescence at the solid state upon excitation with UV light, attributed to S₁→S₀ decays on the basis of time-resolved measurements and computational calculations. The photoluminescence quantum yield is higher for Na₂[O-Ph-Ph-PHO₂], and the emission and excitation bands are shifted at longer wavelengths. The disodium salt showed affinity towards cellulose, and doped Na₂[O-Ph-Ph-PHO₂]@cellulose samples maintained emission features comparable to those of the pure compound. The nature of the interaction between cellulose and the emitting species was studied by means of periodic density functional theory calculations, that highlighted the role of the sodium cations. Full article

A series of photoacylations of 1,4-naphthoquinone with various aldehydes and using Pyrex-filtered UVB light was conducted under continuous-flow conditions. Acetone served as a triplet photosensitizer and convenient solvent that kept all materials in solution and could be easily removed. The corresponding acylated 1,4-naphthohydroquinone photoproducts were obtained in acceptable to excellent yields of 30–90% with residence times of just 70 min. The photoacylation process was successfully coupled with in-line oxidation to obtain acylated 1,4-naphthoquinones. Full article

Bioactive peptides are promising therapeutic agents due to their antimicrobial and anticancer activities, although their lack of selectivity often limits clinical applications. This study demonstrates the optimal synthetic route for conjugating folic acid (FA) with the bioactive peptide Lunatin-1, aiming to improve selectivity for neoplastic cells. The synthesis combines solid-phase peptide synthesis (SPPS) and Cu(I)-catalyzed cycloaddition to link folic acid to Lunatin-1 via a triazole ring. Using the model tripeptide FIG-_NH2, key intermediates and the final product were characterized by high-performance liquid chromatography (HPLC), mass spectrometry (MALDI-ToF), Fourier-transform infrared spectroscopy (FTIR), and nuclear magnetic resonance (NMR). Reaction yields and purity were optimized with FIG-_NH2, providing a reproducible synthesis pathway. Additionally, the results confirmed successful conjugation, with the FA-Trz-Luna product exhibiting molecular integrity and structural stability, as validated by spectral analyses. This study highlights a potential synthesis route for peptide-folate conjugates to be used as selective and multifunctional therapeutic agents, laying the groundwork for biological evaluations of their cytotoxicity and antimicrobial properties. Full article

Nowadays, PSMA ligands are widely used for radiotheragnostic purposes in prostate cancer. The synthesis of a PSMA-Bisp conjugate was developed and realized with good yield (overall yield ~58% for the last two steps). All newly synthesized compounds were characterized by physicochemical methods: ¹H and ¹³C NMR, HRMS, and LCMS (for biologically tested samples). Subsequently, Bisp1 (diacetate bispidine ligand), Bisp-alkyne (bifunctional derivative of Bisp1), and its conjugate PSMA-Bisp were labeled by ⁶⁴Cu in mild conditions. In vitro studies of the labeled conjugate [⁶⁴Cu]Cu-PSMA-Bisp have shown great stability in model solutions. Finally, [⁶⁴Cu]Cu-PSMA-Bisp was compared to the well-known PSMA-617 conjugate labeled with ⁶⁴Cu and they showed similar stability in excess bovine serum (BVS), and at the same time, labeling PSMA-Bisp with ⁶⁴Cu is characterized by extremely high kinetics in mild conditions, while labeling PSMA-617 with ⁶⁴Cu requires heating (90 °C). Thus, this conjugate can be incredibly promising for nuclear medicine. Full article

Developing new biomolecule–drug conjugates as prodrugs is a promising area for natural products and pharmaceutical chemistry. Herein, a cholesterol–doxorubicin (Chol-DOX) conjugate was synthesized using cholesteryl-4-nitrophenolate as a facile, stable, and controllable activated ester. This approach offers an alternative to the conventional HCl-emitting cholesteryl chloroformate method. Semi-empirical theoretical calculations showed that cholesteryl-4-nitrophenolate exhibits moderate reactivity, greater thermodynamic stability, a higher dipole moment, and a lower HOMO-LUMO energy gap compared to cholesteryl chloroformate, suggesting that cholesteryl-4-nitrophenolate could be used as a more controllable acylating agent. The structure of the synthesized Chol-DOX conjugate was characterized using NMR, MS, and FT-IR techniques. Biological properties of the Chol-DOX conjugate were analyzed with a comparison of theoretical and experimental data. This work provides a facile and controllable method to synthesize natural lipid–DOX prodrugs and offers an in-depth data analysis of the related biological properties. Full article

In this work, we developed a highly efficient and versatile environmentally benign methodology for the vinylation of a broad scope of substances, including alcohols, thiols, and nitrogen compounds. The key advantage of the proposed method is the use of calcium carbide as a robust acetylene source in a stoichiometric ratio to the substrates. Lacking the requirement of acetylene excess, the developed protocol is safe, highly economic, and limits waste production. The procedure allows for a large variety of O-,S-,N-vinyl compounds to be synthesized in up to quantitative yields. Our methodology is scalable, allowing us to obtain vinyl derivatives in Gram-scale quantities. We also demonstrated the significant synthetic value of our approach by performing a label-economic synthesis of ¹³C₂-labeled vinyl derivatives using calcium carbide-¹³C₂. In our well-optimized process, the conversion of Ca¹³C₂ reached 89%. Full article

Ferrocene is an organometallic compound that has attracted considerable scientific interest due to its unique properties, including low toxicity, excellent stability in aqueous and aerobic media, and high lipophilicity, which enhances membrane permeability. The ferrocene moiety has been effectively used as a bioisostere of phenyl rings and heteroaromatic groups in the structures of approved tyrosine kinase inhibitors and histone deacetylase inhibitors (HDACis). HDACis exert their cytotoxic effects by blocking cyclin/CDK complexes, causing cell cycle arrest, inducing apoptosis, inhibiting angiogenesis, and through non-histone-directed mechanisms. This mini-review summarizes the synthesis and biological evaluation of small libraries of compounds in which a ferrocenyl moiety is incorporated into the structure of suberoylanilide hydroxamic acid (SAHA) and a number of analogues. The influence of the organometallic function on the antiproliferative effect is investigated. Both docking analysis and in vitro studies confirm that the ferrocenyl-modified HDACis exhibit potent cytotoxicity and strong inhibitory activity against the various enzyme isoforms. Full article

Heterocyclic compounds are the cornerstone for active pharmaceutical ingredients. Among heterocycles, isoindoline core occupies a special place, as ten commercial bioactive compounds/drugs contain this skeleton decorated with several functional groups required for optimal receptor binding. These drugs are employed for indications such as multiple myeloma, leukemia, inflammation, hypertension, edema, obesity, and insect control. This review presents the pharmacological activities, mechanisms of action, and chemical syntheses of these commercial bioactive molecules/drugs. Full article

The acid–base equilibria of cetirizine were investigated with and without the presence of differently charged micelle-forming surfactants (anionic, cationic, nonionic). The pK_a values were potentiometrically determined at 25 °C and at a constant ionic strength (0.1 M NaCl). Experimental data were analyzed by applying the computer program Hyperquad 5.2.15. Based on a shift in the ionization constants (∆pK_a) in micellar solutions against the pK_a values determined in “pure” water under the same conditions, the effects of micelles on the protolytic equilibria of cetirizine were estimated. Applied micelles caused a shift in the protolytic equilibria of all cetirizine ionizable centers, with the piperazine function connected to aliphatic side moiety (∆pK_a1 from −0.47 to +1.42), carboxyl group (∆pK_a2 from −0.92 to +2.02), and piperazine nitrogen connected to phenyl rings (∆pK_a3 from −2.01 to +2.19). Anionic SDS and nonionic Brij 35 micelles caused an increase in the pK_a values of the ionizable centers of cetirizine, while a decrease in the pK_a values was detected under the influence of cationic CTAB and nonionic TX-100 micelles. The change in the ionization pattern by micelles at pH values with biopharmaceutical significance provides indications of possible interactions of cetirizine with biomolecules of different charge and polarity under physiological conditions. Full article

Heterocyclic pharmaceuticals are emerging contaminants due to their toxic, carcinogenic nature and detrimental impact on the natural ecosystem. These compounds pose a significant environmental concern given their widespread use in medical therapy, constituting over 90% of new medications. Their unique chemical structure contributes to their persistence in various environmental matrices, necessitating urgent measures to mitigate their risks. This review comprehensively examines the sources, environmental fate, toxicity, and long-term risks associated with heterocyclic pharmaceuticals, proposing potential remediation strategies. The article commences with an overview of the diverse types of heterocyclic pharmaceuticals and their applications, focusing on compounds containing heteroatoms such as nitrogen, oxygen, and sulfur. Subsequently, it explores the sources and pathways through which these pollutants enter the environment, including wastewater discharge, agricultural runoff, improper disposal, resistance to biodegradation, and bioaccumulation. The toxic effects and long-term consequences of exposure to heterocyclic pharmaceuticals are then discussed, encompassing neurotoxicity, genotoxicity, mutagenesis, cardiovascular and metabolic toxicity, carcinogenicity, and teratogenesis. Additionally, this review summarizes various remediation strategies and treatment solutions aimed at reducing the environmental impact of these compounds, drawing insights from the literature. The research concludes by identifying critical areas for future research, emphasizing the urgent need for more effective remediation strategies to address the growing concern posed by these emerging contaminants. Full article

Various organic compounds susceptible to anodic polymerization were selected to study the effects of two solvents: acetic acid and ethyl acetate. Phenol and most of its derivatives, as well as resorcinol and 3,5-dihydroxybenzoic acid, exhibited typical electrode deactivation similar to other solvents; however, a continuous decrease in peak currents was not observed for 4-tert-butylphenols or salicylic aldehyde. Similar behavior was noted for monomers unrelated to phenols. In general, peaks were observed only for certain compounds and not in the initial voltammogram. Significant differences between the two solvents were observed in the subsequent voltammetric curves for some monomers. Microelectrode studies using 4-methoxyphenol as a model compound revealed notable differences between acetic acid and ethyl acetate in terms of curve shapes and the onset potentials of the plateaus. Plateau currents were used to estimate the solvent composition, demonstrating relatively high sensitivity to the acetic acid content. Full article

The pursuit of sustainable energy sources has led to significant advances in solar cell technology, with conducting polymers (CPs) emerging as key innovations. This review examines how CPs improve the performance and versatility of three important types of solar cells: dye-sensitized solar cells (DSSCs), perovskite solar cells (PSCs), and organic solar cells (OSCs). Polymers such as polyaniline, polypyrrole, and poly(3,4-ethylenedioxythiophene) have shown significant potential to increase the efficiency of solar cells. In DSSCs, conducting polymers act as counter electrodes, electrolytes, and dyes, contributing to improved efficiency and stability. In PSCs, they serve as hole transport materials and electron transport materials that improve charge separation and reduce recombination losses. In OSCs, conducting polymers act as HTMs and active layers, significantly impacting device performance and enabling advances in both binary and ternary solar cell configurations. Recent research highlights the important role of conducting polymers in improving both the efficiency and stability of solar cells under different indoor and outdoor lighting conditions. Recent advances have led to impressive energy conversion efficiencies, particularly in low-light environments. This report also highlights the environmental and economic benefits associated with these materials. At the same time, it highlights the challenges associated with optimizing the materials, scalability, and ensuring long-term stability. Future research directions are outlined to overcome these obstacles and promote the commercial viability of next-generation solar technologies. Full article