Predicting enantioselectivity across broad substrate spaces remains a central challenge in asymmetric catalysis and is typically addressed through extensive experimental screening. Here, we demonstrate that meaningful predictions can emerge from small, carefully curated datasets. Using chalcone epoxidation and thia–Michael addition as magnesium-catalyzed benchmark reactions, we developed a machine-learning framework trained on internally consistent experimental data. Systematic evaluation shows that reactivity classification is robust even for highly homogeneous datasets, whereas predictive regression requires broader distributions of enantioselectivity. Experimental validation confirms that the models capture selectivity trends across previously untested substrates. These results establish that small, high-quality datasets can support practical prediction in asymmetric catalysis, providing a foundation for AI-assisted reaction design and substrate prioritization.

In this study, we describe the synthesis of novel dipeptide analogs of (E)-α-fluorovinylphosphonates, with a key step involving the Horner-Wadsworth-Emmons (HWE) reaction. The synthesized compounds were evaluated as potential reversible inhibitors of the cathepsin C enzyme. Comprehensive characterization of the target molecules was performed, and their inhibitory activity was assessed. Additionally, molecular docking studies were conducted to elucidate the binding interactions of the synthesized derivatives within the cathepsin C active site. The results highlight promising structural features for the design of effective enzyme inhibitors and provide a foundation for further optimization of fluorovinylphosphonate-based dipeptides.

Complexes of colchicine, colchiceine, and 10-methylthiocolchicine with Li+, Na+, and K+ cations in the form of chlorides were synthesized and then subjected to spectral analysis, DFT theoretical studies, and molecular modeling. The values for water solubility and lipophilicity were also determined using various platforms; both factors are very important for determining the bioavailability of the tested compounds. These compounds were also tested for their fungicidal, herbicidal, insecticidal, and cytotoxic activities. Preliminary in silico studies showed that colchicine, colchiceine, 10-methylthio-colchicine, and their chloride complexes are inactive against selected fungi, weeds, and insects. Colchicine did not show antifungal properties in biological tests and was only active against Aureobasidium pullulans, as were its chloride complexes. The process of complexing colchiceine with metal cations in chloride salts significantly improved the antifungal potency against the selected species A. pullulans and Chaetomium globosum. The highest efficacy of colchiceine complexes was observed only against A. pullulans (MIC = 130 µg/mL) and Ch. globosum (MIC = 65 μg/mL). In contrast to the antifungal activity results, anticancer studies showed that 10-methylthiocolchicine complexes are more active against the SKOV-3 cell line (~IC50 = 2 nM) than colchicine or colchiceine. Molecular-modeling studies confirmed that lithium-coordinated compounds strongly stabilized the active ligand-tubulin complex, which may contribute to the observed cytotoxic activity.

The phenolics present in different parts of Trifolium repens, mainly flowers and leaves and sometimes also roots, have been extensively studied, however, the data on the phenolic compounds occurring in the Trifolium repens seeds are very limited. Here, we report results of high pressure liquid chromatography-mass spectrometry (HPLC-MS) analysis of methanol extract of white clover seeds. Myricetin and quercetin, were detected as the main flavonoids, and for each of them three isomeric galactosides were detected. The structures of the myricetin and quercetin glycosides, including identification of glycosylation sites C-3, C-4 ' and C-7, were elucidated on the basis of relative abundances of precursor ions and Y0+, Y0- and [Y0-H]-center dot product ions, and on the basis of quantum chemical calculations.

Kavalactones are psychoactive substances that naturally occur in some plants, such as Piper methysticum, Alpinia zerumbet, and Achyrocline satureioides, which are considered to have a significantly positive effect on human organisms. For example, Alpinia zerumbet is classified as a life-expanding plant. Although high-pressure liquid chromatography-mass spectrometry has been used for kavalactone analysis in plant material, the fragmentation pathways of protonated kavalactone molecules are not fully known and require further detailed study. In this paper, the fragmentation pathways of [M+H]+ ions of twelve kavalactones, including three pairs of isomers, are discussed in detail. Special emphasis has been placed on diagnostic product ions, which are characteristic of kavalactone structures. It has been demonstrated that diagnostic ions and structure-fragmentation relationships enable the differentiation of isomeric kavalactones and may be useful for the identification of other kavalactone conjugates, such as kavalactone dimers or kavalactone glycosides.

The future 6G networks are expected to utilize large antenna arrays and follow the user-centric architecture, where the user is being served by all base stations. This work evaluates such a system within an advanced system-level simulator, which utilizes an accurate 3D Ray-Tracing radio channel model. Results show that the novel user-centric network architecture can increase the cell-edge users throughput by a fold of 3.

The electrochromic naphthalenediimide (NDI) based monomer containing styrene pedant groups, which are capable of polymerization, was prepared, and the formation of its polymer via a photopolymerization reaction was described. Both the monomer and polymer exhibited a color change in the visible range from transparent or slightly yellow, respectively, followed by brown-red to green. This was the result of a two-step reduction reaction of NDI core to radical anion and dianion, respectively. The device constructed using the polymer as an active material was found to exhibit good electrochromic stability over 500 redox cycles. The switching times were calculated to be 18 s and 6 s for the coloration and bleaching steps, respectively. The presented results showed the usability of the photopolymerization of styrene-based monomers in the generation of the stable electrochromic layers of polymers.

Phosphonate analogues of alpha-amino acids are increasingly valued for their significant potential in medicinal chemistry. Fluorine is a "magic" element that plays a huge role in modulating the properties of organic compounds. In this work, we combined the two pharmacophores in the synthesis of three series of new alpha-aminophosphonates. These compounds were obtained by diastereoselective hydrophosphonylation of imines prepared by an environmentally friendly mechanochemical approach. Results of computational SwissADME analysis suggested favorable drug-like properties of the alpha-aminophosphonates and indicated their potential for interaction with diverse biological targets including proteases, showing promising pharmacokinetic profiles compared to 5-fluoro-2 '-deoxyuridine (FdU) used as a standard anticancer drug. Screening against ten cancer cell lines from seven types of cancer showed that five of the twenty compounds tested (1c, 2a, 2h, 3e, and 3f) exhibited superior activity against the HeLa cell line and lower cytotoxicity against normal MRC-5 cells than FdU. Compound 3e showed notable inhibitory effect on the MDA-MB-231 cell line, while 3a, 3h, and 3g demonstrated significant cytotoxic activity against U-87 MG and U-251 MG lines. Molecular docking highlighted the strong binding of compound 2a to the urokinase-type plasminogen activator (uPA) protein, with a binding affinity of -6.41 kcal/mol, suggesting the anti-metastatic potential of the compound. These findings enable to position the newly synthesized alpha-aminophosphonates as promising scaffolds for developing targeted anticancer therapies for metastatic cancers characterized by elevated uPA expression.

Polyphenols make a numerous and diverse group of plant secondary metabolites exhibiting remarkable anticancer activities, often attributed to their G-quadruplex binding properties. Therefore, there is a need to develop a high–throughput screening assay which would permit the evaluation of polyphenols’ binding properties toward G-quadruplex. As deoxyguanosine and guanosine are essential and key building blocks of G-quadruplexes, the stabilities of their adducts with polyphenols may reflect the stabilities of polyphenols–G-quadruplex adducts. In this study, deoxyguanosine/guanosine post-column addition experiments have been performed during HPLC-MS analysis of Achyrocline satureioides extract. The stabilities of the deoxyguanosine/guanosine adducts with 3-O-methylquercetin-7-O-glucoside, 4′-hydroxydehydrokawain-4′-O-glucoside, and 3,5-di-O-caffeoylquinic acid—compounds identified in the Achyrocline satureioides extract—have been tested by using collision-induced dissociation ‘in-source’. The obtained results show that the identified compounds form more stable adducts with deoxyguanosine and guanosine than the standards used for comparison, namely isoquercitrin and rutin. The performed molecular docking provided some insight into the structure of the adducts and revealed that multiple interactions are of key importance for their stabilities.

The main goal of our research was to examine (1S,4R,5R)-4-(4-phenyl-1H-1,2,3-triazol-1-yl)-2-((S)-1-phenylethyl)-2-azabicyclo[3.2.1]octane (L) and its complex-forming abilities with platinum(II) ions. Herein, we present three new square planar platinum(II) complexes of the general formulas trans-[PtCl2L2] (1), cis-[PtCl2(DMSO)(L)] (2) and [Pt(DMSO)(L)(mal)] (3), where DMSO: dimethyl sulfoxide; mal: malonate. Based on the experimental spectroscopic results (1H, 13C, 15N, 195Pt NMR, IR, X-ray analyses) and density functional theoretical calculation (DFT), a square planar geometry was proposed with one or two monodentate bound N3' heterocyclic ligands (L). Surrounding the central atom, there are monodentate chloride (1) and (2) or chelated O,O-donor malonate ligands (3). The coordination spheres in (2) and (3) were completed by the S-donor monodentate dimethyl sulfoxide molecule. Theoretical investigations into the heterocyclic ligand coordination site and geometry around the central ion were performed by DFT calculation, and the results were consistent with the experimental data. The DFT calculations elucidate the thermodynamic preferences for cis versus trans arrangements of the ligands in the isolated platinum(II) complexes (1) and (2), suggesting that the trans arrangement of chloride anions observed in the crystals of (2a) probably results from the crystal packing. The obtained platinum(II) complexes were examined with regard to their therapeutic anticancer potential. In comparison to cisplatin, lipophilic complexes (1) and (3) exhibit lower affinity toward glutathione. According to observations, (1) presents the most satisfactory in vitro activity with the mechanism of its cytotoxic effect on cancer cells different from that of cisplatin.

The series of bis(triphenylamine)s consisting of different aromatic central cores has been designed and synthesized. This was done to test the dependence of the electrochemical properties and electropolymerization ability on the central core of bis(triphenylamine). It was observed that the compound containing a 1,3-substituted phenylene core most easily electropolymerize on the electrode surface, while dyes containing thiophene and EDOT cores do not undergo electropolymerization. This was further explained by DFT calculations of SOMO orbitals, which revealed that the amount of charge at the 4 ' position of the phenyl rings of the triphenylamine group varies depending on the central aromatic core. Electrochromic properties of obtained polymers were also tested. The polymers containing electron-withdrawing groups change their color from red via brown to blue, while the polymers obtained via electropolymerization of phenylene derivatives exhibited colorless <-> brown <-> blue transition. Electrochromic parameters, such as color contrast, long-term stability, response times and coloration efficiency were also investigated. It was found that the electropolymerized layer of derivative with benzooxadiazole as a central core exhibited the best long term stability and it was able to switch between neutral and oxidized states over 700 cycles without loss in color contrast. It was also observed that the photophysical properties also depend on the central core of the dye. The compounds containing electron-withdrawing cores were found to exhibit solvatochromic properties, while the shift of the emission maxima with the solvent polarity was smaller for compounds containing phenylene groups and negligible for compounds containing thiophene and EDOT cores.

In this study, we used ultraviolet-visible (UV-Vis), fluorescence, and circular dichroism (CD) techniques, as well as molecular modeling, to probe the interactions between carbazole derivatives and the G-quadruplex structure formed in the promoter region of gene Bcl-2. This gene is a rational target for anticancer therapy due to its high expression in a variety of tumors as well as resistance to chemotherapy-induced apoptosis. We employed a sequence with a specific dual G-to-T mutation that may form a mixed-type hybrid G-quadruplex structure in the Bcl-2 P1 promoter region. The three tested carbazole compounds differing in substitution on the nitrogen atom of carbazole interact with the Bcl-2 G-quadruplex by the same binding mode with the very comparable binding affinities in the order of 105 M−1. During absorption and fluorescence measurements, large changes in the ligand spectra were observed at higher G4 concentrations. The spectrophotometric titration results showed a two-step complex formation between the ligands and the G-quadruplex in the form of initial hypochromicity followed by hyperchromicity with a bathochromic shift. The strong fluorescence enhancement of ligands was observed after binding to the DNA. All of the used analytical techniques, as well as molecular modeling, suggested the π–π interaction between carbazole ligands and a guanine tetrad of the Bcl-2 G-quadruplex. Molecular modeling has shown differences in the interaction between each of the ligands and the tested G-quadruplex, which potentially had an impact on the binding strength.

The incorporation of fluorine atoms within the structure of organic compounds is known to exert a significant impact on their electronic properties, thereby modulating their reactivity in diverse chemical transformations. In the context of our investigation, we observed a striking illustration of this phenomenon. A Michael addition involving gem-difluorovinyl and trifluorovinyl acceptors was successfully achieved, demonstrating high stereoselectivity. This selectivity was further elucidated through theoretical calculations. Using this methodology, a series of new α,β-unsaturated amides, both fluorinated and nonfluorinated, were synthesized.

In the contemporary era, the exploration of machine learning (ML) has gained widespread attention and is being leveraged to augment traditional methodologies in quantitative structure-activity relationship (QSAR) investigations. The principal objective of this research was to assess the anticancer potential of colchicine-based compounds across five distinct cell lines. This research endeavor ultimately sought to construct ML models proficient in forecasting anticancer activity as quantified by the IC50 value, while concurrently generating innovative colchicine-derived compounds. The resistance index (RI) is computed to evaluate the drug resistance exhibited by LoVo/DX cells relative to LoVo cancer cell lines. Meanwhile, the selectivity index (SI) is computed to determine the potential of a compound to demonstrate superior efficacy against tumor cells compared to its toxicity against normal cells, such as BALB/3T3. We introduce a novel ML system adept at recommending novel chemical structures predicated on known anticancer activity. Our investigation entailed the assessment of inhibitory capabilities across five cell lines, employing predictive models utilizing various algorithms, including random forest, decision tree, support vector machines, k-nearest neighbors, and multiple linear regression. The most proficient model, as determined by quality metrics, was employed to predict the anticancer activity of novel colchicine-based compounds. This methodological approach yielded the establishment of a library encompassing new colchicine-based compounds, each assigned an IC50 value. Additionally, this study resulted in the development of a validated predictive model, capable of reasonably estimating IC50 values based on molecular structure input.

In the field of anticancer therapy study it is of great interest to find effective G-quadruplex ligands which may be of potential use in medical treatment or cancer prevention. Since among the compounds of natural origin, flavonoids have attracted notable attention because of their unique properties and promising therapeutic applications, an interesting question was to identify the flavonoid structural features that could provide effective binding properties toward G-quadruplex. By using electrospray ionization mass spectrometry, followed by the survival yield method, it has been shown that the flavonoid molecules which contain an available C4=O carbonyl group form more stable adducts with G-tetrads than the other ones. Molecular docking has shown that C4=O carbonyl group can be a source of hydrogen bonds and/or π-stacking interactions. Therefore, the flavonoid molecules which contain an available C4=O carbonyl group can be regarded as good binders of G-quadruplexes.

We present a methodology for the synthesis of inorganic-organic Janus-type molecules based on mono-T8 and difunctionalized double-decker silsesquioxanes (DDSQs) via hydrosilylation reactions, achieving exceptionally high yields and selectivities. The synthesized compounds were extensively characterized using various spectroscopic techniques, and their sizes and spatial arrangements were predicted through molecular modelling and density functional theory (DFT) calculations. Quantum chemical calculations were employed to examine the interactions among four molecules of the synthesized compounds. These computational results allowed us to determine the propensity for molecular aggregation, identify the functional groups involved in these interactions, and understand the changes in interatomic distances during aggregation. Understanding the aggregation behaviour of silsesquioxane molecules is crucial for tailoring their properties for specific applications, such as nanocomposites, surface coatings, drug delivery systems, and catalysts. Through a combination of experimental and computational approaches, this study provides valuable insights into the design and optimization of silsesquioxane-based Janus-type molecules for enhanced performance across various fields.

For thousands years Ephedrae herba has been used in traditional Chinese herbal medicine. Its main bioactive constituents are ephedrine and pseudoephedrine. Nowadays, these alkaloids have found application in various clinical treatments, as sports-enhancing drugs and for the illicit production of amphetamine-like drugs. Ephedrine and pseudoephedrine are diastereomers, and because of their high polarity and similar pKa values, their chromatographic separation may be a challenge. In this study a possible application of direct infusion mass spectrometry and direct infusion tandem mass spectrometry has been proposed for differentiation of ephedrine and pseudoephedrine as well as the relative determination of the contents of these compounds in a mixture. At low collision energy condition, the ratio of relative abundances of ions [M+H-H2O]+ and [M+H]+ permit distinction of the analyzed diastereomers, and enable evaluation of their relative content in a mixture with no need of chromatographic separation. The performed quantum chemical calculation have shown that protonated pseudoephedrine contains stronger hydrogen bond than protonated ephedrine, which can justify the observed higher relative abundance of ion [M+H-H2O]+ in the mass spectrum of pseudoephedrine, in comparison to that of ephedrine.

In this study, we subjected 5,5-diethoxy-4-oxopent-2-enal (DOPE), a model amino acids cross-linking reagent, to reactions with N -acetylcysteine (Ac-Cys) and N α -acetyllysine (Ac-Lys), and identified three pyrrole cross-links. The compounds were isolated and their structures were rigorously determined by spectrometric and spectroscopic methods, including 2D NMR experiments. The use of 2D NMR spectroscopy was crucial to determine the position of the substituents in the pyrrole rings. The products were identified as 2,4-, 2,3-, and 2,5-substituted pyrroles. The data obtained from their structural characterisation can help similar studies on amino acids modifications induced by analogous bifunctional carbonyl compounds. Our results show that the study of pathways in which model electrophiles modify amino acids may be helpful for similar studies dealing with identification of structural changes in cysteine- and lysine-containing proteins associated with oxidative stress.