Solvent effects govern the majority of chemical transformations, yet experimentally accessible and universally applicable tools for predicting solvating ability remain limited. Here, we introduce iSolv, a simple but information-rich solvatochromic descriptor derived from the color of diluted iodine solutions in organic solvents. Using a combined experimental-computational approach, we demonstrate that iSolv directly reflects the nature and strength of intermolecular interactions, including dispersion interaction, halogen bonding, donor-acceptor interactions and hydrogen bonding. We establish clear correlations between iSolv and key electronic, physicochemical, and empirical solvent parameters, such as HOMO energy, donor number, log P, Kamlet-Taft parameters, and reaction rates in diverse organic transformations. Machine-learning modelling confirms that iSolv enables predictive assessment of solvent behavior using easily accessible input parameters. Unlike existing multi-parameter solvent scales, iSolv offers a low-cost, rapid, and visually interpretable method applicable across chemical research, education, and chemical technology. The practical and computational relevance of iSolv positions it as a versatile tool for solvent selection, reaction optimization, and broader chemical informatics. This work introduces a convenient indicator-based strategy for assessing solvating ability and lays the foundation for integrating visual color response into the digital chemistry framework.

The discovery of new chemical transformations is central to advancing modern chemistry, yet conventional approaches often require months or years of extensive experimental screening. Here, we present a machine‐learning‐assisted and expert‐guided pipeline for reaction discovery applied to the search for atom‐economic cycloaddition reactions. Candidate reactions were generated from publicly available quantum chemical data, filtered through unsupervised machine learning, and clustered to reduce redundancy. A digital co‐expert then enabled rapid prioritization, after which human expertise provided final selection and experimental validation. This hybrid workflow is fully compatible with current laboratory infrastructure and addresses the most time‐consuming stage of reaction discovery, accelerating the expert screening bottleneck by approximately 180‐fold (from > 1200 days to 7 days). Within ∼1 week, two novel cycloaddition reactions were identified and experimentally confirmed, yielding previously undescribed products. While fully autonomous robotic platforms represent a long‐term vision, their high cost and limited availability restrict immediate application. In contrast, our approach demonstrates the practicality of human‐AI collaboration for reaction discovery, combining computational screening, machine learning and expert knowledge to efficiently expand the accessible chemical space.

The unique phenomenon of high morphological diversity of quaternary phosphonium salts (QPSs) has been observed via electron and optical microscopy. The molecular structure of the QPSs, which differ by one methylene group, was shown to be reflected in the microstructure of the crystallized droplets. Here, we describe experimental datasets of scanning electron and optical microscopy images at different magnifications, illustrating the versatile microstructures of 19 homologous QPSs. The unique patterns that appear in the microscopy images of the QPS are related to the molecular structure. The described datasets of microscopy images are made openly available for scientific purpose and include hierarchical morphological patterns and fractal elements. Importantly, the datasets are suitable for both directions of machine learning exploration: recognizing molecular formulas from microscopy images and, conversely, predicting morphological patterns from molecular structures. This bidirectionality establishes a benchmark for bridging the molecule-morphology gap and advancing data-driven materials design.

Magnetic stirrers, the most widely used and ubiquitous devices for performing chemical reactions in laboratory settings, may cause reproducibility problems. Reproducibility in a range of chemical processes can be affected by various factors, ranging from minor to significant effects, including yield, composition, and glassware contamination. In this study, we illustrate the reproducibility issues that may arise from the use of a magnetic stirrer for three fundamental types of chemical reactions. Significant differences were found in the reaction rates and sizes of the nanoparticles obtained via parallel synthesis with the same magnetic stirrer. For catalyst preparation, differences were observed in the morphology of the metal nanoparticles and the process rate depending on the location of the reaction vessel on the magnetic stirrer. In the case of organic synthesis examples, the conversions of parallel catalytic cross-coupling reactions in vessels standing beside each other on the same magnetic stirrer can be significantly different. The results of these experiments revealed the influence of previously unaccounted-for factors, and here, we suggest a control experiment to improve reproducibility. Given the ubiquitous use of magnetic stirrers in chemistry, biology, life sciences, and material sciences, the revealed reproducibility-affecting factor is of broad concern.

Working with liquid/gas-phase systems in chemical laboratories is a fundamentally important but difficult operation, mainly due to the explosion risk associated with conventional laboratory equipment. Such systems, in the case of improper operation or destruction, may pose a significant threat to researchers. To address this challenge, our work explores the potential of additive technologies, particularly fused filament fabrication (FFF), for improving laboratory safety. We have successfully utilized FFF to produce compact safety modules, including integrated bursting discs, which can be easily made on demand and adapted to various types of reaction setups. Compared with traditional glassware, these modules, when integrated with laboratory reactors, significantly enhance operational safety. Our research highlights that in the event of excessive internal pressure, 3D-printed reactor parts undergo delamination and cracking of the wall, a mechanism that notably avoids the creation of hazardous fragments from the whole reaction vessel. This study demonstrated the efficiency and safety of additively manufactured reactors in organic synthesis using a variety of gases, including acetylene, carbon dioxide, and hydrogen. We systematically tested these reactors in vinylation and azide-alkyne cycloaddition reactions. Our findings confirm that 3D-printed reactors not only provide increased safety during pressurized operations but also maintain operational efficiency. The discussed approach offers a transformative solution for safer and more effective handling of gaseous reagents in laboratory settings, marking a significant advancement in flexible reactor design and chemical laboratory safety practices. Working with liquid/gas-phase systems in chemical laboratories is a fundamentally important but difficult operation, mainly due to the explosion risk associated with conventional laboratory equipment.

Dimeric 5-HMF derivatives have been used in a cascade 2 × [4 + 2] cycloaddition reaction with alkynes leading to a drastic increase in molecular complexity. The reaction proceeds under thermodynamic control, diastereoselectively and regioselectively.

Exploring the free energy surface of the R–NHC coupling reaction in the key intermediates of the Mizoroki–Heck and cross-coupling catalytic cycles has been conducted by the methods of biased and unbiased molecular dynamics. Molecular dynamics simulations were carried out both in vacuum and in a polar solvent, with the following main observations on the influence of the media: (1) the solvent prevents the dissociation of the solvate ligand, so the R–NHC coupling proceeds in a four-coordination complex (rather than in a three-coordination one, as in the case of a gas-phase reaction); (2) in the condensed phase, the potential barrier of the reaction is significantly higher compared to the same process in vacuum (17.7 vs. 21.8 kcal mol-1); (3) polar solvent stabilizes the R–NHC coupling product. The reaction in a polar medium is exergonic (ΔG = −3.9 kcal mol-1), in contrast to the in vacuum modeling, where the process is endergonic (ΔG = 0.4 kcal mol-1).

A simple methodology for testing FFF parts was developed to examine key factors for chemical applications. Carbon-filled polyamide (PA6-CF) was found superior for digital design of chemical reactors due to advantageous combination of properties.

Carbon-carbon and carbon-heteroatom bond formations via direct reductive elimination as one of the possible mechanisms of reductive elimination in Pd(II) complexes are the key stages of catalytic processes in fine organic synthesis. For the (R)(2)Pd(L)(2), (X)(2)Pd(L)(2) and (R)(X)Pd(L)(2) complexes (where R = Me, Vin, Ph, or Eth; X = B, N, O, Si, P, S, Se, or Te; L = PPh3), the R-R, R-X, and X-X bond formation barriers and reaction energies were calculated. The reaction barriers for C-C and C-X coupling decrease in the series C-sp(3) > C-sp > C-sp(2). The activity of coupling groups X containing a heteroatom decreases in the series of heteroatoms P, S, Se >> N >> O (for C-sp(2) and C-sp types of carbon centers) and P > S, Se >> N >> O (for C-sp(3) type of carbon center). The relationship between the structural lability of the (R)(2)Pd(L)(2) complexes and the probability of reductive elimination was determined by DFT molecular dynamics. An analysis of the calculated bond formation barriers and reaction energy showed that, in most cases, their values for unsymmetrical RX coupling are intermediate between the values for the reactions of symmetrical RR and XX coupling. The influence of the electronic properties of the coupling groups on the stabilization of the cis form of the complexes, which are suitable pre-reaction complexes for reductive elimination, was shown. The additivity of the energy difference between the cis and trans isomers was established: the cis-trans isomerization energies for the (R)(X)Pd(L)(2) complexes are intermediate between the corresponding energies for the (R)(2)Pd(L)(2) and (X)(2)Pd(L)(2) complexes. A high degree of additivity of the QTAIM charge of the palladium atom in all of the considered complexes was analyzed. In the present detailed study, we establish a hierarchy in bond formation barriers, emphasizing the influence of carbon center types, and discern the impact of coupling groups containing heteroatoms, revealing distinct trends based on carbon center types.

Additive manufacturing demonstrates tremendous progress and is expected to play an important role in the creation of construction materials and final products. Contactless (remote) mechanical testing of the materials and 3D printed parts is a critical limitation since the amount of collected data and corresponding structure/strength correlations need to be acquired. In this work, an efficient approach for coupling mechanical tests with thermographic analysis is described. Experiments were performed to find relationships between mechanical and thermographic data. Mechanical tests of 3D-printed samples were carried out on a universal testing machine, and the fixation of thermal changes during testing was performed with a thermal imaging camera. As a proof of concept for the use of machine learning as a method for data analysis, a neural network for fracture prediction was constructed. Analysis of the measured data led to the development of thermographic markers to enhance the thermal properties of the materials. A combination of artificial intelligence with contactless nondestructive thermal analysis opens new opportunities for the remote supervision of materials and constructions.

The interaction between diphenylacetylene and dichlorophenylphosphine under various conditions is a simple method for the preparation of pentaphenylphosphole derivatives exhibiting fluorescence properties. Depending on the electronic state of the various centers of the phospholic structure, it was possible to obtain molecules with fluorescence, as in the blue area for 1,2,3,4,5-pentaphenyl-2,5-dihydro-phosphole-1-oxide (H2PPPO), in the yellow area for 1,2,3,4,5-pentaphenylphosphole-1-oxide (PPPO) and in the cyan area for 1,2,3,4,5-pentaphenylphosphole (PPP). The effect of the structure and π-conjugation on the optical properties of these compounds was studied using PPP derivatives as examples. Unusual changes in the optical properties of PPP derivatives in solution and in the crystalline state are explained. In the case of agglomeration of PPPO and PPP molecules, the effect of aggregation-induced emission (AIE) was observed to have weak fluorescence in solution and strong fluorescence in the aggregated state. However, for H2PPPO, the AIE effect remains mild. With the help of experimental studies, supported by theoretical calculations, the main mechanism of the optical properties of pentaphenylphosphole derivatives has been revealed. It was observed that the intramolecular motions of PPPO and PPP are more limited in the solid state than the motions of H2PPPO, which is associated with less conjugation of the phenyl rotors of H2PPPO. The analysis of the structure and distribution of electron density showed why hydrogenation of the phosphole ring leads to a sharp change in the optical properties of pentaphenylphosphole derivatives, while the oxidation of phosphorus does not lead to the disappearance of the AIE effect and to a lesser extent affects the change in the fluorescence wavelength. Thus, it was shown how the regulation of various structural features of the phospholic ring helps to control the optical properties of such compounds.

Solubility in water, interactions with the solvent medium and tuning of molecular conformation in the liquid phase are the key issues to discover new biologically active molecules and to understand the mechanisms of their action. In the present article, we report synthesis, structural and biological activity studies, and computational modeling of new ionic compounds. Structural frameworks of well-known imidazolium, pyridinium and cholinium ionic liquids (ILs) were combined with naturally occurring cinnamic acid (CA), which is known to possess a wide spectrum of biological activity. Different combinations of these two structural elements (IL and Cin (cinnamic moiety)) allowed modulating the solubility, physicochemical properties and biological activity of the resulting molecules. A significant increase in the biological activity was achieved for the three studied hybrid molecules -[C(4)mim-Cin][Cl], [C(4)py- Cin][Cl], and [C4mim-Cin][Cin]. Multiparameter cytotoxicity mapping was performed to visualize the biological activity of the 28 studied molecules. Detailed experimental investigation and molecular dynamics simulation were performed to gain insight into the structure-activity relationship. Of note, a folding conformational change in the structure of [Cnmim-Cin][Cl] hybrid molecules in solution resulted in a substantial change in chemical reactivity, with the activation energy of the hydrolysis reaction decreasing from 32.1 to 23.9 kcal/mol. (c) 2022 Elsevier B.V. All rights reserved.

Imidazolium salts have ubiquitous applications in energy research, catalysis, materials and medicinal sciences. Here, we report a new strategy for the synthesis of diverse heteroatom-functionalized imidazolium and imidazolinium salts from easily available 1,4-diaza-1,3-butadienes in one step. The strategy relies on a discovered family of unprecedented nucleophilic addition/cyclization reactions with trialkyl orthoformates and heteroatomic nucleophiles. To probe general areas of application, synthesized N-heterocyclic carbene (NHC) precursors were feasible for direct metallation to give functionalized M/carbene complexes (M= Pd, Ni, Cu, Ag, Au), which were isolated in individual form. The utility of the chloromethyl function for the postmodification of the synthesized salts and Pd/carbene complexes was demonstrated. The obtained complexes and imidazolium salts demonstrated good activities in Pd- or Ni-catalyzed model cross-coupling and C-H activation reactions.

Visible light photocatalysis is a rapidly developing branch of chemical synthesis with outstanding sustainable potential and improved reaction design. However, the challenge is that many particular chemical reactions may require dedicated tuned photoreactors to achieve maximal efficiency. This is a critical stumbling block unless the possibility for reactor design becomes available directly in the laboratories. In this work, customized laboratory photoreactors were developed with temperature stabilization and the ability to adapt different LED light sources of various wavelengths. We explore two important concepts for the design of photoreactors: reactors for performing multiple parallel experiments and reactors suitable for scale-up synthesis, allowing a rapid increase in the product amount. Reactors of the first type were efficiently made of metal using metal laser sintering, and reactors of the second type were successfully manufactured from plastic using fused filament fabrication. Practical evaluation has shown good accuracy of the temperature stabilization in the range typically required for organic synthesis for both types of reactors. Synthetic application of 3D printed reactors has shown good utility in test reactions—furan C–H arylation and thiol-yne coupling. The critical effect of temperature stabilization was established for the furan arylation reaction: heating of the reaction mixture may lead to the total vanishing of photochemical effect.

C–C coupling reactions are of great importance in metal-catalyzed synthetic transformations. Reductive elimination of two carbon centers is the key stage, which takes place in the metal coordination sphere. In the present study, we provide a detailed analysis of nonclassical R–NHC coupling in the model (NHC)Pdii(Ph)(X)(Solv) complex, which is a representative intermediate of the Mizoroki–Heck and cross-coupling reactions. This C–C bond formation stage proceeds as Ph ligand movement and insertion into the Pd–NHC bond, rather than classical C–C coupling. Based on the analysis by the quantum theory of atoms in molecules (QTAIM) of the reaction path structures, the atomic rearrangements and alterations in the electronic system during the R–NHC coupling process were characterized in detail.

Protic imidazolium ionic liquids (PILs) have shown great potential as regents and catalysts in liquid -phase chemistry. However, their biological activity/toxicity and solvation properties are rather under-studied compared to those of more common aprotic ionic liquids (APILs). In this work, for the first time, we studied the cytotoxicity of nine chemically relevant imidazolium PILs with various alkyl side chains in the cation and compared it with the cytotoxicity of the corresponding aprotic analogues. The experimen-tal data were supported by computational modeling. The results suggested the type of anion to be the major factor governing the cytotoxicity of the studied ILs with short alkyl side chains. Of note, even low-toxic PILs imposed considerable deleterious effects on eukaryotic cells when used as cryopreserva-tion agents. According to a scanning electron microscopy (SEM) study, due to the weak amphiphilic prop-erties of imidazolium cations with short alkyl side chains, the studied IL/water mixtures tended to produce simple solid hydrates rather than complex liquid systems with microdomain organization.(c) 2022 Elsevier B.V. All rights reserved.

The reaction space of the furanics-to-aromatics (F2A) conversion process for 5-hydroxymethylfurfural (HMF)-based platform chemicals has been explored both experimentally and by quantum chemistry methods. For the first time, a structure-activity relationship was established in furan-yne cycloaddition for a number of different HMF derivatives. Correlations between the activation energy of the cycloaddition stage and the structure of the substrates were established by molecular modeling methods. Analysis of the concerted and stepwise mechanisms of cycloaddition in the singlet and triplet electronic states of the molecular system was carried out. A series of biobased 7-oxanorbornadienes was obtained in the reaction with dimethyl acetylenedicarboxylate. Various methods of aromatization of the obtained [4+2] adducts have been examined. Rearrangement catalyzed by a Lewis acid leads to the formation of a phenol derivative, whereas reduction by diiron nonacarbonyl leads to the formation of functionalized benzene. Systematic study of the cycloaddition process has revealed a simple way to analyze and predict the relative reactivity of furanic substrates.

The ability to distinguish molecular catalysis from nanoscale catalysis provides a key to success in the field of catalyst development, particularly for the transition to sustainable economies. Complex evolution of catalyst precursors, facilitated by dynamic interconversions and leaching, makes the identification of catalytically active forms an important task, which is sometimes very difficult. We propose a simple method for in situ capturing of nanoparticles with carbon-coated grids directly from reaction mixtures. Application of this method to the Mizoroki-Heck reaction allowed visualization of dynamic changes of the dominant form of palladium particles in the reaction mixtures with homogeneous and heterogeneous catalyst precursors. Changes in the size and shape of the palladium particles reflecting the progress of the catalytic chemical reaction were demonstrated. Detailed computational modeling was carried out to confirm the generality of this approach and its feasibility for different catalytic systems. The computational models revealed strong binding of metal particles to the carbon coating comprising efficient binding sites. The approach was tested for trapping Cr, Co, Ag, Ni, Cu, Pd, Cd, Ir, Ru and Rh nanoparticles from solutions containing micromolar starting concentrations of the metal precursors. The developed approach provides a unique tool for studying intrinsic properties of catalytic systems.

In this article, we suggest a new organocatalytic approach based on the dynamic covalent interaction of imidazolium cations with ketones. A reaction of N-alkyl imidazolium salts with acetone-d(6) in the presence of oxygenated bases generates a dynamic organocatalytic system with a mixture of protonated carbene/ketone adducts acting as H/D exchange catalysts. The developed methodology of the pH-dependent deuteration showed high selectivity of labeling and good chiral functional group tolerance. Here we report a unique methodology for efficient metal-free deuteration, which enables labeling of various types of alpha-acidic compounds without trace metal contamination.

A new family of protic ammonium ionic liquids (ILs) with various inorganic anions was synthesized from bio-derived 5-HMF. Starting with cellulose biomass, a complete preservation of the C-6 unit was achieved throughout the synthetic sequence (no carbon loss). Evaluation of green metrics showed a significant advantage of the developed bio-derived pathway to access ILs from a natural renewable source, depending on feasible routes to 5-HMF manufacturing. The reduced number of synthetic steps and availability of the starting materials were the key advantages. Experimental physicochemical and biological studies, as well as computational modeling revealed a unique multifunctional intrinsic organization of these bio-derived ILs. The nature of interactions between the cations and anions of the novel ILs was mapped at the molecular level. The substituents in the cationic core and the nature of the original building blocks had a prominent impact on cytotoxicity of the novel ILs. The obtained results suggest possible sustainable applications of the least toxic ILs, while the regulation of biological activity of the ILs via the corresponding structural adjustments can find biological and medicinal applications. The 5-HMF-derived IL with a sulfate anion demonstrated potentially useful properties in dissolution of microcrystalline cellulose.