Mechanisms of Biological Effects of Ionic Liquids: From Single Cells to Multicellular Organisms

Egorova K.S., Kibardin A.V., Posvyatenko A.V., Ananikov V.P., Chem. Rev., 2024, 124, 4679–4733.
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The review presents a detailed discussion of the evolving field studying interactions between ionic liquids (ILs) and biological systems. Originating from molten salt electrolytes to present multiapplication substances, ILs have found usage across various fields due to their exceptional physicochemical properties, including excellent tunability. However, their interactions with biological systems and potential influence on living organisms remain largely unexplored. This review examines the cytotoxic effects of ILs on cell cultures, biomolecules, and vertebrate and invertebrate organisms. Our understanding of IL toxicity, while growing in recent years, is yet nascent. The established findings include correlations between harmful effects of ILs and their ability to disturb cellular membranes, their potential to trigger oxidative stress in cells, and their ability to cause cell death via apoptosis. Future research directions proposed in the review include studying the distribution of various ILs within cellular compartments and organelles, investigating metabolic transformations of ILs in cells and organisms, detailed analysis of IL effects on proteins involved in oxidative stress and apoptosis, correlation studies between IL doses, exposure times and resulting adverse effects, and examination of effects of subtoxic concentrations of ILs on various biological objects. This review aims to serve as a critical analysis of the current body of knowledge on IL-related toxicity mechanisms. Furthermore, it can guide researchers toward the design of less toxic ILs and the informed use of ILs in drug development and medicine.

Tailoring metal complexes with N-heterocyclic carbene ligands using Electron-Withdrawing Groups: Impact on catalytic activity and property development

Pankov R.O., Prima D.O., Ananikov V.P. , Coord. Chem. Rev., 2024, 516, 215897.
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In the field of catalytic chemistry, metal complexes containing N-heterocyclic carbenes (NHCs) have gained significant attention due to their versatile nature and wide range of potential applications. In the synthetic applications, the catalytic properties of M/NHC complexes are affected by the incorporation of sterically hindered donor substituents into NHC ligands. However, a comparative analysis of M/NHC complexes with electron-acceptor substituents revealed significant differences in catalytic activity and selectivity. The complexes exhibit enhanced performance in several catalytic transformations. Therefore, this review focuses on substituents with electron-acceptor properties to explore their impact on the catalytic efficiency, stability and general characteristics of the resulting M/NHC complexes. Additionally, the potential for their use in catalytic processes is examined. Both experimental and computational methodologies have been employed to shed light on this phenomenon, revealing that electron-withdrawing groups play a significant role in altering the electronic properties of the molecule and creating unique spatial environments around the metal center. This, in turn, greatly influences the reactivity, stability and selectivity of M/NHC catalysts. The findings analyzed in this review elucidate the critical contribution of electron-withdrawing substituents in the design and optimization of efficient M/NHC catalysts. This opens up new avenues for innovation in the development of novel catalysts and applications in the ever-evolving field of catalysis.

Revealing the mechanism of combining best properties of homogeneous and heterogeneous catalysis in hybrid Pd/NHC systems

Prima D.O., Kulikovskaya N.S., Novikov R.A., Kostyukovich A.Yu., Burykina J.V., Chernyshev V.N., Ananikov V. P., Angew. Chem. Int. Ed., 2024, e202317468.
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The formation of transient hybrid nanoscale metal species from homogeneous molecular precatalysts has been demonstrated by in situ NMR studies of catalytic reactions involving transition metals with N-heterocyclic carbene ligands (M/NHC). These hybrid structures provide benefits of both molecular complexes and nanoparticles, enhancing the activity, selectivity, flexibility, and regulation of active species. However, they are challenging to identify experimentally due to the unsuitability of standard methods used for homogeneous or heterogeneous catalysis. Utilizing a sophisticated solid-state NMR technique, we provide evidence for the formation of NHC-ligated catalytically active Pd nanoparticles (PdNPs) from Pd/NHC complexes during catalysis. The coordination of NHCs via C(NHC)-Pd bonding to the metal surface was first confirmed by observing the Knight shift in the 13C NMR spectrum of the frozen reaction mixture. Computational modeling revealed that as little as few NHC ligands are sufficient for complete ligation of the surface of the formed PdNPs. Catalytic experiments combined with in situ NMR studies confirmed the significant effect of surface covalently bound NHC ligands on the catalytic properties of the PdNPs formed by decomposition of the Pd/NHC complexes. This observation shows the crucial influence of NHC ligands on the activity and stability of nanoparticulate catalytic systems.

Sulfur in Waste-Free Sustainable Synthesis: Advancing Carbon- Carbon Coupling Techniques

Shlapakov N.S., Kobelev A.D., Burykina J.V., You S.-L., Ananikov V. P., Angew. Chem. Int. Ed., 2024, e202314208.
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This review explores the pivotal role of sulfur in advancing sustainable carbon-carbon (C–C) coupling reactions. The unique electronic properties of sulfur, as a soft Lewis base with significant mesomeric effect make it an excellent candidate for initiating radical transformations, directing C–H-activation, and facilitating cycloaddition and C–S bond dissociation reactions. These attributes are crucial for developing waste-free methodologies in green chemistry. Our mini-review is focused on existing sulfur-directed C–C coupling techniques, emphasizing their sustainability and comparing state-of-the-art methods with traditional approaches. The review highlights the importance of this research in addressing current challenges in organic synthesis and catalysis. The innovative use of sulfur in photocatalytic, electrochemical and metal-catalyzed processes not only exemplifies significant advancements in the field but also opens new avenues for environmentally friendly chemical processes. By focusing on atom economy and waste minimization, the analysis provides broad appeal and potential for future developments in sustainable organic chemistry.

Reversible Radical Addition Guides Selective Photocatalytic Intermolecular Thiol-Yne-Ene Molecular Assembly

Shlapakov N.S., Kobelev A.D., Burykina J.V., Kostyukovich A.Yu., König B., Ananikov V. P., Angew. Chem. Int. Ed., 2024, e202314208.
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In the realm of modern organic chemistry, harnessing the power of multicomponent radical reactions presents both significant challenges and extraordinary potential. This article delves into this scientific frontier by addressing the critical issue of controlling selectivity in such complex processes. We introduce a novel approach that revolves around the reversible addition of thiyl radicals to multiple bonds, reshaping the landscape of multicomponent radical reactions. The key to selectivity lies in the intricate interplay between reversibility and the energy landscapes governing C-C bond formation in thiol-yne-ene reactions. The developed approach not only allows to prioritize the thiol-yne-ene cascade, dominating over alternative reactions, but also extends the scope of coupling products obtained from alkenes and alkynes of various structures and electron density distributions, regardless of their relative polarity difference, opening doors to more versatile synthetic possibilities. In the present study, we provide a powerful tool for atom-economical C-S and C-C bond formation, paving the way for the efficient synthesis of complex molecules. Carrying out our experimental and computational studies, we elucidated the fundamental mechanisms underlying radical cascades, a knowledge that can be broadly applied in the field of organic chemistry.

Revealing Catalyst Self-Adjustment in C–S Cross-Coupling through Multiscale Liquid-Phase Electron Microscopy

Kashin A.S., Arkhipova D.M., Sahharova L.T., Burykina J.V., Ananikov V.P., ACS Catal., 2024, 14, 5804–5816.
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Carbon–carbon and carbon–heteroatom bond formation mediated by transition metals is a powerful and convenient methodology for organic synthesis. To effectively meet the demands of catalyst design, an in-depth understanding of the reaction mechanisms and pathways of active species evolution is essential. Advances in electron microscopy now offer unprecedented multilevel visualization of liquid-phase chemical systems, providing a powerful tool for mechanistic studies. In this work, we found that the use of either nickel- or copper-based catalyst precursors with preinstalled thiolate groups in combination with pyridinium ionic liquid as the reaction medium leads to a positive synergistic effect, resulting in the formation of transition metal species with high catalytic activity in the C–S cross-coupling reaction between aryl halides and thiols or disulfides. Through multiscale in situ and operando electron microscopy in the liquid phase, we elucidated the self-adjustment of the catalytic system and revealed the simultaneous emergence of metallic nanoparticles and corresponding thiolate species, leading to the independent activation of the C- and S-substrates and the subsequent elimination of the product via organic group metathesis. The proposed methodology for the catalytic preparation of aromatic organosulfides was used for the design of synthetic routes to pharmacologically important substances.

4D Catalysis Concept Enabled by Multilevel Data Collection and Machine Learning Analysis

Galushko A.S., Ananikov V.P., ACS Catal., 2024, 14, 161-175.
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The influence of catalysis on the development of modern science and industry cannot be overestimated. Production of pharmaceutical substances and drugs, the oil industry, developments in the field of ecology and material science, and many other areas with a great impact on the world economy are progressing through the active use of catalysts. In the almost two hundred years that have passed since the description of the phenomenon of catalysis, the understanding of the principle of operation of catalysts has developed to a very high degree. Initially, it was assumed that the catalyst remains unchanged in the reaction in which it participates, while it is now well established that catalysis is a dynamic phenomenon in many systems. Catalytically active particles change as the catalyzed reaction proceeds and pass from one phase to another, which often leads to significant changes in catalytic activity and selectivity. In many cases, uncontrolled dynamic changes in the catalytic system lead to degradation and a loss of activity and selectivity. Understanding the mechanisms of the dynamic nature of active centers is very important for designing highly active catalysts, which in turn will have a positive impact on the environment, industry, economics, and numerous other areas.

Establishing the main determinants of the environmental safety of catalytic fine chemical synthesis with catalytic cross-coupling reactions

Egorova K.S., Kolesnikov A.E., Posvyatenko A.V., Galushko A.S., Shaydullin R.R., Ananikov V. P., Green Chem., 2024, ASAP.
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Fine chemical synthesis is the key area of industry and academic research, with a strong focus on catalytic C–C bond formation targeted at drug design, biologically active compounds and new materials. Until recently, such catalytic technologies had been employed without a rigorous analysis of a plausible ecological impact, which is now a key question that cannot be neglected. In this work, we experimentally classified the complete range of harmful compounds used in common Sonogashira and Mizoroki–Heck cross-coupling reactions by means of bio-Profiles (bio-Strips) built on the basis of 24 h CC 50 values of individual reaction substances measured in three cell lines of different origins. For a comprehensive evaluation, 864 individual reactions and 2592 bio-Strips supplemented with bio-factors (BFs) and cytotoxicity potentials (CPs) were evaluated. According to the results, from the viewpoint of the contribution of the tested chemicals to the "overall cytotoxicity" of the synthetic routes analyzed, close attention should be paid to the selection of the catalysts due to their high cytotoxicity and to the solvents because they are used in significant quantities in the reaction. The choice of the base can also have a significant impact on the bio-Profile, whereas the effect of the starting materials seems lower in comparison. We also describe a new approach to unambiguous and quantitative comparisons of biological objects (in this case, cell cultures) in terms of their response to the continually varying conditions in reaction systems. In addition, we support the earlier-suggested notion that the choice of a particular cell line for CC50 measurements can be of secondary importance for the resulting bio-Strips. Nevertheless, the actual cytotoxicity of a given compound should not be ignored when selecting the participant components for a target reaction, as evidenced by the newly introduced "tumor selectivity index" (tSI) of individual chemicals. A detailed analysis of these two practically important catalytic reactions also provides a guide and a global view for assessing the bio-risks of other catalytic processes.

A 60-times faster digital-discovery-compatible reaction setup with enhanced safety for chemical applications

Lebedev A.N., Rodygin K.S., Vakhrusheva S.A., Ananikov V. P., Green Chem., 2024, ASAP.
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Modern laboratory practices demand safer, efficient, and more green and sustainable solutions, especially given the often dangerous nature of the chemicals used. This study introduces a technique for addressing these challenges by encapsulating chemicals within 3D-printed polymeric cylinders designed for various chemical transformations. The studied encapsulation method not only exhibits reaction yields comparable to those of established methodologies, but also significantly increases the safety and procedural efficiency of laboratory practice. The specially designed capsules are soluble in prevalent organic solvents, facilitating the controlled release of their chemical contents when subjected to reactions. The inherent compatibility of these capsules with multiple reagents underscores their potential to be considered as a new approach in sustainable laboratory practices. Encapsulation technology presents a safer alternative to manual handling of volatile, toxic, and flammable reagents, thus mitigating potential hazards. This translates to a significant reduction in the risks associated with chemical handling while simultaneously simplifying traditional time-consuming procedures. Varying the geometric and chemical properties of the capsules allows for the encapsulation of a diverse range of substances and reactions, demonstrating their adaptability. Given its transformative potential, this technique provides new opportunities for future endeavors in the chemical domain. The approach of encapsulating chemicals could contribute to an expected digital discovery paradigm shift, ushering in an era of streamlined, safer, and sustainable chemical practices. The potential benefits, from safety to sustainability, of this approach make it appealing for a broad spectrum of chemical applications.

Computational analysis of R–X oxidative addition to Pd nanoparticles

Polynski M.V., Vlasova Yu.S., Solovev Ya.V., Kozlov S.M., Ananikov V.P. , Chem. Sci., 2024, ASAP.
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Oxidative addition (OA) is a necessary step in mechanisms of widely used synthetic methodologies such as the Heck reaction, cross-coupling reactions, and the Buchwald–Hartwig amination. This study pioneers the exploration of OA of aryl halide to palladium nanoparticles (NPs), a process previously unaddressed in contrast to the activity of well-studied Pd(0) complexes. Employing DFT modeling and semi-empirical metadynamics simulations, the oxidative addition of phenyl bromide to Pd nanoparticles was investigated in detail. Energy profiles of oxidative addition to Pd NPs were analyzed and compared to those involving Pd(0) complexes forming under both ligand-stabilized (phosphines) and ligandless (amine base) conditions. Metadynamics simulations highlighted the edges of the (1 1 1) facets of Pd NPs as the key element of oxidative addition activity. We demonstrate that OA to Pd NPs is not only kinetically facile at ambient temperatures but also thermodynamically favorable. This finding accentuates the necessity of incorporating OA to Pd NPs in future investigations, thus providing a more realistic view of the involved catalytic mechanisms. These results enhance the understanding of aryl halide (cross-)coupling reactions, reinforcing the concept of a catalytic "cocktail". This concept posits dynamic interconversions between diverse active and inactive centers, collectively affecting the outcome of the reaction. High activity of Pd NPs in direct C–X activation paves the way for novel approaches in catalysis, potentially enhancing the field and offering new catalytic pathways to consider.

Recent Trends in Supercapacitor Research: Sustainability in Energy and Materials

Chernysheva D., Smirnova N., Ananikov V.P. , ChemSusChem, 2024, 16, e202301367.
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Supercapacitors (SCs) have emerged as critical components in applications ranging from transport to wearable electronics due to their rapid charge-discharge cycles, high power density, and reliability. This review offers an analysis of recent strides in supercapacitor research, emphasizing pivotal developments in sustainability, electrode materials, electrolytes, and 'smart SCs' designed for modern microelectronics with attributes such as flexibility, stretchability, and biocompatibility. Central to this discourse are two dominant electrode materials: carbon materials (CMs), primarily in Electric Double Layer Capacitors (EDLCs), and pseudocapacitive materials, involving oxides/hydroxides, chalcogenides, metal-organic frameworks, conductive polymers and metal nitrides such as MXene. Despite EDLCs' historical use, challenges such as low energy density persist, with heteroatom introduction into the carbon lattice posed as a solution. Concurrently, pseudocapacitive materials dominate recent studies, with efficiency enhancement strategies, such as the creation of hybrids based on different types of materials, surface structural engineering and doping, under exploration. Emphasis is given to smart SCs with novel attributes such as self-charging, self-healing, biocompatibility, and environmentally conscious designs. In summary, the article underscores the drive in sustainable supercapacitor research to achieve high energy and power density, steering towards SCs that are efficient and versatile and involving bioderived/biocompatible SC materials.

Aerobic bacteria-supported biohybrid palladium catalysts for efficient cross-coupling reactions

Rybochkin P.V., Perchikov R.N., Karlinskii B.Ya., Kamanina O.A., Arlyapov V.A., Kashin A.S., Ananikov V.P. , J. Cat., 2024, 429, 115238.
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Palladium-based catalysts are of key importance in organic synthesis due to their versatility and tolerance for a wide range of functional groups. However, their use challenged by increasing sustainability issues and complex preparation methods. Consequently, the development of new heterogeneous catalysts with enhanced sustainability is of significant interest. Typically, the synthesis of carbon supports for palladium is associated with high energy consumption or the generation of substantial chemical waste, prompting extensive research into the creation of sustainable biological supports. In this study, the potential use of aerobic bacterial cells as a support for palladium nanoparticles was explored, using Paracoccus yeei VKM B-3302 as a model organism. Electron microscopy, powder X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) studies demonstrated the formation of palladium particles on the cell surface as well as inside microorganisms following deposition from a solution. Control experiments established that bacterial cells do not interact with either the reactants or the products of selected cross-coupling processes. Furthermore, bacteria do not affect the analysis of reaction mixtures by nuclear magnetic resonance (NMR) spectroscopy and gas chromatography-mass spectrometry (GC–MS). At the same time, palladium/Paracoccus yeei demonstrated efficient catalysis of the Mizoroki-Heck and Suzuki-Miyaura reactions, yielding results comparable to commercial palladium on carbon (Pd/C) catalysts. Employing a fresh start procedure and catalyst separation method, the catalyst was successfully recycled and reused across five cycles, maintaining good catalytic activity. In a broader aspect, bacteria-supported biohybrid palladium catalysts can represent a new type of catalysts worth to explore in a number of processes, where sustainability issues are concerned.

Boosting the generality of catalytic systems by the synergetic ligand effect in Pd-catalyzed C-N cross-coupling

Grebennikov N.O., Boiko D.A., Prima D.O., Madiyeva M., Minyaev M.E., Ananikov V.P., J. Cat., 2024, 429, 115240.
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In the areas of catalysis and organic chemistry, the development of versatile and efficient catalytic systems has long been a challenge, primarily due to the intricate relationship between ligands and transition metal centers. This study addresses this challenge by exploring the concept of ligand synergy to enhance the generality of catalytic systems, a crucial metric for their practical utility. By combining N-heterocyclic carbene (NHC) and phosphine ligands, we unveil a novel catalytic system that exhibits high level of generality in the Buchwald-Hartwig cross-coupling reaction. Our findings not only demonstrate the enhanced efficiency of this system, leading to the synthesis of valuable compounds with applications in organic electroluminescent devices and the pharmaceutical industry, but also shed light on the broader potential of ligand synergy in catalysis. Through machine learning analysis, we uncover the critical role of specific ligand properties, further paving the way for rational catalyst design.

Unraveling the transformative pathways of Au-NHC and Au-alkynyl complexes and bridging the gap between molecular and nanoscale gold systems

Grudova M.V., Galushko A.S., Ilyushenkova V.V., Minyaev M.E., Fakhrutdinov A.N., Prima D.O., Ananikov V.P., Inorg. Chem. Front., 2024, 11, 1839-1851.
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The aim of the present study was to explore the transformations of heteroleptic and homoleptic Au( I) complexes in detail and to systematically map their chemical evolutionary pathways. The relationships between these Au(I) complexes and the formation of gold nanoparticles and between the leaching processes of Au species from nanoparticles by NHC carbenes were studied. Moreover, Au-based reaction systems exhibit a wide variety of gold complexes and metallic gold particles depending on the conditions. The evolutionary pathways and transformations of homoleptic and heteroleptic Au(I) complexes were mapped using NMR, ESI-HRMS and electron microscopy. Depending on the conditions, a diverse range of metallic gold nanoparticles was formed. Interestingly, the formation of an NHC-Au(I) complex during the leaching of Au species from metallic nanoparticles in the presence of NHC carbenes was also noted. Our findings illustrate that the composition of Au-based reaction systems can simultaneously include various gold complexes and gold particles, reinforcing the potential of gold complexes to activate and transform molecules in a variety of reactions. By studying and understanding the physical and chemical properties of NHC-Au(I) complexes and the transformations they undergo under various conditions, we provide new opportunities for future research using gold-based systems for the development of dynamic catalytic systems.

Base-Ionizable Anionic NHC Ligands in Pd-catalyzed Reactions of Aryl Chlorides

Chernenko A., Baydikova V., Kutyrev V., Astakhov A., Minyaev M., Chernyshev V., Ananikov V. P. , ChemCatChem, 2024, e202301471.
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Aryl chlorides, due to their affordability and accessibility, are preferred reagents in Pd-catalyzed arylation reactions. However, the reactivity of aryl chlorides is often reduced compared to aryl bromides and iodides due to the significantly higher barriers of the oxidative addition stage. This research introduces a novel design for NHC ligands, which notably enhances the efficiency of Pd/NHC catalytic systems in reactions where oxidative addition of aryl chloride is the rate-limiting step. This design leverages a synergy between specific steric characteristics and the anionic nature of the newly fashioned 1,2,4-triazol-5-ylidene ligands. These ligands, inspired by Nitron-type designs, can be ionized under basic conditions due to their NH-acidic aryl(alkyl)amino groups. Detailed experimental and DFT studies revealed that the deprotonation of these NHCs promotes electron donation to the metal center, promoting the oxidative addition of aryl chloride. The specially optimized ATPr ligand, featuring 2,6-diisopropylphenyl groups, displayed remarkable catalytic efficacy in the Suzuki-Miyaura reaction and improved outcomes in ketone α-arylation and Buchwald-Hartwig reactions with unactivated aryl chlorides. The insights and strategies established in this study provide rational considerations for further advancements in NHC designs and their applications in metal-catalyzed reactions.

Mechanistic Insight into Palladium-Catalyzed Asymmetric Alkylation of Indoles with Diazoesters Employing Bipyridine-N,N’-dioxides as Chiral Controllers

Fukazawa Ya., Vaganov V.Yu., Burykina J.V., Fakhrutdinov A.N., Safiullin R.I., Plasser F., Rubtsov A.E., Ananikov V.P., Malkov A.V. , Adv.Synth.Catal., 2024, 366, 121-133.
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Metal-catalyzed asymmetric alkylation of indoles with α-diazoesters is well-known, however, the underlying mechanisms of this reaction, particularly the origin of stereoselectivity, remain uncertain. For the Pd catalysis, we address this cutting-edge challenge from two complementary viewpoints – i) the molecular level regarding a single catalytically active Pd center; and ii) nano-level Pd species investigating the factors favoring the appearance of the preferred catalytic centers. The formation of the active catalytic species was monitored by structural methods (NMR and ESI-MS), and metal particles were characterized with electron microscopy (SEM, EDX). On the molecular level, chiral bipyridine-N,N'-dioxides proved to be competent chiral controllers. The kinetic and DFT computational data revealed a crucial role of water in the rate and selectivity determining steps and showed that the enantioselectivity of the process is controlled by the protodepalladation step. On the nano-scale, the important effect of catalyst precursor on the overall reaction performance was shown.

Structure and Dynamic Rearrangements of the Pt2dba3 and Pd2dba3 Complexes in Solution

Kulikovskaya N.S., Ondar E.E., Perepukhov A.M., Kostyukovich A.Yu., Novikov R.A., Ananikov V.P., Inorg. Chem., 2024, 63, 2967–2976.
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Although the tris(dibenzylideneacetone)diplatinum complex (Pt 2dba3) is an important source of Pt(0) used in catalysis and materials science, its structure has not yet been fully elucidated. A thorough study of the three-dimensional structure of Pt2dba3 and its dynamic behavior in solution was carried out using NMR spectroscopy methods at a high field (600 MHz) and molecular modeling. The complex was shown to contain three dba ligands in the s-cis,s-trans, s-trans,s-cis, and s-trans,s-trans conformations, which are uniformly oriented around the Pt2 backbone. In solution, the Pt2dba3 and Pd2dba3 complexes undergo rapid dynamic rearrangements, as evidenced by the exchange between the signals of the olefin protons of various dba ligands in the EXSY NMR spectra. According to the experimental measurements, the activation energies of the rearrangements were estimated to be 19.9 ± 0.2 and 17.9 ± 0.2 kcal/mol for the platinum and palladium complexes, respectively. Three possible mechanisms for this chemical exchange process were considered within the framework of DFT calculations. According to the calculated data, M2dba3 complexes undergo fluxional isomerization involving successive rotations of the dihedral angles formed by the carbonyl group and the C═C bond. Dissociation of dba ligands does not occur within these processes.

Quantitative Determination of Active Species Transforming the R‐NHC Coupling Process under Catalytic Conditions

Patil E.D., Burykina J.V., Eremin D.B., Boiko D.A., Shepelenko K.E., Ilyushenkova V.V., Chernyshev V.M., Ananikov V.P., Inorg. Chem., 2024, 63, 2967–2976.
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Palladium complexes with N-heterocyclic carbenes (Pd/NHC) serve as prominent precatalysts in numerous Pd-catalyzed organic reactions. While the evolution of Pd/NHC complexes, which involves the cleavage of the Pd–C(NHC) bond via reductive elimination and dissociation, is acknowledged to influence the catalysis mechanism and the performance of the catalytic systems, conventional analytic techniques [such as NMR, IR, UV–vis, gas chromatography–mass spectrometry (GC–MS), and high-performance liquid chromatography (HPLC)] frequently fail to quantitatively monitor the transformations of Pd/NHC complexes at catalyst concentrations typical of real-world conditions (below approximately 1 mol %). In this study, for the first time, we show the viability of using electrospray ionization mass spectrometry (ESI-MS). This approach was combined with the use of selectively deuterated H-NHC, Ph-NHC, and O-NHC coupling products as internal standards, allowing for an in-depth quantitative analysis of the evolution of Pd/NHC catalysts within actual catalytic systems. The reliability of this approach was affirmed by aligning the ESI-MS results with the NMR spectroscopy data obtained at greater Pd/NHC precatalyst concentrations (2–5 mol %) in the Mizoroki–Heck, Sonogashira, and alkyne transfer hydrogenation reactions. The efficacy of the ESI-MS methodology was further demonstrated through its application in the Mizoroki–Heck reaction at Pd/NHC loadings of 5, 0.5, 0.05, and 0.005 mol %. In this work, for the first time, we present a methodology for the quantitative characterization of pivotal catalyst transformation processes commonly observed in M/NHC systems.

Role of Acetylene in the Chemical Evolution of Carbon Complexity

Pentsak E.O., Murga M.S., Ananikov V. P., ACS Earth and Space Chemistry, 2024, ASAP.
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Acetylene, among the multitude of organic molecules discovered in space, plays a distinct role in the genesis of organic matter. Characterized by its unique balance of stability and reactivity, acetylene is the simplest unsaturated organic molecule known to have a triple bond. In addition to its inherent chemical properties, acetylene is one of the most prevalent organic molecules found across the Universe, spanning from the icy surfaces of planets and satellites and the cold interstellar medium with low temperatures to hot circumstellar envelopes where temperatures surge to several thousand kelvins. These factors collectively position acetylene as a crucial building block in the molecular diversification of organic molecules and solids present in space. This review comprehensively discusses the formation and expansion of carbon skeletons involving acetylene, ranging from the formation of simple molecules to the origination of the first aromatic ring and ultimately to the formation of nanosized carbon particles. Mechanisms pertinent to both hot environments, such as circumstellar envelopes, and cold environments, including molecular clouds and planetary atmospheres, are explored. In addition, this review contemplates the role of acetylene in the synthesis of prebiotic molecules. A distinct focus is accorded to the recent advancements and future prospects of research into catalytic processes involving acetylene molecules, which is a significant instrument in driving the evolution of carbon complexity in the Universe. The insights garnered from this review underscore the significance of acetylene in astrochemistry and potentially contribute to our understanding of the chemical evolution of the Universe.

Comparative Study of Pd-Mediated Carbon−Carbon, Carbon−Heteroatom, and Heteroatom−Heteroatom Bond Formation/Breakage (C = Csp3, Csp2, Csp; X = B, N, O, Si, P, S, Se, Te)

Gordeev E.G., Musaev D.G., Ananikov V.P., Organometallics, 2024, 43, 1-13.
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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)2Pd(L)2, (X)2Pd(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 Csp3 > Csp > Csp2. The activity of coupling groups X containing a heteroatom decreases in the series of heteroatoms P, S, Se ≫ N ≫ O (for Csp2 and Csp types of carbon centers) and P > S, Se ≫ N ≫ O (for Csp3 type of carbon center). The relationship between the structural lability of the (R)2Pd(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)2Pd(L)2 and (X)2Pd(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.

Assembly of (2×C2+C`2)×n Molecular Complexity Using a Sequence of Pt‑ and Pd-Catalyzed Transformations with Calcium Carbide

Potorochenko A.N., Rodygin K.S., Ananikov V. P., Eur. J. Org. Chem., 2024, e202301012.
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Constructing molecular complexity from simple precursors stands as a cornerstone in contemporary organic synthesis. Systems harnessing easily accessible starting materials, which offer control over stereochemistry and support a modular assembly approach, are particularly in demand. In this research, we utilized calcium carbide, presenting a sustainable pathway to generate acetylene gas - a fundamental C2 building block. We performed a Pt-facilitated linkage of two C2-units sourced from two calcium carbide molecules to craft a conjugated C4 core with exceptional stereoselectivity. As a benchmark, we selected the synthesis of (E,E)-1,4-diiodobuta-1,3-diene, executing it in a two-chamber reactor. Compartmentalization of the reactions across these chambers resulted in the desired product in 85% yield. Furthermore, highenergy polymeric substances were derived by marrying the molecular intricacy between (E,E)-1,4-diiodobuta-1,3-diene and calcium carbide, underpinning a unique C4 + C2 assembly blueprint. The structure and morphology of the polymeric material were characterized by IR and NMR spectroscopy, scanning electron microscopy, and energy dispersive X-ray spectroscopy. Overall, two complementary 2×C2-to-C4 and (2×C2+C`2)×n assembly schemes were developed using Pt and Pd catalysis.