Catalysis with Chalcogen Bonds

Herein, we introduce catalysts that operate with chalcogen bonds. Compared to conventional hydrogen bonds, chalcogen bonds are similar in strength but more directional and hydrophobic, thus ideal for precision catalysis in apolar solvents. For the transfer hydrogenation of quinolines and imines, rate enhancements well beyond a factor of 1000 are obtained with chalcogen bonds. Better activities with deeper σ holes and wider bite angles, chloride inhibition and correlation with computed anion binding energies are consistent with operational chalcogen bonds. Comparable to classics, such as 2,2′‐bipyrroles or 2,2′‐bipyridines, dithieno[3,2‐b;2′,3′‐d]thiophenes (DTTs), particularly their diimides, but also wide‐angle cyclopentadithiazole‐4‐ones are identified as privileged motifs to stabilize transition states in the focal point of the σ holes on their two co‐facial endocyclic sulfur atoms.     

Chalcogen Bonding: An Overview

In the last few decades, “unusual” noncovalent interactions like anion‐π and halogen bonding have emerged as interesting alternatives to the ubiquitous hydrogen bonding in many research areas. This is also true, to a somewhat lesser extent, for chalcogen bonding, the noncovalent interaction involving Lewis acidic chalcogen centers. Herein, we aim to provide an overview on the use of chalcogen bonding in crystal engineering and in solution, with a focus on the recent developments concerning intermolecular chalcogen bonding in solution‐phase applications. In the solid phase, chalcogen bonding has been used for the construction of nano‐sized structures and the self‐assembly of sophisticated self‐complementary arrays. In solution, until very recently applications mostly focused on intramolecular interactions which stabilized the conformation of intermediates or reagents. In the last few years, intermolecular chalcogen bonding has increasingly also been exploited in solution, most notably in anion recognition and transport as well as in organic synthesis and organocatalysis.     

The Dominant Role of Chalcogen Bonding in the Crystal Packing of 2D/3D Aromatics

The chalcogen bond is a nonclassical σ‐hole‐based noncovalent interaction with emerging applications in medicinal chemistry and material science. It is found in organic compounds, including 2D aromatics, but has so far never been observed in 3D aromatic inorganic boron hydrides. Thiaboranes, harboring a sulfur heteroatom in the icosahedral cage, are candidates for the formation of chalcogen bonds. The phenyl‐substituted thiaborane, synthesized and crystalized in this study, forms sulfur???π type chalcogen bonds. Quantum chemical analysis revealed that these interactions are considerably stronger than both in their organic counterparts and in the known halogen bond. The reason is the existence of a highly positive σ‐hole on the positively charged sulfur atom. This discovery expands the possibilities of applying substituted boron clusters in crystal engineering and drug design.     

Quantifying the Bonding Strength of Gold‐Chalcogen Bonds in Block Copolymer Systems

Gold‐chalcogen interactions are ubiquitous in gold biological and medicinal systems. Understanding the nature of these interactions can provide the basis for regulating their structures and functionalities, and a reasonable way to interpret the differences in various properties. However, the relative strength of gold‐chalcogen bonds remains controversial, and the conclusions of many related works are inconsistent. Thus, in this work, we successfully quantified the relative strength of Au‐X (X=S, Se, and Te from chalcogenide‐containing A‐B‐A type block copolymers) interactions at the single‐molecule level through single‐molecule force spectroscopy (SMFS) from a kinetic point of view and quantum chemical studies from a thermodynamic point of view. Both sets of results suggested that the strength of the Au‐X bonds decreases as Au‐Te>Au‐Se>Au‐S. Our findings unveiled the relative strength and nature of gold‐chalcogen interactions, which may help expand their application in electronics, catalysis, medicine and many other fields.     

Chalcogen Bonding Catalysis of a Nitro‐Michael Reaction

Chalcogen bonding is the non‐covalent interaction between Lewis acidic chalcogen substituents and Lewis bases. Herein, we present the first application of dicationic tellurium‐based chalcogen bond donors in the nitro‐Michael reaction between trans‐β‐nitrostyrene and indoles. This also constitutes the first activation of nitro derivatives by chalcogen bonding (and halogen bonding). The catalysts showed rate accelerations of more than a factor of 300 compared to strongly Lewis acidic hydrogen bond donors. Several comparison experiments, titrations, and DFT calculations support a chalcogen‐bonding‐based mode of activation of β‐nitrostyrene.     

Supramolecular Wiring of Benzo‐1,3‐chalcogenazoles through Programmed Chalcogen Bonding Interactions

The high‐yielding synthesis of 2‐substituted benzo‐1,3‐tellurazoles and benzo‐1,3‐selenazoles through a dehydrative cyclization reaction has been reported, giving access to a large variety of benzo‐1,3‐chalcogenazoles. Exceptionally, these aromatic heterocycles proved to be very stable and thus very handy to form controlled solid‐state organizations in which wire‐like polymeric structures are formed through secondary N???Y bonding interactions (SBIs) engaging the chalcogen (Y=Se or Te) and nitrogen atoms. In particular, it has been shown that the recognition properties of the chalcogen centre at the solid state could be programmed by selectively barring one of its σ‐holes through a combination of electronic and steric effects exerted by the substituent at the 2‐position. As predicted by the electrostatic potential surfaces calculated by quantum chemical modelling, the pyridyl groups revealed to be the stronger chalcogen bonding acceptors, and thus the best ligand candidate for programming the molecular organization at the solid state. In contrast, the thiophenyl group is an unsuitable substituent for establishing SBIs in this molecular system as it gives rise to chalcogen–chalcogen repulsion. The weaker chalcogen donor properties of the Se analogues trigger the formation of feeble N???Se contacts, which are manifested in similar solid‐state polymers featuring longer nitrogen–chalcogen distances.     

Regenerable Antioxidants—Introduction of Chalcogen Substituents into Tocopherols

To improve the radical‐trapping capacity of the natural antioxidants, alkylthio‐, alkylseleno‐, and alkyltelluro groups were introduced into all vacant aromatic positions in β‐, γ‐ and δ‐tocopherol. Reaction of the tocopherols with electrophilic chalcogen reagents generated by persulfate oxidation of dialkyl dichalcogenides provided convenient but low‐yielding access to many sulfur and selenium derivatives, but failed in the case of tellurium. An approach based on lithiation of the appropriate bromo‐tocopherol, insertion of chalcogen into the carbon‐lithium bond, air‐oxidation to a dichalcogenide, and final borohydride reduction/alkylation turned out to be generally applicable to the synthesis of all chalcogen derivatives. Whereas alkylthio‐ and alkylseleno analogues were generally poorer quenchers of lipid peroxyl radicals than the corresponding parents, all tellurium compounds showed a substantially improved radical‐trapping activity. Introduction of alkyltelluro groups into the tocopherol scaffold also caused a dramatic increase in the regenerability of the antioxidant. In a two‐phase lipid peroxidation system containing N‐acetylcysteine as a water‐soluble co‐antioxidant the inhibition time was up to six‐fold higher than that recorded for the natural antioxidants.     

The Crucial Role of Charge Accumulation and Spin Polarization in Activating Carbon‐Based Catalysts for Electrocatalytic Nitrogen Reduction

Cost‐effective carbon‐based catalysts are promising for catalyzing the electrochemical N₂ reduction reaction (NRR). However, the activity origin of carbon‐based catalysts towards NRR remains unclear, and regularities and rules for the rational design of carbon‐based NRR electrocatalysts are still lacking. Based on a combination of theoretical calculations and experimental observations, chalcogen/oxygen group element (O, S, Se, Te) doped carbon materials were systematically evaluated as potential NRR catalysts. Heteroatom‐doping‐induced charge accumulation facilitates N₂ adsorption on carbon atoms and spin polarization boosts the potential‐determining step of the first protonation to form *NNH. Te‐doped and Se‐doped C catalysts exhibited high intrinsic NRR activity that is superior to most metal‐based catalysts. Establishing the correlation between the electronic structure and NRR performance for carbon‐based materials paves the pathway for their NRR application.     

Unusually Short Chalcogen Bonds Involving Organoselenium: Insights into the Se–N Bond Cleavage Mechanism of the Antioxidant Ebselen and Analogues

Structural studies on the polymorphs of the organoselenium antioxidant ebselen and its derivative show the potential of organic selenium to form unusually short Se???O chalcogen bonds that lead to conserved supramolecular recognition units. Se???O interactions observed in these polymorphs are the shortest such chalcogen bonds known for organoselenium compounds. The FTIR spectral evolution characteristics of this interaction from solution state to solid crystalline state further validates the robustness of this class of supramolecular recognition units. The strength and electronic nature of the Se???O chalcogen bonds were explored using high‐resolution X‐ray charge density analysis and atons‐in‐molecules (AIM) theoretical analysis. A charge density study unravels the strong electrostatic nature of Se???O chalcogen bonding and soft‐metal‐like behavior of organoselenium. An analysis of the charge density around Se?N and Se?C covalent bonds in conjunction with the Se???O chalcogen bonding modes in ebselen and its analogues provides insights into the mechanism of drug action in this class of organoselenium antioxidants. The potential role of the intermolecular Se???O chalcogen bonding in forming the intermediate supramolecular assembly that leads to the bond cleavage mechanism has been proposed in terms of electron density topological parameters in a series of molecular complexes of ebselen with reactive oxygen species (ROS).     

The Carbonyl⋅⋅⋅Tellurazole Chalcogen Bond as a Molecular Recognition Unit: From Model Studies to Supramolecular Organic Frameworks

In the last years, chalcogen bonding, the noncovalent interaction involving chalcogen centers, has emerged as interesting alternative to the ubiquitous hydrogen bonding in many research areas. Here, we could show by means of high‐level quantum chemical calculations that the carbonyl???tellurazole chalcogen bond is at least as strong as conventional hydrogen bonds. Using the carbonyl???tellurazole binding motif, we were able to design complex supramolecular networks in solid phase starting from tellurazole‐substituted cyclic peptides. X‐ray analyses reveal that the rigid structure of the cyclic peptides is caused by hydrogen bonds, whereas the supramolecular network is held together by chalcogen bonding. The type of the supramolecular network depends on peptide used; both linear wires and a honeycomb‐like supramolecular organic framework (SOF) were observed. The unique structure of the SOF shows two channels filled with different types of solvent mixtures that are either locked or freely movable.     

Chalcogen‐Bonding Catalysis: From Neutral to Cationic Benzodiselenazole Scaffolds

Benzodiselenazoles (BDS) are emerging as privileged structures for chalcogen‐bonding catalysis in the focal point of conformationally immobilized σ holes on strong selenium donors in a neutral scaffold. Whereas much attention has been devoted to work out the advantages of selenium compared to the less polarizable sulfur donors, high expectations concerning bidentate, rigid, and neutral scaffolds have been generated with little experimental support. Here we report design, synthesis and evaluation of the necessary catalysts to confirm that i) bidentate BDS are more effective than their monodentate analogs, ii) conformationally immobilized scaffolds are more effective than more flexible ones, iii) cationic BDS scaffolds are more effective than neutral ones, and iv) in dicationic‐bidentate BDS, contributions from chalcogen‐bonding dominate possible contributions from ion‐pairing catalysis. These conclusions result from rate enhancements found for a Ritter‐type anion‐binding reaction and an X‐ray crystal structure of dicationic BDS with a triflate anion bound with highest precision in the focal point of the σ holes.     

Catalysis with Pnictogen,Chalcogen, and Halogen Bonds

Halogen‐ and chalcogen‐based σ‐hole interactions have recently received increased interest in non‐covalent organocatalysis. However, the closely related pnictogen bonds have been neglected. In this study, we introduce conceptually simple, neutral, and monodentate pnictogen‐bonding catalysts. Solution and in silico binding studies, together with high catalytic activity in chloride abstraction reactions, yield compelling evidence for operational pnictogen bonds. The depth of the σ holes is easily varied with different substituents. Comparison with homologous halogen‐ and chalcogen‐bonding catalysts shows an increase in activity from main group VII to V and from row 3 to 5 in the periodic table. Pnictogen bonds from antimony thus emerged as by far the best among the elements covered, a finding that provides most intriguing perspectives for future applications in catalysis and beyond.     

Catalysis with Pnictogen,Chalcogen, and Halogen Bonds

Halogen‐ and chalcogen‐based σ‐hole interactions have recently received increased interest in non‐covalent organocatalysis. However, the closely related pnictogen bonds have been neglected. In this study, we introduce conceptually simple, neutral, and monodentate pnictogen‐bonding catalysts. Solution and in silico binding studies, together with high catalytic activity in chloride abstraction reactions, yield compelling evidence for operational pnictogen bonds. The depth of the σ holes is easily varied with different substituents. Comparison with homologous halogen‐ and chalcogen‐bonding catalysts shows an increase in activity from main group VII to V and from row 3 to 5 in the periodic table. Pnictogen bonds from antimony thus emerged as by far the best among the elements covered, a finding that provides most intriguing perspectives for future applications in catalysis and beyond.     

Strong σ‐Hole Activation on Icosahedral Carborane Derivatives for a Directional Halide Recognition

Crystal engineering based on σ‐hole interactions is an emerging approach for realization of new materials with higher complexity. Neutral inorganic clusters derived from 1,2‐dicarba‐closo‐dodecaborane, substituted with ‐SeMe, ‐TeMe, and ‐I moieties on both skeletal carbon vertices are experimentally demonstrated herein as outstanding chalcogen‐ and halogen‐bond donors. In particular, these new molecules strongly interact with halide anions in the solid‐state. The halide ions are coordinated by one or two donor groups (μ₁‐ and μ₂‐coordinations), to stabilize a discrete monomer or dimer motifs to 1D supramolecular zig‐zag chains. Crucially, the observed chalcogen bond and halogen bond interactions feature remarkably short distances and high directionality. Electrostatic potential calculations further demonstrate the efficiency of the carborane derivatives, with V_s,max being similar or even superior to that of reference organic halogen‐bond donors, such as iodopentafluorobenzene.     

New Forms and Functions of Tellurium: From Polycations to Metal Halide Tellurides

Metal chalcogenides and metal chalcogenide halides are distinguished by their structural diversity and by their very different physical properties. Therefore, the synthesis of novel compounds from this class is always a rewarding goal for the preparatively oriented solid-state chemist. Over the past few years, many syntheses and structural investigations have stimulated the field. The emphasis of the research has been placed on selenium-rich and tellurium-rich compounds, which are characterized by directed covalent bonds between the chalcogen atoms. Compounds with novel chalcogen polycations have also become accessible during the past few years by reacting the chalcogen elements with transition metal halides, or from chemical vapor deposition in the sense of chemical transport reactions. In these compounds, tellurium differs from its lighter homologues by a pronounced tendency towards greater covalence. This article attmepts to provide an overview of new developments in the field of compounds with chalcogen polycations and of metal chalcogenide halides, with an emphasis on compounds containing molybdenum and tungsten as the transition metals and tellurium as the chalcogen.     

The Opening of 1,2‐Dithiolanes and 1,2‐Diselenolanes: Regioselectivity,Rearrangements, and Consequences for Poly(disulfide)s,Cellular Uptake and Pyruvate Dehydrogenase Complexes

The thiol‐mediated opening of 3‐alkyl‐1,2‐dithiolanes and diselenolanes is described. The thiolate nucleophile is shown to react specifically with the secondary chalcogen atom, against steric demand, probably because the primary chalcogen atom provides a better leaving group. Once released, this primary chalcogen atom reacts with the obtained secondary dichalcogenide to produce the constitutional isomer. Thiolate migration to the primary dichalcogenide equilibrates within ca. 20 ms at room temperature at a 3 : 2 ratio in favor of the secondary dichalcogenide. The clarification of this focused question is important for the understanding of multifunctional poly(disulfide)s obtained by ring opening disulfide exchange polymerization of 3‐alkyl‐1,2‐dithiolanes, to rationalize the cellular uptake mediated by 3‐alkyl‐1,2‐diselenolanes as molecular walkers and, perhaps, also of the mode of action of pyruvate dehydrogenase complexes. The isolation of ring‐opened diselenolanes is particularly intriguing because dominant selenophilicity disfavors ring opening strongly.     

A Chalcogen‐Bonding Cascade Switch for Planarizable Push–Pull Probes

Planarizable push–pull probes have been introduced to demonstrate physical forces in biology. However, the donors and acceptors needed to polarize mechanically planarized probes are incompatible with their twisted resting state. The objective of this study was to overcome this “flipper dilemma” with chalcogen‐bonding cascade switches that turn on donors and acceptors only in response to mechanical planarization of the probe. This concept is explored by molecular dynamics simulations as well as chemical double‐mutant cycle analysis. Cascade switched flipper probes turn out to excel with chemical stability, red shifts adding up to high significance, and focused mechanosensitivity. Most important, however, is the introduction of a new, general and fundamental concept that operates with non‐trivial supramolecular chemistry, solves an important practical problem and opens a wide chemical space.     

Ligand‐Stabilized Chalcogen Dications

Chalcogen‐transfer reagents? The bonding in the dicationic rings C₂N₂E²⁺ (see picture) differs from that in N‐heterocyclic carbenes and their isovalent p‐block analogues in accommodating a lone pair of electrons with π symmetry, as well as σ symmetry, on the chalcogen center. The labile electrophilic chalcogenium dications (E²⁺) are potentially versatile chalcogen‐transfer reagents in reactions with a variety of inorganic and organic substrates.

     

Evaluation of Electron Donation as a Mechanism for the Stabilisation of Chalcogenate‐Protected Gold Nanoclusters

Models based on Au(111) face have been extensively used to describe self‐assembled monolayers, as well nanoparticles and nanoclusters. However, for very small clusters (<2 nm), the chemisorption of ligands leads to surface reconstruction, making necessary the use of a more reliable model that is able to simulate the main electronic and geometrical features of these small systems. In this work, a simple model to describe the geometries and the metal–ligand bonding in chalcogenate‐protected gold nanoclusters is proposed. Three different models with Au_n⁺ and [XCH₃]^? (n=10, 15, 19, 22 and X=S, Se, Te) are used in this work. The obtained structures are in close agreement not only with the available crystallographic data, but also with much more expensive computational procedures, confirming that the proposed models are robust enough to describe the metal–ligand bonding. The results reveal that the Au–X distances are dependent on both the nature of the chalcogen and the coordination mode. The shortest Au–X distances are observed in the face‐centred cubic mode, indicating that the central gold atom seems to play a role in determining the adsorption strength. The proposed models show unambiguously chalcogen→cluster σ‐donation, as supported by energy decomposition analysis coupled with the natural orbitals for chemical valence and natural bond orbital analyses. In all cases, the metal–ligand interactions are characterised as being more covalent than electrostatic.