Graham J. Tizzard

Subvalent hydride species of heavier main-group elements are notoriously elusive due to their intrinsic instability and rapid decomposition, generating hydrogen. Nevertheless, they offer significant potential for small-molecule activation and catalysis. Herein, we report the synthesis and characterization of the first stable, crystalline subvalent indium hydride, supported by bis(N-heterocyclic carbene)borate ligands and featuring a covalent In–In bond. This compound has been comprehensively characterized by NMR spectroscopy, FT-IR, single-crystal X-ray diffraction, and computational calculations, and experimental and theoretical studies reveal key features that underpin its exceptional stability. Preliminary reactivity investigations demonstrate that this discrete In(II) hydride acts as a nucleophile, opening new avenues for bond activation involving hydrides derived from the heaviest p-block elements.

Herein, we describe a new class of zwitterionic heavier pnictogen species with bis ( N ‐heterocyclic carbene)borate as ligands, enabling the isolation of stable Sb and Bi species in multiple oxidation states. Computational analysis of zwitterionic pnictinidenes revealed their cationic character at the metal centre while holding unique electronic properties that contribute to their nucleophilicity and stability. These systems participate in oxidative addition and reductive elimination processes, and display redox catalytic activity in hydrodefluorination reactions, marking a unique example of cationic pnictinidene catalysing a redox transformation and providing reactivity beyond the constraints of pincer ligands. Additionally, we report on a novel dehydrogenative thiolation of silanes. This work expands the scope of low‐valent pnictogen chemistry, providing a novel platform for main group redox catalysis.

Herein, we describe a new class of zwitterionic heavier pnictogen species with bis ( N ‐heterocyclic carbene)borate as ligands, enabling the isolation of stable Sb and Bi species in multiple oxidation states. Computational analysis of zwitterionic pnictinidenes revealed their cationic character at the metal centre while holding unique electronic properties that contribute to their nucleophilicity and stability. These systems participate in oxidative addition and reductive elimination processes, and display redox catalytic activity in hydrodefluorination reactions, marking a unique example of cationic pnictinidene catalysing a redox transformation and providing reactivity beyond the constraints of pincer ligands. Additionally, we report on a novel dehydrogenative thiolation of silanes. This work expands the scope of low‐valent pnictogen chemistry, providing a novel platform for main group redox catalysis.

Herein we describe a new class of zwitterionic heavier pnictogen species with bis(NHC)borate as stabilizing ligands, enabling the isolation of Sb and Bi species in +1, +2, and +3 oxidation states. Computational analysis of zwitterionic pnictinidines revealed their cationis character, as well as unique electronic properties that contribute to their nucleophilicity and stability. These systems participate in key organometallic transformations, including oxidative addition and reductive elimination pro-cesses, and display redox catalytic activity in hydrodefluorination reactions, marking a rare example of pnictinidine-catalyzed redox transformation beyond the constraints of pincer ligands. Additionally, we report on a novel dehydrogenative thiolation of silanes. This work expands the scope of low-valent pnictogen chemistry, providing a novel platform for main group redox catalysis.

The P2X purinergic receptor 7 (P2X7) has an essential role in inflammation, innate immunity, tumor progression, neurodegenerative diseases, and several other diseases, leading subsequently to the development of P2X7 modulators. AZ11645373 is a frequently studied P2X7 antagonist tool com-pound, but always as a racemic mixture. Racemic AZ11645373 can be separated, into its respective enantiomers by chiral chromatography, albeit in small batches, and these were stereochemically in-tact over a year later, by chiral HPLC analysis. On a higher scale, significant decomposition is ob-served. One of the enantiomers was crystallised as a palladium complex and its (R)-configuration was determined by single crystal X-ray diffraction, further confirmed, in solution, by vibrational circular dichroism. Biological studies demonstrated that both (S)- and (R)-forms were able to fully inhibit human P2X7, but (R)-AZ11645373 was more potent, with an IC50 of 32.9 nM. Contrary to its effect on human P2X7, (S)-AZ11645373 was ineffective on mouse P2X7, while the (R)-AZ11645373 enantiomer was a full antagonist. These results demonstrated that the antagonistic effects of racemic AZ11645373 are mainly due to its (R)-enantiomer. Site-directed mutagenesis and molecular dynam-ics simulations indicated that the (R)-enantiomer may form specific interactions with Phe95 and the antagonists bound to the other P2X7 monomers. Phe95 is situated at the channel pore and appears to be the pivotal molecular gateway between AZ11645373 allosteric binding and locking of the closed state of the P2X7 channel. All together, these structure-function relationships should be helpful for drug design of P2X7 modulators.

Since the metal templated synthesis of catenanes by Sauvage, many mechanically chelating ligands, in which the donor atoms are provided by more than one interlocked covalent component, have been reported. However, despite the importance of controlling metal ion properties in a range of applications from catalysis to medicine, and the unusual properties of metal ions bound in the cavity of a catenane being reported as early as 1985, very few studies focus on the effect of the mechanical bond on the metal complex; typically, it is simply an intermediate en route to a metal-free synthetic target or used to control mechanical motion in prototypical molecular machines. Here we report perhaps the starkest demonstration of the ability of the mechanical bond to control metal ion properties, the unexpected isolation of an interlocked di-nuclear Cu complex in which these typically kinetically labile metal ions are sequestered such that it takes days to remove them from the ligand even under relatively harsh conditions. DFT modelling suggests that the complex is formed as a trapped intermediate in the Cu-mediated alkyne-azide cycloaddition reaction which represents the first unambiguous observation of such a species in this important “click” reaction.

N-alkylated C₂-symmetric amino acid amide derivatives were shown to catalyse the Michael addition of 2-hydroxy-1,4-napthoquinone to β-nitrostyrene, achieving a maximum ee of 44%. The corresponding trifluoroacetic acid salts also catalysed the aldol reaction between 4-nitrobenzaldehyde and hydroxyacetone, leading to the formation of predominantly syn-aldol products in up to 55% ee. Aspects of the solvent dependence of the aldol reaction and the H-bonding of the catalyst were investigated.

The catalytic hydrogenation of CO₂ to formate was achieved using the previously reported dichloro(η⁶‐p‐cymene){diphenyl(3‐methyl‐2‐indolyl)phosphine}ruthenium (1) as a catalyst under mild conditions. In this complex, the phosphorus‐based ligand adopts a κ¹‐P coordination mode. The catalytic activity was achieved in the presence of DBU as a base providing a TON_max value of 3,800. In order to explore potential transformations occurring within the catalytic reactions, a series of stoichiometric tests were performed. Complex 1 was reacted with DBU to form chloro(η⁶‐p‐cymene){diphenyl(3‐methyl‐2‐indolide)phosphine}ruthenium (2). Structural characterization of complex 2 confirmed a κ²‐P,N coordination mode for the ligand resulting in a four membered metallacycle. Reaction of 2 with H₂ led to the formation of hydrochloro(η⁶‐p‐cymene){diphenyl(3‐methyl‐indolyl)phosphine}ruthenium (3), albeit not with a clean conversion. This is the product resulting from the formal addition of hydrogen across the Ru−N bond of the metallacycle. Complex 3 was also synthesized via an alternative route involving the reaction of complex 1 with Me₂NH • BH₃ as a means of converting Ru−Cl to Ru−H

A new hydroxo‐bridged ruthenium (II) complex [{Ru(η⁶‐p‐cymene)(ⁱPr₂P−O)}₂(μ‐OH)]Cl (2) has fortuitously been isolated from the reaction between the known ruthenium(II) complex [RuCl₂(η⁶‐p‐cymene)(ⁱPr₂P‐OH)] (1) in either CDCl₃ or CHCl₃ solutions in the presence of excess DBU (1,8‐diazabicyclo(5.4.0)undec‐7‐ene) at room temperature. Complex 2 is only formed under specific conditions as an orange‐colored air and moisture stable binuclear complex. It is formed via the deprotonation of the P−OH unit in [RuCl₂(η⁶‐p‐cymene)(ⁱPr₂P‐OH)]. Complex 2 has been fully characterized by spectroscopic and analytical methods. Its structure was determined by single crystal X‐ray diffraction which reveals a boat‐shaped motif containing a bridging hydroxide unit which undergoes hydrogen bonding with a chloride counterion. Complex 2 was utilized as a catalyst for the hydrogenation of CO₂ to formic acid salt using molecular hydrogen. The catalytic reactions were performed at 100 °C in THF in the presence of DBU as a base to isolate [DBU+H][OC(O)H] salt as the final product. Using catalyst loadings down to 0.01 mol%, it was possible to hydrogenate gaseous CO₂ with TONs up to 9900.