Experimental and Computational Studies of Ruthenium Complexes Bearing Z-Acceptor Aluminum-Based Phosphine Pincer Ligands

Reaction of [Ru(C 6H 4PPh 2) 2(Ph 2PC 6H 4AlMe(THF))H] with CO results in clean conversion to the Ru-Al heterobimetallic complex [Ru(AlMePhos)(CO) 3] (1), where AlMePhos is the novel P-Al(Me)-P pincer ligand (o-Ph 2PC 6H 4) 2AlMe. Under photolytic conditions, 1 reacts with H 2to give [Ru(AlMePhos)(CO) 2(μ-H)H] (2) that is characterized by multinuclear NMR and IR spectroscopies. DFT calculations indicate that 2 features one terminal and one bridging hydride that are respectively anti and syn to the AlMe group. Calculations also define a mechanism for H 2addition to 1 and predict facile hydride exchange in 2 that is also observed experimentally. Reaction of 1 with B(C 6F 5) 3results in Me abstraction to form the ion pair [Ru(AlPhos)(CO) 3][MeB(C 6F 5) 3] (4) featuring a cationic [(o-Ph 2PC 6H 4) 2Al] +ligand, [AlPhos] +. The Ru-Al distance in 4 (2.5334(16) Å) is significantly shorter than that in 1 (2.6578(6) Å), consistent with an enhanced Lewis acidity of the [AlPhos] +ligand. This is corroborated by a blue shift in both the observed and computed ν COstretching frequencies upon Me abstraction. Electronic structure analyses (QTAIM and EDA-ETS) comparing 1, 4, and the previously reported [Ru(ZnPhos)(CO) 3] analogue (ZnPhos = (o-Ph 2PC 6H 4) 2Zn) indicate that the Lewis acidity of these pincer ligands increases along the series ZnPhos &lt; AlMePhos &lt; [AlPhos] +. copy; 2022 American Chemical Society.</p

Increased autophagy-related 5 gene expression is associated with collagen expression in the airways of refractory asthmatics

Background: Fibrosis, particularly excessive collagen deposition, presents a challenge for treating asthmatic individuals. At present, no drugs can remove or reduce excessive collagen in asthmatic airways. Hence, the identification of pathways involved in collagen deposition would help to generate therapeutic targets to interfere with the airway remodeling process. Autophagy, a cellular degradation process, has been shown to be dysregulated in various fibrotic diseases, and genetic association studies in independent human populations have identified autophagy-related 5 (ATG5) to be associated with asthma pathogenesis. Hence, the dysregulation of autophagy may contribute to fibrosis in asthmatic airways. Objective: This study aimed to determine if (1) collagen deposition in asthmatic airways is associated with ATG5 expression and (2) ATG5 protein expression is associated with asthma per se and severity. Methods: Gene expression of transforming growth factor beta 1, various asthma-related collagen types [collagen, type I, alpha 1; collagen, type II, alpha 1; collagen, type III, alpha 1; collagen, type V, alpha 1 (COL5A1) and collagen, type V, alpha 2], and ATG5 were measured using mRNA isolated from bronchial biopsies of refractory asthmatic subjects and assessed for pairwise associations. Protein expression of ATG5 in the airways was measured and associations were assessed for asthma per se, severity, and lung function. Main results: In refractory asthmatic individuals, gene expression of ATG5 was positively associated with COL5A1 in the airways. No association was detected between ATG5 protein expression and asthma per se, severity, and lung function. Conclusion and clinical relevance: Positive correlation between the gene expression patterns of ATG5 and COL5A1 suggests that dysregulated autophagy may contribute to subepithelial fibrosis in the airways of refractory asthmatic individuals. This finding highlights the therapeutic potential of ATG5 in ameliorating airway remodeling in the difficult-to-treat refractory asthmatic individuals

Single-crystal to cingle-crystal addition of H2to [Ir(iPr-PONOP)(propene)][BArF4] and comparison between solid-state and solution reactivity

The EPSRC (EP/M024210/2, EP/T019867/1), SCG Chemicals, The Clarendon Trust, The Leverhulme Trust (RPG-2020-184), Diamond Light Source for funding (PhD studentship to AM).The reactivity of the Ir(I) PONOP pincer complex [Ir(iPr-PONOP)(η2-propene)][BArF4], 6, [iPr-PONOP = 2,6-(iPr2PO)2C6H3N, ArF= 3,5-(CF3)2C6H3] was studied in solution and the solid state, both experimentally, using molecular density functional theory (DFT) and periodic-DFT computational methods, as well as in situ single-crystal to single-crystal (SC-SC) techniques. Complex 6 is synthesized in solution from sequential addition of H2and propene, and then the application of vacuum, to [Ir(iPr-PONOP)(η2-COD)][BArF4], 1, a reaction manifold that proceeds via the Ir(III) dihydrogen/dihydride complex [Ir(iPr-PONOP)(H2)H2][BArF4], 2, and the Ir(III) dihydride propene complex [Ir(iPr-PONOP)(η2-propene)H2][BArF4], 7, respectively. In solution (CD2Cl2) 6 undergoes rapid reaction with H2to form dihydride 7 and then a slow (3 d) onward reaction to give dihydrogen/dihydride 2 and propane. DFT calculations on the molecular cation in solution support this slow, but productive, reaction, with a calculated barrier to rate-limiting propene migratory insertion of 24.8 kcal/mol. In the solid state single-crystals of 6 also form complex 7 on addition of H2in an SC-SC reaction, but unlike in solution the onward reaction (i.e., insertion) does not occur, as confirmed by labeling studies using D2. The solid-state structure of 7 reveals that, on addition of H2to 6, the PONOP ligand moves by 90° within a cavity of [BArF4]-anions rather than the alkene moving. Periodic DFT calculations support the higher barrier to insertion in the solid state (ΔG‡= 26.0 kcal/mol), demonstrating that the single-crystal environment gates onward reactivity compared to solution. H2addition to 6 to form 7 is reversible in both solution and the solid state, but in the latter crystallinity is lost. A rare example of a sigma amine-borane pincer complex, [Ir(iPr-PONOP)H2(η1-H3B·NMe3)][BArF4], 5, is also reported as part of these studies.Peer reviewe

Groups 1, 2 and Zn(II) Heterodinuclear Catalysts for Epoxide/CO2 Ring-Opening Copolymerization

A series of heterodinuclear complexes are reported where both Zn(II) and a metal from Group 1 or 2 are chelated by a macrocyclic diphenolate-tetra-amine ligand. The complexes are characterized in the solid state, where relevant by single crystal X-ray crystallography and elemental analysis, and in solution, using NMR spectroscopy and mass spectrometry. The complex synthesis is achieved by reaction of the ligand with diethyl zinc to form the monozinc complex, in situ, followed by subsequent coordination of the second metal; this method enables heterodinuclear conversions >90% as determined by NMR spectroscopy. Alternatively, the same heterodinuclear complexes are accessed by reaction between the two homodinuclear complexes at elevated temperatures for extended periods. These findings suggest that most of the heterodinuclear complexes are the thermodynamic reaction products; the only exception is the Na(I)/Zn(II) complex which is unstable with respect to the homodinuclear counterparts. The catalytic activities and selectivity of the stable heterodinuclear complexes are compared, against each other and the relevant homodinuclear analogues, for the ring-opening copolymerization of CO2 and CHO. Nearly all the heterodinuclear complexes are less active than the dizinc analogues, but the Mg(II)/Zn(II) catalyst is more active. The co-ligand influences the product selectivity, with iodide ligands resulting in cyclic carbonate formation and carboxylate ligands giving a high selectivity for polycarbonate