NMR Studies of Ruthenium and Rhodium Complexes. In-situ and Ex-situ Photochemistry

Catalytic processes often involve organometallic complexes, the aims of this thesis were to study some specific ruthenium and rhodium complexes using photochemistry. This allowed their behaviour towards small molecules to be investigated since the coordination and activation of small molecules are fundamental parts of catalytic cycles. A further aim was to study suitable complexs with parahydrogen using time-resolved NMR methods with the intention of measuring p-H2 addition and/or the evolution of the p-H2-derived singlet state The photochemistry of CpRh(CH2CHSiMe3)2 (2.1), CpRh(COE)2 (2.2) and CpRh(COD) (2.3) with DMSO PhSOMe, trimethylvinylsilane and triethylsilane was probed. The photoactivity of 2.3 proved minimal with the main products being associated with the loss of the COD ligand. By contrast, 2.1 and 2.2 undergo the substitution of one or both of the alkene ligands, depending on the nature of the reacting ligand. Complexes 2.1, CpRh(CH2CHSiMe3)(DMSO) (2.4) and CpRh(P*Ph)(C2H4) (3.2) were deemed suitable for time-resolved studies with p-H2. 2.1 was found to form the expected dihydride (3.1) on a 50 ms timescale. 2.4 was also formed 3.1 but its PHIP enhancement was poor and whilst 3.1 did form the expected dihydride product PHIP was not observed. [Ru(H)2(CO)(PPh3)(Xantphos)] 5.1 was also synthesised and its reactivity towards a range of small molecules, which included DMSO, CO, ethene and Et3SiH, investigated. These studies revealed that its H2, CO and PPh3 ligands could all be lost photochemically and that the xantphos ligand could switch between κ2-PP and κ3-POP coordination. Time-resolved NMR studies on 5.1, with p-H2, found the H2 addition to the intermediate to occur with a rate of the order of 0.5 s−1. cis-[Ru(H)2(dppp)2] 6.1 was also studied using time-resolved NMR, in this case the rate of H2 addition was faster than the NMR timescales. This allowed the evolution of the p-H2 singlet state to be probed and shown to be as a function of the difference in scalar coupling between the hydrides and the equatorial 31P nuclei

NMR Studies of Ruthenium and Rhodium Complexes. In-situ and Ex-situ Photochemistry

Catalytic processes often involve organometallic complexes, the aims of this thesis were to study some specific ruthenium and rhodium complexes using photochemistry. This allowed their behaviour towards small molecules to be investigated since the coordination and activation of small molecules are fundamental parts of catalytic cycles. A further aim was to study suitable complexs with parahydrogen using time-resolved NMR methods with the intention of measuring p-H2 addition and/or the evolution of the p-H2-derived singlet state The photochemistry of CpRh(CH2CHSiMe3)2 (2.1), CpRh(COE)2 (2.2) and CpRh(COD) (2.3) with DMSO PhSOMe, trimethylvinylsilane and triethylsilane was probed. The photoactivity of 2.3 proved minimal with the main products being associated with the loss of the COD ligand. By contrast, 2.1 and 2.2 undergo the substitution of one or both of the alkene ligands, depending on the nature of the reacting ligand. Complexes 2.1, CpRh(CH2CHSiMe3)(DMSO) (2.4) and CpRh(P*Ph)(C2H4) (3.2) were deemed suitable for time-resolved studies with p-H2. 2.1 was found to form the expected dihydride (3.1) on a 50 ms timescale. 2.4 was also formed 3.1 but its PHIP enhancement was poor and whilst 3.1 did form the expected dihydride product PHIP was not observed. [Ru(H)2(CO)(PPh3)(Xantphos)] 5.1 was also synthesised and its reactivity towards a range of small molecules, which included DMSO, CO, ethene and Et3SiH, investigated. These studies revealed that its H2, CO and PPh3 ligands could all be lost photochemically and that the xantphos ligand could switch between κ2-PP and κ3-POP coordination. Time-resolved NMR studies on 5.1, with p-H2, found the H2 addition to the intermediate to occur with a rate of the order of 0.5 s−1. cis-[Ru(H)2(dppp)2] 6.1 was also studied using time-resolved NMR, in this case the rate of H2 addition was faster than the NMR timescales. This allowed the evolution of the p-H2 singlet state to be probed and shown to be as a function of the difference in scalar coupling between the hydrides and the equatorial 31P nuclei

Coherent evolution of parahydrogen induced polarisation using laser pump, NMR probe spectroscopy : Theoretical framework and experimental observation

We recently reported a pump-probe method that uses a single laser pulse to introduce parahydrogen (p-H2) into a metal dihydride complex and then follows the time-evolution of the p-H2-derived nuclear spin states by NMR. We present here a theoretical framework to describe the oscillatory behaviour of the resultant hyperpolarised NMR signals using a product operator formalism. We consider the cases where the p-H2-derived protons form part of an AX, AXY, AXYZ or AA′XX′ spin system in the product molecule. We use this framework to predict the patterns for 2D pump-probe NMR spectra, where the indirect dimension represents the evolution during the pump-probe delay and the positions of the cross-peaks depend on the difference in chemical shift of the p-H2-derived protons and the difference in their couplings to other nuclei. The evolution of the NMR signals of the p-H2-derived protons, as well as the transfer of hyperpolarisation to other NMR-active nuclei in the product, is described. The theoretical framework is tested experimentally for a set of ruthenium dihydride complexes representing the different spin systems. Theoretical predictions and experimental results agree to within experimental error for all features of the hyperpolarised 1H and 31P pump-probe NMR spectra. Thus we establish the laser pump, NMR probe approach as a robust way to directly observe and quantitatively analyse the coherent evolution of p-H2-derived spin order over micro-to-millisecond timescales

Assessment, endoscopy, and treatment in patients with acute severe ulcerative colitis during the COVID-19 pandemic (PROTECT-ASUC): a multicentre, observational, case-control study

BackgroundThere is a paucity of evidence to support safe and effective management of patients with acute severe ulcerative colitis during the COVID-19 pandemic. We sought to identify alterations to established conventional evidence-based management of acute severe ulcerative colitis during the early COVID-19 pandemic, the effect on outcomes, and any associations with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and severe COVID-19 outcomes. MethodsThe PROTECT-ASUC study was a multicentre, observational, case-control study in 60 acute secondary care hospitals throughout the UK. We included adults (≥18 years) with either ulcerative colitis or inflammatory bowel disease unclassified, who presented with acute severe ulcerative colitis and fulfilled the Truelove and Witts criteria. Cases and controls were identified as either admitted or managed in emergency ambulatory care settings between March 1, 2020, and June 30, 2020 (COVID-19 pandemic period cohort), or between Jan 1, 2019, and June 30, 2019 (historical control cohort), respectively. The primary outcome was the proportion of patients with acute severe ulcerative colitis receiving rescue therapy (including primary induction) or colectomy. The study is registered with ClinicalTrials.gov, NCT04411784. FindingsWe included 782 patients (398 in the pandemic period cohort and 384 in the historical control cohort) who met the Truelove and Witts criteria for acute severe ulcerative colitis. The proportion of patients receiving rescue therapy (including primary induction) or surgery was higher during the pandemic period than in the historical period (217 [55%] of 393 patients vs 159 [42%] of 380 patients; p=0·00024) and the time to rescue therapy was shorter in the pandemic cohort than in the historical cohort (p=0·0026). This difference was driven by a greater use of rescue and primary induction therapies with biologicals, ciclosporin, or tofacitinib in the COVID-19 pandemic period cohort than in the historical control period cohort (177 [46%] of 387 patients in the COVID-19 cohort vs 134 [36%] of 373 patients in the historical cohort; p=0·0064). During the pandemic, more patients received ambulatory (outpatient) intravenous steroids (51 [13%] of 385 patients vs 19 [5%] of 360 patients; p=0·00023). Fewer patients received thiopurines (29 [7%] of 398 patients vs 46 [12%] of 384; p=0·029) and 5-aminosalicylic acids (67 [17%] of 398 patients vs 98 [26%] of 384; p=0·0037) during the pandemic than in the historical control period. Colectomy rates were similar between the pandemic and historical control groups (64 [16%] of 389 vs 50 [13%] of 375; p=0·26); however, laparoscopic surgery was less frequently performed during the pandemic period (34 [53%] of 64] vs 38 [76%] of 50; p=0·018). Five (2%) of 253 patients tested positive for SARS-CoV-2 during hospital treatment. Two (2%) of 103 patients re-tested for SARS-CoV-2 during the 3-month follow-up were positive 5 days and 12 days, respectively, after discharge from index admission. Both recovered without serious outcomes. InterpretationThe COVID-19 pandemic altered practice patterns of gastroenterologists and colorectal surgeons in the management of acute severe ulcerative colitis but was associated with similar outcomes to a historical cohort. Despite continued use of high-dose corticosteroids and biologicals, the incidence of COVID-19 within 3 months was low and not associated with adverse COVID-19 outcomes