Dual photosensitizer cycles working synergistically in a C(sp)-C(sp3) cross-coupling reaction

Funding: Authors thank the University of St Andrews, Syngenta and the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT) for financial support [Ph.D. studentship to “M.B.”; Grant code: EP/L016419/1]. We thank Umicore AG for the gift of materials. E.Z.-C. and P.C. acknowledge the European Union H2020 research and innovation program under the Marie Skłodowska Curie Grant Agreement (PhotoReAct, No 956324).To assess the value and reactivity of new photocatalysts (PCs), their performance should be evaluated in one or more established reactions and benchmarked against the performance using known PCs. Here, we evaluated our recently developed PC, pDTCz- DPmS, in a C(sp)-C(sp3) cross-coupling reaction that had been documented in the literature. Previous findings indicated this reaction could not proceed in the absence of PC; however, under our conditions this was not the case. Without PC, a moderate product yield was obtained, while this yield increased significantly upon addition of pDTCz-DPmS. UV-Vis absorption studies indicated that the Hantzsch ester (HE) additive was acting as a competitive absorber of the light from the excitation source, and quenching studies confirmed that the HE was quenched by the radical precursor, N-(acyloxy)phthalimide. Mechanistic investigations established that two parallel photosensitization pathways were in operation; a reductive quenching photocatalytic pathway (using pDTCz-DPmS) and a sacrificial photoreductant pathway (employing HE). These pathways work synergistically to enhance the yield of target product.Publisher PDFPeer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Employing organic donor-acceptor thermally activated delayed fluorescence (TADF) compounds as photocatalysts

Abstract redacted"This work was supported by Syngenta and the EPSRC (grant code: SCH0 MAB30E)."--Fundin

Organic thermally activated delayed fluorescence (TADF) compounds used in photocatalysis

We thank Syngenta and the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT) for financial support [Ph.D. studentship to “M.B.”; Grant code: EP/L016419/1].Organic compounds that show Thermally Activated Delayed Fluorescence (TADF) have become wildly popular as next-generation emitters in organic light emitting diodes (OLEDs). Since 2016, a subset of these have found increasing use as photocatalysts. This review comprehensively highlights their potential by documenting the diversity of the reactions where an organic TADF photocatalyst can be used in lieu of a noble metal complex photocatalyst. Beyond the small number of TADF photocatalysts that have been used to date, the analysis conducted within this review reveals the wider potential of organic donor-acceptor TADF compounds as photocatalysts. A discussion of the benefits of compounds showing TADF for photocatalysis is presented, which paints a picture of a very promising future for organic photocatalyst development.Publisher PDFPeer reviewe

Dual Photosensitizer Cycles Working Synergistically in a C(sp)-C(sp3) Cross-Coupling Reaction

To assess the value and reactivity of new photocatalysts (PCs), their performance should be evaluated in one or more established reactions and benchmarked against the performance using known PCs. Here, we evaluated our recently developed PC, pDTCz-DPmS, in a C(sp)-C(sp3) cross-coupling reaction that had been documented in the literature. Previous findings indicated this reaction could not proceed in the absence of PC; however, under our conditions this was not the case. Without PC, a moderate product yield was obtained, while this yield increased significantly upon addition of pDTCz-DPmS. UV-Vis absorption studies indicated that the Hantzsch ester (HE) additive was acting as a competitive absorber of the light from the excitation source, and quenching studies confirmed that the HE was quenched by the radical precursor, N-(acyloxy)phthalimide. Mechanistic investigations established that two parallel photosensitization pathways were in operation; a reductive quenching photocatalytic pathway (using pDTCz-DPmS) and a sacrificial photoreductant pathway (employing HE). These pathways work synergistically to enhance the yield of target product

Moving beyond cyanoarene thermally activated delayed fluorescence compounds as photocatalysts : an assessment of the performance of a pyrimidyl sulfone photocatalyst in comparison to 4CzIPN

Funding: We are grateful to the University of St Andrews, Syngenta, the EPSRC Centre for Doctoral Training in Critical Resource Catalysis (CRITICAT) for financial support [Ph.D. studentship to “M.B.”; Grant code: EP/L016419/1].EZ-C is a Royal Society Leverhulme Trust Senior Research fellow (SRF\R1\201089). E.Z.-C., S.C. and P.C. acknowledge the European Union H2020 research and innovation program under the Marie Skłodowska Curie Grant Agreement (PhotoReAct, No 956324).Carbazolyl dicyanobenzene (CDCB) derivates exhibiting thermally activated delayed fluorescence (TADF) have shown themselves to be excellent photocatalysts over recent years, particularly 4CzIPN, although investigation into organic TADF compounds as photocatalysts outside of the CDCB group has been limited. Herein, we report an alternative donor-acceptor TADF structure, 9,9′-(sulfonylbis(pyrimidine-5,2diyl))bis(3,6-di-tert-butyl-9H-carbazole), pDTCz-DPmS, for use as a photocatalyst (PC). A comparison of the electrochemical and photophysical properties of pDTCzDPmS with 4CzIPN in a range of solvents identifies the former as a better ground state reducing agent and photoreductant, while both exhibit similar oxidation capabilities in the ground and excited state. The increased conjugation of pDTCz-DPmS relative to 4CzIPN presents a more intense CT band in the UV-Vis absorption spectrum, aiding in the light absorption of this molecule. Prompt and delayed emission lifetimes are observed for pDTCz-DPmS, confirming the TADF nature, both of which are significantly long lived to participate in productive photochemistry. These combined properties make pDTCz-DPmS useful in photocatalysis reactions, covering a range of photoredox oxidative and reductive quenching reactions, as well as those involving a dual Ni(II) cocatalyst, alongside energy transfer processes. The higher triplet energy and increased photostability of pDTCz-DPmS compared with 4CzIPN were found to be advantages of this organic photocatalyst.Publisher PDFPeer reviewe

Lessons Learnt in Photocatalysis - the Influence of Solvent Polarity and the Photostability of the Photocatalyst

The yields obtained in a photocatalysis reaction are frequently dependent on the choice of solvent. Yet, the intrinsic optoelectronic properties of photocatalysts (PCs) that form the basis for the thermodynamic driving force of the photocatalysis are often acquired in a solvent different to that used in the photocatalytic reaction, despite these crucial parameters being solvent dependent. Herein, we report the detailed computational modelling and optoelectronic characterization of eight popular PCs, encompassing transition metal complexes and organic compounds, in four commonly used solvents of varying polarity. Significant variation of up to 270 mV in the experimental ground-state and excited-state redox potentials is noted as a function of solvent polarity, while experimental triplet energies are found to be dependent on solvent (up to 110 meV) when the excited state is charge transfer, rather than locally excited, in nature. A range of photocatalytic electron and energy transfer reactions were investigated using a subset of the PCs and solvents to verify the impact of the changes in optoelectronic properties on the yields of the reactions. For the photoredox reactions, the yields are not correlated with solvent polarity. Instead, when the PC could promote the formation of the target product, we observed photodegradation for all PCs across all solvents, something that is rarely investigated in the literature. This, therefore, makes it difficult to ascertain whether the parent PC and/or the photodegraded product is responsible for the photochemistry, or indeed, whether photodegradation is actually detrimental to the reaction yield. Conversely, the PCs were found to be photostable for energy transfer reactions; however, yields were not correlated to the triplet energies of the PCs, highlighting that triplet energies alone are not a suitable descriptor to discriminate the performance between PCs in photoinduced energy transfer processes

Moving Beyond Cyanoarene Thermally Activated Delayed Fluorescence Compounds as Photocatalysts: An Assessment of the Performance of a Pyrimidyl Sulfone Photocatalyst in Comparison to 4CzIPN

Carbazolyl dicyanobenzene (CDCB) derivates exhibiting thermally activated delayed fluorescence (TADF) have shown themselves to be excellent photocatalysts over recent years, particularly 4CzIPN, although investigation into organic TADF compounds as photocatalysts outside of the CDCB group has been limited. Herein, we report an alternative donor-acceptor TADF structure, 9,9′-(sulfonylbis(pyrimidine-5,2-diyl))bis(3,6-di-tert-butyl-9H-carbazole), pDTCz-DPmS, for use as a photocatalyst (PC). A comparison of the electrochemical and photophysical properties of pDTCz-DPmS with 4CzIPN in a range of solvents identifies the former as a better ground state reducing agent and photoreductant, while both exhibit similar oxidation capabilities in the ground and excited state. The increased conjugation of pDTCz-DPmS relative to 4CzIPN presents a more intense CT band in the UV-Vis absorption spectrum, aiding in the light absorption of this molecule. Prompt and delayed emission lifetimes are observed for pDTCz-DPmS, confirming the TADF nature, both of which are significantly long lived to participate in productive photochemistry. These combined properties make pDTCz-DPmS useful in photocatalysis reactions, covering a range of photoredox oxidative and reductive quenching reactions, as well as those involving a dual Ni(II) cocatalyst, alongside energy transfer processes. The higher triplet energy and increased photostability of pDTCz-DPmS compared with 4CzIPN were found to be particular advantages of this organic photocatalyst