Luminescent bis-tridentate iridium(III) complexes: Overcoming the undesirable reactivity of trans-disposed metallated rings using –N^N^N–coordinating bis(1,2,4-triazolyl)pyridine ligands

Nine new iridium(III) complexes featuring two tridentate ligands have been synthesised of the form Ir(N^C^N)(–N^N^N–), where N^C^N represents a cyclometallating ligand based on 1,3-di(2-pyridyl)benzene and –N^N^N– is a doubly deprotonated bis(1,2,4-triazolyl)pyridine. Three examples of each ligand have been used, with different substituents in the central aryl ring of the former and para-substituted aryl groups in the 5-positions of the triazole rings of the latter. Two of the complexes have been structurally characterised in the solid-state by X-ray diffraction, confirming the mutually orthogonal arrangement of the two ligands. Unlike related tris-cyclometallated complexes of the type Ir(N^C^N)(C^N^C), which are unstable with respect to photoactivated cleavage of the trans-disposed Ir–C bonds, the new complexes show no evidence of instability. They are phosphorescent in the green region of the spectrum with lifetimes around 200 ns and quantum yields up to 3%, apparently limited by non-radiative decay processes in particular. Although there is some variation in performance with substitution pattern, the only discernible trend is that complexes of the 4-methoxy-substituted N^C^N ligand are the better emitters. Three examples of related complexes of the form Ir(N^C^N)(N^N–)Cl – incorporating a bidentate 1,2,4-triazolylpyridine – have also been prepared. They show no room-temperature emission but the properties at 77 K are similar to those of the bis-tridentate systems

Strategies for the synthesis of HBGl3, a glutamic acid derived ligand bearing phenolic and azacarboxylate donor groups at the nitrogen atom

The development of a route applicable to the preparation of acyclic glutamic acid-based chelating ligands bearing two different auxiliary donor groups linked to the nitrogen atom by methylene spacers is described and applied to the synthesis of the new polydentate ligand HBGl3, the first example of such a structure. The synthesis is accomplished using a strategy employing reductive amination and t-butyl ester protected intermediates. The most basic pKa values for the HBGl3 ligand have been estimated via potentiometric and UV–Visible titration techniques

Rigidly linked dinuclear platinum( ii ) complexes showing intense, excimer-like, near-infrared luminescence

Many luminescent platinum(ii) complexes undergo face-to-face interactions between neighbouring molecules, leading to bimolecular excited states that may emit at lower energy (dimers and/or excimers). Detailed photophysical studies are reported on dinuclear complexes, in which two NCN-coordinated Pt(ii) units are covalently linked by a xanthene such that intramolecular formation of such dimeric or excimeric states is possible. These complexes display strong excimer-like photoluminescence at low concentrations where their monometallic analogues do not. However, a striking difference emerges between complexes where the Pt(NCN) units are directly connected to the xanthene through the tridentate ligand (denoted Class a) and a new class of compounds reported here (Class b) in which the attachment is through a monodentate acetylide ligand. The former require a substantial geometrical rearrangement to move the metal centres of the Pt(NCN) units to a distance short enough to form excimer-like states. The latter require only a small deformation. Consequently, Class a compounds display negligible excimer-like emission in solid films, as the rigid environment hinders the requisite geometric rearrangement. Class b complexes, in contrast, display strong excimer-like emission in film, even at very low loadings. The new dinuclear molecular architecture may thus offer new opportunities in the quest for efficient NIR-emitting devices

The National COVID Cohort Collaborative (N3C): Rationale, design, infrastructure, and deployment.

OBJECTIVE: Coronavirus disease 2019 (COVID-19) poses societal challenges that require expeditious data and knowledge sharing. Though organizational clinical data are abundant, these are largely inaccessible to outside researchers. Statistical, machine learning, and causal analyses are most successful with large-scale data beyond what is available in any given organization. Here, we introduce the National COVID Cohort Collaborative (N3C), an open science community focused on analyzing patient-level data from many centers. MATERIALS AND METHODS: The Clinical and Translational Science Award Program and scientific community created N3C to overcome technical, regulatory, policy, and governance barriers to sharing and harmonizing individual-level clinical data. We developed solutions to extract, aggregate, and harmonize data across organizations and data models, and created a secure data enclave to enable efficient, transparent, and reproducible collaborative analytics. RESULTS: Organized in inclusive workstreams, we created legal agreements and governance for organizations and researchers; data extraction scripts to identify and ingest positive, negative, and possible COVID-19 cases; a data quality assurance and harmonization pipeline to create a single harmonized dataset; population of the secure data enclave with data, machine learning, and statistical analytics tools; dissemination mechanisms; and a synthetic data pilot to democratize data access. CONCLUSIONS: The N3C has demonstrated that a multisite collaborative learning health network can overcome barriers to rapidly build a scalable infrastructure incorporating multiorganizational clinical data for COVID-19 analytics. We expect this effort to save lives by enabling rapid collaboration among clinicians, researchers, and data scientists to identify treatments and specialized care and thereby reduce the immediate and long-term impacts of COVID-19

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

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

The luminescence properties of multinuclear platinum complexes

Platinum(II) complexes featuring conjugated aromatic ligands are widely studied in the context of luminescence. Many such compounds have been discovered that display intense phosphorescence from triplet excited states, offering potential applicability to numerous areas of contemporary interest, including as phosphors for light-emitting devices and imaging agents in cell biology. Aside from the large number of mononuclear Pt(II) complexes that have been reported in the context of luminescence, there are several examples of multinuclear systems – ones that incorporate two or more Pt(II) ions or Pt(II) in combination with other platinum group metal ions. The introduction of a second metal ion can lead to very different luminescence properties compared to the mononuclear analogues. This review aims to provide an overview of some of the key features of multinuclear Pt(II) complexes and their luminescence. It proves to be convenient to subdivide the examples into three classes, according to whether or not there are significant intramolecular interfacial interactions between the square-planar units. In some cases (Class A), for example with aromatic bridging ligands, the units are rigidly held apart from one another and no such intramolecular interactions are possible. In some such complexes, however, the presence of a second metal ion can nevertheless lead to very different properties compared to mononuclear analogues. In particular, recent work has shown that large red shifts in absorption and emission can be accompanied by an increase in the phosphorescence radiative rate constant, offering a way to efficient red and near-infrared emitters. In Class B, on the other hand, the planar Pt(II) units are rigidly held in a conformation that facilitates interfacial interactions. In many cases they involve overlap of Pt 5dz2 and 6pz orbitals, leading to the generation of low-energy 3MMLCT excited states similar to those seen in aggregates of mononuclear Pt(II) complexes. Finally, complexes in Class C – of which there are very many and we cover only a selection of examples – are those in which there is some flexibility in the linkers between the Pt(II) units. They may display dual emission both from excited states that resemble those of the isolated units, and from lower-energy excited states similar to aggregates or excimers, owing to the ability of the Pt(II) moieties to approach one another in the appropriate conformation

Homoleptic platinum(ii) complexes with pyridyltriazole ligands: excimer-forming phosphorescent emitters for solution-processed OLEDs

Two new homoleptic platinum(II) complexes are reported that feature aryl-appended 5-(2-pyridyl)-1,2,4- triazole chelates acting as N^N ligating ions, PtL1 2 and PtL2 2. Readily prepared from easily accessible proligands, they offer good solubility in organic solvents, allowing them to be incorporated into OLEDs through solution processing. Crystal structures reveal staggered, face-to-face packing of the p systems in adjacent complexes, but with no close PtPt interactions. The complexes display bright unimolecular phosphorescence: for PtL1 2 and PtL2 2 respectively, lmax = 502 and 514 nm; F = 0.21 and 0.48; t = 5.1 and 4.6 ms in deoxygenated CH2Cl2 at 295 K. Both complexes show a strong propensity to form intensely emissive excimers at higher concentrations: lmax = 585 and 625 nm for PtL1 2 and PtL2 2. The photophysical properties in doped and neat thin films have been investigated using steady-state and time-resolved methods. These studies highlight the presence of different environments of bimolecular excited states with different lifetimes, those emitting at lowest energy apparently having the longest lifetimes, contrary to what is normally found for unimolecular emitters through the effects of vibrational deactivation. The prototype solution-processed OLEDs gave EQEs of 9.6–12.5% for PtL1 2 and 8.8–11.4% for PtL2 2, impressive values for solution-processed devices incorporating such simple complexes and only a little inferior to the EQE of 15% achieved using PtL1 2 in a device prepared by evaporation. Compounds of this type have potential to provide the red and green components for white light OLEDs, due to their tunable, uni- and bimolecular excited state emission