A Generally Applicable Method for Disentangling the Effect of Individual Noncovalent Interactions on the Binding Energy.

We introduce the fragment-pairwise Local Energy Decomposition (fp-LED) scheme for precise quantification of individual interactions contributing to the binding energy of arbitrary chemical entities, such as protein-ligand binding energies, lattice energies of molecular crystals, or association energies of large biomolecular assemblies. Using fp-LED, we can assess whether the contribution to the binding energy arising from noncovalent interactions between pairs of molecular fragments in any chemical system is attractive or repulsive, and accurately quantify its magnitude at the coupled cluster level - commonly considered as the "gold standard" of computational chemistry. Such insights are crucial for advancing molecular and material design strategies in fields like catalysis and therapeutic development.

Oxidation States: Intrinsically Ambiguous?

The oxidation state ( ) formalism is a much-appreciated good in chemistry, receiving wide application. However, like all formalisms, limitations are inescapable, some of which have been recently explored. Providing a broader context, we discuss the and its interpretation from a computational perspective for transition metal (TM) complexes.

Integration of primary care and palliative care services to improve equality and equity at the end-of-life: Findings from realist stakeholder workshops.

Background: Inequalities in access to palliative and end of life care are longstanding. Integration of primary and palliative care has the potential to improve equity in the community. Evidence to inform integration is scarce as research that considers integration of primary care and palliative care services is rare.

Valence Tautomerism Induced Proton Coupled Electron Transfer:X-H Bond Oxidation with a Dinuclear Au(II) Hydroxide Complex.

We report the preparation and characterization of the dinuclear Au hydroxide complex Au (L)(OH) (L=N,N'-bis (2,6-dimethyl) phenylformamidinate) and study its reactivity towards weak X-H bonds. Through the interplay of kinetic analysis and computational studies, we demonstrate that the oxidation of cyclohexadiene follows a concerted proton-coupled electron transfer (cPCET) mechanism, a rare type of reactivity for Au complexes. We find that the Au-Au σ-bond undergoes polarization in the PCET event leading to an adjustment of oxidation levels for both Au centers prior to C(sp)-H bond cleavage.

Understanding patient views and experiences of the IDENTIfication of PALLiative care needs (IDENTI-PALL): a qualitative interview study.

Background: Palliative care improves quality of life for people with life-threatening illnesses. There are longstanding inequalities in access to palliative care, with many people never identified as having palliative care needs, particularly frail older people, those with non-malignant disease, and people from ethnic minority backgrounds. Little is known about the process of identification of palliative care needs from a patient perspective.

Revisiting sp Dilithio Methandiides: From Geometric Curiosity to Simple Bonding Description.

The reported tetracoordinate dilithio methandiide complex from Liddle and co-workers (1) is investigated from a coordination chemistry perspective, to probe the origin of its intriguing geometry. Through the application of a variety of computational techniques, non-covalent (steric, electrostatic) interactions are found to be dominant. Further, we arrive at a bonding description which emphasizes the tricoordinate sp -hybridized nature of the central methandiide carbon, differing somewhat from the original proposal.

Ideas, concerns, expectations, and effects on life (ICEE) in GP consultations: an observational study using video-recorded UK consultations.

Background: Eliciting patients' ideas, concerns, expectations, and whether a problem has an 'effect' on their life (ICEE), is a widely recommended communication technique. However, it is not known how frequently ICEE components are raised in UK GP consultations.

Aim: To assess the frequency of ICEE in routine GP consultations with adult patients and explore variables associated with ICEE.

Stories of hope created together: A pilot, school-based workshop for sharing eco-emotions and creating an actively hopeful vision of the future.

The climate and ecological crises challenge all communities across the world, with the greatest impact upon the most vulnerable and the youngest. There are multiple impacts on mental health, including the psychological burdens that arise with increasing awareness of the loss, threat and injustice caused by these crises. Large numbers of young people globally are understandably concerned and distressed about these crises, whilst simultaneously reporting that their concerns are regularly dismissed and ignored, particularly by those in power.

Revisiting Formal Copper(III) Complexes: Bridging Perspectives with - Configurations.

The formal Cu(III) complex [Cu(CF)] has often served as a paradigmatic example of challenging oxidation state assignment - with many reports proposing conflicting descriptions. Here we report a computational analysis of this compound, employing Energy Decomposition Analysis and Intrinsic Bond Orbital Analysis. We present a perspective of the metal centre, resulting from ambiguities in electron counting.

Spectroscopic Manifestations and Implications for Catalysis of Quasi-d Configurations in Formal Gold(III) Complexes.

Several gold +I and +III complexes are investigated computationally and spectroscopically, focusing on the d-configuration and physical oxidation state of the metal center. Density functional theory calculations reveal the non-negligible electron-sharing covalent character of the metal-to-ligand σ-bonding framework. The bonding of gold(III) is shown to be isoelectronic to the formal Cu complex [Cu(CF ) ] , in which the metal center tries to populate its formally unoccupied 3d orbital via σ-bonding, leading to a reduced d Cu description.

On the Role of Noncovalent Ligand-Substrate Interactions in Au(I) Catalysis: An Experimental and Computational Study of Protodeauration.

A systematic study of protodeauration, a crucial step often found in gold catalysis, was performed using isolated vinyl gold(I) complexes. By varying substituents on gold complexes, we explore how their properties influence protodeauration. Phenols were employed as the proton source, and their substituents were also varied, providing insight through variation of their acidity.

Formation and Reactivity of a Fleeting Ni Bisphenoxyl Diradical Species.

Cytochrome P450s and Galactose Oxidases exploit redox active ligands to form reactive high valent intermediates for oxidation reactions. This strategy works well for the late 3d metals where accessing high valent states is rather challenging. Herein, we report the oxidation of Ni (salen) (salen=N,N'-bis(3,5-di-tert-butyl-salicylidene)-1,2-cyclohexane-(1R,2R)-diamine) with mCPBA (meta-chloroperoxybenzoic acid) to form a fleeting Ni bisphenoxyl diradical species, in CH CN and CH Cl at -40 °C.

How reduced are nucleophilic gold complexes?

Nucleophilic formal gold(-I) and gold(I) complexes are investigated Intrinsic Bond Orbital analysis and Energy Decomposition Analysis, based on density functional theory calculations. The results indicate gold(0) centres engaging in electron-sharing bonding with Al- and B- based ligands. Multiconfigurational (CASSCF) calculations corroborate the findings, highlighting the gap between the electonic structures and the formalism.

Understanding patient views and experiences of the IDENTIfication of PALLiative care needs (IDENTI-Pall): a qualitative interview study protocol.

Introduction: More people are living with multimorbidity, defined as two or more long-term physical or mental health conditions. Multimorbidity is associated with poor quality of life and high treatment burden. Palliative care identification tools have been developed for use in primary care to seek out patients who could benefit from a palliative approach to their care.

Homolytic X-H Bond Cleavage at a Gold(III) Hydroxide: Insights into One-Electron Events at Gold.

C(sp )-H and O-H bond breaking steps in the oxidation of 1,4-cyclohexadiene and phenol by a Au(III)-OH complex were studied computationally. The analysis reveals that for both types of bonds the initial X-H cleavage step proceeds via concerted proton coupled electron transfer (cPCET), reflecting electron transfer from the substrate directly to the Au(III) centre and proton transfer to the Au-bound oxygen. This mechanistic picture is distinct from the analogous formal Cu(III)-OH complexes studied by the Tolman group (J.

Efficient Computation of Geometries for Gold Complexes.

Computationally obtaining structural parameters along a reaction coordinate is commonly performed with Kohn-Sham density functional theory which generally provides a good balance between speed and accuracy. However, CPU times still range from inconvenient to prohibitive, depending on the size of the system under study. Herein, the tight binding GFN2-xTB method [C.

Eliminating Fatigue in Surface-Bound Spiropyrans.

This paper describes an experimental approach to eliminating the loss of reversibility that surface-bound spiropyrans exhibit when switched with light. Although such fatigue can be controlled in other contexts, on surfaces, the photochromic compounds are held in close proximity to each other and relatively few molecules modulate the properties of a device, leading to a loss of functionality after only a few switching cycles. The switching process was characterized by photoelectron spectroscopy and differences in tunneling currents in the spiropyran and merocyanine forms using eutectic Ga-In.

PR interval genome-wide association meta-analysis identifies 50 loci associated with atrial and atrioventricular electrical activity.

Electrocardiographic PR interval measures atrio-ventricular depolarization and conduction, and abnormal PR interval is a risk factor for atrial fibrillation and heart block. Our genome-wide association study of over 92,000 European-descent individuals identifies 44 PR interval loci (34 novel). Examination of these loci reveals known and previously not-yet-reported biological processes involved in cardiac atrial electrical activity.

Translational overview of cytokine inhibition in acute myocardial infarction and chronic heart failure.

Many cytokines are currently under investigation as potential target to improve cardiac function and outcome in the setting of acute myocardial infarction (MI) or chronic heart failure (HF). Here we aim to provide a translational overview of cytokine inhibiting therapies tested in experimental models and clinical studies. In various experimental studies, inhibition of interleukin-1 (IL-1), -6 (IL-6), -8 (IL-8), monocyte chemoattractant protein-1 (MCP-1), CC- and CXC chemokines, and tumor necrosis factor-α (TNF-α) had beneficial effects on cardiac function and outcome.

Management of the Infected Total Hip Arthroplasty.

In the United Kingdom approximately 80,000 total hip arthroplasties are undertaken on an average each year. The popularity and demand for this operation are continually increasing. Our understanding of arthroplasty surgery and its complications has evolved greatly, and as a result infection rates are undeniably at an all-time low.

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci.

Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation.

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.

New genetic loci link adipose and insulin biology to body fat distribution.

Body fat distribution is a heritable trait and a well-established predictor of adverse metabolic outcomes, independent of overall adiposity. To increase our understanding of the genetic basis of body fat distribution and its molecular links to cardiometabolic traits, here we conduct genome-wide association meta-analyses of traits related to waist and hip circumferences in up to 224,459 individuals. We identify 49 loci (33 new) associated with waist-to-hip ratio adjusted for body mass index (BMI), and an additional 19 loci newly associated with related waist and hip circumference measures (P < 5 × 10(-8)).