Electronic structure of Li1,2,3 +,0,- and nature of the bonding in Li2,3 +,0,.

The current study of the small lithium molecules Li2 +,0,- and Li3 +,0,- focuses on the nature of the bonding in these molecules as well as their structures and energetics (bond energies, ionization energies, and electron affinities). Valence CASSCF (2s,2p) calculations incorporate nondynamical electron correlation in the calculations, while the corresponding multireference configuration interaction and coupled cluster calculations incorporate dynamical electron correlation. Treatment of nondynamical correlation is critical for properly describing the Li2,3 +,0,- molecules as well as the Li- anion with dynamical correlation, in general, only fine-tuning the predictions. All lithium molecules and ions are bound, with the Li3 + and Li2 + ions being the most strongly bound, followed by Li3 - , Li2 , Li2 - and Li3 . The minimum energy structures of Li3 +,0,- are, respectively, an equilateral triangle, an isosceles triangle, and a linear structure. The results of SCGVB calculations are analyzed to obtain insights into the nature of the bonding in these molecules. An important finding of this work is that interstitial orbitals, a concept first put forward by McAdon and Goddard in 1985, play an essential role in the bonding of all lithium molecules considered here except for Li2 . The interstitial orbitals found in the Li3 +,0 molecules likely give rise to the non-nuclear attractors/maxima observed in these molecules.

Dynamical electron correlation and the chemical bond. II. Recoupled pair bonds in the a4Σ- states of CH and CF.

We extended our studies of the effect of dynamical electron correlation on the covalent bonds in the AH and AF series (A = B-F) to the recoupled pair bonds in the excited a4Σ- states of the CH and CF molecules. Dynamical correlation is energetically less important in the a4Σ- states than in the corresponding X2Π states for both molecules, which is reflected in smaller changes in bond energies (De). Changes in the equilibrium bond distance (Re) and vibrational frequency (ωe), on the other hand, are influenced by the changes in the slope and curvature of the dynamical electron correlation energy as a function of the internuclear distance R, EDEC(R). In the CH(a4Σ-) state, these changes are much smaller than in the CH(X2Π) state, but in the CF(a4Σ-) state, they are larger, reflecting a significant difference in the shapes of EDEC(R) curves. At large R, the shape of EDEC(R) curves for covalent and recoupled pair bonds is similar although different in magnitude. For the CH(a4Σ-) state, EDEC(R) has a minimum at R = Re + 0.72 Å as the orbitals associated with the formation of the recoupled pair bond switch places. EDEC(R) for the CF(a4Σ-) state decreases continuously throughout the bound region of the potential energy curve because the dynamical correlation energy associated with the electrons in the lone pair orbitals is increasing. These results support our earlier conclusion that we still have much to learn about the nature of dynamical electron correlation in molecules.

Dynamical electron correlation and the chemical bond. I. Covalent bonds in AH and AF (A = B-F).

Dynamical electron correlation has a major impact on the computed values of molecular properties and the energetics of molecular processes. This study focused on the effect of dynamical electron correlation on the spectroscopic constants (Re, ωe, De), and potential energy curves, ΔE(R), of the covalently bound AH and AF molecules, A = B-F. The changes in the spectroscopic constants (ΔRe, Δωe, ΔDe) caused by dynamical correlation are erratic and, at times, even surprising. These changes can be understood based on the dependence of the dynamical electron correlation energies of the AH and AF molecules as a function of the bond distance, i.e., ΔEDEC(R). At large R, the magnitude of ΔEDEC(R) increases nearly exponentially with decreasing R, but this increase slows as R continues to decrease and, in many cases, even reverses at very short R. The changes in ΔEDEC(R) in the region around Re were as unexpected as they were surprising, e.g., distinct minima and maxima were found in the curves of ΔEDEC(R) for the most polar molecules. The variations in ΔEDEC(R) for R ≲ Re are directly correlated with major changes in the electronic structure of the molecules as revealed by a detailed analysis of the spin-coupled generalized valence bond wave function. The results reported here indicate that we have much to learn about the nature of dynamical electron correlation and its effect on chemical bonds and molecular properties and processes.

Cluster randomised controlled trial of screening for atrial fibrillation in people aged 70 years and over to reduce stroke: protocol for the pilot study for the SAFER trial.

INTRODUCTION: Atrial fibrillation (AF) is a common arrhythmia associated with 30% of strokes, as well as other cardiovascular disease, dementia and death. AF meets many criteria for screening, but there is limited evidence that AF screening reduces stroke. Consequently, no countries recommend national screening programmes for AF. The Screening for Atrial Fibrillation with ECG to Reduce stroke (SAFER) trial aims to determine whether screening for AF is effective at reducing risk of stroke. The aim of the pilot study is to assess feasibility of the main trial and inform implementation of screening and trial procedures. METHODS AND ANALYSIS: SAFER is planned to be a pragmatic randomised controlled trial (RCT) of over 100 000 participants aged 70 years and over, not on long-term anticoagulation therapy at baseline, with an average follow-up of 5 years. Participants are asked to record four traces every day for 3 weeks on a hand-held single-lead ECG device. Cardiologists remotely confirm episodes of AF identified by the device algorithm, and general practitioners follow-up with anticoagulation as appropriate. The pilot study is a cluster RCT in 36 UK general practices, randomised 2:1 control to intervention, recruiting approximately 12 600 participants. Pilot study outcomes include AF detection rate, anticoagulation uptake and other parameters to incorporate into sample size calculations for the main trial. Questionnaires sent to a sample of participants will assess impact of screening on psychological health. Process evaluation and qualitative studies will underpin implementation of screening during the main trial. An economic evaluation using the pilot data will confirm whether it is plausible that screening might be cost-effective. ETHICS AND DISSEMINATION: The London-Central Research Ethics Committee (19/LO/1597) and Confidentiality Advisory Group (19/CAG/0226) provided ethical approval. Dissemination will be via publications, patient-friendly summaries, reports and engagement with the UK National Screening Committee. TRIAL REGISTRATION NUMBER: ISRCTN72104369.

New Insights into the Remarkable Difference between CH5- and SiH5.

It has long been known that there is a fundamental difference in the electronic structures of CH5- and SiH5-, two isoelectronic molecules. The former is a saddle point for the SN2 exchange reaction H- + CH4 → [CH5-]‡ → CH4 + H-, while the latter is a stable molecule that is bound relative to SiH4 + H-. SCGVB calculations indicate that this difference is the result of a dramatic difference in the nature of the axial electron pairs in these anions. In SiH5-, the axial pairs represent two stable bonds-a weak recoupled pair bond dyad. In CH5-, the axial electron pairs represent an intermediate transition between the electron pairs in the reactants and those in the products. Furthermore, the axial orbitals at the saddle point in CH5- are highly overlapping, giving rise to strong Pauli repulsion and a high barrier for the SN2 exchange reaction.

Nature of the Bonding in the Bifluoride Anion, FHF.

The nature of the bonding in the bifluoride anion, FHF-, has long been a topic of discussion with little resolution. A recent (2021) spectroscopic-theoretical study concluded that the bonds in this molecule represent a "crossover from hydrogen to chemical bonding." Spin-coupled generalized valence bond (SCGVB) theory is an advanced orbital theory that describes a broad range of molecules and molecular processes, and its application has provided valuable insights in the electronic structure of many molecules with "unusual" bonding motifs. SCGVB calculations on the FHF- anion indicate that the bonding in this molecule cannot be attributed to a traditional hydrogen bond or a traditional covalent bond. Instead, the bonds in FHF- represent a new bonding motif-two polarized, delocalized F- anions held together by a positively charged hydrogen atom, i.e., the bonding resembles that for a proton-bound anion pair.

Spin-Coupled Generalized Valence Bond Theory: New Perspectives on the Electronic Structure of Molecules and Chemical Bonds.

Spin-Coupled Generalized Valence Bond (SCGVB) theory provides the foundation for a comprehensive theory of the electronic structure of molecules. SCGVB theory offers a compelling orbital description of the electronic structure of molecules as well as an efficient and effective zero-order wave function for calculations striving for quantitative predictions of molecular structures, energetics, and other properties. The orbitals in the SCGVB wave function are usually semilocalized, and for most molecules, they can be interpreted using concepts familiar to all chemists (hybrid orbitals, localized bond pairs, lone pairs, etc.). SCGVB theory also provides new perspectives on the nature of the bonds in molecules such as C2, Be2 and SF4/SF6. SCGVB theory contributes unparalleled insights into the underlying cause of the first-row anomaly in inorganic chemistry as well as the electronic structure of organic molecules and the electronic mechanisms of organic reactions. The SCGVB wave function accounts for nondynamical correlation effects and, thus, corrects the most serious deficiency in molecular orbital (RHF) wave functions. Dynamical correlation effects, which are critical for quantitative predictions, can be taken into account using the SCGVB wave function as the zero-order wave function for multireference configuration interaction or coupled cluster calculations.

Nurse-driven Clinical Pathway Based on an Innovative Asthma Score Reduces Admission Time for Children.

We recently demonstrated that an innovative asthma score independent of auscultation could accurately predict the requirement for bronchodilator nebulization compared to the physician's routine clinical judgment to administer bronchodilators. We aimed to standardize inpatient care for children with acute asthma by implementing a clinical pathway based on this innovative asthma score. METHODS: We designed a nurse-driven clinical pathway. This pathway included standardized respiratory assessments and a protocol for the nursing staff to administer bronchodilators without a specific order from the physician. We compared the length of stay and the number of readmissions to a historical cohort. RESULTS: Seventy-nine patients with moderate acute asthma completed the pathway. We obtained a total of 858 Childhood asthma scores in these patients, with a median of 11 scores per patient (interquartile range 8-17). Patients treated according to the nurse-driven protocol were 3.3 times more likely to be discharged earlier (hazard ratio, 3.29; 95% confidence interval, 2.33-4.66; P < 0.05), and length of stay was significantly reduced (median 28 versus 53 h) compared to the historical standard practice. On request, the attending physician assessed the patient's respiratory status 42 times (4.9% of all childhood asthma score assessments). Patient safety was not compromised, and none of the patients were removed from the pathway. In each group, we readmitted two (2.5%) patients within 1 week after discharge. CONCLUSION: This nurse-driven clinical pathway for children with acute asthma based on an asthma score independent of auscultation findings significantly decreased length of stay without compromising patient safety.

A cautionary tale: Problems in the valence-CASSCF description of the ground state (X1Σ+) of BF.

In the full optimized reaction space and valence-complete active space self-consistent field (vCAS) methods, a set of active orbitals is defined as the union of the valence orbitals on the atoms, all possible configurations involving the active orbitals are generated, and the orbitals and configuration coefficients are self-consistently optimized. Such wave functions have tremendous flexibility, which makes these methods incredibly powerful but can also lead to inconsistencies in the description of the electronic structure of molecules. In this paper, the problems that can arise in vCAS calculations are illustrated by calculations on the BH and BF molecules. BH is well described by the full vCAS wave function, which accounts for molecular dissociation and 2s-2p near-degeneracy in the boron atom. The same is not true for the full vCAS wave function for BF. There is mixing of core and active orbitals at short internuclear distances and swapping of core and active orbitals at large internuclear distances. In addition, the virtual 2π orbitals, which were included in the active space to account for the 2s-2p near degeneracy effect, are used instead to describe radial correlation of the electrons in the F2pπ-like pairs. Although the above changes lead to lower vCAS energies, they lead to higher vCAS+1+2 energies as well as irregularities and/or discontinuities in the potential energy curves. All of the above problems can be addressed by using the spin-coupled generalized valence bond-inspired vCAS wave function for BF, which includes only a subset of the atomic valence orbitals in the active space.

The nature of the chemical bond and the role of non-dynamical and dynamical correlation in Be2.

In the spin-coupled generalized valence bond (SCGVB) description of Be2, there is a pair of electrons in highly overlapping "inner" orbitals corresponding to a traditional σ bond, but this bond is compromised by Pauli repulsion arising from its overlap with a second "outer" pair. The presence of this outer pair of electrons leads to a repulsive potential energy curve at long range and a bound, but metastable molecule at short range. To obtain further insights into the nature of the bond in Be2, we determined the non-dynamical and dynamical correlation contributions to the potential energy curve of Be2 using four different choices for the zero-order wave function: Restricted Hartree-Fock (RHF), SCGVB, valence-CASSCF(4,4), and valence-CASSCF(4,8). The SCGVB and valence-CASSCF(4,4) wave functions yield similar breakdowns of the total correlation energy, with non-dynamical correlation being the more important contribution. For the RHF and valence-CASSCF(4,8) wave functions, dynamical correlation is critical, without which the potential energy curve is purely repulsive. High accuracy calculations on the HBen-1Be-BeBen-1H molecule as a function of n (n = 1-6) suggest that the intrinsic strength of a Be-Be σ bond uncompromised by Pauli repulsion is on the order of 62-63 kcal/mol, and its length is 2.13-2.14 Å, ∼60 kcal/mol stronger and ∼0.35 Å shorter than in Be2.

Resolving a puzzling anomaly in the spin-coupled generalized valence bond description of benzene.

In an earlier study of benzene, Small and Head-Gordon found that the spin-coupled generalized valence bond (SCGVB) wave function for the π system predicted a distorted (non-D6h ) geometry, one with alternating CC bond lengths. However, the variations in the energy were very small and the predictions were made using a very small basis set (STO-3G). We re-examined this prediction using a much larger basis set (aug-cc-pVTZ) to determine the dependence of the energy of benzene on the distortion angle, ΔθCXC (ΔθCXC = 0° corresponds to the D6h structure). We also found a distorted geometry with the optimum ΔθCXC being 0.31° with an energy 0.040 kcal mol-1 lower than that for the D6h structure. In the optimum geometry, adjacent CC bond lengths are 1.3861 Å and 1.4004 Å. Analysis of the SCGVB wave function led us to conclude that the cause of the unusual non-D6h geometry predicted by the SCGVB calculations seems to be a result of the interaction between the Kekulé and Dewar components of the full SCGVB wave function. The addition of doubly ionic configurations to the SCGVB wave function leads to the prediction of a D6h geometry for benzene and a dependence on ΔθCXC essentially the same as that predicted by the complete active space self-consistent field wave function.

Orbital Hybridization in Modern Valence Bond Wave Functions: Methane, Ethylene, and Acetylene.

The concept of hybrid orbitals is one of the key theoretical concepts used by chemists to explain the structures and other properties of molecules. Recent work found that the hybrid orbitals from modern ab initio valence bond wave functions differ significantly from traditional hybrid orbitals. We report a detailed analysis of the orbitals of methane, ethylene, and acetylene from spin-coupled generalized valence bond (SCGVB) wave functions, a variationally optimized valence bond wave function that places no constraints on the orbitals and spin function. The carbon-centered orbitals in the SCGVB wave functions are found to be 2s-2p hybrid orbitals largely localized on the carbon atom and pointed directly at the hydrogen atoms to which they are bonded. However, the SCGVB orbitals for methane, ethylene, and acetylene differ markedly from the sp3, sp2, and sp hybrid orbitals traditionally associated with these molecules. It is now clear that the orbitals in modern valence bond wave functions do not follow the hybridization rules of traditional valence bond theory. These findings imply that, in modern valence bond theories, other factors are responsible for the structures and properties of molecules that are traditionally attributed to orbital hybridization.

Spin-Coupled Generalized Valence Bond Description of Group 14 Species: The Carbon, Silicon and Germanium Hydrides, XH n ( n = 1-4).

Although elements in the same group in the Periodic Table tend to behave similarly, the differences in the simplest Group 14 hydrides-XH n (X = C, Si, Ge; n = 1-4)-are as pronounced as their similarities. Spin-coupled generalized valence bond (SCGVB) as well as coupled cluster [CCSD(T)] calculations are reported for all of the molecules in the CH n/SiH n/GeH n series to gain insights into the factors underlying these differences. It is found that the relative weakness of the recoupled pair bonds of SiH and GeH gives rise to the observed differences in the ground state multiplicities, molecular structures, and bond energies of SiH n and GeH n. A number of factors that influence the strength of the recoupled pair bonds in CH, SiH, and GeH were examined. Two factors were identified as potential contributors to the decrease in the strengths of these bonds from CH to SiH and GeH: (i) a decrease in the overlap between the orbitals involved in the bond and (ii) an increase in Pauli repulsion between the electrons in the two lobe orbitals centered on the X atoms. Finally, an analysis of the hybridization of the SCGVB orbitals in XH4 indicates that they are closer to sp hybrids than sp3 hybrids, which implies that the underlying cause of the tetrahedral structure of the XH4 molecules is not a direct result of the hybridization of the X atom orbitals.

Clear or almost clear skin improves the quality of life in patients with moderate-to-severe psoriasis: a systematic review and meta-analysis.

Psoriasis Area and Severity Index (PASI) 75 response is currently considered the gold standard for assessing treatment efficacy in moderate-to-severe psoriatic patients. PASI 90 response denotes better clinical improvement compared to PASI 75. Very few studies have assessed if a greater PASI clinical response is associated with greater improvements in Dermatology Life Quality Index (DLQI). A systematic review and meta-analysis was performed to assess the association between PASI response and DLQI. The study was conducted to assess whether greater improvement in PASI scores from PASI 75-89 to PASI 90 is associated with greater Quality of life (QoL) improvements, specifically DLQI scores. Systematic searches were conducted in MEDLINE, EMBASE and Cochrane Library to identify studies evaluating biologic interventions in adult moderate-to-severe psoriasis patients reporting PASI response and their corresponding DLQI change from baseline score. The quality of evidence was assessed through Jadad score for randomized controlled trials and Downs and Black's checklist for observational studies. Meta-analysis estimated change from baseline in DLQI for PASI 75-89 responders to be 78% (95% credible intervals [CrI]: 75-82%) and for PASI 90 responders to be 90% (95% CrI: 88-93%). This implies 12% greater improvement in DLQI score for PASI 90 responders compared with PASI 75-89 responders. In addition, the meta-analysis also showed a statistically significant difference in DLQI score of 0/1 between PASI 75-89 and PASI 90 responders (45% [95% Crl]; 41.0-50.0% and 73% [95% Crl]; 70.0-76.0%), respectively, Bayesian P < 0.0001). In conclusion, substantial improvement in clinical efficacy is associated with improved QoL in patients with moderate-to-severe psoriasis suggesting that PASI 90 responders (clear or almost clear skin) could achieve a superior QoL compared to PASI 75-89 responders.

Fundamental Aspects of Recoupled Pair Bonds. III. The Frustrated Recoupled Pair Bond in Oxygen Monofluoride.

In a previous paper in this series, we discussed the formation of recoupled pair bonds in the a4Σ- states of CF and SF in which the recoupling process was essentially complete at the equilibrium geometry of the molecule. In this paper, we examine the a4Σ- state of oxygen monofluoride (OF), which could also have a recoupled pair bond. Unlike the other two molecules, generalized valence bond calculations predict that the recoupling in OF is woefully incomplete at Re and the resulting potential energy curve for the OF(a4Σ-) state is purely repulsive; the binding energy, ≈11 kcal/mol, is entirely due to dynamical correlation. A number of factors account for these differences, but the nature of the dominant correlation effect in the oxygen 2p lone pair as well as the spatial extent of the 2p orbital are paramount.

Generalized Valence Bond Description of Chalcogen-Nitrogen Compounds. III. Why the NO-OH and NS-OH Bonds Are So Different.

Crabtree et al. recently reported the microwave spectrum of nitrosyl-O-hydroxide (trans-NOOH), an isomer of nitrous acid, and found that this molecule has the longest O-O bond ever observed: 1.9149 Å ± 0.0005 Å. This is in marked contrast to the structure of the valence isoelectronic trans-NSOH molecule, which has a normal NS-OH bond length and strength. Generalized valence bond calculations show that the long bond in trans-NOOH is the result of a weak through-pair interaction that singlet couples the spins of the electrons in singly occupied orbitals on the hydroxyl radical and nitrogen atom, an interaction that is enhanced by the intervening lone pair of the oxygen atom in NO. The NS-OH bond is the result of the formation of a stable recoupled pair bond dyad, which accounts for both its length and strength.

Variations in the Nature of Triple Bonds: The N2, HCN, and HC2H Series.

The inertness of molecular nitrogen and the reactivity of acetylene suggest there are significant variations in the nature of triple bonds. To understand these differences, we performed generalized valence bond as well as more accurate electronic structure calculations on three molecules with putative triple bonds: N2, HCN, and HC2H. The calculations predict that the triple bond in HC2H is quite different from the triple bond in N2, with HCN being an intermediate case but closer to N2 than HC2H. The triple bond in N2 is a traditional triple bond with the spins of the electrons in the bonding orbital pairs predominantly singlet coupled in the GVB wave function (92%). In HC2H, however, there is a substantial amount of residual CH(a(4)Σ(-)) fragment coupling in the triple bond at its equilibrium geometry with the contribution of the perfect pairing spin function dropping to 82% (77% in a full valence GVB calculation). This difference in the nature of the triple bond in N2 and HC2H may well be responsible for the differences in the reactivities of N2 and HC2H.

Insights into the Electronic Structure of Ozone and Sulfur Dioxide from Generalized Valence Bond Theory: Addition of Hydrogen Atoms.

Ozone (O3) and sulfur dioxide (SO2) are valence isoelectronic species, yet their properties and reactivities differ dramatically. In particular, O3 is highly reactive, whereas SO2 is chemically relatively stable. In this paper, we investigate serial addition of hydrogen atoms to both the terminal atoms of O3 and SO2 and to the central atom of these species. It is well-known that the terminal atoms of O3 are much more amenable to bond formation than those of SO2. We show that the differences in the electronic structure of the π systems in the parent triatomic species account for the differences in the addition of hydrogen atoms to the terminal atoms of O3 and SO2. Further, we find that the π system in SO2, which is a recoupled pair bond dyad, facilitates the addition of hydrogen atoms to the sulfur atom, resulting in stable HSO2 and H2SO2 species.