Code generation in ORCA: progress, efficiency and tight integration.

An improved version of ORCA's automated generator environment (ORCA-AGE II) is presented. The algorithmic improvements and the move to C++ as the programming language lead to a performance gain of up to two orders of magnitude compared to the previously developed PYTHON toolchain. Additionally, the restructured modular design allows for far more complex code engines to be implemented readily. Importantly, we have realised an extremely tight integration with the ORCA host program. This allows for a workflow in which only the wavefunction Ansatz is part of the source code repository while all actual high-level code is generated automatically, inserted at the appropriate place in the host program before it is compiled and linked together with the hand written code parts. This construction ensures longevity and uniform code quality. Furthermore the new developments allow ORCA-AGE II to generate parallelised production-level code for highly complex theories, such as fully internally contracted multireference coupled-cluster theory (fic-MRCC) with an enormous number of contributing tensor contractions. We also discuss the automated implementation of nuclear gradients for arbitrary theories. All these improvements enable the implementation of theories that are too complex for the human mind and also reduce development times by orders of magnitude. We hope that this work enables researchers to concentrate on the intellectual content of the theories they develop rather than be concerned with technical details of the implementation.

Comparing divisome organization between vegetative and sporulating Bacillus subtilis at the nanoscale using DNA-PAINT.

Spore-forming bacteria have two distinct division modes: sporulation and vegetative division. The placement of the foundational division machinery component (Z-ring) within the division plane is contingent on the division mode. However, investigating if and how division is performed differently between sporulating and vegetative cells remains challenging, particularly at the nanoscale. Here, we use DNA-PAINT super-resolution microscopy to compare the 3D assembly and distribution patterns of key division proteins SepF, ZapA, DivIVA, and FtsZ. We determine that ZapA and SepF placement within the division plane mimics that of the Z-ring in vegetative and sporulating cells. We find that DivIVA assemblies differ between vegetative and sporulating cells. Furthermore, we reveal that SepF assembles into ~50-nm arcs independent of division mode. We propose a nanoscale model in which symmetric or asymmetric placement of the Z-ring and early divisome proteins is a defining characteristic of vegetative or sporulating cells, respectively, and regulation of septal thickness differs between division modes.

J Coupling Constants of <1 Hz Enable 13C Hyperpolarization of Pyruvate via Reversible Exchange of Parahydrogen.

Observing pyruvate metabolism in vivo has become a focal point of molecular magnetic resonance imaging. Signal amplification by reversible exchange (SABRE) has recently emerged as a versatile hyperpolarization technique. Tuning of the spin order transfer (SOT) in SABRE is challenging as the small 1H-13C J couplings, in the 13C-pyruvate case, result in SOT being not readily discernible. We demonstrate an experimental method using frequency-selective excitation of parahydrogen-derived polarization SOT sequence (SEPP-SPINEPT); its application led to up to 5700-fold 13C signal gain. In this way, we estimated the lifetime of two Ir-pyruvate SABRE complexes alongside the individual probing of eight small 1H-13C J couplings that connect the hydride protons in these complexes to 1- and 2-13C pyruvate spins, affording values between 0 and 2.69 Hz. Using electronic structure calculations, we define the low-energy structure of the corresponding complexes. Hence, this study demonstrates a novel approach to analyzing the spin topology of short-lived organometallic complexes.

Elucidating the Electronic Nature of Rh-based Paddlewheel Catalysts from 103 Rh NMR Chemical Shifts: Insights from Quantum Mechanical Calculations.

The tremendous importance of dirhodium paddlewheel complexes for asymmetric catalysis is largely the result of an empirical optimization of the chiral ligand sphere about the bimetallic core. It was only recently that a H(C)Rh triple resonance 103 Rh NMR experiment provided the long-awaited opportunity to examine - with previously inconceivable accuracy - how variation of the ligands impacts on the electronic structure of such catalysts. The recorded effects are dramatic: formal replacement of only one out of eight O-atoms surrounding the metal centers in a dirhodium tetracarboxylate by an N-atom results in a shielding of the corresponding Rh-site of no less than 1000 ppm. The current paper provides the theoretical framework that allows this and related experimental observations made with a set of 19 representative rhodium complexes to be interpreted. In line with symmetry considerations, it is shown that the shielding tensor responds only to the donor ability of the equatorial ligands along the perpendicular principal axis. Axial ligands, in contrast, have no direct effect on shielding but may come into play via the electronic c i s ${cis}$ -effect that they exert onto the neighboring equatorial sites. On top of these fundamental interactions, charge redistribution within the core as well as the electronic t r a n s ${trans}$ -effect of ligands of different donor strengths is reflected in the recorded 103 Rh NMR shifts.

A Cooperative Cobalt-Driven System for One-Carbon Extension in the Synthesis of (Z)-Silyl Enol Ethers from Aldehydes: Unlocking Regio- and Stereoselectivity.

The research presented herein explores a cobalt-based catalytic system, distinctively featuring a cooperative boron-centric element within its intricate ligand architecture. This system is strategically engineered to enable the integration of a singular carbon atom into aldehydes, a process culminating in the production of (Z)-silyl enol ethers. Beyond offering an efficient one-pot synthesis route, this method adeptly overcomes challenges inherent to conventional techniques, such as the need for large amounts of additives, restrictive functional group tolerance, and extreme reaction temperatures. Initial mechanistic studies suggest the potential role of a cobalt-carbene complex as a catalytically significant species and underscore the importance of the borane segment. Collectively, these observations highlight the potential of this system in advancing complex bond activation pursuits.

Mechanistic Studies on the Bismuth-Catalyzed Transfer Hydrogenation of Azoarenes.

Organobismuth-catalyzed transfer hydrogenation has recently been disclosed as an example of low-valent Bi redox catalysis. However, its mechanistic details have remained speculative. Herein, we report experimental and computational studies that provide mechanistic insights into a Bi-catalyzed transfer hydrogenation of azoarenes using p-trifluoromethylphenol (4) and pinacolborane (5) as hydrogen sources. A kinetic analysis elucidated the rate orders in all components in the catalytic reaction and determined that 1 a (2,6-bis[N-(tert-butyl)iminomethyl]phenylbismuth) is the resting state. In the transfer hydrogenation of azobenzene using 1 a and 4, an equilibrium between 1 a and 1 a ⋅ [OAr]2 (Ar=p-CF3 -C6 H4 ) is observed, and its thermodynamic parameters are established through variable-temperature NMR studies. Additionally, pKa -gated reactivity is observed, validating the proton-coupled nature of the transformation. The ensuing 1 a ⋅ [OAr]2 is crystallographically characterized, and shown to be rapidly reduced to 1 a in the presence of 5. DFT calculations indicate a rate-limiting transition state in which the initial N-H bond is formed via concerted proton transfer upon nucleophilic addition of 1 a to a hydrogen-bonded adduct of azobenzene and 4. These studies guided the discovery of a second-generation Bi catalyst, the rate-limiting transition state of which is lower in energy, leading to catalytic transfer hydrogenation at lower catalyst loadings and at cryogenic temperature.

Realignment of the ventricular septum in tetralogy of Fallot using (partial) direct closure of the ventricular septal defect: Long-term follow-up and comparison to conventional patch repair.

Objectives: Aortic dilatation and regurgitation after surgical repair of tetralogy of Fallot (TOF) is known, and beside other factors, mainly addressed to an intrinsic aortopathy. In 2011, we reported the influence of realingement of the left ventricular outflow tract (LVOT) by (partial) direct closure of the ventricular septal defect (VSD) in TOF on aortic structures and function. We now evaluated the further follow-up of this cohort and compared the results to a matched group of TOF patients with classical VSD patch closure. Patients and Methods: Forty patients with TOF treated between 2003 and 2008 are included in the study, with 20 patients each in the VSD (a) (partial) direct closure and (b) patch closure group. Follow-up time after surgery was 12.3 years (11.3-13.0). Results: Patient characteristics, echocardiographic measurements, and surgical and intensive care unit parameters were not significantly different between both groups. After surgery and during long-term follow-up, realignement of the LVOT, shown by the angle between the interventricular septum and the anterior aortic annulus in long axis view in echocardiography, was lower in Group A (34 vs. 45°, P < 0.0001). No differences in LVOT or aortic annulus size, aortic regurgitation, or dilation of the ascending aorta and right ventricular outflow tract gradients were found. Transient rhythm disturbances were found in 3 patients in each group, with only one persistent complete atrioventricular block in Group B. Conclusion: (Partial) direct closure of the VSD in TOF leads to a better realignement of the LVOT and showed comparable short- and long-term results without higher risk for rhythm disturbances during follow-up.

A Cooperative Rhodium/Secondary Phosphine Oxide [Rh/P(O)nBu2 ] Template for Catalytic Hydrodefluorination of Perfluoroarenes.

The selective activation of C-F bonds under mild reaction conditions remains an ongoing challenge of bond activation. Here, we present a cooperative [Rh/P(O)nBu2 ] template for catalytic hydrodefluorination (HDF) of perfluoroarenes. In addition to substrates presenting electron-withdrawing functional groups, the system showed an exceedingly rare tolerance for electron-donating functionalities and heterocycles. The high chemoselectivity of the catalyst and its readiness to be deployed at a preparative scale illustrate its practicality. Empirical mechanistic studies and a density functional theory (DFT) study have identified a rhodium(I) dihydride complex as a catalytically relevant species and the determining role of phosphine oxide as a cooperative fragment. Altogether, we demonstrate that molecular templates based on these design elements can be assembled to create catalysts with increased reactivity for challenging bond activations.

Radical Activation of N-H and O-H Bonds at Bismuth(II).

The development of unconventional strategies for the activation of ammonia (NH3) and water (H2O) is of capital importance for the advancement of sustainable chemical strategies. Herein we provide the synthesis and characterization of a radical equilibrium complex based on bismuth featuring an extremely weak Bi-O bond, which permits the in situ generation of reactive Bi(II) species. The ensuing organobismuth(II) engages with various amines and alcohols and exerts an unprecedented effect onto the X-H bond, leading to low BDFEX-H. As a result, radical activation of various N-H and O-H bonds─including ammonia and water─occurs in seconds at room temperature, delivering well-defined Bi(III)-amido and -alkoxy complexes. Moreover, we demonstrate that the resulting Bi(III)-N complexes engage in a unique reactivity pattern with the triad of H+, H-, and H• sources, thus providing alternative pathways for main group chemistry.

Between Two Chairs: Combination of Theory and Experiment for the Determination of the Conformational Dynamics of Xylosides.

The conformational properties of monosaccharides constitute fundamental features of oligosaccharides. While the energy landscape of monosaccharides can be altered by a specific biochemical environment or by chemical modifications, the analysis of resulting dynamic conformational equilibria is not feasible by experimental means alone. In this work, a series of ß-d-xylopyranosides is used to outline how a combination of experimental NMR parameters and computed molecular properties can be used to determine conformers and quantify the composition of conformational equilibria. We demonstrate that identifying the most stable conformers using energy calculations is challenging and computing of NMR shieldings is typically not sensitive enough. On the other hand, computed spin-spin coupling constants for the xyloside ring can be used to unambiguously assign experimental NMR data of dynamic conformational equilibria and quantify the ratio of different conformers in the mixture. As a proof of principle, this procedure allowed to analyze a hitherto unknown dynamic equilibrium of a diamino-xyloside as a precursor of a molecular switch.

Prehospital triage optimization of patients with large vessel occlusion by Austrian Prehospital Stroke Scale.

OBJECTIVES: The Austrian Prehospital Stroke Scale (APSS) score was developed to predict large vessel occlusion (LVO) and improve prehospital transportation triage. Its accuracy has been previously analyzed retrospectively. We now aimed to investigate the accuracy, as well as the impact of the implementation of a triage strategy using this score on treatment times and outcome in a prospective study. MATHERIAL & METHODS: Prospective diagnostic test accuracy and before-after interventional study. EMS prospectively evaluated APSS in patients suspected of stroke. Accuracy was compared with other LVO scores. Patients with APSS ≥4 points were brought directly to the comprehensive stroke center. Treatment time frames, neurological, and radiological outcome before and after the APSS implementation were compared. RESULTS: A total of 307 patients with suspected stroke were included from October 2018 to February 2020. Treatable LVO was present in 79 (26%). Sensitivity of APSS to detect those was 90%, specificity 79%, positive predictive value 66%, negative predictive value 95%, and area under the curve 0.87 (95% CI 0.83-0.91). This was similar to in-hospital NIHSS (AUC 0.89 95% CI 0.89-0.92, p = .06) and superior to CPSS (AUC 0.83 95% CI 0.78-0.87, p = .01). Implementation of APSS triage increased direct transportation rate for LVO patients (21% before vs. 52% after; p < .001) with a significant time benefit (alert to groin puncture time benefit: 51 min (95% CI 28-74; p < .001). Neurological and radiological outcome did not differ significantly. CONCLUSIONS: Austrian Prehospital Stroke Scale triage showed an accuracy comparable with in-hospital NIHSS, and lead to a significant optimization of prehospital workflows in patients with potential LVO.

Comparing London dispersion pnictogen-π interactions in naphthyl-substituted dipnictanes.

Using a combination of NMR, single crystal X-ray diffraction (sc-XRD) and quantum chemistry, the structure-directing role of London Dispersion (LD) is demonstrated for dibismuthane Bi2Naph2 (1). 1 shows intermolecular Bi⋯π contacts in the solid-state, while π⋯π interactions as observed in the lighter homologues are missing. Comparison of the whole series of dipnictanes revealed the influence of the pnictogen atom on the strength of London dispersion and highlights its importance in heavy main group element chemistry.

High Level Electronic Structure Calculation of Molecular Solid-State NMR Shielding Constants.

In this work, we present a quantum mechanics/molecular mechanics (QM/MM) approach for the computation of solid-state nuclear magnetic resonance (SS-NMR) shielding constants (SCs) for molecular crystals. Besides applying standard-DFT functionals like GGAs (PBE), meta-GGAs (TPSS), and hybrids (B3LYP), we apply a double-hybrid (DSD-PBEP86) functional as well as MP2, using the domain-based local pair natural orbital (DLPNO) formalism, to calculate the NMR SCs of six amino acid crystals. All the electronic structure methods used exhibit good correlation of the NMR shieldings with respect to experimental chemical shifts for both 1H and 13C. We also find that local electronic structure is much more important than the long-range electrostatic effects for these systems, implying that cluster approaches using all-electron/Gaussian basis set methods might offer great potential for predictive computations of solid-state NMR parameters for organic solids.

Triple Resonance Experiments for the Rapid Detection of 103Rh NMR Shifts: A Combined Experimental and Theoretical Study into Dirhodium and Bismuth-Rhodium Paddlewheel Complexes.

A H(C)Rh triple resonance NMR experiment makes the rapid detection of 103Rh chemical shifts possible, which were previously beyond reach. It served to analyze a series of dirhodium and bismuth-rhodium paddlewheel complexes of the utmost importance for metal-carbene chemistry. The excellent match between the experimental and computed 103Rh shifts in combination with a detailed analysis of the pertinent shielding tensors forms a sound basis for a qualitative and quantitative interpretation of these otherwise (basically) inaccessible data. The observed trends clearly reflect the influence exerted by the equatorial ligands (carboxylate versus carboxamidate), the axial ligands (solvents), and the internal "metalloligand" (Rh versus Bi) on the electronic estate of the reactive Rh(II) center.

Are Heavy Pnictogen-π Interactions Really "π Interactions"?

The noncovalent interactions of heavy pnictogens with π-arenes play a fundamental role in fields like crystal engineering or catalysis. The strength of such bonds is based on an interplay between dispersion and donor/acceptor interactions, and is generally attributed to the presence of π-arenes. Computational studies of the interaction between the heavy pnictogens As, Sb and Bi and cyclohexane, in comparison with previous studies on the interaction between heavy pnictogens and benzene, show that this concept probably has to be revised. A thorough analysis of all the different energetic components that play a role in these systems, carried out with state-of-the-art computational methods, sheds light on how they influence one another and the effect that their interplay has on the overall system. Furthermore, the analysis of such interactions leads us to the unexpected finding that the presence of the pnictogen compounds strongly affects the conformational equilibrium of cyclohexane, reversing the relative stability of the chair and boat-twist conformers, and thus suggesting a possible application of tuneable dispersion energy donors to stabilise the desired conformation.

Detecting structural heterogeneity in single-molecule localization microscopy data.

Particle fusion for single molecule localization microscopy improves signal-to-noise ratio and overcomes underlabeling, but ignores structural heterogeneity or conformational variability. We present a-priori knowledge-free unsupervised classification of structurally different particles employing the Bhattacharya cost function as dissimilarity metric. We achieve 96% classification accuracy on mixtures of up to four different DNA-origami structures, detect rare classes of origami occuring at 2% rate, and capture variation in ellipticity of nuclear pore complexes.

DLPNO-MP2 second derivatives for the computation of polarizabilities and NMR shieldings.

We present a derivation and efficient implementation of the formally complete analytic second derivatives for the domain-based local pair natural orbital second order Møller-Plesset perturbation theory (MP2) method, applicable to electric or magnetic field-response properties but not yet to harmonic frequencies. We also discuss the occurrence and avoidance of numerical instability issues related to singular linear equation systems and near linear dependences in the projected atomic orbital domains. A series of benchmark calculations on medium-sized systems is performed to assess the effect of the local approximation on calculated nuclear magnetic resonance shieldings and the static dipole polarizabilities. Relative deviations from the resolution of the identity-based MP2 (RI-MP2) reference for both properties are below 0.5% with the default truncation thresholds. For large systems, our implementation achieves quadratic effective scaling, is more efficient than RI-MP2 starting at 280 correlated electrons, and is never more than 5-20 times slower than the equivalent Hartree-Fock property calculation. The largest calculation performed here was on the vancomycin molecule with 176 atoms, 542 correlated electrons, and 4700 basis functions and took 3.3 days on 12 central processing unit cores.

Complex multicomponent patterns rendered on a 3D DNA-barrel pegboard.

DNA origami, in which a long scaffold strand is assembled with a many short staple strands into parallel arrays of double helices, has proven a powerful method for custom nanofabrication. However, currently the design and optimization of custom 3D DNA-origami shapes is a barrier to rapid application to new areas. Here we introduce a modular barrel architecture, and demonstrate hierarchical assembly of a 100 megadalton DNA-origami barrel of ~90 nm diameter and ~250 nm height, that provides a rhombic-lattice canvas of a thousand pixels each, with pitch of ~8 nm, on its inner and outer surfaces. Complex patterns rendered on these surfaces were resolved using up to twelve rounds of Exchange-PAINT super-resolution microscopy. We envision these structures as versatile nanoscale pegboards for applications requiring complex 3D arrangements of matter, which will serve to promote rapid uptake of this technology in diverse fields beyond specialist groups working in DNA nanotechnology.

Computation of NMR Shielding Constants for Solids Using an Embedded Cluster Approach with DFT, Double-Hybrid DFT, and MP2.

In this work, we explore the accuracy of post-Hartree-Fock (HF) methods and double-hybrid density functional theory (DFT) for the computation of solid-state NMR chemical shifts. We apply an embedded cluster approach and investigate the convergence with cluster size and embedding for a series of inorganic solids with long-range electrostatic interactions. In a systematic study, we discuss the cluster design, the embedding procedure, and basis set convergence using gauge-including atomic orbital (GIAO) NMR calculations at the DFT and MP2 levels of theory. We demonstrate that the accuracy obtained for the prediction of NMR chemical shifts, which can be achieved for molecular systems, can be carried over to solid systems. An appropriate embedded cluster approach allows one to apply methods beyond standard DFT even for systems for which long-range electrostatic effects are important. We find that an embedded cluster should include at least one sphere of explicit neighbors around the nuclei of interest, given that a sufficiently large point charge and boundary effective potential embedding is applied. Using the pcSseg-3 basis set and GIAOs for the computation of nuclear shielding constants, accuracies of 1.6 ppm for 7Li, 1.5 ppm for 23Na, and 5.1 ppm for 39K as well as 9.3 ppm for 19F, 6.5 ppm for 35Cl, 7.4 ppm for 79Br, and 7.5 ppm for 25Mg as well as 3.8 ppm for 67Zn can be achieved with MP2. Comparing various DFT functionals with HF and MP2, we report the superior quality of results for methods that include post-HF correlation like MP2 and double-hybrid DFT.

The first microsolvation step for furans: New experiments and benchmarking strategies.

The site-specific first microsolvation step of furan and some of its derivatives with methanol is explored to benchmark the ability of quantum-chemical methods to describe the structure, energetics, and vibrational spectrum at low temperature. Infrared and microwave spectra in supersonic jet expansions are used to quantify the docking preference and some relevant quantum states of the model complexes. Microwave spectroscopy strictly rules out in-plane docking of methanol as opposed to the top coordination of the aromatic ring. Contrasting comparison strategies, which emphasize either the experimental or the theoretical input, are explored. Within the harmonic approximation, only a few composite computational approaches are able to achieve a satisfactory performance. Deuteration experiments suggest that the harmonic treatment itself is largely justified for the zero-point energy, likely and by design due to the systematic cancellation of important anharmonic contributions between the docking variants. Therefore, discrepancies between experiment and theory for the isomer abundance are tentatively assigned to electronic structure deficiencies, but uncertainties remain on the nuclear dynamics side. Attempts to include anharmonic contributions indicate that for systems of this size, a uniform treatment of anharmonicity with systematically improved performance is not yet in sight.