Optical properties and exciton transfer between N-heterocyclic carbene iridium(III) complexes for blue light-emitting diode applications from first principles.

N-heterocyclic carbene (NHC) iridium(III) complexes are considered as promising candidates for blue emitters in organic light-emitting diodes. They can play the roles of the emitter as well as of electron and hole transporters in the same emission layer. We investigate optical transitions in such complexes with account of geometry and electronic structure changes upon excitation or charging and exciton transfer between the complexes from first principles. It is shown that excitation of NHC iridium complexes is accompanied by a large reorganization energy ∼0.7 eV and a significant loss in the oscillator strength, which should lead to low exciton diffusion. Calculations with account of spin-orbit coupling reveal a small singlet-triplet splitting ∼0.1 eV, whereas the oscillator strength for triplet excitations is found to be an order of magnitude smaller than for the singlet ones. The contributions of the Förster and Dexter mechanisms are analyzed via the explicit integration of transition densities. It is shown that for typical distances between emitter complexes in the emission layer, the contribution of the Dexter mechanism should be negligible compared to the Förster mechanism. At the same time, the ideal dipole approximation, although giving the correct order of the exciton coupling, fails to reproduce the result taking into account spatial distribution of the transition density. For charged NHC complexes, we find a number of optical transitions close to the emission peak of the blue emitter with high exciton transfer rates that can be responsible for exciton-polaron quenching. The nature of these transitions is analyzed.

Formation of carbon propeller-like molecules from starphenes under electron irradiation.

Formation of carbon propeller-like molecules (CPLMs) from starphenes on a graphene substrate under electron irradiation with about 100% yield is observed in molecular dynamics simulations using the REBO-1990EVC_CH potential and CompuTEM algorithm. A CPLM consists of three carbon atomic chains connected to the central hexagon and is formed as a result of the spontaneous breaking of bonds between zigzag atomic rows in starphene arms after hydrogen removal by electron impacts. In the absence of the substrate, the CPLM yield is slightly decreased due to sticking between forming chains, while the formation time is increased threefold. The increase of the kinetic electron energy from 45 to 80 keV has no effect on the CPLM formation. Density functional theory (DFT) calculations performed show the stability of CPLMs with respect to the formation of new bonds between carbon atoms in the chains. DFT calculations using the accurate hybrid B3LYP functional provide an insight into the electronic structure of these new molecules.

Precise graphene cutting using a catalyst at a probe tip under an electron beam.

The method of precise cutting of 2D materials by simultaneous action of a catalyst at the tip of the scanning microscope probe and an electron beam in a high-resolution transmission electron microscope is proposed and studied using atomistic simulations by the example of graphene and a nickel catalyst. Reactive molecular dynamics simulations within the Compu-TEM approach for the description of electron impact effects show that the combination of the nickel catalyst and electron irradiation is crucial for graphene cutting. Cuts with straight edges with widths of about 1-1.5 nm can be obtained. The detailed atomistic mechanism of graphene cutting is investigated via the analysis of statistics on atom ejection and bond reorganization reactions induced by the irradiation. The principal and secondary channels of atom ejection which lead to propagation of the cut are shown to be ejection of two-coordinated atoms at the cut edges bonded to the nickel tip and three-coordinated atoms from the defective graphene structure near the tip. At the same time, the ejection of two-coordinated atoms not bonded to the tip and atoms in chains at the cut edges favors smoothing of free cut edges behind the tip. A considerable difference from the atomistic mechanism of cutting a carbon nanotube via the simultaneous action of electron irradiation and nickel catalyst is discussed. The ab initio calculations performed show a decrease of the binding energy of two-coordinated carbon atoms bonded to the nickel cluster in comparison with the same cut edge in the absence of the cluster confirming that the principal channel of atom ejection is related to the cut propagation.

Pan-sarbecovirus prophylaxis with human anti-ACE2 monoclonal antibodies.

Human monoclonal antibodies (mAbs) that target the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike protein have been isolated from convalescent individuals and developed into therapeutics for SARS-CoV-2 infection. However, therapeutic mAbs for SARS-CoV-2 have been rendered obsolete by the emergence of mAb-resistant virus variants. Here we report the generation of a set of six human mAbs that bind the human angiotensin-converting enzyme-2 (hACE2) receptor, rather than the SARS-CoV-2 spike protein. We show that these antibodies block infection by all hACE2 binding sarbecoviruses tested, including SARS-CoV-2 ancestral, Delta and Omicron variants at concentrations of ~7-100 ng ml-1. These antibodies target an hACE2 epitope that binds to the SARS-CoV-2 spike, but they do not inhibit hACE2 enzymatic activity nor do they induce cell-surface depletion of hACE2. They have favourable pharmacology, protect hACE2 knock-in mice against SARS-CoV-2 infection and should present a high genetic barrier to the acquisition of resistance. These antibodies should be useful prophylactic and treatment agents against any current or future SARS-CoV-2 variants and might be useful to treat infection with any hACE2-binding sarbecoviruses that emerge in the future.

Modular implementation of the linear- and cubic-scaling orbital minimization methods in electronic structure codes using atomic orbitals.

We present a code modularization approach to design efficient and massively parallel cubic- and linear-scaling solvers for electronic structure calculations using atomic orbitals. The modular implementation of the orbital minimization method, in which linear algebra and parallelization issues are handled via external libraries, is demonstrated in the SIESTA code. The distributed block compressed sparse row (DBCSR) and scalable linear algebra package (ScaLAPACK) libraries are used for algebraic operations with sparse and dense matrices, respectively. The MatrixSwitch and libOMM libraries, recently developed within the Electronic Structure Library, facilitate switching between different matrix formats and implement the energy minimization. We show results comparing the performance of several cubic-scaling algorithms, and also demonstrate the parallel performance of the linear-scaling solvers, and their supremacy over the cubic-scaling solvers for insulating systems with sizes of several hundreds of atoms.

Reconstruction of Zigzag Graphene Edges: Energetics, Kinetics, and Residual Defects.

Ab initio calculations are performed to study consecutive reconstruction of a zigzag graphene edge. According to the obtained energy profile along the reaction pathway, the first reconstruction step, formation of the first pentagon-heptagon pair, is the slowest one, while the growth of an already nucleated reconstructed edge domain should occur steadily at a much higher rate. Domains merge into one only in 1/4 of cases when they get in contact, while in the rest of the cases, residual defects are left. Structure, energy, and magnetic properties of these defects are studied. It is found that spontaneous formation of pairs of residual defects (i.e., spontaneous domain nucleation) in the fully reconstructed edge is unlikely at temperatures below 1000 K. Using a kinetic model, we show that the average domain length is several micrometers at room temperature and it decreases exponentially upon increasing the temperature at which the reconstruction takes place.

Precision genetic cellular models identify therapies protective against ER stress.

Rare monogenic disorders often share molecular etiologies involved in the pathogenesis of common diseases. Congenital disorders of glycosylation (CDG) and deglycosylation (CDDG) are rare pediatric disorders with symptoms that range from mild to life threatening. A biological mechanism shared among CDG and CDDG as well as more common neurodegenerative diseases such as Alzheimer's disease and amyotrophic lateral sclerosis, is endoplasmic reticulum (ER) stress. We developed isogenic human cellular models of two types of CDG and the only known CDDG to discover drugs that can alleviate ER stress. Systematic phenotyping confirmed ER stress and identified elevated autophagy among other phenotypes in each model. We screened 1049 compounds and scored their ability to correct aberrant morphology in each model using an agnostic cell-painting assay based on >300 cellular features. This primary screen identified multiple compounds able to correct morphological phenotypes. Independent validation shows they also correct cellular phenotypes and alleviate each of the ER stress markers identified in each model. Many of the active compounds are associated with microtubule dynamics, which points to new therapeutic opportunities for both rare and more common disorders presenting with ER stress, such as Alzheimer's disease and amyotrophic lateral sclerosis.

Transformation of a graphene nanoribbon into a hybrid 1D nanoobject with alternating double chains and polycyclic regions.

Molecular dynamics simulations show that a graphene nanoribbon with alternating regions which are one and three hexagons wide can transform into a hybrid 1D nanoobject with alternating double chains and polycyclic regions under electron irradiation in HRTEM. A scheme of synthesis of such a nanoribbon using Ullmann coupling and dehydrogenation reactions is proposed. The reactive REBO-1990EVC potential is adapted for simulations of carbon-hydrogen systems and is used in combination with the CompuTEM algorithm for modeling of electron irradiation effects. The atomistic mechanism of formation of the new hybrid 1D nanoobject is found to be the following. Firstly hydrogen is removed by electron impacts. Then spontaneous breaking of bonds between carbon atoms leads to the decomposition of narrow regions of the graphene nanoribbon into double chains. Simultaneously, thermally activated growth of polycyclic regions occurs. Density functional theory calculations give barriers along the growth path of polycyclic regions consistent with this mechanism. The electronic properties of the new 1D nanoobject are shown to be strongly affected by the edge magnetism and make this nanostructure promising for nanoelectronic and spintronic applications. The synthesis of the 1D nanoobject proposed here can be considered as an example of the general three-stage strategy of production of nanoobjects and macromolecules: (1) precursors are synthesized using a traditional chemical method, (2) precursors are placed in HRTEM with the electron energy that is sufficient only to remove hydrogen atoms, and (3) as a result of hydrogen removal, the precursors become unstable or metastable and transform into new nanoobjects or macromolecules.

The CECAM electronic structure library and the modular software development paradigm.

First-principles electronic structure calculations are now accessible to a very large community of users across many disciplines, thanks to many successful software packages, some of which are described in this special issue. The traditional coding paradigm for such packages is monolithic, i.e., regardless of how modular its internal structure may be, the code is built independently from others, essentially from the compiler up, possibly with the exception of linear-algebra and message-passing libraries. This model has endured and been quite successful for decades. The successful evolution of the electronic structure methodology itself, however, has resulted in an increasing complexity and an ever longer list of features expected within all software packages, which implies a growing amount of replication between different packages, not only in the initial coding but, more importantly, every time a code needs to be re-engineered to adapt to the evolution of computer hardware architecture. The Electronic Structure Library (ESL) was initiated by CECAM (the European Centre for Atomic and Molecular Calculations) to catalyze a paradigm shift away from the monolithic model and promote modularization, with the ambition to extract common tasks from electronic structure codes and redesign them as open-source libraries available to everybody. Such libraries include "heavy-duty" ones that have the potential for a high degree of parallelization and adaptation to novel hardware within them, thereby separating the sophisticated computer science aspects of performance optimization and re-engineering from the computational science done by, e.g., physicists and chemists when implementing new ideas. We envisage that this modular paradigm will improve overall coding efficiency and enable specialists (whether they be computer scientists or computational scientists) to use their skills more effectively and will lead to a more dynamic evolution of software in the community as well as lower barriers to entry for new developers. The model comes with new challenges, though. The building and compilation of a code based on many interdependent libraries (and their versions) is a much more complex task than that of a code delivered in a single self-contained package. Here, we describe the state of the ESL, the different libraries it now contains, the short- and mid-term plans for further libraries, and the way the new challenges are faced. The ESL is a community initiative into which several pre-existing codes and their developers have contributed with their software and efforts, from which several codes are already benefiting, and which remains open to the community.

Octopus, a computational framework for exploring light-driven phenomena and quantum dynamics in extended and finite systems.

Over the last few years, extraordinary advances in experimental and theoretical tools have allowed us to monitor and control matter at short time and atomic scales with a high degree of precision. An appealing and challenging route toward engineering materials with tailored properties is to find ways to design or selectively manipulate materials, especially at the quantum level. To this end, having a state-of-the-art ab initio computer simulation tool that enables a reliable and accurate simulation of light-induced changes in the physical and chemical properties of complex systems is of utmost importance. The first principles real-space-based Octopus project was born with that idea in mind, i.e., to provide a unique framework that allows us to describe non-equilibrium phenomena in molecular complexes, low dimensional materials, and extended systems by accounting for electronic, ionic, and photon quantum mechanical effects within a generalized time-dependent density functional theory. This article aims to present the new features that have been implemented over the last few years, including technical developments related to performance and massive parallelism. We also describe the major theoretical developments to address ultrafast light-driven processes, such as the new theoretical framework of quantum electrodynamics density-functional formalism for the description of novel light-matter hybrid states. Those advances, and others being released soon as part of the Octopus package, will allow the scientific community to simulate and characterize spatial and time-resolved spectroscopies, ultrafast phenomena in molecules and materials, and new emergent states of matter (quantum electrodynamical-materials).

Two Phases with Different Domain Wall Networks and a Reentrant Phase Transition in Bilayer Graphene under Strain.

The analytical two-chain Frenkel-Kontorova model is used to describe domain wall networks in bilayer graphene upon biaxial stretching of one of the layers. We show that the commensurate-incommensurate phase transition leading to formation of a regular triangular domain wall network at the relative biaxial elongation of 3.0×10^{-3} is followed by the transition to another incommensurate phase with a striped network at the elongation of 3.7×10^{-3}. The reentrant transition to the phase with a triangular domain wall network is predicted for the elongation ∼10^{-2}.

PI3Kγ/δ and NOTCH1 Cross-Regulate Pathways That Define the T-cell Acute Lymphoblastic Leukemia Disease Signature.

PI3K/AKT and NOTCH1 signaling pathways are frequently dysregulated in T-cell acute lymphoblastic leukemias (T-ALL). Although we have shown that the combined activities of the class I PI3K isoforms p110γ and p110δ play a major role in the development and progression of PTEN-null T-ALL, it has yet to be determined whether their contribution to leukemogenic programing is unique from that associated with NOTCH1 activation. Using an Lmo2-driven mouse model of T-ALL in which both the PI3K/AKT and NOTCH1 pathways are aberrantly upregulated, we now demonstrate that the combined activities of PI3Kγ/δ have both overlapping and distinct roles from NOTCH1 in generating T-ALL disease signature and in promoting tumor cell growth. Treatment of diseased animals with either a dual PI3Kγ/δ or a γ-secretase inhibitor reduced tumor burden, prolonged survival, and induced proapoptotic pathways. Consistent with their similar biological effects, both inhibitors downregulated genes involved in cMYC-dependent metabolism in gene set enrichment analyses. Furthermore, overexpression of cMYC in mice or T-ALL cell lines conferred resistance to both inhibitors, suggesting a point of pathway convergence. Of note, interrogation of transcriptional regulators and analysis of mitochondrial function showed that PI3Kγ/δ activity played a greater role in supporting the disease signature and critical bioenergetic pathways. Results provide insight into the interrelationship between T-ALL oncogenic networks and the therapeutic efficacy of dual PI3Kγ/δ inhibition in the context of NOTCH1 and cMYC signaling. Mol Cancer Ther; 16(10); 2069-82. ©2017 AACR.

Formation of Nickel Clusters Wrapped in Carbon Cages: Toward New Endohedral Metallofullerene Synthesis.

Despite the high potential of endohedral metallofullerenes (EMFs) for application in biology, medicine and molecular electronics, and recent efforts in EMF synthesis, the variety of EMFs accessible by conventional synthetic methods remains limited and does not include, for example, EMFs of late transition metals. We propose a method in which EMF formation is initiated by electron irradiation in aberration-corrected high-resolution transmission electron spectroscopy (AC-HRTEM) of a metal cluster surrounded by amorphous carbon inside a carbon nanotube serving as a nanoreactor and apply this method for synthesis of nickel EMFs. The use of AC-HRTEM makes it possible not only to synthesize new, previously unattainable nanoobjects but also to study in situ the mechanism of structural transformations. Molecular dynamics simulations using the state-of-the-art approach for modeling the effect of electron irradiation are performed to rationalize the experimental observations and to link the observed processes with conditions of bulk EMF synthesis.

Energetics of atomic scale structure changes in graphene.

The presence of defects in graphene has an essential influence on its physical and chemical properties. The formation, behaviour and healing of defects are determined by energetic characteristics of atomic scale structure changes. In this article, we review recent studies devoted to atomic scale reactions during thermally activated and irradiation-induced processes in graphene. The formation energies of vacancies, adatoms and topological defects are discussed. Defect formation, healing and migration are quantified in terms of activation energies (barriers) for thermally activated processes and by threshold energies for processes occurring under electron irradiation. The energetics of defects in the graphene interior and at the edge is analysed. The effects of applied strain and a close proximity of the edge on the energetics of atomic scale reactions are overviewed. Particular attention is given to problems where further studies are required.

The atomistic mechanism of carbon nanotube cutting catalyzed by nickel under an electron beam.

The cutting of single-walled carbon nanotubes by an 80 keV electron beam catalyzed by nickel clusters is imaged in situ using aberration-corrected high-resolution transmission electron microscopy. Extensive molecular dynamics simulations within the CompuTEM approach provide insight into the mechanism of this process and demonstrate that the combination of irradiation and the nickel catalyst is crucial for the cutting process to take place. The atomistic mechanism of cutting is revealed by a detailed analysis of irradiation-induced reactions of bond reorganization and atom ejection in the vicinity of the nickel cluster, showing a highly complex interplay of different chemical transformations catalysed by the metal cluster. One of the most prevalent pathways includes three consecutive stages: formation of polyyne carbon chains from the carbon nanotube, dissociation of the carbon chains into single and pairs of adatoms adsorbed on the nickel cluster, and ejection of these adatoms leading to the cutting of the nanotube. Significant variations in the atom ejection rate are discovered depending on the process stage and nanotube diameter. The revealed mechanism and kinetic characteristics of the cutting process provide fundamental knowledge for the development of new methodologies for control and manipulation of carbon structures at the nanoscale.

AA stacking, tribological and electronic properties of double-layer graphene with krypton spacer.

Structural, energetic, and tribological characteristics of double-layer graphene with commensurate and incommensurate krypton spacers of nearly monolayer coverage are studied within the van der Waals-corrected density functional theory. It is shown that when the spacer is in the commensurate phase, the graphene layers have the AA stacking. For this phase, the barriers to relative in-plane translational and rotational motion and the shear mode frequency of the graphene layers are calculated. For the incommensurate phase, both of the barriers are found to be negligibly small. A considerable change of tunneling conductance between the graphene layers separated by the commensurate krypton spacer at their relative subangstrom displacement is revealed by the use of the Bardeen method. The possibility of nanoelectromechanical systems based on the studied tribological and electronic properties of the considered heterostructures is discussed.

Approaches to modelling irradiation-induced processes in transmission electron microscopy.

The recent progress in high-resolution transmission electron microscopy (HRTEM) has given rise to the possibility of in situ observations of nanostructure transformations and chemical reactions induced by electron irradiation. In this article we briefly summarise experimental observations and discuss in detail atomistic modelling of irradiation-induced processes in HRTEM, as well as mechanisms of such processes recognised due to modelling. Accurate molecular dynamics (MD) techniques based on first principles or tight-binding models are employed in the analysis of single irradiation-induced events, and classical MD simulations are combined with a kinetic Monte Carlo algorithm to simulate continuous irradiation of nanomaterials. It has been shown that sulphur-terminated graphene nanoribbons are formed inside carbon nanotubes as a result of an irradiation-selective chemical reaction. The process of fullerene formation in HRTEM during continuous electron irradiation of a small graphene flake has been simulated, and mechanisms driving this transformation analysed.

Ab initio study of edge effect on relative motion of walls in carbon nanotubes.

Interwall interaction energies of double-walled nanotubes with long inner and short outer walls are calculated as functions of coordinates describing relative rotation and displacement of the walls using van der Waals corrected density functional theory. The magnitude of corrugation and the shape of the potential energy relief are found to be very sensitive to changes of the shorter wall length at subnanometer scale and atomic structure of the edges if at least one of the walls is chiral. Threshold forces required to start relative motion of the short walls and temperatures at which the transition between diffusive and free motion of the short walls takes place are estimated. The edges are also shown to provide a considerable contribution to the barrier to relative rotation of commensurate nonchiral walls. For such walls, temperatures of orientational melting, i.e., the crossover from rotational diffusion to free relative rotation, are estimated. The possibility to produce nanotube-based bolt∕nut pairs and nanobearings is discussed.

Chiral graphene nanoribbon inside a carbon nanotube: ab initio study.

The dispersion-corrected density functional theory (DFT-D) is applied for investigation of structure and electronic properties of a sulfur-terminated graphene nanoribbon (S-GNR) encapsulated in a carbon nanotube. Two mechanisms of accommodation of the GNR in the carbon nanotube, distortion of the nanotube cross-section into an elliptic shape accompanied by bending of the GNR and transformation of the GNR to a helical conformation, are analyzed. Three types of elastic distortions of the nanotube and encapsulated GNR are revealed depending on the ratio of the diameter of the nanotube cavity to the GNR width. Helical states of the GNR are shown to be stabilized by the van der Waals attraction of sulfur atoms at neighbouring edges of adjacent turns of the GNR. The results of calculations are correlated with the experimental observations for the S-GNR synthesized recently inside the carbon nanotube. The hybrid DFT calculations of band structures of zigzag GNRs terminated with different atoms demonstrate that as opposed to O- and H-GNRs, the S-GNR is metallic even when deformed inside carbon nanotubes. Possible applications of GNRs encapsulated in carbon nanotubes are discussed.

Sensitive and specific fluorescent probes for functional analysis of the three major types of mammalian ABC transporters.

An underlying mechanism for multi drug resistance (MDR) is up-regulation of the transmembrane ATP-binding cassette (ABC) transporter proteins. ABC transporters also determine the general fate and effect of pharmaceutical agents in the body. The three major types of ABC transporters are MDR1 (P-gp, P-glycoprotein, ABCB1), MRP1/2 (ABCC1/2) and BCRP/MXR (ABCG2) proteins. Flow cytometry (FCM) allows determination of the functional expression levels of ABC transporters in live cells, but most dyes used as indicators (rhodamine 123, DiOC(2)(3), calcein-AM) have limited applicability as they do not detect all three major types of ABC transporters. Dyes with broad coverage (such as doxorubicin, daunorubicin and mitoxantrone) lack sensitivity due to overall dimness and thus may yield a significant percentage of false negative results. We describe two novel fluorescent probes that are substrates for all three common types of ABC transporters and can serve as indicators of MDR in flow cytometry assays using live cells. The probes exhibit fast internalization, favorable uptake/efflux kinetics and high sensitivity of MDR detection, as established by multidrug resistance activity factor (MAF) values and Kolmogorov-Smirnov statistical analysis. Used in combination with general or specific inhibitors of ABC transporters, both dyes readily identify functional efflux and are capable of detecting small levels of efflux as well as defining the type of multidrug resistance. The assay can be applied to the screening of putative modulators of ABC transporters, facilitating rapid, reproducible, specific and relatively simple functional detection of ABC transporter activity, and ready implementation on widely available instruments.