COLOCdb: a comprehensive resource for multi-model colocalization of complex traits.

Large-scale genome-wide association studies (GWAS) have provided profound insights into complex traits and diseases. Yet, deciphering the fine-scale molecular mechanisms of how genetic variants manifest to cause the phenotypes remains a daunting task. Here, we present COLOCdb (https://ngdc.cncb.ac.cn/colocdb), a comprehensive genetic colocalization database by integrating more than 3000 GWAS summary statistics and 13 types of xQTL to date. By employing two representative approaches for the colocalization analysis, COLOCdb deposits results from three key components: (i) GWAS-xQTL, pair-wise colocalization between GWAS loci and different types of xQTL, (ii) GWAS-GWAS, pair-wise colocalization between the trait-associated genetic loci from GWASs and (iii) xQTL-xQTL, pair-wise colocalization between the genetic loci associated with molecular phenotypes in xQTLs. These results together represent the most comprehensive colocalization analysis, which also greatly expands the list of shared variants with genetic pleiotropy. We expect that COLOCdb can serve as a unique and useful resource in advancing the discovery of new biological mechanisms and benefit future functional studies.

Cyclin-G-associated kinase GAK/dAux regulates autophagy initiation via ULK1/Atg1 in glia.

Autophagy is a major means for the elimination of protein inclusions in neurons in neurodegenerative diseases such as Parkinson's disease (PD). Yet, the mechanism of autophagy in the other brain cell type, glia, is less well characterized and remains largely unknown. Here, we present evidence that the PD risk factor, Cyclin-G-associated kinase (GAK)/Drosophila homolog Auxilin (dAux), is a component in glial autophagy. The lack of GAK/dAux increases the autophagosome number and size in adult fly glia and mouse microglia, and generally up-regulates levels of components in the initiation and PI3K class III complexes. GAK/dAux interacts with the master initiation regulator UNC-51like autophagy activating kinase 1/Atg1 via its uncoating domain and regulates the trafficking of Atg1 and Atg9 to autophagosomes, hence controlling the onset of glial autophagy. On the other hand, lack of GAK/dAux impairs the autophagic flux and blocks substrate degradation, suggesting that GAK/dAux might play additional roles. Importantly, dAux contributes to PD-like symptoms including dopaminergic neurodegeneration and locomotor function in flies. Our findings identify an autophagy factor in glia; considering the pivotal role of glia under pathological conditions, targeting glial autophagy is potentially a therapeutic strategy for PD.

Harnessing Electro-Descriptors for Mechanistic and Machine Learning Analysis of Photocatalytic Organic Reactions.

Photocatalysis has emerged as an effective tool for addressing the contemporary challenges in organic synthesis. However, the trial-and-error-based screening of feasible substrates and optimal reaction conditions remains time-consuming and potentially expensive in industrial practice. Here, we demonstrate an electrochemical-based data-acquisition approach that derives a simple set of redox-relevant electro-descriptors for effective mechanistic analysis and performance evaluation through machine learning (ML) in photocatalytic synthesis. These electro-descriptors correlate to the quantification of shifted charge transfer processes in response to the photoirradiation and enabled construction of reactivity diagram where high-yield reactive "hot zones" can reflect subtle changes of the reaction system. For the model reaction of photocatalytic deoxygenation reaction, the influence of varying carboxylic acids (substrate A, oxidation-intended) and alkenes (substrate B, reduction-intended) and varying reaction conditions on the reaction yield can be visualized, while mathematical analysis of the electro-descriptor patterns further revealed distinct mechanistic/kinetic impacts from different substrates and conditions. Additionally, in the application of ML algorithms, the experimentally derived electro-descriptors reflect an overall redox kinetic outcome contributed from vast reaction parameters, serving as a capable means to reduce the dimensionality in the case of complex multiparameter chemical space. As a result, utilization of electro-descriptors enabled efficient and robust quantitative evaluation of chemical reactivity, demonstrating promising potential of introducing operando-relevant experimental insights in the data-driven chemistry.

Cluster-in-Molecule Local Correlation Method for Dispersion Interactions in Large Systems and Periodic Systems.

ConspectusThe noncovalent interactions, including dispersion interactions, control the structures and stabilities of complex chemical systems, including host-guest complexes and the adsorption process of molecules on the solid surfaces. The density functional theory (DFT) with empirical dispersion correction is now the working horse in many areas of applications. Post-Hartree-Fock (post-HF) methods have been well recognized to provide more accurate descriptions in a systematic way. However, traditional post-HF methods are mainly limited to small- or medium-sized systems, and their applications to periodic condensed phase systems are still very limited due to their expensive computational costs.To extend post-HF calculations to large molecules, the cluster-in-molecule (CIM) local correlation approach has been established, allowing highly accurate electron correlation calculations that are routinely available for very large systems. In the CIM approach, the electron correlation energy of a large molecule could be obtained from electron correlation calculations on a series of clusters, each of which contains a subset of occupied and virtual localized molecular orbitals. The CIM method could be massively and efficiently parallelized on general computer clusters. The CIM method has been implemented at various electron correlation levels, including second-order MoÌ·ller-Plesset perturbation theory (MP2), coupled cluster singles and doubles (CCSD), CCSD with perturbative triples correction [CCSD(T)], etc. The CIM-MP2 energy gradient algorithm was developed and applied to the geometry optimizations of large systems. The CIM method has also been extended to condensed-phase systems under periodic boundary conditions (PBC-CIM). For periodic systems, the correlation energy per unit cell could be evaluated with correlation energy contributions from a series of clusters that are built with localized Wannier functions.CIM-based electron correlation calculations have been employed to investigate a number of chemical problems in which the dispersion interaction is important. CIM-based post-HF methods including CIM domain-based local pair natural orbital (DLPNO) CCSD(T) are applied to compute the relative or binding energies of biological systems or supramolecular complexes, the reaction barrier in a relatively complex chemical reaction. The CIM-MP2 method is used to obtain the optimized geometry of large systems. CIM-based post-HF calculations have also been used to compute the cohesive energies of molecular crystals and adsorption energies of molecules on the solid surfaces. The CIM and its PBC variant are expected to become a powerful theoretical tool for accurate calculations of the energies and structures for a broad range of large systems and condensed-phase systems with significant dispersion interactions.

Benefits of Chinese family caregivers of patients with urostomy: a qualitative study.

BACKGROUND: Family caregivers, also known as informal caregivers, are critical for the home care of patients with urostomy. The present study aimed to investigate the benefits of family caregivers in China while taking care of patients with urostomy from a positive perspective. METHODS: A qualitative research design was adopted, with a thematic analysis. The qualitative research software NVivo was used for data analysis. Twenty-two family caregivers of urostomy patients participated in an in-depth interview for 60-90 min. A qualitative analysis was performed using a thematic approach in accordance with the six-stage thematic analysis process reported by Braun and Clarke (2006). RESULTS: The following four benefits were identified: mastering knowledge and skills, promoting self-growth, establishing close family ties, and changing the way of life. Among these four themes, 11 sub-themes were constructed by coders. CONCLUSIONS: This study provides new insights into intervention measures for family caregivers of patients with urostomy, which could play an important role in developing the overall model of family-centered nursing.

Glia-derived temporal signals orchestrate neurogenesis in the Drosophila mushroom body.

Intrinsic mechanisms such as temporal series of transcription factors orchestrate neurogenesis from a limited number of neural progenitors in the brain. Extrinsic regulations, however, remain largely unexplored. Here we describe a two-step glia-derived signal that regulates neurogenesis in the Drosophila mushroom body (MB). In a temporal manner, glial-specific ubiquitin ligase dSmurf activates non-cell-autonomous Hedgehog signaling propagation by targeting the receptor Patched to suppress and promote the exit of MB neuroblast (NB) proliferation, thereby specifying the correct α/ß cell number without affecting differentiation. Independent of NB proliferation, dSmurf also stabilizes the expression of the cell-adhesion molecule Fasciclin II (FasII) via its WW domains and regulates FasII homophilic interaction between glia and MB axons to refine α/ß-lobe integrity. Our findings provide insights into how extrinsic glia-to-neuron communication coordinates with NB proliferation capacity to regulate MB neurogenesis; glial proteostasis is likely a generalized mechanism in orchestrating neurogenesis.

Analysis of the cause of retrolingual obstruction in patients with moderate-severe obstructive sleep apnea.

PURPOSE: To evaluate the percentage of obstructive sleep apnea (OSA) patients with retrolingual obstruction in all moderate-severe OSA patients and the proportions of different causes in all moderate-severe OSA patients with retrolingual obstruction and to discuss the accuracy of the Friedman tongue position (FTP) and retrolingual cross-sectional area (RCSA) in assessing the retrolingual obstruction. METHODS: Two hundred and twenty moderate-severe OSA patients were enrolled. After retrolingual obstruction was diagnosed, the percentage of OSA patients with retrolingual obstruction in all moderate-severe OSA patients was calculated. After that, the different causes of retrolingual obstruction were diagnosed based on different diagnostic criteria, and the proportions of different causes in all moderate-severe OSA patients with retrolingual obstruction were calculated. Finally, the correlations between FTP, RCSA, and apnea-hypopnea index after nasopharyngeal tube insertion (NPT-AHI) were analyzed, and the proportions of different causes of retrolingual obstruction based on different FTP and RCSA were observed. RESULTS: There were 128 patients with retrolingual obstruction, accounting for 58.2% of all moderate-severe OSA patients. In 128 patients with retrolingual obstruction, the proportions of glossoptosis (48.4%), palatal tonsil hypertrophy (28.1%), and lingual hypertrophy (8.6%) were relatively high. Both FTP and RCSA did not correlate with NPT-AHI. The proportion of lingual hypertrophy increased gradually with the increase of FTP and the proportions of glossoptosis in all FTP classifications were high. The patients with RCSA > 180 mm2 were mainly affected by glossoptosis and palatal tonsil hypertrophy, while patients with RCSA ≤ 180 mm2 were mainly affected by lingual hypertrophy. CONCLUSION: The percentage of patients with retrolingual obstruction in all moderate-severe OSA patients is relatively high, mainly glossoptosis, palatal tonsil hypertrophy, and lingual hypertrophy. FTP classification and RCSA can only reflect the retrolingual anatomical stenosis, but cannot fully reflect the retrolingual functional stenosis, especially the presence of glossoptosis.

Magnetoelectricity-Mediated Tunable Absorption and Release of Peroxide Dianions.

Peroxide dianion (O22-) has strong oxidizing activity and ease of proton abstraction and is extremely unstable. Direct and controllable adsorption and release of O22- has large application implication and is a large challenge so far. Here, we use a unique metal (Ni)-organic (diphenylalanine, DPA) framework (MOF), Ni(DPA)2, as adsorbents for absorption and release of O22-. This MOF structure has room-temperature magnetoelectricity via distortion of the Ni-centered octahedron {NiN2O4} and thus possesses a tunable ferroelectric polarization under applied electric/magnetic fields. Controllable adsorption and release of O22- are realized in such a MOF system via electrochemical redox measurements. Structural/spectroscopic characterization and calculations reveal that a number of NH active sites in the nanopores of MOF can effectively adsorb O22- by hydrogen bonds and then tunable ferroelectric polarization induces controllable release of O22- under applied magnetic fields. This work presents a constructive way for controllable adsorption and release of reactive oxygen species.

Role of serum alkaline phosphatase as a potential biomarker of severity and prognosis in intracerebral hemorrhage.

OBJECTIVES: Alkaline phosphatase (ALP) catalyzes the hydrolysis of pyrophosphate and facilitates vascular calcification. We aimed at investigating serum ALP levels in intracerebral hemorrhage (ICH) patients and ascertaining its relationship to severity and prognosis. METHODS: Serum ALP levels from 148 patients and 148 healthy controls were detected. Glasgow coma scale (GCS) score and hematoma volume at admission were recorded to evaluate hemorrhagic severity. Modified Rankin Scale (mRS) score > 2 at 90 days after onset was judged as a poor prognosis. RESULTS: Serum ALP levels in patients with ICH were substantially elevated compared with healthy controls, and were significantly related to hematoma volume and GCS score. Serum ALP levels significantly distinguished ICH patients at risk for unfavorable prognosis. Serum ALP levels > 78.5 U/L in ICH patients may indicated a unfavorable prognosis with 69.1 % sensitivity and 83.6 % specificity, and served as an independent predictor for unfavorable prognosis. CONLUSIONS: Elevated serum ALP levels were intimately connected with increased severity and 90-day unfavorable prognosis in patients with ICH. Serum ALP could be a potential biomarker for severity and prognosis of ICH.

Translational development of a novel BAFF-R CAR-T therapy targeting B-cell lymphoid malignancies.

Several CD19-targeting CAR-T cells are used to treat leukemias and lymphomas; however, relapsed and/or refractory (R/R) disease is still observed in a significant number of patients. Additionally, the success of CD19-CAR-T cell therapies is not uniform across hematological malignancies, particularly in chronic lymphocytic leukemia (CLL). In this study, we present the development of a novel CAR-T cell therapy targeting B-cell activating factor receptor (BAFF-R), a key regulator of B-cell proliferation and maturation. A new monoclonal antibody against BAFF-R was generated from a hybridoma clone and used to create a novel MC10029 CAR construct. Through a series of in vitro and in vivo models using the Nalm-6 cell line for leukemia and the Z138 cell line for lymphoma, we demonstrated the antigen-specific cytotoxicity of MC10029 CAR-T cells against tumor cells. Additionally, MC10029 CAR-T cells exhibited potent antitumor effects against CD19 knockout tumor cells, mimicking CD19-negative R/R disease. MC10029 CAR-T cells were specifically targeted to CLL, in which BAFF-R is nearly always expressed. The cytotoxicity of MC10029 CAR-T cells was first shown in the MEC-1 CLL cell line, before we turned our efforts to subject-derived samples. Using healthy donor-engineered MC10029 CAR-T cells against enriched primary tumor cells, followed by subject-derived MC10029 CAR-T cells against autologous tumor cells, we showed the efficacy of MC10029 CAR-T cells against CLL subject samples. With these robust data, we have advanced to the production of MC10029 CAR-T cells, using GMP lentivirus, and obtained an IND approval in preparation for a Phase 1 clinical trial.

Mechanistic Insights into the Metal-Free Deoxygenative Borylation of Ketones and Aldehydes with Bis(catecholato)diborane.

The mechanisms of direct deoxygenative borylation of acetone and benzaldehyde with bis(catecholato)diborane (B2 cat2 ) in the solvent N,N-dimethylacetamide (DMA) are investigated through detailed density functional theory calculations. These calculations show that the isomer 1,2-B2 cat2 in situ generated from 1,1-B2 cat2 induced by DMA is the reactive boron intermediate for the reactions. The addition of the B-B bond of 1,2-B2 cat2 to the C=O bond of acetone or benzaldehyde via a concerted [2σ+2π]-cycloaddition-like transition state is the rate-limiting step for both the triboration reaction of acetone and the monoboration reaction of benzaldehyde. DMA not only acts as the solvent but also promotes the structural isomerization of B2 cat2 , the deoxygenation of acetone to form the vinyl boronate intermediate and subsequent diboration of vinyl boronate with 1,2-B2 cat2 , as well as the protodeboronation of the gem-diboronate intermediate in the deoxygenative borylation of benzaldehyde. The presented computational results can explain the observed experimental facts and provide insight into the roles of the isomeric 1,2-B2 cat2 and the solvent DMA in related reactions.

Combined molecular dynamics and coordinate driving method for automatically searching complicated reaction pathways.

The combined molecular dynamics and coordinate driving (MD/CD) method is updated and generalized in this work to broaden its applications in automatically searching reaction pathways for complicated reactions. In this updated version, MD simulations are performed with the GFN's family of methods to systematically sample conformers for almost any systems with atomic numbers Z ≤ 86. The improved CD procedure is greatly accelerated by applying a pre-screening stage at the semiempirical GFN2-xTB level. An automatic module based on the Marcus theory and its improved version (the Wolynes theory) is designed to include single electron transfer (SET) processes into reaction pathways. The capabilities of this method are demonstrated by exploring the most possible reaction pathways of three experimentally reported reactions: the organophosphine-catalyzed trans phosphinoboration, the Fe(II) complex-mediated C(sp2)-H borylation reaction, and the SET-triggered deaminative radical cross-coupling reaction. Comprehensive reaction networks are obtained for all three reactions with reasonable computational costs. Detailed mechanisms for these reactions can account for the reported experimental facts.

Predicting the structures and vibrational spectra of molecular crystals containing large molecules with the generalized energy-based fragmentation approach.

The generalized energy-based fragmentation (GEBF) approach under periodic boundary conditions (PBCs) has been developed to facilitate calculations of molecular crystals containing large molecules. The PBC-GEBF approach can help predict structures and properties of molecular crystals at different theory levels by performing molecular quantum chemistry calculations on a series of non-periodic subsystems constructed from the studied systems. A more rigorous formula of the forces on translational vectors of molecular crystals was proposed and implemented, enabling more reliable predictions of crystal structures. Our benchmark results on several typical molecular crystals show that the PBC-GEBF approach could reproduce the forces on atoms and the translational vectors and the optimized crystal structures from the corresponding conventional periodic methods. The improved PBC-GEBF approach is then applied to predict the crystal structures and vibrational spectra of two molecular crystals containing large molecules. The PBC-GEBF approach can provide a satisfactory description on the crystal structure of a molecular crystal containing 312 atoms in a unit cell at density-fitting second-order Møller-Plesset perturbation theory and density functional theory (DFT) levels and the infrared vibrational spectra of another molecular crystal containing 864 atoms in a unit cell at the DFT level. The PBC-GEBF approach is expected to be a promising theoretical tool for electronic structure calculations on molecular crystals containing large molecules.

Clinical Manifestations of Subjective Sleep Disorders in Chinese Patients with Parkinson's Disease and Their Relationship with Dopaminergic Drugs.

INTRODUCTION: Sleep disorders are common in Parkinson's disease (PD) and significantly impact quality of life. Herein, we surveyed the incidence and severity of sleep disorders in Chinese PD patients and observed their relationship with dopaminergic drugs. METHODS: We collected the demographic and disease information of 232 PD patients. The incidence and severity of sleep disorders were surveyed with the Parkinson's disease sleep scale (PDSS) Chinese version. Data on dopaminergic drug intake were collected and converted to levodopa equivalent doses (LED). RESULTS: The average total score of PDSS in 232 patients was 119.3 ± 19.7. There was a significant difference in PDSS scores between groups classified by the Hoehn-Yahr (H&Y) stage, but not between the groups classified by the type of dopaminergic drugs. Stepwise regression analysis revealed that the LED of dopaminergic drugs taken before bedtime (p < 0.00), LED of dopaminergic drugs taken over a 24-h period (p < 0.00), and scores of the Hamilton Rating Scale for Depression (HAMD) (p = 0.01) were determinants of PDSS. CONCLUSION: Sleep disorders in PD patients may be multifactorial. High dosage of dopaminergic drugs taken prior to sleep, daily total high dosage of dopaminergic drugs, and depression exert negative effects on subjective sleep. The timing and dosage of dopaminergic drugs taken before bedtime should be considered in PD management.

Genetic diversity of 23 STR loci of the Guizhou Tujia ethnic minority and the phylogenetic relationships with 22 other populations.

BACKGROUND: Short tandem repeats (STR) are highly polymorphic DNA markers utilised in forensic personal identification and human population genetic research. Guizhou Tujia is one of the ancient minority groups in southwest China, however, the population has not been studied using the highly discriminating 23 STR Huaxia Platinum Kit. AIM: To obtain genetic data from 23 autosomal STRs in Guizhou Tujia and examine the population's relationship with others. SUBJECTS AND METHODS: A total of 480 individuals from the Guizhou Tujia population were analysed using 23 STR loci of Huaxia Platinum Kit. Allele frequencies and forensic parameters were estimated. Population genetic relationships were calculated by Nei's genetic distances and visualised using a variety of biostatistical methods. RESULTS: A total of 264 alleles were found, with allelic frequencies ranging from 0.0010 to 0.5104. The combined discrimination power (CDP) and the combined probability of paternity (CPE) of 23 STR loci were 0.9999999999999999999999999996 and 0.999999999710422, respectively. Guizhou Tujia showed closer genetic relationships with Hubei Tujia, Guizhou Gelao, and Guizhou Miao than with other populations. CONCLUSION: We first obtained the population genetic data of Guizhou Tujia using the 23 STR system and demonstrated its value in forensic applications. Comprehensive population comparisons showed an evident genetic affinity pattern between populations that are geographically, ethnically and linguistically related.

Bedside nurses' antimicrobial stewardship practice scope and competencies in acute hospital settings: A scoping review.

AIM: To identify and map bedside nurses' practice scope and competencies regarding antimicrobial stewardship in acute hospital settings, and develop a competency framework for them. BACKGROUND: Antimicrobial stewardship requires multidisciplinary engagement including nursing. However, bedside nurses' antimicrobial stewardship practice scope and competencies in acute hospital settings remain unclear. DESIGN: Scoping review. METHODS: Using a five-stage framework proposed by Arksey and O'Malley and following the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines. RESULTS: A total of 1422 records were retrieved, and 41 studies were included. In addition to the six practices recommended, this review summarized bedside nurses' contributions to five additional fields as well. Correspondingly, the competencies required by bedside nurses were summarized into eight domains: specialized knowledge, safety medication administration, leadership, education, diagnostic stewardship, infection prevention and control, professional development and professional quality. CONCLUSION: Nurses' practice scope overlaps greatly with routine nursing practice in antimicrobial stewardship, confirming the evidence that nurses are ideal partners in antimicrobial stewardship. This review developed a competency framework at both basic and advanced levels. Among them, professional knowledge is the foundation, while professional quality motivates nurses to participate. In addition to competency assessment, it can also be used for training and human resource deployment based on seniority or professional level. This could bridge the knowledge gap and improve the engagement of nurses in heavy workload situations. RELEVANCE TO CLINICAL PRACTICE: This practice scope will provide opportunities for nurses to engage in antimicrobial stewardship. Moreover, nursing competencies identified in this field could facilitate the development of competency-based education interventions, talent assessments, training and recruitment programs. DATA RESOURCES: PubMed, EMBASE, Web of Science, CINHAL, PsycINFO, Cochrane Library, ProQuest and Scopus were searched from inception to November 2022, with an updated search in March 2023. IMPACT: This scoping review provides evidence for best nursing practice scope and competency in antimicrobial stewardship in hospitals. However, it is also in line with the commitment of all nurses in the global community to combat antimicrobial resistance, which has become a global threat. An antimicrobial stewardship competency framework for bedside nurses was developed at both the basic and advanced levels. It would facilitate talent assessment, training, recruitment and human resource management by guiding the development of competency-based education interventions. PATIENT OR PUBLIC CONTRIBUTION: No Patient or Public Contribution.

Light-Induced Tunable Ferroelectric Polarization in Dipole-Embedded Metal-Organic Framework.

Reversible regulation of ferroelectric polarization possesses great potentials recently in bionic neural networks. Photoinduced cis-trans isomers have changeable dipole moments, but they cannot be directed to some specific orientation. Here, we construct a host-guest composite structure which consists of a porous ferroelectric metal (Ni)-organic framework [Ni(DPA)2] as host and photoisomer, azobenzene (AZB), as guest molecules. When AZB molecules are embedded in the nanopores of Ni(DPA)2 in the form of a single molecule, polarization strength tunable regulation is realized after ultraviolet irradiation of 365 and 405 nm via cis-trans isomerism transformation of AZB. An intrinsic built-in field originating from the distorted {NiN2O4} octahedra in Ni(DPA)2 directs the dipole moments of AZB to the applied electric field. As a result, the overlapped ferroelectric polarization strength changes with content of cis-AZB after ultraviolet and visible irradiation. Such a connection of ferroelectric Ni(DPA)2 structure with cis-trans isomers provides an important strategy for regulating the ferroelectric polarization strength.

Structures and properties of ionic crystals and condensed phase ionic liquids predicted with the generalized energy-based fragmentation method.

The generalized energy-based fragmentation (GEBF) approach is extended to facilitate ab initio investigations of structures, lattice energies, vibrational spectra and 1 H NMR chemical shifts of ionic crystals and condensed-phase ionic liquids (ILs) with the periodic boundary conditions (PBC). For selected periodic systems, our results demonstrate that the so-called PBC-GEBF approach can provide satisfactory descriptions on ground-state energies, structures, and vibrational spectra of ionic crystals and IL crystals. The PBC-GEBF approach is then applied to three realistic condensed phase systems. For three ionic crystals (LiCl, NaCl, and KCl), we apply the PBC-GEBF approach with MP2 theory as well as some popular DFT methods to investigate their crystal structures and lattice energies. Our calculations indicate that the crystal structures obtained with PBC-GEBF-MP2/6-311 + G** are very close to the corresponding X-ray structures, while PBC-GEBF-ωB97X-D/6-311 + G** provides satisfactory prediction for crystal structures and lattice energies. For two polymorphs of [n-C4 mim][Cl] crystals, we find that the PBC-GEBF approach at the M06-2X/6-311 + G** level can give a satisfactory descriptions on structures and Raman spectra of these two crystals. Furthermore, for [C2 mim][BF4 ] ILs, we demonstrate that their 1 H NMR chemical shifts can be estimated from averaging over 5 typical snapshots (extracted from MD simulations) with the PBC-GEBF approach at the B97-2/pcSseg-2 level. The calculated results account for the observed experimental data quite well. Therefore, we expect that the PBC-GEBF approach, combined with various quantum chemistry methods, will become an effective tool in predicting structures and properties of ionic crystals and condensed-phase ILs.

Structures and Spectroscopic Properties of Large Molecules and Condensed-Phase Systems Predicted by Generalized Energy-Based Fragmentation Approach.

ConspectusThe structures and spectroscopic properties of molecules and condensed-phase systems are usually experimentally characterized by X-ray, infrared (IR), Raman, nuclear magnetic resonance (NMR), and electronic absorption/emission spectra. Quantum mechanics (QM) calculations are critical in quantitatively understanding the relationship between the structure and physicochemical properties of various chemical systems. However, it is very challenging to apply traditional QM methods to large molecules and condensed-phase systems with large unit cells due to their steep computational scaling with the system size. To overcome this difficulty, theoretical chemists have developed various linear (or low) scaling QM methods, among which energy-based fragmentation methods have achieved great success for large molecules or clusters. One of the most popular energy-based fragmentation methods is the generalized energy-based fragmentation (GEBF) approach developed by us.In this approach, the ground-state energy of a large molecule can be evaluated from the ground-state energies of a series of embedded subsystems. In this Account, we focus on the recent developments and applicability of the GEBF approach for the structures and spectroscopic properties of complicated large molecules and condensed-phase systems. With new fragmentation schemes, the GEBF approach can now describe ionic liquid clusters and metal-containing supramolecular systems accurately and can provide accurate binding energies for host-guest complexes. In addition, the GEBF approach is now available for describing the localized excited states of large systems including a chromophore. More importantly, the GEBF approach under periodic boundary conditions (PBC-GEBF) has been developed to deal with periodic molecular crystals and liquids. Then, the ground-state energy (or property) per unit cell of a periodic condensed phase system can be predicted with QM calculations on nonperiodic embedded subsystems. This feature enables accurate electron correlation calculations on molecular crystals and liquids to be feasible on ordinary workstations. The PBC-GEBF approach has been applied to predict the crystal structures, lattice energies, and spectroscopic properties of some typical molecular crystals and solutions. By combining the GEBF method and machine learning (ML) method, a GEBF-ML force field has been developed for long normal alkanes, and the IR spectra of long alkanes can be obtained from the GEBF-ML molecular dynamics (MD) simulations. The GEBF and its periodic variant are expected to play increasingly important roles in investigating real-life chemical systems of broad interests at the ab initio levels.

Mechanistic Insight into Hydroboration of Imines from Combined Computational and Experimental Studies.

Boron Lewis acid-catalyzed and catalyst-free hydroboration reactions of imines are attractive due to the mild reaction conditions. In this work, the mechanistic details of the hydroboration reactions of two different kinds of imines with pinacolborane (HBpin) are investigated by combining density functional theory calculations and some experimental studies. For the hydroboration reaction of N-(α-methylbenzylidene)aniline catalyzed by tris[3,5-bis(trifluoromethyl)phenyl]borane (BArF 3 ), our calculations show that the reaction proceeds through a boron Lewis acid-promoted hydride transfer mechanism rather than the classical Lewis acid activation mechanism. For the catalyst- and solvent-free hydroboration reaction of imine, N-benzylideneaniline, our calculations and experimental studies indicate that this reaction is difficult to occur under the reaction conditions reported previously. With a combination of computational and experimental studies, we have established that the commercially available BH3 ⋅ SMe2 can serve as an efficient catalyst for the hydroboration reactions of N-benzylideneaniline and similar imines. The hydroboration reactions catalyzed by BH3 ⋅ SMe2 are most likely to proceed through a hydroboration/B-H/B-N σ-bond metathesis pathway, which is very different from that of the reaction catalyzed by BArF 3 .