Core Binding Research Articles

Is age just a number? Intensive therapy for core binding factor acute myeloid leukemia in older adults.

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Long-term survival can be achieved in a significant fraction of older patients with core binding factor acute myeloid leukemia treated with intensive chemotherapy.

Acute Myeloid Leukemia is mainly a disease of the elderly: however, the knowledge on the outcomes of treatment in core binding factor AML (CBFAML) in older population, is limited. We retrospectively collected data on 229 patients with CBF- AML followed long-term in the last two decades. A 5-year overall survival (OS) of 44.2% (95%CI, 39.9-47.5) and a 5-year event - free survival (EFS) of 32.9% (95%CI, 25.5-40.1) was observed. In a subgroup of >70-year patients who completed intensive therapy (induction + >3 courses of consolidation including autologous stem cell transplant: 10 patients) the median EFS was 11.8 months (95%CI, 9.4 - 15.2) and OS was 40.0% (95%CI, 36.4 - 44.1) at 5yr. In univariate analysis, age >70 (hazard ratio (HR) 1.78, [95%CI, 1.15 - 2.54], p=.008), failure to achieve remission following induction (HR, 8.96 [95%CI, 5.5 - 13.8], p=<.0001), no consolidation therapy (HR, 0.75 [95%CI, 0.47 - 1.84], p=.04) and less than 3 cycles of consolidation (HR, 1.48 [95%CI, 0.75 - 3.2], p=.0004), predicted poorer EFS. Our study shows that intensive therapy, in selected older CBF-AML patients, leads to longer survival. Achieving a CR seems to be the most important first step and at least 3 cycles of consolidation, an important second one. The analysis suggests that these patients should not be excluded from studies with intensive therapies.

Recent progress in AML with recurrent genetic abnormalities.

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by various molecular abnormalities that significantly impact its pathogenesis and prognosis. Currently, the prognosis of AML patients is stratified on the basis of co-existing chromosomal and genetic abnormalities. AML patients with NPM1 or CEBPA mutations, which are frequently identified in cytogenetically normal AML, are classified in the favorable-risk group, although approximately 40% of patients relapse. Similarly, a clinical high-risk group has been identified among patients with acute promyelocytic leukemia, but the underlying molecular abnormalities remain unclear. FLT3 mutations frequently overlap in these favorable-risk AMLs, including core binding factor AML, and their prognostic impact is still controversial. As such, further risk stratification and treatment optimization based on various molecular abnormalities are warranted to improve the prognosis of favorable-risk AMLs. These molecular abnormalities are also considered therapeutic targets, and targeted therapies have been developed over the years. In recent years, several targeted agents have been approved and demonstrated to improve the prognosis of AML. However, resistance to targeted therapies is also a challenge. This Progress in Hematology features current trends and challenges in favorable-risk AML and FLT3 mutations that are frequently identified in these patients.

The Functional and Prognostic Impact of TIGIT Expression on Bone Marrow NK Cells in Core Binding Factor-Acute Myeloid Leukemia Patients at Diagnosis.

Background: The effect of the expression of the newly identified immune checkpoint, T cell immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT) on NK cells in core binding factor-acute myeloid leukemia (CBF-AML) remains to be investigated. Methods: Fresh bone marrow samples from a total of 39 newly diagnosed CBF-AML patients and 25 healthy donors (HDs) were collected for testing the phenotype and function state of total NK, CD56bright, and CD56dim NK cell subsets after in vitro stimulation. Results: The frequencies of TIGIT+ cells in total NK, CD56bright, and CD56dim NK cell subsets had no significant difference between patients and HDs. TNF-α and INF-γ levels were uniformly lower in TIGIT+ cells than the corresponding TIGIT- cells in all HDs, whereas those for TIGIT+ to TIGIT- cells in patients were highly heterogenous; TIGIT expression was not related to PFP and GZMB expression in HDs, whereas it was related to higher intracellular PFP and GZMB levels in patients. Patients' TIGIT+ NK cells displayed lower K562 cell-killing activity than their TIGIT- NK cells. In addition, high frequencies of TIGIT+ cells in total NK and CD56dim NK cells were associated with poor RFS. Conclusions: TIGIT expression affected the diagnostic bone marrow-sited NK cell function and had prognostic significance in CBF-AML patients.

Phylogenomic instructed target analysis reveals ELAV complex binding to multiple optimally spaced U-rich motifs.

ELAV/Hu RNA-binding proteins are gene-specific regulators of alternative pre-mRNA processing. ELAV/Hu family proteins bind to short AU-rich motifs which are abundant in pre-mRNA, making it unclear how they achieve gene specificity. ELAV/Hu proteins multimerize, but how multimerization contributes to decode degenerate sequence environments remains uncertain. Here, we show that ELAV forms a saturable complex on extended RNA. Through phylogenomic instructed target analysis we identify the core binding motif U5N2U3, which is repeated in an extended binding site. Optimally spaced short U5N2U3 binding motifs are key for high-affinity binding in this minimal binding element. Binding strength correlates with ELAV-regulated alternative poly(A) site choice, which is physiologically relevant through regulation of the major ELAV target ewg in determining synapse numbers. We further identify a stem-loop secondary structure in the ewg binding site unwound upon ELAV binding at three distal U motifs. Base-pairing of U motifs prevents ELAV binding, but N6-methyladenosine (m6A) has little effect. Further, stem-loops are enriched in ELAV-regulated poly(A) sites. Additionally, ELAV can nucleate preferentially from 3' to 5'. Hence, we identify a decisive mechanism for ELAV complex formation, addressing a fundamental gap in understanding how ELAV/Hu family proteins decode degenerate sequence spaces for gene-specific mRNA processing.

Mapping snoRNA-target RNA interactions in an RNA binding protein-dependent manner with chimeric eCLIP.

Small nucleolar RNAs (snoRNAs) are non-coding RNAs that function in ribosome and spliceosome biogenesis, primarily by guiding modifying enzymes to specific sites on ribosomal RNA (rRNA) and spliceosomal RNA (snRNA). However, many orphan snoRNAs remain uncharacterized, with unidentified or unvalidated targets, and studies on additional snoRNA-associated proteins are limited. We adapted an enhanced chimeric eCLIP approach to comprehensively profile snoRNA-target RNA interactions using both core and accessory snoRNA binding proteins as baits. Using core snoRNA binding proteins, we confirmed most annotated snoRNA-rRNA and snoRNA-snRNA interactions in mouse and human cell lines and called novel, high-confidence interactions for orphan snoRNAs. While some of these interactions result in chemical modification, others may have modification-independent functions. We then showed that snoRNA ribonucleoprotein complexes containing certain accessory proteins, like WDR43 and NOLC1, enriched for specific subsets of snoRNA-target RNA interactions with distinct roles in ribosome and spliceosome biogenesis. Notably, we discovered that SNORD89 guides 2'-O-methylation at two neighboring sites in U2 snRNA that are important for activating splicing, but also appear to ensure imperfect splicing for a subset of near-constitutive exons. Thus, chimeric eCLIP of snoRNA-associating proteins enables a comprehensive framework for studying snoRNA-target interactions in an RNA binding protein-dependent manner, revealing novel interactions and regulatory roles in RNA biogenesis.

Regulation of Skeletal Development and Maintenance by Runx2 and Sp7.

Runx2 (runt related transcription factor 2) and Sp7 (Sp7 transcription factor 7) are crucial transcription factors for bone development. The cotranscription factor Cbfb (core binding factor beta), which enhances the DNA-binding capacity of Runx2 and stabilizes the Runx2 protein, is necessary for bone development. Runx2 is essential for chondrocyte maturation, and Sp7 is partly involved. Runx2 induces the commitment of multipotent mesenchymal cells to osteoblast lineage cells and enhances the proliferation of osteoprogenitors. Reciprocal regulation between Runx2 and the Hedgehog, fibroblast growth factor (Fgf), Wnt, and parathyroid hormone-like hormone (Pthlh) signaling pathways and Dlx5 (distal-less homeobox 5) plays an important role in these processes. The induction of Fgfr2 (Fgf receptor 2) and Fgfr3 expression by Runx2 is important for the proliferation of osteoblast lineage cells. Runx2 induces Sp7 expression, and Runx2+ osteoprogenitors become Runx2+Sp7+ preosteoblasts. Sp7 induces the differentiation of preosteoblasts into osteoblasts without enhancing their proliferation. In osteoblasts, Runx2 is required for bone formation by inducing the expression of major bone matrix protein genes, including Col1a1 (collagen type I alpha 1), Col1a2, Spp1 (secreted phosphoprotein 1), Ibsp (integrin binding sialoprotein), and Bglap (bone gamma carboxyglutamate protein)/Bglap2. Bglap/Bglap2 (osteocalcin) regulates the alignment of apatite crystals parallel to collagen fibrils but does not function as a hormone that regulates glucose metabolism, testosterone synthesis, and muscle mass. Sp7 is also involved in Co1a1 expression and regulates osteoblast/osteocyte process formation, which is necessary for the survival of osteocytes and the prevention of cortical porosity. SP7 mutations cause osteogenesis imperfecta in rare cases. Runx2 is an important pathogenic factor, while Runx1, Runx3, and Cbfb are protective factors in osteoarthritis development.

VHL synthetic lethality screens uncover CBF-β as a negative regulator of STING.

Clear cell renal cell carcinoma (ccRCC) represents the most common form of kidney cancer and is typified by biallelic inactivation of the von Hippel-Lindau (VHL) tumour suppressor gene. Here, we undertake genome-wide CRISPR/Cas9 screening to reveal synthetic lethal interactors of VHL, and uncover that loss of Core Binding Factor β (CBF-β) causes cell death in VHL-null ccRCC cell lines and impairs tumour establishment and growth in vivo. This synthetic relationship is independent of the elevated activity of hypoxia inducible factors (HIFs) in VHL-null cells, but does involve the RUNX transcription factors that are known binding partners of CBF-β. Mechanistically, CBF-β loss leads to upregulation of type I interferon signalling, and we uncover a direct inhibitory role for CBF-β at the STING locus controlling Interferon Stimulated Gene expression. Targeting CBF-β in kidney cancer both selectively induces tumour cell lethality and promotes activation of type I interferon signalling.

The efficacy and safety of avapritinib in the treatment of molecular biologically positive core binding factor-acute myeloid leukemia with KIT mutation after allogeneic hematopoietic stem cell transplantation

Objective: To investigate the efficacy and safety of avapritinib in the treatment of molecular biologically positive core binding factor-acute myeloid leukemia (CBF-AML) with KIT mutation after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: We retrospectively analyzed the clinical data of six patients with molecular biologically positive CBF-AML with KIT mutation after allo-HSCT, who were treated with avapritinib at Henan Cancer Hospital from December 2021 to March 2023, and evaluated the efficacy and safety of avapritinib. Results: After 1 month of treatment with avapritinib, the transcription level of the fusion gene decreased in six patients, and the transcription level decreased by ≥1 log in five patients. In four patients who received avapritinib for ≥3 months, the fusion gene turned negative, and the median time to turn negative was 2.0 (range: 1.0-3.0) months. Up to the end of follow-up, four patients had no recurrence. The most common adverse reaction of avapritinib was myelosuppression, including neutropenia in two cases, thrombocytopenia in two cases, and anemia in one case. The non-hematological adverse reactions were nausea in two cases, edema in one case, and memory loss in one case, all of which were grades 1-2. Conclusion: Avapritinib was effective for molecular biologically positive CBF-AML patients with KIT mutation after allo-HSCT. The main adverse reaction was myelosuppression, which could generally be tolerated.

Real-world outcomes of intensive induction approaches in core binding factor acute myeloid leukemia.

Core-binding factor acute myeloid leukemia (CBF-AML) is characterized by the presence of inv(16)/t(16;16) or t(8;21) and is classified as a favorable risk by the 2022 European LeukemiaNet (ELN) guidelines. The CD33-targeting antibody-drug conjugate, gemtuzumab ozogamicin (GO), is commonly added to intensive chemotherapy (IC) in CBF-AML. We sought to compare outcomes in patients treated with IC with or without GO in CBF-AML. We included 200 patients with CBF-AML treated with IC across seven academic centers. Induction treatment regimens were categorized as IC alone, IC with GO, or IC with KIT inhibitor (dasatinib or midostaurin). Median follow-up for the whole cohort was 2.5 years. Three-year overall survival (OS) was 70% and 3-year event-free survival (EFS) was 51%. Patients treated with IC with GO experienced a 3-year EFS of 50% compared to those treated with IC alone who experienced a 3-year EFS of 47%, with no statistically significant difference (p=0.62). Similarly, those treated with IC with GO did not experience an improved OS compared to those treated with IC alone (p=0.67). Patients treated with IC with KIT inhibitor experienced a significantly improved 3-year EFS of 85% compared to those with IC with or without GO (p=0.04). We find in our study that there is no survival benefit in patients treated with IC with the addition of GO; improved EFS was seen in patients with CBF-AML treated with IC plus KIT inhibitors, consistent with outcomes noted in prospective studies utilizing this approach.

Biosafety and osteogenic properties of a new type of absorbable magnesium-based amorphous alloy

The treatment of bone defects has always been a difficult problem in orthopedic clinical practice, and research on new materials is currently a hot topic. In this study, the biological safety and bone induction ability of a new magnesium-based amorphous alloy (Mg66Zn30Ca3Sr1) and zinc–magnesium powder were verified and compared in animal experiments. Thirty Sprague–Dawley rats were randomly divided into three groups, and a bone defect was made in the lateral condyle of the femur of the left hind limb. The blank group closed the wound after establishing the bone defect model, the control group added zinc–magnesium powder and chondroitin sulfate gel, and the experimental group added magnesium–zinc–calcium–strontium alloy and chondroitin sulfate gel with the same volume. Peripheral venous blood of rats was collected at 4, 8, and 12 weeks postoperatively, and alanine aminotransferase (ALT), aspartate transferase, creatinine, blood urea nitrogen, magnesium ion, and zinc ion levels were evaluated. The expression levels of bone morphogenetic protein 2 (BMP-2), osteoprotegerin (OPG), osteopontin (OPN), core binding factor α1 (RUNX2), and alkaline phosphatase (ALP) were detected using enzyme-linked immunosorbent assay (ELISA). After the rats were euthanized, samples were taken. X-rays and micro-computed tomography (CT) images of the bone defect were obtained, and hematoxylin and eosin and Masson staining were performed. This study shows that amorphous magnesium–zinc–calcium–strontium alloy is a biodegradable metal with good biocompatibility and bone induction and has good application prospects in treating bone defects.

Pleiotropic effects of an eQTL in the CELSR2/PSRC1/SORT1 cluster that associates with LDL-C and resting metabolic rate.

The locus CELSR2-PSRC1-SORT1, a primary genetic signal for lipids, has recently been implicated in different metabolic processes. Our investigation identified its association with energy metabolism. To determine biological mechanisms that govern diverse functions of this locus. Genotypes for 491,265 variants in 7,000 clinically characterized American Indians were previously determined using a custom-designed array specific for this longitudinally studied American Indian population. Among the genotyped individuals, 5,205 had measures of fasting lipid levels and 509 had measures of resting metabolic rate (RMR) and substrate oxidation rate assessed through indirect calorimetry. A genome-wide association study (GWAS) for LDL-C levels identified a variant in CELSR2 and the molecular impact of this variant on gene expression was assessed in skeletal muscle biopsies from 207 participants, followed by functional validation in mouse myoblasts using a luciferase assay. A GWAS in American Indians identified rs12740374 in CELSR2 as the top signal for LDL-C levels (P = 1 × 10-22); further analysis of this variant identified an unexpected correlation with reduced RMR (effect = -44.3 kcal/day/minor-allele) and carbohydrate oxidation rate (effect = -5.21 mg/hour/kg-EMBS). Tagged variants showed a distinct linkage disequilibrium architecture in American Indians, highlighting a potential functional variant, rs6670347 (minor-allele frequency = 0.20). Positioned in the glucocorticoid receptor's core binding motif, rs6670347 is part of a skeletal muscle-specific enhancer. Human skeletal muscle transcriptome analysis showed CELSR2 as the most differentially expressed gene (P = 1.9 × 10-7), with the RMR-lowering minor allele elevating gene expression. Experiments in mouse myoblasts confirmed enhancer-based regulation of CELSR2 expression, dependent on glucocorticoids. Rs6670347 also associated with increased oxidative phosphorylation gene expression; CELSR2 as a regulator of these genes, suggests potential influence on energy metabolism through muscle oxidative capacity. Variants in the CELSR2/PSRC1/SORT1 locus exhibit tissue-specific effects on metabolic traits, with an independent role in muscle metabolism through glucocorticoid signaling.

High-dose cytarabine plus gemtuzumab ozogamicin as consolidation therapy in patients with favorable- or intermediate-risk acute myeloid leukemia.

Previous prospective randomized trials have investigated the efficacy of gemtuzumab ozogamicin in the frontline treatment of acute myeloid leukemia (AML). We evaluated the efficacy of high-dose cytarabine with GO as consolidation therapy in 20 patients with favorable- or intermediate-risk AML in first complete remission. They included six patients with wild-type nucleophosmin (NPM1) core binding factor (CBF), ten with NPM1-mutated non-CBF, and four with wild-type NPM1 non-CBF. The median follow-up for the entire cohort was 62.0months. The three-year overall survival (OS) and relapse-free survival (RFS) rates were 72.2% and 77.8%, respectively. OS and RFS were significantly higher for NPM1-mutated non-CBF AML than for wild-type NPM1 non-CBF AML (p = 0.001). We also examined the CD33 single-nucleotide polymorphism (SNP) rs12459419, which has been reported to influence the therapeutic efficacy of GO and CD33 expression. The CD33 expression ratio was higher in CD33 SNP C/C than in C/T (83.1% vs. 49.8%, p = 0.035), but 3-year OS and RFS did not differ significantly. These results suggest that consolidation therapy with high-dose cytarabine plus GO is highly effective in transplant-ineligible elderly patients and may be a reasonable treatment, especially for NPM1-mutated AML.

Antiviral activity of luteolin against porcine epidemic diarrhea virus in silico and in vitro

BackgroundPorcine epidemic diarrhea virus (PEDV) mainly causes acute and severe porcine epidemic diarrhea (PED), and is highly fatal in neonatal piglets. No reliable therapeutics against the infection exist, which poses a major global health issue for piglets. Luteolin is a flavonoid with anti-viral activity toward several viruses.ResultsWe evaluated anti-viral effects of luteolin in PEDV-infected Vero and IPEC-J2 cells, and identified IC50 values of 23.87 µM and 68.5 µM, respectively. And found PEDV internalization, replication and release were significantly reduced upon luteolin treatment. As luteolin could bind to human ACE2 and SARS-CoV-2 main protease (Mpro) to contribute viral entry, we first identified that luteolin shares the same core binding site on pACE2 with PEDV-S by molecular docking and exhibited positive pACE2 binding with an affinity constant of 71.6 µM at dose-dependent increases by surface plasmon resonance (SPR) assay. However, pACE2 was incapable of binding to PEDV-S1. Therefore, luteolin inhibited PEDV internalization independent of PEDV-S binding to pACE2. Moreover, luteolin was firmly embedded in the groove of active pocket of Mpro in a three-dimensional docking model, and fluorescence resonance energy transfer (FRET) assays confirmed that luteolin inhibited PEDV Mpro activity. In addition, we also observed PEDV-induced pro-inflammatory cytokine inhibition and Nrf2-induced HO-1 expression. Finally, a drug resistant mutant was isolated after 10 cell culture passages concomitant with increasing luteolin concentrations, with reduced PEDV susceptibility to luteolin identified at passage 10.ConclusionsOur results push forward that anti-PEDV mechanisms and resistant-PEDV properties for luteolin, which may be used to combat PED.

Transcriptional upregulation of the myo-inositol biosynthesis pathway is enhanced by NFAT5 in hyperosmotically stressed tilapia cells.

Euryhaline fish experience variable osmotic environments requiring physiological adjustments to tolerate elevated salinity. Mozambique tilapia (Oreochromis mossambicus) possess one of the highest salinity tolerance limits of any fish. In tilapia and other euryhaline fish species, the myo-inositol biosynthesis (MIB) pathway enzymes, myo-inositol phosphate synthase (MIPS) and inositol monophosphatase 1 (IMPA1.1), are among the most upregulated mRNAs and proteins indicating the high importance of this pathway for hyperosmotic (HO) stress tolerance. These abundance changes must be precluded by HO perception and signaling mechanism activation to regulate the expression of MIPS and IMPA1.1 genes. In previous work using a O. mossambicus cell line (OmB), a reoccurring osmosensitive enhancer element (OSRE1) in both MIPS and IMPA1.1 was shown to transcriptionally upregulate these enzymes in response to HO stress. The OSRE1 core consensus (5'-GGAAA-3') matches the core binding sequence of the predominant mammalian HO response transcription factor, nuclear factor of activated T-cells (NFAT5). HO-challenged OmB cells showed an increase in NFAT5 mRNA suggesting NFAT5 may contribute to MIB pathway regulation in euryhaline fish. Ectopic expression of wild-type NFAT5 induced an IMPA1.1 promoter-driven reporter by 5.1-fold (P < 0.01). Moreover, expression of dominant negative NFAT5 in HO media resulted in a 47% suppression of the reporter signal (P < 0.005). Furthermore, reductions of IMPA1.1 (37-49%) and MIPS (6-37%) mRNA abundance were observed in HO-challenged NFAT5 knockout cells relative to control cells. Collectively, these multiple lines of experimental evidence establish NFAT5 as a tilapia transcription factor contributing to HO-induced activation of the MIB pathway.NEW & NOTEWORTHY In our study, we use a multi-pronged synthetic biology approach to demonstrate that the fish homolog of the predominant mammalian osmotic stress transcription factor nuclear factor of activated T-cells (NFAT5) also contributes to the activation of hyperosmolality inducible genes in cells of extremely euryhaline fish. However, in addition to NFAT5 the presence of other strong osmotically inducible signaling mechanisms is required for full activation of osmoregulated tilapia genes.

Revealing molecular determinants governing mambalgin-3 pharmacology at acid-sensing ion channel 1 variants

Acid-sensing ion channels (ASICs) are trimeric proton-gated cation channels that play a role in neurotransmission and pain sensation. The snake venom-derived peptides, mambalgins, exhibit potent analgesic effects in rodents by inhibiting central ASIC1a and peripheral ASIC1b. Despite their distinct species- and subtype-dependent pharmacology, previous structure-function studies have focussed on the mambalgin interaction with ASIC1a. Currently, the specific channel residues responsible for this pharmacological profile, and the mambalgin pharmacophore at ASIC1b remain unknown. Here we identify non-conserved residues at the ASIC1 subunit interface that drive differences in the mambalgin pharmacology from rat ASIC1a to ASIC1b, some of which likely do not make peptide binding interactions. Additionally, an amino acid variation below the core binding site explains potency differences between rat and human ASIC1. Two regions within the palm domain, which contribute to subtype-dependent effects for mambalgins, play key roles in ASIC gating, consistent with subtype-specific differences in the peptides mechanism. Lastly, there is a shared primary mambalgin pharmacophore for ASIC1a and ASIC1b activity, with certain peripheral peptide residues showing variant-specific significance for potency. Through our broad mutagenesis studies across various species and subtype variants, we gain a more comprehensive understanding of the pharmacophore and the intricate molecular interactions that underlie ligand specificity. These insights pave the way for the development of more potent and targeted peptide analogues required to advance our understating of human ASIC1 function and its role in disease.

Development of a Prognostic Model for Overall Survival Adult Patients with Core Binding Factor Acute Myeloid Leukaemia

To analyze the factors affecting overall survival (OS) of adult patients with core-binding factor acute myeloid leukemia (CBF-AML) and establish a prediction model. A total of 216 newly diagnosed patients with CBF-AML in the First Affiliated Hospital of Zhengzhou University from May 2015 to July 2021 were retrospectively analyzed. The 216 CBF-AML patients were divided into the training and the validation cohort at 7∶3 ratio. The Cox regression model was used to analyze the clinical factors affecting OS. Stepwise regression was used to establish the optimal model and the nomogram. Receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used to evaluate the model performance. Age(≥55 years old), peripheral blood blast(≥80%), fusion gene (AML1-ETO), KIT mutations were identified as independent adverse factors for OS. The area under the ROC curve at 3-year was 0.772 and 0.722 in the training cohort and validation cohort, respectively. The predicted value of the calibration curve is in good agreement with the measured value. DCA shows that this model performs better than a single factor. This prediction model is simple and feasible, and can effectively predict the OS of CBF-AML, and provide a basis for treatment decision.

Core Binding Energy Calculations: A Scalable Approach with the Quantum Embedding-Based Equation-of-Motion Coupled-Cluster Method.

We investigated the use of density matrix embedding theory to facilitate the computation of core ionization energies (IPs) of large molecules at the equation-of-motion coupled-cluster singles doubles with perturbative triples (EOM-CCSD*) level in combination with the core-valence separation (CVS) approximation. The unembedded IP-CVS-EOM-CCSD* method with a triple-ζ basis set produced ionization energies within 1 eV of experiment with a standard deviation of ∼0.2 eV for the core65 data set. The embedded variant contributed very little systematic error relative to the unembedded method, with a mean unsigned error of 0.07 eV and a standard deviation of ∼0.1 eV, in exchange for accelerating the calculations by many orders of magnitude. By employing embedded EOM-CC methods, we computed the core ionization energies of the uracil hexamer, doped fullerene, and chlorophyll molecule, utilizing up to ∼4000 basis functions within 1 eV from experimental values. Such calculations are not currently possible with the unembedded EOM-CC method.

Anion-Dependent Strength Scale of Interactions in Ionic Liquids from X-ray Photoelectron Spectroscopy, Ab Initio Molecular Dynamics, and Density Functional Theory.

Using a combination of experiments and calculations, we have gained new insights into the nature of anion-cation interactions in ionic liquids (ILs). An X-ray photoelectron spectroscopy (XPS)-derived anion-dependent electrostatic interaction strength scale, determined using XPS core-level binding energies for IL cations, is presented here for 39 different anions, with at least 18 new anions included. Linear correlations of experimental XPS core-level binding energies for IL cations with (a) calculated core binding energies (ab initio molecular dynamics (AIMD) simulations were used to generate high-quality model IL structures followed by single-point density functional theory (DFT) to obtain calculated core binding energies), (b) experimental XPS core-level binding energies for IL anions, and (c) other anion-dependent interaction strength scales led to three main conclusions. First, the effect of different anions on the cation can be related to ground-state interactions. Second, the variations of anion-dependent interactions with the identity of the anion are best rationalized in terms of electrostatic interactions and not occupied valence state/unoccupied valence state interactions or polarizability-driven interactions. Therefore, the XPS-derived anion-dependent interaction strength scale can be explained using a simple electrostatic model based on electrostatic site potentials. Third, anion-probe interactions, irrespective of the identity of the probe, are primarily electrostatic, meaning that our electrostatic interaction strength scale captures some inherent, intrinsic property of anions independent of the probe used to measure the interaction strength scale.

Coordination Polymer Based on a Triangular Carboxylate Core {Fe(μ3-O)(μ-O2CR)6} and an Aliphatic Diamine.

Interaction of the pre-organized complex of iron(II) trimethylacetate and 1,10-phenanthroline (phen) [Fe2(piv)4(phen)2] (1) (piv = (Me)3CCO2-)) with 1,6-diaminohexane (dahx) in anhydrous acetonitrile yielded a 1D coordination polymer [Fe3O(piv)6(dahx)1.5]n (2) and an organic salt of pivalic acid (H2dahx)(piv)2 (3). The structure of the obtained compounds was determined by single-crystal X-ray diffraction analysis. The phase purity of the complexes was determined by powder X-ray diffraction analysis. According to the single-crystal X-ray analysis, coordination polymer 2 is formed due to the binding of a triangular carboxylate core {Fe3(μ3-O)(μ-piv)6} with an aliphatic diamine ligand. Thermal behavior was investigated for compounds 1 and 2 in an argon atmosphere.