Search

Purpose: Safety, efficacy, and exploratory biomarker analyses were evaluated in patients with advanced HER2-negative germline breast cancer susceptibility gene (gBRCA)-associated breast cancer enrolled in the BROCADE3 trial who received crossover veliparib monotherapy after disease progression on placebo plus carboplatin/paclitaxel. Patients and Methods: Eligible patients (N = 513) were randomized 2:1 to veliparib plus carboplatin/paclitaxel or placebo plus carboplatin/paclitaxel; patients had variable platinum-free intervals (PFI) at progression. In the placebo arm, patients were eligible to receive crossover veliparib monotherapy (300–400 mg twice daily continuous). Antitumor activity and adverse events were assessed during crossover veliparib treatment. BRCA reversion mutations at crossover were analyzed retrospectively using next-generation sequencing on plasma circulating tumor DNA (ctDNA). Results: Seventy-five patients in the placebo plus carboplatin/paclitaxel arm received ≥1 dose of crossover veliparib postprogression (mean treatment duration: 154 days). Eight of 50 (16%) patients with measurable disease had a RECIST v1.1 response. Activity was greater in patients with PFI ≥180 days compared with Conclusions: Crossover veliparib monotherapy demonstrated limited antitumor activity in patients who experienced disease progression on placebo plus carboplatin/paclitaxel. PFI appeared to affect veliparib activity. BRCA reversion mutations may promote cross-resistance and limit veliparib activity following progression on platinum.

International audience; Covalent Organic Frameworks RIO-13, RIO-12, RIO-11, and RIO-11m were investigated towards their CO2 capture properties by thermogravimetric analysis at 1 atm and 40 °C. These microporous COFs bear in common the azine backbone composed of hydroxy-benzene moieties but differ in the relative number of hydroxyl groups present in each material. Thus, their sorption capacities were studied as a function of their textural and chemical properties. Their maximum CO2 uptake values showed a strong correlation with an increasing specific surface area, but that property alone could not fully explain the CO2 uptake data. Hence, the specific CO2 uptake, combined with DFT calculations, indicated that the relative number of hydroxyl groups in the COF backbone acts as an adsorption threshold, as the hydroxyl groups were indeed identified as relevant adsorption sites in all the studied COFs. Additionally, the best performing COF was thoroughly investigated, experimentally and theoretically, for its CO2 capture properties in a variety of CO2 concentrations and temperatures, and showed excellent isothermal recyclability up to 3 cycles.

Contains fulltext : 235681.pdf (Publisher’s version ) (Open Access) AIMS: Uterine fibroids are benign tumours that cause various complaints. These complaints may significantly compromise quality of life, necessitating a clinical intervention in 25-50% of the affected women. Hysterectomy, myomectomy or embolization may offer symptomatic relief, but are costly, include a recovery period, can cause serious side-effects, sometimes fail to treat symptoms completely and are not always desired by patients. Ulipristal is a conservative long-term treatment that has a fibroid-volume decreasing effect, acceptable side-effects while preserving fertility and may be an alternative to surgical alternatives. Currently, ulipristal is investigated by the European Medicine Agency and suspended from marketing authorization because it may cause drug-induced liver injury (DILI). However, many drugs can cause severe DILI and prospective studies estimate 14-19 DILI cases/100 000 people. METHODS: This overview will discuss the risk-benefit balance between ulipristal and DILI, describe the safety-efficacy balance of ulipristal and its alternative treatments and the arguments that led to the suspension of its marketing authorization. RESULTS: Ulipristal may be associated with DILI resulting in a risk of severe liver injury in 1.5:100 000 patients and fatal liver injury in 0.1:100 000 patients. This risk needs to be weighed against the higher mortality risk of >1:1000 and higher incidence of severe complications after surgery. CONCLUSION: The DILI risk of ulipristal is considerably lower than that of other medicines that are not suspended, nor need additional safety measures. When evaluating drugs and drug safety, risks that apply to the alternative nonpharmacological treatment options should be taken into consideration.

A thermally stable carbocationic covalent organic network (CON), named RIO-70 was prepared from pararosaniline hydrochloride, an inexpensive dye, and triformylphloroglucinol in solvothermal conditions. This nanoporous organic material has shown a specific surface area of 990 m2 g-1 and pore size of 10.3 A. The material has CO2 uptake of 2.14 mmol g-1 (0.5 bar), 2.7 mmol g-1 (1 bar), and 6.8 mmol g-1 (20 bar), the latter corresponding to 3 CO2 molecules adsorbed per pore per sheet. It is shown to be a semiconductor, with electrical conductivity (σ) of 3.17×10-7 S cm-1 , which increases to 5.26×10-4 S cm-1 upon exposure to I2 vapor. DFT calculations using periodic conditions support the findings.

The development of efficient catalytic systems is a fundamental aspect for the straightforward production of chemicals. During the last years, covalent organic frameworks (COFs) emerged as an exciting class of organic nanoporous materials. Due to their pre-designable structure, they can be prepared with distinct physicochemical characteristics, specific pore sizes, and tunable functional groups. Moreover, associated with their stability in different media, these materials are considered promising supports for enzyme immobilization. Herein, it is highlighted the recent literature of enzyme immobilization in COFs, the main immobilization strategies, and the catalytic applications of these composites.

Non-fullerene acceptor (NFA) based organic solar cells have outperformed fullerene-based devices, yet their photophysics is less well understood. Herein, changes in the donor polymer backbone side-...

Sustainability in chemistry heavily relies on heterogeneous catalysis. Enzymes, the main catalyst for biochemical reactions in nature, are an elegant choice to catalyze reactions due to their high activity and selectivity, although they usually suffer from lack of robustness. To overcome this drawback, enzyme-decorated nanoporous heterogeneous catalysts were developed. Three different approaches for Candida antarctica lipase B (CAL-B) immobilization on a covalent organic framework (PPF-2) were employed: physical adsorption on the surface, covalent attachment of the enzyme in functional groups on the surface and covalent attachment into a linker added post-synthesis. The influence of the immobilization strategy on the enzyme uptake, specific activity, thermal stability, and the possibility of its use through multiple cycles was explored. High specific activities were observed for PPF-2-supported CAL-B in the esterification of oleic acid with ethanol, ranging from 58 to 283 U mg-1 , which was 2.6 to 12.7 times greater than the observed for the commercial Novozyme 435.

Background: Veliparib (Vel) is a potent PARP1/2 inhibitor with demonstrated antitumor activity when administered alone or combined with carboplatin and paclitaxel (C/P). The phase 3 randomized, double-blind, multicenter BROCADE3 study (NCT02163694) evaluated the efficacy and safety of Vel + C/P treatment compared with placebo (Pbo) + C/P treatment in patients (pts) with germline BRCA1/2 mutations and HER2-negative metastatic or locally advanced breast cancer (BC). Vel + C/P significantly prolonged progression-free survival (PFS) compared with Pbo + C/P treatment (14.5 months [mo] vs 12.6 mo, hazard ratio [HR]=0.71 [95% CI: 0.57, 0.88]; P=0.002). Previous studies have identified increased acute hematologic toxicity in response to chemotherapy in pts with BC carrying BRCA1 mutations compared with BRCA2 mutations or wildtype BRCA1/2. Herein we report a subgroup analysis of the efficacy and safety of Vel + C/P treatment in pts with BRCA1- or BRCA2-positive BC. Methods: Pts ≥18 years of age who received ≤2 prior lines of cytotoxic chemotherapy for metastatic disease were randomized 2:1 to receive Vel + C/P or Pbo + C/P: Vel (120 mg PO BID) or Pbo on days -2 to 5, C (AUC 6 IV) on day 1, and P (80 mg/m2 IV) on days 1, 8, and 15 in 21-day cycles. Pts who discontinued C/P in the absence of disease progression could continue receiving Vel or Pbo monotherapy (300-400 mg BID continuous). Subgroup analysis of PFS stratified by BRCA1/2 status was preplanned. The primary endpoint was investigator-assessed PFS. Adverse events (AEs) were graded according to NCI CTCAE version 4.0. Ten pts with both BRCA1 and BRCA2 mutations were excluded from the analyses presented here. Results: In the intent-to-treat population, 256 pts had BRCA1 mutations and 243 pts had BRCA2 mutations. The proportion of as-treated pts with BRCA1 or BRCA2 mutations was comparable between the Vel + C/P (51.4% BRCA1, 48.6% BRCA2) and Pbo + C/P (50.9% BRCA1, 49.1% BRCA2) study arms. Investigator-assessed PFS for the Vel + C/P and Pbo + C/P arms was 14.2 mo vs 12.6 mo, respectively, in the BRCA1 subgroup (HR=0.75 [95% CI: 0.55, 1.03]; P=0.073) and 14.6 mo vs 12.6 mo, respectively, in the BRCA2 subgroup (HR=0.69 [95% CI: 0.50, 0.95]; P=0.021). Safety data in the as-treated population are presented in the Table. Regarding any grade AEs, thrombocytopenia and anemia were slightly more frequent in pts in the BRCA1 subgroup compared with the BRCA2 subgroup, whereas pts in the BRCA2 subgroup experienced slightly more frequent nausea, fatigue, and neuropathy. Conclusions: Globally, there was no clinically relevant difference in toxicity between BRCA1 and BRCA2 subgroups. Comparisons between treatment arms were generally consistent with findings in the overall study population, with more frequent thrombocytopenia and anemia of any grade reported in the Vel + C/P arm within both the BRCA1 and BRCA2 subgroups. Vel + C/P treatment improved PFS similarly in both BRCA1 and BRCA2 subgroups over C/P alone. BRCA1-Positive Subgroup (n=253)BRCA2-Positive Subgroup (n=241)Vel + C/P (n=168)Pbo + C/P (n=85)Vel + C/P (n=159)Pbo + C/P (n=82)Any grade AE [≥50% of pts], n (%)Any event167 (99.4)85 (100)158 (99.4)82 (100)Neutropenia151 (89.9)78 (91.8)140 (88.1)74 (90.2)Thrombocytopenia140 (83.3)66 (77.6)124 (78.0)54 (65.9)Anemia139 (82.7)64 (75.3)122 (76.7)52 (63.4)Nausea118 (70.2)49 (57.6)119 (74.8)58 (70.7)Alopecia89 (53.0)43 (50.6)89 (56.0)41 (50.0)Fatigue79 (47.0)37 (43.5)87 (54.7)48 (58.5)Peripheral sensory neuropathy69 (41.1)37 (43.5)82 (51.6)49 (59.8)Any grade ≥3 AE [≥30% of pts], n (%)Any event164 (97.6)82 (96.5)152 (95.6)77 (93.9)Anemia73 (43.5)31 (36.5)67 (42.1)35 (42.7)Leukopenia54 (32.1)20 (23.5)44 (27.7)25 (30.5)Neutropenia136 (81.0)72 (84.7)131 (82.4)67 (81.7)Thrombocytopenia72 (42.9)30 (35.3)59 (37.1)18 (22.0)Serious AEs, n (%)58 (34.5)26 (30.6)56 (35.2)22 (26.8)AEs of special interest, n (%)Infections within 14 days of neutropenia64 (38.1)34 (40.0)59 (37.1)25 (30.5)Hemorrhages within 14 days of thrombocytopenia14 (8.3)5 (5.9)17 (10.7)7 (8.5)Any AE leading to study drug discontinuation not due to disease progression, n (%)16 (9.5)5 (5.9)15 (9.4)4 (4.9)Any AE leading to study drug interruption, n (%)153 (91.1)77 (90.6)139 (87.4)67 (81.7)Any AE leading to study drug reduction, n (%)28 (16.7)6 (7.1)27 (17.0)7 (8.5)Any AE leading to death with reasonable possibility related to study drug, n (%)0 (0)0 (0)0 (0)0 (0)AE, adverse event; BRCA, breast cancer susceptibility gene; C/P, carboplatin plus paclitaxel; Pbo, placebo; pts, patients; Vel, veliparib. Citation Format: Hans Wildiers, Jean-Pierre Ayoub, Michael Friedlander, Bella Kaufman, Banu K. Arun, Hyo S. Han, Shannon L. Puhalla, David Maag, Dai Feng, Christine K. Ratajczak, Bruce A. Bach, Véronique Diéras. Safety and efficacy of veliparib plus carboplatin/paclitaxel in patients with HER2-negative metastatic or locally advanced breast cancer: A subgroup analysis of germline BRCA1 or BRCA2 mutations from the phase 3 BROCADE3 trial [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS11-03.

Angiogenesis is critical for many diseases. Previously, we reported that Down Syndrome Candidate Region 1 isoform 1L (DSCR1–1L) was one of the most up-regulated genes in endothelial cells induced by VEGF and histamine, and regulated endothelial cell proliferation and Matrigel angiogenesis in mice. However, it was not known whether DSCR1–1L regulated angiogenesis in vivo and what was the molecular mechanism underlying it. In this study, gene knockdown and overexpression models were established to study the role of DSCR1–1L in angiogenesis in vivo. Further, the downstream regulatory target of DSCR1–1L was explored with molecular biological methods in vascular endothelial cells. We found that DSCR1–1L shRNAs significantly inhibited angiogenesis induced by VEGF in mice (p < 0.0001). In the gain-of-function assay, overexpression of DSCR1–1L cDNA in mouse endothelium of EC-FH-DSCR1–1L transgenic mice was sufficient to induce angiogenesis significantly (p < 0.01). DSCR1–1L regulated angiogenesis in the early stage by down-regulation of the VE-cadherin expression through targeting its transcription, but not mRNA stability. Three DSCR1–1L-targeted DNA elements in the VE-cadherin promoter were identified by promoter reporter assays, among which, a novel specific transcriptional complex was found. The DNA sequence (CTTCTG) in the VE-cadherin promoter was identified to directly interact with proteins by Electrophoresis Mobility Shift Assays and DNase I footprint assay. Hence, DSCR1–1L is an excellent therapeutic target for angiogenic diseases through down-regulating the formation of a novel transcriptional complex on the VE-cadherin promoter. DSCR1–1L shRNAs and cDNA have the potential to be developed for clinical application. Our results also contribute significantly to the field of mechanistic studies.

Thalidomide analogues exert their therapeutic effects by binding to the CRL4CRBN E3 ubiquitin ligase, promoting ubiquitination and subsequent proteasomal degradation of specific protein substrates. Drug-induced degradation of IKZF1 and IKZF3 in B-cell malignancies demonstrates the clinical utility of targeting disease-relevant transcription factors for degradation. Here, we found that avadomide (CC-122) induces CRBN-dependent ubiquitination and proteasomal degradation of ZMYM2 (ZNF198), a transcription factor involved in balanced chromosomal rearrangements with FGFR1 and FLT3 in aggressive forms of hematologic malignancies. The minimal drug-responsive element of ZMYM2 is a zinc-chelating MYM domain and is contained in the N-terminal portion of ZMYM2 that is universally included in the derived fusion proteins. We demonstrate that avadomide has the ability to induce proteasomal degradation of ZMYM2–FGFR1 and ZMYM2–FLT3 chimeric oncoproteins, both in vitro and in vivo. Our findings suggest that patients with hematologic malignancies harboring these ZMYM2 fusion proteins may benefit from avadomide treatment. Significance: We extend the potential clinical scope of thalidomide analogues by the identification of a novel avadomide-dependent CRL4CRBN substrate, ZMYM2. Avadomide induces ubiquitination and degradation of ZMYM2–FGFR1 and ZMYM2–FLT3, two chimeric oncoproteins involved in hematologic malignancies, providing a proof of concept for drug-induced degradation of transcription factor fusion proteins by thalidomide analogues.

Carbon is an extremely versatile element and can generate a plethora of structures with distinct properties. Proposing new possible metastable allotropic structures for carbon has been the subject of increasing interest over the past few years. In this contribution, we present a new carbon allotrope, named ABF-Carbon, based on the connection of spiropentadiene molecular motif and sp3 carbon atoms. This new structure is a metastable carbon allotrope formed by 6 carbon atoms, being 2 sp2 and 4 sp3, in a body-centered tetragonal with space group I4m2 (space group 119) and point group D2d11. By first-principles calculations using the density functional theory (DFT), we predict that this new structure is mechanically and structurally stable and presents thermal stability up to 900 K. The calculations also show that ABF-Carbon presents a direct bandgap of 2.39 eV and higher cohesive energy than other carbon allotropes, such as T-Carbon and Y-Carbon/1-diamondyne.

All-organic infrared (IR)-to-visible upconversion organic light-emitting diodes (OLEDs) with an IR sensitivity up to 1100 nm were fabricated using a low-band-gap polymer as the organic IR sensitizi...

The co-halogenation reaction of alkynes with tri-bromoisocyanuric acid in acetic acid, followed by aqueous work-up produced α,α-di-bromoketones (44-84%), while the reaction in aqueous acetonitrile in the presence of KBr produced vicinal di-bromoalkenes (66-86%). The usefulness of the methodology was demonstrated employing green metrics for the comparison of TBCA with analogous N-halo reagents in co-halogenation reactions of alkynes.

Solution-processable small molecules (SMs) that can serve as donors in bulk-heterojunction (BHJ) solar cells are practical alternatives to their polymer counterparts. However, SM–fullerene blends c...

The connectivity between ordered domains in semiconducting polymers has been implicated as a bottleneck to charge transport. Crystallites in stiff-chain polymers have been shown to have ordered quasi-epitaxial domain boundaries using electron microscopy, but the factors affecting their formation have not been elucidated. A series of poly(benzo[1,2-b:4,5-b′]dithiophene–thieno[3,4-c]pyrrole-4,6-dione) (PBDTTPD) polymers with varying side chains were studied to determine the role of molecular structure on the formation of domain boundaries. Grazing incidence wide-angle X-ray scattering revealed the texture of ordered domains in these polymers as a function of thickness and thermal processing. High-resolution transmission electron microscopy (HRTEM) of thin films revealed that crystallites overlapped in an ordered fashion based on a geometric rule for the length of the crystallographic repeat length and the separation of the backbone by the side chains. All of the PBDTTPD polymers had polymorphic crystallites...

Background: Depressive symptoms and impaired physical functioning are prevalent among older adults. Supplementation with vitamin D might improve both conditions, particularly in persons with low vitamin D status. \ud Objective: The D-Vitaal study primarily aimed to investigate the effect of vitamin D supplementation on depressive symptoms, functional limitations and physical performance in a high-risk older population with low vitamin D status. Secondary aims included examining the effect of vitamin D supplementation on anxiety symptoms, cognitive functioning, mobility, hand grip strength and health-related quality of life.\ud Design: This study was a randomized placebo-controlled trial with 155 participants aged 60-80 years who had clinically relevant depressive symptoms, ≥1 functional limitation and serum 25-hydroxyvitamin D (25(OH)D) concentrations of 15-50/70 nmol/L (depending on season). Participants received 1200 IU/day vitamin D3 (n=76) or placebo tablets (n=77) for 12 months. Serum 25(OH)D was measured at baseline and 6 months; outcomes were assessed at baseline, 6 and 12 months. Linear mixed models analyses were conducted according to the intention-to-treat principle to assess the effect of the intervention.\ud Results: The supplementation increased serum 25(OH)D concentrations in the intervention group to a mean of 85 nmol/L (SD: 16) against 43 nmol/L (SD: 18) in the placebo group after 6 months (P

The development of complexes featuring low‐valent, multiply bonded metal centers is an exciting field with several potential applications. In this work, we describe the design principles and extensive computational investigation of new organometallic platforms featuring the elusive manganese‐manganese bond stabilized by experimentally realized N‐heterocyclic carbenes (NHCs). By using DFT computations benchmarked against multireference calculations, as well as MO‐ and VB‐based bonding analyses, we could disentangle the various electronic and structural effects contributing to the thermodynamic and kinetic stability, as well as the experimental feasibility, of the systems. In particular, we explored the nature of the metal‐carbene interaction and the role of the ancillary η 6 coordination to the generation of Mn2 systems featuring ultrashort metal‐metal bonds, closed‐shell singlet multiplicities, and positive adiabatic singlet‐triplet gaps. Our analysis identifies two distinct classes of viable synthetic targets, whose electrostructural properties are thoroughly investigated., The Mn2 survival guide. DFT calculations were used to design synthetically achievable compounds featuring ultrashort Mn−Mn bonds stabilized by N‐heterocyclic carbenes (NHCs). We investigated the nature of the metal–carbene interaction and the role of the ancillary η 6 coordination in the generation of ultrashort Mn2 bonds in organometallic platforms featuring closed‐shell singlet multiplicities and positive adiabatic singlet–triplet gaps. Our analysis identified two classes of potential synthetic targets, whose electrostructural properties were thoroughly examined.

Toxoplasma gondiiis a ubiquitous, intracellular parasite that envelopes its parasitophorous vacuole with a protein-laden membrane (PVM). The PVM is critical for interactions with the infected host cell such as nutrient transport and immune defense. Only a few parasite and host proteins have so far been identified on the host-cytosolic side of the PVM. We report here the use of human foreskin fibroblasts expressing the proximity-labeling enzyme miniTurbo, fused to a domain that targets it to this face of the PVM, in combination with quantitative proteomics to specifically identify proteins present at this crucial interface. Out of numerous human and parasite proteins with candidate PVM localization, we validate three novel parasite proteins (TGGT1_269950, TGGT1_215360, and TGGT1_217530) and four new host proteins (PDCD6IP/ALIX, PDCD6, CC2D1A, and MOSPD2) as localized to the PVM in infected human cells through immunofluorescence microscopy. These results significantly expand our knowledge of proteins present at the PVM and, given that three of the validated host proteins are components of the ESCRT machinery, they further suggest that novel biology is operating at this crucial host-pathogen interface.ImportanceToxoplasmais an intracellular pathogen which resides and replicates inside a membrane-bound vacuole in infected cells. This vacuole is modified by both parasite and host proteins which participate in a variety of host-parasite interactions at this interface, including nutrient exchange, effector transport, and immune modulation. Only a small number of parasite and host proteins present at the vacuolar membrane and exposed to the host cytosol have thus far been identified. Here we report the identification of several novel parasite and host proteins present at the vacuolar membrane using enzyme-catalyzed proximity-labeling, significantly increasing our knowledge of the molecular players present and novel biology occurring at this crucial interface.

PAX5 and EBF1 work synergistically to regulate genes that are involved in B lymphocyte differentiation. We used the KIS-1 diffuse large B cell lymphoma cell line, which is reported to have elevated levels of PAX5 expression, to investigate the mechanism of EBF1- and PAX5-regulated gene expression. We demonstrate the lack of expression of hallmark B cell genes, including CD19, CD79b, and EBF1, in the KIS-1 cell line. Upon restoration of EBF1 expression we observed activation of CD19, CD79b and other genes with critical roles in B cell differentiation. Mass spectrometry analyses of proteins co-immunoprecipitated with PAX5 in KIS-1 identified components of the MLL H3K4 methylation complex, which drives histone modifications associated with transcription activation. Immunoblotting showed a stronger association of this complex with PAX5 in the presence of EBF1. Silencing of KMT2A, the catalytic component of MLL, repressed the ability of exogenous EBF1 to activate transcription of both CD19 and CD79b in KIS-1 cells. We also find association of PAX5 with the MLL complex and decreased CD19 expression following silencing of KMT2A in other human B cell lines. These data support an important role for the MLL complex in PAX5-mediated transcription regulation.

Arylation reactions are an important class of reactions and allow the synthesis of natural and synthetic products. Despite the efficient, but high cost and toxic methodologies involving transition metals, radical arylations have gained importance after the advent of photoredox catalysis. Arylation of enol acetates is an important tool for obtaining aryl ketones but the scope of the reaction is limited to the pattern of substitution at phenyl radical and α-carbon of the enol. Theoretical calculations ((U)BHandHLYP/6-311G**) show that the polar effect is the key factor in this reaction. A good correlation of calculated rate constants with field effect explained why phenyl radicals with electron-withdrawing groups react faster toward enol acetate. The presence of alkyl groups at α carbon at the enol showed some influence of enthalpic effect but strong influence of steric effect, evidenced by great correlations with Taft and Charton parameters. Finally, substitution at β carbon showed no significant effect at reaction rates.

This work presents some modifications in the post-synthetic processing for a classical arsenic reagent: AsI3. In comparison with the widely used analog, the trichloride, arsenic triiodide presents several advantages such as low toxicity, air stability, and low volatility. It was used as a synthetic precursor in the preparation of a variety of arsenic(III) derivatives like arsines, arsenites, and thioarsenites. Besides that, AsI3 was submitted to a diversity-oriented Grignard reaction in the preparation of a homologous series of trialkyl arsines ranging from AsC3H9 to AsC12H27. The series was analyzed by comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry to provide a trialkyl arsines library that can be used for the direct analysis of natural samples.

Meniscus-guided coating methods, such as zone casting, dip coating and solution shearing, are scalable laboratory models for large-area solution coating of functional materials for thin-film electronics. Unfortunately, the general lack of understanding of how the coating parameters affect the dry-film morphology upholds trial-and-error experimentation and delays lab-to-fab translation. We present herein a model that predicts dry-film morphologies produced by meniscus-guided coating of a crystallizing solute. Our model reveals how the interplay between coating velocity and evaporation rate determines the crystalline domain size, shape anisotropy and regularity. If coating is fast, evaporation drives the system quickly past supersaturation, giving isotropic domain structures. If coating is slow, depletion due to crystallization stretches domains in the coating direction. The predicted morphologies have been experimentally confirmed by zone-casting experiments of the organic semiconductor 4-tolyl-bithiophenyl-diketopyrrolopyrrole. Although here we considered a small molecular solute, our model can be applied broadly to polymers and organic-inorganic hybrids such as perovskites.

A new family of carbon allotropes, called n-diamondynes, is proposed based on the insertion of acetylide units between the sp3-hybridized carbon atoms of diamond. We perform density-functional theory calculations in order to predict their structural, mechanical, vibrational and electronic properties. The variation of these properties with respect to the number of the acetylide moieties is systematically investigated. In addition, using grand-canonical Monte-Carlo simulations with classical force fields, we explore the potential of these porous materials for gas adsorption.

Covalent organic frameworks (COFs) were prepared through imine condensation reaction of hydrazine hydrate with hydroxy-1,3,5-triformylbenzenes, containing a varying number of hydroxyl groups, affording the microporous materials called RIO-11, RIO-12, and RIO-13. The role of intramolecular hydrogen bonding formation (conformational locking effects) in the crystallinity of the resulting COFs was evaluated. The results indicate that the increase of the number of conformational locks increases the symmetry of moieties during nucleation and crystal growth, resulting in less defects in the product structure. The use of aniline as modulator, with in situ formation of an intermediate imine, was also evaluated and proved to be beneficial in the case where the number of conformational locks is insufficient to afford high crystallinity. The use of the modulator for RIO-11 resulted in greater crystallinity and a 5.3-fold increase of its pristine BET surface area. Narrower monomodal pore size distributions, with cylin...

End-group-directed molecular self-assembly can be an effective strategy in the design of “organic electronics” amenable to specific morphologies and charge transport patterns for device applications. In this study, we report on the design, self-ordering, and transistor characteristics of an analogous set of pyrene-functionalized diketopyrrolopyrroles (DPP; namely, SM1–3) obtained by “successive incorporation” of DPP motifs. The well-defined pyrene-substituted DPP analogues are systematically examined in correlation of (i) the number of incorporated DPP motifs in the π-extended main-chain and (ii) the solution-processing conditions employed for the thin film formation. Solvent vapor enhanced drop-casting (SVED) from chloroform (CHCl3) and tetrahydrofuran (THF) are found to promote very distinct, long-range morphologies of SM1–3. During THF-mediated SVED, the growth of a one-dimensional fiber of SM1–3 originates from the formation of initial aggregates in THF. In particular, extending the π-conjugation of t...

A structurally stable microporous metallic carbon allotrope, poly(spiro[2.2]penta-1,4-diyne) or, for short, spiro-carbon, with I41 /amd (D4h ) symmetry is predicted by first-principles calculations using density functional theory (DFT). The calculations of electronic, vibrational, and structural properties show that spiro-carbon has lower relative energy than other elusive carbon allotropes such as T-Carbon and 1-diamondyne (Y-Carbon). Its structure can be pictured as a set of trans-cisoid-polyacetylene chains tangled and interconnected together by sp3 carbon atoms. Calculations reveal a metallic electronic structure arising from an "intrinsic doping" of trans-cisoid-polyacetylene chains with sp3 carbon atoms. Possible synthetic routes and various simulated spectra (XRD, NMR, and IR absorption) are provided in order to guide future efforts to synthesize this novel material.

The tandem TUDOR domains present in the non-catalytic C-terminal half of the KDM4A, 4B and 4C enzymes play important roles in regulating their chromatin localizations and substrate specificities. They achieve this regulatory role by binding to different tri-methylated lysine residues on histone H3 (H3-K4me3, H3-K23me3) and histone H4 (H4-K20me3) depending upon the specific chromatin environment. In this work, we have used a 2D-NMR based fragment screening approach to identify a novel fragment (1a), which binds to the KDM4A-TUDOR domain and shows modest competition with H3-K4me3 binding in biochemical as well as in vitro cell based assays. A co-crystal structure of KDM4A TUDOR domain in complex with 1a shows that the fragment binds stereo-specifically to the methyl lysine binding pocket forming a network of strong hydrogen bonds and hydrophobic interactions. We anticipate that the fragment 1a can be further developed into a novel allosteric inhibitor of the KDM4 family of enzymes through targeting their C-terminal tandem TUDOR domain.

FeCl3·6H2O was anchored in the pores of a layered crystalline imine-based mesoporous covalent organic framework (TPB-DMTP-COF) with surface area of 1200 m2/g and pores of 34 A, affording the material FeCl3@TPB-DMTP-COF that worked as iron based heterogeneous catalyst. This new porous material was used in the decarboxylative oxidation cross-coupling reaction of cinnamic acids showing good to excellent catalytic activity with good chemical yields and short reaction time. FeCl3@TPB-DMTP-COF exhibit moderate surface area (235 m2/g) and high thermal and chemical stability allowing it use for several catalytic cycles.

Small-molecule “nonfullerene” acceptors are promising alternatives to fullerene (PC61/71BM) derivatives often used in bulk heterojunction (BHJ) organic solar cells; yet, the efficiency-limiting processes and their dependence on the acceptor structure are not clearly understood. Here, we investigate the impact of the acceptor core structure (cyclopenta-[2,1-b:3,4-b′]dithiophene (CDT) versus indacenodithiophene (IDTT)) of malononitrile (BM)-terminated acceptors, namely CDTBM and IDTTBM, on the photophysical characteristics of BHJ solar cells. Using PCE10 as donor polymer, the IDTT-based acceptor achieves power conversion efficiencies (8.4%) that are higher than those of the CDT-based acceptor (5.6%) because of a concurrent increase in short-circuit current and open-circuit voltage. Using (ultra)fast transient spectroscopy we demonstrate that reduced geminate recombination in PCE10:IDTTBM blends is the reason for the difference in short-circuit currents. External quantum efficiency measurements indicate that...

Tin-doped indium oxide (ITO) transparent conducting electrodes are widely used across the display industry, and are currently the cornerstone of photovoltaic device developments, taking a substantial share in the manufacturing cost of large-area modules. However, cost and supply considerations are set to limit the extensive use of indium for optoelectronic device applications and, in turn, alternative transparent conducting oxide (TCO) materials are required. In this report, we show that aluminum-doped zinc oxide (AZO) thin films grown by atomic layer deposition (ALD) are sufficiently conductive and transparent to outperform ITO as the cathode in inverted polymer solar cells. Reference polymer solar cells made with atomic-layer-deposited AZO cathodes, PCE10 as the polymer donor and PC71BM as the fullerene acceptor (model systems), reach power conversion efficiencies of ca. 10% (compared to ca. 9% with ITO-coated glass), without compromising other figures of merit. These ALD-grown AZO electrodes are promising for a wide range of optoelectronic device applications relying on TCOs.

Pure-silica chabazite is a promising material for capturing CO2 from flue gases in adsorption-based carbon capture and storage. The adsorption of CO2 and N2 on pure-silica chabazite has been studied at the molecular level with Density Functional Theory in the finite cluster/supermolecule approach. Molar enthalpies of adsorption of CO2 and N2 have been calculated with excellent agreement (

The mechanism of electrophilic aromatic substitution (SEAr) is still matter of debate and interest in the literature. In this work, the Friedel-Crafts alkylation and the acylation in the gas phase were investigated in the context of the unified mechanism for SEAr. In this unified proposal three kinds of intermediates can potentially be formed: oriented and unoriented π-complexes, intimate single electron transfer (SET) intermediates and σ-complexes. Quantum chemical calculations at M06-2X/6–311++G(d,p) level were carried out for the investigation of the reaction of benzene with acetyl and tert-butyl ions as model non-oxidant electrophiles for acylation and alkylation, respectively, in the gas phase. It was found that both the tert-butyl and the acetyl cations prefer to form oriented π-complexes. Both electrophiles do not react through a SET pathway with benzene. The π-complex between tert-butyl cation and benzene can evolve to a σ-complex, while in the case of the acetyl cation and benzene the σ-complex was not found as a minimum on the potential energy surface. Instead, it corresponds to a transient species or a very shallow minimum. The outcome of this is that the π-complex would only react with the aromatic ring evolving to the product with nucleophilic assistance by a species of the reaction medium, in either through a concerted mechanism or a specific interaction. This is also observed for aromatics with low ionization energies/nucleophilicities. However, very electron rich aromatic systems afford σ-complexes, and as their ionization energies increases (i.e., less nucleophilic), the more the resulting complex resembles a π-complex, more or less continuously. This suggests out that electrophilic aromatic substitution reactions cannot be rationalized within a single mechanistic framework. Instead, a continuum of mechanistic possibilities may be involved.

Branched-alkyl-substituted poly(thieno[3,4-c]pyrrole-4,6-dione-alt-3,4-difluorothiophene) (PTPD[2F]T) can be used as a polymer acceptor in bulk heterojunction (BHJ) solar cells with a low-band-gap polymer donor (PCE10) commonly used with fullerenes. The “all-polymer” BHJ devices made with PTPD[2F]T achieve efficiencies of up to 4.4 %. While, to date, most efficient polymer acceptors are based on perylenediimide or naphthalenediimide motifs, our study of PTPD[2F]T polymers shows that linear, all-thiophene systems with adequately substituted main chains can also be conducive to efficient BHJ solar cells with polymer donors.