Domain-based local pair natural orbital methods within the correlation consistent composite approach

Ab initio composite approaches have been utilized to model and predict main group thermochemistry within 1 kcal mol⁻¹, on average, from well-established reliable experiments, primarily for molecules with less than 30 atoms. For molecules of increasing size and complexity, such as biomolecular complexes, composite methodologies have been limited in their application. Therefore, the domain-based local pair natural orbital (DLPNO) methods have been implemented within the correlation consistent composite approach (ccCA) framework, namely DLPNO-ccCA, to reduce the computational cost (disk space, CPU (central processing unit) time, memory) and predict energetic properties such as enthalpies of formation, noncovalent interactions, and conformation energies for organic biomolecular complexes including one of the largest molecules examined via composite strategies, within 1 kcal mol⁻¹, after calibration with 119 molecules and a set of linear alkanes. © 2019 Wiley Periodicals, Inc.     

Boosting Conjugate Addition to Nitroolefins Using Lithium Tetraorganozincates: Synthetic Strategies and Structural Insights

We report the first transition metal catalyst- and ligand-free conjugate addition of lithium tetraorganozincates (R₄ZnLi₂) to nitroolefins. Displaying enhanced nucleophilicity combined with unique chemoselectivity and functional group tolerance, homoleptic aliphatic and aromatic R₄ZnLi₂ provide access to valuable nitroalkanes in up to 98 % yield under mild conditions (0 °C) and short reaction time (30 min). This is particularly remarkable when employing β-nitroacrylates and β-nitroenones, where despite the presence of other electrophilic groups, selective 1,4 addition to the C=C is preferred. Structural and spectroscopic studies confirmed the formation of tetraorganozincate species in solution, the nature of which has been a long debated issue, and allowed to unveil the key role played by donor additives on the aggregation and structure of these reagents. Thus, while chelating N,N,N’,N’-tetramethylethylenediamine (TMEDA) and (R,R)-N,N,N’,N’-tetramethyl-1,2-diaminocyclohexane (TMCDA) favour the formation of contacted-ion pair zincates, macrocyclic Lewis donor 12-crown-4 triggers an immediate disproportionation process of Et₄ZnLi₂ into equimolar amounts of solvent-separated Et₃ZnLi and EtLi.     

Blocking Sets of Certain Line Sets Related to a Conic

In this paper we classify point sets of minimum size of two types (1) point sets meeting all secants to an irreducible conic of the desarguesian projective plane PG(2,q), q odd; (2) point sets meeting all external lines and tangents to a given irreducible conic of the desarguesian projective plane PG(2,q), q even.     

Effects of NR1 splicing on NR1/NR3B-type excitatory glycine receptors

Background  

N-methyl-D-aspartate receptors (NMDARs) are the most complex of ionotropic glutamate receptors (iGluRs). Subunits of this subfamily assemble into heteromers, which – depending on the subunit combination – may display very different pharmacological and electrophysiological properties. The least studied members of the NMDAR family, the NR3 subunits, have been reported to assemble with NR1 to form excitatory glycine receptors in heterologous expression systems. The heterogeneity of NMDARs in vivo is in part conferred to the receptors by splicing of the NR1 subunit, especially with regard to proton sensitivity.     

Dissipative operators and additive perturbations in locally convex spaces

Let be a densely defined operator on a Banach space X. Characterizations of when generates a C₀‐semigroup on X are known. The famous result of Lumer and Phillips states that it is so if and only if is dissipative and is dense in X for some . There exists also a rich amount of Banach space results concerning perturbations of dissipative operators. In a recent paper Tyran–Kamińska provides perturbation criteria of dissipative operators in terms of ergodic properties. These results, and others, are shown to remain valid in the setting of general non–normable locally convex spaces. Applications of the results to concrete examples of operators on function spaces are also presented.     

Assessing views of coaching via a video-based tool

Mathematics coaches represent a unique group of didacticians, or individuals who work with practicing teachers. Twenty-eight mathematics coaches participated in this exploratory study, which used video viewing to examine the coach–teacher dynamic. To gather data about participants’ views of effective coaching practices, we developed the Video Assessment of Coaching instrument, which provided coaches with opportunities to express their views of effective practice and implementation. The participants expressed views of effective coaching that often did not align with those of coaching authors. The significance of this research lies in its efforts to document the views that mathematics coaches develop as practitioners, as an early step in the examination of the relationships between the views of coaches and coaches’ effectiveness in improving teacher practice, knowledge, and attitudes.     

Quinazoline Derivatives Designed as Efflux Pump Inhibitors: Molecular Modeling and Spectroscopic Studies

Multidrug resistance of bacteria is a worrying concern in the therapeutic field and an alternative method to combat it is designing new efflux pump inhibitors (EPIs). This article presents a molecular study of two quinazoline derivatives, labelled BG1189 and BG1190, proposed as EPIs. In silico approach investigates the pharmacodynamic and pharmacokinetic profile of BG1189 and BG1190 quinazolines. Molecular docking and predicted ADMET features suggest that BG1189 and BG1190 may represent attractive candidates as antimicrobial drugs. UV-Vis absorption spectroscopy was employed to study the time stability of quinazoline solutions in water or in dimethyl sulfoxide (DMSO), in constant environmental conditions, and to determine the influence of usual storage temperature, normal room lighting and laser radiation (photostability) on samples stability. The effects of irradiation on BG1189 and BG1190 molecules were also assessed through Fourier-transform infrared (FTIR) spectroscopy. FTIR spectra showed that laser radiation breaks some chemical bonds affecting the substituents and the quinazoline radical of the compounds.     

Photoactivated Psoralens Elicit Defense Genes and Phytoalexin Production in the Pea Plant

In the pea plant ( Pisum sativum ), compounds that intercalate into DNA induce the production of ∼20 major proteins similar to the pattern induced during nonhost disease resistance to the bean fungal pathogen, Fusarium solani f.sp. phaseoli . The pea phytoalexin, pisatin, as well as RNA homologous to several disease-resistance response (DRR) genes accumulate following treatment with these compounds. Psoralen was chosen to characterize this interaction further because it intercalates into DNA and, following irradiation with 365 nm UV light (UV₃₆₅), forms covalent bonds with pyrimidines on either or both strands of DNA. This produces monoadducts or cross-links, respectively. Dose experiments showed that 60 μg/mL 4'-aminomethyl-4,5',8-trimethylpsoralen followed by 18 J/cm² UV₃₆₅ was sufficient to produce an accumulation of pisatin similar to that produced in response to the fungus. Under these inducing conditions, there was an average of 0.19 adducts per kb of pea genomic DNA. The accumulation of pisatin and the RNA of several DRR genes by psoralen required photoactivation, which suggests that covalent binding to DNA was necessary for induction. As the promoters of several putative fungal-induced pea genes contain long stretches of d(AT)_n, which is the preferred psoralen photobinding site, restriction fragments spanning DRR genes were examined after in vivo psoralen treatment. The rate of crosslinking was compared between fungal-induced and noninduced genes using a modified Southern blot analysis. Implications of the induction of the DRR due to psoralen binding are discussed.     

Reactions of Molecules with Two Equivalent Functional Groups. 5. Anomalous Reactivity of 1,10-Cyclooctadecanedione. Crystal and Molecular Structures of cis,cis-1,10-Diphenyl-1,10-cyclooctadiene and the Stereoisomers of 1,10-Diphenyl-1,10-cyclooctadecanediol(1)

The reaction of the title diketone (3) with phenyl Grignard produces (with rate constant k(1)) the conjugate base (6-M) of 10-hydroxy-10-phenylcyclooctadecanone (6), which is subsequently converted (with rate constant k(2)) to the conjugate base of the title diol, as a mixture of the cis (7, 55%) and trans (8, 45%) isomers. The ratio k(2)/k(1), 2.2 +/- 0.4, indicates that the carbonyl group in 6-M is 4.4 times as reactive as each carbonyl in 3. Competition experiments further demonstrate that the relative rates (per carbonyl) for addition of phenylmagnesium bromide to 3, 10-methylenecyclooctadecanone (11), and cyclopentadecanone (12) are 1.0:0.60:1.92. Possible reasons for this order of reactivity are discussed. Diols 7 and 8 undergo facile double dehydration to form the title diene 13, which is predicted by molecular mechanics calculations to be the most stable of the four possible symmetrical diene isomers. The structures of 7, 8, and 13 were secured by single-crystal X-ray studies.