Disappearing Polymorphs in Metal–Organic Framework Chemistry: Unexpected Stabilization of a Layered Polymorph over an Interpenetrated Three-Dimensional Structure in Mercury Imidazolate

The “disappearing polymorph” phenomenon is well established in organic solids, and has had a profound effect in pharmaceutical materials science. The first example of this effect in metal-containing systems in general, and in coordination-network solids in particular, is here reported. Specifically, attempts to mechanochemically synthesize a known interpenetrated diamondoid (dia) mercury(II) imidazolate metal–organic framework (MOF) yielded a novel, more stable polymorph based on square-grid (sql) layers. Simultaneously, the dia-form was found to be highly elusive, observed only as a short-lived intermediate in monitoring solvent-free synthesis and not at all from solution. The destabilization of a dense dia-framework relative to a lower dimensionality one is in contrast to the behavior of other imidazolate MOFs, with periodic density functional theory (DFT) calculations showing that it arises from weak interactions, including structure-stabilizing agostic C−H⋅⋅⋅Hg contacts. While providing a new link between MOFs and crystal engineering of organic solids, these findings highlight a possible role for agostic interactions in directing topology and stability of MOF polymorphs.     

Attraction behaviour of Anagrus nilaparvatae to remote lemongrass (Cymbopogon distans) oil and its volatile compounds

Utilisation of Anagrus nilaparvatae is a promising and effective method for planthoppers manipulation. Twenty-seven components of remote lemongrass (Cymbopogon distans) oil were identified by GC/MS and nine volatiles were selected for behavioural experiments. In this study, we noted that the remote lemongrass oil was attractive to female A. nilaparvatae at concentrations of 0.1 and 1 mg/L. α-Pinene, β-pinene, eucalyptol, carveol and D-carvone attracted female wasps in the dose-dependent bioassays. Blend 1 (a mixture of eucalyptol, D-carvone, carveol, α-pinene, and β-pinene with ratios of remote lemongrass oil volatiles of 625:80:11:5:3) attracted female wasps at 10 mg/L, while blend 2 (a mixture of the same five volatiles at the same loading ratio) attracted them at 0.1 and 1 mg/L. These results suggested that plant essential oils could be attractants for natural enemies to control pests. The ratios of volatiles in the mixtures affect the attractiveness of the synthetic mixtures.     

A note on the two-stage hybrid flow shop problem with dedicated machines

In this paper we introduce a new dominance rule for the two-stage hybrid flow shop problem with dedicated machines. The rule is then used to construct a dominating set. The efficiency of the proposed rule is shown through an analysis of the dominating set cardinality.     

Dislocation density crystalline plasticity modeling of lath martensitic microstructures in steel alloys

A three-dimensional multiple-slip dislocation density-based crystalline formulation, specialized finite-element formulations and Voronoi tessellations adapted to martensitic orientations were used to investigate large strain inelastic deformation modes and dislocation density evolution in martensitic microstructures. The formulation is based on accounting for variant morphologies and orientations, retained austenite and initial dislocation densities that are uniquely inherent to martensitic microstructures. The effects of parent austenite orientation and retained austenite were also investigated for heterogeneous fcc/bcc crystalline structures. Furthermore, the formulation was used to investigate microstructures mapped directly from SEM/EBSD images of martensitic steel alloys. The analysis indicates that variant morphology and orientations have a direct effect on dislocation density accumulation and inelastic localization in martensitic microstructures, and that lath directions, orientations and arrangements are critical characteristics of high strength martensitic deformation and behavior.     

Deciphering the Role of Filamin B Calponin-Homology Domain in Causing the Larsen Syndrome,Boomerang Dysplasia,and Atelosteogenesis Type I Spectrum Disorders via a Computational Approach

Filamins (FLN) are a family of actin-binding proteins involved in regulating the cytoskeleton and signaling phenomenon by developing a network with F-actin and FLN-binding partners. The FLN family comprises three conserved isoforms in mammals: FLNA, FLNB, and FLNC. FLNB is a multidomain monomer protein with domains containing an actin-binding N-terminal domain (ABD 1–242), encompassing two calponin-homology domains (assigned CH1 and CH2). Primary variants in FLNB mostly occur in the domain (CH2) and surrounding the hinge-1 region. The four autosomal dominant disorders that are associated with FLNB variants are Larsen syndrome, atelosteogenesis type I (AOI), atelosteogenesis type III (AOIII), and boomerang dysplasia (BD). Despite the intense clustering of FLNB variants contributing to the LS-AO-BD disorders, the genotype-phenotype correlation is still enigmatic. In silico prediction tools and molecular dynamics simulation (MDS) approaches have offered the potential for variant classification and pathogenicity predictions. We retrieved 285 FLNB missense variants from the UniProt, ClinVar, and HGMD databases in the current study. Of these, five and 39 variants were located in the CH1 and CH2 domains, respectively. These variants were subjected to various pathogenicity and stability prediction tools, evolutionary and conservation analyses, and biophysical and physicochemical properties analyses. Molecular dynamics simulation (MDS) was performed on the three candidate variants in the CH2 domain (W148R, F161C, and L171R) that were predicted to be the most pathogenic. The MDS analysis results showed that these three variants are highly compact compared to the native protein, suggesting that they could affect the protein on the structural and functional levels. The computational approach demonstrates the differences between the FLNB mutants and the wild type in a structural and functional context. Our findings expand our knowledge on the genotype-phenotype correlation in FLNB-related LS-AO-BD disorders on the molecular level, which may pave the way for optimizing drug therapy by integrating precision medicine.     

Synthesis and antimicrobial evaluation of some 1,3-thiazole, 1,3,4-thiadiazole, 1,2,4-triazole, and 1,2,4-triazolo[3,4-b][1,3,4]-thiadiazine derivatives including a 5-(benzofuran-2-yl)-1-phenylpyrazole moiety

Abstract  

Potassium hydrazinecarbodithioate were prepared by treatment of acid hydrazides with carbon disulfide in the presence of potassium hydroxide. Reaction of this potassium salt with hydrazine hydrate, phenacyl bromide, or hydrazonoyl chlorides afforded 1,2,4-triazole, 1,3-thiazole, and 1,3,4-thiadiazoles. Reaction of 1,2,4-triazole with phenacyl bromide or hydrazonoyl chlorides afforded the corresponding 1,2,4-triazolo[3,4-b][1, 3, 4]-thiadiazines. All these new compounds were screened for antibacterial and antifungal activity. Some had promising activity.     

Inclusion complexes of a nucleotide analogue with hydroxypropyl-beta-cyclodextrin

Bis(tbutyl-S-acyl-2-thioethyl)-AraCMP (UA911) is a mononucleotide prodrug developed to overcome some of the cellular resistance to cytotoxic deoxynucleosides analogues. Its use for in vivo studies is limited due to its poor solubility in water. Thus, 2-hydroxypropyl-beta-cyclodextrin (HP-β-CD) was proposed to solubilize UA911 in water, in order to obtain concentrations needed for in vivo experiments. A molar ratio of HP-β-CD: UA911 of 3:1 was sufficient to obtain complete solubilization of the prodrug. The corresponding inclusion complex was characterized by differential scanning calorimetry and ¹H NMR spectroscopy study provided a definitive proof of the formation of the inclusion complex. The complex retained its cytotoxic activity as shown by in vitro cell survival assays on murine leukemia cells, and was evaluated in vivo. HP-β-CD is therefore suitable for the preparation of adequate solutions for the study of the antitumoral activity of nucleotide prodrugs such as UA911.