Applying reticular synthesis to the design of Cu-based MOFs with mechanically interlocked linkers

The concept of“robust dynamics”describes the incorporation of mechanically interlocked molecules(MIMs)into metal-organic framework(MOF)materials such that large amplitude motions(e.g.,rotation or translation of a macrocycle)can occur inside the free volume pore of the MOF.To aid in the preparation of such materials,reticular synthesis was used herein to design rigid molecular building blocks with predetermined ordered structures starting from the well-known MOF NOTT-101.New linkers were synthesized that have a T-shape,based on a triphenylene tetra-carboxylate strut,and their incorporation into Cu(II)-based MOFs was investigated.The single-crystal structures of three new MOFs,UWCM-12(fof),β-UWCM-13(loz),UWCM-14(lil),with naked T-shaped linkers were determined;β-UWCM-13 is the first reported example of the loz topology.A fourth MOF,UWDM-14(lil)is analogous to UWCM-14(lil)but contains a[2]rotaxane linker.Variable-temperature,²H solid-state NMR was used to probe the dynamics of a 24-membered macrocycle threaded onto the MOF skeleton.     

Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

Preparation and physicochemical study of jute and glass composites of epoxy resin of (2E, 6E)-bis(4-hydroxybenzylidene)cyclohexanone

Polymer Bulletin - Jute and glass composites of epoxy resin of (2E, 6E)-bis(4-hydroxybenzylidene)cyclohexanone (EBHBC) were prepared by compressing molding technique using three different hardeners...     

The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.     

Synthesis and Application of Novel Nano Fe-BTC/GO Composites as Highly Efficient Photocatalysts in the Dye Degradation

Topics in Catalysis - Nano Fe-BTC/graphene oxide (GO) composites were successfully synthesized by hydrothermal treatment with a microwave-assisted method. Samples were characterized by X-ray...     

Similarities and differences between male and female novice designers on color‐concept associations for warnings,action required,and signs and equipment status messages

This research examined the male and female novice designers toward color associations for the concepts used for ‘warnings’, ‘action required’, and ‘signs and equipment status’ through a questionnaire‐based study. A total of 178 Hong Kong Chinese final year undergraduate design students (89 males and 89 females) participated in the study. The test used required the participants to indicate their choice of one of nine colors to associations with each of 38 concepts in a color‐concept table, so that any one color could be associated with any one of the concepts. For both male and female groups of novice designers, chi‐square tests revealed a strong color association for each concept tested in this study (P < .05). The results showed males and females agreed on some color‐concept association stereotypes which were therefore gender neutral. The male and female novice designers had the same color associations and similar levels of stereotype strengths for 21 concepts. The nine strongest and therefore most useful color‐concept association stereotypes for both male and female novice designers were: red‐danger, red‐fire, red‐hot, red‐stop, red‐emergency, red‐error, blue‐cold, blue‐male, and green‐exit. However, the male and female novice designers had different color association stereotypes for the standby (green vs. yellow), emergency exit (green vs. red), and toxic (purple vs. black) concepts, and the strengths of the 14 remaining associations for both groups were not at equivalent levels. Overall, it is anticipated that the findings of this study will act as a useful reference for novice designers and other design practitioners to optimize color coding in the design of ‘warnings’, ‘action required’, and ‘signs and equipment status’ messages.     

CuInS2/SiNWs/Si composite material for application as potential photoelectrode for photoelectrochemical hydrogen generation

This work aims at developing a new composite material based on nanosized semiconducting CuInS₂ (CIS) particles combined with silicon nanowires grown on a silicon substrate (SiNWs/Si) for photoelectrochemical (PEC)-splitting of water. The CIS particles were prepared via a colloidal method using N-methylimidazole (NMI) as the solvent and an annealing treatment. The SiNWs were obtained by chemical etching of silicon (100) substrates assisted by a metal. The CIS/SiNWs/Si composite material was obtained by deposition of an aliquot of a suspension of CIS particles onto the SiNWs/Si substrate, using spin coating followed by a drying step. The XRD pattern demonstrated that CuInS₂ grows in the tetragonal/chalcopyrite phase, while SiNWs/Si presents a cubic structure. The SEM images show semi-spherical particles (～10 nm) distributed on the surface of silicon nanowires (～10 μm). The EIS measurements reveal n-type conductivity for CIS, SiNWs/Si and CIS/SiNWs/Si materials, which could favour the oxidation reaction of water molecules.     

Moderate lameness leads to marked behavioral changes in dairy cows

Lameness is one of the most prevalent diseases affecting the welfare of cows in modern dairy production. Lameness leads to behavioral changes in severely lame cows, which have been investigated in much detail. For early detection of lameness, knowledge of the effects of moderate lameness on cow behavior is crucial. Therefore, the behavior of nonlame and moderately lame cows was compared on 17 Swiss dairy farms. On each farm, 5 to 11 nonlame (locomotion score 1 of 5) and 2 to 7 moderately lame (locomotion score 3 of 5) cows were selected for data collection in two 48-h periods (A, B) separated by an interval of 6 to 10 wk. Based on visual locomotion scoring, 142 nonlame and 66 moderately lame cows were examined in period A and 128 nonlame and 53 moderately lame cows in period B. Between these 2 periods, the cows underwent corrective hoof trimming. Lying behavior, locomotor activity, and neck activity were recorded by accelerometers (MSR145 data logger, MSR Electronics GmbH, Seuzach, Switzerland), and feeding and rumination behaviors by noseband sensors (RumiWatch halter, ITIN + HOCH GmbH, Liestal, Switzerland). Furthermore, visits to the brush and the concentrate feeder, and the milking order position were recorded. In comparison with nonlame cows, moderately lame cows had a longer lying duration, a longer average lying bout duration, and a greater lateral asymmetry in lying duration. Average locomotor activity, locomotor activity during 1 h after feed delivery or push-ups, and average neck activity were lower in moderately lame cows. Eating time and the number of eating chews (jaw movements) were reduced in moderately lame compared with nonlame cows, whereas no effect of moderate lameness was evident for ruminating time, number of ruminating chews and boluses, and average number of ruminating chews per bolus. Moderately lame cows visited the concentrate feeder and the brush less frequently, and they were further back in the milking order compared with nonlame cows. In conclusion, nonlame and moderately lame cows differed in a biologically relevant way in many of the behavioral variables investigated in this study. Therefore, the use of these behavioral changes seems to be promising to develop a tool for early lameness detection.