High-throughput screening against $$\sim $$6.1 million structurally diverse,lead-like compounds to discover novel ROCK inhibitors for cerebral injury recovery

Rho-associated protein kinase (ROCK) has been recognized as an attractive therapeutic target to promote neurogenesis, neuroregeneration, and neurorecovery after cerebral injury. Here, a high-throughput screening protocol was described to discover novel ROCK inhibitors from a large chemical library containing \(\sim \)6.1 million structurally diverse, lead-like compounds. The protocol employed empirical rules such as ADMET evaluation and chemical similarity analysis to exclude those of drug-unlike candidates, and then molecular docking and binding affinity predictions were performed to suggest few promising candidates with high scores. Consequently, five compounds were successfully identified to have satisfactory activity profile with \(\hbox {IC}_{50}\) values at nanomolar level. In order to elucidate the molecular mechanism of inhibitor binding to target, the complex structures of ROCK kinase domain with the five identified compounds were modeled and examined in detail. A number of polar chemical forces such as hydrogen bonds and cation-\(\pi \) interactions as well as nonpolar contacts such as \(\pi \)–\(\pi \) stacking and hydrophobic forces were revealed at the complex interface, conferring high affinity and strong specificity to inhibitor binding. In addition, several key residues around the kinase active site, including Val90, Lys105, Asn203, and Phe368, were found to play an important role in binding.     

Electrical conductivity,optical properties and mechanical stability of 3, 4, 9, 10-perylenetetracarboxylic dianhidride based organic semiconductor

The 3, 4, 9, 10-perylenetetracarboxylic dianhydride (PTCDA) doped polymer films were prepared with Polypyrrole (PPy) and Polyvinyl alcohol (PVA) polymers by solution-casting. The change in structure and chemical composition of samples was identified by XRD and FTIR respectively. The UV–visible spectroscopy demonstrates the optical characteristics and band gap properties of sample. The homogeneous morphology of sample for higher wt% of PTCDA was examined by atomic force microscopy (AFM). The differential scanning calorimetry (DSC) results demonstrate the decrease in melting temperature (T_m) and degree of crystallinity (χ_c%) of polymeric organic semiconductor. The mechanical property demonstrates the high tensile strength and improved plasticity nature. Impedance spectroscopy was evaluated to determine the conductivity response of polymeric organic semiconductor. The highest DC conductivity (2.08×10⁻³ S/m) was obtained for 10 wt% of PTCDA at 140 °C. The decrease in activation energy (E_a) represents the non-Debye process and was evaluated from the slope of ln σ_dc vs. 10³/T plot.     

Ferroelectric phase transition and optical performance of PLZnNZT transparent ceramics

Lead-based Pb_0.97La_0.02(Zn_1/3Nb_2/3)_0.3(Zr_0.53Ti_0.47)_0.7O₃ (PLZnNZT) transparent ceramics with the addition of 2 wt% excess PbO were prepared by hot-pressing sintering method. The hot-pressing sintered PLZnNZT ceramics exhibit dense and large-grained microstructure, and perovskite structure with distorted cubic-like symmetry. The ceramics exhibit normal ferroelectric-like dielectric behavior with slightly diffused ferroelectric phase transition characteristic. The PLZnNZT ceramics exhibit fully developed, symmetric and saturated P–E hysteresis loop and large piezoelectric constant d₃₃, being 468 pC/N. The ceramics with 120 μm thickness exhibit maximum transmittance of 53% at 850 nm when Fresnel losses was not included, almost totally transparent in the mid IR region (2500–5600 nm), and low-lying optical band gap energy E_g of 3.23 eV. Three diffused Raman bands centering around 240 cm⁻¹, 560 cm⁻¹ and 750 cm⁻¹ are observed by micro-Raman spectroscopy, which can be attributed to F2g [BO₆] bending vibration, A1g [BO₆] stretching vibration and “soft mode” mixed by the bending and stretching vibrations, respectively, confirming the normal ferroelectric-like characteristic.     

Cooling-down of thermal thick probes after flash excitation – A measure for the real energy density?

Though flash lamps are one of the most applied heat sources in the field of Thermographic Testing (TT) using active thermography, only little is known about the actually achieved energy input into test objects. In this paper, an easy to realize sensor concept is proposed and experimentally evaluated. The concept is based on the measurement of the surface temperature of a thermal thick probe after flash excitation. After considering the sensor concept with FEM simulations the experimental investigation of four materials (two polymer and two building materials) is described. It will be shown that a suited coating is essential for the realization of the sensor concept. The experimental results prove the suitability of black rigid PVC as the most promising material. Using a coated PVC sample the energy density of short laser pulses, similar to flashes of flash lamps, could be determined exactly with an estimated relative uncertainty of only a few percent.     

The structural and catalytic properties of nanoparticles@MOF composites: A case study of Au@ZIF-8 hybrid crystals

Strain analysis of the MOF and its composites using high-resolution X-ray diffractionmeter (XRD) was carried out and the presence of non-uniform, depth-related strain in the MOF crystals was confirmed. Further analysis showed that the magnitude and distribution of strain in MOF crystals can be tuned with the incorporation of nanoparticles (NPs). Moreover, the spatial controlled structures can also optimize functionalities of the NPs@MOF, which was exemplified by their applications on the catalytic reduction of nitroarenes. It is anticipated that the investigation of MOF structure evolution through controlling the architectures of the MOF/NPs hybrid materials will shed a light on the study of optimizing the mechanical and chemical properties of MOF composites.     

On a new FeOF polymorph: Synthesis and stability

A new polymorph of FeOF (up to now only known in its rutile type structure) was prepared by using a new synthesis approach formally based on anionic exchange using the well-known layered FeOCl as precursor. The synthesis was achieved using [CH₃C(CH₂O–)₂(COO–)B] to vehicle fluorine through the formation of soluble (CH₃)₄N⁺ [CH₃C(CH₂O–)₂(COO–)BF]⁻ and using N,N-dimethylformamide (DMF) as the reacting medium. The XRD pattern of layered FeOF can be indexed with an orthorhombic cell which doubles along the b axis (which is the direction perpendicular to the layers) with respect to that of pristine FeOCl (a = 3.792(1) Å, b = 12.699(1) Å, c = 3.321(1) Å). Both thermal analysis and diffraction indicate similar stability for the layered and rutile polymorphs. Such findings are rationalized through Density Functional Theory calculations. It is found that the energy difference between the more stable rutile and layered polymorphs is practically nul. The origin of the similar stability lies in the fact that although the number of Fe–F and Fe–O bonds is different in the two structures, the strength of both the total number of Fe–O as well as Fe–F bonds are found to be almost identical. Even if the crystal and electronic structures are considerably different, the total bonding and thus, the stability of the two polymorphs, is comparable. The stability of different FeOF rutile type structures is also analyzed.     

Neo‐Fused Hexaphyrin: A Molecular Puzzle Containing an N‐Linked Pentaphyrin

The first neo‐confused hexaphyrin(1.1.1.1.1.0) was synthesized by oxidative ring closure of a hexapyrrane bearing two terminal “confused” pyrroles. The new compound displays a folded conformation with a short interpyrrolic C???N distance of 3.102 Å, and thus it readily underwent ring fusion to afford a neo‐fused hexaphyrin with an unprecedented 5,5,5,7‐tetracyclic ring structure. Furthermore, coordination of Cu^II triggered a ring opening/contracting reaction to afford a Cu^II complex of an N‐linked pentaphyrin derivative. The roles of reactive N? C bonds in the porphyrinoid macrocycles were demonstrated.     

Intrinsic Peroxidase‐like Activity of Porous CuO Micro‐/nanostructures with Clean Surface

Porous CuO micro‐/nanostructures with clean surface, prepared through Cu₂(OH)₂CO₃ precursor followed by calcination in air, were proven to be an effective peroxidase mimic. They can quickly catalyze oxidation of the peroxidase substrate 3,3′,5,5′‐tetramethylbenzidine (TMB) in the presence of H₂O₂, producing a blue color. The obtained porous CuO micro‐/nanostructure have potential application in wastewater treatment. The apparent steady‐state kinetic parameter was studied with TMB as the substrate. In addition, the potential application of the porous CuO in wastewater treatment was demonstrated with phenol‐containing water as an example. Such investigation not only confirms the intrinsic peroxidase‐like activity of micro‐/nanostructured CuO, but also suggests its potential application in wastewater treatment.     

固载化烷基咪唑离子液体对盐酸体系中Fe(Ⅲ)的吸附性能研究

分别将N-甲基咪唑和N-丁基咪唑通过共价键固定于树脂载体上,制备了固载化甲基咪唑离子液体(MCl)和固载化丁基咪唑离子液体(BCl),MCl和BCl可作为一种新型的强碱型阴离子交换树脂。研究了MCl和BCl对盐酸体系中Fe(III)的吸附性能,其吸附平衡时间为6h,拟二级动力学模型能更好地描述MCl和BCl对Fe(III)的吸附动力学过程;随着温度的升高,MCl和BCl对Fe(III)的吸附量增大,表明该过程是一个吸热反应,在298K时,MCl和BCl对Fe(III)的最大吸附量分别为24.9mg/g和71.1mg/g;随着盐酸浓度的增加,MCl和BCl对Fe(III)的吸附量增大,而且溶液中Cl-浓度的增加,也会提高MCl和BCl对Fe(III)的吸附量。MCl和BCl可从盐酸体系中回收Fe(III),而且BCl的效果要优于MCl。