Synthesis and Biological Evaluation of Novel Isonucleosides with 1,2,4‐Triazole‐3‐Carboxamide

Novel 1,2,4‐triazole isonucleosides (1 and 2) were efficiently synthesized starting from D‐ribose and D‐xylose, respectively. The key steps were condensation of cyclic sulfate 8 with methyl‐1,2,4‐triazole‐3‐carboxylate and nucleophilic displacement of the tosylate 15 with methyl‐1,2,4‐triazole‐3‐carboxylate, respectively.     

Synthesis of 1,5-diphenylpent-3-en-1-yne derivatives utilizing an aqueous B-alkyl Suzuki cross coupling reaction

1,5-Diphenylpent-3-en-1-yne derivatives were isolated in minor quantities from terrestrial plants and exhibited strong anti-inflammatory activity. A cross coupling reaction between B-benzyl-9-BBN and chloroenynes under mild condition was developed resulting in the formation of different 1,5-diphenylpent-3-en-1-yne derivatives with a full control on the E/Z selectivity. Several substrates bearing electron-donating and electron-withdrawing substituents were tolerable under the reaction conditions affording the corresponding products in good yields. This is the first study to report the synthesis of a vast array of novel 1,5-diphenylpent-3-en-1-yne derivatives paving the way for the preparation of tailored derivatives on mass scale necessary for biological studies and drug development.     

Dual‐micropillar‐based microfluidic platform for single embryonic stem cell‐derived neuronal differentiation

We developed the dual‐micropillar‐based microfluidic platform to direct embryonic stem (ES) cell fate. 4 × 4 dual‐micropillar‐based microfluidic platform consisted of 16 circular‐shaped outer micropillars and 8 saddle‐shaped inner micropillars in which single ES cells were cultured. We hypothesized that dual‐micropillar arrays would play an important role in controlling the shear stress and cell docking. Circular‐shaped outer micropillars minimized the shear stress, whereas saddle‐shaped inner micropillars allowed for docking of individual ES cells. We observed the effect of saddle‐shaped inner micropillars on cell docking in response to hydrodynamic resistance. We also demonstrated that ES cells cultured for 6 days within the dual‐micropillar‐based microfluidic platform differentiated into neural‐like cells. Therefore, this dual‐micropillar‐based microfluidic platform could be a potentially powerful method for screening of lineage commitments of single ES cells.     

Ionic hexagonal columnar metallomesogens derived from tetrabenzo[b,f,j,n] [1,5,9,13]tetraazacyclohexadecine

A series of transition metal (Ni, Cu, Pd) complexes derived from macrocyclic tetrabenzo[b,f,j,n] [1,5,9,13]tetraazacyclohexadecine (TAAB) was synthesized and their mesomorphic properties studied by differential scanning calorimetry, polarized optical microscopy and X-ray powder diffraction (XRD). These compounds have eight alkoxy side chains attached around the central molecular core and form disc-like molecules. All the derivatives exhibited columnar mesophases over a wide range of temperature. The mesomorphic behaviour was found to be dependent on the incorporated metal and the carbon length of the alkoxy side chains. The clearing temperatures decreased in the order M = Ni > Pd > Cu; this decrease was probably due to the size of the metal ions. Some derivatives with shorter side chains (n = 10, 12) were room temperature liquid crystals. All compounds were found to exhibit hexagonal columnar (Col_h) phases which were confirmed by powder XRD.     

Heterocyclic 1,3,4-oxadiazole as columnar core

The synthesis, characterization and mesomorphic properties of a new type of liquid crystalline compound, the 2,5-bis(3,4,5-trialkoxyphenyl)-1,3,4-oxadiazoles, 3a-3h, are reported. These heterocyclic compounds are derived from unsaturated 1,3,4-oxadiazole as the core group, and obtained by the condensation reaction of 3,4,5-trialkoxybenzoic acid N-(3,4,5-trialkoxybenzoyl)-hydrazides and phosphorus oxychloride in toluene under reflux. All compounds were characterized by ¹H and ¹³C NMR spectroscopy, and elemental analysis. The mesomorphic properties of these and the related compounds 1, 2 were characterized and studied by differential scanning calorimetry and polarizing optical microscopy. The formation of columnar mesophases was found to be dependent on the numbers of alkoxy sidechains. The compounds 3 exhibited hexagonal columnar (Col_h) phases, however compounds 1, 2 formed crystalline phases. Compounds 3b-3e with shorter carbon chains were room temperature liquid crystals. Polar induction by nitrogen and/or oxygen atoms on the heterocyclic core ring might be responsible for the formation and better observed mesomorphic properties in this type of compound.     

Dual pH‐ and Temperature‐Responsive Metallosupramolecular Block Copolymers with Tunable Critical Micelle Temperature by Modulation of the Self‐Assembly of NIR‐Emissive Alkynylplatinum(II) Complexes Induced by Changes in Hydrophilicity and Electrostatic Effects

Terpyridylplatinum(II)‐based metallosupramolecular triblock copolymers with hydrophilic alkynyl ligands have been synthesised and characterised. As a result of the intrinsic properties of Pluronics, reversible temperature‐induced micellisation occurred at high temperature leading to aggregation of the platinum(II) complex moieties through Pt???Pt and π–π interactions, resulting in significant UV/Vis absorption and near‐infrared (NIR) emission spectral changes. The critical micelle temperatures of the complexes were found to vary from 21 to 30 °C due to differences in the hydrophilicity of the alkynyl ligands and the electrostatic repulsions between the positively charged platinum(II) complex moieties. One of the complexes with pH‐responsive CH₂NMe₂ groups on the alkynyl ligand was found to show NIR emission that is sensitive to both pH and temperature. Such dual‐responsive behaviour has been ascribed to the modulation of the self‐assembly of the complex moieties by temperature‐induced micellisation and the changes in the hydrophilicity as well as electrostatic interactions upon protonation/deprotonation of the CH₂NMe₂ groups on the alkynyl ligand.     

Synthesis of Poly(benzothiadiazole‐co‐dithienobenzodithiophenes) and Effect of Thiophene Insertion for High‐Performance Polymer Solar Cells

We describe herein the synthesis of novel donor–acceptor conjugated polymers with dithienobenzodithiophenes (DTBDT) as the electron donor and 2,1,3‐benzothiadiazole as the electron acceptor for high‐performance organic photovoltaics (OPVs). We studied the effects of strategically inserting thiophene into the DTBDT as a substituent on the skeletal structure on the opto‐electronic performances of fabricated devices. From UV/Vis absorption, electrochemical, and field‐effect transistor analyses, we found that the thiophene‐containing DTBDT derivative can substantially increase the orbital overlap area between adjacent conjugated chains and thus dramatically enhance charge‐carrier mobility up to 0.55 cm² V^?1 s^?1. The outstanding charge‐transport characteristics of this polymer allowed the realization of high‐performance organic solar cells with a power conversion efficiency (PCE) of 5.1 %. Detailed studies on the morphological factors that enable the maximum PCE of the polymer solar cells are discussed along with a hole/electron mobility analysis based on the space‐charge‐limited current model.     

Structural and Dynamic Basis of Human Cytochrome P450 7B1: A Survey of Substrate Selectivity and Major Active Site Access Channels

Cytochrome P450 (CYP) 7B1 is a steroid cytochrome P450 7α‐hydroxylase that has been linked directly with bile salt synthesis and hereditary spastic paraplegia type 5 (SPG5). The enzyme provides the primary metabolic route for neurosteroids dehydroepiandrosterone (DHEA), cholesterol derivatives 25‐hydroxycholesterol (25‐HOChol), and other steroids such as 5α‐androstane‐3β,17β‐diol (anediol), and 5α‐androstene‐3β,17β‐diol (enediol). A series of investigations including homology modeling, molecular dynamics (MD), and automatic docking, combined with the results of previous experimental site‐directed mutagenesis studies and access channels analysis, have identified the structural features relevant to the substrate selectivity of CYP7B1. The results clearly identify the dominant access channels and critical residues responsible for ligand binding. Both binding free energy analysis and total interaction energy analysis are consistent with the experimental conclusion that 25‐HOChol is the best substrate. According to 20 ns MD simulations, the Phe cluster residues that lie above the active site, particularly Phe489, are proposed to merge the active site with the adjacent channel to the surface and accommodate substrate binding in a reasonable orientation. The investigation of CYP7B1–substrate binding modes provides detailed insights into the poorly understood structural features of human CYP7B1 at the atomic level, and will be valuable information for drug development and protein engineering.