A 3D‐QSAR Study of Celebrex‐Based Pdk1 Inhibitors Using Comfa Method

A 3D‐QSAR study of celebrex‐based compounds of PDK1 inhibitors using comparative molecular field analysis (CoMFA) was carried out. The structures of the compounds were obtained using quantum chemistry calculation. CoMFA calculations for a number of grouped subsets of compounds gave q² values of correlation in the range from 0 to 0.8. The low q² values should be mainly due to the narrow span of biological activity. Calculations for several subsets of 11–13 compounds gave high q² values, with 0.5–0.8. Factors affecting the results of the calculations are discussed. Calculated results with high q² values suggest that further chemical modifications of the compounds could lead to enhanced activity and could be an aid in the design of celebrex‐based cancer drugs.     

Sensitivity Enhancement in Nickel Hydroxide/3D‐Graphene as Enzymeless Glucose Detection

A nickel hydroxide (Ni(OH)₂)/3D‐graphene composite is used as monolithic free‐standing electrode for enzymeless electrochemical detection of glucose. Ni(OH)₂ nanoflakes are synthesized by using a simple solution growth procedure on 3D‐graphene foam which was grown by chemical vapor deposition (CVD). The pore structure of 3D‐graphene allows easy access to glucose with high surface area, which leads to glucose detection with an ultrahigh sensitivity of 3.49 mA mM^?1 cm^?2 and a significant lower detection limit up to 24 nM. Cyclic voltammetry (CV) and potentionstatic mode is used for non‐enzymatic glucose sensing. The impedance and effective surface area have been studied well. The high sensitivity, low detection limit and simple configuration of Ni(OH)₂/three dimensional (3D)‐graphene composite electrodes can evoke its industrial application in glucose sensing devices.     

An Improved Preparation of D‐Glyceraldehyde 3‐Phosphate and Its Use in the Synthesis of 1‐Deoxy‐D‐xylulose 5‐Phosphate

D ‐Glyceraldehyde 3‐phosphate (=D ‐GAP; 2 ) was prepared by an improved chemical method (Scheme 2), and it was then employed to synthesize 1‐deoxy‐D ‐xylulose 5‐phosphate (=DXP; 3 ) which is enzymatically one of the key intermediates in the MEP ( 4 ) terpenoid biosynthetic pathway (Scheme 1). The recombinant DXP synthase of Rhodobacter capsulatus was used to catalyze the condensation of D ‐glyceraldehyde 3‐phosphate ( 2 ) and pyruvate (=2‐oxopropanoate; 1 ) to produce the sugar phosphate 3 (Scheme 2). The simple two‐step chemoenzymatic route described affords DXP ( 3 ) with more than 70% overall yield and higher than 95% purity. The procedure may also be used for the synthesis of isotope‐labeled DXP ( 3 ) by using isotope‐labeled pyruvate.     

3D‐Printing inside the Glovebox: A Versatile Tool for Inert‐Gas Chemistry Combined with Spectroscopy

3D‐Printing with the well‐established ‘Fused Deposition Modeling’ technology was used to print totally gas‐tight reaction vessels, combined with printed cuvettes, inside the inert‐gas atmosphere of a glovebox. During pauses of the print, the reaction flasks out of acrylonitrile butadiene styrene were filled with various reactants. After the basic test reactions to proof the oxygen tightness and investigations of the influence of printing within an inert‐gas atmosphere, scope and limitations of the method are presented by syntheses of new compounds with highly reactive reagents, such as trimethylaluminium, and reaction monitoring via UV/VIS, IR, and NMR spectroscopy. The applicable temperature range, the choice of solvents, the reaction times, and the analytical methods have been investigated in detail. A set of reaction flasks is presented, which allow routine inert‐gas syntheses and combined spectroscopy without modifications of the glovebox, the 3D‐printer, or the spectrometers. Overall, this demonstrates the potential of 3D‐printed reaction cuvettes to become a complementary standard method in inert‐gas chemistry.     

2－脱氧－烟酰胺基－β－D－氨基葡萄糖的合成和表征

A new nicotinic acid derivative,2-deoxy-2-nicotinoylamido-β-D-glucopyranose, was synthesized with β-configuration exclusively. The structure and properties of the product were characterized by ^1H NMR, PT-IR, MS, DSC and polarimeter. The details of ^1H NMR spectrum and the mass spectrum proved that there are a great amount of hydrogen bonds in the product.     

Separation of D‐psicose and D‐fructose using simulated moving bed chromatography

Simulated moving bed (SMB) processes have been widely used in the sugar industries with ion‐exchange resin as a stationary phase. D ‐Psicose, a rare monosaccharide known as a valuable pharmaceutical substrate, was synthesized by the enzymatic conversion from D ‐fructose. The SMB process was adopted to separate D ‐psicose from D ‐fructose. Before the SMB experiment, the reaction mixture including D ‐psicose and D ‐fructose was treated by a deashing process to remove contaminants, such as buffers, proteins, and other organic materials. Four columns packed with Dowex 50WX4‐Ca²⁺ (200–400 mesh) ion‐exchange resins were used in the four‐zone SMB. Single‐step frontal analysis was performed to estimate the isotherm parameters of each monosaccharide. The operating conditions of the SMB process were determined based on the Equilibrium Theory. According to the simulation of the SMB process, the purity and yield of extract product (D ‐psicose) achieved were 99.04 and 97.46%, respectively and those of raffinate product (D ‐fructose) were 99.06 and 99.53%, respectively. Under the optimized operating condition, complete separation (extract purity = 99.36%, raffinate purity = 99.67%) was achieved experimentally.     

A solvation‐free‐energy functional: A reference‐modified density functional formulation

The three‐dimensional reference interaction site model (3D‐RISM) theory, which is one of the most applicable integral equation theories for molecular liquids, overestimates the absolute values of solvation‐free‐energy (SFE) for large solute molecules in water. To improve the free‐energy density functional for the SFE of solute molecules, we propose a reference‐modified density functional theory (RMDFT) that is a general theoretical approach to construct the free‐energy density functional systematically. In the RMDFT formulation, hard‐sphere (HS) fluids are introduced as the reference system instead of an ideal polyatomic molecular gas, which has been regarded as the appropriate reference system of the interaction‐site‐model density functional theory for polyatomic molecular fluids. We show that using RMDFT with a reference HS system can significantly improve the absolute values of the SFE for a set of neutral amino acid side‐chain analogues as well as for 504 small organic molecules. © 2015 Wiley Periodicals, Inc.     

Three pillars for achieving quantum mechanical molecular dynamics simulations of huge systems: Divide‐and‐conquer,density‐functional tight‐binding,and massively parallel computation

The linear‐scaling divide‐and‐conquer (DC) quantum chemical methodology is applied to the density‐functional tight‐binding (DFTB) theory to develop a massively parallel program that achieves on‐the‐fly molecular reaction dynamics simulations of huge systems from scratch. The functions to perform large scale geometry optimization and molecular dynamics with DC‐DFTB potential energy surface are implemented to the program called DC‐DFTB‐K. A novel interpolation‐based algorithm is developed for parallelizing the determination of the Fermi level in the DC method. The performance of the DC‐DFTB‐K program is assessed using a laboratory computer and the K computer. Numerical tests show the high efficiency of the DC‐DFTB‐K program, a single‐point energy gradient calculation of a one‐million‐atom system is completed within 60 s using 7290 nodes of the K computer. © 2016 Wiley Periodicals, Inc.     

3D‐Printed Titanium Cage with PVA‐Vancomycin Coating Prevents Surgical Site Infections (SSIs)

Many coating materials have been studied to prevent surgical site infections (SSIs). However, antibacterial coating on surfaces show weak adhesion using the traditional titanium (Ti) cage, resulting in low efficacy for preventing SSIs after spinal surgery. Herein, a 3D‐printed Ti cage combined with a drug‐releasing system is developed for in situ drug release and bacteria killing, leading to prevention of SSIs in vitro and in vivo. First, a 3D‐printed Ti cage is designed and prepared by the Electron Beam Melting (EBM) method. Second, polyvinyl alcohol (PVA) containing hydrophilic vancomycin hydrochloride (VH) is scattered across the surface of 3D‐printed porous Ti (Ti‐VH@PVA) cages. Ti‐VH@PVA cages show an efficient drug‐releasing profile and excellent bactericidal effect for three common bacteria after more than seven days in vitro. In addition, Ti‐VH@PVA cages exhibit reliable inhibition of inflammation associated with Staphylococcus aureus and effective bone regeneration capacity in a rabbit model of SSIs. The results indicate that Ti‐VH@PVA cages have potential advantages for preventing SSIs after spinal surgery.     

Placevent: An algorithm for prediction of explicit solvent atom distribution—Application to HIV‐1 protease and F‐ATP synthase

We have created a simple algorithm for automatically predicting the explicit solvent atom distribution of biomolecules. The explicit distribution is coerced from the three‐dimensional (3D) continuous distribution resulting from a 3D reference interaction site model (3D‐RISM) calculation. This procedure predicts optimal location of solvent molecules and ions given a rigid biomolecular structure and the solvent composition. We show examples of predicting water molecules near the KNI‐272 bound form of HIV‐1 protease and predicting both sodium ions and water molecules near the rotor ring of F‐adenosine triphosphate (ATP) synthase. Our results give excellent agreement with experimental structure with an average prediction error of 0.39–0.65 Å. Further, unlike experimental methods, this method does not suffer from the partial occupancy limit. Our method can be performed directly on 3D‐RISM output within minutes. It is extremely useful for examining multiple specific solvent–solute interactions, as a convenient method for generating initial solvent structures for molecular dynamics calculations, and may assist in refinement of experimental structures. © 2012 Wiley Periodicals, Inc.     

Efficient treatment of solvation shells in 3D molecular theory of solvation

We developed a technique to decrease memory requirements when solving the integral equations of three‐dimensional (3D) molecular theory of solvation, a.k.a. 3D reference interaction site model (3D‐RISM), using the modified direct inversion in the iterative subspace (MDIIS) numerical method of generalized minimal residual type. The latter provides robust convergence, in particular, for charged systems and electrolyte solutions with strong associative effects for which damped iterations do not converge. The MDIIS solver (typically, with 2 × 10 iterative vectors of argument and residual for fast convergence) treats the solute excluded volume (core), while handling the solvation shells in the 3D box with two vectors coupled with MDIIS iteratively and incorporating the electrostatic asymptotics outside the box analytically. For solvated systems from small to large macromolecules and solid–liquid interfaces, this results in 6‐ to 16‐fold memory reduction and corresponding CPU load decrease in MDIIS. We illustrated the new technique on solvated systems of chemical and biomolecular relevance with different dimensionality, both in ambient water and aqueous electrolyte solution, by solving the 3D‐RISM equations with the Kovalenko–Hirata (KH) closure, and the hypernetted chain (HNC) closure where convergent. This core–shell‐asymptotics technique coupling MDIIS for the excluded volume core with iteration of the solvation shells converges as efficiently as MDIIS for the whole 3D box and yields the solvation structure and thermodynamics without loss of accuracy. Although being of benefit for solutes of any size, this memory reduction becomes critical in 3D‐RISM calculations for large solvated systems, such as macromolecules in solution with ions, ligands, and other cofactors. © 2012 Wiley Periodicals, Inc.     

Neue Zirconiumphosphatfluoride mit 3D‐Gerüststruktur

New Zirconium Phosphate Fluorides with 3D‐Framework From aqueous solutions of ZrOCl₂, H₃PO₄, HF, and various amines, two new compounds of the general formula [amH₂]_1/2[Zr₂(HPO₄)(PO₄)₂F] · nH₂O ( I : am = N,N‐dimethylethylenediamine, n = 0,5; II : am = N,N‐dimethyl‐1,3‐diaminopropane, n = 0) adopting the ZrPOF‐1 structure type have been synthesized under hydrothermal conditions. In contrast to the monoclinic ZrPOF‐1, both compounds crystallize in the space group P 1 with a = 6.611(3), b = 9.109(4), c = 11.560(5) Å, α = 85.62(4), β = 89.60(4), γ = 70.57(4)° in I , and a = 6.616(2), b = 9.045(3), c = 11.565(4) Å, α = 85.26(4), β = 88.86(4), γ = 71.46(4)° in II . Compound III (am = ethylenediamine, n = 0) has been obtained by dehydration of ZrPOF‐1 and occurs in the space group P1 with a = 6.605(2), b = 8.787(3), c = 11.499(5) Å, α = 93.07(4), β = 90.42(4) and γ = 104.66(4)°. The structural motifs of the frameworks of the three compounds have much in common. The template and the PO₃OH tetrahedra in I and II are disordered. Differences in the water content in both compounds are due to differences in the chain lengths of the amines. The absence of crystal water in compound III breaks the template disordering which is present in ZrPOF‐1. The rotation of the PO₃OH tetrahedra in II and III compared with I and ZrPOF‐1 is discussed in regard with the absence of stabilizing H‐bridges in the former compounds.     

Tailoring Excited State Properties and Energy Levels Arrangement via Subtle Structural Design on D‐π‐A Materials

The donor‐π‐conjugated‐acceptor (D‐π‐A) structure is an important design for the luminescent materials because of its diversity in the selections of donor, π‐bridge and acceptor groups. Herein, we demonstrate two examples of D‐π‐A structures capable to finely modulate the excited state properties and arrangement of energy levels, TPA‐AN‐BP and CZP‐AN‐BP , which possess the same acceptor and π‐bridge but different donor. The investigation of their photophysical properties and DFT calculation revealed that the D‐π‐A structure with proper donor, π‐bridge and acceptor can result in separation of frontier molecular orbitals on the corresponding donor and acceptor with an obvious overlap on the π‐bridge, resulting in a hybridized local and charge‐transfer (HLCT ) excited state with high photoluminescent (PL ) efficiencies. Meanwhile, their singlet and triplet states are arranged on corresponding moieties with large energy gap between T₂ and T₁ , and a small energy gap between S₁ and T₂ , which favor the reverse intersystem crossing (RISC ) from high‐lying triplet levels to singlet levels. As a result, the sky‐blue emission non‐doped OLED based on the TPA‐AN‐BP reached maximum external quantum efficiency (EQE ) of 4.39% and a high exciton utilization efficiency (EUE ) of 77%. This study demonstrates a new strategy to construct highly efficient OLED materials.     

A Robust 3D Cage‐like Ultramicroporous Network Structure with High Gas‐Uptake Capacity

A three‐dimensional (3D) cage‐like organic network (3D‐CON) structure synthesized by the straightforward condensation of building blocks designed with gas adsorption properties is presented. The 3D‐CON can be prepared using an easy but powerful route, which is essential for commercial scale‐up. The resulting fused aromatic 3D‐CON exhibited a high Brunauer–Emmett–Teller (BET) specific surface area of up to 2247 m² g^?1. More importantly, the 3D‐CON displayed outstanding low pressure hydrogen (H₂, 2.64 wt %, 1.0 bar and 77 K), methane (CH₄, 2.4 wt %, 1.0 bar and 273 K), and carbon dioxide (CO₂, 26.7 wt %, 1.0 bar and 273 K) uptake with a high isosteric heat of adsorption (H₂, 8.10 kJ mol^?1; CH₄, 18.72 kJ mol^?1; CO₂, 31.87 kJ mol^?1). These values are among the best reported for organic networks with high thermal stability (ca. 600 °C).     

Amperometric Magnetoimmunosensors for Direct Determination of D‐Dimer in Human Serum

Two different D‐dimer disposable amperometric immunosensing designs based on indirect competitive or sandwich formats and the use of carboxylic acid‐modified magnetic beads (COOH‐MBs) and screen‐printed carbon electrodes (SPCEs) have been developed and compared. In both approaches, the resulting modified MBs were magnetically captured on the surface of a SPCE which was used as the transducer for the electrochemical detection at ?0.20 V upon addition of H₂O₂, and hydroquinone (HQ). Both configurations exhibited linear ranges of clinical usefulness and detection limits quite below the clinical threshold (0.5 µg mL^?1 D‐dimer). The sandwich configuration has been successfully tested with serum samples.     

2,2,2‐trifluoroacetophenone‐based D‐π‐A type photoinitiators for radical and cationic photopolymerizations under near‐UV and visible LEDs

Two D‐π‐A‐type 2,2,2‐trifluoroacetophenone derivatives, namely, 4′‐(4‐( N,N‐diphenyl)amino‐phenyl)‐phenyl‐2,2,2‐trifluoroacetophenone (PI‐Ben) and 4′‐(4‐(7‐(N,N‐diphenylamino)‐9,9‐dimethyl‐9H‐fluoren‐2‐yl)‐phenyl‐2,2,2‐trifluoroacetophenone (PI‐Flu), are developed as high‐performance photoinitiators combined with an amine or an iodonium salt for both the free‐radical polymerization of acrylates and the cationic polymerization of epoxides and vinyl ether upon exposure to near‐UV and visible light‐emitting diodes (LEDs; e.g., 365, 385, 405, and 450 nm). The photochemical mechanisms are investigated by UV‐Vis spectra, molecular‐orbital calculations, fluorescence, cyclic voltammetry, photolysis, and electron‐spin‐resonance spin‐trapping techniques. Compared with 2,2,2‐trifluoroacetophenone, both photoinitiators exhibit larger redshift of the absorption spectra and higher molar‐extinction coefficients. PI‐Ben and PI‐Flu themselves can produce free radicals to initiate the polymerization of acrylate without any added hydrogen donor. These novel D‐π‐A type trifluoroacetophenone‐based photoinitiating systems exhibit good efficiencies (acrylate conversion = 48%–66%; epoxide conversion = 85%–95%; LEDs at 365–450 nm exposure) even in low‐concentration initiators (0.5%, w/w) and very low curing light intensities (1–2 mW cm^?2). © 2016 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016 , 54, 1945–1954     

3D－QSAR Study on Diindolylmethane and Its Analogues with Comparative Molecular Field Analysis(CoMFA)

Comparative molecular field analysis (CoMFA),a three dimensional quantitative structure-activity relationship (3D-QSAR) method was applied to a series of diindolylmethane(DIM) analogs to study the relationship between their structure and their induction of CYP 1A1-associated ethoxyresorufin-O-deethylase(EROD) activity.A DISCO model of pharmacophore was derved to guide the superposition of the compounds.The coefficient of cross-validation (q^2) and non cross-validation(r^2) for the model established by the study are 0.827 and 0.988 respectively,the value of variance ratio (F) is 103.53 and standard error estimate (SEE)is 0.044.These values indicate that the CoMFA model derived is significant and might have a good prediction for the catalytic activity of DIM compounds.As a consequence,the predicted activity values of new designed compounds were all higher than that of the reported value.     

Novel and Stereospecific Synthesis of (2S)‐3‐(2,4,5‐Trifluorophenyl)propane‐1,2‐diol from D‐Mannitol

A stereospecific synthesis of (2S)‐3‐(2,4,5‐trifluorophenyl)propane‐1,2‐diol from D ‐mannitol has been developed. The reaction of 2,3‐O‐isopropylidene‐D ‐glyceraldehyde with 2,4,5‐trifluorophenylmagnesium bromide gave [(4R)‐2,2‐dimethyl‐1,3‐dioxolan‐4‐yl](2,4,5‐trifluorophenyl)methanol in 65% yield as a mixture of diastereoisomers (1 : 1). The Ph₃P catalyzed reaction of the latter with C₂Cl₆ followed by reduction with Pd/C‐catalyzed hydrogenation gave (2S)‐3‐(2,4,5‐trifluorophenyl)propane‐1,2‐diol with >99% ee and 65% yield.