Configuration-Odor Relationships in 5β-Ambrox

The four possible A/B cis-fused diastereoisomers of Ambrox® have been synthesized and their configurations and conformations established by X-ray and NMR analysis. Only 5β-ambrox (= 1,2,3a,4,5,5β,6,7,8,9,9a,9bα-dodecahydro-3aβ,6,6,9aβ-tetramethylnaphtho[2,1-b]furan; 5 ) has an odor quality comparable to Ambrox®. The 1,3-synperiplanar/diaxial conformation of the substituents at C(8) ( = C(3a)) and C(10) (= C(9a)) has thus been confirmed to be a compulsory structure element for the particular odor.     

Targeting apoptosis via chemical design: inhibition of bid-induced cell death by small organic molecules

Bid is a key member of the Bcl-2 family proteins involved in the control of the apoptotic cascade in cells, leading to cell death. Uncontrolled cell death is associated with several human pathologies, such as neurodegenerative diseases and ischemic injuries. Therefore, Bid represents a potential yet unexplored and challenging target for strategies aimed at the development of therapeutic agents. Here we show that a multidisciplinary NMR-based approach that we named SAR by ILOEs (structure activity relationships by interligand nuclear Overhauser effect) allowed us to rationally design a series of 4-phenylsulfanyl-phenylamine derivatives that are capable of occupying a deep hydrophobic crevice on the surface of Bid. These compounds represent the first antiapoptotic small molecules targeting a Bcl-2 protein as shown by their ability to inhibit tBid-induced SMAC release, caspase-3 activation, and cell death.     

A general mass spectrometry-based assay for the quantitation of protein-ligand binding interactions in solution

A new method that utilizes matrix-assisted laser desorption/ionization (MALDI) mass spectrometry and exploits the hydrogen/deuterium (H/D) exchange properties of proteins was developed for measuring the thermodynamic properties of protein-ligand complexes in solution. Dissociation constants (Kd values) determined by the method for five model protein-ligand complexes that included those with small molecules, nucleic acids, peptides, and other proteins were generally in good agreement with Kd values measured by conventional methods. Important experimental advantages of the described method over existing methods include: the ability to make measurements in a high-throughput and automated fashion, the ability to make measurements using only picomole quantitities of protein, and the ability to analyze either purified or unpurified protein-ligand complexes.     

Neue Phellandren-Derivate aus dem Wurzelöl von Angelica archangelicaL

New Phellandrene Derivatives from the Root Oil of Angelica archangelica L . 2-Nitro-1,5-p-menthadiene ( 5 ), trans- and cis-6-nitro-1(7), 2-p-menthadiene ( 6 and 7 ), trans-1(7), 5-p-menthadien-2-yl acetate ( 9 ) and a formal phellandrene derivative, 7-isopropyl-5-methyl-5-bicyclo [2.2.2]octen-2-one ( 16 ), have been identified in the root oil of Angelica archangelica L . Starting from (?)-(R)-α-phellandrene ( 1 ) (R)- 5 , (4R, 6S)- 6 /(4R, 6R)- 7 , (2S, 4R)- 9 and (1R, 4R, 7R)- 16 as well as (2S, 4R)- 11 , (2R, 4R)- 12 and (2R, 4R)- 10 have been prepared.     

Effect of polymer and ion concentration on mechanical and drug release behavior of gellan hydrogels using factorial design

Developing optimized hydrogel products requires an in-depth understanding of the mechanisms that drive hydrogel tunability. Here, we performed a full 4 × 4 factorial design study investigating the impact of gellan, a naturally derived polysaccharide (1%, 2%, 3%, or 4% w/v) and CaCl₂ concentration (1, 3, 7, or 10 mM) on the viscoelastic, swelling, and drug release behavior of gellan hydrogels containing a model drug, vancomycin. These concentrations were chosen to specifically provide insight into gellan hydrogel behavior for formulations utilizing polymer and salt concentrations expanding beyond those commonly reported by previous studies exploring gellan. With increasing gellan and CaCl₂ concentration, the hydrogel storage moduli (0.1–100 kPa) followed a power-law relationship and on average these hydrogels had higher liquid absorption capability and greater total drug release over 6 days. We suggest that the effects of gellan and CaCl₂ concentration and their interactions on hydrogel properties can be explained by various phenomena that lead to increased swelling and increased resistance to network expansion.     

Multiobjective Optimal Control Methods for the Navier-Stokes Equations Using Reduced Order Modeling

In a wide range of applications it is desirable to optimally control a dynamical system with respect to concurrent, potentially competing goals. This gives rise to a multiobjective optimal control problem where, instead of computing a single optimal solution, the set of optimal compromises, the so-called Pareto set, has to be approximated. When the problem under consideration is described by a partial differential equation (PDE), as is the case for fluid flow, the computational cost rapidly increases and makes its direct treatment infeasible. Reduced order modeling is a very popular method to reduce the computational cost, in particular in a multi query context such as uncertainty quantification, parameter estimation or optimization. In this article, we show how to combine reduced order modeling and multiobjective optimal control techniques in order to efficiently solve multiobjective optimal control problems constrained by PDEs. We consider a global, derivative free optimization method as well as a local, gradient-based approach for which the optimality system is derived in two different ways. The methods are compared with regard to the solution quality as well as the computational effort and they are illustrated using the example of the flow around a cylinder and a backward-facing-step channel flow.

     

Engineering Multifunctional Gold Decorated Dendritic Mesoporous Silica/Tantalum Oxide Nanoparticles for Intraperitoneal Tumor‐Specific Delivery

Nonspecific high‐energy radiation for treatment of metastatic ovarian cancer is limited by damage to healthy organs, which can be mitigated by the use of radiosensitizers and image‐guided radiotherapy. Gold (Au) and tantalum oxide (TaO_x) nanoparticles (NPs), by virtue of their high atomic numbers, find utility in the design of bimetallic NP systems capable of high‐contrast computed tomography (CT) imaging as well as a potential radiosensitizing effect. These two radio‐dense metals are integrated into dendritic mesoporous silica NPs (dMSNs) with radial porous channels for high surface‐area loading of therapeutic agents. This approach results in stable, monodispersed dMSNs with a uniform distribution of Au on the surface and TaO_x in the core that exhibits CT attenuation up to seven times greater than iodine or monometallic dMSNs without either TaO_x or Au. Tumor targeting is assessed in a metastatic ovarian cancer mouse model. Ex vivo micro‐CT imaging of collected tumors shows that these NPs not only accumulate at tumor sites but also penetrate inside tumor tissues. This study demonstrates that after intraperitoneal administration, rationally designed bimetallic NPs can simultaneously serve as targeted contrast agents for imaging tumors and to enhance radiation therapy in metastatic ovarian cancer.     

Effect of tensile load on the actuation performance of pH‐sensitive hydrogels

pH‐responsive hydrogels are capable of converting chemical energy to mechanical work. To optimize their use as actuators, their response when operating against an external load must be fully characterized. Here, the actuation strain of a model pH‐sensitive hydrogel as a function of different constant loads is studied. The experimental actuation strain, produced by switching the pH from 2 to 12, decreases significantly and monotonically with increasing initial tensile load. Two models are developed to predict the actuation strain as a function of applied stress. Simple mechanical models based on the change in hydrogel modulus and cross sectional area due to the change in pH are unsatisfactory as they predict only a small change in actuation strain with increasing external stress. However, the model based on the elastic and mixing free energy functions derived from the Flory–Huggins theory is found to accurately account for the actuation strain as a function of stress. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2015 , 53, 218–225     

Copper‐Catalyzed Amidation of Primary and Secondary Alkyl Boronic Esters

The oxidative copper‐catalyzed cross‐coupling of functionalized alkyl boronic esters with primary amides is reported. Through the identification of appropriate diketimine ligands, conditions for efficient coupling of both primary and secondary alkyl boronic esters with diverse primary amides, including acetamide, have been developed.     

Generation and recombination in two-dimensional bipolar transistors

We study the effects of recombination and generation process on the operation of bipolar junction transistor based on two-dimensional materials, and in particular, graphone. Here, we use Shockley–Read–Hall model to study these process. First, we investigate the current–voltage characteristics of a graphone p–n junction considering generation and recombination process. Then, we calculate the estimated changes in current gain, cutoff frequency, and output characteristics of a graphone bipolar junction transistor designed in a recent study.