CHARMM general force field: A force field for drug‐like molecules compatible with the CHARMM all‐atom additive biological force fields

The widely used CHARMM additive all‐atom force field includes parameters for proteins, nucleic acids, lipids, and carbohydrates. In the present article, an extension of the CHARMM force field to drug‐like molecules is presented. The resulting CHARMM General Force Field (CGenFF) covers a wide range of chemical groups present in biomolecules and drug‐like molecules, including a large number of heterocyclic scaffolds. The parametrization philosophy behind the force field focuses on quality at the expense of transferability, with the implementation concentrating on an extensible force field. Statistics related to the quality of the parametrization with a focus on experimental validation are presented. Additionally, the parametrization procedure, described fully in the present article in the context of the model systems, pyrrolidine, and 3‐phenoxymethylpyrrolidine will allow users to readily extend the force field to chemical groups that are not explicitly covered in the force field as well as add functional groups to and link together molecules already available in the force field. CGenFF thus makes it possible to perform “all‐CHARMM” simulations on drug‐target interactions thereby extending the utility of CHARMM force fields to medicinally relevant systems. © 2009 Wiley Periodicals, Inc. J Comput Chem, 2010     

A modified strategy for Pictet-Spengler reaction leading to the synthesis of imidazoquinoxalines on solid phase

An alternative strategy for Pictet-Spengler reaction involving an N-1 linked aromatic amine of imidazole and aldehydes is described. This is in contrast to a typical Pictet-Spengler reaction, which involves an aliphatic amine attached to the carbon of an activated aromatic nucleus and an aldehyde. Our strategy commences with the nucleophilic replacement of fluorine in resin-bound o-fluoro-nitrobenzoic acid with mono- or disubstituted imidazole, followed by reduction of the nitro group to give an N1 linked aromatic amine of the resin-bound imidazole. This was subsequently treated with an aldehyde in toluene at 80 degrees C and then oxidized in the presence of DDQ to give resin-bound imidazoquinoxalines. Finally, acidolytic cleavage furnished the desired compounds in high yields and purities.     

Helical water chain mediated proton conductivity in homochiral metal-organic frameworks with unprecedented zeolitic unh-topology

Four new homochiral metal-organic framework (MOF) isomers, [Zn(l-L(Cl))(Cl)](H(2)O)(2) (1), [Zn(l-L(Br))(Br)](H(2)O)(2) (2), [Zn(d-L(Cl))(Cl)](H(2)O)(2) (3), and [Zn(d-L(Br))(Br)](H(2)O)(2) (4) [L = 3-methyl-2-(pyridin-4-ylmethylamino)butanoic acid], have been synthesized by using a derivative of L-/D-valine and Zn(CH(3)COO)(2)·2H(2)O. A three-periodic lattice with a parallel 1D helical channel was formed along the crystallographic c-axis. Molecular rearrangement results in an unprecedented zeolitic unh-topology in 1-4. In each case, two lattice water molecules (one H-bonded to halogen atoms) form a secondary helical continuous water chain inside the molecular helix. MOFs 1 and 2 shows different water adsorption properties and hence different water affinity. The arrangement of water molecules inside the channel was monitored by variable-temperature single-crystal X-ray diffraction, which indicated that MOF 1 has a higher water holding capacity than MOF 2. In MOF 1, water escapes at 80 °C, while in 2 the same happens at a much lower temperature (～40 °C). All the MOFs reported here shows reversible crystallization by readily reabsorbing moisture. In MOFs 1 and 2, the frameworks are stable after solvent removal, which is confirmed by a single-crystal to single-crystal transformation. MOFs 1 and 3 show high proton conductivity of 4.45 × 10(-5) and 4.42 × 10(-5) S cm(-1), respectively, while 2 and 4 shows zero proton conductivity. The above result is attributed to the fact that MOF 1 has a higher water holding capacity than MOF 2.     

Baryogenesis and damping in nonminimal electroweak models

We calculate the baryon asymmetry of the Universe in the standard model of the electroweak theory with CP violation appropriate for simple extensions of the Higgs sector. The propagation of quarks of masses up to about 5 GeV are considered, taking into account the effect of damping rate. We find that the contribution of the b quark can still account for the observed baryon asymmetry to within the theoretical uncertainties of such models.

     

Shape-influenced magnetic properties of CoO nanoparticles

Despite uncertainty about the potential human health and environmental risks of nanotechnology, major stakeholders such as regulatory agencies and the nanotechnology industry are already negotiating the emerging regulatory framework for nanotechnology. Because of a relative lack of nano-specific regulations, the future of nanotechnology development will depend greatly on the views held by the nanotechnology industry. This study fills the research gap in understanding how the nanotechnology industry perceives the risks of nanotechnology. This is the first interview-based study of the nanotechnology industry in the United States. Semi-structured, open-ended phone interviews were conducted with 17 individuals involved in the commercialization of nanotechnology in the United States. Results indicate that while the industry acknowledges uncertainty about the potential risks of nanotechnology and takes significant precaution in ensuring the safety of their products, they do not see nanotechnology as novel or risky. They do not believe that uncertainty over risk ought to delay the further development of nanotechnology. The industry sees itself as the primary agent in ensuring consumer safety and believes that consumers are adequately protected. They are also largely benefit-centric and view product labeling as inefficacious.     

Soft mode and related behaviour in the SmA and SmC* phases of a ferroelectric liquid crystalline polymer by dielectric spectroscopy

Anomalous dielectric relaxation behaviour is observed in the ferroelectric liquid crystalline polymer (viz. ferroelectric copolysiloxane (R)-COPS 11-10) around the ferroelectric SmC* to paraelectric SmA phase transition. Measurements have been performed on sample of thickness ～10 μm in indium-tin-oxide coated cell in the frequency range 10 Hz to 13 MHz. With increase of temperature, a gradual shift of the soft mode frequency towards the higher frequency side was observed, while a decrease in the relaxation strength was seen with the corresponding increase in temperature. The shifts of the soft modes in the SmC* and SmA phase are considered to be due to change in the viscosity of the polymer, as an increase in viscosity increases fluctuations of the coupling between the dipoles in the network even far from the paraelectric-ferroelectric phase transition. Application of a bias field causes a shift of the critical frequency towards the higher frequency side, while the dielectric strength (δε) decreases under the bias field. The Cole-Cole fitting parameters obtained from the best fit of the dielectric constant data are found to be consistent with other similar materials. Another relaxation mode (molecular mode) was also observed which comes into play in both the smectic phases (SmC% and SmA) and contributes to the dielectric permittivity.     

A Next-Generation Air-Stable Palladium(I) Dimer Enables Olefin Migration and Selective C−C Coupling in Air

We report a new air-stable Pd^I dimer, [Pd(μ-I)(PCy₂^tBu)]₂, which triggers E-selective olefin migration to enamides and styrene derivatives in the presence of multiple functional groups and with complete tolerance of air. The same dimer also triggers extremely rapid C−C coupling (alkylation and arylation) at room temperature in a modular and triply selective fashion of aromatic C−Br, C−OTf/OFs, and C−Cl bonds in poly(pseudo)halogenated arenes, displaying superior activity over previous Pd^I dimer generations for substrates that bear substituents ortho to C−OTf.     

Diversity Oriented Synthesis of Indoloazepinobenzimidazole and Benzimidazotriazolobenzodiazepine from N1‐Alkyne‐1,2‐diamines

A one‐pot protocol for the diversity oriented synthesis of two N‐polyheterocycles indoloazepinobenzimidazole and benzimidazotriazolobenzodiazepine from a common N¹‐alkyne‐1,2‐diamine building block is described. The approach involves sequential formation of benzimidazole through cyclocondensation and oxidation, which is followed by the formation of either an azepine ring (through alkyne activation and 6‐endo‐dig cyclization, 1,2‐migration with ring expansion, and re‐aromatization), or diazepine and triazole rings through 1,3‐dipolar cycloaddition.     

Light-charged-particle emission from hot <Superscript>32</Superscript>S<Superscript>*</Superscript>formed in <Superscript>20</Superscript>Ne + <Superscript>12</Superscript>C reaction

Inclusive energy distributions for light charged particles (p , d , t and have been measured in the ²⁰Ne (158, 170, 180, 200 MeV) + ¹²C reactionsintheangularrange$10^°$ - - $50^°$.Exclusivelight-charged-particleenergydistributionmeasurementswerealsodoneforthesamesystemat158 MeVbombardingenergybyin - planelightchargedparticle - - fragmentcoincidence.Pre - equilibriumcomponentshavebeenseparatedoutfromprotonenergyspectrausingthemovingsourcemodelconsideringtwosources.ThedatahavebeencomparedwiththepredictionsofthestatisticalmodelcodeCASCADE.Ithasbeenobservedthatsignificantdeformationeffectswereneededtobeintroducedinthecompoundnucleusinordertoexplaintheshapeoftheevaporated$d$,$t$energyspectra.Forprotons, evaporatedenergyspectrawereratherinsensitivetonucleardeformation, thoughangulardistributionscouldnotbeexplainedwithoutdeformation.Thedecaysequenceofthehot$³²S$nucleushasbeeninvestigatedthroughexclusivelight - - charged - particlemeasurementsusingthe$²⁰Ne$$(158 MeV) + $¹²C reaction. Information on the sequential decay chain has been extracted through a comparison of the experimental data with the predictions of the statistical model. It is observed from the present analysis that exclusive light-charged-particle data may be used as a powerful tool to probe the decay sequence of hot light compound systems.     

Possibility of Love wave propagation in a porous layer under the effect of linearly varying directional rigidities

The present paper investigates the Love wave propagation in an anisotropic porous layer under the effect of rigid boundary. Effect of initial stresses on the propagation of Love waves in a fluid saturated, anisotropic, porous layer having linear variation in directional rigidities lying in contact over a pre-stressed, inhomogeneous elastic half-space has also been considered. The dispersion equation of phase velocity has been derived and the influence of medium characteristic such as porosity, rigid boundary, initial stress, anisotropy and inhomogeneity over it has been discussed. The velocities of Love waves have been calculated numerically as a function of KH (where K is the wave number and H is the thickness of the layer) and are presented in a number of graphs.