The preparation of hot-pressed chalcogenide spinels. II. Stoichiometry and optical transparency in CdCr2S4 and CoCr2S4

The compounds CdCr₂S₄ and CoCr₂S₄ have been hot pressed into disks that are highly transparent in the infrared. Stoichiometry has been altered by varying the $\text{Cr}{}^{\mathrm{3+}}\text{M}{}^{\mathrm{2+}}$ ratio, where M²⁺ is Cd²⁺ or Co²⁺. The effects of nonstoichiometry on optical transmission were determined. Excess M²⁺ attenuates the transmission much more than excess Cr³⁺.     

Additions of enantiopure alpha-sulfinyl carbanions to (S)-N-sulfinimines: asymmetric synthesis of beta-amino sulfoxides and beta-alphamino alcohols

The addition of the lithium anions derived from (R)- and (S)-methyl and -ethyl p-tolyl sulfoxides to (S)-N-benzylidene-p-toluenesulfinamide provides an easy access route to enantiomerically pure beta-(N-sulfinyl)amino sulfoxides. Stereoselectivity can be achieved when the configurations at the sulfur atoms of the two reagents are opposite (matched pair), thus resulting in only one diastereoisomer, even for the case in which two new chiral centers are created. The N-sulfinyl group primarily controls the configuration of the carbon bonded to the nitrogen, whereas the configuration of the alpha-sulfinyl carbanion seems to be responsible for the level of asymmetric induction, as well as for the configuration of the new stereogenic C-SO carbon in the reactions with ethyl p-tolyl sulfoxides. An efficient method for transforming the obtained beta-(N-sulfinyl)amino sulfoxides into optically pure beta-amino alcohols, based on the stereoselective non-oxidative Pummerer reaction, is also reported.     

Free energy derivatives: A new method for probing the convergence problem in free energy calculations

The convergence behavior of free energy calculations has been explored in more detail than in any previously reported work, using a model system of two neon atoms in a periodic box of water. We find that for thermodynamic integration-type free energy calculations as much as a nanosecond or more molecular dynamics sampling is required to obtain a fully converged value for a single λ point of the integrand. The concept of “free energy derivatives” with respect to the individual parameters of the force field is introduced. This formalism allows the total convergence of the simulation to be deconvoluted into components. A determination of the statistical “sampling ratio” from these simulations indicates that for window-type free energy calculations carried out in a periodic waterbox of typical size at least 0.6 ps of sampling should be performed at each window (0.7 ps if constraint contributions to the free energy are being determined). General methods to estimate and reduce the error in thermodynamic integration and free energy perturbation calculations are discussed. We show that the difficulty in applying such methods is determining a reliable estimate of the correlation length from a short series of data. © 1994 by John Wiley & Sons, Inc.     

(Z)-3-p-tolylsulfinylacrylonitrile as a chiral dienophile: diels-alder reactions with furan and acyclic dienes

The behavior of (Z)-3-p-tolylsulfinylacrylonitrile (1) as a chiral dienophile has been evaluated from its reactions with furan and acyclic dienes. Electrostatic interactions of the cyano group with the sulfinyl one restrict the conformational mobility around the C-S bond, thus controlling the pi-facial selectivity, which is almost complete in all cases, the approach of the diene from the less-hindered face of the dienophile (that bearing the lone electron pair) in the predominant rotamer being the favored one. The regioselectivity is also completely controlled by the cyano group. Additionally, the reactivity of compound 1 as well as its endo-selectivity are both higher than those observed for the corresponding (Z)-3-sulfinylacrylates, thus proving the potential of sulfinylnitriles as chiral dienophiles.     

A Novel Electron-Conformational Approach to Molecular Modeling for QSAR by Identification of Pharmacophore and Anti-Pharmacophore Shielding

Abstract

A novel method of pharmacophore identification and activity prediction in structure-activity (structure-property) relationships is worked out as an essential extension and improvement of previous publications. In this method each conformation of the molecular systems in the training set of the SAR problem is presented by both electronic structure and geometry parameters arranged in a matrix form. Multiple comparisons of these matrices for the active and inactive compounds allows one to separate a smaller number of matrix elements that are common for all the active compounds and are not present in the same arrangement in the inactive ones. This submatrix of activity represents the pharmacophore (Pha).

By introducing the Anti-Pharmacophore Shielding (APS) defined as molecular groups and competing charges outside the Pha that hinder the proper docking of the Pha with the bioreceptor, the procedure of Pha identification is essentially reduced to the treatment of a smaller number of simplest in structure most active and inactive compounds. A simple empirical scheme is suggested to estimate the APS numerically, while the contributions of different conformations of the same compound are taken into account by means of Boltzmann distribution. This enables us to make approximate quantitative predictions of activities.

In application to rice blast activity we reached an approximately 100% (within experimental error) prediction probability of the activity qualitatively (yes, no), and with r ² = 70% quantitatively.     

The preparation of hot-pressed chalcogenide spinels

The preparation of chalcogenide spinel powders is reviewed. Microcrystalline powders are formed by the thermal reaction of mixtures of anhydrous cadmium and chromium chlorides or coprecipitated cadmium and chromium hydroxides with H₂S, Ar + CS₂, or H₂ + Se. These spinel powders are hot pressed to form highly dense, polycrystalline disks. The effects of pressing variables on optical absorption coefficients are given. The spinel powders and hot-pressed disks are characterized and optical spectra, refractive index, and Faraday rotation data are given.     

Spin-singlet clusters in the ladder compound NaV2O5

The space group of alpha(')-NaV2O5 turns below T(c) = 34 K from Pmmn with all V sites equivalent, into Fmm2 with three independent vanadium sites per layer. This is incompatible with models of charge ordering into V4+ and V5+. Our structure determination indicates that the phase transition consists of a charge ordering with three distinct valence states, formally V4+, V4.5+, and V5+. The singlet formation is not associated with dimerization on the spin ladder, but with the formation of spin clusters. Finally, we ascribe the quadrupling of the c axis to the large polarizability of the V2O5 skeleton.     

Dependence of pulser driving responses on electrical and motional characteristics of NDE ultrasonic probes

Acoustic performance in ultrasonic transmitters can be improved by means of a suitable electrical driving response and matching/tuning networks. It is important to predict this electrical response, but doing so is not easy because it departs notably from the nominal pattern with the loading probes. In practice, the analysis of HV pulser spikes in NDE applications requires fairly complex models in the transient regime and, in addition, non-linear problems could arise, especially in the case of tuned transmitters. In this paper, the most relevant influences of loading characteristics of NDT ultrasonic probes on the pulser electrical driving responses are evaluated in time and frequency domains. Conventional pulse generators and typical NDE pulsers are considered. Driving responses are analysed across commercial ultrasonic probes and, alternatively, across similar purely electrical loads. Distinct influences on pulser responses from electrical and motional sections of the probes are identified. All these aspects are studied on the basis of experimental and computer results.     

AAK1 identified as an inhibitor of neuregulin-1/ErbB4-dependent neurotrophic factor signaling using integrative chemical genomics and proteomics

Target identification remains challenging for the field of chemical biology. We describe an integrative chemical genomic and proteomic approach combining the use of differentially active analogs of small molecule probes with stable isotope labeling by amino acids in cell culture-mediated affinity enrichment, followed by subsequent testing of candidate targets using RNA interference-mediated gene silencing. We applied this approach to characterizing the natural product K252a and its ability to potentiate neuregulin-1 (Nrg1)/ErbB4 (v-erb-a erythroblastic leukemia viral oncogene homolog 4)-dependent neurotrophic factor signaling and neuritogenesis. We show that AAK1 (adaptor-associated kinase 1) is a relevant target of K252a, and that the loss of?AAK1?alters ErbB4 trafficking and expression levels,?providing evidence for a previously unrecognized role for AAK1 in Nrg1-mediated neurotrophic?factor signaling. Similar strategies should lead to the discovery of novel targets for therapeutic development.