Comparative analysis of the full set of methylated β‐cyclodextrins as chiral selectors in capillary electrophoresis

The chiral separation ability of the full library of methylated‐β‐cyclodextrins towards pharmacologically significant racemic drugs including basic compounds was studied by chiral CE. The syntheses of all the methylated, single isomer β‐cyclodextrins were revised and optimized and the aqueous solubility of the derivatives was unambiguously established. The three most relevant commercially available methylated isomeric mixtures were also included in the screening, so a total of ten various methylated CDs were investigated. The effects of the selector concentration on the enantiorecognition properties at acidic pH were investigated. Among the dimethylated β‐cyclodextrins, the heptakis (2,6‐di‐O‐methyl)‐β‐cyclodextrin isomer (2,6‐DIMEB) resulted to be the most versatile chiral selector. Terbutaline was selected as a model compound for the in‐depth investigation of host‐guest enantiodiscrimination ability. The association constants between the two terbutaline enantiomers and 2,6‐DIMEB were determined in order to support that the enantioseparation is driven by differences is host‐guest binding. The migration order of the enantiomers was confirmed by performing spiking experiments with the pure enantiomers. 1D and 2D NMR spectroscopy was applied to the 2,3‐, and 2,6‐DIMEB/terbutaline systems to rationalize at molecular level the different enantioseparation ability of the dimethylated β‐cyclodextrin selectors.     

Chemical microcharacterization of ultrathin iodide conversion layers and adsorbed thiocyanate surface layers on silver halide microcrystals with time-of-flight SIMS.

The technique of imaging time-of-flight secondary ion mass spectrometry (TOF-SIMS) and dual beam depth profiling has been used to study the composition of the surface of tabular silver halide microcrystals. Analysis of individual microcrystals with a size well below 1 microm from a given emulsion is possible. The method is successfully applied for the characterization of silver halide microcrystals with subpercent global iodide concentrations confined in surface layers with a thickness below 5 nm. The developed TOF-SIMS analytical procedure is explicitly demonstrated for the molecular imaging of adsorbed thiocyanate layers (SCN) at crystal surfaces of individual crystals and for the differentiation of iodide conversion layers synthesized with KI and with AgI micrates (nanocrystals with a size between 10 and 50 nm). It can be concluded that TOF-SIMS as a microanalytical, surface-sensitive technique has some unique properties over other analytical techniques for the study of complex structured surface layers of silver halide microcrystals. This offers valuable information to support the synthesis of future photographic emulsions.     

Asymmetric synthesis of 4,4-disubstituted-2-imidazoli-dinones: potent NK1 antagonists

[structure: see text] A highly efficient and practical synthesis of 4,4-Disubstituted-2-Imidazolidinones utilizing a "self-reproduction of the center of chirality" strategy is described.     

Small Data Can Play a Big Role in Chemical Discovery

The chemistry community is currently witnessing a surge of scientific discoveries in organic chemistry supported by machine learning (ML) techniques. Whereas many of these techniques were developed for big data applications, the nature of experimental organic chemistry often confines practitioners to small datasets. Herein, we touch upon the limitations associated with small data in ML and emphasize the impact of bias and variance on constructing reliable predictive models. We aim to raise awareness to these possible pitfalls, and thus, provide an introductory guideline for good practice. Ultimately, we stress the great value associated with statistical analysis of small data, which can be further boosted by adopting a holistic data-centric approach in chemistry.     

Influence of cultivation conditions on the production of cellulolytic enzymes withTrichoderma reesei Rutgers C30 in aqueous two-phase systems

Cellulolytic enzyme production in aqueous two-phase systems withTrichoderma reesei Rutgers C30 has been investigated. The influ ence of different phase systems, as well as addition of media compo nents and substrate on enzyme production have been studied. Extractive enzyme production in fed-batch cultivations was per formed in a phase system composed of PEG 8000 5%-Dextran T500 7% with 1% Solka-Floc BW 200 as substrate. The cellulolytic enzyme system was intermittently withdrawn with the top phase. Addition of media components every 24 h and cellulose every 72 h gave an aver age enzyme activity in the withdrawn top phase of 2.2 FPU/mL dur ing 170 h cultivation. The corresponding productivity was 18 FPU/lh. The productivity was increased to 24 FPU/l.h when media compo nents and cellulose were added every 72 h. The average enzyme con centration was then 1.6 FPU/mL. The results are discussed in relation to methods for cellulolytic enzyme production involving immobiliza tion and cell recycling.     

Conformational energies and rotational barriers in 3-methyl-1-butene and 1-butene: An ab initio and molecular mechanics study

The calculated result obtained with MM2(87) for the rotation of the isopropyl group in 3-methyl-1-butene is not in agreement with experimental data. In order to reparametrize the C_sp2-C_sp3-C_sp-C_sp3 torsional angle, 3-methyl-1-butene and 1-butene have been studied by molecular mechanics (MM2(87)) and ab initio (MP2/6-31G* and MP3/6-31G*) calculations. The reparametrization of the torsional angle gives calculated results from MM2(87) in agreement with experimental data and ab initio calculations for both 3-methyl-1-butene and 1-butene. The calculated barriers for the rotation of alkyl groups in alkylbenzenes are improved with these new parameters.     

A comparison of conformational energies calculated by several molecular mechanics methods

Several commonly used molecular mechanics force fields have been tested for accuracy in conformational energy calculations. Differences in performance between the force fields are discussed for different classes of structures. MMFF93 and force fields based on the MM2 or MM3 functional form are found to perform significantly better than other force fields in the test, with average conformational energy errors around 0.5 kcal/mol. CFF91 also reaches this accuracy for the subset in which fully determined parameters are used, but it doubles the overall error due to use of estimated parameters. Harmonic force fields generally have average errors exceeding 1 kcal/mol. Factors influencing accuracy are identified and discussed. © 1996 by John Wiley & Son s, Inc.     

Synthesis of 2′-Deoxy-5-(isothiazol-5-yl)uridine and Its Interaction with the HSV-1 Thymidine Kinase

2′-Deoxy-5-(isothiazol-5-yl)uridine ( 12 ) was synthesized starting from 2′-deoxy-5-iodouridine using a Pd-catalysed cross-coupling reaction with propiolaldehyde diethyl acetal followed by deprotection and ring closure using thiosulfate. 2′-Deoxyuridine 12 has a particular place among the 5-heteroaryl-substituted 2′-deoxyuridines in that it has a high affinity for herpes simplex virus type 1 (HSV-1)-encoded thymidine kinase (TK) without antiviral activity. Biochemical studies revealed that 12 is a substrate for viral TK. We further investigated the interaction of 12 with the HSV-1 thymidine kinase. The conformation of 12 in solution was established by NMR spectroscopy. The most stable conformer 12A has the S-atom of the isothiazole ring placed in the neighbourhood of the C(4)?O group of the pyrimidine moiety. The compound was docked in its most stable conformation in the active site of HSV-1 TK and subjected to energy minimization. This demonstrated that the isothiazole moiety binds in a cavity lined by the side chains of Tyr-132, Arg-163, Ala-167, and Ala-168 and that the C(3) atom of the isothiazole moiety is located in close proximity of the phenolic O-atom of Tyr-132 and the aliphatic part of the Arg-163 side chain.     

Fast Exfoliation and Functionalisation of Two‐Dimensional Crystalline Carbon Nitride by Framework Charging

Two‐dimensional (2D) layered graphitic carbon nitride (gCN) nanosheets offer intriguing electronic and chemical properties. However, the exfoliation and functionalisation of gCN for specific applications remain challenging. We report a scalable one‐pot reductive method to produce solutions of single‐ and few‐layer 2D gCN nanosheets with excellent stability in a high mass yield (35 %) from polytriazine imide. High‐resolution imaging confirmed the intact crystalline structure and identified an AB stacking for gCN layers. The charge allows deliberate organic functionalisation of dissolved gCN, providing a general route to adjust their properties.     

An improved nicotinic pharmacophore and a stereoselective CoMFA-model for nicotinic agonists acting at the central nicotinic acetylcholine receptors labelled by [3H]-N-methylcarbamylcholine

A study of a series of compounds with agonistic effect at the alpha4beta2 nicotinic acetylcholine receptors resulted in an improved pharmacophore model as well as a CoMFA model. The pharmacophore was composed of three pharmacophoric elements: (1) a site point (a) corresponding to a protonated nitrogen atom, (2) a site point (b) corresponding to an electronegative atom capable of forming a hydrogen bond, and (3) the centre of a heteroaromatic ring or a C=O bond (c). The pharmacophoric elements were related by the following parameters: (a-b) 7.3-8.0 A, (a-c) 6.5-7.4 A, and the angle between the two distance vectors (delta bac) 30.4-35.8 degrees. In addition to this, a stereoselective CoMFA model was developed, which showed good predictability even for compound classes not present in the training set.