Spherical coordinate representations of solvent composition for liquid chromatography method development using experimental design

One of the major techniques used for the method development of ternary and quaternary high performance liquid chromatography (HPLC) systems has been to use mixture designs, often referred to as "Glajch's Triangle". This technique does not allow for the systematic and simultaneous optimization of other factors such as gradient time, pH and temperature that affect the quality of separations. An alternative approach is to use experimental designs. The condition, however, that the composition of all components of the mobile phase must total 100% presents a problem when trying to mathematically represent ranges of each mobile phase constituent of a ternary or quaternary system. A method is described here, based on spherical coordinate representations, that adheres to the constraints of the mobile phase composition and allows experimental designs, such as central composite and factorial designs, to be applied to the simultaneous optimization of the mobile phase composition. Other factors, in particular temperature and gradient time, can then be included in the design. As a result of applying these designs to the HPLC separation of phenols and corticosteroids, it was found necessary to include three-way interactions between experimental factors in the model. The significance of these interactions shows that they need to be considered in HPLC method development.     

The de novo design of median molecules within a property range of interest

Summary In this paper an application is presented of the median molecule workflow to the de novo design of novel molecular entities with a property profile of interest. Median molecules are structures that are optimised to be similar to a set of existing molecules of interest as an approach for lead exploration and hopping. An overview of this workflow is provided together with an example of an instance using the similarity to camphor and menthol as objectives. The methodology of the experiments is defined and the workflow is applied to designing novel molecules for two physical property datasets: mean molecular polarisability and aqueous solubility. This paper concludes with a discussion of the characteristics of this method.     

Dynamic molecular recognition in the generation of a new crystal-engineering motif: a unique case study of a dicarboxylic acid with a ditopic receptor favouring a polymeric over a dimeric hydrogen-bonded supramolecular complex

A new crystal-engineering motif has been developed where a ditopic receptor 1 shows a novel syn-syn hydrogen-bonded polymeric supramolecular complex (Fig. 4b) (instead of a 1:1 dimeric syn-syn or polymeric syn-anti complex) giving rise to a hydrogen-bonded stair-like polymeric ribbon structure between the binding groups of the receptor pyridine amide and the carboxyl groups of the guest substrate.     

Three-dimensional hydrogen-bond geometry and probability information from a crystal survey

Summary An extensive crystal survey of the Cambridge Structural Database has been carried out to provide hydrogen-bond data for use in drug-design strategies. Previous crystal surveys have generated 1D frequency distributions of hydrogen-bond distances and angles, which are not sufficient to model the hydrogen bond as a ligand-receptor interaction. For each hydrogen-bonding group of interest to the drug designer, geometric hydrogen-bond criteria have been derived. The 3D distribution of complementary atoms about each hydrogen-bonding group has been ascertained by dividing the space about each group into bins of equal volume and counting the number of observed hydrogen-bonding contacts in each bin. Finally, the propensity of each group to form a hydrogen bond has been calculated. Together, these data can be used to predict the potential site points with which a ligand could interact and there-fore could be used in molecular-similarity studies, pharmacophore query searching of databases, or de novo design algorithms.     

不依赖于统计模型的手性毛细管电泳分离多指标同时优化

考虑到手性毛细管电泳分离机理的复杂性，提出了不依赖于统计模型的二进制编码遗传算法多目标优化策略。根据实验参数的多少及其重要性，采用均匀设计安排完成初步实验。并用Derringer功效函数作为多指标同时优化的评价指标，以取得较高的分离度和较快分离速度；通过对实验参数给予编码，转化为二进制字符串，根据得到的总功效函数值大小进行遗传算法操作，产生新的一组实验条件。重复上述过程直到得到最佳分离条件为止。此方法成功地应用于华法令对映体的毛细管电泳分离条件优化。     

SciFinder-guided rational design of fluorescent carbon dots for ratiometric monitoring intracellular pH fluctuations under heat shock

Intracellular pH plays a significant role in various biological processes, including cell proliferation, apoptosis, metabolism, enzyme activity and homeostasis. In this work, a novel design strategy for the preparation of pH responsive carbon dots (CDs-pH) for ratiometric intracellular imaging was reported. By using SciFinder database, fluorescent CDs-pH with the required pK_a value of 6.84 were rationally designed, which is vital important for precise sensing of intracellular pH. As a result, the synthesized CDs-pH demonstrated robust ability to test pH fluctuations within the physiological range of 5.4-7.4. The CDs-pH was further utilized for fluorescent ratiometric imaging of pH in living HeLa cells, effectively avoided the influence of autofluorescence from native cellular species. Moreover, real-time monitoring of intracellular pH fluctuation under heat shock was successfully realized. This SciFinder-guided design strategy is simple and flexible, which has a great potential to be used for the development of other types of CDs for various applications.     

Fractionation and Bioaccessibility of Manganese,Copper, Zinc,Cadmium, and Lead in Commercial Vegetable and Rice Baby Foods Using Inductively Coupled Plasma - Mass Spectrometry (ICP-MS) with Central Composite Design (CCD)

Abstract

Herein the bioaccessibility of Mn, Cu, Zn, Cd, and Pb, selected from essential and toxic elements, was determined in commercially sold vegetable purees intended for infant and toddler consumption. Chemical fractionation studies using water, acetone, diethyl ether, chloroform:methanol, and n-hexane were employed to predict the importance of the protein and lipid parts of a matrix to assess the bioaccessibility data. In addition, in-vitro gastrointestinal digestion was performed to determine the bioaccessibility of the elements using a five level, three factor central composite design (CCD) to maximize the elemental solubility. The total elemental concentrations in all of the fractions were determined by inductively coupled plasma – mass spectrometry (ICP-MS). Based on the consumption of one jar of vegetable/rice-based baby food, Zn was 1.3% of the recommended dietary allowance and Mn was 4.2% of the adequate intake level, while Cu was almost 100% of the adequate intake level. Additionally, Pb was always below the detection limit and Cd was sometimes under the detection limit for the percent bioaccessibility. However, in some samples, Cd was as high as 80% of the tolerable weekly intake level depending on the body weight.     

Automated site-directed drug design: An assessment of the transferability of atomic residual charges (CNDO) for molecular fragments

Summary In this paper a database of atomic residual charges has been constructed for all the molecular fragments defined previously in a combinatorial search of the Cambridge Structural Database. The charges generated for the atoms in each fragment are compared with charges calculated for whole molecules containing those fragments. The fragment atomic charges lie within 1 S.D. of the mean for 68%, and within 2 S.D. for 91%, of the atoms whose charges were computed for whole molecules. The actual charges on any atom are strongly influenced by the adjacent connected atoms. There is a large spread of atomic residual charge within the fragments database.     

Synthesis, structure, and spectroscopy of phenylacetylenylene rods incorporating meso-substituted dipyrrin ligands

The synthesis, structure, and spectroscopic characterization of a series of phenylacetylenylene rodlike molecules containing dipyrromethene (dipyrrin) ligands are described. The combination of the phenylacetylenylene groups with the porphyrinogenic dipyrrin moieties results in a rich absorption spectroscopy for these compounds, although the fluorescence of the phenylacetylenylene moiety is quenched by presence of the dipyrrin chelator. The Cu(2+) and Fe(3+) complexes of these ligands have been prepared and three of these compounds have been structurally characterized by using single-crystal X-ray diffraction. Unlike other octahedral metal-dipyrrin complexes described to date, one of the iron complexes demonstrates ideal threefold symmetry in the solid-state. The elongated structure and high symmetry of these complexes suggests the use of these meso-substituted phenylacetylenylene ligands as an interesting class of extended, branched molecules for the construction of supramolecular architectures.     

Plasma Thermal Conversion of Methane to Acetylene

This paper describes a re-examination of a known process for the direct plasma thermal conversion of methane to acetylene. Conversion efficiencies (% methane converted) approached 100% and acetylene yields in the 90–95% range with 2–4% solid carbon production were demonstrated. Specificity for acetylene was higher than in prior work. Improvements in conversion efficiency, yield, and specificity were due primarily to improved injector design and reactant mixing, and minimization of temperature gradients and cold boundary layers. At the 60-kilowatt scale cooling by wall heat transfer appears to be sufficient to quench the product stream and prevent further reaction of acetylene resulting in the formation of heavier hydrocarbon products or solid carbon. Significantly increasing the quenching rate by aerodynamic expansion of the products through a converging–diverging nozzle led to a reduction in the yield of ethylene but had little effect on the yield of other hydrocarbon products. While greater product selectivity for acetylene has been demonstrated, the specific energy consumption per unit mass of acetylene produced was not improved upon. A kinetic model that includes the reaction mechanisms resulting in the formation of acetylene and heavier hydrocarbons, through benzene, is described.