计算有机化合物脂水分配系数的新方法

A new method is presented for the calculation of octanol/water partition coefficients. On the basis of summation of atomic contributions, our algorithm, namely; XLOGP, also incorporate correction factors into the calculation. Multivariate regression analysis was performed on a training database of 1831 organic compounds with diverse structures to give the final model. The correlation coefficients for the whole set fitting is 0.968 and the standard deviation is 0.37. The result shows that our model is accurate enough for logP estimation in QSAR studies. Compared to other similar approaches, our method gives better results and is more convenient to use.     

Inhibition of beta-amyloid fibrillization by directed evolution of a beta-sheet presenting miniature protein

We describe the directed evolution of a miniature beta-sheet protein for targeting beta-amyloid oligomers implicated in Alzheimer's disease. Circular dichroism spectroscopy, thermal denaturation experiments, and immunoglobulin binding assays established that our beta-amyloid-targeted miniature protein, TJ10, presents a well-folded thermostable beta-sheet. TJ10 was found to prevent beta-amyloid fibrillization at stoichiometric concentrations and was also an effective inhibitor at substoichiometric concentrations. Thus our results provide a new and potent beta-sheet chemical template for effectively targeting beta-amyloid while also demonstrating a general strategy for targeting proteins implicated in other amyloidogenic diseases.     

Gene analysis of multiple oral bacteria by the polymerase chain reaction coupled with capillary polymer electrophoresis

Capillary polymer electrophoresis is identified as a promising technology for the analysis of DNA from bacteria, virus and cell samples. In this paper, we propose an innovative capillary polymer electrophoresis protocol for the quantification of polymerase chain reaction products. The internal standard method was modified and applied to capillary polymer electrophoresis. The precision of our modified internal standard protocol was evaluated by measuring the relative standard deviation of intermediate capillary polymer electrophoresis experiments. Results showed that the relative standard deviation was reduced from 12.4–15.1 to 0.6–2.3%. Linear regression tests were also implemented to validate our protocol. The modified internal standard method showed good linearity and robust properties. Finally, the ease of our method was illustrated by analyzing a real clinical oral sample using a one‐run capillary polymer electrophoresis experiment.     

Highly selective artificial gel antibodies for detection and quantification of biomarkers in clinical samples. II. Albumin in body fluids of patients with neurological disorders

We have previously used the molecular‐imprinting method for the synthesis of artificial gel antibodies, highly selective for various proteins. In the present work, we have synthesized artificial gel antibodies against human albumin with the aim to develop a simple and rapid procedure to measure the concentration of this protein in samples of clinical interest. The procedure, based on the design of a standard curve (see the preceding paper), was applied on a quantitative analysis of albumin in human plasma and cerebrospinal fluid (CSF). We found that our technique permitted detection of albumin in these body fluids with high precision and that the concentration of this protein was significantly enhanced in CSF from patients with amyotrophic lateral sclerosis (ALS), compared to control samples. This finding is in agreement with results from earlier studies, which confirms the validity of our analysis technique and suggests that the barrier permeability may be affected in ALS, perhaps also for other proteins. No enhancement in plasma levels of albumin was seen in patients with ALS, but rather a decrease. The results further indicate that our approach might also apply well to other biomarkers for the actual neurological disease and other disorders.     

C60亮氨酸衍生物的合成及其理论研究

用1,3-偶极环加成方法合成了含吡咯环C₆₀衍生物C₆₆NH₁₃,并以FTIR、UV-Vis、¹HNMR和LD-TOFMS进行表征.用AM1方法对两种可能的加成产物-[6,6]和[6,5]异构体进行几何构型优化.结果表明,[6,6]异构体更稳定.以优化构型为基础,用INDO/CI方法计算两种加成产物的UV谱,结果表明,[6,6]异构体的特征吸收与实验值一致.本文对这两种异构体的电子跃迁进行理论指认,并分析了光谱红移的原因.     

High-throughput screening using porous photoelectrode for the development of visible-light-responsive semiconductors

A high-throughput screening system for new visible-light-responsive semiconductors for photoelectrodes and photocatalysts was developed in this study. Photoelectrochemical measurement was selected to evaluate visible-light responsiveness, and an automated semiconductor synthesis system that can be used to prepare porous thin-film photoelectrodes of various materials was also developed. As an example application of our system, iron-based binary oxides were selected as target materials for n-type semiconductors. Fe-Ti, Fe-Nb, and Fe-V with various composition ratios were synthesized. Fe-Ti and Fe-Nb binary oxide systems have been studied previously, and our results showed good consistency with previous reports, demonstrating the capability of our system. In the Fe-V system, the highest photocurrent was observed with 50% vanadium. This ratio corresponds to FeVO4, which is expected to be a new visible-light-responsive material. As another example, screening targets of bismuth-based binary oxides were investigated for p-type semiconductor photoelectrodes, and CuBi2O4 was found as a new visible-light-responsive p-type semiconductor.     

Calculation of pressure using the virtual-volume-variation method and the virial method from chain conformations obtained by Monte Carlo simulations on the second nearest neighbor diamond lattice

For a model system of polyethylene of chain lengths 40 and 100 carbon atoms, we calculated the pressure at different densities and compared them with the experimental values. The simulation was conducted on the second nearest neighbor diamond lattice, and the pressure was calculated using the virtual-volume-variation method after the system was reverse mapped to its fully atomistic form in continuous space and energy minimized. In addition, the pressure was also calculated from the virial route by conducting a short molecular dynamics simulation starting from the energy minimized structure. We show that the pressure obtained from our simulations is quite reasonable in the length of simulation time (in Monte Carlo steps) normally employed in our group. These results provide additional evidence for the equilibration of our model systems, and methodology to calculate the pressure in our lattice models.     

A simple and efficient approach for calculating permeability coefficients and HETP for rectangular columns

There had been little progress in development of the theoretical basis of rectangular chromatography columns until Spangler made great progress by using a more exact model than Golay's. Unfortunately, there was a deficiency in his calculations, which led to a conclusion inconsistent with the previous theories. In this paper, a simpler formula with defined variables was first established to calculate the mean permeability coefficient for a rectangular GC column. A formula was also established to calculate the height equivalent to a theoretical plate (HETP) for a rectangular column based on this work and the correction of Spangler's theory. By comparing both our predictions and Spangler's predictions with Golay's, respectively, we could demonstrate that our theory is more exact. Further, one parameter (A) was found to be not monotonous. This finding leads to the conclusion that the square column has the highest performance among all the rectangular-shaped columns used for chromatography, and that a width/depth ratio of around three is desirable if the column is used for mixing reactants in lab-on-a-chip systems, instead of for chromatography. The conclusions are applicable not only for gas but also for liquid chromatography columns.     

Supramolecular gels from lipopeptide gelators: Template improvement and strategies for the in-situ preparation of inorganic nanomaterials and for the dispersion of carbon nanomaterials

Lipopeptide amphiphiles are an important class of biobased and biomimetic surfactants that are easily prepared from the cheapest organic reagents, such as natural fatty and amino acids, and in many cases, the resulting compounds are able to harden not only common organic solvents but also waxes, water and ionic liquids. Well-tailored, these gelators can be selective for one variety of liquid, which leads to the formation of a robust gel that is able to incorporate various different elements. In this review, we attempted to provide our opinion regarding the molecular design of the lipopeptide gelator candidates. In addition, we summarized each type of element that is necessary for creating potent supramolecular gel templates that are useful for inorganic nano- and micro-material preparation. This review is not only limited to recent papers found in the literature; a portion of our unpublished results are also provided as a supplement to illustrate our point of view regarding this subject.     

Expedient synthesis of a novel asymmetric selectively deprotectable derivative of the ATAC scaffold

An efficient multigram scale synthesis of a new asymmetric triazacyclophane scaffold, the ATAC (Asymmetric-TAC) scaffold, bearing three selectively removable groups is described. This scaffold is slightly more rigid than our frequently used TAC (TriAzaCyclophane) scaffold. The synthesis of the required triamine is very high yielding without difficult steps or purifications and was also applied to a much improved synthesis of our original TAC scaffold. Especially the tedious first reaction step, that is, mono-oNBS-protection of a triamine could be omitted. The rigidity of the triazacyclophane ring in both TAC- and ATAC scaffolds has also been investigated using variable temperature ¹H NMR experiments.     

Time lapse confocal microscopy studies of bacterial adhesion to self-assembled monolayers and confirmation of a novel approach to the thermodynamic model

In this study, we use thermodynamic theory to develop a novel model that allows for the quantitative determination of the Gibbs free energy of adhesion for the initial bacterial attachment process. This model eliminates the need to calculate interfacial free energies and instead relies on easily measurable contact angles to determine DeltaG(adh). We experimentally verify our model using real-time observation of the initial attachment of Pseudomonas putida to methyl- and hydroxyl-terminated self-assembled monolayers. We also test the applicability of our model to a variety of experimental conditions using data available in the literature. We show that the initial attachment process is governed by dispersion forces and is accurately predicted by our model. Also, we find that our model is simple to apply and accurate for a variety of experimental conditions.     

聚丁二烯形变中内能贡献的预报

理想弹性体的统计理论假设弹性力完全由形变的构象熵所贡献的, 忽略了能量的贡献. 对于真实橡胶来说, 统计理论反映了它的主要特征, 然而真实橡胶与理想模型还是有差别的, 在拉伸过程中弹性力的贡献不完全是由熵所贡献的, 内能也会对弹性力有贡献, 并且, 不同的材料内能对弹性力的贡献(fe/f)不同[1], 这已为大量的实验事实所证实.     

Detection of characteristic clusters in IMS-Spectrograms of exhaled air polluted with environmental contaminants

Detection of special disease markers in exhaled breath is a method becoming more and more relevant in medical diagnostic. The test environment plays a big role in the analysis of exhaled air when using ion mobility spectrometry (IMS). Environmental contaminants appear also in exhaled air of test persons, potentially even in other forms then in the ambient air. Different ways to deal with these environmental factors will be discussed and our method of choice will be presented. It was possible to identify specific fingerprints for dedicated features of probands as well as for specific environmental pollution. By using statistical evaluation it was also possible to identify characteristic features of probands notwithstanding the environmental burden for correct assignment into specific groups, reaching correct classification rates above 0.85.     

Tighter multipole-based integral estimates and parallel implementation of linear-scaling AO-MP2 theory

Within an atomic-orbital-based (AO-based) formulation of second-order M?ller-Plesset perturbation theory (MP2), we present a novel screening procedure which allows us to preselect numerically significant two-electron integrals more efficiently, especially for large basis sets. The screening is based on our recently introduced multipole-based integral estimates (MBIE) method [J. Chem. Phys., 2005, 123, 184102], that allows to exploit the 1/R(4) or 1/R(6) coupling between electronic charge distributions in transformed integral products within AO-MP2. In this way, linear scaling is attained with fully-controlled numerical accuracy. Furthermore, a parallel implementation of our linear-scaling AO-MP2 method is described, which also allows us to perform calculations with larger basis sets. First calculations reveal that for e.g. linear alkanes the scaling of the number of required transformed integral products is almost equal for 6-31G* and cc-pVTZ basis sets. Using the improved MBIE screening, the largest parallel calculation was performed for a ribozyme fragment consisting of 497 atoms and 5697 basis functions, while our largest AO-MP2 calculation was performed for a stacked DNA system (16 base pairs) comprising 1052 atoms and 10 674 basis functions on a single processor.     

Zirconium-Catalyzed Atom-Economical Synthesis of 1,1-Diborylalkanes from Terminal and Internal Alkenes

A general and atom-economical synthesis of 1,1-diborylalkanes from alkenes and a borane without the need for an additional H₂ acceptor is reported for the first time. The key to our success is the use of an earth-abundant zirconium-based catalyst, which allows a balance of self-contradictory reactivities (dehydrogenative boration and hydroboration) to be achieved. Our method avoids using an excess amount of another alkene as an H₂ acceptor, which was required in other reported systems. Furthermore, substrates such as simple long-chain aliphatic alkenes that did not react before also underwent 1,1-diboration in our system. Significantly, the unprecedented 1,1-diboration of internal alkenes enabled the preparation of 1,1-diborylalkanes.     

Efficient method development strategy for challenging separation of pharmaceutical molecules using advanced chromatographic technologies

In this paper, we describe a strategy that can be used to efficiently develop a high-performance liquid chromatography (HPLC) separation of challenging pharmaceutical molecules. This strategy involves use of advanced chromatographic technologies, such as a computer-assisted chromatographic method development tool (ChromSword) and an automated column switching system (LC Spiderling). This process significantly enhances the probability of achieving adequate separations and can be a large time saver for bench analytical scientists. In our study, the ChromSword was used for mobile phase screening and separation optimization, and the LC Spiderling was used to identify the most appropriate HPLC columns. For proof of concept, the analytes employed in this study are the structural epimers betamethylepoxide and alphamethylepoxide (also known as 16-beta methyl epoxide and 16-alpha methyl epoxide). Both of these compounds are used in the synthesis of various active pharmaceutical ingredients that are part of the steroid pharmaceutical products. While these molecules are relatively large in size and contain various polar functional groups and non-polar cyclic carbon chains, their structures differ only in the orientation of one methyl group. To our knowledge, there is no reported HPLC separation of these two molecules. A simple gradient method was quickly developed on a 5 cm YMC Hydrosphere C(18) column that separated betamethylepoxide and alphamethylepoxide in 10 min with a resolution factor of 3.0. This high resolution provided a true baseline separation even when the concentration ratio between these two epimers was 10,000:1. Although outside of the scope of this paper, stability-indicating assay and impurity profile methods for betamethylepoxide and for alphamethylepoxide have also been developed by our group based on a similar method development strategy.