Phthalate esters, such as di-(2-ethylhexyl) phthalate (DEHP) used as a plasticizer, are known as activators of a peroxisome proliferator-activated receptor alpha (PPAR alpha). We investigated stable structures and electronic properties for the complexes of PPAR alpha and phthalate esters as well as an adipate ester, by molecular simulations based on molecular mechanics and molecular orbital methods. The obtained HOMO-LUMO energy gaps of the optimized complexes were found to be related to the level of PPAR alpha-related enzyme expression obtained by our previous experiment.
In synthesizing target compounds, synthetic chemists search for and examine papers concerning syntheses to create their own synthetic routes. Synthetic route design system programs such as AIPHOS and EROS can also create many synthetic routes for targets compounds. However, it takes a long time to experimentally test all the routes created by these programs. Therefore, computational chemistry has been used to investigate mechanisms of chemical reactions which have already been examined experimentally. It is feasible to consider theoretical methods as effective in examining whether or not synthetic routes from chemoinformatics can be used practically for synthesizing target compounds. There are many difficulties associated with the aforementioned application, because theoretical calculations have to be done without information from experimental works. In the present study, we proved that this concept works well for synthetic routes of benzyl methacrylate, created from the KOSP and TOSP programs.
Chemical information activities in Japan during the past fifty years have been reviewed with specific attention to development of electronic information processing and dissemination. Activities of CAS and JAICI are described as a particular example. Recent topics, such as electronic journals and open access, are also discussed.
In this paper, independent component analysis (ICA) and regression analysis are combined to extract significant components. ICA is a method that extracts mutually independent components from explanatory variables. We propose a new method that selects combination of independent components by using genetic algorithm (GA). It can construct a PLS model that has high predictive accuracy. This method is named ICA-GAPLS. In order to verify the superiority of ICA-GAPLS, this method was applied to QSPR analysis of aqueous solubility. The result of comparison with PLS and other regression methods is shown. R2, Q2 and Rpred2 values of the PLS model are 0.826, 0.821 and 0.790, respectively. These values of the ICA-GAPLS model are 0.945, 0.882 and 0.889, respectively. ICA-GAPLS achieved higher predictive accuracy than PLS. ICA-GAPLS showed better result regarding Q2 and Rpred2 value than other methods. ICA-GAPLS could extract effective components from explanatory variables and construct the regression model having high predictive accuracy.
In the hydrogen production through the steam reforming reaction of the methane, the technology of the separation and purification influences the production cost of hydrogen directly. We have developed the simulation system concerning the structure design of the separation module in order to take out hydrogen with high purity. This system uses computational fluid dynamics (CFD) engine developed for the simulation of gas permeation through membranes. It can simulate the performance of the separation membrane module by considering the calculated gas stream with the aid of CFD at the stage of complex modular design. The purpose of this system is to propose the modular structure parameter set in order to attain the best separation performance of the module at the design stage of the separation membrane module. The calculated results showed that the optimization of the structural parameter combined with CFD simulation was important for the design of the separation membrane module with high efficiency.
The various empirical solvent parameters to explain the solvent effect on the chemical reactions have been advocated because the solvent effect can not be frequently interpreted by dielectric constant, solubility parameter, et al. of the bulk physical properties of the solvents. Since the solvent molecules are considered to serve to the solutes as the electron acceptor and/or electron donor, the strength of the electron acceptor and electron donor of the solvents is expressed as the acceptor number (AN) and donor number (DN) by Gutmann et al.. It has been pointed that the correlation of reaction rates and the free energies of solvation of ions with AN or DN is parallel with the correlation based on the lowest unoccupied (LUMO) or the highest occupied molecular (HOMO) eigenvalues of 8 solvent molecules (DMSO, DMF, AN, Ac, EtOH, MeOH, FA, H2O). In this study, the eigenvalues of ELUMO and EHOMO of 31 solvent molecules including the reported 8 solvent molecules have been calculated by the ab initio method. The eigenvalues of ELUMO of protic solvents increase especially as the AN values increase though the decrease of ELUMO eigenvalues is predicted. The AN values are obtained from 31P NMR chemical shift of triethylphosphine oxide (Et3PO) in neat solvents (S). The hydrogen bond interaction between Et3PO and S rather than the electron accepting to the LUMO of the solvent molecule is presumed to be the main factor in determining the solvation effects. Thus, in this work, the MO calculations on the 1:1 solvation (Et3POoS) between Et3PO and 20 solvent molecules (S) have been carried out by ab initio and semi-empirical MO methods. The correlation of the charge distribution on P and O atoms in Et3POoS, the P-O bond distance, and the hydrogen bond distance between Et3PO and S with the AN values is discussed. The solvents are divided into two groups; one is aprotic solvents with nonpolar, smaller polar (AN <10) and larger polar properties (10< AN <20), and the other is polar protic solvents (AN >20). For the aprotic solvents with AN <10 and the protic solvents with AN >20 except for H2O, the correlation coefficients R with the AN values are 0.79-0.88, resulting in the similar solvation structures in these solvents as well as in the gas phase by the MO calculations. On the other hand, the large deviation from the correlation with the AN values is found at polar aprotic (10< AN <20) solvents (DMSO, DMA, DMF, et al.) and H2O (AN=54.8). The liquid structures of polar aprotic solvents and H2O form the aggregation (cluster) among the solvent molecules based on the large dipole moment and hydrogen bond interaction, respectively. Thus, the large deviation from the linear correlation with the AN values is considered to be due to the solvation to Et3PO molecule by the aggregation (cluster) of a number of the solvents in solution.
Micellar electrokinetic chromatography(MEKC) is one of the separation modes of capillary electrophoresis(CE) with high resolution. MEKC is useful for enantioseparations of organic compounds within a short analysis time even though sample volumes are very low. It has been considered that the hydrophobic interaction between solute and micelles is very important for enantioseparation of compounds. However, it has not been clearly understood what parameters are closely related to the separation mechanism of the MEKC. In the present study, The GA-PLS method was applied to find important parameters for the enantioseparations of amino acids using the MEKC with bile acids. For that purpose, the technique was used to enantioseparate eleven amino acids. Four bile acids such as cholic acid(CA), taurocholic acid(TCA), chenodeoxycholic acid(CDCA) and deoxycholic acid(DA) were adopted to make micellars interacting with the amino acids. The resolution values were calculated from the experimental results. The value is an index for the ability of the MEKC to enantioseparate the amino acids. Experimental values and physical properties such as hydropathy index of amino acids and isoelectric points of amino acids were used as explanatory variables for the statistical method. It was confirmed that three or four variables are enough to expect the experimental Rs values for CDCA and DCA while it is impossible to explain those for CA and TCA. It was considered that the difference of the hydrophilic property of the bile acids is the key to understanding the enantioseparations observed.
Various proteases are participating in cancer invasion. To elucidate the role of these proteases, we developed a model of cancer invasion mechanism by using cellular simulator E-CELL. The invasion characteristic for five kinds of cancer cells was investigated to obtain the comparable results to the experimental. The involvement of urokinase-type plasminogen activator receptor (uPAR) in the pathology of human cancers is well documented. The simulated results elucidated that the binding of urokinase-type plasminogen activator (uPA) to uPAR existing on a cancer cell membrane is important for the cancer invasion. Therefore, these data allow us to speculate that the blocking of the uPA/uPAR binding is effective for the inhibition of cancer invasion.
The Fragment-Molecular-Orbital (FMO) method is an approximate quantum chemical method for huge systems like biological macromolecules and is known to provide not only an accurate total energy but also properties of the system with sufficient precision compared with conventional first principle methods. In the present study we report the spectroscopic properties such as dipole moment, polarizability and their derivatives by the FMO in order to examine the accuracy of the method in predicting IR and Raman spectroscopies of biological macromolecules. The results show the promising features of the method as a theoretical tool in the spectroscopic study of large bio-systems.
In the performance simulation of the gas separator membrane module, it is important to model the concentration polarization on the surface of the separation membrane, and to calculate the gas flow in the module. The system that can estimate the performance of separation membrane module has been developed by applying the CFD engine modified for the performance simulation of the gas separator membrane. This study unveils the influence that the structural parameters of the separation membrane module exert on the separation performance. In conclusion, the optimization of not only the separation membrane area, but also the arrangement pattern of the separation element is important for the structural design of the separation membrane module with good performance.
Hydrolysis reaction is one of the major sources of degradants in the biodegradation test of Chemical Substance Control Law. We intended to add a new view in the biodegradation prediction using activation energy of hydrolysis reaction derived from the reaction analysis through quantum chemical calculation. In the process of above study, we developed a program, Hydrolysis Reaction Analysis System as an interface enabling easy calculations of activation energy by using MOPAC program. Substitution method was applied as an effective method to construct initial molecular structures for reactants, products and transition states of the ester hydrolysis. The developed system calculated activation energy of the acid hydrolysis reactions of esters with drastic reduction of computation time in comparison with those using other molecular modeling programs. If more precise calculation of the activation energies are required, it could be a solution to utilize the higher level of theory such as Density Functional Theory or ab initio MO calculation.
Predictive models for representing the ionic conductivity and viscosity of ionic liquids (ILs) were constructed using a polynomial expansion model, coupled with descriptors of group contribution type. These equations could be applied to cations of alkyl amine, pyrole, piperidine, pyridine, imidazole and pyrazole, with the following anions: TFSI, Br, Cl, PF6, BF4, CF3SO3, CF3BF3, and C2F5BF3. To determine coefficients in non-linear equations, genetic algorithms were adapted. Calculated results gave good correlation accuracy of ionic conductivity and viscosity. An examination of the predictive performance was also attempted by comparing the calculated with experimental values not used for the determination of the parameters.