ELECT++: Faster conformational search method for docking flexible molecules using molecular similarity

We have developed a program, ELECT++ (Effective LEssening of Conformations by Template molecules in C++), to speed up the conformational search for small flexible molecules using the similar property principle. We apply this principle to molecular shape and, importantly, to molecular flexibility. After molecules in a database are clustered according to flexibility and shape (FCLUST++), additional reagents are generated to screen the conformational space of molecules in each cluster (TEMPLATE++). We call these representative reagents of each cluster template reagents. Template reagents and clustered reagents produce, after reaction, template molecules and clustered molecules, respectively (tREACT++). The conformations of a template molecule are searched in the context of a macromolecular target. Acceptable conformational choices are then applied to all molecules in its cluster, thus effectively biasing conformational space to speed up conformational searches (tSEARCH++). In our incremental search method, it is necessary to calculate the root-mean-square deviations (RMSD) matrix of distances between different conformations of the same molecule to reduce the number of conformations. Instead of calculating the RMSD matrix for all molecules in a cluster, the RMSD matrix of a template molecule is chosen as a reference and applied to all the molecules in its cluster. We demonstrate that FCLUST++ clusters the primary amine reagents from the Available Chemicals Directory (ACD) successfully. The program tSEARCH++ was applied to dihydrofolate reductase with virtual molecules generated by tREACT++ using clustered primary amine reagents. The conformational search by the program tSEARCH++ was about 4.8 times faster than by SEARCH++, with an acceptable range of errors. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1834–1852, 1998     

Highly sensitive determination of lanthanides by capillary electrophoresis with direct visible detection after precapillary complexation with aromatic polyaminocarboxylate and additionally applying dynamic ternary complexation with nitrilotriacetic acid

A newly synthesized aromatic polyaminocarboxylate (NBD-ABEDTA, H(4)L) was applied to precapillary derivatizing capillary electrophoresis as a chelating reagent for lanthanide ions (Ln(3+)). The Ln-L complexes provide both kinetic stability on dissociation due to their methyl-EDTA coordinating structure, and high light absorptivity (epsilon(max) = 2.4 x 10(4) cm(-1) mol(-1) dm(3)) in the visible region at 469 nm thanks to their nitrobenzofurazan moiety. A ligand was employed for capillary zone electrophoresis based on a unique concept: both precapillary and dynamic on-capillary complexation were carried out on one center-metal ion to achieve high resolution. As a ternary complex-formation agent, iminodiacetate (IDA), bound to the mother complex (Ln-L), was added to the carrier buffer solution. The carrier buffer solution of 9.5 mmol.dm(-3) (pH 9.45) borate and 33.5 mmol.dm(-3) IDA, drastically improved the resolution among Ln(3+) ions. Each of the Ln complexes was effectively separated, except for Pr-Sm. Furthermore, the absence of L from the carrier solution, which stabilizes the baseline fluctuation, provided low LOD (typically 4.2 x 10(-7) mol.dm(-3)). This strongly suggests that Ln-L complexes are kinetically stable even with a large excess of IDA. Quite unexpectedly, the order of migration differs from that of the atomic number, inverting at Nd. This is due to the effect of the cavity size of the residual coordination sites on the ternary complexation and the electronic density of Ln(3+).     

Parameter estimation by decoherence in the double-slit experiment

We discuss a parameter estimation problem using quantum decoherence in the double-slit interferometer. We consider a particle coupled to a massive scalar field after the particle passing through the double slit and solve the dynamics non-perturbatively for the coupling by the WKB approximation. This allows us to analyze the estimation problem which cannot be treated by master equation used in the research of quantum probe. In this model, the scalar field reduces the interference fringes of the particle and the fringe pattern depends on the field mass and coupling. To evaluate the contrast and the estimation precision obtained from the pattern, we introduce the interferometric visibility and the Fisher information matrix of the field mass and coupling. For the fringe pattern observed on the distant screen, we derive a simple relation between the visibility and the Fisher matrix. Also, focusing on the estimation precision of the mass, we find that the Fisher information characterizes the wave-particle duality in the double-slit interferometer.     

1H-1,2,3-triazole,a promising precursor for chemical vapor deposition of hydrogenated carbon nitride

Well-crystallized hydrogenated carbon nitride thin films have been prepared by microwave plasma enhanced chemical vapor deposition (MWPECVD). 1H-1,2,3-triazole+N₂ and Si (1 0 0) were used as precursor and substrate, respectively. Substrate temperature during the deposition was recorded to be 850 °C. The synthesized samples were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and X-ray photo-electron spectroscopy (XPS) analyses. The plasma compositions were checked by optical emission spectroscopy (OES). XRD observation strongly suggests that the films contain polycrystalline carbon nitride with graphitic structure of (1 0 0), (0 0 2), (2 0 0) and (0 0 4). XPS peak quantification reveals that the atomic ratio of the materials C:N:O:Si is 32:41:18:9. X-ray photo-electron peak deconvolution shows that the most dominant peak of C (1s) and N (1s) narrow scans correspond to sp² hybrid structure of C₃N₄. These observations indicate that 1H-1,2,3-triazole favors the formation of hydrogenated carbon nitride with graphitic phase by CVD method and thus is in good agreement with XRD results. SEM of surface and OES of plasma also support the formation of polycrystalline carbon nitride films from 1H-1,2,3-triazole+N₂ by CVD.     

Synthesis, crystal structures, and properties of 6,12-diaryl-substituted indeno[1,2-b]fluorenes

Fused polycyclic indeno[1,2-b]fluorene derivatives with aryl substituents at the 6,12-positions have been prepared as a potential antiaromatic 20π electronic system. They showed strong absorptions in the visible region and amphoteric redox properties. The quinoid-type molecular structures were revealed by X-ray crystal-structure analysis, which indicated that the bond lengths of the quinoid unit depend on the aryl substituents. Whereas nucleus-independent chemical shift NICS(1) calculations indicate the antiaromatic nature of the s-indacene core, they have higher stability than substituted acene derivatives. The derivatives with difluorophenyl or anthryl groups were stable in solution. Vapor-deposited thin films showed ambipolar carrier transportation in the field-effect transistor devices.     

A reversible near-infrared fluorescence probe for reactive oxygen species based on Te-rhodamine

We have designed and synthesized a reversible near-infrared (NIR) fluorescence probe, 2-Me TeR, for reactive oxygen species (ROS), utilizing the redox properties of the tellurium (Te) atom. 2-Me TeR is oxidized to fluorescent 2-Me TeOR by various ROS, while the generated 2-Me TeOR is quickly reduced in the presence of glutathione to regenerate 2-Me TeR. This redox-induced reversible NIR-fluorescence response of 2-Me TeR allowed us to detect the endogenous production of ROS and subsequent homeostatic recovery of the intracellular reductive environment in hydrogen peroxide-stimulated HL-60 cells. This probe is expected to be useful for monitoring the dynamics of ROS production continuously in vivo.     

Visible-light-triggered release of nitric oxide from N-pyramidal nitrosamines

Although many organic/inorganic compounds that release nitric oxide (NO) upon photoirradiation (phototriggered caged-NOs) have been reported, their photoabsorption wavelengths mostly lie in the UV region, because X-NO bonds (X=heteroatom and metal) generally have rather strong π-bond character. Thus, it is intrinsically difficult to generate organic compounds that release NO under visible light irradiation. Herein, the structures and properties of N-pyramidal nitrosamine derivatives of 7-azabicyclo[2.2.1]heptanes that release NO under visible light irradiation are described. Bathochromic shifts of the absorptions of these nitrosamines, attributed to HOMO (n)-LUMO (π*) transitions associated with the nonplanar structure of the N-NO moiety, enable the molecules to absorb visible light, which results in N-NO bond cleavage. Thus, these compounds are innate organic caged-NOs that are uncaged by visible light.     

Mechanofluorochromism of carbazole-type D–π–A fluorescent dyes

We have newly designed and synthesized unsymmetrical carbazole-type D–π–A fluorescent dyes. The dyes show a bathochromic shift-type mechanofluorochromism (MFC): grinding of as-recrystallized dyes induces a bathochromic shift of fluorescent color and the fluorescent color is recovered by heating or exposure to solvent vapor. In order to clarify the MFC mechanism for the carbazole-type D–π–A fluorescent dyes, time-resolved fluorescence spectroscopy, X-ray powder diffractometry, single-crystal X-ray structural analysis, IR spectroscopy, and differential scanning calorimetry are performed before and after grinding of the solids. On the basis of experimental results and semi-empirical molecular orbital calculations (AM1 and INDO/S), we have revealed that the MFC is attributed to a reversible switching between crystalline and amorphous states with changes of intermolecular hydrogen bonding and π–π interaction.