Molecular dynamics simulations of the Hras‐GTP complex and the Hras‐GDP complex

We study the structures of the Hras‐GTP complex and the Hras‐GDP complex in water to investigate the mechanism of GTP hydrolysis of the Hras‐GTP complex. We performed molecular dynamics simulations of these complexes to investigate the structures of these complexes using the potential parameters of AMBER ff03 and our potential parameters around Mg²⁺. Our simulations show that the averaged structure differences between the Hras‐GTP complex and Hras‐GDP complex are found in the switch I and II regions. In particular, in the switch II region, the α2 ‐ helix of Hras‐GDP is shorter than the α2 ‐ helix of Hras‐GTP. The averaged number of water molecules in the first hydration sphere in Hras‐GDP complex is larger than that in Hras‐GTP complex. The occurrence ratio of the duration time of waters in the first hydration sphere of PA has long tail both in Hras‐GTP and in Hras‐GDP. In Hras‐GDP complex, β‐phosphate is hard to be hydrolyzed, while the number of waters in the first hydration sphere is larger than those in Hras‐GTP. This suggests that there is a special direction for the hydrolysis. © 2013 Wiley Periodicals, Inc.     

Development of Luminescent Coelenterazine Derivatives Activatable by β‐Galactosidase for Monitoring Dual Gene Expression

Two bioluminogenic caged coelenterazine derivatives (bGalCoel and bGalNoCoel) were designed and synthesized to detect β‐galactosidase activity and expression by means of bioluminescence imaging. Our approach addresses the instability of coelenterazine by introducing β‐galactose caging groups to block the auto‐oxidation of coelenterazine. Both probes contain β‐galactosidase cleavable caging groups at the carbonyl group of the imidazo–pyrazinone moiety. One of the probes in particular, bGalNoCoel, displayed a fast cleavage profile, high stability, and high specificity for β‐galactosidase over other glycoside hydrolases. bGalN‐oCoel could detect β‐galactosidase activity in living HEK‐293T cell cultures that expressed a mutant Gaussia luciferase. It was determined that coelenterazine readily diffuses in and out of cells after uncaging by β‐galactosidase. We showed that this new caged coelenterazine derivative, bGalNoCoel, could function as a dual‐enzyme substrate and detect enzyme activity across two separate cell populations.     

Synthetic studies of venturicidins: stereoselective synthesis of the C15-C27 segment based on two types of stereospecific epoxide opening reactions

The C15-C27 segment of venturicidins was stereoselectively synthesized by using two types of stereospecific methyl substitution reactions of epoxides and subsequent stereocontrolled methylation reactions of lactone derivatives as the key steps.     

Synthetic studies of the lichen macrolide lepranthin. Stereoselective synthesis of the diolide framework based on regioselective epoxide-opening reactions

Stereoselective synthesis of the 16-membered diolide 27, a fully functionalized congener of lepranthin (1), is described. The requisite five asymmetric carbon centers in monomer 23 were constructed in a highly stereoselective manner by using different epoxide-opening reactions of α,β-unsaturated γ,δ-epoxy esters and epoxy alcohol derivatives as the key steps. The monomer 23 was successfully transformed into the MOM protected diolide 27 by Yamaguchi macrolactonization.     

Integral analysis of condensation in a paper drum with a scraper

An integral analysis is made for laminar film condensation in a rotating paper drum with a scraper. The analysis includes the nonlinear inertial terms in the equation of motion, with the interface shear stress being considered. The results of numerical solutions show that the inertial terms cannot be neglected except in the cases of a very thin condensate film or a very large Froude number, that the condensation heat transfer will be, to some extent, enhanced by the inertial effect, and that the vapor shear at the vapor-liquid interface proves to be negligible. Distributions of the interface velocity and film thickness as well as heat transfer results are obtained and discussed. Included also in this paper is the investigation for transition of the condensate flow from steady state to unsteady one. Received on 6 December 1996     

Structure and infrared spectroscopy of group 6 transition-metal carbonyls in the gas phase: DFT studies on M(CO)n (M = Cr, Mo, and W; n = 6, 5, 4, and 3)

B3LYP-based density functional theory (DFT) calculations with effective core potentials (ECPs) (LANL2DZ) on M and 6-311+G(2d) all-electron basis function sets on C and O are used to interpret the symmetry characteristic vibrational absorption patterns of CO ligands in the "naked" coordinatively unsaturated transition-metal carbonyls M(CO)n-1 (M = Cr, Mo, and W; n = 4-6) observed by a time-resolved infrared absorption spectroscopy after the UV pulse laser photolysis of M(CO)6 in the gas phase. The UV photolysis results can be reasonably explained by the trends in the calculated bond dissociation enthalpies of M(CO)n-1-CO for group 6 metal carbonyls. M(CO)n-1 produced through one CO elimination from M(CO)n is found out to keep its parent skeleton, resulting in the structure with symmetry of C4v for M(CO)5, C2v for M(CO)4, and C3v for M(CO)3.     

Novel construction of hydro-2-benzazepines based on 7-endo selective Friedel-Crafts-type reaction of vinyloxiranes

The TMSOTf-promoted Friedel-Crafts-type reaction of vinyloxirane 3 having a nitrogen atom at the benzylic position was found to proceed with a highly selective 7-endo mode to afford hydro-2-benzazepine 4 in high yield.     

Mesoporous silica nanoparticles for 19F magnetic resonance imaging,fluorescence imaging,and drug delivery

Multifunctional mesoporous silica nanoparticles (MSNs) are good candidates for multimodal applications in drug delivery, bioimaging, and cell targeting. In particular, controlled release of drugs from MSN pores constitutes one of the superior features of MSNs. In this study, a novel drug delivery carrier based on MSNs, which encapsulated highly sensitive ¹⁹F magnetic resonance imaging (MRI) contrast agents inside MSNs, was developed. The nanoparticles were labeled with fluorescent dyes and functionalized with small molecule-based ligands for active targeting. This drug delivery system facilitated the monitoring of the biodistribution of the drug carrier by dual modal imaging (NIR/¹⁹F MRI). Furthermore, we demonstrated targeted drug delivery and cellular imaging by the conjugation of nanoparticles with folic acid. An anticancer drug (doxorubicin, DOX) was loaded in the pores of folate-functionalized MSNs for intracellular drug delivery. The release rates of DOX from the nanoparticles increased under acidic conditions, and were favorable for controlled drug release to cancer cells. Our results suggested that MSNs may serve as promising ¹⁹F MRI-traceable drug carriers for application in cancer therapy and bio-imaging.     

Behaviour of Hydrotalcite and Its Fe (CN)64- Pillared Derivative on Heat Treatment

Mg-Al L(ayered) D(ouble) H(ydroxide) was prepared and its thermal behaviour was characterized by thermoanalytical methods (TG, DTG, DTA), ²⁷Al M(agic) A(ngle) S(pinning) NMR spectroscopy, X-ray diffractometry (XRD) and S(canning) E(lectron) M(icroscopy). Heat treatment destroyed the layered structure, which could only be partially reconstituted by rehydration. On calcination mixed oxide with the predominance of basic sites were formed. Pillaring the LDH with Fe(CN)₆ ^4- anions was also performed. The material was characterized by XRD and BET measurements. Heat stability of the pillared substance was investigated, too. Pillaring proved to be successful, however, decreased heat resistance was found in the intercalated material relative to the guest LDH. This revised version was published online in July 2006 with corrections to the Cover Date.