Enhanced up-conversion of entangled photons and quantum interference under a localized field in nanostructures.

We theoretically investigate the up-conversion process of two entangled photons on a molecule, which is coupled by a cavity or nanoscale metallic structure. Within one-dimensional input-output theory, the propagators of the photons are derived analytically and the up-conversion probability is calculated numerically. It is shown that the coupling with the nanostructure clearly enhances the process. We also find that the enhancement becomes further pronounced for some balanced system parameters, such as the quantum correlation between photons, radiation decay, and coupling between the nanostructure and molecule. The nonmonotonic dependencies are reasonably explained in view of quantum interference between the coupled modes of the whole system. This result indicates that controlling quantum interference and correlation is crucial for few-photon nonlinearity, and provides a new guidance to wide variety of fields, e.g., quantum electronics and photochemistry.

Model of the photoexcitation processes of a two-level molecule coherently coupled to an optical antenna.

We theoretically investigate photoexcitation processes of a two-level molecular system coherently coupled with an antenna system having a significant dissipation. The auxiliary antenna enables the whole system to exhibit anomalous optical effects by controlling the coupling with the molecule. For example, in the weak excitation regime, the quantum interference yields a distinctive energy transparency through the antenna, which drastically reduces the energy dissipation. On the other hand, in the strong excitation regime, a population inversion of the two-level molecule appears due to the nonlinear effect. Both phenomena can be explained by regarding the antenna and molecule as one quantum-mechanically coupled system. Such an approach drives further research to exploit the full potential of the coupled systems.

Lowly-buffered biorelevant dissolution testing is not necessarily biopredictive of human bioequivalence study outcome: Relationship between dissolution and pharmacokinetics.

It has been revealed that buffer capacity of aspirated human intraluminal fluid is much lower than that of in vitro compendial dissolution media. Since buffer capacity significantly alters the dissolution profile of certain drug products, dissolution testing in highly buffered media dictates poor predictability of in vivo drug performance. To mitigate this inconsistency, low buffer capacity medium was suggested as an in vivo representation (biorelevant dissolution testing). The purpose of this study was to characterize the dissolution profiles of enteric-coated drug products in different buffer capacity media in a flow through cell dissolution apparatus, and to evaluate the in vivo predictability of human bioequivalence study outcomes conducted in the fasted state. It was confirmed that the lower the buffer capacity of dissolution media, the higher the discriminatory power of esomeprazole magnesium hydrate enteric-coated pellets, reflecting human bioequivalence failure. In the meantime, two duloxetine hydrochloride enteric-coated pellets also exhibited distinct dissolution profiles in such a lowly buffered medium despite the fact that these two are bioequivalent in human. Biopharmaceutical and pharmacokinetic characteristics comparison suggested that low intestinal permeability and small systemic elimination rate of duloxetine hinders the clear impact of different dissolution profile on its in vivo performance. These data suggest that dissolution comparison in physiologically-relevant low buffer capacity media is not always indicative of human bioequivalence. Instead, biopharmaceutical and pharmacokinetic aspects must be taken into consideration to make biorelevant dissolution testing biopredictive.

Inhibitory activity of garenoxacin against DNA gyrase of Mycoplasma pneumoniae.

OBJECTIVES: Garenoxacin, a des-fluoro(6)-quinolone, exhibits potent activity against Mycoplasma pneumoniae, including macrolide-resistant strains. There has been no report on the inhibitory activity of garenoxacin against the target enzyme of M. pneumoniae. METHODS: Subunits of DNA gyrase (GyrA and GyrB) proteins of M. pneumoniae FH were separately expressed as His-tagged proteins in Escherichia coli Chaperone Competent Cell BL21 by IPTG induction of plasmids containing the respective gyrA and gyrB genes. The inhibitory activities of garenoxacin, moxifloxacin, gatifloxacin and levofloxacin against DNA gyrase were evaluated by the inhibition of supercoiling activity (n = 3). RESULTS: Against M. pneumoniae FH, garenoxacin showed 2- to 16-fold more potent activity than the other quinolones. The mean IC(50) of garenoxacin for DNA gyrase of M. pneumoniae was 2.5 mg/L. Garenoxacin showed the most potent inhibitory activity against M. pneumoniae DNA gyrase among the quinolones tested. The IC(50) values of the quinolones for DNA gyrase roughly correlated with each MIC value. CONCLUSIONS: The antimycoplasmal activity of the quinolones was almost certainly due to inhibition of the supercoiling activity of DNA gyrase. Garenoxacin was considered a valuable quinolone in the treatment of infectious diseases caused by M. pneumoniae.

In vitro antichlamydial activity of garenoxacin against Chlamydia trachomatis.

Garenoxacin showed the most potent chlamydial activity against Chlamydia trachomatis D/UW-3/Cx among three tested quinolones and azithromycin. The DNA gyrase genes, gyrA and gyrB, of C. trachomatis D/UW-3/Cx were cloned and the GyrA and GyrB subunits of DNA gyrase protein were separately expressed as histidine-tagged proteins in Escherichia coli. The mean 50% inhibitory concentration (IC(50)) of garenoxacin against the supercoiling activity of C. trachomatis D/UW-3/Cx gyrase was 2.9 ± 0.4 µg/ml, which was the most potent inhibitory activity against DNA gyrase among the quinolones tested in this study. At an extracellular concentration of 0.5 µg/ml, the cellular-to-extracellular concentration ratio of garenoxacin was 15.3 ± 1.3, equivalent to that of moxifloxacin and greater than that of levofloxacin. In a time-kill experiment, after exposure to garenoxacin at a concentration of 0.5 µg/ml at 0-6, 5-11, and 24-30 h after infection, the percentages of recoverable chlamydial inclusion-forming units were 11.1 ± 3.3, 0.6 ± 0.1, and 2.6 ± 0.5%, respectively. On transmission electron microscopy observation, after exposure to garenoxacin at 24-30 h after infection, some C. trachomatis elementary bodies remained in the inclusion body; however, the reticulate bodies were completely disrupted. In conclusion, garenoxacin is expected to be a useful quinolone in the treatment of infectious diseases caused by C. trachomatis.

Hinge sugar as a movable component of an excimer fluorescence sensor.

[reaction: see text] The ring flip of a carbohydrate is employed for the tongs-like movable component of a metal ion sensor. A pair of separated pyrene groups attached to the carbohydrate component are placed side by side when it recognizes metal ions, affording excimer fluorescence. This novel molecular sensor is selective for Zn(2+) and Cd(2+).

Exploitation of sugar ring flipping for a hinge-type tether assisting a [2 + 2] cycloaddition.

Methyl 3-O-p-methoxybenzyl-beta-D-xylopyranoside (2) was exploited as a novel hinge-type tether for the [2 + 2] cycloaddition of cinnamate. The major ring conformation occupied by the 2,4-dicinnamate derivative of 2 was 4C1, which extends two cinnamates along a diequatorial orientation. However, 3-O-deprotected dicinnamate 5, when in a non-polar solvent, favours the 1C4 conformation, which assists the approach of two cinnamates with the 1,3-diaxial scaffold. Photoirradiation of compound at 313 nm in CHCl3 afforded the intramolecular cycloaddition of cinnamates to give methyl beta-, delta-, and xi-truxinates in a 86 : 8 : 6 ratio after transesterification with methanol. The regio- and stereoselectivities are comparable to those reported by others for tethered cinnamates. The per-deuterated dicinnamate derivative of 5 facilitated the conformation analyses of the pyranoside rings by 1H NMR, indicating that all the products of photoirradiation had 1C4-fixed pyranosides. Excellent beta-selectivity was achieved when m-bromocinnamate was subjected to hinge-tethered [2 + 2] cycloaddition.

A tong-like fluorescence sensor for metal ions: perfect conformational switch of hinge sugar by pyrene stacking.

Carbohydrates are among the potential materials for molecular devices, since they are abundant natural resources. However, their rigidity has restricted their use for movable devices. Hinge sugars, 2,4-diamino-2,4-dideoxy-xylopyranosides, shed light on the use of carbohydrates as movable components, as demonstrated by the motion by which all four equatorial substituents can change to an axial orientation in synchronization with a chelation-driven 4C1-1C4 ring flip. In this study, we synthesized a tong-like metal ion sensor, 1,3-di-O-pyrenylmethylated hinge sugar (1), and its model compound, methyl 2,4-di-O-pyrenecarbonyl-xylopyranoside (2), to extend the abilities of hinge sugars as molecular components. From observations of the solvent-dependent conformational and fluorescent behavior of 2, we found that the pyrene stacking assists the 1C4 formation of xylopyranoside by 1.7 kcal mol(-1). We also found that compound 1 produced excimer fluorescence by chelation to Pt2+, Zn2+, Cd2+, Mg2+ or Mn2+, and unexpectedly by addition of acids. 1H NMR measurements ascribed this behavior to the 4C1-1C4 ring flip of hinge sugar in response to chelation or protonation at N2, and revealed rapid and perfect 1C4 formation in the case of Zn2+. These findings will extend the scope of hinge sugars as movable components.