Bioorthogonal release of anticancer drugs via gold-triggered 2-alkynylbenzamide cyclization

Metal-based uncaging of biomolecules has become an emerging approach for in vivo applications, which is largely due to the advantageous bioorthogonality of abiotic transition metals. Adding to the library of metal-cleavable protecting groups, this work introduces the 2-alkynylbenzamide (Ayba) moiety for the gold-triggered release of secondary amines under mild and physiological conditions. Studies were further performed to highlight some intrinsic benefits of the Ayba protecting group, which are (1) its amenable nature to derivatization for manipulating prodrug properties, and (2) its orthogonality with other commonly used transition metals like palladium and ruthenium. With a focus on highlighting its application for anticancer drug therapies, this study successfully shows that gold-triggered conversion of Ayba-protected prodrugs into bioactive anticancer drugs (i.e. doxorubicin, endoxifen) can proceed effectively in cell-based assays.

With the 2-alkynylbenzamide (Ayba) group, this study shows that secondary amines can be released under mild and physiological conditions. Its amenable nature and orthogonality with other metals also allows greater control in prodrug design.     

Furopyridines. XXIV. Nitration,chlorination, acetoxylation and cyanation of 2,3-dihydrofuro[2,3-b]-, -[3,2-b]-, -[2,3-c]- and -[3,2-c]pyridine N-Oxides

Nitration of 2,3-dihydrofuro[3,2-b]- N-oxide 3b and -[2,3-c]pyridine N-oxide 3c afforded the nitropyridine compounds 4b, 5b and 6 from 3b and 4c, 5c, 5′c and 7 from 3c , while -[2,3-b]- N-oxide 3a and -[3,2-c]pyridine N-oxide 3d did not give the nitro compound. Chlorination of 3b and 3c with phosphorus oxychloride yielded mainly the chloropyridine derivatives 15b, 15′b from 3b and 15c and 15′c from 3c , whereas 3a and 3d gave pyridine derivatives formed through fission of the 1–2 ether bond of the furo-pyridines 13a , 14 and 13d . Acetoxylation of 3b and 3c gave 3-acetoxy derivatives 18b and 18c and the parent compound 1b and 1c . Acetoxylation of 3a yielded compounds formed through fission of the 1–2 bond 16 and 17 and 3d gave furopyridones 19 and 19 ′. Cyanation of 3b and 3c yielded mainly the cyanopyridine compounds 20b, 20c and 20′c . Cyanation of 3a and 3d gave the cyanopyridine compounds 20a , 20d and 20′d accompanying formation of the pyridine derivatives 21a, 21d and 21′d .     

Method Development of Enantiomer Separations by Affinity Capillary Electrophoresis,Cyclodextrin Electrokinetic Chromatography and Capillary Electrophoresis-Mass Spectrometry

 Capillary electrophoresis (CE) has become a powerful tool for enantiomer separations during the last decade. Since 1993, the author has investigated enantiomer separations by affinity capillary electrophoresis (affinity CE) with some proteins and by cyclodextrin electrokinetic chromatography (CDEKC) with some charged cyclodextrins (CDs). Many successful enantiomer separations are demonstrated from our study in this review article. In the enantiomer separations by affinity CE, the deterioration of detection     

One-way isomerization and internal rotation in anthrylethylenes in the excited triplet state

1-(2-Anthryl)-2-(bromophenyl)ethylene and 1-(2-anthryl)-2-(4-methoxyphenyl)ethylene undergo cis→trans one-way isomerization in the excited triplet state through an adiabatic process from the cis-triplet to the trans-triplet states. The trans-isomers of these compounds undergo one-way internal rotation in the excited triplet state with an activation barrier of }7 kcal mol^?1 and a frequency factor of }10¹² s^?1, while no internal rotation takes place in the excited singlet state.     

Effects of Contrast and Character Size upon Legibility of Japanese Text Stimuli Presented on Visual Display Terminal

We examined effects of contrast and character size upon legibility of Japanese text stimuli presented on visual display terminal (VDT). In the experiment, three different character sizes were employed and the text stimulus was presented under a variety of conditions where contrast between the text and the background changed. Reading speed and the rate of readable characters were measured. Subjective rating for legibility was also evaluated. Results showed that legibility increases with luminance contrast for all character sizes examined here. A strong correlation was found between the subjective rating index and reading speed.     

Synthesis and electrochemical properties of vanadium pentoxide nanotube arrays

Nanotube arrays of amorphous vanadium pentoxide (V(2)O(5)) were synthesized via template-based electrodeposition, and its electrochemical properties were investigated for Li-ion intercalation applications. The nanotubes have a length of 10 microm, outer diameter of 200 nm and inner diameter of 100 nm. Electrochemical analyses demonstrate that the V(2)O(5) nanotube array delivers a high initial capacity of 300 mAh/g, about twice that of the electrochemically prepared V(2)O(5) film. Although the V(2)O(5) nanotube array shows a more drastic degradation than the film under electrochemical redox cycles, the nanotube array reaches a stabilized capacity of 160 mAh/g, which remains about 1.3 times the stabilized capacity of the film.     

ACOUSTIC POWER SUPPRESSION OF A PANEL STRUCTURE USING H∞OUTPUT FEEDBACK CONTROL

This paper presents a robust control system design for suppressing the radiated acoustic power emitted from a vibrating planar structure, and spillover effect caused by neglected high-frequency modes. A state-space model of a simply supported panel structure is derived and an output equation is formed based on the one-dimensional PVDF film sensors. An output feedback H_∞control is designed by introducing a multiplicative perturbation which represents unmodelled high-frequency dynamics in the control system. The simulation and experimental results demonstrated significant decrease in sound radiation for the considered structural power modes in control.     

Diffractive phase element for shrinking focal spot diameter: Design, fabrication, and application to laser beam lithography

A diffractive phase element (DPE) capable of shrinking the main-lobe of the focal spot of an incident beam has been developed. The DPE is expected to be used in laser beam lithography to improve the resolution. Special constraints, which force the focal spot to be small while permitting increase of the side-lobes, are introduced in the design of the DPE using an iterative method based on the Gerchberg-Saxton algorithm. Two kinds of DPEs are fabricated by a laser beam lithography system of our own composition and their performances are experimentally measured. The minimum line width obtained by the system is improved from 1.2 μm to 1.0 μm with the fabricated DPE. Focal depth of the focusing system is discussed.     

Recent Progress in Polyhedral Harmonics

Polyhedral harmonics is a subject which deals with the problem of characterizing the continuous functions satisfying the mean value property with respect to a polytope. The main feature of it is the finite dimensionality of the space of polyhedral harmonic functions. The theory involves not only analysis but also algebra and combinatorics, and has a rather different flavor from classical harmonic analysis. This paper aims at providing a survey on the subject, focusing on the author's recent results.     

Tensor Products of Type III Factor Representations of Cuntz–Krieger Algebras

We introduced a non-symmetric tensor product of any two states or any two representations of Cuntz–Krieger algebras associated with a certain non-cocommutative comultiplication in our previous work. In this paper, we show that a certain set of KMS states is closed with respect to the tensor product. From this, we obtain formulae of tensor products of type III factor representations of Cuntz–Krieger algebras which are different from results of the tensor product of factors of type III.