In vivo metal-catalyzed SeCT therapy by a proapoptotic peptide

Selective cell tagging (SeCT) therapy is a strategy for labeling a targeted cell with certain chemical moieties via a catalytic chemical transformation in order to elicit a therapeutic effect. Herein, we report a cancer therapy based on targeted cell surface tagging with proapoptotic peptides (Ac-GGKLFG-X; X = reactive group) that induce apoptosis when attached to the cell surface. Using either Au-catalyzed amidation or Ru-catalyzed alkylation, these proapoptotic peptides showed excellent therapeutic effects both in vitro and in vivo. In particular, co-treatment with proapoptotic peptide and the carrier–Ru complex significantly and synergistically inhibited tumor growth and prolonged survival rate of tumor-bearing mice after only a single injection. This is the first report of Ru catalyst application in vivo, and this approach could be used in SeCT for cancer therapy.

The combination of a proapoptotic peptide with covalent tagging and a carrier-Ru-complex inhibited tumor growth in mice after a single injection.     

Iridium complex-catalyzed allylic amination of allylic esters

Iridium complex-catalyzed allylic amination of allylic carbonates was studied. The solvent strongly affected the catalytic activity. The use of a polar solvent such as EtOH is essential for obtaining the products in high yield. The reaction of (E)-3-substituted-2-propenyl carbonate and 1-substituted-2-propenyl carbonate with pyrrolidine in the presence of a catalytic amount of [Ir(COD)Cl](2) and P(OPh)(3) (P/Ir = 2) gave a branch amine with up to 99% selectivity. Both secondary and primary amines could be used for this reaction. When a primary amine was used, selective monoallylation occurred. No diallylation product was obtained. The reaction of 1,1-disubstituted-2-propenyl acetate with amines exclusively gave an alpha,alpha-disubstituted allylic amine. This reaction provides an alternative route to the addition of an organometallic reagent to ketimines for the preparation of such amines. The reaction of (Z)-3-substituted-2-propenyl carbonate with amines gave (Z)-linear amines with up to 100% selectivity. In all cases, no (E)-linear amine was obtained. The selectivities described here have not been achieved in similar palladium complex-catalyzed reactions.     

Micelles for signal enhancement and novel selectivity of dansyl amino acids

Fluorescence intensity of various chemical species is enhanced in the microenvironment provided by micelles. Parameters which affect fluorescence intensities are examined by using dansyl (Dns) amino acids as the probe. The retention behavior of Dns-amino acids in micellar LC is examined by using ion-exchange-induced stationary phases. The type and concentration of micellar agent and modifier ion as well as concentration of acetonitrile in the mobile phase affect the retention and signal intensity of Dns-amino acids. The order of elution of Dns-amino acids obtained with the micellar mobile phase is very different from that observed in conventional reversed-phase LC. Fluorescence intensities of Dns-amino acids are enhanced by the micellar mobile phase.     

A first–passage time random walk distribution with five transition probabilities: a generalization of the shifted inverse trinomial

In this paper a univariate discrete distribution, denoted by GIT, is proposed as a generalization of the shifted inverse trinomial distribution, and is formulated as a first-passage time distribution of a modified random walk on the half-plane with five transition probabilities. In contrast, the inverse trinomial arises as a random walk on the real line with three transition probabilities. The probability mass function (pmf) is expressible in terms of the Gauss hypergeometric function and this offers computational advantage due to its recurrence formula. The descending factorial moment is also obtained. The GIT contains twenty-two possible distributions in total. Special cases include the binomial, negative binomial, shifted negative binomial, shifted inverse binomial or, equivalently, lost-games, and shifted inverse trinomial distributions. A subclass GIT_3,1 is a particular member of Kemp’s class of convolution of pseudo-binomial variables and its properties such as reproductivity, formulation, pmf, moments, index of dispersion, and approximations are studied in detail. Compound or generalized (stopped sum) distributions provide inflated models. The inflated GIT_3,1 extends Minkova’s inflated-parameter binomial and negative binomial. A bivariate model which has the GIT as a marginal distribution is also proposed.     

Structural study on gold nanoparticle functionalized with DNA and its non-cross-linking aggregation

Hybridization of DNA tethered on colloidal nanoparticles with fully matched complementary one induces the aggregation of the particles in a non-cross-linking configuration. Here, we performed a structural study on DNA-functionalized gold nanoparticle and its non-cross-linking aggregation mainly using synchrotron radiation small-angle X-ray scattering. To understand the non-cross-linking aggregation, the nanoparticles with various DNA lengths and core sizes were used. In the aggregation, the surface distance between the gold nanoparticles increased with the length of DNA duplex, although the increment of the distance per base pair was not constant and showed the tendency to become small with increasing DNA length, meaning the interdigitation of DNA layers. The aggregation was also found to occur between the identical cores, without being affected by tethered DNA. Furthermore, it was proved that the relative increase in DNA length to core size leads to the increase in colloidal stability. Even the nanoparticles with full-matched DNA duplex were dispersed stably. These facts suggested that van der Waals interaction between core particles rather than end-to-end stacking between DNA duplexes is a dominant attractive interaction. The steric repulsion force arising from entropic loss of thermal fluctuation of DNA molecules might be a key factor to characterize the non-cross-linking aggregation.     

Supramolecular dye inclusion single crystals created from 2,3,6-trimethyl-β-cyclodextrin and porphyrins

In Nature, chromophoric groups play various roles, such as oxygen carriers, electron donors, light sensitizers, which are achieved in many cases by control of their aggregation modes in proteins. Host-guest chemistry between cyclodextrins and porphyrins has attracted great interest from supramolecular chemists because of their unique structures and functions that mimic those of proteins with chromophoric prosthetic groups. To mimic Nature's contrivances, the host-guest systems between cyclodextrins and porphyrins have frequently been studied. It is really surprising, however, that to date no detailed structural information of these complexes has been obtained from single-crystal analysis. In 2011, we reported the first successful isolation of a dye inclusion single crystal (DISC) between 2,3,6-trimethyl-β-cyclodextrin (TMβCD) and 5,10,15,20-tetrapyridylporphyrin (TPyP), and analyzed its X-ray crystal structure. The crystal structure revealed not only the real complex mode but also the attractive orientation of TPyP in the DISC. Herein, we present new strategies to prepare DISCs of TMβCD for several porphyrins and provide crystal structures, details of the complex modes, and optical properties. We believe that the present study has various important implications not only for the basic crystal analysis of inclusion complexes but also for potential applications that use these single crystals.     

Failure diagnosis of organic photovoltaic using electro-optic probe

This paper describes the measurement of an organic photovoltaic using an electro-optic probe. We verify the validity of the electro-optic probe by comparing it with a conventional electric probe. The electric field distribution of the organic photovoltaic is examined on the basis of results of the test board measurement using the electro-optic probe and results of the test board simulation using an electromagnetic field simulator. We succeed in failure diagnosis of the organic photovoltaic in three failure modes. We found that the organic photovoltaic has a failure cell, and the electro-optic probe is successfully applied to failure diagnosis of organic photovoltaic.     

Femtosecond fluorescence study of the reaction pathways and nature of the reactive S1 state of cis-stilbene

We report a femtosecond time-resolved fluorescence study of cis-stilbene, a prototypical molecule showing ultrafast olefinic photoisomerization and photocyclization. The time-resolved fluorescence signals were measured in a nonpolar solvent over a wide ultraviolet-visible region with excitation at 270 nm. The time-resolved fluorescence traces exhibit non-single exponential decays which are well fit with bi-exponential functions with time constants of τ(A) = 0.23 ps and τ(B) = 1.2 ps, and they are associated with the fluorescence emitted from different regions of the S(1) potential energy surface (PES) in the course of the structural change. Quantitative analysis revealed that the two fluorescent components exhibit similar intrinsic time-resolved spectra extending from 320 nm to 700 nm with the (fluorescence) oscillator strength of f(A) = 0.32 and f(B) = 0.21, respectively. It was concluded that the first component is assignable to the fluorescence from the untwisted S(1) PES region where the molecule reaches immediately after the initial elongation of the central C[double bond, length as m-dash]C bond, while the second component is the fluorescence from the substantially twisted region around a shallow S(1) potential minimum. The quantitative analysis of the femtosecond fluorescence data clearly showed that the whole isomerization process proceeds in the one-photon allowed S(1) state, thereby resolving a recent controversy in quantum chemical calculations about the reactive S(1) state. In addition, the evaluated oscillator strengths suggest that the population branching into the isomerization/cyclization pathways occurs in a very early stage when the S(1) molecule still retains a planar Ph-C[double bond, length as m-dash]C-Ph skeletal structure. On the basis of the results obtained, we discuss the dynamics and mechanism of the isomerization/cyclization reactions of cis-stilbene, as well as the electronic structure of the reaction precursor.