Structures of a n * Ions Derived from Protonated Pentaglycine and Pentaalanine: Results from IRMPD Spectroscopy and DFT Calculations

Infrared multiple-photon dissociation (IRMPD) spectroscopy and DFT calculations have been used to probe the most stable structures of a ₃ ^* and a ₄ ^* ions derived from both protonated pentaglycine (denoted G₅) and pentaalanine (A₅). The a ₃ ^* and a ₄ ^* ions derived from protonated A₅ feature a CHR=N-CHR’- group at the N-terminus and an oxazolone ring at the C-terminus, as proposed previously [J. Am. Soc. Mass Spectrom. 19, 1788–1798 (2008)]. The isomeric a ₄ ^* ion derived from A₅ with a 3,5-dihydro-4H-imidazol-4-one ring structure was calculated to have a slightly better energy than the oxazolone, but the barrier to its formation is higher and there was no evidence of this ion in the IRMPD spectrum. By contrast, the a ₄ ^* and [a ₄ – H₂O]⁺ (denoted a ₄ ⁰ ) ions from G₅ gave strikingly similar IRMPD spectra and both have the 3,5-dihydro-4H-imidazol-4-one ring structure similar to that recently reported for the [GGGG + H – H₂O]⁺ ion [Int. J. Mass Spectrom. 316–318, 268–272 (2012)]. In the absence of a solvent molecule, the pathway to the oxazolone is calculated to be lower than those to thermodynamically more stable products, the a ₄ ⁰ and the a ₄ ^* with the 3,5-dihydro-4H-imidazol-4-one ring structure. Incorporation of one water molecule is sufficient to reduce the barrier to formation of the a ₄ ⁰ of G₅ to below that for formation of the oxazolone. On the equivalent potential energy surface for protonated A₅ the barrier to formation of the a ₄ ⁰ ion is 12.3 kcal mol^–1 higher than that for oxazolone formation and the a ₄ ⁰ ion is not observed experimentally.

Increased accumulation of paclitaxel and doxorubicin in proliferating capillary cells and prostate cancer cells following ultrasound exposure

Introduction

We have previously reported enhanced cytotoxic effects of both doxorubicin and antisense oligonucleotides using an optimized ultrasound regime of a single 10 s exposure in burst-mode (4 MHz, 32 W/cm²(SaTa), 50 ms burst period) in both PC3 (prostate cancer) cells and angiogenic Huvec (human umbilical cord endothelial cells). The objective of this study was to investigate the effect of ultrasound on the cellular uptake of both hydrophilic agents (rhodamine R123, doxorubicin hydrochloride and mannitol) and hydrophobic agents (rhodamine R6G and paclitaxel) using the same 4 MHz ultrasound exposure system.

Methods

PC3 cells and Huvec were incubated with solutions of radioactive or fluorescent compounds for 1 h and ultrasound was then applied to cells. Following washing and lysis of cells, the degree of drug uptake was measured using liquid scintillation counting or fluorescence spectroscopy.

Results

Ultrasound exposure resulted in the enhanced uptake of both hydrophilic and hydrophobic compounds into cells. For paclitaxel, approximately 100% increased uptake was observed when the drug was encapsulated in a nanoparticulate micellar formulation compared to approximately 50% for free drug.

Conclusions

The 4 MHz, 32 W/cm² ultrasound exposure regime (using burst-mode with 50 ms burst period) allows for the enhanced uptake of both water soluble and insoluble compounds into proliferating cancer and angiogenic cells.     

Abstract convergence theorem for quasi-convex optimization problems with applications

Abstract

Quasi-convex optimization is fundamental to the modelling of many practical problems in various fields such as economics, finance and industrial organization. Subgradient methods are practical iterative algorithms for solving large-scale quasi-convex optimization problems. In the present paper, focusing on quasi-convex optimization, we develop an abstract convergence theorem for a class of sequences, which satisfy a general basic inequality, under some suitable assumptions on parameters. The convergence properties in both function values and distances of iterates from the optimal solution set are discussed. The abstract convergence theorem covers relevant results of many types of subgradient methods studied in the literature, for either convex or quasi-convex optimization. Furthermore, we propose a new subgradient method, in which a perturbation of the successive direction is employed at each iteration. As an application of the abstract convergence theorem, we obtain the convergence results of the proposed subgradient method under the assumption of the Hölder condition of order p and by using the constant, diminishing or dynamic stepsize rules, respectively. A preliminary numerical study shows that the proposed method outperforms the standard, stochastic and primal-dual subgradient methods in solving the Cobb–Douglas production efficiency problem.     

The Luteolinidin and Petunidin 3-O-Glucoside: A Competitive Inhibitor of Tyrosinase

The enzyme tyrosinase plays a key role in the early stages of melanin biosynthesis. This study evaluated the inhibitory activity of anthocyanidin (1) and anthocyanins (2–6) on the catalytic reaction. Of the six derivatives examined, 1–3 showed inhibitory activity with IC₅₀ values of 3.7 ± 0.1, 10.3 ± 1.0, and 41.3 ± 3.2 μM, respectively. Based on enzyme kinetics, 1–3 were confirmed to be competitive inhibitors with K_i values of 2.8, 9.0, and 51.9 μM, respectively. Molecular docking analysis revealed the formation of a binary encounter complex between 1–3 and the tyrosinase catalytic site. Luteolinidin (1) and petunidin 3-O-glucoside (2) may serve as tyrosinase inhibitors to block melanin production.     

6-Formyl Umbelliferone,a Furanocoumarin from Angelica decursiva L., Inhibits Key Diabetes-Related Enzymes and Advanced Glycation End-Product Formation

Over the years, great attention has been paid to coumarin derivatives, a set of versatile molecules that exhibit a wide variety of biological activities and have few toxic side effects. In this study, we investigated the antidiabetic potential of 6-formyl umbelliferone (6-FU), a novel furanocoumarin isolated from Angelica decursiva. Numerous pharmacological activities of 6-FU have been previously reported; however, the mechanism of its antidiabetic activity is unknown. Therefore, we examined the action of 6-FU on a few candidate-signaling molecules that may underlie its antidiabetic activity, including its inhibition of protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, human recombinant aldose reductase (HRAR), and advanced glycation end-product (AGE) formation (IC₅₀ = 1.13 ± 0.12, 58.36 ± 1.02, 5.11 ± 0.21, and 2.15 ± 0.13 μM, respectively). A kinetic study showed that 6-FU exhibited mixed-type inhibition against α-glucosidase and HRAR and competitive inhibition of PTP1B. Docking simulations of 6-FU demonstrated negative binding energies and close proximity to residues in the binding pockets of those enzymes. We also investigated the molecular mechanisms underlying 6-FU’s antidiabetic effects. 6-FU significantly increased glucose uptake and decreased PTP1B expression in insulin-resistant C2C12 skeletal muscle cells. Moreover, 6-FU (0.8–100 μM) remarkably inhibited the formation of fluorescent AGEs in glucose-fructose-induced human serum albumin glycation over the course of 4 weeks. The findings clearly indicate that 6-FU will be useful in the development of multiple target-oriented therapeutic modalities for the treatment of diabetes and diabetes-related complications.     

Circulant weighing matrices of weight 22t

A weighing matrix of weight k is a square matrix M with entries 0, ± 1 such that MM ^T = kI _n . We study the case that M is a circulant and k = 2^2t for some positive integer t. New structural results are obtained. Based on these results, we make a complete computer search for all circulant weighing matrices of order 16.      

Constructions of Partial Difference Sets and Relative Difference Sets on p-Groups

By using some finite local rings, we construct some new partialdifference sets and relative difference sets on pgroups wherep is any prime. When p = 2, some of partial difference setsconstructed are reversible difference sets which include Dillon'sdifference sets.     

Electrospray mass spectrometry: a study on some aqueous solutions of metal salts

Aqueous metal salt solutions were used as models to probe the origin of the species observed in the electrospray mass spectrum. A qualitative or semiquantitative correlation among different species was observed between electrospray responses and calculated equilibrium aqueous solution concentrations. Quantitative correlations were obtained, however, when ions that were identical in charge and similar in type were selected for comparison. In these experiments the ions experienced very similar electrospray-related processes and their effects on the responses were canceled in a comparison of these ions. Consequently, the relative abundances of these ions in the electrospray mass spectrum closely matched the calculated relative abundances in aqueous solution. Our results suggest that the basic principle that determines ionic distribution in the electro spray mass spectrum in aqueous solution chemistry.     

Microwave-assisted immobilization of β-cyclodextrin on PEGylated Merrifield resins

β-Cyclodextrin was immobilized on PEGylated Merrifield resin through cross-linking with 1,6-hexamethylene diisocyanate (HMDI) reagent, using conventional and microwave-assisted methodologies. FT-IR analysis of the solid intermediates indicated the attachment of the linker arm to the resin due the appearance of characteristic bands centered at 1716 and 2270 cm⁻¹ and the attachment of cyclodextrin to the resin was accompanied with increased absorption at the OH stretching regions (3330-3400 cm⁻¹). β-Cyclodextrin linked PEGylated resins are water insoluble and can be used to trap volatile organic compounds (VOCs) from water and subsequently be analyzed by headspace HS/GC, after simple filtration and drying steps.