Cystic fibrosis: a label-free detection approach based on thermally modulated electrochemical impedance spectroscopy

Cystic fibrosis is one of the most common genetically inherited diseases in northern Europe, with the DF508 mutation being the most common, and among the Caucasian population being responsible for almost 70% of cases. In this work, we report on the use of thermally modulated electrochemical impedance spectroscopy for the discrimination of the DF508 mutation from the wild-type sequence. DNA probes (15 and 21 bases long) were immobilised on the surface of gold electrodes and the variation of the charge-transfer resistance was monitored as a function of hybridisation. Two sets of targets were used in this work: synthetic 15-mer sequences and two single-stranded synthetic analogues of PCR products 82 (mutant) and 85 (wild type) bases long. Hybridisation with short targets resulted in very sequence specific charge-transfer-resistance variation with a discrimination factor at room temperature between fully complementary and mismatched sequences of approximately fivefold. However, in the case of the single-stranded synthetic PCR product analogues, a lower discrimination factor was recorded (1.5-fold). The effect of temperature was investigated to improve discrimination and the use of a posthybridisation wash at elevated temperature resulted in a fivefold improvement in the discrimination factor. Using an electrode array with probes immobilised against each of the mutant and wild-type sequences, we achieved an unequivocal detection of the DF508 mutation.     

One-pot synthesis of ortho-hydroxycinnamate esters

Phenols are converted to salicylaldehydes with paraformaldehyde, MgCl₂-Et₃N in THF, and subsequent treatment with methyl (triphenylphosphoranylidene)acetate gave the corresponding methyl ortho-hydroxycinnamate derivatives. The sequence is conveniently carried out as a one-pot procedure.     

T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei

A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thionicotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipment or anhydrous solvents, could be performed as either two or three component reactions, and gave moderate–good yields as high as 63%. This provides ready access to N-phenyl compounds in this family, which have been generally difficult to prepare. As part of the study, the first crystal structure of neutral thionicotinic acid is also reported, and showed the molecule to be in the form of the thione tautomer. Additionally, the synthesized compounds were tested against T. brucei, the causative agent of Human African Sleeping Sickness. Screening at 50 µM concentration showed that five of the compounds strongly inhibited growth and killed parasites.     

Synthesis and cytotoxic evaluation of novel brominated N-alkyl pyrano[3,2-c]quinolinones

A novel series of 6-alkyl-4-bromopyrano[3,2-c]quinoline-2,5-diones ( 2a–c ), 6-alkyl-3,4-dibromopyrano[3,2-c]quinoline-2,5-diones ( 4a–c ), and 6-alkyl-3-amino-bromopyrano[3,2-c]quinoline-2,5-diones ( 6a–c ) were synthesized via appropriate conventional methods and in good yields. The structures of target compounds were approved by elemental analysis, IR, ¹H NMR, ¹³C NMR, and mass spectrometry. The antitumor inhibitory activities of the new compounds were evaluated on several cancer cell lines, A-549 (human lung cancer), HCT-116 (human colon cancer), MCF-7 (breast cancer), and HePG-2 (human liver cancer). Moreover, 50% inhibitory concentrations, IC₅₀, were established. 5-Fluorouracil was used as a positive control in the viability assay. The screening results showed that most of the examined compounds exposed powerful inhibition activity toward various cell lines. Particularly, Compound 4c exhibited higher cytotoxic activity against four tumor cell lines than the reference drug, 5-fluorouracil, with significantly lower IC₅₀ values. Accordingly, most of the synthesized compounds would be a better prospective growth in the anticancer drug discovery.     

Subordination of Regular Kernels and Abelian Theorems for Quotients

We prove general boundary limit theorems of abelian type for quotients of functions defined in the half space . The functions considered are defined as convolutions of a kernel with Borel measures defined on the boundary . Our theorems are of the form

A new technique of using homotopy analysis method for solving high‐order nonlinear differential equations

In this paper, a new technique of homotopy analysis method (HAM) is proposed for solving high‐order nonlinear initial value problems. This method improves the convergence of the series solution, eliminates the unneeded terms and reduces time consuming in the standard homotopy analysis method (HAM) by transform the nth‐order nonlinear differential equation to a system of n first‐order equations. Second‐ and third‐ order problems are solved as illustration examples of the proposed method. Copyright © 2010 John Wiley & Sons, Ltd.     

Responsive solids from cross-linked block copolymers

Novel responsive solids were prepared by randomly cross-linking the polyisoprene chains of a disordered polystyrene-polyisoprene block copolymer. Our experiments show that block copolymer chains, composed of hundreds of repeat units, can undergo reversible order-disorder transitions despite the quenched randomness that arises due to the attachment of one of the blocks to a cross-linked network. The structure, properties, and phase behavior of these materials are determined by a delicate interplay between the density of cross-links and the nature of the ordered state.     

Synthesis,Characterization, and Antimicrobial Evaluation of Some Novel 4-Hydroxyquinolin-2(1H)-ones

Vilsmeier–Haack formylation of 3-acetyl-1-methyl-4-hydroxyquinolin-2(1H)-one (2) produced the novel 6-methyl-4,5-dioxo-5,6-dihydro-4H-pyrano[3,2-c]quinoline-3-carboxaldehyde (3). Reactions of carboxaldehyde 3 with a diversity of nucleophilic reagents were studied and a variety of products were obtained via ring-opening, ring-closing (RORC) sequence. Also, some novel heteroannulated pyrano[3,2-c]quinolines were prepared. Structures of the new synthesized products were deduced on the basis of their analytical and spectral data.     

Synthesis of Spiro‐Heterocycles with the Thiazolidinone Moiety from Nitrilimines

The 2‐phenylimino‐1,3‐thiazolidin‐4‐one 2 was obtained by thermal cyclization of 4‐amino‐5‐phen‐yl‐3, 5‐thiaaza‐4‐pentenoic acid 1 using DCC as dehydration agent. Treatment of 2‐phenylimino‐1,3‐thiazolidin‐4‐one 2 with various hydrazonoyl halides 3 (nitrilimines 4 precursor) yielded 6‐aryl‐9‐phenyl‐8‐substituted‐1,4,6,7,9‐thiatetrazaspiro‐[4.4]non‐7‐en‐3‐ones 5a‐1. Both analytical and spectroscopic data of all the synthesized compounds are in full agreement with the proposed structures.