Substituent effects on scalar J(13C, 13C) couplings in pyrimidines. An experimental and DFT study

One- two- and three 13C, 13C (n = 1, 2, 3) scalar couplings, (n)J(C,C) in a set of pyrimidine derivatives were studied both experimentally at natural abundance and theoretically by their DFT calculation of all four contributions. Trends of non-contact terms are discussed and substituent effects are rationalized, comparing some of them with the corresponding values in benzene and pyridine. Although substituent effects on non-contact terms are relatively important, the whole trend is dominated by the Fermi contact term. According to the current literature, substituent effects on 1J(C,C) couplings in benzene derivatives are dominated by the inductive effect, which, apparently, is also the case in nitrogen heteroaromatic compounds. However, some differences observed in this work for substituent effects on 1J(C,C) couplings in pyrimidine derivatives suggest that in the latter type of compounds substituent effects can be affected by the orientation of the ring nitrogen lone pairs.     

Dilithiation of 1-benzenesulfonylindoles

Benzenesulfonylindole is converted to a dilithio derivative by 2.2 equivalents of lithiating reagent. The dilithio derivative gives rise to sultones on reaction with carbonyl compounds. This reaction proceeds by an intramolecular displacement of the indole group from the bis-adduct. Fair to poor yields of the 2-indolycarbinols can also be isolated. Benzoyl chloride forms a thiazine dioxide ring by addition at both the 2-indolyl and 2′-phenylsulfonyl positions. 3-Methyl-1-benzenesulfonylindole is also easily dilithiated.     

Chondroitin/polypyrrole nanocomposite hydrogels for the accurate release of 5-fluorouracil by electrical stimulation

The development of electro-stimulated drug release devices is an innovative approach to attain the drug delivery in accurate doses at target sites in a programmed manner. In this work, novel electroactive nanocomposite hydrogels were prepared by encapsulating green-synthesized polypyrrole (PPy) colloids within chondroitin sulfate (CS) networks during the self-crosslinking of CS via N-ethyl-N′-(3-dimethylaminopropyl) carbodiimide chemistry. The structural and morphological properties of CS/PPy hydrogels were studied by Fourier-transformed infrared spectroscopy, scanning electron microscopy, and swelling kinetic measurements. The chemotherapeutic agent 5-fluorouracil (5-FU) was loaded into CS/PPy samples by hydrogel swelling method, or alternatively, by pre-incubating the drug in polymer mixture before crosslinking. Different electrical stimulations can be used to switch ON and accurately tune the 5-FU delivery from GG/PPy hydrogels. A single pulse potential of 5 V switched on the drug delivery up to 90% from nanocomposite hydrogel, in contrast to the low 5-FU amount released in a passive form (< 20%). PPy electroactive behavior played a determining role as the main driving force in 5-FU release activation. Cytotoxicity of hydrogels with and without 5-FU was examined in normal and cancer cells. Considering the high cytotoxicity of 5-FU, the ON/OFF 5-FU release patterns evidenced the potential of CS/PPy hydrogels for electrically controlled drug delivery in implantable or transdermal drug release devices.     

Targeting a Large Active Site: Structure-Based Design of Nanomolar Inhibitors of Trypanosoma brucei Trypanothione Reductase

Trypanothione reductase (TR) plays a key role in the unique redox metabolism of trypanosomatids, the causative agents of human African trypanosomiasis (HAT), Chagas’ disease, and leishmaniases. Introduction of a new, lean propargylic vector to a known class of TR inhibitors resulted in the strongest reported competitive inhibitor of Trypanosoma (T.) brucei TR, with an inhibition constant K_i of 73 nm , which is fully selective against human glutathione reductase (hGR). The best ligands exhibited in vitro IC₅₀ values (half-maximal inhibitory concentration) against the HAT pathogen, T. brucei rhodesiense, in the mid-nanomolar range, reaching down to 50 nm. X-Ray co-crystal structures confirmed the binding mode of the ligands and revealed the presence of a HEPES buffer molecule in the large active site. Extension of the propargylic vector, guided by structure-based design, to replace the HEPES buffer molecule should give inhibitors with low nanomolar K_i and IC₅₀ values for in vivo studies.     

Emergent SU(N) symmetry in disordered SO(N) spin chains

The European Physical Journal B - We report the first observation of the low-frequency Raman spectra of 2-propanol from ambient to supercritical condition. Phenomenological analysis is applied to...     

Lectin arrays for profiling cell surface carbohydrate expression

We present a strategy for the analysis of cell surface carbohydrate expression patterns using lectin arrays fabricated on gold surfaces. Antibody and glycoprotein binding experiments showed that the lectins were effectively immobilized on the surface and retained their carbohydrate-binding specificities. The approach was demonstrated in the analysis of carbohydrate expression on two mammalian cell lines.     

Pure-silica-zeolite MEL low-k films from nanoparticle suspensions

Following our previous works on pure-silica-zeolite (PSZ) MFI, in this study we explore PSZ MEL as a new option for low-k dielectric films. Our motivation has been to increase the microporosity of the spin-on films by moving to structures with a framework density (FD) lower than MFI. Nanoparticle PSZ MEL suspensions were synthesized by a two-stage method that allowed the yield of nanocrystals to be significantly enhanced, while the zeolite nanocrystals remain small. For the first time zeolite nanocrystals of about 50 nm were synthesized with a yield as high as 57%. Nanoparticle suspensions with different particle sizes and crystallinities were spun on silicon wafers to prepare continuous thin films. An ultralow-k value as low as 1.5 was obtained with MEL nanoparticle suspension of high relative crystallinity. The surface roughness of the PSZ MEL film with high relative crystallinity is greatly improved (R(rms) approximately 5.6 nm) compared to MFI films with high relative crystallinity (R(rms) approximately 12 nm).