Dendrimers as scaffolds for multifunctional reversible addition–fragmentation chain transfer agents: Syntheses and polymerization

The synthesis and characterization of novel first‐ and second‐generation true dendritic reversible addition–fragmentation chain transfer (RAFT) agents carrying 6 or 12 pendant 3‐benzylsulfanylthiocarbonylsulfanylpropionic acid RAFT end groups with Z‐group architecture based on 1,1,1‐hydroxyphenyl ethane and trimethylolpropane cores are described in detail. The multifunctional dendritic RAFT agents have been used to prepare star polymers of poly(butyl acrylate) (PBA) and polystyrene (PS) of narrow polydispersities (1.4 < polydispersity index < 1.1 for PBA and 1.5 < polydispersity index < 1.3 for PS) via bulk free‐radical polymerization at 60 °C. The novel dendrimer‐based multifunctional RAFT agents effect an efficient living polymerization process, as evidenced by the linear evolution of the number‐average molecular weight (M_n) with the monomer–polymer conversion, yielding star polymers with molecular weights of up to M_n = 160,000 g mol^?1 for PBA (based on a linear PBA calibration) and up to M_n = 70,000 g mol^?1 for PS (based on a linear PS calibration). A structural change in the chemical nature of the dendritic core (i.e., 1,1,1‐hydroxyphenyl ethane vs trimethylolpropane) has no influence on the observed molecular weight distributions. The star‐shaped structure of the generated polymers has been confirmed through the cleavage of the pendant arms off the core of the star‐shaped polymeric materials. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 42: 5877–5890, 2004     

Dihalodimethyltin(IV) complexes of 2‐(pyrazol‐1‐ylmethyl)pyridine

Reaction of dichloro‐ and dibromodimethyltin(IV) with 2‐(pyrazol‐1‐ylmethyl)pyridine (PMP) afforded [SnMe₂Cl₂(PMP)] and [SnMe₂Br₂(PMP)] respectively. The new complexes were characterized by elemental analysis and mass spectrometry and by IR, Raman and NMR (¹H, ¹³C) spectroscopies. Structural studies by X‐ray diffraction techniques show that the compounds consist of discrete units with the tin atom octahedrally coordinated to the carbon atoms of the two methyl groups in a trans disposition (Sn? C = 2.097(5), 2.120(5) Å and 2.110(6), 2.121(6) Å in the chloro and in the bromo compounds respectively), two cis halogen atoms (Sn? Cl = 2.4908(16), 2.5447(17) Å; Sn? Br = 2.6875(11), 2.7464(9) Å) and the two donor atoms of the ligand (Sn? N = 2.407(4), 2.471(4) Å and 2.360(5), 2.455(5) Å). In both cases, the Sn? N(pyridine) bond length is markedly longer than the Sn? N(pyrazole) distance. Copyright © 2003 John Wiley & Sons, Ltd.     

Saturated heterocycles, 162 [1]. synthesis and steric structures of 3,4-disubstituted 1,6,7,11b-tetrahydropyrimido[6,1-a]isoquinolin-2-ones

The reaction of 1-(hydrazidomethyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline 3 with aromatic aldehydes yield hydrazones 4a,b or pyrimido[6,1-a]isoquinolines 5a-c depending upon the proportions of the reagents. With ketones, 3 gives only hydrazones 4a-d and 7 , which can be transformed to pyrimidoisoquinolines 10a-e and 11 with aldehydes. The ring closures are stereospecific; the relative configurations were determined by DNOE measurements.     

Polymer collapse, protein folding, and the percolation threshold

We study the transition of polymers in the dilute regime from a swollen shape at high temperatures to their low-temperature structures. The polymers are modeled by a single self-avoiding walk (SAW) on a lattice for which l of the monomers (the H monomers) are self-attracting, i.e., if two nonbonded H monomers become nearest neighbors on the lattice they gain energy of interaction (epsilon = -/epsilon/); the second type of monomers, denoted P, are neutral. This HP model was suggested by Lau and Dill (Macromolecules 1989, 22, 3986-3997) to study protein folding, where H and P are the hydrophobic and polar amino acid residues, respectively. The model is simulated on the square and simple cubic (SC) lattices using the scanning method. We show that the ground state and the sharpness of the transition depend on the lattice, the fraction g of the H monomers, as well as on their arrangement along the chain. In particular, if the H monomers are distributed at random and g is larger than the site percolation threshold of the lattice, a collapsed transition is very likely to occur. This conclusion, drawn for the lattice models, is also applicable to proteins where an effective lattice with coordination number between that of the SC lattice and the body centered cubic lattice is defined. Thus, the average fraction of hydrophobic amino acid residues in globular proteins is found to be close to the percolation threshold of the effective lattice.     

2',7'-Difluorofluorescein excited-state proton reactions: correlation between time-resolved emission and steady-state fluorescence intensity

The presence of excited-state buffer-mediated proton exchange reactions influences the steady-state fluorescence signals from dyes in solution. Since biomolecules in general have some chemical groups that can act as proton acceptors/donors and are usually dissolved in buffer solutions which can also behave as appropriate proton acceptors/donors, the excited-state proton exchange reactions may result in distorted steady-state fluorescence signals. In a previous paper (J. Phys. Chem. A 2005, 109, 734-747), we evaluated kinetic and other pertinent parameters for the excited-state proton reactions of the prototropic forms of 2',7'-difluorofluorescein (Oregon Green 488, OG488), recording a fluorescence decay surface at different pH values and acetate buffer concentrations, analyzed by means of global compartmental analysis. In this article we use the rate constants and the corrected pre-exponential factors from the previously recorded fluorescence decay traces to simulate the decay times and associated pre-exponentials at different acetate buffer concentrations and constant pH and compare these theoretically calculated values with new experimental data. We also calculate the steady-state fluorescence intensity vs pH and vs acetate buffer concentration (at constant pH) and compare these calculated emission values with the experimental data previously published. The agreement between the experimental and simulated data is excellent.     

The PEST sequence does not contribute to the stability of the cystic fibrosis transmembrane conductance regulator.

Background  

Endoplasmic reticulum retention of misfolded cystic fibrosis transmembrane conductance regulator (CFTR) mutants and their rapid degradation is the major cause of cystic fibrosis (CF). An important goal is to understand the mechanism of how the misfolded proteins are recognized, retained, and targeted for degradation.     

An Approach to Minimize Tumour Proliferation by Reducing the Formation of Components for Cell Membrane

Isoprenoids are natural compounds essential for a great number of cellular functions. One of them is farnesol (FOH), which can reduce cell proliferation, but its low solubility in aqueous solvents limits its possible clinical use as a pharmacological tool. One alternative is the use of cyclodextrins (CDs) which house hydrophobic molecules forming inclusion complexes. To assess FOH potential application in anticancer treatments, Sulfobutylated β-cyclodextrin Sodium Salt (SBE-β-CD) was selected, due to it has high solubility, approbation by the FDA, and numerous studies that ensure its safety to be administered parenterally or orally without nephrotoxicity associated. The therapeutic action of farnesol and complex were studied in different carcinoma cells, compared with a normal cell line. Farnesol showed selectivity, affecting the viability of colon and liver cancer cells more than in breast cancer cells and fibroblasts. All cells suffered apoptosis after being treated with 150 μM of free FOH, but the complex reduced their cell viability between 50 and 75%. Similar results were obtained for both types of isomers, and the addition of phosphatidylcholine reverses this effect. Finally, cell cycle analysis corroborates the action of FOH as inducer of a G0/G1 phase; when the cells were treated using the complex form, this viability was reduced, reaching 50% in the case of colon and liver, 60% in fibroblasts, and only 75% in breast cancer.     

Heterotrimeric liquid crystalline thiadiazole derivatives

Abstract

Various trimeric co-oligomers combining 2-phenyl-1,3,4-thiadiazole mesogenic moieties with a biphenyl mesogenic moiety were synthesized and their mesomorphic behaviour investigated by polarizing microscopy, calorimetry and X-ray scattering. Such co-oligomeric structures provide an opportunity to combine different mesogenic units. Thus readily accessible homochiral biphenyl mesogenic units were connected with thiadiazole mesogenic units leading to an oligomeric liquid crystal material with ferroelectric properties.