Hydrophobically modified polyelectrolytes as potential drugs reservoirs of n-alkyl-nitroimidazoles

Indexación: ScieloThe solubilization of three commercial drugs (ornindazole, metronidazole and tinidazole) and model compounds (N-alkyl-2-methyl-4-nitroimidazoles) on aggregates formed by anionic polyelectrolytes, carrying alkyl side chains of different length, have been investigated in aqueous solution at pH 3.0, 7.0 and 11.0. Potassium salts of poly(maleic acid-co-1-olefins), PA-nK2 with n ranging from 8 to 18, were used as micelle-forming polymers. The partition of these drugs between water and the hydrophobic microdomains provided by PA-nK2 was studied by the pseudo-phase model to determinate the distribution coefficient KS, and the standard free energy of transfer Δμºt. The results indicate that solubility of alkyl-nitroimidazoles on these polymer micelles depends moderately on the length of the alkyl chain, and therefore is mainly determined by the heterocyclic group. On the other hand, the solubilization of 1-hexyl-2-methyl-4-nitroimidazole increase with decreasing length of the side alkyl chain; i.e. KS follows the order PA-8K2 > PA-10K2 > PA-12K2 > PA-14K2 > PA-16K2 >PA-18K2.http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0717-97072007000100014&nrm=is

Polyphenol alkyl ester inhibits membrane cholesterol domain formation through an antioxidant mechanism based, in nonlinear fashion, on chain length

Under conditions of oxidative stress, cholesterol aggregates into discrete membrane bilayer domains that precipitate the formation of extracellular crystals, a hallmark feature of the advanced atheroma in cardiovascular disease. Molecular intervention using membrane-directed antioxidants, such as polyphenolic esters, alkylated to increase their lipophilicity and bioavailability, may reduce cholesterol domain formation and associated pathology. In this study, we tested the effects of rosmarinic acid (R0) and rosmarinic esters, with alkyl chain lengths ranging from 4 to 16 carbons (R4-R16), on membrane lipid oxidation and cholesterol domain formation. Model membranes were prepared as binary mixtures of dilinoleoylphosphatidylcholine and cholesterol (at a cholesterol-to-phospholipid mole ratio of 0.6:1), in the absence or presence of each of the various rosmarinic compounds, and exposed to oxidative conditions for up to 72 hr. Changes in lipid hydroperoxide (LOOH) and cholesterol domain formation were measured using iodometric and small angle x-ray diffraction approaches, respectively. Rosmarinic acid and the various esters were observed to have differential effects on LOOH formation based on alkyl chain length. R8 had the greatest antioxidant effect, reducing LOOH levels by 60 ± 18% as compared to vehicle. R8 also inhibited cholesterol domain formation. By contrast, R0 and R16 failed to inhibit LOOH formation (6 ± 19% reduction, 5 ± 13% increase compared to vehicle, respectively), resulting in cholesterol domain formation. These data indicate that the membrane antioxidant potential of rosmarinic acid esters is dependent, in a nonlinear manner, on alkyl chain length. The mechanism for this effect is attributed to the influence of alkyl chain length on the optimal depth of the polyphenols into the lipid bilayer. These findings provide insight into novel atheroprotective benefits of polyphenol esters that are dependent on their membrane location

Antioxidant activity of alkyl gallates and glycosyl alkyl gallates in fish oil in water emulsions: Relevance of their surface active properties and of the type of emulsifier

The antioxidant activity of gallic acid and a series of alkyl gallates (C4-C18) and glycosylated alkyl gallates (C4-C18) on fish oil-in-water emulsions was studied. Three types of emulsifiers, lecithin, Tween-20 and sodium dodecyl sulphate (SDS) were tested. A nonlinear behavior of the antioxidant activity of alkyl gallates when increasing alkyl chain length was observed for emulsions prepared with lecithin. Medium-size alkyl gallates (C6-C12) were the best antioxidants. In contrast, for emulsions prepared with Tween-20, the antioxidants seem to follow the polar paradox. Glucosyl alkyl gallates were shown previously to be better surfactants than alkyl gallates. Nevertheless, they exhibited a worse antioxidant capacity than their corresponding alkyl gallates, in emulsions prepared with lecithin or Tween-20, indicating the greater relevance of having three OH groups at the polar head in comparison with having improved surfactant properties but just a di-ortho phenolic structure in the antioxidant

Free radical 5-exo-dig cyclization as the key step in the synthesis of bis-butyrolactone natural products: experimental and theoretical studies

Radical cyclization reactions were performed by 5-exo-dig mode to yield cis-fused bicyclic systems, leading to the synthesis of bis-butyrolactone class of natural products. The study was aimed at understanding the impact of alkyl side chains of furanoside ring systems in L-ara configuration on the radical cyclization. It was amply demonstrated by experimental studies that the increase in the length of the alkyl side chain has an effect on the cyclization: while efficient cyclization reactions could be realized with methyl and ethyl side chains, the yields were significantly reduced in the case of n-pentyl side chain. Theoretical studies using DFT and (RO)MP2 methods were carried out to analyze the influence of the substitution pattern on the cyclization barriers

Copper(0)-mediated radical polymerisation in a self-generating biphasic system

Herein, we demonstrate the synthesis of well-defined poly(n-alkyl acrylate)s via copper(0)-mediated radical polymerisation in a self-generating biphasic system. During the polymerisation of n-butyl acrylate in DMSO, the polymer phase separates to yield a polymer-rich layer with very low copper content (ICP-MS analysis: 0.016 wt%). The poly(n-butyl acrylate) has been characterized by a range of techniques, including GPC, NMR and MALDI-TOF, to confirm both the controlled character of the polymerisation and the end group fidelity. Moreover, we have successfully chain extended poly(n-butyl acrylate) in this biphasic system several times with n-butyl acrylate to high conversion without intermediate purification steps. A range of other alkyl acrylates have been investigated and the control over the polymerisation is lost as the hydrophobicity of the polymer increases due to the increase in alkyl chain length indicating that it is important for the monomer to be soluble in the polar solvent

Temperature dependence of the electrical conductivity of imidazolium ionic liquids.

The electrical conductivities of 1-alkyl-3-methylimidazolium tetrafluoroborate ionic liquids and of 1-hexyl-3-methylimidazolium ionic liquids with different anions were determined in the temperature range between 123 and 393 K on the basis of dielectric measurements in the frequency range from 1 to 10^7 Hz. Most of the ionic liquids form a glass and the conductivity values obey the Vogel-Fulcher-Tammann equation. The glass transition temperatures are increasing with increasing length of the alkyl chain. The fragility is weakly dependent on the alkyl chain length but is highly sensitive to the structure of the anion.ionic liquids; molten salts;

Surface mobility and structural transitions of poly(n-alkyl methacrylates) probed by dynamic contact angle measurements

Dynamic contact angles and contact-angle hysteresis of a series of poly(n-alkyl methacrylates) (PAMA) were investigated using the Wilhelmy plate technique. The mobility of polymer surface chains, segments, and side groups affected the measured contact angles and their hysteresis. A model is presented in which contact-angle hysteresis of PAMA's is explained in terms of the reorientation of polymer chains and segments at the interface of the polymers with water and air. The contact angles observed also indicated structural transitions in the polymer surfaces of PAMA's that were dependent on alkyl side chain length and temperature

Effects of alkyl chain length of gallate on self-association and membrane-binding

Alkyl gallates are anticipated for their use as antibacterial and antiviral agents. Although their pharmacological activities depend on their alkyl chain length, no mechanism has yet been clarified. As described herein, we investigated the membrane binding properties of a series of alkyl gallates using fluorescence measurement to elucidate their different pharmacological activities. Membrane binding of the alkyl gallates increased concomitantly with increasing alkyl chain length, except for cetyl gallate and stearyl gallate. Dynamic light scattering revealed that alkyl gallates with a long alkyl chain are prone to self-association in the solution. Membrane binding abilities of the alkyl gallates are correlated with antibacterial and antivirus activities, as described in previous reports. The partition constants of the alkyl gallates to lipid membranes depend on the membrane components and the membrane phase. Self-association and lipid binding of the alkyl gallates might be primary biophysical factors associated with their pharmacological activities

Photoionization mass spectrometry of ω-phenylalkylamines: Role of radical cation-π interaction

Linear ω-phenylalkylamines of increasing alkyl chain length have been investigated employing synchrotron radiation in the photon energy range from 7 to 15 eV. These molecules have received considerable interest because they bear the skeleton of biologically relevant compounds including neurotransmitters and because of the possible interaction between the amino moiety and the phenyl ring. Recently, the contribution of this interaction has been assayed in both neutral and protonated species, pointing to a role of the polymethylene chain length. In this work, the ionization energy (IE) values of benzylamine (BA), 2-phenylethylamine (2-PEA), 3-phenylpropylamine (3-PPA), and 4-phenylbutylamine (4-PBA) were investigated in order to ascertain the impact of the different alkyl chain lengths and to verify an amino radical cation-π interaction. The IEs obtained experimentally, 8.54, 8.37, 8.29, and 8.31 eV for BA, 2-PEA, 3-PPA and 4-PBA, respectively, show a decreasing trend that is discussed employing calculations at the CBS-QB3 level. Moreover, the appearance energy values for major fragments produced by the photofragmentation process are reported