Cholesterol-nitrone conjugates as protective agents against lipid oxidation: A model membrane study.

Free radical scavengers such as α-phenyl-N-tert-butylnitrone (PBN) have been widely used as protective agents in several biological models. We recently designed two PBN derivatives by adding a cholesterol moiety to the parent nitrone to increase its lipophilicity. In addition to the cholesterol, a sugar group was also grafted to enhance the hydrophilic properties at the same time. In the present work we report on the synthesis of a third derivative bearing only a cholesterol moiety and the physical chemical and antioxidant characterization of these three derivatives. We demonstrated they were able to form stable monolayers at the air/water interface and with the two derivatives bearing a sugar group, repulsive interactions with 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLPC) were observed. We next investigated the interaction with DLPC on a liposome model. Fluorescence spectroscopy experiments showed the addition of a cholesterol moiety causes an ordering effect whereas the presence of the sugar group led to a disordering effect. The protective effect against lipid oxidation was then investigated using dynamic light scattering and the formation of conjugated dienes was quantified spectrophotometrically. Two oxidizing systems were tested, i.e. the AAPH-thermolysis which generates peroxyl radicals and the Fenton reagent which is responsible of the formation of hydroxyl radicals. Due to their membrane localization, the three cholesteryl-PBN derivatives are able to prevent lipid oxidation with the two types of radical inducers but with a different mode of action.

Nitrone-Trolox conjugate as an inhibitor of lipid oxidation: Towards synergistic antioxidant effects.

Free radical scavengers like α-phenyl-N-tert-butylnitrone (PBN) and 6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid (Trolox) have been widely used as protective agents in various biomimetic and biological models. A series of three amphiphilic Trolox and PBN derivatives have been designed by adding to those molecules a perfluorinated chain as well as a sugar group in order to render them amphiphilic. In this work, we have studied the interactions between these derivatives and lipid membranes to understand how they influence their ability to prevent membrane lipid oxidation. We showed the derivatives better inhibited the AAPH-induced oxidation of 1,2-dilinoleoyl-sn-glycero-3-phosphocholine (DLiPC) small unilamellar vesicles (SUVs) than the parent compounds. One of the derivatives, bearing both PBN and Trolox moieties on the same fluorinated carrier, exhibited a synergistic antioxidant effect by delaying the oxidation process. We next investigated the ability of the derivatives to interact with DLiPC membranes in order to better understand the differences observed regarding the antioxidant properties. Surface tension and fluorescence spectroscopy experiments revealed the derivatives exhibited the ability to form monolayers at the air/water interface and spontaneously penetrated lipid membranes, underlying pronounced hydrophobic properties in comparison to the parent compounds. We observed a correlation between the hydrophobic properties, the depth of penetration and the antioxidant properties and showed that the location of these derivatives in the membrane is a key parameter to rationalize their antioxidant efficiency. Molecular dynamics (MD) simulations supported the understanding of the mechanism of action, highlighting various key physical-chemical descriptors.

Evaluation of the corrosion inhibiting efficacy of a newly synthesized nitrone against St37 steel corrosion in acidic medium: Experimental and theoretical approaches.

A novel amphiphilic nitrone, N-phenyl-1-(4-((11-(pyridin-1-ium-1yl) undecanoyl) oxy)phenyl)methanimine oxide bromide (NP-1-4-11-PUOPMOB) has been synthesized from a fatty acid derivative as a starting material. Structural characterization of the new compound has been realized by spectroscopic techniques (FTIR, 1H NMR, and 13C NMR). The corrosion inhibition effect of the compound for St37 steel corrosion in 1 M HCl medium has been investigated using experimental (weight loss, electrochemical impedance spectroscopy, potentiodynamic polarization, dynamic electrochemical impedance spectroscopy) and theoretical approaches complemented by surface morphological examination using energy dispersive X-ray spectroscopy, scanning electron microscope, and atomic force spectroscopy. Results from both chemical and electrochemical techniques reveal that the presence of the nitrone in the acid solution impedes St37 steel corrosion. The inhibition efficiency obtained at 125 ppm and 150 ppm concentrations for all methods is found to be over 90%. NP-1-4-11-PUOPMOB behaves as a mixed type corrosion inhibitor according to the potentiodynamic polarization studies. The adsorption of NP-1-4-11-PUOPMOB molecules onto the metal surface follows Langmuir adsorption isotherm and the calculated Kads (equilibrium constant of the adsorption process) value reflects strong interaction. There is evidence of NP-1-4-11-PUOPMOB adsorption on the metal surface from SEM, EDAX, and AFM studies. Experimental and theoretical results are in good agreement.