Maria Rosa Infante

SYNTHESIS OF SOME CATIONIC GEMINI SURFACTANTS AND THEIR INHIBITIVE EFFECT ON IRON CORROSION IN HYDROCHLORIC ACID MEDIUM

Some gemini surfactants in the series of 1,2-ethane bis(dimethyl alkyl (CnH2n+1) ammonium bromide) referred as n-2-n have been synthesised, where n=10, 12 and 14. The purity of surfactants synthesised was checked by rutinary methodologies (1H-NMR, MS and elemental analysis). Their surface active properties at equilibrium in water at 25°C were determined. The inhibitive effect of these compounds, in the case of iron immersed in 1 M HCl, was investigated through mass-loss, potentiokinetic methods and electrochemical impedance spectroscopy. Polarisation data indicate that these compounds act as very good cathodic inhibitors of iron in 1 M HCl. In the anodic range, the surfactants studied do not show an inhibition effect at iron electrode potential more positive than −100 mV/Saturated Calomel Electrode. Impedance plots of iron in the presence of various concentrations of surfactants studied are similar to semicircles in the capacitive quadrant. The associated values of transfer resistances increase by increasing the additive concentrations. From all measurements performed, the variation of the inhibition efficiency versus concentration shows the same trend. The gemini surfactants appear to be adsorbed in the metal/liquid interface through the general adsorption mode following the Frumkin adsorption isotherm model. The electrochemical impedance spectroscopy shows that the maximum inhibition efficiency is attributed to a formation of an adsorbed layer at the iron surface. From tensiometric measurements, it was found that the ability of gemini surfactants studied to adsorb at the interface air/water is concordant with their order of the inhibition efficiency of iron corrosion.

Corrosion inhibition of iron in 1 M HCl by some gemini surfactants in the series of alkanediyl-α, ω-bis-(dimethyl tetradecyl ammonium bromide)

Three new gemini surfactants in the series of alkanediyl-,-bis-(dimethylalkyl ammonium bromide) were synthesised and tested as corrosion inhibitors of iron in hydrochloric acid medium using gravimetric, electrochemical polarisation and electrochemical impedance spectroscopy (EIS) measurements. Results obtained show that the surfactants studied are good cathodic inhibitors and act on the cathodic hydrogen reaction without modifying its mechanism. EIS results show that the changes in the impedance parameters (RT and Cdl) with concentration of surfactants studied is indicative of the adsorption of molecules of surfactant leading to the formation of a protective layer on the surface of iron. The effect of the temperature on the iron corrosion in both 1 M HCl and 1 M HCl with addition of various concentrations of 1,2-ethane bis-(dimethyl tetradecyl ammonium bromide) in the range of temperature 20–60 ◦ C was studied. The associated apparent activation corrosion energy has been determined.

In vitro antitumor activity of methotrexate via pH-sensitive chitosan nanoparticles

Nanoparticles with pH-sensitive behavior may enhance the success of chemotherapy in many cancers by efficient intracellular drug delivery. Here, we investigated the effect of a bioactive surfactant with pH-sensitive properties on the antitumor activity and intracellular behavior of methotrexate-loaded chitosan nanoparticles (MTX-CS-NPs). NPs were prepared using a modified ionotropic complexation process, in which was included the surfactant derived from N(α),N(ε)-dioctanoyl lysine with an inorganic lithium counterion. The pH-sensitive behavior of NPs allowed accelerated release of MTX in an acidic medium, as well as membrane-lytic pH-dependent activity, which facilitated the cytosolic delivery of endocytosed materials. Moreover, our results clearly proved that MTX-CS-NPs were more active against the tumor HeLa and MCF-7 cell lines than the free drug. The feasibilty of using NPs to target acidic tumor extracellular pH was also shown, as cytotoxicity against cancer cells was greater in a mildly acidic environment. Finally, the combined physicochemical and pH-sensitive properties of NPs generally allowed the entrapped drug to induce greater cell cycle arrest and apoptotic effects. Therefore, our overall results suggest that pH-sensitive MTX-CS-NPs could be potentially useful as a carrier system for tumor and intracellular drug delivery in cancer therapy.

Amino Acid-based Surfactants: Enzymatic Synthesis, Properties and Potential Applications

Amino acid-based surfactants constitute a class of bio-based surfactants with excellent adsorption and aggregation properties, low potential toxicity and broad biological activity. In this review, the enzymatic synthesis, physicochemical and biological properties as well as the potential uses of these compounds are described.

Gemini surfactants from natural amino acids

In this review, we report the most important contributions in the structure, synthesis, physicochemical (surface adsorption, aggregation and phase behaviour) and biological properties (toxicity, antimicrobial activity and biodegradation) of Gemini natural amino acid-based surfactants, and some potential applications, with an emphasis on the use of these surfactants as non-viral delivery system agents. Gemini surfactants derived from basic (Arg, Lys), neutral (Ser, Ala, Sar), acid (Asp) and sulphur containing amino acids (Cys) as polar head groups, and Geminis with amino acids/peptides in the spacer chain are reviewed.

Chemo‐enzymatic synthesis of arginine‐based gemini surfactants

A novel chemo-enzymatic synthesis of arginine-based gemini cationic surfactants bis(Args) is reported. These compounds consist of two single N(alpha)-acyl-arginine structures connected through the alfa-carboxylic groups of the arginine residues by a alpha, omega-diaminoalkane spacer chain. N(alpha)-Acyl-L-arginine alkyl ester derivatives were the starting building blocks for the synthesis. The best strategy found consisted of two steps. First, the quantitative acylation of one amino group of the spacer by the carboxylic ester of the N(alpha)-acyl-arginine took place spontaneously, at the melting point of the alpha,omega-diaminoalkane, in a solvent-free system. The second step was the papain-catalyzed reaction between another N(alpha)-acyl-arginine alkyl ester and the free aliphatic amino group of the derivative formed in the first step. Reactions were carried out in solid-to-solid and solution systems using low-toxic potential solvents. Changes in reaction performance and product yield were studied for the following variables: organic solvent, support for enzyme deposition and substrate concentration. The best yields (70%) were achieved in solid-to-solid systems and in ethanol at a(w) = 0.07. Bis(Args) analogs of 8, 10 and 12 carbon atoms using 1,3-diaminopropane and 1, 3-diamino-2-hydroxy-propane as hydrocarbon spacers were prepared at the 6-7 gram level employing the methodology developed. The overall yields which include reaction and purification varied from 51% to 65% of pure (97-98% by HPLC) product.

Erythrocyte hemolysis and shape changes induced by new lysine-derivate surfactants.

The effects of new synthetic lysine-derived anionic surfactants on human and rat erythrocytes were studied. The surfactants were salts of Nalpha,Nepsilon-dioctanoyl lysine with different counterions: lysine (77KK), tris (trishydroxymethyl amminomethane) (77KT), sodium (77KS), and lithium (77KL). 77KK and 77KT showed a biphasic hemolytic behavior in the erythrocytes. The surfactants 77KS and 77KL showed concentration-dependent hemolysis with a CH50 of about 3.4 and 2.6 mmol/l, respectively. 77KK and 77KT induced protection against hypotonic hemolysis in rat erythrocytes at the concentration which showed the least hemolytic activity under isotonic conditions. With human erythrocytes, 77KT did not show biphasic behavior in isotonic medium, but under hypotonic conditions biphasic behavior was present. Changes in shape of the erythrocyte, from discocytic to stomatocytic were observed after incubation with the anionic surfactants studied. Such shape changes occurred progressively over time, with total alteration in shape occuring after about 20 min of incubation.

Relation of foam stability to solution and surface properties of gemini cationic surfactants derived from arginine

Abstract The dynamic surface tensions, under constant area and pulsating area are reported for one cationic monomeric surfactant LAM (Nα-lauroyl arginine methyl ester) and three related bicationic gemini surfactants Cn(LA)2, or bis (Args), with a spacer chain of n=3, 6, or 9 methylene groups. The tension equilibrates faster the higher the concentration, even beyond the cmc, indicating a substantial micellar contribution to tension dynamics. Both LAM and the gemini surfactants form more stable foams at 25°C as the concentration increases up to about half the cmc of LAM or half the second cmc of the geminis. The geminis are about twenty times more efficient foam stabilizers than LAM. The foam stability correlates strongly with tension equilibration time. The logarithm of the time t50f, for the initial foam height to drop by 50%, is a linear function of t50γ, which is the time for the tension to drop 50% of its equilibrium change. At comparable concentrations, the gemini surfactant with the shorter spacer chain (n=3 or 6) equilibrate faster and form more stable foams than the one with n=9.

Physicochemical and toxicological properties of novel amino acid-based amphiphiles and their spontaneously formed catanionic vesicles

The design of efficient liposomal systems for drug delivery is of considerable biomedical interest. In this context, vesicles prepared from cationic/anionic surfactants may offer several advantages, mainly due to their spontaneity in formation and long-term stability. There is also an impending need to produce less toxic, more biocompatible amphiphiles, while maintaining the desirable aggregation properties. In this work, we present data for acute toxicity to Daphnia magna (IC(50)), and potential ocular irritation (HC(50)) for some newly prepared ionic surfactants with dodecyl chains, derived from the amino acids tyrosine (Tyr), serine (Ser), hydroxyproline (Hyp) and lysine (Lys). The micellization behavior of the compounds, evaluated from surface tension measurements, is presented and compared to more conventional ionic amphiphiles. Two types of spontaneouly formed catanionic vesicles, composed either by a dodecyltrimethylammonium bromide (DTAB)/Lys-derivative and or Ser-/Lys-derivative mixture, have also been tested for their ecotoxicity and hemolytic potential. All the micelle-forming surfactants as well as the vesicle-containing mixtures are found to have lower ecotoxicity than the reference surfactant DTAB. Moreover, the results from hemolysis and hemoglobin denaturation tests show that the Tyr- and Lys-derivatives are moderately irritant, whereas the Hyp- and Ser- ones are just slightly irritant. Even more significantly, the vesicle-containing mixtures exhibit lower hemolytic activity than the neat surfactants, a positive result for their potential use in liposomal formulations.

Enzymatic synthesis of arginine-based cationic surfactants.

A novel enzymatic approach for the synthesis of arginine N-alkyl amide and ester derivatives is reported. Papain deposited onto solid support materials was used as catalyst for the amide and ester bond formation between Z-Arg-OMe and various long-chain alkyl amines and alcohols (H2N-Cn2, HO-Cn; n = 8-16) in organic media. Changes in enzymatic activity and product yield were studied for the following variables: organic solvent, aqueous buffer content, support for the enzyme deposition, presence of additives, enzyme loading, substrate concentration, and reaction temperature. The best yields (81-89%) of arginine N-alkyl amide derivatives were obtained at 25 degrees C in acetonitrile with an aqueous buffer content ranging from 0 to 1% (v/v) depending on the substrate concentration. The synthesis of arginine alkyl ester derivatives was carried out in solvent-free systems at 50 or 65 degrees C depending on the fatty alcohol chain length. In this case, product yields ranging from 86 to 89% were obtained with a molar ratio Z-Arg-OMe/fatty alcohol of 0.01. Papain deposited onto polyamide gave, in all cases, both the highest enzymatic activities and yields. Under the best reaction conditions the syntheses were scaled up to the production of 2 g of final product. The overall yields, which include reaction, Nalpha-benzyloxycarbonyl group (Z) deprotection and purification, varied from 53 to 77% of pure (99.9% by HPLC) product.