Cationic Surfactants Derived from Lysine: Effects of Their Structure and Charge Type on Antimicrobial and Hemolytic Activities

Abstract

Three different sets of cationic surfactants from lysine have been synthesized. The first group consists of three monocatenary surfactants with one lysine as the cationic polar head with one cationic charge. The second consists of three monocatenary surfactants with two amino acids as cationic polar head with two positive charges. Finally, four gemini surfactants were synthesized in which the spacer chain and the number and type of cationic charges have been regulated. The micellization process, antimicrobial activity, and hemolytic activity were evaluated. The critical micelle concentration was dependent only on the hydrophobic character of the molecules. Nevertheless, the antimicrobial and hemolytic activities were related to the structure of the compounds as well as the type of cationic charges. The most active surfactants against the bacteria were those with a cationic charge on the trimethylated amino group, whereas all of these surfactants showed low hemolytic character.

Membrane-destabilizing activity of pH-responsive cationic lysine-based surfactants: role of charge position and alkyl chain length

“…The commercial cationic surfactant hexadecyl trimethyl ammonium bromide ( HTAB) was used as the reference compound. These lysine-based surfactants were synthesized in our laboratory as previously described (Colomer et al 2011a;Pérez et al 2009) and made from natural fatty acid and amino acid organic building blocks. The chemical structure of these compounds was checked by nuclear magnetic resonance and their purity, higher than 99%, was confirmed by elemental analysis and high-performance liquid chromatography.…”

“…Here, the enhanced hemolysis with increasing surfactant concentration could also be due to increased ionic interactions between the negatively charged lipid membranes and positively charged amino groups of the surfactant molecule (Seo and Kim 2010). Furthermore, surfactant properties such as alkyl chain length, position of the cationic charge and head group hydrophobicity can significantly affect surfactant interaction with cell membranes (Colomer et al 2011a). Our results here showed that the compounds with the positive charge in the α-amino group (MKM and PKM) had lower disruptive potency at physiological pH and higher membrane lytic activity in the late endosomal pH range.…”

“…In contrast, PKM disrupted membranes at micellar concentrations in physiological conditions and in its monomer form in the pH range of endosomal compartments. The CMC was determined by conductivity measurements at 25 ºC of each surfactant aqueous solution at the adequate concentration range, following the procedure described by Colomer et al (2011a). The CMC values of MKM and PKM were previously reported by our research group (Colomer et al 2011b).…”

“…Furthermore, surfactants with pHresponsive membrane-disruptive activity may further destabilize endosomal compartments (Nogueira et al 2011;Wang et al 2007). The physicochemical and biological properties of cationic amino acid-based surfactants, as well as their synthesis, have been widely reported by our group (Colomer et al 2011a;Lozano et al 2011;Infante et al 2010;Pérez et al 2002Pérez et al , 2009). Therefore, we selected biocompatible cationic surfactants from the amino acid lysine (hydrochloride salts of N ε -and N α -acyl lysine methyl ester) since they display lower toxicity potential and are classified as biodegradable (Pérez et al 2009), and thus suitable for practical applications.…”

Synthesis and antimicrobial properties of binaphthyl derived quaternary ammonium bromides

“…Since it was found that cationic lipids, known as cytofectins, are efficient for delivering functional genes (Brigham et al, 1989), the use of cationic amphiphiles for mediating DNA transfection has increased. Development of resistance in microorganisms towards disinfectants or antibiotics (Heinzel, 1988) brings a necessity to supply presently applied antimicrobial agents by new ones, and thus search for new and effective molecules goes on (Semenov et al, 2011, LaDow et al, 2011, Cole et al, 2011, Colomer et al, 2011, Chanawanno et al, 2010. The strong bactericidal activity of QUATs with long alkyl chains have been known from 1915 (Jacobs & Heidelberger, 1915a, 1915b and studied further on a broad range of microorganisms such as bacteria (both G+ and G-) (Merianos, 1991), fungi (Lukáč et al, 2010, Struga et al, 2008, Pernak & Chwala 2003 and certain viruses (Wong et al, 2002).…”