Novel Gemini Pyridinium Surfactants: Synthesis and Study of Their Surface Activity, DNA Binding, and Cytotoxicity

Abstract

New pyridinium gemini amphiphiles having ethane-1,2-dithiol spacer have been synthesized by regioselective electrophilic cobromination of alpha-olefins. Ethane-1,2-dithiol (1) and N-bromosuccinimide (6) on reaction with alpha-olefins (dodecene (2), tetradecene (3), hexadecene (4), and octadecene (5)) gave the respective 1,2-bis(2-bromoalkylthio)ethane (7-10). The bromoalkylthio ethers when reacted with pyridine (11) gave the respective gemini bispyridinium bromide (12-15). The surface properties of new geminis were evaluated by surface tension and conductivity measurements. These gemini surfactants have also been found to be having low cytotoxicity by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay on C6 glioma cells. The DNA binding capabilities of these amphiphiles have been determined below as well as above critical micelle concentration. The preliminary studies by agarose gel electrophoresis indicated chain length dependent DNA binding abilities which has further been proved by ethidium bromide exclusion experiments and transmission electron microscopy (TEM).

Properties of binary surfactant systems of nonionic surfactants C12E10, C12E23, and C12E42 with a cationic gemini surfactant in aqueous solutions

“…They have been widely used in the fields of soil remediation, enhanced oil recovery, drug entrapment and release, gene therapy, etc. and are usually used in combination with nonionic surfactants [15][16][17][18][19][20].…”

pH-Sensitive Surfactants from Lysine: Assessment of Their Cytotoxicity and Environmental Behavior

“…49 Notice that except the MKM TM , all the other lysine derivatives studied in this work have alkyl chains of 12 carbons atoms. In the case of single chain surfactants it is expected that the toxicity increases with longer alkyl chains.…”

Recent progress in gene therapy to deliver nucleic acids with multivalent cationic vectors

“…The cationic groups commonly used are ammonium [53,54], imidazolium [55][56][57], pyridinium [58,59], lysine or arginine [60][61][62], and/or amine/polyamines [63][64][65][66][67].…”

“…TEM and/or cryo-TEM studies have reported many micrographs to characterize the size, shape, and morphology of a wide variety of lipoplexes as: (a) pDNA with GCLs [45,54,57,62,64,75,93,115,117,118,120], MVCLs [63], cationic polymers [107,133,[169][170][171] or polycations [40,84,100,136]; and (b) siRNA with cationic polymers [90,104]. Fig.…”

“…The results confirm that all these optimized formulations did not report any toxicity to the cell lines studied, the cell viability after transfection being considerably better than the commercial control Lipo2000. The cell viability/cytotoxicity of several complexes between nucleic acids and a wide variety of recent synthesized MVCVs has been analyzed: (i) GCLs as cholesterol-based with alkyl or oligo-oxyethylene spacers [118,119,121,206,207], aromatic-based with alkyl or oligo-oxyethylene spacers [46], ammonium derivatives [54,71,93] imidazolium derivatives [45,75,99] and pyridinium derivatives [57] with alkyl type spacers, aminoacid-based [64,208], SS14 linkers [66], gemini-like amphiphilic peptides [150] or cyclen-based CLs [120,180]; (ii) several MVCLs [67,72,122,181,182]; (iii) cationic polymer-derivatives from PEI [124,127,183,209], PAMAM [140], PDMAEMA [123,133], chitosan [188], polyphosphoramidates [189], polyhydroxyalkanoates [92], polyamines [107,187] or polyaminoacids [127,190]; (iv)…”