Synthesis, Physicochemical Characterization, and Interaction with DNA of Long‐Alkyl‐Chain Gemini Pyridinium Surfactants

Abstract

Pyridinium gemini surfactants with hexadecyl chains linked to nitrogen atoms and a tuned aliphatic spacer that bridges the two pyridinium polar heads in 2,2′‐positions have been synthesized and characterized. A multitechnique approach allowed us to study the aggregation behavior, using conductivity, surface tension, and fluorescence. Graphs of the specific conductivity (κ) versus the surfactant molar concentration (C), and graphs of the molar conductivity (Λ) versus C0.5 suggest pre‐aggregation phenomena of these amphiphiles at very low concentration. The trends of Amin as a function of the spacer length confirm the hypothesis of a conformational change of the molecule with four methylene groups as spacer owing to stacking interactions between the two pyridinium rings mediated by the counterion. Moreover, the trends of Amin and counterion binding (β) suggest that the spacer must be longer than eight carbon atoms to fold efficiently toward the micellar core. The opportunity to tune the surfactant structure and aggregation properties make those surfactants—particularly the long‐chain ones for which the DNA complexing ability was shown by means of atomic force microscopy (AFM) imaging—desirable candidates for gene‐delivery experiments.

Gene-Delivery Ability of New Hydrogenated and Partially Fluorinated Gemini bispyridinium Surfactants with Six Methylene Spacers

“…The two new compounds here reported have attached to the cationic heads two different chains: one is an alkyl C16 hexadecane and the other a fluorinated 3,3,4,4,5,5,6,6,7,7,8,8-tridecafluorooctane. We prepared the 1,6-bis(2-pyridyl)hexane and the two new surfactants following and adapting, when necessary, the procedures previously reported [15,19,20]. The synthetic scheme is reported in supporting information (SI).…”

“…Two novel gemini pyridinium surfactants having the 6 methylene group as a spacer between the cationic heads were synthesized following and adapting, if necessary, the procedures previously reported [15,19,20]. The NMR spectra were recorded using a Bruker 300 Avance (Billerica, MA, USA) spectrometer and a Bruker 400 Avance (Billerica, MA, USA) spectrometer.…”

“…13 C NMR (100 MHz); chemical shifts (δ scale) are reported in parts per million (ppm). 19 F-NMR (376.5 MHz); chemical shifts (δ scale) are reported in parts per million (ppm). IR spectra were recorded using a Agilent Technologies Cary 630 FTIR Spectrometer (Santa Clara, CA, USA) in the region 700-4000 without KBr support.…”

“…For many years, in fact, we have been studying from synthetic, thermodynamic, and biomedical point of view, new cationic lipids with the aim to determine structureactivity relationships useful for the optimization of their gene delivery ability [14][15][16][17][18][19][20][21]. Particularly, we devoted our attention to the gemini cationic surfactants-i.e., surfactants consisting of two or more identical hydrophobic chains and two or more polar positive head groups covalently bound together by a spacer.…”

Reducible Amino Acid Based Cationic Lipids as Highly Efficient and Serum‐Tolerant Gene Vectors

“…Although viral vectors are significantly more efficient mediators of gene delivery, their immunogenicity and toxicity have impeded their clinic use . Nonviral vectors, such as cationic lipids constitute a safe alternative, and are advantageous due to their simplicity of preparation, excellent ability to bind nucleic acids, potential commercial value and wide range of clinical applications . Cationic lipids are amphiphilic organic molecules and are typically characterized structurally by three components: a cationic headgroup, a hydrophobic tail and a linking group between these domains .…”