Gemini Pyridinium Surfactants:  Synthesis and Conductometric Study of a Novel Class of Amphiphiles¹

Abstract

A new series of pyridinium cationic gemini surfactants was prepared by quaternization of the 2,2'-(alpha,omega-alkanediyl)bispyridines with N-alkylating agents, whose reactivity is briefly discussed. Particularly useful was the use of long-chain alkyl triflates (trifluoromethanesulfonates) for both overcoming the sterical hindrance in the pyridines and obtaining higher synthetic yields. Well-known 4,4'-(alpha,omega-alkanediyl)bis(1-alkylpyridinium) structures showed narrow temperature ranges for practical applications, due to their high Krafft points, while the new 2,2'-(alpha,omega-alkanediyl)bis(1-alkylpyridinium) series, accounted for good surface active properties. Due to the Krafft points below 0 degrees C, they could be exploited as solutions in water at any temperature. The characterization of the behavior of the series was performed by conductivity measurements. Some of the proposed structures exhibited unusual surface active behavior, which was interpreted in terms of particular conformational arrangements.

Is the counterion responsible for the unusual thermodynamic behaviour of the aqueous solutions of gemini bispyridinium surfactants?

“…In fact, they have been proposed as noncovalent functionalization agents for carbon nanotubes-based formulations for drug delivery [5] and as non viral vectors in gene therapy [6][7][8][9], owing their multiple positive charges, suitable for binding and compacting DNA, and their superior surface activity. We are for some time collecting chemico physical, particularly thermodynamic, and biological data about homologous series of cationic gemini surfactants with the idea of correlating in a quantitative way their structure with their biological activity, particularly gene delivery ability [9][10][11][12][13][14]. In this perspective, synthetic vectors present the advantage that their constituent parts can be quite easily modified, thereby facilitating the elucidation of structure-activity relationships.…”

“…In this perspective, synthetic vectors present the advantage that their constituent parts can be quite easily modified, thereby facilitating the elucidation of structure-activity relationships. Following this idea we designed and synthesized new gemini compounds having, as polar head, two pyridinium groups, bridged together by an aliphatic chain [10], in the assumption that the aromatic rings bearing the positive charges could facilitate the interaction with the DNA. We have already measured as a function of concentration the apparent and partial molar enthalpies of these compounds having the methansulfonate as counterion and we were amazed by their very peculiar behaviour as a function of the spacer length, never found before in the literature, not allowing for the determination of a -CH 2 -group contribution when this group is added to the spacer [13].…”

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

“…The structure of novel surfactants 1-4 (called 16Py-n-Py16-X, in which X = CF 3 SO 3 ,C l) is described in Scheme 1a long with the previously reported surfactants 5-8 (called 12Py-n-Py12-X, in which X = CF 3 SO 3 ,C l) [10] and the structurally related monomers 9b and 10 b. [49,50] Their synthesis (Scheme 2) was performed by the use of hexadecyltrifluoromethanesulfonate as the quaternizing agent of suitable a,w-bis(2-pyridyl)alkane, prepared as previously described.…”

“…[2][3][4][5][6][7][8][9][10] Owing to these properties, the interesti ng emini surfactants, particularly cationic ones, has increased recently in the field of pharmaceuticals, both as noncovalent components in carbon-nanotubebased formulations [11] and as nonviral vectors in gene therapy. [12][13][14][15][16][17][18][19][20] Gene therapy (GT) is finding more and more clinical applications for monogenic disorders, cancer, and infectious diseases.…”

“…[17] We then synthesized cationic gemini surfactants that contained two pyridinium groups with dodecyl [10] and fluoroalkyl chains. [48] Thep yridinium group should account for better interaction with the DNA phosphate group owing to higherc harge dispersion with respect to ammonium head groups;c hloride counterion is normally used since it is nontoxic.…”