Comparative Study of Aqueous Solutions of Cationic Surfactants: Structure/Activity Relation in Their Aggregation and Solubilization Behavior and Complexation with an Oligonucleotide

Abstract

For mono-and dicationic surfactants with trimethylammonium (TMA), triphenylphosphonium (TPP), and 4-aza-1-alkyl-1-azoniabicyclo[2.2.2]octane (DABCO) polar groups, and also for pyrimidinic amphiphiles, a correlation is revealed between their aggregation and solubilization properties and their complexation capacity toward an oligonucleotide. Mixed cationic surfactantcalixarene systems demonstrate controllable binding/ release properties.Cationic surfactants are very attractive for the design of catalytic systems, analytical separation, antimicrobial compositions, and synthetic vectors for gene delivery.1,2 In these strategies, the capacity of surfactants to adsorb on surfaces or to bind guest molecules is utilized. Nanocontainers based on surfactants are noncovalently bound dynamic structures, and they should therefore be competitive with carriers based on covalently formed polymer containers and polyelectrolyte capsules fabricated by the layer-by-layer technique. The advantages of surfactant-based nanocontainers are their easy preparation, versatile uses, controlled morphology and size, low required concentration, and biocompatibility. Therefore, to be competitive from the viewpoint of current technologies, cationic surfactants have to meet the above criteria and exhibit high micellization and solubilization capacities and low toxicity. The morphology of aggregates, their binding capacity, and hence, their functional activity depend to a great extent on the chemical structure of amphiphiles. Herein, micellar systems based on cationic surfactants are studied with variation of the nature of the charge atoms. In particular, mono-and dicationic surfactants with trimethylammonium (TMA-n), triphenylphosphonium (TPP-n), and 4-aza-1-alkyl-1-azoniabicyclo[2.2.2]octane (DABCO-n) polar groups, as well as pyrimidinic mono-and dicationic amphiphiles, are considered, with the number of carbon atoms in the alkyl chain n varied from 8 to 18. The data obtained are exemplified by the hexadecyl derivatives TMA-16, Generally, different methods are used to estimate the aggregation behavior, in particular, tensiometry, conductometry, NMR self-diffusion, dye solubilization studies, and so on. The data obtained are analyzed in terms of the concentration dependences of the measured parameters, and breakpoints in the plots are identified as critical micelle concentrations (cmc's). These values indicate the onset of micellization in the systems. In our earlier works, 36 the micellization of cationic surfactants with different headgroups was studied through a combination of methods. Surfactants with charged nitrogen (TMA and DABCO series) showed very similar cmc's of around 1 mM, while phosphonium salts demonstrated much lower cmc values.3,5 The advantages in terms of micellization capacity may result in more effective functional activity. Therefore, the purpose of this study is to compare their binding capacity toward different guests, including hydrophobic organic substrates and an oligonucleotide.As seen in Figure 1, a higher solubiliza...

Cationic Surfactants: Self-Assembly, Structure-Activity Correlation and Their Biological Applications

“…It has been shown that dimeric pyrimidinic gemini with enhanced hydrophobicity and high micellization capacity demonstrated highest condensing activity exceeding that of conventional m-s-m geminis and bola-form analogs. It was shown that complexation activity of surfactants toward oligonucleotide increases from ammonium surfactants < phosphonium surfactants < 1,4-diazabicyclo[2.2.2]octane based surfactants [132]. Gemini pyrimidine surfactant (SPYRIT 68) showed better in vitro transfection efficiency than monomer cationic lipid (SPYRIT 7), but also higher cytotoxicity.…”

Soft Nanocontainers Based on Hydroxyethylated Geminis: Role of Spacer in Self-Assembling, Solubilization, and Complexation with Oligonucleotide

“…Most of these events are controlled by the structural behavior of surfactants, in particular, their aggregation activity, morphology, surface potential, solubilization capacity, etc. The present work is a continuation of our studies focusing on the complexation of cationic surfactants with oligonucleotide and DNA. − ,,,− The promising results were obtained for DNA transfection by gemini bearing hydroxyethylated head groups 16-s-16­(OH) (Figure ), with the spacer length playing key role. , These gemini demonstrated advanced properties as compared to their 16-s-16 unsubstituted counterparts and single-head analogs. Meanwhile, the latter are well-studied and their functional activity documented, whereas few works are available on the structural behavior of hydroxyalkylated gemini, , with extremely scarce information reported on their functional activity.…”

“…Simplicity of protocols and possibility for their large-scale production provide principle benefits for nonviral vectors over natural agents. In this field numerous studies, including our work, focus on cationic surfactants exhibiting high affinity toward negatively charged phosphate backbone of DNA. − Transfection efficacy has been summarized to increase markedly with the transition from conventional single head surfactants to gemini analogs; therefore, much attention has recently been paid to DNA complexation with dimeric cationic surfactants . Two main aspects were highlighted in the literature, i.e., (i) structural behavior of lipoplexes, including their charge, size, and morphology characteristics, the mechanism of interactions, etc.…”

“…Those publications focused primarily on classical m - s - m surfactants. Meanwhile, modification of the chemical structure of both single head and dimeric surfactants (head groups and a spacer) is one of the ways to tailor their functionality, including binding capacity toward nucleotide moiety. − …”

“…The influence of headgroup structure on the complexation with DNA received much attention in literature including our work. − Along with ammonium gemini, their single head and dimeric analogs with imidazolium (Im), phosphonium (Ph), morpholinium (Mph), and diazabicyclooctane (DABCO) head groups were studied. The neutralization effect correlating with the contribution of electrostatic interactions of components enhances as follows for hexadecyl derivatives: Mph-16 ≈ DABCO-16 > Ph-16 ≈ CTAB > Im-16, with the latter demonstrating no recharging activity toward ONu. − , Nontypical complexation was demonstrated for monocationic imidazolium surfactant and DNA decamer . While strong binding of the components was revealed by the ethidium bromide exclusion assay, regardless of the alkyl tail length, no charge compensation occurred in the zeta potential measurement study, even at a high excess of surfactants.…”