Supramolecular Systems Based on Novel Mono‐ and Dicationic Pyrimidinic Amphiphiles and Oligonucleotides: A Self‐Organization and Complexation Study

Novel mono‐ and dicationic pyrimidinic surfactants are synthesized and their aggregation behavior is studied by methods of tensiometry and nuclear magnetic resonance (NMR) self‐diffusion. To estimate their potentiality as gene delivery agents, the complexation with oligonucleotides (ONus) is explored by dynamic light scattering (DLS) and zeta‐potential titration methods and ethidium bromide exclusion experiments. Bola‐type pyrimidinic amphiphile (BPM) demonstrates rather a weak affinity to ONus. Although it induces mixed associations with ONus, only slight charge compensation changes occur at a large excess of bola, with no recharging reached. Similarly, the ethydium bromide exclusion study reveals a slow increase in the binding capacity toward an ONu with an increment in BPM concentration. The monocationic pyrimidinic surfactant (MPM) and its gemini analogue (GPM‐1) are ranked as intermediates in both their aggregative activity and complexing properties toward ONus. They both form mixed associates with ONus well below the critical micelle concentrations (cmcs) of 2 and 15 mM respectively. However, GPM‐1 has a much lower isoelectric point at the molar ratio surfactant/ONu r～1 compared to r～3 for MPM. This probably indicates a larger electrostatic contribution to the ONu complexation in the case of GPM‐1. The most hydrophobic pyrimidinic surfactant (GPM‐2), bearing three alkyl tails, demonstrates enhanced aggregative activity and binding capacity toward ONus as compared to former pyrimidinic surfactants. Due to effective aggregative (low cmc of 0.04 mM ) plus binding properties (fraction of bound ONu β=0.76 at r=2.5), GPM‐2 may be ranked as a promising agent for wider biological applications.