A E Arbuzov Institute of Organic and Physical Chemistry of Kazan Scientific Center of the Russian Academy of Sciences, Kazan, Russia.
Chemphyschem. 2012 Feb;13(3):788-96. doi: 10.1002/cphc.201100888. Epub 2012 Jan 27.
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 r1 compared to r3 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.
新型单阳离子和双阳离子嘧啶表面活性剂被合成，并通过张力法和核磁共振（NMR）自扩散法研究其聚集行为。为了评估它们作为基因传递剂的潜力，通过动态光散射（DLS）和zeta-电位滴定法以及溴化乙锭排除实验探索了与寡核苷酸（ONus）的络合。棒状嘧啶两亲分子（BPM）对 ONus 的亲和力较弱。尽管它与 ONus 诱导混合缔合，但在大量棒状存在时仅发生轻微的电荷补偿变化，不会发生再充电。同样，溴化乙锭排除实验表明，随着 BPM 浓度的增加，与 ONu 的结合能力缓慢增加。单阳离子嘧啶表面活性剂（MPM）及其双子类似物（GPM-1）在其聚集活性和与 ONus 的络合性质方面均处于中间状态。它们都在低于临界胶束浓度（cmc）分别为 2 和 15 mM 以下的条件下与 ONus 形成混合配合物。然而，与 MPM 的 r1 相比，GPM-1 在摩尔比表面活性剂/ONu r3 下具有更低的等电点。这可能表明在 GPM-1 的情况下，静电对 ONu 络合的贡献更大。具有三个烷基尾的最疏水嘧啶表面活性剂（GPM-2）与前几种嘧啶表面活性剂相比，表现出增强的聚集活性和与 ONus 的结合能力。由于有效的聚集（低 cmc 为 0.04 mM）加上结合性质（r=2.5 时结合的 ONu 分数β=0.76），GPM-2 可能是一种很有前途的更广泛生物应用的试剂。
