Synthesis and surfactant properties of novel acrylic acid co-oligomers containing fluoroalkylated end-groups: a new approach to polymeric inhibitors of human immunodeficiency virus type-1

Abstract

Reactions of fluoroalkanoyl peroxides with acrylic acid, and with alkyl methacrylates or trimethylvinylsilane, give a series of new fluoroalkylated acrylic acid/alkyl methacrylate and /trimethylvinylsilane co-oligomers in excellent to moderate yield under very mild conditions. Fluoroalkylated acrylic acid/alkyl methacrylate co-oligomers are soluble in common organic solvents such as methanol, DMSO and tetrahydrofuran, and slightly soluble in non-polar aromatic solvents such as benzene, toluene and xylene. However, these co-oligomers do not have good solubility in both water and aromatic solvents. In contrast, fluoroakylated acrylic acid/trimethylvinylsilane co-oligomers are readily soluble in not only in water but also in common organic solvent such as methanol, ethanol, tetrahydrofuran, carbon tetrachloride, chloroform, DMF, DMSO, benzene, toluene and xylene. This feature is due to the trimethylsilyl side-chains possessing good oleophilic properties. Fluoroalkylated co-oligomers, in particular fluoroalkylated acrylic acid/trimethylvinylsilane co-oligomers, reduce the surface tension of both water and m-xylene effectively to around 15–20 mN m −1, the same as for low-molecular weight fluorinated surfactants, though the co-oligomers have high molecular weights. These fluoroalkylated silicon-containing co-oligomers exhibit a clear break point resembling a CMC, which suggest that they form intra- or inter-molecular aggregations in aqueous solutions owing to their unique structure (fluoroalkylated end-capped structure). The fluoroalkylated acrylic acid co-oligomers inhibit HIV-1 induced cytopathogenesis. Relative to dextran sulfate, superior anti-HIV-1 activity could be obtained with fluoroalkylated acrylic acid/trimethylvinylsilane co-oligomers; however, fluoroalkylated acrylic acid cooligomers containing hydroxy groups were inactive. An obvious correlation exists between anti-HIV-1 activity and the hydrophilic or lipophilic property of these co-oligomers, i.e. they provide a most adequate HLB value for anti-HIV-1 activity. More hydrophilic or more oleophilic fluoroalkylated co-oligomers were less active (or inactive), suggesting that more hydrophilic or more oleophilic fluoroalkylated co-oligomers have a weaker effect on the interaction between gp/120 (or gp41) in HIV-1 and CD4 receptors. In fluoroalkylated silicon co-oligomers, as the degree of the reduction in surface tension of water becomes higher the anti-HIV-1 activity becomes higher, suggesting that the more adsorbable co-oligomers at the water/air interface have a higher anti-HIV-1 activity. A new correlation between anti-HIV-1 activity and properties of fluoroalkylated acrylic acid co-oligomers is indicated, affording a useful new strategy for exploring potent new polymeric inhibitors of HIV-1.