Synthesis and Toxicology of p-Phosphonic Acid Calixarenes and O-Alkylated Analogues as Potential Calixarene-Based Phospholipids

A series of p-phosphonic acid calix[n]arenes 1 a–g bearing hydroxy groups, n=4 and 5, or alkyl chains of varying lengths at their lower rim, n=4, were synthesised, and in vitro assessments of their effect on cell viability in rat PC12 cells and primary cultures of mixed retinal cells were conducted. Compounds 1 a and 1 g, bearing hydroxy groups at their lower rim, displayed lower toxicity towards PC12 cells than their alkylated counterparts; concentrations of up to 1 mg mL−1 did not affect the number of viable cells. Mixed retinal cultures showed a higher susceptibility towards toxic effects for all calixarenes tested. Compound 1 b self-assembles into nanofibres from a toluene solution, and 1 c assembles into micelles from an aqueous solution, with these nanoscale architectures showing potential applications for various biological roles, such as solubilising p-nitrophenol and curcumin.