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 1a-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 1a and 1g, bearing hydroxy groups at their lower rim, displayed lower toxicity towards PC12 cells than their alkylated counterparts; concentrations of up to 1 mgmL ^-1 did not affect the number of viable cells. Mixed retinal cultures showed a higher susceptibility towards toxic effects for all calixarenes tested. Compound 1b self-assembles into nanofibres from a toluene solution, and 1c 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.