Fluorinated tetrapodal anion transporters

Abstract

Summary: Synthetic anion transporters show potential in treating life-threatening diseases like cystic fibrosis and cancer. However, with increasingly complex transporter architectures designed to control anion binding and transport, it is important to consider solubility and deliverability during transporter design. The fluorination of synthetic anion transporters has been shown to tune the transporter lipophilicity, transport rates, and binding strength. In this work, we expand on our previously reported tetrapodal (thio)urea transporters with a series of fluorinated tetrapodal anion transporters. The effects of fluorination on tuning the lipophilicity, solubility, deliverability, and anion transport selectivity of the tetrapodal scaffold were investigated using anion-binding and transport assays. The primary mode of anion transport was H+/X− cotransport, with the most fluorinated tetrathiourea (8) displaying the highest transport activity in the 8-hydroxypyrene-1,3,6-trisulfonic acid (HPTS) assay. Intriguingly, inversion of the transmembrane Cl− vs NO3− transport selectivity compared with previously reported tripodal (thio)urea transporters was observed under a modified HPTS assay.

Keywords

• Chemistry
• Organic chemistry
• Organic synthesis