Studies towards small-molecule-receptors selective for phospholipid anionic head groups in bacterial membranes

Abstract

Receptors specific for inorganic anions have been described for several decades. Several of these anions, i.e. chloride, phosphate, and acetate are essential in biology. A novel neutral anion receptor specific for the phosphate containing head group of bacterial membrane fatty acids was conceptualized as part of a possible broad spectrum antibiotic. The receptor and several related derivatives were synthesized over fourteen steps. The most important step which involved placing ureidomethylene groups to a bis‐phenolic scaffold was developed as a novel method. The method was probed for scope and utility with a variety of aromatic nucleophiles. The aforementioned anion receptors were tested for binding capabilities against several inorganic anions, and against a synthetic tetrabutylammonium salt of a phospholipid. Several of the derivatives were also tested for antibiotic activity against several species of gram negative bacteria. Finally, the receptors were used to bind chloride anion in solvents containing a variable amount of water to determine if the presence of water would result in stronger anion binding.