Synthesis and Study of Membrane Active Compounds

This dissertation describes the design, synthesis, and activity of molecules that interact specifically with vesicle or cellular membranes. The first section describes a series of second generation Zn2+ bis DPA coordination complexes that selectively target negatively charged membrane surfaces including those found in apoptotic cells and bacteria. Several types of conjugates were constructed including fluorescent versions suitable for microscopy, multivalent receptors designed for increased membrane affinity, and lipophilic derivatives. The synthesis and membrane activity of each is discussed. The second portion of this dissertation describes general strategies for the synthesis of sn-2 functionalized phospholipids from DPPC. Phospholipases were utilized for selective headgroup and side chain modification of commercially available phospholipids circumventing a de novo synthetic approach. Several classes of functionalized phosphatidylcholine derivatives were constructed including bolaamphiphiles which in some cases were found to destabilize membranes and chloride anion transporters that function by a novel relay mechanism. Other phospholipid derivatives include phosphatidylserine and phosphatidylethanolamine conjugates that were designed for receptor-mediated delivery of cargo into cells.