The synthesis of macrocycles can be challenging for many chemists. There is not a set system in place for synthesis, many are unique to the desired molecule in question. Some require two or fewer steps to form more complicated structures. Some utilize metals for ring closing metastases and can function as ligands for various metals. The Rahman et al.’s review provides several different examples of macrocycle synthesis for several different families of macrocycles. Largely the synthesis will depend on the starting material and the desired product.
Anion transport is vital for all living organisms as it regulates ion build up in human cells. There are many different synthetic molecules chemists synthesize and utilize in order to bind, identify, and transport anions, one being macrocycles. There are two major designs for macrocycles for anion binding: cyclic amides and cyclic ureas and thioureas. Both designs rely on dipole-dipole interactions and hydrogen bonding to affectively bind various anions in differing solvents. This review provides several examples of macrocycles that have been synthesized for anion binding. A specific example is Evgeny Kataev et al.’s work with three new synthesized macrocycles, pictured in Figure 2. Their macrocycles include several amine and amide functional groups with favorable pH to act as hydrogen bond donors without deprotonating the macrocycle. They tested the binding with fluoride anion and saw a turn on response for Receptor 1, Figure 2, and found up to three fluoride anions can bind.
Historically, there were two sources of macrocycles for drug delivery, natural products and peptides, however, more synthetic macrocycles have been developed and studied in recent years.
Macrocycles are preferred for drug delivery for the following reasons:
1) Their strict conformations limit the products produced and the ability to react so there are reduced side effects.