Anion Binding and Transport with Aromatic Pentaamide Macrocycles

Adf macrocycle

Hosts with an affinity towards specifically charged guest species are crucial for combating a variety of diseases. Synthetic supramolecular structures are designed to bind to either cations or anions. The pore of a macrocycle may be crafted to attain either a negative charge to interact with cations or a positive charge to bind and transport anions, by utilizing the influence of the functional groups. Building hosts into biomembranes with anion binding specificity by forcing the pore to be positively charged is important to combating malfunctioning chloride transport and treat cystic fibrosis. In a recent study, a host pentaamide macrocycle was functionalized specifically to force amide groups to orient themselves into the pore through forced N-H—O hydrogen bonding. Such an adaptation put a sizable positive charge into the cavity of the pentaamide and flipped the carbonyl to be outside of the macrocycle. With NH and CH positive charges in the pore, these pentaamide macrocycles have a specially designed affinity for anions.

Hirshfeld charges and electrostatic potentials on the pentaamide macrocycle along with the dipole moment of the monomeric building block, all computed with ADF, support the strong positive charge of the cavity. Geometry optimizations showed that a plethora of anionic guests are attracted to the positively charged cavity of the pentaamide macrocycle. Computed association constants and binding energies revealed that desolvation of the host cavity was preferred to allow for each anionic guest to accommodate the pore. Particular focus was placed on the optimized structures of chloride, bromide, and iodide guests within the host. Calculations showed that iodide binds the strongest to the pentaamide cavity, followed by chloride, and bromide binding the weakest. This goes against general trends that N-H—Cl interactions are stronger than N-H—Br interactions, with N-H—I interactions being the weakest. The structural optimizations revealed that iodide binds the strongest to the pentaamide macrocycle due to its larger size providing the capability to interact with all the N-H groups in the pore. Due to the smaller sizes of chloride and bromide, these two anions can only muster two N-H group coordinations. Given chloride’s stronger binding than bromide but not filling up the pore overly so like iodide, chloride was found to transport the best relative to the other halides. Therefore, the pentaamide macrocycles are ideal for combating cystic fibrosis and replenishing normal transportation of chloride, as supported by ADF computations.

ADF macrocycle
Go to overview

Stay up to date!

Subscribe to our newsletter (5 times a year) to stay up to date about news, job openings, functionality and events such as webinars and workshops!

No sales. No spam. Occasional notifications. Unsubscribe anytime.