Anion Transport with Halogen Bonds

Abstract

This review covers the application of halogen bonds to transport anions across lipid bilayer membranes. The introduction provides a brief description of biological and synthetic transport systems. Emphasis is on examples that explore interactions beyond the coordination with lone pairs or hydrogen bonds for the recognition of cations and anions, particularly cation-π and anion-π interactions, and on structural motifs that are relevant for transport studies with halogen bonds. Section 2 summarizes the use of macrocyclic scaffolds to achieve transport with halogen bonds, focusing on cyclic arrays of halogen-bond donors of different strengths on top of calixarene scaffolds. This section also introduces methods to study anion binding in solution and anion transport in fluorogenic vesicles. In Sect. 3, transport studies with monomeric halogen bond-donors are summarized. This includes the smallest possible organic anion transporter, trifluoroiodomethane, a gas that can be bubbled through a suspension of vesicles to turn on transport. Anion transport with a gas nicely illustrates the power of halogen bonds for anion transport. Like hydrogen bonds, they are directional and strong, but compared to hydrogen-bond donors, halogen-bond donors are more lipophilic. Section 3 also offers a concise introduction to the measurement of ion selectivity in fluorogenic vesicles and conductance experiments in planar bilayer membranes. Section 4 introduces the formal unrolling of cyclic scaffolds into linear scaffolds that can span lipid bilayers. As privileged transmembrane scaffolds, the importance of hydrophobically matching fluorescent p-oligophenyl rods is fully confirmed. The first formal synthetic ion channel that operates by cooperative multiion hopping along transmembrane halogen-bonding cascades is described. Compared to homologs for anion-π interactions, transport with halogen bonds is clearly more powerful.

Halogen bonding in the co-crystallization of potentially ditopic diiodotetrafluorobenzene: a powerful tool for constructing multicomponent supramolecular assemblies

“…In recent years, the research focus has been extended towards halogen bonds from the well-known hydrogen bonds as they have been proven to be another powerful tool in crystal engineering and supramolecular chemistry [ 23–25 ], encompassing a wide range from fundamental studies (e.g. the nature of the halogen bond [ 26 , 27 ]) to materials science (photoelectric materials [ 28–30 ], liquid crystals [ 31 , 32 ], supramolecular gels [ 33 ], anion recognition [ 34 , 35 ], etc.) to biological systems [ 36 ].…”

Halogen bonding in polymer science: from crystal engineering to functional supramolecular polymers and materials

“…18,19 It is worth noting that the role of XB in biological systems has been recently highlighted, 20,21 and investigations are actually achieving increasing prominence since the halogen bond interactions tend to be less sensitive to polar or aqueous environments. [22][23][24][25] Here, we decided to highlight the use of halogen bonding in polymer science. XB is still in its infancy and therefore only a few papers are devoted to covalently bonded macromolecular structures.…”

Halogen Bonding: An Underestimated Player in Membrane–Ligand Interactions

“…XBs are observed in solution, 52 including in aqueous media, 53,54 and can be exploited in the design of synthetic transmembrane anion transporters with potential therapeutic applications. This concept, initially reported by Matile and co-workers 55 was further developed [56][57][58] exploring also other noncovalent interactions. 59,60 As for anion transporters that are known to interact directly with lipid membranes by establishing HBs with several nucleophilic sites from the phospholipid headgroups, i.e.…”