Directing Traffic: Halogen‐Bond‐Mediated Membrane Transport

Abstract

The plasma membrane regulates the transport of molecules into the cell. Small hydrophobic molecules can diffuse directly across the lipid bilayer. However, larger molecules require specific transporters for their entry into the cell. Regulating the cellular entry of small molecules and proteins is a challenging task. The introduction of halogen, particularly iodine, to small molecules and proteins is emerging to be a promising strategy to improve the cellular uptake. Recent studies reveal that a simple substitution of hydrogen atom with iodine not only increases the cellular uptake, but also regulates the membrane transport. The strong halogen‐bond‐forming ability of iodine atoms plays a crucial role in the transport and the introduction of iodine may provide an efficient strategy for studying membrane activity and cellular functions and improving the delivery of therapeutic agents. This Concept article does not provide a comprehensive picture of membrane transport but highlights halogen‐substitution as a novel strategy for understanding and regulating the cell‐membrane traffic.

Endocrine, Metabolic and Pharmacological Effects of Thyronamines (TAM), Thyroacetic Acids (TA) and Thyroid Hormone Metabolites (THM) – Evidence from in vitro, Cellular, Experimental Animal and Human Studies

“…Which of the THTT synthesized in beta cells is actually involved in uptake of 3-T1AM and export of TA1 has not been described yet [38]. Recently, strong evidence has been presented that introduction of iodine atoms into various biomolecules markedly facilitates transport across cellular membranes in comparison to molecules carrying other halogen atoms or no iodine [43,44]. Obviously, comparable studies are needed to delineate potential 3-T1AM effects on pancreatic glucagon-secreting alpha cells.…”

Thermodynamic contribution of iodine atom to the binding of heterogeneously polyhalogenated benzotriazoles by the catalytic subunit of human protein kinase CK2

“…Iodine‐containing compounds are known to permeate the cellular membrane . The attachment of iodine atom increases the transport of naphtalimide‐based fluorescent probes across the cellular membrane .…”

Anion Transport in Lipid Bilayer Membranes Using Halogen Bonds

“…This delicate equilibrium can and has been exploited in many ways. Although, it was not explicitly discussed in this chapter, halogen bonding has an important effect on membrane permeation [78], which can also enable the transport of actual (macro)molecules [79,80]. To these additional functional properties, it is important to add the arrival of other sigma-hole interactions [26] which have been proven as good and relevant as halogen bonding.…”