A single heteroatom controls halogen- versus chalcogen-bond-driven cellular uptake

Area of Science:

• Supramolecular chemistry
• Chemical biology

Background:

• Halogen bonds and chalcogen bonds are non-covalent interactions that can mediate molecular recognition.
• These interactions play roles in biological systems, including membrane interactions.

Purpose of the Study:

• To investigate the distinct roles of halogen and chalcogen bonding in membrane recognition within a single molecular scaffold.
• To compare the uptake mechanisms of oxygen, sulfur, and selenium analogues.

Main Methods:

• Synthesis of molecular scaffolds containing oxygen, sulfur, and selenium analogues.
• Assays to measure membrane recognition and uptake.
• Spectroscopic and computational analyses to probe bonding interactions.

Main Results:

• Oxygen analogues demonstrated uptake primarily dependent on halogen bonding.
• Sulfur and selenium analogues showed uptake predominantly mediated by chalcogen bonding.
• The same scaffold exhibited differential recognition based on the chalcogen atom.

Conclusions:

• Halogen and chalcogen bonds play distinct, complementary roles in membrane recognition.
• The nature of the chalcogen atom dictates whether halogen or chalcogen bonding dominates membrane interactions.
• This provides a basis for designing molecules with tailored membrane recognition properties.