Neighboring Chalcogen Bonding for Controlling Dynamic Imine Chemistry in Aqueous Media

Area of Science:

• Organic Chemistry
• Supramolecular Chemistry
• Chemical Biology

Background:

• Dynamic imine chemistry is crucial for various applications, including bioconjugation and materials science.
• Chalcogen bonding, interactions involving heavier Group 16 elements, is increasingly recognized for its role in molecular recognition and catalysis.
• Understanding how chalcogen bonding influences dynamic covalent chemistry in aqueous media is essential for developing new chemical tools.

Purpose of the Study:

• To investigate the impact of different chalcogen bonds (sulfur, selenium, tellurium, telluronium) on the kinetics and thermodynamics of imine formation and exchange in aqueous solution.
• To explore the potential of incorporating carboxylate or cationic telluronium groups into arylaldehydes to modulate chalcogen bonding interactions.
• To demonstrate the utility of chalcogen bonding, specifically with telluronium compounds, for bioconjugation applications, such as labeling amino acids.

Main Methods:

• Synthesis of functionalized arylaldehydes bearing carboxylate or telluronium groups.
• Experimental studies including kinetic and thermodynamic measurements of imine formation/exchange reactions in aqueous solutions.
• Computational modeling (e.g., DFT calculations) to elucidate the mechanisms and energetic contributions of chalcogen bonding.
• Application of telluronium-containing aldehydes for the selective labeling of the N-terminus of amino acids under neutral buffer conditions.

Main Results:

• Varied chalcogen bonds exert a significant influence on the dynamic imine chemistry in aqueous solution.
• Tellurium and telluronium compounds demonstrated the most pronounced effect on imine formation and exchange kinetics and thermodynamics.
• The introduction of a carboxylate group or a cationic telluronium moiety effectively modulated the chalcogen bonding interactions.
• Telluronium-containing aldehydes successfully enabled the labeling of the N-terminus of amino acids in neutral buffer via multivalent chalcogen bonding.

Conclusions:

• Chalcogen bonding, especially involving tellurium and telluronium, serves as a powerful tool for regulating dynamic imine chemistry in aqueous environments.
• The developed telluronium-based aldehyde chemistry offers a novel and efficient method for bioconjugation, specifically for N-terminal amino acid labeling.
• This work expands the understanding of non-covalent interactions in dynamic covalent chemistry and provides a platform for designing advanced functional molecules and bioconjugates.