Chirality Makes or Breaks Chemically Driven Self-Assembly.

Area of Science:

• Chemical Biology
• Supramolecular Chemistry
• Origins of Life Research

Background:

• Chirality is fundamental in biology, with nature selecting homochiral molecules for recognition, catalysis, and self-assembly.
• The role of chirality in chemically driven reaction networks, beyond biological systems, is largely unexplored.

Purpose of the Study:

• To investigate how chiral building blocks influence self-assembly and reaction pathways in synthetic chemical systems.
• To demonstrate that molecular configuration, not functional groups, can dictate chemical reactivity and supramolecular behavior.

Main Methods:

• Synthesis and use of enantiopure aminoacyl phosphate esters as chiral acylating agents.
• Analysis of self-assembly dynamics and supramolecular architecture formation.
• Investigation of cascade reactions and stereochemical control propagation.

Main Results:

• Chiral aminoacyl phosphate esters drive self-assembly and reaction pathways modulated solely by their configuration.
• Enantiopure agents generate transient epimeric esters from peptide substrates, leading to distinct supramolecular structures and dynamics.
• Chirality regulates downstream reactivity in cascade reactions and selectively modulates different reaction cycles.

Conclusions:

• Stereochemical programming using chiral acylating agents provides precise control over reactivity and self-assembly.
• This approach offers novel strategies for encoding chirality into chemical networks and functionalizing them.
• Chirality acts as a fundamental parameter to control complex chemical behavior.