Constitutional adaptation to pK_a modulation by remote ester hydrolysis

Area of Science:

• Supramolecular Chemistry
• Chemical Biology
• Systems Chemistry

Background:

• Environmental factors significantly influence biomolecule structure, function, and reaction pathways in nature.
• Minimalistic artificial systems exhibiting adaptive behaviors in response to environmental changes are underexplored.
• Amino acid ester hydrolysis causes significant pH changes, affecting molecular protonation states.

Purpose of the Study:

• To investigate adaptive behaviors in artificial dynamic covalent libraries (DCvLs) triggered by environmental stimuli.
• To explore how chemical modifications, like ester hydrolysis, induce constitutional adaptation in DCvLs.
• To understand the emergence of complexity and organization from simple chemical systems.

Main Methods:

• Construction and analysis of dynamic covalent libraries based on amino acid methyl esters and aldehydes.
• Induction of hydrolysis in amino acid methyl esters to alter library composition.
• Introduction of scavengers to observe selective up-regulation of specific library constituents.
• Enzymatic modification of DCvLs to induce simplified constitutional distributions and transient chirality.

Main Results:

• Amino acid methyl ester hydrolysis in DCvLs leads to constitutional adaptation by favoring non-zwitterionic forms for imine formation.
• Enzyme-mediated reactions simplify constitutional distributions and generate transient chirality within the libraries.
• The presence of hydrolysis-resistant scavengers results in the selective up-regulation of scavenger-derived constituents.
• Complex behaviors, including micelle formation and the emergence of organized distributions, arise from these adaptive chemical systems.

Conclusions:

• Minimalistic artificial systems can exhibit adaptive responses to environmental changes, mirroring biological regulation.
• Dynamic covalent chemistry provides a platform for creating systems that adapt their composition and structure.
• Remote chemical modifications can trigger site-specific inhibition and control molecular behavior, akin to enzyme regulation.