Quantitative Reactivity Scales for Dynamic Covalent and Systems Chemistry

Area of Science:

• Dynamic covalent chemistry (DCC)
• Materials Science
• Organic Chemistry

Background:

• Dynamic covalent chemistry (DCC) is crucial for creating molecular assemblies and complex systems.
• Imine-based dynamic covalent reactions (DCRs) are widely used but lack quantitative reactivity scales.
• Controlling equilibrium in DCRs is essential for predictable synthesis and material design.

Purpose of the Study:

• To develop the first quantitative reactivity scales for predicting the equilibrium of dynamic covalent reactions (DCRs).
• To establish a unified framework for evaluating and modeling DCRs.
• To provide tools for DCR discovery, bioconjugation, and catalysis.

Main Methods:

• Investigated DCRs between aromatic imines and various O-, N-, and S- mononucleophiles.
• Analyzed substituent effects (electron-donating groups and electron-withdrawing groups) on imine stability and adduct formation.
• Developed and validated a quantitative reactivity scale based on nucleophilicity and electrophilicity parameters.

Main Results:

• Established quantitative reactivity scales correlating and predicting DCR equilibrium.
• Demonstrated that substituent effects on aromatic imines influence equilibrium through quinoidal resonance or intramolecular hydrogen bonding.
• Observed unique nonlinear Hammett behavior with cyclic secondary amines, a novel finding in thermodynamically controlled systems.
• Developed nucleophilicity (R(N), S(N)) and electrophilicity (R(E)) parameters for DCRs.

Conclusions:

• The proposed quantitative reactivity scales provide a general and useful tool for evaluating and modeling DCRs.
• The developed parameters are complementary to existing kinetic parameters and applicable to DCR discovery, bioconjugation, and catalysis.
• This work represents a significant advancement in the quantitative understanding and application of dynamic covalent chemistry.