Tuning Pore Microenvironments in Covalent Organic Frameworks for Controlled Enzyme Loading and Release
Wenlu Fan1, Joshua Phipps1, Kui Tan2
1Department of Chemistry, University of North Texas, Denton, USA.
Small (Weinheim an Der Bergstrasse, Germany)
|August 6, 2026
Summary
Covalent Organic Frameworks (COFs) with tunable pores were synthesized to study enzyme delivery. Hydrophilic COFs enhance enzyme loading and slow release, while hydrophobic ones show the opposite effects, guiding COF design for biocatalysis.
Area of Science:
- Materials Science
- Chemical Engineering
- Biotechnology
Background:
- Covalent Organic Frameworks (COFs) offer tunable pore environments for enzyme delivery.
- The influence of COF pore microenvironments on enzyme loading and release kinetics is not well understood.
Purpose of the Study:
- To investigate the impact of COF pore microenvironment characteristics on enzyme loading, release, and activity.
- To establish design principles for COF-based enzyme delivery systems.
Main Methods:
- Synthesis of TPE-based imine-linked COFs using varying dialdehyde linkers to create distinct pore environments.
- Systematic investigation of papain loading, release, and activity in different COF models.
- In situ FTIR spectroscopy to probe enzyme-framework interactions during loading.
Main Results:
- Hydrophobic COFs showed lower enzyme loading, faster release, and reduced activity.
- Hydrophilic COFs demonstrated efficient enzyme loading, slow release, and slightly lower retained activity.
- In situ FTIR provided molecular-level evidence of microenvironment-governed enzyme behavior.
Conclusions:
- The pore microenvironment of COFs significantly regulates enzyme loading, release, and retained activity.
- Rational design of COFs based on pore hydrophobicity/hydrophilicity is crucial for optimizing enzyme delivery and biocatalysis.
- This study provides key insights for developing advanced COF-based protein delivery and biocatalytic platforms.


