Synthesis of Click-Ready Aminooxy-Terminated Poly(ε-caprolactone) Oligomers for Oxime Ligation

Area of Science:

• Polymer Chemistry
• Organic Synthesis
• Bioconjugation

Background:

• Oxime ligation is a versatile conjugation method for creating chemical linkages under mild, aqueous conditions.
• Degradable polymers like poly(ε-caprolactone) (PCL) are valuable in biomedical applications but require efficient functionalization strategies.

Purpose of the Study:

• To develop a straightforward, one-pot synthesis of aminooxy-functionalized PCL oligomers.
• To demonstrate the utility of these "click-ready" polymers in water-tolerant oxime ligation reactions.

Main Methods:

• A bifunctional initiator was used for simultaneous ring-opening polymerization of ε-caprolactone and in situ deprotection.
• Methanesulfonic acid (MSA) catalyzed both polymerization and deprotection, yielding aminooxy-functionalized PCL oligomers.
• The resulting oligomers were reacted with various aldehydes and ketones under diverse solvent conditions.

Main Results:

• High conversion rates (>95%) were achieved for both polymerization and deprotection under optimized conditions.
• Well-defined PCL oligomers with controlled degrees of polymerization (DP = 5-20) were synthesized.
• Rapid and efficient oxime ligation (>90% conversion in 1-2 h) was observed with diverse carbonyl compounds, including sugars, in mixed aqueous solvents.

Conclusions:

• A facile, water-tolerant synthetic platform for "click-ready" degradable polymers was established.
• This method enables broad integration of degradable polymers with biobased and functional substrates via oxime ligation.
• The synthesized aminooxy-functionalized PCL oligomers offer a versatile tool for advanced material design and bioconjugation.