Design, Synthesis, and Application of a Water-soluble Photocage for Aqueous Cyclopentadiene-based Diels-Alder Photoclick Chemistry in Hydrogels

Sophia J Bailey; Erik Hopkins; Kiara D Rael; Arsalan Hashmi; Juan Manuel Urueña; Maxwell Z Wilson; Javier Read de Alaniz

doi:10.1002/anie.202301157

Design, Synthesis, and Application of a Water-soluble Photocage for Aqueous Cyclopentadiene-based Diels-Alder Photoclick Chemistry in Hydrogels

Angew Chem Int Ed Engl. 2023 Apr 11;62(16):e202301157. doi: 10.1002/anie.202301157. Epub 2023 Mar 10.

Authors

Sophia J Bailey¹, Erik Hopkins², Kiara D Rael^{1

3}, Arsalan Hashmi¹, Juan Manuel Urueña⁴, Maxwell Z Wilson^{2

4}, Javier Read de Alaniz^{1

4}

Affiliations

¹ Department of Chemistry and Biochemistry, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.
² Department of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.
³ Department of Chemistry, New Mexico Highlands University, Las Vegas, NM, 87701, USA.
⁴ BioPACIFIC Materials Innovation Platform, University of California, Santa Barbara, Santa Barbara, CA, 93106, USA.

PMID: 36821552
DOI: 10.1002/anie.202301157

Abstract

Spatiotemporally functionalized hydrogels have exciting applications in tissue engineering, but their preparation often relies on radical-based strategies that can be deleterious in biological settings. Herein, the computationally guided design, synthesis, and application of a water-soluble cyclopentadienone-norbornadiene (CPD-NBD) adduct is disclosed as a diene photocage for radical-free Diels-Alder photopatterning. We show that this scalable CPD-NBD derivative is readily incorporated into hydrogel formulations, providing gels that can be patterned with dienophiles upon 365 nm uncaging of cyclopentadiene. Patterning is first visualized through conjugation of cyanine dyes, then biological utility is highlighted by patterning peptides to direct cellular adhesion. Finally, the ease of use and versatility of this CPD-NBD derivative is demonstrated by direct incorporation into a commercial 3D printing resin to enable the photopatterning of structurally complex, printed hydrogels.

Keywords: 3D Printing; Cyclopentadiene; Diels-Alder; Hydrogels; Photoclick.

Abstract

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