Synthesis and Photophysical and Photocatalytic Properties of a Highly Fluorinated and Durable Phthalocyanine–Peptide Bioconjugate for Potential Theranostic Applications

The functionalized, asymmetric fluoro–fluoroalkyl scaffold F 48 H 7 COOHPcZn ( 3 ) was used to prepare F 48 H 7 COOPcZn-6-amino-hexanoate-CTVALPGGYVRVC ( 5 ), a Pep42 peptide bioconjugate envisioned for photodynamic therapy, which can specifically target the GRP78 chaperone protein overexpressed and exclusively localized on some cancer cell surfaces. The analogous F 48 H 7 COOHPcCu ( 4 ) has also been prepared, and its single-crystal X-ray structure was elucidated. Despite reduced steric hindrance relative to the nonfunctionalized, single-site complexes of the F 64 Pc scaffold, no aggregation was detected in solution via UV–vis spectroscopy, for either 3, 4, or 5, consistent with the lack of π stacking observed for the crystalline 4 . The 6-aminohexanoic acid-Pep42 moiety diminishes the fluorescence efficiency of 5, relative to 3, but for singlet oxygen ( 1 O 2 ) generation, photochemical hydroperoxidation of β-(−)-citronellol using 5 and 3 occurs with comparable substrate turnover efficiency, albeit at a slower initial triplet oxygen uptake for 5 . The bioconjugate 5 is durable; it does not decompose under 1 O 2 photoreaction conditions. These results suggest a synthetic coupling pathway for obtaining diverse biotargeting polypeptide-fluorinated phthalocyanine bioconjugates of potential utility as both fluorescence reporters and photocatalysts and highlight the importance of fluorinated scaffolds for generating chemically resilient, catalytic, theranostic materials.