Computational Design, Synthesis, and Photochemistry of Cy7-PPG, an Efficient NIR-Activated Photolabile Protecting Group for Therapeutic Applications

Georgios Alachouzos*, Albert M. Schulte, Anirban Mondal, Wiktor Szymanski*, Ben L. Feringa*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Scopus)
14 Downloads (Pure)

Abstract

Photolabile Protecting Groups (PPGs) are molecular tools used, for example, in photopharmacology for the activation of drugs with light, enabling spatiotemporal control over their potency. Yet, red-shifting of PPG activation wavelengths into the NIR range, which penetrates the deepest in tissue, has often yielded inefficient or insoluble molecules, hindering the use of PPGs in the clinic. To solve this problem, we report herein a novel concept in PPG design, by transforming clinically-applied NIR-dyes with suitable molecular orbital configurations into new NIR-PPGs using computational approaches. Using this method, we demonstrate how Cy7, a class of NIR dyes possessing ideal properties (NIR-absorption, high molecular absorptivity, excellent aqueous solubility) can be successfully converted into Cy7-PPG. We report a facile synthesis towards Cy7-PPG from accessible precursors and confirm its excellent properties as the most redshifted oxygen-independent NIR-PPG to date (λmax=746 nm).

Original languageEnglish
Article numbere202201308
Number of pages8
JournalAngewandte Chemie-International Edition
Volume61
Issue number27
Early online date10-Mar-2022
DOIs
Publication statusPublished - 4-Jul-2022

Keywords

  • Density Functional Theory
  • NIR Light
  • Photochemistry
  • Photolabile Protecting Groups
  • Photopharmacology
  • BODIPY PHOTOPROTECTING GROUPS
  • HEPTAMETHINE CYANINE DYES
  • ORGANIC-PHOTOCHEMISTRY
  • SPECTRAL PROPERTIES
  • LIGHT
  • CLEAVAGE

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