Dendrimer Conjugation Enables Multiphoton Chemical Neurophysiology Studies with an Extended π-Electron Caging Chromophore

Matthew T. Richers, Stefan Passlick, Hitesh Agarwal, Graham C.R. Ellis-Davies

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

Abstract

We have developed a caged neurotransmitter using an extended π-electron chromophore for efficient multiphoton uncaging on living neurons. Widely studied in a chemical context, such chromophores are inherently bioincompatible due to their highly lipophilic character. Attachment of two polycarboxylate dendrimers, a method we call “cloaking”, to a bisstyrylthiophene (or BIST) core effectively transformed the chromophore into a water-soluble optical probe, whilst maintaining the high two-photon absorption of over 500 GM. Importantly, the cloaked caged compound was biologically inert at the high concentrations required for multiphoton chemical physiology. Thus, in contrast to non-cloaked BIST compounds, the BIST-caged neurotransmitter can be safely delivered onto neurons in acutely isolated brain slices, thereby enabling high-resolution two-photon uncaging without any side effects. We expect that our cloaking method will enable the development of new classes of cell-compatible photolabile probes using a wide variety of extended π-electron caging chromophores.

Original languageEnglish
Pages (from-to)12086-12090
Number of pages5
JournalAngewandte Chemie - International Edition
Volume58
Issue number35
DOIs
StatePublished - 26 Aug 2019

Keywords

  • caged compounds
  • dendrimers
  • neurophysiology
  • photopharmacology
  • two-photon uncaging

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