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A Molecular Hybrid for Mitochondria‐Targeted NO Photodelivery
Author(s) -
Sodano Federica,
Gazzano Elena,
Fraix Aurore,
Rolando Barbara,
Lazzarato Loretta,
Russo Marina,
Blangetti Marco,
Riganti Chiara,
Fruttero Roberta,
Gasco Alberto,
Sortino Salvatore
Publication year - 2018
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201700608
Subject(s) - moiety , chemistry , photochemistry , chromophore , phototoxicity , conjugate , superoxide , rhodamine , fluorescence , combinatorial chemistry , stereochemistry , organic chemistry , biochemistry , mathematical analysis , physics , mathematics , quantum mechanics , in vitro , enzyme
The design, synthesis, spectroscopic and photochemical properties, and biological evaluation of a novel molecular hybrid that is able to deliver nitric oxide (NO) into mitochondria are reported. This molecular conjugate unites a tailored o ‐CF 3 ‐ p ‐nitroaniline chromophore, for photo‐regulated NO release, and a rhodamine moiety, for mitochondria targeting, in the same molecular skeleton via an alkyl spacer. A combination of steady‐state and time‐resolved spectroscopic and photochemical experiments demonstrate that the two chromogenic units preserve their individual photophysical and photochemical properties in the conjugate quite well. Irradiation with violet light triggers NO release from the nitroaniline moiety and photoionization in the rhodamine center, which also retains considerable fluorescence efficiency. The molecular hybrid preferentially accumulates in the mitochondria of A549 lung adenocarcinoma cells where it induces toxicity at a concentration of 1 μ m , exclusively upon irradiation. Comparative experiments, carried out with ad‐hoc‐synthesized model compounds, suggest that the phototoxicity observed at such a low concentration is probably not due to NO itself, but rather to the formation of the highly reactive peroxynitrite that is generated from the reaction of NO with the superoxide anion.