Bioorganic & Medicinal Chemistry Letters
A mitochondria-selective near-infrared-emitting fluorescent dye for
cellular imaging studies
Peter Choi a, Katsuya Noguchi b, Munetaka Ishiyama b, William A. Denny a, Jiney Jose a,
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a Auckland Cancer Society Research Centre, School of Medical Sciences, University of Auckland, Private Bag 92019, Auckland 1142, New Zealand
b Dojindo Laboratories Co., Ltd, Techno-Research Park Tabaru 2025-5 Mashiki-machi, Kamimashiki-gun, 861-2202, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
This communication details the synthesis, evaluation of photophysical properties, and cellular imaging
studies of cyanine chromophore based fluorescent dye 1 as a selective imaging agent for mitochondria.
Ó 2018 Elsevier Ltd. All rights reserved.
Received 23 January 2018
Revised 26 April 2018
Accepted 1 May 2018
Available online xxxx
Keywords:
Near infrared fluorescent dyes
Mitochondria
Amoxapine
Cyanine dye
Organelle selective fluorescent dyes
Introduction
by a process called oxidative phosphorylation. Any defect in this
pathway of ATP production will inevitably affect the cellular func-
Organelle selective fluorescent probes are useful tools for delin-
eating functional and morphological changes of various organelles,
especially in a diseased state.1 There are number of such probes
reported in the literature, exemplifying the detailed synthetic
efforts various groups have put in over the years to make them
available to the scientific community.2–4 These probes are biocom-
patible, nontoxic and mostly selective towards their target.5
Although much work has been accomplished with molecules emit-
ting in the 400–600 nm range, there still exists an opportunity to
fine tune their emission towards the near infrared region (700–
1000 nm) wherein there is minimal back ground fluorescence
due to absorbing cellular entities and much greater tissue penetra-
tion. There is also minimal tissue damage caused by photons in this
region of the spectrum.
An ongoing research project in our group focuses on developing
organelle selective fluorescent probes for studying disease initia-
tion at a cellular level. As our understanding of disease progression
continues to advance it is becoming increasingly clear that certain
organelles undergo changes during the onset of disease. Among
them are mitochondria, the organelles responsible for energy pro-
duction for various cellular functions, which have a major role
associated with disease onset.6 Mitochondria are often referred
to as the powerhouse of mammalian cells as they produce ATP
tions and ultimately lead to various disorders.7 Mitochondrial mal-
function is associated with many diseases such as cancer, arthritis
and heart disease.8
We have chosen to work with the cyanine scaffold due to its
ease of synthetic manipulation and the subsequent fluorescence
shift that can be achieved towards longer wavelength.9 In general,
straight chain polymethine cyanine dyes suffer from photo stabil-
ity issues due to photo oxidation caused by reactive oxygen species
in aqueous media, which has hampered their widespread use as a
class of dyes in biological conditions.10 However, their photo sta-
bility can be improved by introducing a cyclohexenyl ring as part
of the polymethine chain.11 IR-786 is one such heptamethine cya-
nine dye, incorporating a cyclohexenyl ring with a meso-chloro
group which serves as a suitable electrophile to undergo reaction
with various nucleophiles. There are many examples in the litera-
ture where the reactive chloro group is utilized to append various
nucleophiles to modulate fluorescence properties which can then
be used to monitor cellular processes and pH changes in cellular
environment.12–14
Fluorescent dyes have also been used to develop fluorescently
tagged drug molecules in order to study the interaction of drugs
with various receptor targets at the cellular level.15 One advantage
of such a strategy is the ability to delineate the specific or non-
specific interaction of a drug with various receptors which could
then be used to improve the efficacy of the drug. Development of
drugs targeting G-protein coupled receptors for therapeutic
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Corresponding author.
0960-894X/Ó 2018 Elsevier Ltd. All rights reserved.