DOI: 10.1002/open.201500167
A Structurally-Tunable 3-Hydroxyflavone Motif for Visible
Light-Induced Carbon Monoxide-Releasing Molecules
(
CORMs)**
[
a]
[a]
[b]
[b]
[c]
Stacey N. Anderson, Jason M. Richards, Hector J. Esquer, Abby D. Benninghoff, Atta M. Arif, and
Lisa M. Berreau*
[
a]
Molecules that can be used to deliver a controlled amount of
carbon monoxide (CO) have the potential to facilitate investi-
gations into the roles of this gaseous molecule in biology and
advance therapeutic treatments. This has led to the develop-
ment of light-induced CO-releasing molecules (photoCORMs).
A goal in this field of research is the development of molecules
that exhibit a combination of controlled CO release, favorable
biological properties (e.g., low toxicity and trackability in cells),
and structural tunability to affect CO release. Herein, we report
a new biologically-inspired organic photoCORM motif that ex-
hibits several features that are desirable in a next-generation
photoCORM. We show that 3-hydroxyflavone-based com-
pounds are easily synthesized and modified to impart changes
in absorption features and quantum yield for CO release, ex-
hibit low toxicity, are trackable in cells, and can exhibit both
Figure 1. Structural motifs of selected previously reported CORMs
clude photoCORMs, which release CO from a metal carbonyl
[
4]
O -dependent and -independent CO release reactivity.
2
unit upon illumination with UV or visible light. Recent advan-
ces in the field of metal carbonyl photoCORMs demonstrate
that CO release can be tuned to occur upon illumination with
low-energy red or near infrared (NIR) light through modifica-
tion of supporting ligands or through approaches using nano-
Carbon monoxide (CO)-releasing molecules (CORMs) are of sig-
nificant current interest due to the potential of CO as a thera-
[
1]
[4]
peutic molecule. The vast majority of CORMs developed to
date are based on a metal carbonyl unit as the CO-releasing
particles. However, a concern associated with some metal-
carbonyl-based photoCORMs are side effects related to the
[
2]
[6]
moiety. Many molecules of this type, including protein-bound
metal-containing photoproducts. A limited number of organ-
derivatives of [RuCl(glycinato)(CO) ] (CORM-3) and analogues,
ic photoCORMs (1–3, Figure 1) have also been recently report-
3
[
7]
release CO spontaneously through ligand exchange in an
ed. However, these molecules also have limitations. For ex-
ample, 1 and 2 are derived from relatively low-yield, multistep
synthetic routes that have not been shown to be amenable to
structural modification for the tuning of physical properties or
biological targeting. Diels–Alder product 3 can be generated in
good yield and subsequently undergoes CO release. However,
this compound cannot be isolated and stored.
[3]
aqueous environment.
The lack of temporal control of CO release in such systems
has led to the use of metal carbonyl complexes that release
[4,5]
CO only when triggered.
Examples of such complexes in-
[
a] S. N. Anderson, J. M. Richards, Prof. L. M. Berreau
Department of Chemistry & Biochemistry, Utah State University
Desirable features in a next-generation organic photoCORM
motif include: 1) a high-yield synthesis that enables the prepa-
ration of gram quantities of analytically pure compound; 2) sol-
ubility in water or aqueous dimethyl sulfoxide (DMSO); 3) ther-
mal stability in aerobic, aqueous environments; 4) controllable,
triggered CO release, preferably using light at wavelengths
that do not have the potential to impart cellular damage;
0
300 Old Main Hill, Logan, UT 84322-0300 (USA)
E-mail: lisa.berreau@usu.edu
[
b] H. J. Esquer, Prof. A. D. Benninghoff
Department of Animal, Dairy, & Veterinary Science, Utah State University
4
815 Old Main Hill, Logan, UT 84322-4815 (USA)
[
c] Dr. A. M. Arif
Department of Chemistry, University of Utah
3
5
) low toxicity of the photoCORM and its post-CO-release by-
[
products; 6) ease of structural modification to modulate aque-
ous solubility, photochemical properties (e.g., light absorption
properties), and biocompatibility; and 7) exhibits fluorescence
so as to enable tracking of the localization and CO-release re-
ꢀ
distribution in any medium, provided the original work is properly cited,
the use is non-commercial and no modifications or adaptations are
made.
[8]
activity of the molecule within cells. In the results reported
herein, we describe a new class of biologically inspired photo-
CORMs that exhibit all of the desirable features noted above.
ChemistryOpen 2015, 4, 590 – 594
590
ꢀ 2015 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim