Synthesis,
Spectroscopic Properties, and Photoinduced CO-Release Studies of Functionalized
Ruthenium(II) Polypyridyl Complexes: Versatile Building Blocks for
Development of CORM–Peptide Nucleic Acid Bioconjugates
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Abstract
A series of ruthenium(II)
dicarbonyl complexes of formula [RuCl<sub>2</sub>(L)(CO)<sub>2</sub>] (L = bpy<sup>CH3,CH3</sup> = 4,4′-dimethyl-2,2′-bipyridine,
bpy<sup>CH3,CHO</sup> = 4′-methyl-2,2′-bipyridine-4-carboxyaldehyde,
bpy<sup>CH3,COOH</sup> = 4′-methyl-2,2′-bipyridine-4-carboxylic
acid, CppH = 2-(pyridin-2-yl)pyrimidine-4-carboxylic acid, dppzcH
= dipyrido[3,2-a:2′,3′-c]phenazine-11-carboxylic acid),
and [RuCl(L)(CO)<sub>2</sub>]<sup>+</sup> (L = tpy<sup>COOH</sup> =
6-(2,2′:6′,2″-terpyridine-4′-yloxy)hexanoic
acid) has been synthesized. In addition, a high-yield synthesis of
a peptide nucleic acid (PNA) monomer containing the 2-(pyridin-2-yl)pyrimidine
ligand was also developed, and this compound was used to prepare the
first Ru(II) dicarbonyl complex, [RuCl<sub>2</sub>(Cpp-L-PNA)(CO)<sub>2</sub>],(Cpp-L-PNA = <i>tert</i>-butyl-<i>N</i>-[2-(<i>N</i>-9-fluorenylmethoxycarbonyl)aminoethyl]-<i>N</i>-[6-(2-(pyridin-2-yl)pyrimidine-4-carboxamido)hexanoyl]glycinate)
attached to a PNA monomer backbone. Such metal-complex PNA–bioconjugates
are attracting profound interest for biosensing and biomedical applications.
Characterization of all complexes has been undertaken by IR and NMR
spectroscopy, mass spectrometry, elemental analysis, and UV–vis
spectroscopy. Investigation of the CO-release properties of the Ru(II)
complexes in water/dimethyl sulfoxide (49:1) using the myoglobin assay
showed that they are stable under physiological conditions in the
dark for at least 60 min and most of them even for up to 15 h. In
contrast, photoinduced CO release was observed upon illumination at
365 nm, the low-energy shoulder of the main absorption maximum centered
around 300 nm, establishing these compounds as a new class of PhotoCORMs.
While the two 2,2′-bipyridine complexes release 1 equiv of
CO per mole of complex, the terpyridine, 2-(2′-pyridyl)pyrimidine,
and dipyrido[3,2-a:2′,3′-c]phenazine complexes are less
effective CO releasers. Attachment of the 2-(2′-pyridyl)pyrimidine
complex to a PNA backbone as in [RuCl<sub>2</sub>(Cpp-L-PNA)CO<sub>2</sub>] did not significantly change the spectroscopic or CO-release
properties compared to the parent complex. Thus, a novel class of
Ru(II)-based PhotoCORMs has been established which can be coupled
to carrier delivery vectors such as PNA to facilitate cellular uptake
without loss of the inherent CORM properties of the parent compound