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where.[21] For illumination, LED light sources (red: l=622–770 nm;
green: l=492–577 nm; and blue: l=470–475 nm; 60 LED clusters,
3 W, 220 V) were used. The set-up was placed in a cardboard box
to shield off any unwanted light such as daylight.
in DMSO, D2O, and physiological saline/D2O. All the complexes
release CO under illumination of visible light (blue, green, and
red). The CO-releasing efficiency under photoinduction by
either blue or green light decreased in the order of 1 (ClÀ), 2
(BrÀ), and 3 (IÀ). Their photoinduced CO release probably pro-
ceeds via two mechanisms, namely the direct decomposition
induced by the illumination and the reaction of the excited
species with solvent or other nucleophiles. In other words, the
involvement of a nucleophile promotes the photoinduced de-
composition probably in a concerted manner. On the other
hand, the auxiliary ligands of the complexes exert a profound
influence on their CO-releasing behaviour through altering the
bonding nature of the metal–ligand bond and the energy
levels of the frontier orbitals that are associated with the re-
duction potentials of the complexes. As a category of iron(II)
complexes with the core {FeII(cis-CO)2}, there is much space to
manoeuvre in altering the auxiliary ligand(s) since there is a fur-
ther fourth coordination number to be satisfied. Along with
the low cytotoxicity of the examined complexes in normal
human liver cell line (QSG-7702) with/without illumination, the
prospect of this type of iron(II) carbonyl complexes is extreme-
ly promising as potential PhotoCORMs and worthy of further
exploration.
Synthesis of complexes 1–3
[(h5-C5H5)Fe(cis-CO)2Cl] (1): Concentrated HCl (12 molLÀ1, 5 mL) was
added to a solution of [{CpFe(m-CO)(CO)}2][20] (0.5 g, 1.4 mmol) in
ethanol (30 mL). After being stirred overnight, the solvent was re-
moved under reduced pressure to produce a residue that was puri-
fied with column chromatography (eluent: ethyl acetate/petroleum
ether 1:4) to produce a red solid (yield: 234 mg, 1.1 mmol, 40%). IR
1
(CH2Cl2, n˜CO/cmÀ1): 2049, 2004; H NMR (CDCl3, ppm): 5.04 (5H, Cp-
H).
[(h5-C5H5)Fe(cis-CO)2Br] (2): Complex 2 was synthesised analogously
to complex 1 by using HBr (6.8 molLÀ1, 5 mL) rather than HCl
(yield: 334 mg, 1.3 mmol, 45%). IR (CH Cl , nCO/cmÀ1): 2054, 2007;
˜
2
2
1H NMR (CDCl3, ppm): 5.03 (5H, Cp-H).
[(h5-C5H5)Fe(cis-CO)2I] (3): A solution of I2 (500 mg, 2.0 mmol) in
CH2Cl2 (40 mL) was added dropwise to a flask charged with
[{CpFe(m-CO)(CO)}2] (0.5 g, 1.4 mmol). The reaction was stirred con-
tinuously at room temperature for 2 h. The mixture was washed
with Na2S2O3 (0.13 molLÀ1, 270 mL) and H2O2 (5%, 10 mL) water
solution, respectively. The removal of the solvents under reduced
pressure gave a crude product which was then purified with
column chromatography (eluent: ethyl acetate/petroleum ether
1:4) to produce a dark-red solid (yield: 668 mg, 2.2 mmol, 80%). IR
It is of particular interest to mention the behaviour of the
red light on inducing CO release from the three complexes. Al-
though the CO release under illumination of red light was not
as effective as the other two lights, it did induce CO release
and, the order of releasing efficiency was reversed in the order
of 3 (IÀ), 2 (BrÀ), and 1 (ClÀ). This could be attributed to the
red light exciting the molecule to an overtone energy level of
a certain bond of the complex which is, therefore, activated to
react with the solvent (nucleophile) to release CO. This would
offer us a novel approach to employ low-energy irradiation, in-
cluding irradiation in the near-IR region, to initiate CO release
by combining with the substitution reaction.
1
(CH2Cl2, n˜CO/cmÀ1): 2041, 1997; H NMR (CDCl3, ppm): 5.03 (5H, Cp-
H).
Monitoring the CO release
A typical procedure for the monitoring is as follows: A solution of
complex 1 (8.0 mg, 0.038 mmol) in DMSO (3.0 mL) was exposed to
a LED light (blue: l=470–475 nm; green: l=492–577 nm and red:
l=622–770 nm, 60 LED clusters, 3 W, 220 V). The set-up was
placed in a cardboard box to shield off any unwanted lights. The
light source was positioned right above the solution at a distance
of 13 cm. The reaction was regularly monitored using IR spectros-
copy. The same procedure was used to monitor the CO release in
either D2O or physiological saline in D2O (NaCl, 0.15 molLÀ1). In
both media, a small amount of DMSO (0.5 mL) was added to en-
hance the solubility of the complexes.
Experimental Section
Materials and instrumentation
Unless otherwise stated, all operations were carried out under an
Ar atmosphere using standard Schlenk techniques. Reaction vessels
were oven-dried at 1508C and solvents were freshly distilled using
the appropriate drying agent prior to use. Fe(CO)5 and dicyclopen-
tadiene were purchased from Aladdin and used as received to pre-
pare [{CpFe(m-CO)(CO)}2] by following the previously reported pro-
cedure.[20] Complexes 1–3 were synthesised by following the pro-
cedures described previously with some modifications when neces-
sary.[15] Measures for light shielding was taken during the synthesis
and handling of the complexes owing to their light sensitivity. FTIR
spectra in a solution were recorded on Agilent 640 using a CaF2
cell with a spacer of 0.1 mm. UV/Vis spectra were measured on an
Evolution 201 (Thermo Fisher Scientific). NMR spectra were mea-
sured on a Varian 400-MR spectrometer with tetramethylsilane as
internal standard. Mass spectral data (ESI, positive mode) were col-
lected on LCQ (Finnigan). Electrochemistry was performed in
[tBu4N]BF4–CH3CN by using a gas-tight and self-designed electro-
chemical cell. Potentials are quoted against the ferrocene couple.
Detailed procedures for electrochemistry can be found else-
Cytotoxicity assessment using MTT assay
QSG-7702 cells (100 mL, 5103 cellsmLÀ1) were seeded into 96-well
plates and left to adhere for 24 h. The media was removed from
the wells and replaced with fresh media containing the iron(II)
complexes with different concentrations (100, 200, 300, 400, 500,
600, 700, 800, 900, and 1000 mmolLÀ1), respectively. The cells were
then incubated for another 24 h before the incubation media were
replaced with the complete medium, and MTT (10 mL, 5 mgmLÀ1 in
phosphate buffer solution, PBS) was added to each well of the
plate. The cells were further incubated for 4 h before the media
were replaced with DMSO (100 mL). Absorbance at 490 nm for each
well of the plates was recorded with a microplate reader. In the
MTT assay, DMSO (100 mL) in a well was used as blank and cells in
the well without the addition of any complexes were taken as
a control (100% in cell viability). Relative cell viability is expressed
as (AobsÀAb)/(AcÀAb), where Aobs, Ab, and Ac are the absorbance ob-
served for the cells treated with the complexes, blank, and the
control, respectively. Inhibiting rate (%) was calculated as
Chem. Eur. J. 2015, 21, 13065 – 13072
13071
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