Next generation photoCORMs: Polynuclear tricarbonylmanganese(I)- functionalized polypyridyl metallodendrimers

Article abstract of DOI:10.1021/ic400377k

The first CO-releasing metallodendrimers, based on polypyridyl dendritic scaffolds functionalized with Mn(CO)₃ moieties, of the general formula [DAB-PPI-{MnBr(bpy^CH3,CH=N)(CO)₃}_n], where DAB = 1,4-diaminobutane, PPI = poly(propyleneimine), bpy = bipyridyl, and n = 4 for first- or n = 8 for second-generation dendrimers, were synthesized and comprehensively characterized by analytical (HR-ESI mass spectrometry and elemental analysis) and spectroscopic (¹H, ¹³C{ ¹H}-NMR, infrared, and UV/vis spectroscopy) methods. The CO-release properties of these compounds were investigated in pure buffer and using the myoglobin assay. Both metallodendrimer generations are stable in the dark in aqueous buffer for up to 16 h but show photoactivated CO release upon excitation at 410 nm, representing a novel class of macromolecular photoactivatable CO-releasing molecules (PhotoCORMs). No scaling effects were observed since both metallodendrimers release ～65% of the total number of CO ligands per molecule, regardless of the generation number. In addition, the mononuclear model complex [MnBr(bpy^{CH3,CH=NCH2CH2CH3})(CO)₃] was prepared and comprehensively studied, including DFT/TDDFT calculations. These metallodendrimer-based PhotoCORMs afford new methods of targeted delivery of large amounts of carbon monoxide to cellular systems.

Full text of DOI:10.1021/ic400377k

Article
pubs.acs.org/IC
Next Generation PhotoCORMs: Polynuclear
Tricarbonylmanganese(I)-Functionalized Polypyridyl
Metallodendrimers
Preshendren Govender,† Sandesh Pai,‡ Ulrich Schatzschneider,*,‡ and Gregory S. Smith*,†
†Department of Chemistry, University of Cape Town, Rondebosch, 7701, Cape Town, South Africa
‡Institut fur Anorganische Chemie, Julius-Maximilians-Universitat Wurzburg, Am Hubland, D-97074 Wurzburg, Germany
̈
̈
̈
̈
S
* Supporting Information
ABSTRACT: The first CO-releasing metallodendrimers, based
on polypyridyl dendritic scaffolds functionalized with Mn(CO)3
moieties, of the general formula [DAB-PPI-{MnBr-
(bpyCH3,CHN)(CO)3}n], where DAB = 1,4-diaminobutane, PPI
= poly(propyleneimine), bpy = bipyridyl, and n = 4 for first- or n
= 8 for second-generation dendrimers, were synthesized and
comprehensively characterized by analytical (HR-ESI mass
spectrometry and elemental analysis) and spectroscopic (1H,
13C{1H}-NMR, infrared, and UV/vis spectroscopy) methods.
The CO-release properties of these compounds were investigated
in pure buffer and using the myoglobin assay. Both metallodendrimer generations are stable in the dark in aqueous buffer for up
to 16 h but show photoactivated CO release upon excitation at 410 nm, representing a novel class of macromolecular
photoactivatable CO-releasing molecules (PhotoCORMs). No scaling effects were observed since both metallodendrimers
release ∼65% of the total number of CO ligands per molecule, regardless of the generation number. In addition, the
mononuclear model complex [MnBr(bpyCH3,CHNCH2CH2CH3)(CO)3] was prepared and comprehensively studied, including
DFT/TDDFT calculations. These metallodendrimer-based PhotoCORMs afford new methods of targeted delivery of large
amounts of carbon monoxide to cellular systems.
Motterlini and co-workers have pioneered the development
of CORMs with the use of Mn2(CO)10 (CORM-1)6 and the
synthesis of [RuCl2(CO)3]2 (CORM-2),7 which induce
vasodilatation, attenuate coronary vasoconstriction, and reduce
acute hypertension.7 The poor solubility of CORM-1 and
CORM-2 under physiological conditions led to the synthesis of
the water-soluble complex [fac-RuCl(glycinate)(CO)3]
(CORM-3), which showed more promising results and is
now the most popular compound for many biological studies.8
However, due to the complicated speciation of CORM-3 in
solution,9 researchers directed their attention to other
transition metals.10−15 Alternative CORMs that have been
explored include pyrone-substituted iron and molybdenum
carbonyl complexes, which undergo solvent-assisted CO
INTRODUCTION
■
For decades, the odorless, tasteless, and colorless gas carbon
monoxide has been viewed as highly toxic to humans, due to its
deleterious effects on oxygen metabolism.1 However, small
molecules such as nitric oxide and hydrogen sulfide have now
been established as important, endogenously produced, signal-
ing molecules in higher organisms, including humans.2,3 This is
also true for CO, which is one of the products of the enzymatic
degradation of heme by heme oxygenase (HO), the other two
being ferric iron and biliverdin, with the latter further converted
to bilirubin by biliverdin reductase.4 In addition to the
important vasodilatory effects of CO, it is its cytoprotective
activity, in particular against oxidative stress mediated by
reactive oxygen species (ROS), that has become the focus of
recent research due to potential therapeutic applications of CO
outweighing its toxicity.5 Since the tissue accumulation of CO is
determined by the distribution coefficient between the different
cellular environments, which is a fixed parameter, other carrier
systems for CO with a “drug sphere” that can be tuned for
specific medicinal applications are now actively pursued.
Transition metal carbonyl complexes are a natural choice as
CO-prodrugs, and a number of trigger mechanisms to initiate
CO release from the metal coordination sphere have been
developed for such CO-releasing molecules (CORMs).
release.16,17 More recently, Romao et al. synthesized a series
̃
of Mo(CO)3-based complexes with a wide range of biomedical
applications, focusing on inflammation, infection, and vaso-
relaxation, with a recent review detailing the requirements of
CORMs for clinical applications.18
In addition to compounds in which the CO release is
induced by ligand exchange reactions with solvent or other
dissolved species, enzyme-triggered CO release (ET-CORMs)
Received: February 13, 2013
Published: April 17, 2013
© 2013 American Chemical Society
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has been demonstrated by the group of Schmalz.19−21 Another
important technique is based on the light-induced CO release
in PhotoCORMs developed by Ford, Schatzschneider, and
others.22−26 Light has already been used to elicit biological
responses in “caged” compounds27,28 as well as in the context
of photodynamic therapy, but the latter is based on the
formation of reactive singlet oxygen by photosensitizers29,30
instead of active species with a more well-defined spectrum of
cellular targets. Hence, the synthesis of light-activated water-
soluble molybdenum-containing CORMs [Mo(C
CCR1R2OH)(η5-C5H5)(CO)3] (where R1 = R2 = Me or R1 =
Me, R2 = Ph) was pursued.31 The photoinduced release of
carbonyl ligands and the efficient cellular uptake by HT-29
human colon cancer cells of a Mn-functionalized CORM, i.e.,
[Mn(CO)3(tpm)]PF6 (where tpm = tris(pyrazolyl)methane),32
prompted the investigation into the biocompatibility and the
targeting ability of this novel CORM. With the use of Pd-
catalyzed Sonogashira cross-coupling and “click” reactions,
alkyne-functionalized [Mn(CO)3(tpm)]PF6 was conjugated to
amino acids and model peptides.33 Notably, the incorporation
to the bioconjugate did not alter the CO-release properties of
the metal carbonyl moiety. More recently, grafting of the
substituted [Mn(CO)3(tpm)]+ moiety to silicium dioxide and
carbon nanomaterials, designed to deliver CO to solid tumors,
was demonstrated with photoinduced CO-release properties
similar to the parent compound.34,35 A common problem with
all the reported CORMs, regardless of the trigger mechanism
for CO release, however, is the fact that in addition to the CO
liberated, there is always an inevitable formation of a metal-
coligand fragment, which might possess biological activity of its
own. One strategy to address this problem is based on systems
in which the metal−ligand moiety generated after CO release
remains bound to a macromolecular carrier. In addition to
different polymeric materials,36 dendrimers are an attractive
choice for this purpose due to their monodisperse nature and
facile preparation. Furthermore, such macromolecules are
known to passively accumulate in tumor tissue due to the
enhanced permeability and retention (EPR) effect.37 Metallo-
dendrimers are dendrimers decorated with metal-containing
moieties, which have been extensively explored in the field of
catalysis.38,39 Only recently, have they also been investigated as
potential therapeutic agents,40,41 since their multifunctionality
may lead to an increased interaction between a dendrimer-drug
conjugate and a cellular target bearing multiple receptors. Here,
we report tetranuclear and octanuclear Mn(CO)3-function-
alized CO-releasing metallodendrimers (1, 2) based on a
polypyridyl dendritic scaffold. In order to compare the scaling
of the CO release of these compounds with the number of
metal carbonyl end groups, a mononuclear analogue (3) was
also synthesized as a model for the polynuclear metal-
lodendrimers.
core and arms of the dendritic ligands. With the aid of 2D-
COSY NMR spectra (Figure S4), the aromatic protons of the
bpy moieties and the imine protons are more discernible.
Furthermore, formation of the imine is confirmed by the
diagnostic CHN absorption band at 1648 cm−1 in the IR
spectrum for both L1 and L2. Elemental analysis and ESI-mass
spectrometry additionally confirmed the integrity of the new
ligands.
The peripheral decorated, Mn(CO)3-functionalized tetranu-
clear (1) and octanuclear (2) metallodendrimers were
synthesized via reaction of the ligands L1 and L2 with
manganese pentacarbonyl bromide (Scheme 1) in dichloro-
Scheme 1. Synthesis of Tetra- and Octanuclear CORM-
Dendrimer Conjugates 1 and 2
methane at room temperature in the dark. The metallo-
dendrimers 1 and 2 were obtained as yellow-orange solids in
moderate yield and purified by preparative RP-HPLC using a
gradient of 5−90% CH3CN/H2O with 0.1% TFA. The reaction
and workup were performed with minimal exposure to light. In
the IR spectra of 1 and 2, three strong peaks appear at about
2020, 1920, and 1900 cm−1 as shown in Figure 1 for 1. With
the aid of DFT calculations (vide infra), the one at higher
wavenumbers is assigned to the symmetrical and the other two
to the asymmetrical CO-stretching vibrations of the metal-
tricarbonyl moiety (see also Table 3). Furthermore, three
singlets observed in the 13C{1H}-NMR spectrum (Figures S8
and S9) at about 220, 221, and 223 ppm also confirm the
RESULTS AND DISCUSSION
■
Synthesis of Dendritic Ligands and Complexes. The
dendritic ligands L1 and L2 were prepared via a Schiff-base
condensation reaction of 4′-methyl-2,2′-bipyridine-4-carboxal-
dehyde with DAB-G1-PPI-(NH2)4 (for L1) or DAB-G2-PPI-
(NH2)8 (for L2). A broad singlet at ∼8.3 ppm in the 1H NMR
spectra for L1 and L2 (Figures S1 and S2), which integrates for
four and eight protons respectively, is assigned to the imine
proton and affirms formation of the Schiff-base. Additional
broad multiplets are observed between 1.4 and 3.7 ppm in the
1H NMR spectra for L1 and L2, assigned to the aliphatic of the
Figure 1. IR (ATR) spectra of dendrimer 1 for a freshly prepared
sample (black) and after exposure to daylight for 1.5 h (blue) and 24 h
(red).
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presence and integrity of the Mn(CO)3 group. The shift to
higher wavenumbers of the stretching vibration assigned to the
CN group of the bpy moiety, from 1596 cm−1 (ligand) to
about 1620 cm−1 (complex), indicates that complexation
occurred via the two pyridyl nitrogen atoms and not via the
imine nitrogen atom, as there is no shift in the stretching
vibration of the imine bond. Broad overlapping signals are
1
observed in the H NMR spectra of 1 and 2 (Figures S5 and
S6) and are assigned to the aliphatic protons of the dendritic
core and arms, characteristically seen with other similar
metallodendrimers.42−45 HR-ESI-TOF mass spectrometric
data further confirmed the structural integrity of metal-
lodendrimers 1 and 2 (Figures S11 and S12).
In addition, mononuclear complex 3 (Scheme 2) was
synthesized as a model of the larger metallodendrimers in
Scheme 2. Synthesis of Mononuclear Model Complex 3
Figure 2. Overlay of the electronic absorption spectra of complexes 1
(black), 2 (red), and 3 (blue) in dimethylsulfoxide/water (10:90% v/
v).
Table 1. Absorption Maxima and Molar Extinction
Coefficient of Complexes 1−3
absorption
maxima λ1
[nm]
absorption
maxima λ2
[nm]
compound
ε1 [M−1 cm−1
]
ε2 [M−1 cm−1
]
order to study potential size-dependent scaling effects on the
photoactivated CO release. Monomeric ligand L3 was prepared
in a procedure similar to the dendritic ligands (L1, L2), by
reacting 4′-methyl-2,2′-bipyridine-4-carboxaldehyde with n-
propylamine via a Schiff-base condensation reaction. L3 was
further reacted with manganese pentacarbonyl bromide in
dichloromethane at room temperature in the absence of light to
obtain complex 3 as an orange solid. Complex 3 was purified by
preparative HPLC under conditions similar to metalloden-
drimers 1 and 2.
For complex 3, infrared spectral analysis revealed three
absorption bands at 2021, 1928, and 1899 cm−1, corresponding
to the terminal CO ligands of the Mn(CO)3 fragment. An
absorption band observed at 1644 cm−1 is assigned the imine
bond. HR-ESI-TOF mass spectrometric data confirmed the
structural integrity of complex 3.
Long-Term Stability of Compounds 1−3. When
compounds 1−3 are exposed to natural daylight for an
extended period of time, a pronounced decrease in the
intensity of the signals of the Mn(CO)3 moiety between
2025 and 1900 cm−1 can be observed (Figures 1 and S13 and
S14) in the infrared spectra. This is indicative of significant
structural changes in the metal−carbonyl group and a first
indicator of the CO release from these compounds.
Electronic Absorption Spectra and CO-Release Prop-
erties. The absorbance maxima and molar extinction
coefficients of complexes 1−3 were determined in a mixture
of dimethylsulfoxide and water (10:90% v/v). Two broad bands
are observed for all compounds at around 300 nm and, at
somewhat lower intensity, in the range of 350−450 nm (Figure
2). With the aid of TDDFT calculations (vide infra), these are
attributed to interligand charge transfer (ILCT) and metal-to-
ligand charge transfer (MLCT), respectively (see also Table 4).
The absorption maxima and the molar extinction coefficients
are listed in Table 1. The position of the low-energy MLCT
transition at λ2 increases slightly upon moving from 1 to 2, by
about 10 nm, while the higher energy ILCT band at λ1 remains
unchanged. The increase in molar extinction coefficients for
1
2
3
300
300
290
47 717 1413
91 606 657
13 278 370
410
420
400
10 371 550
18 799 818
3527 194
both bands is more pronounced, on moving from the
mononuclear model compound 3 to the metallodendrimers 1
and 2. There is an increase in the molar extinction coefficient
by a factor of ∼3.3, on moving from complex 3 to complex 1. It
further doubles on moving from 1 to 2, which is expected when
comparing the increase in the number of [MnBr-
(bpyCH3,CHN)(CO)3] groups per compound. This confirms
the linear scaling of the optical properties with increasing
dendrimer generation.
To obtain insight into the dark stability and photoinduced
CO-release from compounds 1−3, these complexes were first
incubated in dimethylsulfoxide/water (10:90% v/v) solution in
the absence of light for an extended period of time and then
irradiated with a custom-made LED cluster at 410 nm,
coincident with the MLCT absorption maximum. Irradiations
were interrupted in 1 min intervals to measure UV/vis spectra.
All three compounds showed good dark stability in aqueous
solution for up to 15 h with only negligible spectral fluctuations
observed at around 300 and 410 nm (Figures S15−S20). In
stark contrast, irradiation at 410 nm resulted in a pronounced
decrease of the broad band centered at around 400 nm to
almost zero toward the end of the experiment and a blue-shift
of the peak at around 300 nm. Plateau values were reached after
about 10−15 min with no further spectral changes upon
extended irradiation.
CO-Release Experiments with the Myoglobin Assay.
The CO release from compounds 1−3 was then studied using
the standard myoglobin assay, which is based on the UV/vis
spectroscopic detection of the conversion of deoxyMb to
MbCO (Mb = myoglobin).46,47 However, prior to the
irradiation experiments, the stability of 1−3 in 0.1 M phosphate
buffer (PBS, pH 7.4) under the reducing conditions of the
myoglobin assay was monitored using UV/vis spectroscopy.
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The two metallodendrimers 1 and 2 showed negligible spectral
changes over 12−16 h when monitored at four different
wavelengths in the Q-band region of myoglobin, between 500
and 600 nm (Figures 3 and S21). This indicates that no CO
Figure 4. Change of absorption in the Q-band region of myoglobin
with increasing irradiation time at 410 nm for a solution of dendrimer
(4 μM) in 0.1 M PBS pH 7.4 in the presence of myoglobin (60 μM)
and sodium dithionite (10 mM) under a dinitrogen atmosphere as
monitored by UV/vis spectroscopy.
upon photoactivation (Figure 5) indicates that approximately
eight CO ligands are released per molecule of 1 (Table 2), with
Figure 3. Change of absorption at selected wavelengths with
increasing incubation time in the dark (0 to 16 h) for a solution of
dendrimer 1 (4 μM) in 0.1 M PBS at pH 7.4 in the presence of
myoglobin (60 μM) and sodium dithionite (10 mM) under a
dinitrogen atmosphere as monitored by UV/vis spectroscopy.
release to myoglobin occurs in the dark during this time and is
a good indicator of the suitability of these compounds as
photoactivatable CO-prodrugs. For model compound 3, some
minor fluctuations were observed in the same spectral region
(Figure S22), in particular during the first few hours of
incubation, but since these affected all wavelengths monitored
to the same degree, they are probably rather indicative of some
precipitation due to poor solubility than a general instability of
the compound.
For photoactivation studies, a custom-made LED cluster with
an emission wavelength of 410 nm, matching the MLCT band,
was used. The violet light photoactivation of the present
compounds 1-3 is quite an attractive feature, since most
PhotoCORMs reported to date only show sensitivity to light at
shorter wavelengths (315−365 nm).31,34,48−50 For deep tissue
penetration, an excitation wavelength of larger than 600−700
nm would be ideal, which would also minimize potential
photodamage to healthy cells.51 By suitable modification of the
substituents in the 4-position of the bipyridine ligand, it is
anticipated that the excitation wavelength can be further shifted
toward the red. The photoexcitation at 410 nm leads to
pronounced changes in the Q-band region of the Mb
absorption. The band at 557 nm slowly decreases in intensity
while two new bands at 540 and 577 nm slowly increases in
intensity, which is characteristic for the conversion of deoxyMb
to MbCO (Figures 4 and S23 and S24).
Figure 5. Amount of MbCO in μM formed with increasing irradiation
time at 410 nm for a solution of compound 1 (4 μM) in 0.1 M PBS at
pH 7.4 in the presence of myoglobin (60 μM) and sodium dithionite
(10 mM) under a dinitrogen atmosphere as determined from UV/vis
spectroscopy.
a t1/2 of 14.5 min. Second-generation metallodendrimer 2 (2
μM) released a significantly higher number of CO ligands,
about 15 equivalents (Figure S25), but only shows a marginally
increased half-life of 16.8 min. For the mononuclear model
complex 3 (10 μM), about two CO ligands per molecule were
released upon exhaustive photoactivation (Figure S26, Table
2), with a significantly shortened t1/2 of 7.4 min. The t1/2 in this
study is defined as the time taken for compounds 1−3 to
release 50% of the total CO ligands present per molecule.
While the absolute number of CO ligands liberated from the
molecules increases from about 1.5 to 15.2 when comparing 1−
3, interestingly, the proportional amount of CO released vs the
remaining bound CO stays remarkably constant, with an
average value of ∼65% for the two metallodendrimers (1, 2)
The concentration of MbCO in solution was determined
from the absorption data by application of the Beer−Lambert
law using a molar extinction coefficient for MbCO of λ540 nm
=
15.4 (mM)−1 L−1.52 Since the concentration of deoxyMb has to
be fixed to keep the absorption in the Q-band region <1, an
excess of deoxyMb over the total amount of potentially labile
CO in 1−3 was always maintained. When 4 μM of 1 was added
to 60 μM of deoxy-Mb, the CO-release profile of complex 1
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Table 2. CO-Release and Kinetic Data for Complexes 1−3
a
b
c
c
d
complex conc. of MbCO [μM] half-life, t1/2 [min] rate constant, kCO [s−1
]
equiv. of CO released percentage CO released [%]
quantum yield, Φ410
1
2
3
30.24 0.08
30.47 0.31
20.29 3.03
14.54 0.25
16.84 0.56
7.41 0.24
0.000795
0.000686
7.56 0.02
15.24 0.15
1.51 0.07
63.0
63.5
50.5
(2.66 0.16) × 10−3
(2.71 0.49) × 10−3
0.001558
b
(3.15 0.27) × 10−3
a
c
Determined under the conditions of the myoglobin assay. Determined from UV/vis spectral studies in DMSO/water solution. Per molecule.
d
Calculated using a photon flux of the LED array determined as (9.9 0.4) × 10−9 Einstein·s−1
and ∼51% for the mononuclear complex 3. Thus, under the
conditions of the myoglobin assay, a maximum of two out of
the three CO ligands per metal carbonyl moiety are photolabile.
Furthermore, these data indicate that the CO release from the
different Mn(CO)3 groups in the dendrimers does not seem to
be a cooperative process due to the linear scaling.
Kinetics and Quantum Yield Measurements. The rate
of CO release from compounds 1−3 was determined in
dimethylsulfoxide/water (10:90% v/v) by recording changes in
the electronic absorption spectrum of each compound at
selected wavelengths (1 at 410 nm, 2 at 420 nm, and 3 at 400
nm) during irradiation with a LED array at 410 nm for
predefined time intervals. It follows a pseudo first-order
behavior and is listed in Table 2. All three compounds show
CO-release rates (kCO) comparable to [Mn(tpm)(CO)3]+,32
one of the first PhotoCORMs reported, and relatively faster
rates than other manganese-functionalized CORMs reported so
far.49,53,54 Also, in comparison to other metal carbonyl
complexes such as the iron compound [Fe(CO)(N4Py)]-
(ClO4)2, CO-release rates are comparable.55
The apparent quantum yield of CO release under the
conditions of the myoglobin assay was determined by
ferrioxalate actinometry.56,57 While the values of Φ are
essentially identical for the two dendrimer conjugates 1 and 2
at about 2.7 × 10−3, again indicating that scaling effects do not
play any role in these systems, for the model compound 3, a
slightly larger value of 3.2 × 10−3 was determined. These values
are much lower than reported for other metal carbonyl
complexes by 1 to 2 orders of magnitude.24,49,58 However,
one has to take into account that our experiments were not
carried out in pure solvent, but rather under the conditions of
the myoglobin assay, using an excitation wavelength of 410 nm,
in a spectral region where substantial absorption of the heme
protein leads to considerable inner filter effects.
DFT and TDDFT Calculations. In order to obtain a degree
of insight into the electronic structure of the metal complex
unit and the optical transitions involved in the CO-release
process, DFT and TDDFT calculations were carried out on the
full molecular unit of 3 without any simplification using the
ORCA program package with the RI-BP86 (geometry
optimization and calculation of vibrational frequencies) or
RIJCOSX-B3LYP functionals (TDDFT) and a TZVP basis set
on all atoms in both cases, taking into account the solvent
(water) with the COSMO model. In addition to the structure
of 3 as shown in Scheme 2 with the bromide ligand
perpendicular to the plane of the bipyridine and the three
carbonyl ligands in a facial arrangement (3-A, here termed as
the “axial” isomer), also the two meridional isomers with the Br
group in plane with the bpy ligand (“equatorial”), either trans
to the imine (3-B) or trans to the methyl group (3-C), were
optimized and characterized as minima due to the absence of
imaginary modes in the calculated vibrational spectra. However,
not unexpectedly, the two mer-isomers were higher in energy
compared to the axial one (3-A) by 103 and 107 kJ mol−1 for 3-
B and 3-C, respectively, and thus not further considered
(Figure S27). The calculated bond distances and angles of
[MnBr(bpyR,R′)(CO)3] (3) showed good accordance with the
values of the reported X-ray structures of closely related
complexes [MnX(bpy)(CO)3] with X = Cl and I (Table
S1).59,60 As also observed for other RI-BP86 studies on metal
carbonyl complexes, the calculated Mn−N/C/X bond distances
were too short compared to the X-ray data by about 0.10 Å (or
5.6%) while the CO bond distances were too long by about
0.04 Å (3.3%) and the average deviation in the bond angles of
an order of 0.1° (or 1.3%). However, with an average difference
of 2.6% over all parameters evaluated, the DFT reproduction of
structural data has to be considered as excellent.
The calculated vibrational frequencies showed no imaginary
modes but significantly deviated from the experimental values
and thus were multiplied with a scaling factor of 1.021.61−63
They are collected in Table 3 for all three isomers 3-A/B/C
calculated and compared to the experimental ones.
Table 3. Comparison of Major Experimental and Scaled
Calculated Vibrational Frequencies for 3-A/B/C, Absolute
Values, and Deviation from Experimental Ones in
Parentheses (all in cm−1)
mode
3 exptl.
3-A calcd.
3-B calcd.
3-C calcd.
ν(CHN)
1644
1899
1928
2021
1674 (+30)
1878 (−21)
1882 (−46)
2007 (−14)
1671 (+27)
1882 (−17)
1907 (−21)
2025 (+4)
1675 (+31)
1880 (−19)
1903 (−25)
2022 (+1)
νasym1(CO)
νasym2(CO)
νsym(CO)
The mode at highest wavenumbers, slightly above 2000
cm−1, is assigned to the symmetrical CO stretching vibration
of the fac-Mn(CO)3, moiety while in the 1880−1930 cm−1
range, there are two asymmetrical CO stretches due to the
low symmetry of the compound. The CN stretch of the
imine is found lowest, at around 1660 cm−1. While the latter is
overestimated in the model chemistry used by about 30 cm−1,
the metal−carbonyl CO stretches are mostly underestimated
by around 10 to 50 cm−1, with a somewhat smaller deviation on
the symmetrical compared to the asymmetrical stretch.
However, the calculated values of the vibrations of the three
isomers 3A, 3B, and 3C are all very similar among themselves
and also to the experimental data that one cannot rely on this
type of DFT calculations to assign the kind of isomer present.
The first 45 singlet excited states were then calculated with
TDDFT for the facial isomer 3-A, and the most prominent
states are listed in Table 4.
In line with the presence of a low-spin 3d6 metal center, the
HOMO to HOMO−2 orbitals are mostly of Mn d character,
but with significant admixture from CO π and Br p orbitals.
The HOMO−3 is a bpy-centered π orbital and the HOMO−4/
−5 a mix of bromide p and imine N lone-pair character,
followed by more orbitals of mixed Br/bpy contributions. The
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subsequent decrease in backdonation to the CO π* orbitals and
thus a weakening of the M−CO bond, facilitating CO release
from the metal coordination sphere, as already demonstrated
for other manganese-based PhotoCORMs.64
Table 4. Energies (in nm), Oscillator Strength (fosc), Main
Orbital Contributions, and Type of Transition Involved in
the Most Important Singlet Excitations for 3-A Calculated
with TDDFT
a
b
state
λ nm
fosc
main transitions
type of transition
EXPERIMENTAL SECTION
■
2
4
506.2
441.4
0.1190
0.0535
113→115 (79%)
113→116 (29%)
114→116 (62%)
113→116 (65%)
114→116 (23%)
114→117 (77%)
MLCT Mn→bpy
MLCT Mn→bpy
General Procedures. All organic reactants were purchased either
from Sigma-Aldrich or from Fluka and were used as received unless
otherwise stated. Manganese pentacarbonyl bromide [MnBr(CO)5]
was obtained from Strem Chemicals. 4′-Methyl-2,2′-bipyridine-4-
carboxaldehyde was prepared according to literature methods.65,66
Infrared spectra were recorded either using a Perkin-Elmer Spectrum
100 FT-IR spectrometer using NaCl solution cells in dichloromethane
(L1−L3) or as pure solid samples using a Nicolet 380 FT-IR-
Spectrometer equipped with a SMART iTR ATR unit (1−3).
Intensities of stretching vibrations are marked as strong (s), medium
(m), or weak (w). Elemental analysis (C, H, N) was carried out using
a Thermo Flash 1112 Series CHNS-O Analyzer. HPLC analysis was
done on a Dionex Ultimate 3000 instrument equipped with a ReproSil
100 column (C18, 5 μm, 4.6 mm or 10 mm diameter, 250 mm length)
using a linear gradient of 5−90% acetonitrile/water containing 0.1%
TFA as the eluent over 40 min at a flow rate of 0.6 mL/min for
analytical and 3.0 mL/min for preparative chromatography,
respectively. Nuclear magnetic resonance (NMR) spectra were
recorded on a Varian Unity XR400 spectrometer (1H, 399.95 MHz;
13C{1H}, 100.58 MHz) or a Bruker Avance 500 spectrometer (1H,
500.13 MHz, 13C{1H}, 125.77 MHz) at ambient temperature.
Chemical shifts δ in parts per million indicate a downfield shift
relative to tetramethylsilane (TMS) and were referenced relative to the
signal of the solvent.67 Coupling constants J are given in hertz.
Individual peaks are marked as singlet (s), doublet (d), doublet-of-
doublet (dd), triplet (t), or multiplet (m). Absorption spectra were
measured using an Agilent 8453 UV/vis diode array spectropho-
tometer in quartz cuvettes (d = 1 cm). Electrospray ionization-mass
spectrometry (ESI-MS) was carried out on a Waters Synapt mass
spectrometer. Data were recorded in positive ion mode. Electron
impact mass spectrometry (EI-MS) was carried out on a JEOL
GCmateII mass spectrometer.
5
431.2
0.0829
MLCT Mn→bpy
7
372.5
351.2
343.0
0.0182
0.0178
0.0297
MLCT Mn→bpy
(pyCH3 part)
9
113→117 (75%)
MLCT Mn→bpy
(pyCH3 part)
10
108→115 (67%)
111→115 (27%)
109→115 (23%)
110→115 (53%)
111→115 (38%)
112→117 (84%)
LLCT Br→bpy
(pyimine part)
11
328.7
0.1895
LLCT Br→bpy
c
12
305.6
320.9
0.2189
0.0385
MLCT Mn→bpy
c
13
MLCT Mn→bpy
(pyCH3 part)
a
Only strong transitions with an oscillator strength >0.01 in the 300−
b
c
600 nm range are reported. Only contributions >20% are listed. The
reversed order is due to state 13 experiencing a much smaller solvent
shift than the others.
LUMO to LUMO+2 are bpy π* orbitals, and at even higher
energies, orbitals have a mixed Mn/Br/CO/bpy contribution.
Inspection of the difference densities of states calculated to
be closest to the excitation wavelength of 410 nm (in particular
states 4 and 5) shows that these are mostly of Mn-to-bpy
MLCT character (Figure 6). This should lead to a decrease of
electron density on the metal center in the excited state, with a
Synthesis of Bipyridyl Ligands (L1−L3). A solution of DAB-G1-
PPI-(NH2)4 (0.481 g, 1.51 mmol for L1), DAB-G2-PPI-(NH2)8
(0.822 g, 1.06 mmol for L2), or n-propylamine (0.360 g, 6.08 mmol
for L3) in dichloromethane (10 mL) was added dropwise to a stirred
solution of 4′-methyl-2,2′-bipyridine-4-carboxaldehyde (1.22 g, 6.15
mmol for L1; 1.70 g, 8.56 mmol for L2; 1.21 g, 6.39 mmol for L3) in
dichloromethane (25 mL) and stirred for 48 h (for 1 and 2) or
overnight (for 3) at room temperature (with DAB = 1,4-
diaminobutane, PPI = poly(propyleneimine)). The solvent was then
removed under vacuum conditions to afford a dark yellow oil. This was
dissolved in dichloromethane (30 mL) and washed with copious
amounts of ultrapure water (15 × 30 mL). The organic layer was
separated, dried over sodium sulfate (∼10 g), and filtered. The solvent
was then removed under reduced pressure and the resulting oil dried
in vacuo.
[DAB-G1-PPI-(bpyCH3,CHN)4] L1. Red-brown oil, yield: 1.41 g,
89.5%. IR, NaCl cell, CH2Cl2, v/cm−1: 1648 (s, imine, CN), 1596
1
(s, pyridyl, CN). H NMR (CDCl3): δ (ppm) 1.45 (br m, 4H,
NCH2CH2 core), 1.84 (br m, 8H, NCH2CH2CH2Nbranch), 2.42 (s, 16H,
NCH2CH2core, CH3), 2.52 (br m, 8H, NCH2CH2CH2Nbranch), 3.68 (br
3
m, 8H, NCH2CH2CH2Nbranch), 7.11 (br d, J = 4.8 Hz, 4H, CHbpy),
7.64 (br d, 3J = 5.0 Hz, 4H, CHbpy), 8.21 (br s, 4H, CHbpy), 8.33 (br s,
3
4H, CHimine), 8.51 (br d, J = 4.9 Hz, 4H, CHbpy), 8.56 (br s, 4H,
CHbpy), 8.67 (br d, 3J = 5.0 Hz, 4H, CHbpy). 13C{1H} NMR (CDCl3):
δ (ppm) 21.2 (CH3); 25.3, 28.4, 51.7, 54.1, 59.9 (CH2); 120.5, 120.9,
122.0, 124.9, 149.1, 149.6 (CHpyr); 144.2, 148.1, 155.6, 157.2 (Cpyr);
159.3 (CHimine). Elemental analysis for C64H72N14 (1037.37), found:
C, 73.92; H, 7.11; N, 18.97%. Calcd.: C, 74.10; H, 7.00; N, 18.90%.
MS (HR-ESI-TOF, m/z): 1038.79 [M + H]+.
Figure 6. TDDFT difference densities for the most important singlet
excitations for 3-A in the 300 to 600 nm range. Isosurface values are
plotted at 0.002, with positive values shown in green and negative
ones in red.
[DAB-G2-PPI-(bpyCH3,CHN)8] L2. Red-brown oil, yield: 2.09 g,
88.7%. IR, NaCl cells, CH2Cl2, ν/cm−1: 1648 (s, imine, CN), 1596
5475
dx.doi.org/10.1021/ic400377k | Inorg. Chem. 2013, 52, 5470−5478

Inorganic Chemistry
Article
1
(s, pyridyl, CN). H NMR (CDCl3): δ (ppm) 1.39 (br m, 4H,
54.7, 58.9 (CH2); 121.0, 123.4, 124.1, 127.8, 153.8, 154.3 (CHAr);
145.2, 151.1, 152.8, 156.0 (CAr); 157.8 (CHimine); 220.9, 221.6, 222.9
(CO). HPLC (CH3CN/H2O (gradient, 5−90%, flow rate, 0.6 mL/
min): tR = 23.1 min. MS (HR-ESI-TOF, m/z): 1344.59 [M + 3H]3+.
[MnBr(bpyCH3,CHNCH2CH2CH3)(CO)3] 3. Orange solid, yield: 0.0731 g,
39.1%. IR, ATR, ν/cm−1: 2021 (s, carbonyl, CO), 1928 (s, carbonyl,
CO), 1899 (s, carbonyl, CO), 1644 (m, imine, CN), 1616 (m,
bpy, CN). 1H NMR ((CD3)2SO): δ (ppm) 0.93 (br t, 3J = 6.85 Hz,
3H, NCH2CH2CH3), 1.72 (br m, 2H, NCH2CH2CH3), 2.55 (br s, 3H,
NCH2CH2core), 1.57 (br m, 8H, NCH2CH2CH2Nfirstbranch), 1.83 (br m,
16H, NCH2CH2CH2Nsecondbranch), 2.31 - 2.59 (overlapping m, 60H,
NCH2CH2core, NCH2CH2CH2Nfirstbranch, NCH2CH2CH2Nfirstbranch
NCH2 CH2 CH2 Ns e c o n d b r a n c h CH3 ), 3.65 (br m, 16H,
NCH2CH2CH2Nsecondbranch), 7.09 (br m, 8H, CHbpy), 7.62 (br d,
,
,
3
8H, J = 5.0 Hz, CHbpy), 8.19 (br s, 8H, CHbpy), 8.30 (br s, 8H,
3
CHimine), 8.49 (br d, J = 4.9 Hz 8H, CHbpy), 8.56 (br s, 8H, CHbpy),
8.64 (br d, 3J = 5.0 Hz, 8H, CHbpy). 13C{1H} NMR (CDCl3): δ (ppm)
= 21.1 (CH3); 24.7, 25.2, 28.3, 51.7, 52.3, 53.4, 54.2, 59.9 (CH2);
120.4, 120.9, 121.9, 124.8, 149.0, 149.5 (CHpyr); 144.2, 148.1, 155.6,
157.2 (Cpyr); 159.2 (CHimine). Elemental analysis for C136H160N30
(2214.96), found: C, 73.74; H, 7.58; N, 18.68%. Calcd.: C, 73.75; H,
7.28; N, 18.97%. MS (HR-ESI-TOF, m/z): 560.25 [M + 4H]4+
[bpyCH3,CHNCH2CH2CH3] L3. Dark yellow oil, yield: 0.920 g, 63.2%. IR,
NaCl cells, CH2Cl2, ν/cm−1: 1649 (s, imine, CN), 1596 (s, pyridyl,
CN). 1H NMR (CDCl3): δ (ppm) 0.94 (t, 3J = 7.4 Hz, 3H,
NCH2CH2CH3), 1.73 (m, 2H, NCH2CH2CH3), 2.41 (s, 3H,CH3b3py),
3
CH3bpy), 3.69 (br t, J = 6.23 Hz, 2H, NCH2CH2CH3), 7.58 (br m,
1H, CHbpy), 7.97 (br m, 1H, CHbpy), 8.53 (br s, 1H, CHimine), 8.59 (br
s, 1H, CHbpy), 8.82 (br s, 1H, CHbpy), 9.02 (br m, 1H, CHbpy), 9.25
(br m, 1H, CHbpy). 13C{1H} NMR ((CD3)2SO): δ (ppm) 11.7, 20.6
(CH3); 23.3, 62.5 (CH2); 120.9, 124.0, 124.3, 127.9, 154.1, 154.4
(CHAr); 145.4, 151.3, 152.8, 158.1 (CAr); 158.2 (CHimine); 221.0,
221.7, 222.0 (CO). HPLC (CH3CN/H2O (gradient, 5−90%, flow
rate, 0.6 mL/min): tR = 22.9 min. MS (HR-ESI-TOF, m/z): 462.02
[M+H]+.
3
4
Myoglobin Assay. A solution of horse skeletal muscle myoglobin
in phosphate buffer (PBS, 0.1 M, pH 7.4) was degassed by bubbling
with dinitrogen and reduced by the addition of sodium dithionite (100
mM, 100 μL) in PBS buffer (0.1 M, pH 7.4). A concentrated stock
solution of metal compounds 1, 2, or 3 in dimethylsulfoxide/water
(10:90, v/v) was added, followed by PBS to give a total volume of
1000 μL and final concentrations of 60 μM of myoglobin, 10 mM of
sodium dithionite and 4 μM of 1, 2 μM of 2, or 10 μM of 3. Solutions
were freshly prepared for the dark stability and photoactivation
experiments. Irradiations were carried out under dinitrogen with a
custom-built LED setup at 410 nm (5 mm round type UV-LEDs,
wavelength range 407−412 nm, model YDG-504VC, Kingbright Elec.
Co., Taipei, Taiwan, http://www.kingbright.com, part no. 181000−
05), positioned perpendicular to the cuvette at a distance of 5 cm. The
irradiation was interrupted in 1 min intervals during the initial 10 min,
followed by 2 min intervals for the next 10 min, and then 5 min
intervals to collect UV/vis spectra on an Agilent 8453 UV/vis diode
array spectrophotometer until no more spectral changes were observed
in the Q-band region of myoglobin. Dark control spectra were
automatically collected for an extended period of time set by the
spectrometer software. All irradiation experiments were carried out in
triplicate.
Ferrioxalate Actinometry. Ferrioxalate actinometry was used to
determine the photon flux of the 410 nm LED array because of its
sensitivity, wide spectral range including ultraviolet, and ease of
use.56,57 The entire ferrioxalate actinometry procedure including the
preparation of solutions was carried out under dim red light. The
moles of ferrous iron formed were determined spectrophotometrically
by complexation with 1,10-phenanthroline (phen) to give the colored
tris-phenanthroline complex, [Fe(phen)3]2+ with λmax = 510 nm. In a 1
cm quartz cell, 0.006 M (3 mL) of potassium ferrioxalate in 0.05 M
sulfuric acid as the chemical actinometer was irradiated with a 410 nm
LED array under efficient stirring. A total of 1 ml of this irradiated
solution was mixed with 0.1% 1,10-phenanthroline in water and 0.5
mL of sodium acetate buffer in water (1 M, pH 3.5) and further
diluted to 10 mL by water. A reference was prepared in the same way
except that it was not irradiated. Both solutions were placed in the dark
(about an hour) to allow the complexation to complete. The
absorbance was then measured at 510 nm (ε = 11.100 M−1 cm−1).
A510 was kept within the range of 0.4−1.0. The photon flux of the 410
nm LED array was then calculated by using Φ410 nm = 1.14 following
the equation:68
4.20 (td, J = 6.9 Hz, J = 1.4 Hz, 2H, NCH2CH2CH3), 7.11 (d, J =
2.4 Hz, 1H, CHbpy), 7.67 (dd, J = 5.0 Hz, J = 1.6 Hz, 1H, CHbpy),
3
4
3
8.22 (s, 1H, CHbpy), 8.32 (s, 1H, CHimine), 8.52 (d, J = 5.4 Hz, 1H,
CHbpy), 8.58 (s, 1H, CHbpy), 8.69 (d, 3J = 5.26 Hz, 1H, CHbpy).
13C{1H} NMR (CDCl3): δ (ppm) 11.8, 21.1 (CH3); 23.8, 63.6
(CH2); 120.5, 120.9, 122.0, 124.9, 149.0, 149.5 (CHpyr); 144.3, 148.1,
155.6, 157.2 (Cpyr); 159.1 (CHimine). Elemental analysis for C15H17N3
(239.32), found: C, 75.26; H, 7.19; N, 17.55%. Calcd.: C, 75.28; H,
7.16; N, 17.56%. MS (EI, m/z): 239.28 [M]+.
Synthesis of Mn(CO)3-Functionalized Metallodendrimers
(1−3). A solution of ligand L1 (0.112 g, 0.108 mmol for 1), L2
(0.116 g, 0.053 mmol for 2), or L3 (0.103 g, 0.429 mmol for 3) in
dichloromethane (5 mL) was added dropwise to a stirred suspension
of [MnBr(CO)5] (0.120 g, 0.439 mmol for 1, 0.116 g, 0.423 mmol for
2, and 0.112 g, 0.408 mmol for 3) in dichloromethane (30 mL). The
reaction mixture was stirred overnight at room temperature while
protected from light by wrapping it in aluminum foil, then filtered by
gravity, and the filtrate was reduced to ∼5 mL. The addition of diethyl
ether (for 1 and 2) or n-pentane (for 3) led to precipitation of the
desired product. The solids were filtered, washed with copious
amounts of diethyl ether or n-pentane, and dried under vacuum
conditions. Single crystals of complex 3 were obtained by slow
diffusion of n-pentane into a concentrated dichloromethane solution of
the compound but did not diffract well enough for a good structure
solution due to disorder.
[DAB-G1-PPI-{MnBr(bpyCH3,CHN)(CO)3}4] 1. Yellow-orange solid,
yield: 0.165 g, 79.1%. IR, ATR, ν/cm−1: 2022 (s, carbonyl, CO),
1921 (s, carbonyl, CO), 1905 (s, carbonyl, CO), 1644 (m, imine,
1
CN), 1618 (m, bpy, CN). H NMR ((CD3)2SO): δ (ppm) 1.39
(overlapping m, 12H, NCH2CH2core, NCH2CH2CH2Nbranch), 1.77
(overlapping m, 12H, NCH2CH2core, NCH2CH2CH2Nbranch), 2.36 (br
m, 12H, CH3), 3.69 (br m, 8H, NCH2CH2CH2Nbranch), 7.52 (br m,
4H, CHbpy), 7.89 (br m, 4H, CHbpy), 8.46 (br s, 4H, CHimine), 8.51 (br
s, 4H, CHbpy), 8.76 (br s, 4H, CHbpy), 8.98 (br m, 4H, CHbpy), 9.19
(br m, 4H, CHbpy). 13C{1H} NMR ((CD3)2SO): δ (ppm) 20.6 (CH3);
24.7, 27.8, 50.9, 53.4, 58.9 (CH2); 121.0, 123.5, 124.2, 127.8, 153.9,
154.3 (CHAr); 145.2, 151.2, 152.8, 156.0 (CAr); 158.0 (CHimine);
221.0, 221.7, 222.0 (CO). HPLC (CH3CN/H2O (gradient, 5−90%,
flow rate, 0.6 mL/min): tR = 23.1 min. MS (HR-ESI-TOF, m/z):
961.57 [M + 2H]2+.
[DAB-G2-PPI-{MnBr(bpyCH3,CHN)(CO)3}8] 2. Yellow-orange solid,
yield: 0.139 g, 65.4%. IR, ATR, ν/cm−1: 2022 (s, carbonyl, CO),
1920 (s, carbonyl, CO), 1904 (s, carbonyl, CO), 1644 (m, imine,
ΔA·V·10−3·V
1
1
3
CN), 1619 (m, bpy, CN). H NMR ((CD3)2SO): δ (ppm) 1.23
⌀p =
(overlapping m, 28H, NCH2CH2core, NCH2CH2CH2Nfirstbranch
,
,
⌀ ·ε510·V ·t
λ
2
NCH2CH2CH2Nsecondbranch), 1.38 (overlapping m, 20H, NCH2CH2core
NCH2CH2CH2Nfirstbranch, NCH2CH2CH2Nfirstbranch), 1.71 (br m, 16H,
NCH2CH2CH2Nsecondbranch), 2.42 (br m, 24H, CH3), 3.63 (br m, 16H,
NCH2CH2CH2Nsecondbranch), 7.48 (br m, 8H, CHbpy), 7.84 (br m, 8H,
CHbpy), 8.43 (br m, 16H, CHimine, CHbpy), 8.69 (br s, 8H, CHbpy), 8.95
(br m, 8H, CHbpy), 9.14 (br m, 8H, CHbpy). 13C{1H} NMR
((CD3)2SO): δ (ppm) 20.6 (CH3); 24.2, 24.9, 27.8, 51.0, 51.5, 53.8,
Density Functional Theory Calculations. DFT calculations
were carried out on the Linux cluster of the Leibniz-Rechenzentrum
(LRZ) in Munich with ORCA version 2.8,69 using the BP86 functional
with the resolution-of-the-identity (RI) approximation, a def2-TZVP/
def2-TZVP/J basis set,70,71 the tightscf and grid4 options, and the
COSMO solvation model with water as the solvent for geometry
5476
dx.doi.org/10.1021/ic400377k | Inorg. Chem. 2013, 52, 5470−5478

Inorganic Chemistry
Article
optimizations and subsequent calculation of vibrational frequencies to
characterize the structures obtained as minima by inspection for the
absence of imaginary modes. The TDDFT calculations employed the
B3LYP functional with the same basis set and settings as above using
the RIJCOSX keyword. The first 45 singlet excited states were
calculated (nroots 45).
ACKNOWLEDGMENTS
■
Financial support from the University of Cape Town (UCT),
the National Research Foundation of South Africa (NRF), the
South African Medical Research Council (MRC), the
Deutscher Akademischer Austausch Dienst (DAAD), and the
Bundesministerium fur Bildung und Forschung (BMBF, project
̈
SUA 10/029) is gratefully acknowledged for several short term
exchange visits between the two laboratories. Even though this
work is supported by the MRC, the views and opinions
expressed are not those of the MRC but of the authors of the
material produced or publicized. We would like to thank Mr.
Wolfgang Obert from the electronics workshop of the Institut
CONCLUSION
■
In the present paper, first- and second-generation polypyridyl
dendritic ligands were synthesized and fully characterized.
Subsequent complexation of the 2,2′-bipyridine dendritic
ligands to manganese pentacarbonyl bromide gave metal-
lodendrimers with four and eight [MnBr(bpyCH3,CHN)(CO)3]
end groups. In addition, a mononuclear model complex was
prepared for comparison. All three manganese compounds are
stable in solution and in the air for an extended period of time
in the absence of light. However, upon photoactivation at 410
nm using a custom-made LED light source, CO-release studies
with the myoglobin assay showed that at least two of the three
carbonyl ligands per Mn(CO)3 moiety can be liberated under
these conditions. The half-life and quantum yield of CO release
were also similar for the first- and second-generation metal-
lodendrimers, indicating that no scaling effects are operative in
these systems and that each [MnBr(bpy)(CO)3] end group
behaves independently from the others. The total amount of
CO-released per molecular unit, on the other hand, of course
increases with the dendrimer generation, reaching a value of 15
CO per molecule of the second-generation metallodendrimer.
In addition, the electronic structure and main transitions
thought to be involved in the photoinduced CO release have
been studied for the model compound using DFT/TDDFT. In
summary, we have successfully attached an increasing number
of CORM groups to dendrimer carrier molecules and will now
further investigate their biological activity in cellular systems.
fur Anorganische Chemie of the Universitat Wurzburg for the
̈
̈
̈
expert construction of the LED setup.
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ASSOCIATED CONTENT
■
S
* Supporting Information
1H NMR (6 figures), 2D-COSY NMR (1 figure), 13C{1H}-
NMR (3 figures) and HR-ESI-TOF (2 figures) spectra of
ligands and complexes, IR spectra showing decrease of the
metal−carbonyl bands for 2 and 3 upon extended exposure to
daylight (2 figures), UV/vis spectral traces showing dark
stability and photolysis of 1−3 in dimethylsulfoxide/water
solution (3 figures), change of absorption at selected
wavelengths for dark stability and photolysis of 1−3 under
the conditions of the myoglobin assay (3 figures), expanded
dark stability experiments for 2 and 3 under the conditions of
the myoglobin assay (2 figures), spectral changes in the Q-band
region of myoglobin upon photoactivation of 2 and 3 (2
figures), formation of MbCO with increasing photoactivation
time of 2 and 3 (2 figures). DFT-optimized geometries of 3-A
to 3-C (1 figure and 3 tables) and comparison with published
data (1 table). This material is available free of charge via the
Internet at http://pubs.acs.org.
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̈
AUTHOR INFORMATION
■
(21) Romanski, S.; Rucker, H.; Stamellou, E.; Guttentag, M.;
Neudorfl, J.-M.; Alberto, R.; Amslinger, S.; Yard, B.; Schmalz, H.-G.
̈
Corresponding Author
*E-mail: ulrich.schatzschneider@uni-wuerzburg.de; gregory.
smith@uct.ac.za.
̈
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Notes
The authors declare no competing financial interest.
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