Luminescent PhotoCORMs: Enabling/Disabling CO Delivery upon Blue Light Irradiation

Article abstract of DOI:10.1021/acs.inorgchem.0c00638

The new luminescent carbonyl compounds [Mn(Oxa-H)(CO)3Br] (1) and [Mn(Oxa-NMe2)(CO)3Br] (2) were synthesized and fully characterized. Complexes 1 and 2 showed CO release under blue light (λ453). Spectroscopic techniques and TD-DFT and SOC-TD-DFT calculati

Full text of DOI:10.1021/acs.inorgchem.0c00638

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Luminescent PhotoCORMs: Enabling/Disabling CO Delivery upon
Blue Light Irradiation
́
Vitor C. Weiss, Giliandro Farias, Andre L. Amorim, Fernando R. Xavier, Tiago P. Camargo,
Mayana B. Bregalda, Matti Haukka, Ebbe Nordlander, Bernardo de Souza, and Rosely A. Peralta*
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ABSTRACT: The new luminescent carbonyl compounds [Mn-
(Oxa-H)(CO)3Br] (1) and [Mn(Oxa-NMe2)(CO)3Br] (2) were
synthesized and fully characterized. Complexes 1 and 2 showed
CO release under blue light (λ453). Spectroscopic techniques and
TD-DFT and SOC-TD-DFT calculations indicated that 1 and 2
release the Oxa-H and Oxa-NMe2 coligands in addition to the
carbonyl ligands, increasing the luminescence during photo-
induction.
In recent years, the development of luminescent photo-
CORMs has emerged as a possible clinical procedure because
of its ability to monitor the release of CO at desired targets.
The general formula of such complexes is [MX(CO)3(β-
diimine)], where M = Re(I) or Mn(I), X is an anion or a
monodentate ligand in the axial position, and β-diimine is a
bidentate ligand such as bipyridine (bpy), 1,10-phenanthroline
(phen), or 2-(2-pyridyl)benzothiazole (pbt).27 These com-
plexes can also exhibit emissive properties associated with the
emission from a singlet or triplet MLCT excited state involving
the metal and the axial ligand X, the β-diimine ligand(s), or
released aromatic ligands.27 This emission allows the complex
to be traceable before and/or after CO release.28
A promising way to monitor intracellular CO release to a
specific target is to measure the luminescence of a photo-
CORM before or after release, or even at both stages. This
technique was studied by Chakraborty and co-workers using
Re(I) photoCORMs (ReX(CO)3(phen)]0/1+, where X = Cl−,
PPh3, or methylimidazole).24 Each of these Re(I) compounds
exhibits an emission, before CO release, in the range 500−620
nm and releases CO in the presence of low power UV light (5
mW cm−2 centered at 302 nm). These species hold significant
promise as theranostic photoCORMs where the prodrug entry
INTRODUCTION
■
Carbon monoxide (CO) administration in patients has been
recognized as a new therapeutic application due to its potential
activity against inflammatory and/or vascular diseases, sickle
cell disease, malaria, diabetes, and acute hepatitis,1 as well as
showing interesting properties for the treatment of infectious
diseases. More recently, CO has been studied as a potential
antitumor agent.2 However, to date, the CO administration
occurs in the gaseous form, which makes storage and
administration in controlled quantities difficult. This limits
the use of this method in the medical context, since high
concentrations of CO are toxic due to its high affinity for
hemoglobin.3−6 One way to overcome these disadvantages is
the use of molecular carriers that act as prodrugs and can carry
carbon monoxide to the body in a controlled manner, releasing
CO only under the influence of a specific trigger.6−8
Several carriers based on organic compounds9,10 or
transition metals, such as tungsten, molybdenum, iron,
ruthenium, rhenium, and manganese,11−20 have been used to
deliver CO to the organism, the latter being preferred due to
the high flexibility in terms of the properties obtained from
both the metal center and the organic framework.21 Correct
selection of these properties is essential in the development of
new metal carbonyl compounds (MCCs),22 which should
preferentially be water-soluble.23,24 Photoactivation of the
MCCs seems to be the most attractive trigger, considering the
temporal and spatial control of the carbon monoxide release.
Metal carbonyl compounds that fall into this category are
called photoCORMs (photoinduced CO-releasing mole-
cules).25,26
Received: February 28, 2020
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can be tracked within the cellular matrixes using confocal
microscopy.24
(Oxa-H), and compound 2 was synthesized using the ligand
2-(4-dimethylamino-phenyl)-5-(2-pyridinyl)-1,3,4-oxadiazole
(Oxa-NMe2). The complexes were characterized using IR,
UV−vis, and NMR spectroscopies, electrochemistry, and, in
the case of 1, single crystal X-ray diffraction. The stability of
the complexes and the CO release under light irradiation were
monitored using an array of techniques. Density functional
theory (DFT) and SOC-TD-DFT (SOC = spin orbit
coupling) calculations were performed to give further insights
into the CO release mechanism.40
Mascharak’s group recently conducted a study on the
eradication of HT-29 human cells from colorectal adenocarci-
noma by releasing carbon monoxide from a green luminescent
Mn photoCORM, ([Mn(CO)3(phen)(Pipdansyl)](CF3SO3),
Pipdansyl = 1-dansylpiperazine), which maintains its lumines-
cence even after CO release.29 Luminescence before and after
CO release was of great importance because the compound
can be visualized by confocal microscopy, allowing a greater
precision in the CO distribution in cells.
Despite recent advances, researchers are seeking to
synthesize carbonyl compounds that can release CO molecules
at wavelengths closer to the visible region30−39 in addition to
being less cytotoxic, focusing on their medicinal applications.
In this context, we report herein two new manganese
photoCORMs, [Mn(Oxa-H)(CO)3Br] (1) and [Mn(Oxa-
NMe2)(CO)3Br] (2) (Chart 1), that have the required
EXPERIMENTAL SECTION
■
Synthesis and Characterization. All chemical reactions were
carried out under an inert atmosphere (argon) using standard Schlenk
techniques. The solvents were purified and dried over molecular
sieves (4 Å) for 72 h prior to use. The starting complex
[Mn(CO)5Br] and the solvents used are commercially available and
were used without further purification, unless otherwise stated.
All ligands used were synthesized (Scheme 1A and B), purified, and
characterized (Figures S1−S6), as described in the Supporting
Information. The organometallic carbonyl compounds were synthe-
sized (Scheme 1C) under dim light conditions and an inert
atmosphere by adding [Mn(CO)5Br] (0.3 mmol, 82.4 mg) to a
frozen CH3CN solution (10 mL) of the ligands (0.3 mmol) in a
Schlenk flask. After reaching ambient temperature, the resulting
solutions were refluxed for 12 h. After this time, the resulting mixtures
were cooled to room temperature and the precipitates were collected
by vacuum filtration and washed three times with cold CH2Cl2,
resulting in the formation of an orange powder for 1 and 2. Infrared
spectroscopy (vide infra) indicated that only the facial isomers, as
depicted in Chart 1, were formed. Orange crystals of 1 were obtained
by slow evaporation from CH3CN solutions at 20 °C.
Chart 1. Schematic Representation of the Mn(I) Carbonyl
Compounds [Mn(Oxa-H)(CO)3Br] (1) and [Mn(Oxa-
NMe2)(CO)3Br] (2)
properties for carbonyl-containing prodrugs, such as CO
release under blue light (λ453) and fast CO release rates. We
also report some mechanistic insights into the carbon
monoxide release process. Compound 1 was synthesized
using the ligand 2-phenyl-5-(2-pyridinyl)-1,3,4-oxadiazole
[Mn(Oxa-H)(CO)3Br] (1): Bright orange solid, 440.92 g mol−1.
Yield: 72%. Selected IR frequencies (ATR, cm−1): 3032−2851 (ν,
CHAr); 2036, 1947, 1930 (ν, CO); 1610 (ν, CCAr). Selected
electronic absorption wavelengths (CH3CN, λmax in nm) and
respective ε values (L mol−1 cm−1): 254 (19466); 369 (2045); 428
Scheme 1. Schematic Representations of the Syntheses of Ligands Oxa-H (A) and Oxa-NMe2 (B) and the Metal Carbonyl
Compounds 1 and 2 (C)
B
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(2134). Elemental analysis for C16H9BrMnN3O4 (calculated values in
parentheses): C, 43.49 (43.47); H, 1.51 (2.05); N, 9.73 (9.50). H
the samples to be irradiated was inserted and subsequently covered,
with the time of exposure to light being computationally controlled.
The light source employed to perform the CO release assays was
1
NMR (400 MHz, DMSO-d6, δ, ppm): 7.75 (dt, J = 14.8; 7.2 Hz 3H);
7.90 (t, J = 6.6 Hz, 1H); 8.25 (d, J = 7.5 Hz 2H); 8.38 (t, J = 7.8 Hz
1H); 8.49 (d, J = 7.8 Hz 1H); 9.29 (d, J = 5.4 Hz 1H). 13C NMR
(100 MHz, DMSO-d6, δ, ppm): 122.2; 124.9; 127.8; 129.2; 130.3;
137.1; 140.6; 141.9; 155.8; 163.71; 166.9; 223.8 (CO).
[Mn(Oxa-NMe2)(CO)3Br] (2): Bright orange solid, 483.96 g
mol−1. Yield: 69%. Selected IR frequencies (ATR, cm−1): 3062−2924
(ν, CHAr); 2036, 1951, 1924 (ν, CO); 1600 (ν, CCAr).
Selected electronic absorption wavelength (CH3CN, λmax in nm) and
its respective ε value (L mol−1 cm−1): 318 (18474); 384 (22051).
Elemental analysis (C18H14BrMnN4O4), Found (calculated): C, 44.28
(44.56); H, 2.96 (2.91); N, 10.77 (11.55). 1H NMR (400 MHz,
DMSO-d6, δ, ppm): 3.09 (s, 6H); 6.93 (d, J = 8.5 Hz, 2H); 7.84 (t, J =
6.4 Hz, 1H); 8.00 (d, J = 8.5 Hz, 2H); 8.36 (dd, J = 20.5 Hz, 7.7 Hz,
2H); 9.24 (d, J = 5.2 Hz, 1H). 13C NMR (100 MHz, DMSO-d6, δ,
ppm): 40.0; 107.9; 112.1; 124; 129.1; 140.2; 141.9; 153.5; 155.2;
162; 167.8; 219.9 (CO); 222.3 (CO); 223.7 (CO).
one set with four LEDs in series, with the following wavelength: λ453
=
453 9 nm (photon flux = 1.03 × 10−8 Einstein s−1). The distance
between the analyte and the lamp was set at 3.0 cm, where the light
source was arranged perpendicularly to the sample. The CO release
rates for compounds 1 and 2 were determined by monitoring the
decrease of the charge transfer band for each compound. The
ferrioxalate actinometry assay14 was used to determine the photon
flow of the light source used, and the myoglobin assay14 (described in
the Supporting Information) was used to determine the number of
equivalents of CO released by 1 and 2 during photoinduction
processes.
RESULTS AND DISCUSSION
Crystal Structure and IR Spectroscopy. The molecular
structure for compound 1 is shown in Figure 1. The crystal
■
Physical Measurements. UV−vis spectroscopy and kinetic
measurements were performed on a Varian Cary 50 UV/vis
spectrophotometer equipped with an 18-position thermostated cell
changer. Infrared spectra were collected on a PerkinElmer
Spectrum100 FTIR spectrometer for solid KBr discs and a Digilab
Excalibur FTIR spectrometer equipped with an Axiom Analytical
DPR 210 dipper system and an MCT detector for liquid samples.
Emission spectra were obtained in solution on a Varian Cary
Eclipse fluorescence spectrophotometer. Analyses were performed
using concentration solutions in the range of 10−5−10−6 mol L−1 in
spectroscopic grade CH3CN and quartz cuvettes with a capacity of 3.0
mL and 1.00 cm optical path at 25 1 °C.
NMR spectra were collected on a Varian Inova 400 MHz
spectrometer in CDCl3 as solvent and referenced to the residual
solvent signal, and the chemical shifts are reported in parts per
million. The redox behavior of the title compounds was investigated
in aerobic acetonitrile solution by cyclic voltammetry using a BASi
model Epsilon potentiostat/galvanostat. Tetrabutylammonium hexa-
fluorophosphate [n-Bu4N](PF6) was used as a supporting electrolyte,
and the measurements were carried out using a 3 mm diameter
Teflon-shrouded glassy carbon working electrode, a Pt wire auxiliary
electrode, and a Ag/Ag+ reference electrode. For correction of the
reference electrode, the ferrocene/ferrocenium pair (Fc/Fc+) was
used (E1/2 vs NHE = 400 mV).41
The X-ray diffraction data were collected on a Nonius Kappa CCD
diffractometer using Mo Kα radiation (λ = 0.71073 Å). The crystals
of 1 were immersed in cryo-oil, mounted in a Nylon loop, and
measured at a temperature of 120 K. The Denzo-Scalepack42 program
package was used for cell refinements and data reductions. The
structures were solved by direct methods using the SIR97,43
SIR2004,44 or SHELXS-9745 programs with the WinGX46 graphical
user interface. A semiempirical absorption correction (XPREP in
SHELXTL,47 SORTAV,48 or SADABS49) was applied to all data.
Structural refinements were carried out using SHELXL-97.45 Other
hydrogens were positioned geometrically and constrained to ride on
their parent atoms, with C−H = 0.95−1.00 Å and Uiso = 1.2−1.5Ueq
(parent atom). The crystallographic details are summarized in the
Supporting Information (Tables S1−S7).
CO Release Assay. First, the stabilities of the organometallic
compounds were determined, monitoring the charge transfer bands
over a 16 h period in the absence of light. The compounds were
dissolved in CH3CN with concentrations of 1.00 × 10−3 mol L−1 and
further diluted so that the initial absorbance was below 1.0.
All CO release studies were carried out on acetonitrile solutions of
compounds 1 and 2 under light exposure, unless stated. The CO
photorelease was investigated by IR, UV−vis, and NMR spectros-
copies and electrochemistry. For each analysis, solutions of
appropriate concentrations were always prepared in the absence of
light and in an inert atmosphere. For the application of electro-
magnetic radiation, a box was used where a quartz cuvette containing
Figure 1. Molecular structure of compound 1. Thermal ellipsoids are
shown at the 50% probability level. Selected bond lengths (Å) and
angles (deg): Br(1)Mn(1) = 2.5329(3), Mn(1)C(2) = 1.807(2),
Mn(1)C(3) = 1.808(2), Mn(1)C(1) = 1.820(2), Mn(1)N(2)
= 2.0202(16), Mn(1)N(1) = 2.0877(16); C(2)Mn(1)C(1) =
91.01(9), N(2)Mn(1)N(1) = 77.91(6), C(3)Mn(1)Br(1)
= 178.77(7).
structure of the Re analogue of 1, [Re(CO)3(Oxa-H)Br]·
CH2Cl2,50 has been reported previously. Both compounds
have a distorted octahedral coordination mode with the three
CO ligands arranged in a fac-coordination and the N2-donor
ligand binding in a bidentate coordination mode. Compared to
similar compounds reported in the literature, compound 1 has
a Mn(1)−Br bond length (2.5329(3) Å) that is very similar to
those found for the complexes [MnBr(CO)3(pbt)]
(2.5254(15) Å),51 [MnBr(CO)3(phS-κ2S)] (2.5288(4) Å),52
[MnBr(CO)3(phSe-κ2Se)] (2.5280(6) Å),52 and [MnBr-
(CO)3(bzlSe-κ2Se) (2.5344(8) Å),52 where pbt = 2-(2-
pyridyl)benzothiazole), phS-κ2S = bis(2-(phenylthio)ethyl)-
amine, phSe-κ2Se = bis(2-(phenylselanyl)ethyl)amine, and
bzlSe-κ2Se = bis(2-(benzylselanyl)ethyl)amine. The Mn(1)−
C and Mn(1)−(N) bonds are also comparable to the
compounds cited above. The Mn(1)−C bonds (1.820(2),
1.807(2), and 1.808(2)) are shorter than Mn(1)−N
(2.087(16) and 2.020(16)) bonds due to the strong π-
backbonding to the carbonyl ligands. The bond lengths for
50
[Re(CO)3(Oxa-H)Br]·CH2Cl2 are larger than the ones
found for 1an effect of the larger ionic radius of Re(I)
compared to Mn(I).
The infrared results (Figures S7 and S8 for 1 and 2,
respectively) corroborate the facial ligand arrangement, since
their symmetry resembles that of a C3v point group, displaying
two intense vibrational stretching bands, around 2050 and
C
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1900 cm−1. The former is associated with the symmetrical CO
stretching, and the latter is attributed to the two non-
degenerate asymmetrical CO stretching bands, which are
directly influenced by the symmetry of the compounds. Since
the infrared spectra of 1 and 2 are very similar, containing
slight changes in the wavelengths of absorption due to the
NMe2 substituent in 2, it is proposed that compounds 1 and 2
have similar structures. Table 1 shows selected IR bands for
compounds 1 and 2 and Oxa-H and Oxa-NMe2 ligands.
three intense bands at 284 nm (ε 19466 L mol−1 cm−1), 369
nm (shoulder), and 428 nm (ε 2045 L mol−1 cm−1);
compound 2 shows two intense bands at 318 nm (ε 18474
L mol−1 cm−1) and 384 nm (ε 22051 L mol−1 cm−1),
respectively.
The low energy band at 428 nm for 1 is likely to arise from a
MLCT (metal(dπ) → Oxa-H(π*)) transition, with consid-
erable XLCT (halide(p) → Oxa-H(π*)) contribution. On the
other hand, for complex 2, the lowest energy band 384 nm is
attributed to a mixed π−π* transition of the dimethylamine
group, together with a MLCT transition. This increases the
molar absorptivity relative to 1 and decreases when compared
Table 1. Selected IR Bands (ATR) of Compounds 1 and 2
and the Oxa-H and Oxa-NMe2 Ligands
to the free Oxa-Me2 ligand (ε = 33500 L mol−1 cm−1).53
A
assignments
Oxa-H
1
Oxa-NMe2
2
similar redshift and decrease of the molar absorptivity for Oxa-
Me2 complexes was reported by Li and co-workers.53 Also, for
complex 2, the second intense band at 318 nm is attributed to
a π−π* transition. The transitions located in the higher energy
region are attributed to the internal ligand transitions for both
complexes.
νCHar
νCCar
νCO
3050−2840 3032−2851
1586−1546 1610
3093−2810 3062−2851
1612−1564 1607
2038, 1957,
1929
2030, 1922,
1896
νCNar
1248
1080
1203
1088
The fine-tuning of these assignments can be rationalized
based on DFT and TD-DFT studies. In the first step, DFT
optimization of the structures of the complexes was performed,
starting from the X-ray coordinates. The optimized structures
of 1 and 2 agree well with respect to bond lengths and angles
based on the structure of 1, as listed in Table S8. Next, TD-
DFT calculations were performed to access information related
to the excited states. The calculated absorption spectrum is
shown for each molecule in Figure 2, along with the
experimental results. The computed frontier orbitals for each
complex are shown in Figure 3. Table S9 displays some of the
most intense calculated transitions, with the corresponding
largest excitation amplitudes.
Spectroscopic Properties and Theoretical Modeling.
Absorption spectra of complexes 1 and 2 were recorded in
acetonitrile and are shown in Figure 2a. Compound 1 presents
For compound 1, analysis of the TD-DFT results suggests
that the lowest energy absorption at 428 nm has its origin from
Figure 2. (a) Absorption spectra of 1 and 2 in acetonitrile solution.
Experimental absorption spectra of 1 (b) and 2 (c) in CH3CN and
the theoretical absorption spectra obtained within the PBE0, ZORA-
def2-TZVP(-f) level of theory; the spectra are convoluted with
Gaussians of 0.25 eV width. The theoretical absorption for 2 was red-
shifted by 0.47 eV to match the experimental data.
Figure 3. Calculated frontier orbitals for complexes 1 and 2.
D
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Figure 4. Monitoring of absorption over 16 h in the absence of light for solutions of 1 and 2. (a) [1] = 3.6 × 10−4 mol L−1 in acetonitrile, (b) [2] =
4.1 × 10−5 mol L−1 in acetonitrile, (c) [1] = 3.3 × 10−5 mol L−1 in dichloromethane, and (d) [2] = 5.7 × 10−5 mol L−1 in dichloromethane. The
insets show the infrared (KBr) spectra for each solution of the compounds.
a mixed HOMO → LUMO (70%), HOMO−1 → LUMO
(11%), and HOMO → LUMO+3 (12%) transition. The
HOMO and HOMO−1 of these complexes are predominantly
π(metal−CO) and p(Br) with bonding character, while the
unoccupied orbitals are composed of π* spread mainly
throughout the pyridine and the oxadiazole moieties and π*
Mn−CO orbitals (Figure 3). For compound 2, the lowest
energy band has a major contribution mostly from two
excitationsa mixed HOMO → LUMO (63%) and HOMO−
1 → LUMO (24%)and from a mixed HOMO → LUMO
(34%), HOMO−1 → LUMO (45%), and HOMO−1 →
LUMO+3 (15%) transition, while the band centered at 318
nm arises mostly from a HOMO → LUMO+1 (75%). In that
case, the HOMO is π spread mainly throughout the benzene
ring with a contribution of a nonbonding orbital centered at
the amine, while the lower energy occupied orbitals (HOMO−
1 and HOMO−2) and the unoccupied orbitals are similar to
those frontier orbitals of complex 1.
We can conclude that, however structurally similar, these
complexes present low-lying excited states of different
character. 1 has a mixture of a π−π*-like state around the
metal−CO bonds and a MLCT, with some extent of transfer of
electron density from the metal−CO system to the chelate
ring; 2 has a strong π−π*-like character over the chelating
ligand, with a contribution of the transitions predicted for
complex 1.
center, making it difficult to stabilize higher oxidation states. In
addition, upon oxidation to Mn(II), it is expected that the
coordinated carbonyl groups will be released from the metal
centers, altering the structure and electronic configuration of
the metal center from low to high spin, causing chemical
irreversibility of these redox processes.54 Similar results were
observed by Pordel and White for the compounds fac-
[Mn(dmebpy)(CO)3Br],55 fac-[Mn(bpy)(CO)3Br],55 and
fac-[Mn(Me2bpy)(CO)3Br]55 that show only one anodic
process attributed to the MnI/II redox couple at 983, 933,
and 833 mV vs NHE (original potentials corrected from Ag/
AgCl to NHE for clarity), where dmebpy = 4,4′-dimethylester-
2,2′-bipyridine, bpy = 2,2′-bipyridine, and Me2bpy = 4,4′-
dimethyl-2,2′-bipyridine.
Stability Studies in Solution. Before studying the CO
photorelease process of compounds 1 and 2, the stability of
both in the absence of electromagnetic radiation was evaluated
via UV−vis spectroscopy in acetonitrile solution by monitoring
the MLCT bands for 16 h in the absence of light. As shown in
Figure 4a and b for 1 and 2, respectively, during this time,
significant spectral changes were observed for both com-
pounds. This may occur due to the substitution of the bromide
present in the first coordination sphere by a coordinating
solvent. Thus, to investigate whether both compounds exhibit
solvatochromism and to obtain more information about these
spectral changes in acetonitrile, and to verify their stability in
the absence of light, the UV−vis spectra of 1 and 2 in
dichloromethane (usually a noncoordinating solvent) were also
followed over a 16 h time period, as shown in Figure 4c and d.
Also, the IR spectra of both complexes were obtained at zero
time and after 16 h under no light in the same solvents,
acetonitrile and dichloromethane.
Electrochemical Properties. The cyclic voltammograms
of compounds 1 and 2 (Figures S9 and S10) showed only one
electrochemically irreversible process at 1089 and 1112 mV
relative to NHE for 1 and 2, respectively, assigned to the MnI/II
redox pairs for 1 and 2. The high oxidation potentials of these
compounds are linked to the presence of the strong π-acceptor
CO groups, which decrease the electron density at the metal
E
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Figure 5. Changes in the infrared spectra of 1 (left) and 2 (right) caused by CO released during λ453 excitation, in acetonitrile solution.
For 1, the initial absorption spectra in acetonitrile and
dichloromethane (Figure 4a and c, respectively) are quite
similar, with the only difference being the shift of the λmax from
428 nm in acetonitrile to 446 nm in dichloromethane. After 16
h of spectral monitoring in the absence of light, in
dichloromethane, the absorption bands do not change
significantly, with only a small increase in absorbance due to
solvent evaporation. On the other hand, in acetonitrile, a
pronounced spectral change was observed, with the formation
of an isosbestic point, indicating the formation of a new species
in solution. The absorption spectra of 2 in different solvents
(Figure 4b and d, respectively) show partially different profiles
even at initial times. In acetonitrile, it is possible to identify two
intense bands at 318 and 384 nm, while in dichloromethane,
they were shifted to 330 nm (as a shoulder) and 396 nm. After
16 h in dichloromethane, the absorption bands of 2 do not
change significantly, while in acetonitrile the band at 384 nm
decreases and the band at 318 nm increases in intensity with
the formation of isosbestic points, also indicating the formation
of a new species in solution.
Similar to the absorption spectra, in dichloromethane and in
the absence of light, the infrared spectra of both compounds
(insets in Figure 4c and d, respectively) showed no changes in
the vibrational stretches of CO, either in energy or intensity
during the same analysis period. In acetonitrile, it is possible to
observe that after 16 h the IR spectra of both complexes show
the formation of a new signal of lower intensity (insets in
Figure 4a and b, respectively) corresponding to a symmetrical
vibrational stretching mode of CO at a slightly higher
frequency.
These results are strong indications that, in the absence of
light in dichloromethane solution, a noncoordinating solvent,
the structures of compounds 1 and 2 are kept unchanged in a
distorted C3v symmetry without carbon monoxide release and
with the bromide coordinated to the metallic center. On the
other hand, in the absence of light and in acetonitrile
solutiona potentially coordinating solventthe coordinated
bromide is being replaced by a solvent molecule, with no
concomitant release of CO, forming a [Mn(L)(CO)3(S)]Br
species in solution, also with distorted C3v symmetry, where S
is the solvent, as seen by the new CO stretching band. For 2, it
seems that only minor replacement of the bromide is observed
over the 16 h incubation period, as seen by the minor
broadening of the symmetrical CO stretching bands compared
to 1.
undergoes minimal ligand dissociation, which is supported by
the increase of the MLCT around 340 nm (Figure 4). Similar
behavior was observed by Amorim and co-workers for the
compounds [MnBr(CO)3(phS-κ2S)],52 [MnBr(CO)3(phSe-
κ2Se)],52 and [MnBr (CO)3(bzlSe-κ2Se)]52 and by Gonzalez
and co-workers for the compound [Mn(pqa)(CO)3]+,56 who
also demonstrated coordinated bromide replacement to the
metallic center by solvent molecules during incubation in the
absence of light.
Despite the replacement of the coordinated bromide to the
metal center by solvent molecules, the infrared spectra in
acetonitrile solutions of 1 and 2 were virtually unchanged
concerning the asymmetric carbonyl stretching area after 16 h,
indicating that these compounds are stable with respect to CO
release in the absence of light.
Even though the title compounds undergo changes in the
coordination sphere during the incubation period, it is a slow
process and only detrimental for compound 1 after 4 h of
incubation, so by using fresh solutions the coexistence of the
initial species [Mn(L)(CO)3(Br)] and the solvent bound
[Mn(L)(CO)3(S)]Br in the solution may be circumvented,
since CO photolysis is fast. The CO photorelease studies for
these compounds were all investigated in acetonitrile solution,
as it is a coordinating solvent similar to water.
CO Release Study. Initial tests of the CO photorelease
were performed in several light sources for complexes 1 and 2.
A wavelength 453
9 nm LED array was chosen for the
photorelease study, as it is closer to the experimental MLCT
inflection point for these compounds and is also a blue color
LED, a region in the visible region, and less harmful to living
organisms. It is important to observe that during the periods
used for the photorelease assays there were no spectral changes
in the absence of light (vide supra).
Changes in the CO stretch signals for compounds 1 and 2
during exposure to electromagnetic radiation at 453 nm were
monitored by IR spectroscopy and are presented in Figure 5.
After a short time of light exposure (about 20 s for 1 and 50 s
for 2), it is possible to observe the emergence of new bands at
lower frequencies associated with the asymmetric CO
stretching of a biscarbonyl intermediate, and considering that
no decay of these biscarbonyl intermediates is detected, it is
feasible to believe that they are stable (for a few minutes) even
under aerobic conditions, as found by other authors.57
After 200 and 280 s of light exposure for 1 and 2,
respectively, the bands for the biscarbonyl intermediate reach
their maximum intensities and start to decrease until they are
almost completely gone, being a strong indication that all CO
groups are released during the photoexcitation process. As
expected, upon exposure to light, the CO stretch bands located
These stability studies in acetonitrile solutions indicate that
1 undergoes substitution of the bromide at a faster rate than 2,
as can be seen by the spectral changes of the MLCT and
symmetric stretching frequencies over time, and that 2
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Figure 6. Changes in the oxidation potentials in cyclic voltammograms of 1 (left) and 2 (right) caused by CO release during excitation with λ453
.
Working electrode, platinum; reference, Ag/Ag+; auxiliary electrode, platinum wire; supporting electrolyte, [NBu4](PF6) = 0.1 mol L−1; [1] and
[2] = 3.0 × 10−3 mol L−1.
between 2050 and 1900 cm−1 presented a steady decrease in
intensity until they virtually disappeared after 560 and 460 s for
1 and 2, respectively, indicating complete release of the CO
molecules. In general, biscarbonyl Mn(I) compounds show a
second CO stretching band at around 1990−1960 cm−1
attributed to a symmetric mode,52 which does not appear in
the IR spectra, as it overlaps with the asymmetric bands of the
initial [Mn(L)(CO)3Br] compounds. This same behavior was
also observed by Amorim for the kinetic study of CO release
from the compounds [MnBr(CO)3(phS-κ2S)],52 [MnBr-
(CO)3(phSe-κ2Se)],52 and [MnBr(CO)3(bzlSe-κ2Se).52
Analysis of the photoproducts of compounds 1 and 2 during
exposure to λ453 light was also followed by cyclic voltammetry
and provided important information for elucidation of the CO
photorelease process, as shown in Figure 6.
The voltammograms of the two compounds show, in the
first 40 and 120 s of light exposure to 1 and 2, respectively, the
redox process at 1080 and 1112 mV vs NHE, that may be
attributed to the Mn(I)/(II) redox couple (vide supra). These
redox processes shift to more positive potentials during the
photoinduction intervals, the trend being much more
pronounced in compound 1 where the potential is shifted to
1215 mV vs NHE, while for 2 the potential is shifted to 1153
mV vs NHE. This displacement to higher potential is
tentatively attributed to a distortion of the complex to a
trigonal bipyramidal geometry, as suggested by the computed
geometry for the S1 state obtained by DFT calculations and is
also supported by the spectroscopic data where the chelating
ligand release is observed upon light (vide infra). Thus, as this
distortion occurs with the decoordination of the pyridine
moiety or replacement by a solvent molecule, both possibilities
should reduce the electron density at the metal center and shift
the oxidation process to a higher potential.
(II) redox processes in the voltammograms of both
compounds, indicating that the concentration of the initial
species decreases during the photoinduction process, another
confirmation of CO release. These low oxidation potentials of
biscarbonyl and monocarbonyl intermediates occur due to the
replacement of the π-acceptor CO groups by solvent
molecules, which increases the electron density at the Mn(I)
metal center, facilitating its oxidation.58 The combination of
these findings with the results obtained in the IR assay
provides strong support for the spectral changes observed
during light exposure in the UV being related to CO release.
In order to obtain more information about the CO
1
photorelease processes for 1 and 2, changes in the H NMR
and 13C NMR spectra during λ453 light exposure were followed.
The spectral profiles of 1 and 2 (Figures S11−S14) presented
very similar features as the free ligands, with the signals of all
aromatic hydrogens and carbons being clearly observed and
shifted to slightly more deshielded values of chemical shift due
1
to the metal coordination. The greatest difference in the H
NMR and 13C NMR spectra of these compounds is the
presence of a singlet signal at 3.09 ppm (1H) and at 40 ppm
(13C) attributed to the methyl hydrogens and the methyl
carbon of the dimethyl amine group present in compound 2.
After the start of irradiation with λ453 light, the signals in the
1H NMR spectrum begin to broaden due to the replacement of
carbonyl groups by solvent molecules leading to the
consequent oxidation and change of spin state of the Mn ion
(Figure 7 for 2 and Figure S15 for 1). The loss of the π-
accepting carbonyl groups leads to increased electron density
at the metal center, leading to the destabilization of the +1
oxidation state indicating the formation of paramagnetic
species (e.g., Mn(II)), even in small quantities, in the final
system,55,59 influencing the H NMR spectrum.
Combining the IR spectra, electrochemical studies and H
1
After 40 s of photoinduction for 1 and 200 s for 2, it is
possible to observe the appearance of new signals at lower
potentials, at 933 and 709 mV vs NHE for 1 and at 702 mV vs
NHE for 2. These new more cathodic processes, at 709 and
702 mV vs NHE for 1 and 2, respectively, are attributed to the
biscarbonyl intermediate, as reported by Sachs et al. for the
compound [Mn(CO)3(tpm)][PF6] (tpm = tris(1-pyrazolyl)-
methane).58 The second cathodic process at 933 mV vs NHE
for 1 is probably due to the formation of an intermediate
species with acetonitrile replacing bromide.
1
NMR analysis of compounds 1 and 2, it was expected that the
1H NMR spectra would include new signals attributable to the
biscarbonyl intermediate, which did not occur. The absence of
peaks related to these intermediates is probably due to the fast
release of CO molecules during the photoinduction process in
DMSO and consequent oxidation of the metal center, leading
to broadening of the resonance lines that may obscure the
formation of new signals. In addition, the biscarbonyl
intermediate of compound 1, as indicated by IR analysis,
tends to release the remaining carbonyls, suggesting a
As photoexcitation continues, it is possible to observe a
decrease in the intensity of the signals related to the Mn(I)/
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are located at the same chemical shift as the free ligands in the
spectra of both compounds after irradiation. These results are
an indication that during the photoinduction process the
ligands Oxa-H and Oxa-NMe2 also dissociate.
The changes in the UV−vis spectra of both compounds in
acetonitrile solution were also monitored spectrophotometri-
cally over time (Figure 9). During light exposure, an intense
decrease in the band centered at 428 nm for 1 could be
observed until stabilization around 260 s (Figure 9, left). This
intense band, as suggested by TD-DFT, is mainly correlated to
the MLCT (metal(dπ) → Oxa-H(π*)) transition, and while it
alone is not an indication of CO dissociation, since some
intermediates coexist simultaneously thus making the MLCT
region convoluted, when coupled with the IR, electro-
chemistry, DFT, and NMR data, it can be correlated with
the photorelease of carbon monoxide. In the first 100 s of the
photorelease process, it is also possible to observe the
emergence of a second band at lower energy, around 578
nm, which begins to decay until it stabilizes. This new band
can be attributed to the biscarbonyl species formed by
replacing a CO molecule with a solvent molecule. The
replacement of CO by CH3CN, a weaker π-acceptor, results in
destabilization of the HOMO centered at Mn, shifting the
MLCT (metal(dπ) → Oxa-H(π*)) to lower energy. Similar
behavior was observed by other groups55,61−64 in photorelease
studies of other Mn(I) carbonyl compounds. For 2, Figure 9
(right), different spectral changes in the UV−vis spectrum
could be observed. The spectrum shows a decrease in the
intense band at 384 nm, which is due to the mixed π → π* and
MLCT (metal(dπ) → Oxa-NMe2(π*)) transition, indicating
CO dissociation. In addition, it is possible to observe an
increase in the band at 343 nm, indicating the formation of
new species in solution. This new band is correlated to the
Oxa-NMe2 free ligand, as can be seen from its UV/vis
spectrum (Figure S17), suggesting ligand dissociation during
the CO release process, in agreement with the 13C NMR
analysis.
Figure 7. Changes in the 1H NMR spectra (400 MHz, DMSO-d6) of
2 during λ453 light exposure.
concurrent process between release of the last two carbonyls
and oxidation of the Mn(I) metal center.
The monitoring of the 13C NMR spectra under light
irradiation of 453 nm for compounds 1 and 2 (in DMSO
solution) allowed some additional observations (Figure 8 for 2
and Figure S16 for 1). For both, in the spectra determined
before light exposure, three signals were detected between 220
and 225 ppm, which are related to the carbonyl groups
attached directly to the manganese metal center. After 560 s of
light exposure at 453 nm, a new resonance line for both
compounds is detected in the 185 ppm region and is assigned
to the free carbonyl in solution. This feature is consistent with
the results obtained using other techniques, such as electro-
chemical and infrared spectroscopy, and was also observed by
our group in a previously reported work about CO release
from other manganese tricarbonyl compounds.60 In addition,
the 13C NMR spectra of 1 and 2 also had the appearance of
lower intensity signals, initially nonexistent. As one can see in
Figure 8 for 2 and Figure S16 for 1, the new resonance lines
Figure 8. Superposition of 13C NMR spectra (100 MHz, DMSO-d6) for 2 without irradiation and after 560 s of light irradiation in 453 nm and the
free ligand Oxa-NMe2.
H
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Figure 9. Changes in the UV−vis spectra for 1 (left) and 2 (right) acetonitrile solution caused by CO release during the λ453 irradiation course. [1]
= 3.75 × 10−4 mol L−1; [2] = 7.70 × 10−5 mol L−1.
Figure 10. Visible emission spectrum for compound 2 (a) and color of solutions of the free Oxa-NMe2 ligand (b) and for 2 before (c) and after (d)
the photoinduction process under UV light.
As the ligands and organometallic compounds show
luminescence under UV light, the emission spectra were
measured for the free ligands and for 1 and 2 during the
photoinduction process (Figure 10 for 2 and Figure S18 for 1).
The emission spectra of 2, Figure 10, show an increase in the
emission band at 508 nm, the same emission band shown by
the free ligand Oxa-NMe2 (Figure S17), which is a further
indication that the ligand is being dissociated along with the
carbonyl molecules during the photoinduction process.
Changes in the color of the solutions before and after
photoinduction could also be observed, from an orange to a
colorless solution under visible light and from a slightly green
to a strong green emission, the same color of emission as for
the Oxa-NMe2 free ligand, as shown in Figure 10. The same
behavior was observed for 1, as shown in Figure S18.
The emission properties of these compounds can be
important for biological applications, since they exhibit
traceable luminescence, i.e., “turn-on” properties after CO
release, making their location in cells identifiable by confocal
microscopy and allowing a better spatial and temporal control
of application of these CORMs, even in the absence of COP-1
(a fluorogenic switch-on probe for CO) as an external sensor.
A similar behavior was observed by Carrington and co-workers
in the CO photorelease study of [MnBr(CO)3(pbt)]51 and
[Re(H2O)(CO)3(pbt)](CF3SO3) (pbt = 2-(2pyridyl)-benzo-
thiazole).65
approximations that we considered in a previous report60 that
considered only the time interval in which the biscarbonyl
intermediate concentration is minimal, cannot be used due to
the initial consumption of a photon to form the trigonal
bipyramidal intermediate.
Taking the above discussion into consideration, the
calculation of a quantum yield is also misleading since the
mechanism involves concomitant reactions and the first
photon is assumed to lead to a change from an octahedral to
a trigonal bipyramidal coordination geometry. The combina-
tion of these processes renders any kind of approximation to
estimate the quantum yield of both the first and second
dissociation unreliable, and therefore they were not calculated.
Bearing this in mind, the strategy employed here in order to
quantify the rates is to use the decay of the absorption of the
initial [Mn(L)(CO)3Br] compounds, as recommended by
Ford’s group. However, this is still a rough approximation,
since both compounds have at least one intermediate with
non-neglectable influence on the MLCT. In addition, these
species are difficult to isolate and, as a consequence, the
deconvolution of the spectra is a quite challenging task that
most researchers do not consider. Analyzing the decrease of
the absorption spectra of 1 and 2 under identical conditions, it
is possible to infer that compound 1 undergoes faster decay
than compound 2.
This may occur due to the contribution of a π−π*-like state
around the metal−CO bonds for complex 1, weakening the
Mn−CO bonds when compared with compound 2 where the
π−π*-like state occurs with a high contribution of the
chelating ligand (cf. HOMOs and LUMOs, Figure 3). Another
explanation is that the excitation wavelength used for the
photorelease, centered at 450 nm, is closer to the MLCT of 1,
that has a maximum molar absorptivity coefficient at 428 nm,
while for 2 the MCLT is centered at 384 nm.
Taking into consideration that both compounds have stable
intermediates even under aerobic conditions, the calculation of
a quantum yield or even a CO release rate cannot be made
with a high degree of certainty. In fact, the calculation of a
pseudo-first-order release rate was already questioned by
Ford’s group, which considered use of the decay of the
absorbance to be a better tool for correlating the CO release
process with the changes in the MLCT.25 Furthermore, the
I
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Scheme 2. Schematic Representation of the Proposed Mechanism of CO Release for 1 (R = H) and 2 (R = NMe2)
The myoglobin assay (Figures S19 and S20 for 1 and 2,
respectively) indicated a lower amount of CO released per
mole of compound (0.70 0.04 and. 0.66 0.12 equiv of CO
for 1 and 2, respectively) than indicated by IR, electro-
chemistry, and UV−vis studies, all of which demonstrate that 1
and 2 release all CO molecules. These differences can be
explained by the interference of the myoglobin Q-band in the
absorption of the radiation of 1 and 2.14 The myoglobin Q-
band, at 557 nm, is relatively near the wavelength (λ453) used
for the photoinduction of these compounds, meaning that
some of the photon flux produced by the magnetic irradiation
is absorbed by the myoglobin heme rather than the carbonyl
compounds, leading to a less than expected value for the
amount of CO released. Considering this, the calculated values
of CO released do not correlate with the values obtained in the
IR and electrochemistry assays, and it is only used as a
qualitative mean to indicate the CO release.
Mechanistic Insights. To improve the understanding of
the photorelease mechanism, the first singlet excited state and
the first triplet state were computationally optimized for all
compounds (Figure S21). Also, the SOC (spin orbit coupling)
matrix elements between the first 10 singlet and triplet states
were calculated using SOC-TD-DFT, on top of the S0
geometry40 (Table S10). For compounds 1 and 2, the higher
SOC matrix element between the low-lying states even for Mn
compounds occurs due to these states’ configuration, which
arises mostly from MLCT transitions and involving the
different d orbitals (compare Figure 3 and Table S9). For
compound 2, the smaller SOC matrix element values occur
due to the π−π*-like character over the chelating ligand
contribution for these states. This high SOC between the low-
lying states for these compounds should lead to facilitated
dissipation of energy through nonradiative processes (i.e.,
inter-system crossing and consequently triplet state quenching)
and thus contribute to decreasing the CO release. Never-
theless, as shown in Figure S21 for compounds 1 and 2, the
calculated geometry of the S1 state exhibited a dissociation of
the pyridyl moiety distorting the complex to a trigonal
bipyramidal geometry and an elongation of metal−CO
bonds, which should facilitate the CO release. This result is
in agreement with the electrochemistry data where an
intermediate is seen before the biscarbonyl formation,
suggesting that the light exposure for 1 and 2 promotes CO
release from the singlet 1MLCT/XLCT state, followed in later
steps by ligand dissociation.
Thus, considering all results presented in this work, a CO
release mechanism can be tentatively proposed, as shown in
Scheme 2. In an initial step, in the early seconds of light
exposure at λ453, the predicted S1 geometry for compounds 1
and 2 by DFT calculations exhibits a distortion of the complex
to a trigonal bipyramidal geometry and an elongation of
metal−CO bonds, which should facilitate the CO release. This
intermediate could be in equilibrium with an excited
hexacoordinated species either with the recoordination of the
pyridine or the coordination of a solvent molecule; then, a CO
molecule can be released, forming the biscarbonyl species.
Evidence for such a transformation were obtained by IR, UV−
vis spectroscopy, and electrochemistry, where signals generally
attributed to the biscarbonyl species were identified, also
showing that this intermediate is stable at least for a few
minutes, allowing its identification even in aerobic media.
After a longer time of exposure to incident light, the release
of all CO molecules is observed, as suggested by IR
spectroscopy where the signals attributed to the CO stretching
bonds disappear completely and the oxidation of the metal
center is indicated by the presence of paramagnetic species
1
observed by H NMR spectroscopy, in accordance with the
observations by Pordel and White55 as well as Mansour and
Friedrich59 where oxidation by O2 becomes important. The
release of the chelating ligand (Oxa-H or Oxa-NMe2) was
proposed on the basis of absorption, emission, and 13C NMR
J
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́
́
analyses where spectroscopic signals similar to those of the free
ligands were observed upon photoirradition.
Andre L. Amorim − Departamento de Quimica, LABINC,
Universidade Federal de Santa Catarina (UFSC), Santa
Catarina 88040-900, Brazil
CONCLUSION
Fernando R. Xavier − Universidade do Estado de Santa
Catarina (UDESC), 89219-710 Joinville, SC, Brazil;
orcid.org/0000-0002-2056-4052
Tiago P. Camargo − Departamento Academico de Quimica e
Biologia, Universidade Tecnologica Federal do Parana
■
Two Mn(I) tricarbonyl compounds ([Mn(Oxa-H)(CO)3Br]
and [Mn(Oxa-NMe2)(CO)3Br]) were synthesized and fully
characterized. The manganese compounds showed a fast
release of CO molecules when exposed to visible blue light
(λ453), thus acting as photoCORMs. Using combined IR, UV−
vis, and NMR measurements, along with electrochemical
studies, we propose that both manganese compounds release
all three CO molecules during the photorelease process and
that this process proceeds via the formation of a biscarbonyl
intermediate.
́
̂
́
́
(UTFPR), Curitiba 81290-000, Brazil
́
̂
Mayana B. Bregalda − Departamento Academico de Quimica e
Biologia, Universidade Tecnologica Federal do Parana
́
́
(UTFPR), Curitiba 81290-000, Brazil
Matti Haukka − Department of Chemistry, University of
Jyvaskyla, FI-400 14 Jyvaskyla, Finland; orcid.org/0000-
0002-6744-7208
̈
̈
̈
̈
Very few studies to date have reported and proven the
release of the chelating ligand together with the carbonyl
molecules, but the present investigation includes studies by
spectroscopic techniques and TD-DFT and SOC-TD-DFT
calculations that strongly indicate that compounds 1 and 2
release the Oxa-H and Oxa-NMe2 ligands, in addition to the
carbonyl ligands, upon irradiation with light at λ = 453 nm.
Furthermore, the release of the ligand in the Mn compounds
1 and 2 promotes an increase in the emission during the
photoinduction process, giving these compounds “turn-off/
turn-on” properties. Such properties are of general interest and
of great importance for possible future medicinal applications,
since they can be visualized by confocal microscopy studies,
eliminating the need to use COP-1 as an external fluorescence
probe and allowing a greater precision in the CO distribution
in cells.
Ebbe Nordlander − Chemical Physics, Department of
Chemistry, Lund University, SE- 22100 Lund, Sweden
́
Bernardo de Souza − Departamento de Quimica, LABINC,
Universidade Federal de Santa Catarina (UFSC), Santa
Catarina 88040-900, Brazil
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.inorgchem.0c00638
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
The authors are grateful to the Brazilian government agencies
CNPq (for grants awarded to A.L.A., G.F., and R.A.P.), IFSC,
■
́
INCT Catalise, CAPES-STINT, FAPESC, and FINEP. This
study was financed in part by the Coordenac o de
oamento de Pessoal de Nivel Superior - Brasil
̧a
̃
ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.inorgchem.0c00638.
́
■
Aperfeic
̧
sı
(CAPES) - Finance Code 001. The authors also thank
CEBIME for the mass spectrometry, CAPES-PRINT, Project
No. 88887.310569/2018-00 and Project No. 88887.310560/
2018-00.
Synthesis of the ligands, NMR spectra, IR spectra, UV
spectra, electrochemical studies, crystallographic data,
and computational methods (PDF)
DEDICATION
■
Dedicated to Professor Ademir Neves, an inspirational
scientist.
Accession Codes
CCDC 1982518 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
via www.ccdc.cam.ac.uk/data_request/cif, or by emailing
data_request@ccdc.cam.ac.uk, or by contacting The Cam-
bridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
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