Tetrachlorocarbonyliridates: Water-soluble carbon monoxide releasing molecules rate-modulated by the sixth ligand

Article abstract of DOI:10.1021/ic102038v

A new family of compounds is presented as potential carbon monoxide releasing molecules (CORMs). These compounds, based on tetrachlorocarbonyliridate (III) derivatives, were synthesized and fully characterized by X-ray diffraction, electrospray mass spect

Full text of DOI:10.1021/ic102038v

ARTICLE
pubs.acs.org/IC
Tetrachlorocarbonyliridates: Water-Soluble Carbon Monoxide
Releasing Molecules Rate-Modulated by the Sixth Ligand
Damian E. Bikiel,† Estefanía Gonzꢀalez Solveyra,† Florencia Di Salvo,† Humberto M. S. Milagre,‡
Marcos N. Eberlin,§ Rodrigo S. Corr^ea,|| Javier Ellena,|| Darío A. Estrin,† and Fabio Doctorovich*,†
†Departamento de Química Inorgꢀanica, Analítica y Química Física, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos
Aires, INQUIMAE-CONICET, Ciudad Universitaria, Pabellꢀon II, C1428EHA, Buenos Aires, Argentina
‡Institute of Biosciences, UNESP-Univ. Estadual Paulista, 13506-900 Rio Claro, SP, Brazil
§ThoMSon Mass Spectrometry Laboratory, Institute of Chemistry, University of Campinas, UNICAMP, 13083-970, Campinas SP,
Brazil
Departamento de Física e Informꢀatica, Instituto de Fisica de S~ao Carlos, Universidad de S~ao Paulo, Caixa postal 369, S~ao Carlos, SP,
CEP 13560-970, Brazil
S Supporting Information
b
ABSTRACT: A new family of compounds is presented as potential
carbon monoxide releasing molecules (CORMs). These compounds,
based on tetrachlorocarbonyliridate(III) derivatives, were synthe-
sized and fully characterized by X-ray diffraction, electrospray mass
spectrometry, IR, NMR, and density functional theory calculations.
The rate of CO release was studied via the myoglobin assay. The results
showed that the rate depends on the nature of the sixth ligand, trans to
CO, and that a significant modulation on the release rate can be
produced by changing the ligand. The reported compounds are soluble
in aqueous media, and the rates of CO release are comparable with those
for known CORMs, releasing CO at a rate of 0.03-0.58 μM min-1 in a
10 μM solution of myoglobin and 10 μM of the complexes.
’ INTRODUCTION
compounds.7,11 This compound with glycinate (gly) released
only one of its CO ligands in water: at 37 ꢀC, the half-life is
98 h; in human plasma, it is reduced to 3.6 min.2 The use of
this compound for biochemical assays is exemplified else-
where.7,12-27 Derivatives of the iron compound were also
explored: complexes bearing pyrone were recently developed,
showing that the releasing rate can be modulated by substitution
in the pyrone ring.28,29 This research was conducted on new
compounds involving Fe(II) and Mo(II), which were named
CORM-F*: 40 μM CORM-F10 releases (in DMSO), toward a
50 μM myoglobin solution, 3.4 μM min-1 of CO in the first
5 min.30 Other iron compounds were based on cyclopentadienyl
and indenyl.31,32 Releasing experiments involving metallic car-
bonyls of Cr, Fe, Mn, V, Mo, and W were made in DMSO or
ethanol solutions, trying to rationalize the observed releasing
rates.33,34 Cobalt-based compounds have also been explored.35
Very recently, Zobi et al. reported Re-based CORMs with pH-
dependent half-lives ranging 6-43 min.36 Besides the interest in
thermally driven CO release, photoinduced release has also been
explored.37-40 A different approach, using a conjugated hemo-
globin-polymer called Hemospan, has been shown to have
The image of CO as just a noxious gas has been changed to
that of an important endogenous biochemical molecule.1-3
Studies on CO showed vasodilatory, anti-inflammatory,
antiapoptotic, antiproliferative, and other pharmacological
properties.4 Human basal production is similar to that of NO,
estimated at 20 μmol h-1, which is increased under pathological
stages. In recent years, several groups around the world devel-
oped different compounds with CO donation capabilities in
order to propose new tools for CO physiology experiments.
These compounds were named CO releasing molecules
(CORMs) by Motterlini et al.5 The molecules range from boron
compounds to transition metal complexes. Regarding the boron
compounds, some of them form adducts with CO.6 For example,
Na[H3BCO2H] decomposes to CO, H2, and boric acid under
physiological pH and 37 ꢀC with a half-life of 20 min.7 Several
derivatives of this compound were synthesized by esterification
and amidation in order to tune the CO releasing rate.8-10 From
an organometallic viewpoint, CO is probably the most important
ligand in the chemistry of transition metals. This property was
therefore explored by Motterlini et al. in order to develop the
first CORMs.7 The first generation of CORMs involved
[Mn2(CO)10], Fe(CO)5, and [Ru(CO)3Cl2]2. Further develop-
ments led to [RuCl(gly)(CO)3], named CORM-3, and related
Received: October 7, 2010
Published: February 15, 2011
r
2011 American Chemical Society
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Inorganic Chemistry
ARTICLE
potential uses as a CO carrier and delivering agent.41 Due to the
high degree of inertness, some Ir(III) compounds have been
studied as therapeuticals.42,43 In this work, we present a new
family of CORMs based on a tetrachlorocarbonyliridate(III)
framework. This quite simple moiety has shown to be robust
enough to stabilize coordinated S-nitrosothiols, N-nitrosamines,
and C-nitroso compounds.44-48 At the same time, the chloride
trans to the CO (or N(OR)) moiety is labile enough to be
replaced by others ligands.49 These compounds are soluble in
water and release CO under physiological conditions at 37 ꢀC
with half-lives on the order of those of known CORMs. The
release rate can be tuned by replacing the ligand located trans to
the CO. Starting with [IrCl5CO]2-, we obtained [IrCl4CO-
(H2O)]- as a product of the hydrolysis in water. We selected
pyridine as a prototypical N-based ligand and explored the
electronic effects by synthesizing the 4-dimethylaminopyridine
derivative. Similarly, we explored another stronger N-based
ligand such as 1-methylimidazole. Since each complex holds
only one CO ligand, the maximum CO dosage is perfectly known
under any experimental condition to be used. Synthesis, struc-
tural characterization, and kinetic characterization are described.
Induced Dissociation (CID) with Ar using energies varying from 15 to
35 eV with high-accuracy orthogonal TOF mass analysis of the CID
ionic fragments. For comparison with experimental data, isotopic
patterns were calculated using the MassLynx software. Additionally,
we performed FT-ICR (Fourier Transform Induced Cyclotron Re-
sonance) measurements. For analysis in both the positive and negative
ion modes, pure methanol was used as the spray solvent. Solvents and
additives were of HPLC grade, purchased from Sigma-Aldrich, and used
as received. Direct infusion automated chip-based nano-ESI-MS was
performed on a Triversa NanoMate 100 system (Advion BioSciences,
Ithaca, NY) in both the positive and negative ion modes. Samples were
loaded into 96-well plates (total volume of 100 μL in each well)
and analyzed using a 7.2T LTQ FT Ultra mass spectrometer
(ThermoScientific, Bremen, Germany). General ESI conditions were
as follows: gas pressure of 0.3 psi and capillary voltage of 1.55 kV and a
flow rate of 250 nL min-1. Mass spectra were the result of over 100
microscans processed via the Xcalibur 2.0 software (ThermoScientific,
Bremen, Germany).
The elemental CHSN-O microanalysis measurements were obtained
using a Carlo Erba EA 1108 system. The analysis was carried out by
combustion in a reactor tube and separated by gaseous chromatography
in a Paropac column of variable length. The detection was performed via
thermal conductivity.
’ METHODOLOGY
All of the kinetic measurements were carried out on a Hewlett-
Packard 8453 diode array spectrometer, equipped with a Lauda RE 207
thermostat. For the hydrolysis experiments, the complexes were dis-
solved directly in water without pH control (ca. 3 mM). The CO
releasing experiments were carried out in a phosphate buffer at pH =
7.35 and 0.001 M, with an ionic strength = 0.08 M KClO4. Horse heart
myoglobin was used in the experiments. The myoglobin solutions were
prepared in a phosphate buffer (ca. 10 μM). Sodium dithionite solution
was used to reduce the myoglobin prior to each kinetic experiment. For
the CO-releasing experiment of 1-Cs, the initial solution of the complex
was added to 9.3ꢀ NaCl (for example, 1 mM 1-Cs þ 9.3 mM NaCl) in
order to avoid water exchange (vide infra). The 4-dimethylaminopyr-
idine (DMApy) derivative was dissolved in DMSO due to its poor
solubility in water.
The kinetic data were analyzed by a program written in MATLA-
B2008a, which allows fitting the experimental data to a particular
proposed mechanism. It is composed by a Singular Value Decomposi-
tion (SVD) subroutine which extracts the relevant data, diminishing the
noise and a minimization subroutine which uses the Simplex algorithm
of Nelder-Mean to adjust the proposed kinetic constants.
DFT Calculations. All gas phase DFT calculations performed in this
work were carried out using the Gaussian 98 software package. Geome-
tries were fully optimized at the BPW9156,57 level with a double plus
polarization (DZPV) basis set for C, N, O, H, and Cl atoms and the
LANL2DZ basis set and effective core potential for the iridium.58-60 A
normal mode analysis was performed in order to obtain vibrational
frequencies, force constants, and zero-point energy corrections for the
total energy.
Synthesis. The synthesis of the compounds presented in this work
has been summarized in a general protocol for clarity. Details regarding
each one of the compounds are given in the corresponding paragraph.
General Procedure. A total of 49.5 mg of Cs2[IrCl5CO] (1-Cs; 663.3 g/
mol, 74.6 μmol) was dissolved in 5 mL of distilled and degassed water.
The solution was stirred between 1-12 h at room temperature or heated
up to 80 ꢀC. Between 1-10 equivalents of the ligand was added, and the
solution was stirred for 1-12 h. If the presence of solid was evidenced, the
solid was separated by centrifugation and washed with distilled water until
reaching a neutral pH. The solid was dried in a vacuum and recrystallized.
If no solid was observed, protocol A, B, or C was employed.
All experimental manipulations were performed under anaerobic
conditions using standard Schlenk procedures. The Cs2[IrCl5CO]
complex (1-Cs) was synthesized according to the procedure of Cleare
and Griffith.50 K3IrCl6, sodium dithionite, and horse heart myoglobin
were purchased from Sigma-Aldrich and used without purification. All of
the solvents were distilled under N2 prior to use. In all of the
experiments, deionized water was employed.
Instrumental Procedures. Data collection and processing of the
X-ray diffraction studies were performed in a Nonius Kappa-CCD
diffractometer, with Mo KR (λ = 0.71073 Å), a graphite monochro-
mator, and T = 298 K. To deal with raw data, the HKL Denzo-Scalepack
software package was used.51,52 All of the reflections were used to obtain
the final parameters of the cell. The data were reduced using the
DENZO-SMN and SCALEPACK programs. A Gaussian method im-
plemented in WinGX was used for the absorption correction.53,54 The
structures were resolved using SHELXS-97 and were refined with
SHELXL-97.55 All of the non-hydrogen atoms were refined with
anisotropic displacement parameters. The hydrogen atoms were located
from the difference synthesis of electron density and refined using the
riding model on their parent atoms with Uiso(H) = 1.5Ueq for water and
methyl H atoms or 1.2Ueq for the remaining H atoms.
1H and 13C NMR spectra were recorded using a Bruker AM500
equipped with a broad-band probe. H and 13C shifts are reported
1
relative to solvent signals with respect to TMS or relative to methanol
signals when water was used as a solvent. Correlations were confirmed
through HSQC experiments. In the 13C experiments, uncoupling and
pulses of 26ꢀ were employed.
IR spectra were recorded using a Nicolet Avatar 320 FTIR spectro-
meter with a Spectra Tech cell for KBr pellets.
Mass spectrometric measurements were performed using a high-
resolution hybrid quadrupole (Q) and orthogonal time-of-flight (TOF)
mass spectrometer (QTof from Micromass, U.K.) using electrospray
ionization in the negative ion mode with potentials from 2100 to 3500 V.
Samples dissolved in a methanol/water solution at room temperature
(RT) under an inert atmosphere were injected through an uncoated
fused-silica capillary, using a syringe pump (Harvard Apparatus, Pump
11, 15 nL min-1). The temperature of the nebulizer and desolvation gas
was set at 100 ꢀC, and the cone voltage was set between 25 and 35 V.
Tandem mass spectra (ESI-MS/MS) were acquired using the product
ion scan mode via selection of the ion of interest, followed by Collision
Protocol A. The aqueous solution was washed three times with
toluene (10 mL) and then one time with dichloromethane. Then,
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Inorganic Chemistry
ARTICLE
Table 1. Details of the X-Ray Data Collections and Refinements for 2-As and 4-As
2-As
4-As
chemical formula
fw
[Ir Cl4(H2O)CO]AsC24H20 H2O
[IrCl4(C4H4N2)CO]AsC24H20
3
781.36
298
827.44
298
temp (K)
cryst syst
space group
unit cell dimensions
a (Å)
triclinic
P1
monoclinic
P21/n
11.0493(2)
12.3015(9)
18.2647(12)
14.5551(7)
90
b (Å)
12.0623(2)
c (Å)
12.5596(2)
R (deg)
111.016(1)
β (deg)
95.379(1)
111.975(4)
90
γ (deg)
111.648(1)
vol (Å3)
1402.22(5)
3032.7(3)
4
Z
2
calcd density (Mg/m3)
1.851
1.812
abs. coeff. (mm-1
)
6.337
5.863
F(000)
752
1600
cryst size (mm3)
0.13 ꢀ 0.13 ꢀ 0.12
0.13 ꢀ 0.10 ꢀ 0.03
2.95-26.39
θ range for data collection (deg)
indices ranges
3.01-26.76
-13 e h e 13, -15 e k e 15, -15 e l e 15
-15 e h e 15, -20 e k e 22, -18 e l e 18
reflns collected
10409
30422
independent reflns
5888 [R(int) = 0.0260]
98.6
6200 [R(int) = 0.0843]
99.8
completeness to θ
absorption correction
max. and min. transmission
data/restraints/params
goodness-of-fit on F2
final R indices [I > 2σ(I)]
R indices (all data)
Gaussian
Gaussian
0.691 and 0.36
5888/0/307
0.824 and 0.516
6200/0/344
1.095
1.036
R1 = 0.0348, wR2 = 0.0706
R1 = 0.0443, wR2 = 0.0758
0.612 and -1.216
R1 = 0.0398, wR2 = 0.0820
R1 = 0.0691, wR2 = 0.0906
1.012 and -1.528
largest diff. peak and hole (e/A3)
cosolvent or a saturated solution of tetraphenylarsonium chloride
(AsPh4Cl) solution was added. The solution was cooled for 1-6 h,
and the solid was centrifuged and dried under vacuum conditions.
Protocol B. A total of 10 mL of dichloromethane was added, and the
mixture was stirred for 1 h. A saturated solution of AsPh4Cl in ethanol
was added to the solution and stirred for 1 h. After the separation of the
phases, the organic one was washed three times with distilled water and
dried with anhydrous sodium sulfate. The filtered solution was concen-
trated in a rotary evaporator up to 0.5 mL. Cosolvent was added, and the
solution was cooled for 1-6 h. The solid was separated by centrifugation
and dried in a vacuum.
AsPh4[IrCl4CO(H2O)] (2-As). The solution was heated to 80 ꢀC for
3 h. Then it was cooled to room temperature, and protocol C was followed
using 2 equivalents of AsPh4Cl. The orange solid was recrystallized using
ethanol-water. Yield: 75%. υCO FT-IR = 2063 cm-1. Microanalysis:
Calcd (þH2O) C = 38.4%; H = 3.1%. Exptl. C = 38.2%; H = 3.3%. 1H
NMR (CDCl3): 7.85 ppm (tt, 4H), 7.78 ppm (tt, 8H), 7.63 (dq, 8H),
2.3 ppm (bs, 3H). 13C NMR (CDCl3): 144.6 ppm (CO), 135.3 ppm
(AsPh4þ), 133.4 ppm (AsPh4þ), 131.9 ppm (AsPh4þ), 120.7 ppm
(AsPh4þ). ESI-MS(-), Calcd: M-, m/z 376.84. Exptl: M-, m/z 376.84
Cs[IrCl4CO(py)] (3-Cs). A total of 10 equivalents of pyridine (py) was
added. The solution was stirred for 6 h at room temperature. Using
protocol A and isopropanol as a cosolvent, a yellow solid was obtained.
Yield: 65%. υCO FT-IR = 2085 cm-1. Microanalysis: Calcd C = 12.55%;
H = 0.88%; N = 2.44%. Exptl. C = 12.1%; H = 1.2%; N = 2.3%. 1H NMR
Protocol C. The solution was concentrated in a rotary evaporator up
to 0.5 mL. Cosolvent or a saturated solution of AsPh4Cl in ethanol was
added. The solution was cooled for 1-6 h, and the solid was centrifuged
and dried under vacuum conditions.
(D2O): 8.95 ppm (dt, 2H), 8.03 ppm (tt, 1H), 7.55 ppm (t, 2H). 13
C
(AsPh4)2[IrCl5CO] (1-As). A total of 60 equivalents of NaCl was
added. Once the solids were completely dissolved, AsPh4Cl (5 equiv-
alents) was added. Then, the solution was evaporated in a rotary
evaporator. The orange solid was recrystallized using acetonitrile-
toluene. Yield: 60%. υCO FT-IR = 2023 cm-1. Microanalysis: Calcd
C = 50.55%; H = 3.46%. Exptl. C = 50.4%; H = 3.8%. 1H NMR
(CD3CN): 7.91 ppm (tt, 4H), 8.03 ppm (tt, 1H), 7.70-7.80 ppm
(m, 16H). 13C NMR (CD3CN): 151.4 ppm (CO), 135.6 ppm
(AsPh4þ), 132.0 ppm (AsPh4þ), 121.0 ppm (AsPh4þ). FT-MS, Calcd:
M-, m/z 441.87; [M2- þ AsPh4þ]-, m/z 776.88. Exptl. m/z 776.88.
NMR: 151.2 ppm, 150.5 ppm (CO), 140.5 ppm, 125.5 ppm. FT-MS,
Calcd: M-, m/z 441.87; [M- þ 2Csþ]þ, m/z 707.68. Exptl: m/z
441.87, m/z 707.68.
AsPh4[IrCl4CO(py)] (3-As). A total of 10 equivalents of py and 10 mL
of dichloromethane were added. The solution was stirred for 6 h at room
temperature. Protocol B was followed using 5 equivalents of AsPh4Cl
and ethanol as a cosolvent. The solid was recrystallized using dichlor-
omethane-ethanol. Yield: 75%. υCO FT-IR = 2062 cm-1. Microana-
lysis: Calcd C = 43.70%; H = 3.06%; N = 1.70%. Exptl C = 43.8%; H =
1
3.1%; N = 1.7%. H NMR (CDCl3): 9.34 ppm (dt, 2H), 7.89 ppm
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Inorganic Chemistry
ARTICLE
Table 2. Selected Geometrical Parameters for 2-As and 4-As
(Experimental X-Ray Data and DFT Calculations)
2-As
4-As
exp.
calc.
exp.
calc.
d Ir1-C1 (Å)
d C1-O1 (Å)
d Ir1-N1 (Å)
d Ir1-O1w (Å)
d Ir1-Cl1 (Å)
d Ir1-Cl2 (Å)
d Ir1-Cl3 (Å)
d Ir1-Cl4 (Å)
—Ir1-C1-O1
1.832(6)
1.127(6)
1.803
1.167
1.854(7)
1.139(7)
2.092(5)
1.835
1.165
2.129
2.110(4)
2.266
2.442
2.442
2.408
2.408
2.3624(11)
2.3392(10)
2.3444(12)
2.3580(11)
2.3651(15)
2.3585(15)
2.3543(14)
2.3568(15)
2.444
2.436
2.436
2.444
178.4(5)
179.5
178.7(6)
180.0
Table 3. Experimental and calculated carbonyl stretching
frequencies (cm-1) for the chlorocarbonyliridates presented
in this work
νCO (cm-1) experimental
νCO (cm-1) calculated
1-As
2023
2065
2063
2062
2085
2052
2073
2054
1990
1-Cs
2-As
2057
2057
3-As
3-Cs
Figure 1. ORTEP diagram at 50% probability ellipsoids for (a) 2-As
and (b) 4-As. For clarity, only the anion is shown.
4-As
2052
2051
4-Cs
5-DMApy
(t, 4H), ∼7.79 ppm (tt, 1H), 7.78 ppm (t, 8H), 7.63 ppm (d, 8H), 7.37
ppm (t, 2H). 13C NMR (CDCl3): 152.7 ppm (py), 151.9 ppm (CO),
139.0 ppm (py), 135.2 ppm (AsPh4þ), 133.1 ppm (AsPh4þ), 131.2 ppm
(AsPh4þ), 124.2 ppm (py), 120.5 ppm (AsPh4þ). ESI-MS(-), Calcd:
M-, m/z 441.87. Exptl: M-, m/z 441.87.
Cs[IrCl4CO(1-MeIm)] (4-Cs). The solution was stirred for 2 h at
80 ꢀC. A total of 1.2 equivalents of 1-methyl-imidazole (1-MeIm) was
added, and the solution was stirred for 30 min. The solution was
concentrated in a rotary evaporator. The solids were washed three times
with toluene and once with acetone. Yield: 65%. υCO FT-IR = 2073
cm-1. Microanalysis: Calcd (þ0.33 1-MeIm) C = 12.6%; N = 6.2%; H =
1.30%. Exptl C = 12.3%; N = 6.2%; H = 1.6%. 1H NMR (D2O):
8.14 ppm (s, 1H), 7.38 ppm (t, J = 1.5 Hz, 1H), 7.11 ppm (t, J = 1.5 Hz, 1H),
3.75 ppm (s, 3H). 13C NMR (D2O): 152.7 ppm (CO), 139.8 (1-MeIm),
127.2 ppm (1-MeIm), 122.0 ppm (1-MeIm), 34.9 ppm (1-MeIm). FT-
MS, Calcd: M-, m/z 444.88; [M- þ 2Csþ]þ, m/z 710.69. Exptl: m/z
444.88, m/z 710.69.
recrystallized with dichloromethane-ethanol. Yield: 45%. υCO FT-
IR = 2054 cm-1. 1H NMR (DMSO-d6): 8.49 ppm (d, J = 7.5 Hz, 1.7H),
8.10 (m, 1.9H), 6.74 ppm (d, J = 7.5 Hz, 2H), 6.60 ppm (m, 2.6H), 3.06
ppm (s, 6H), 2.96 ppm (s, 4H). 13C NMR (DMSO-d6): 156.4 ppm
(CO), 155.1 ppm (DMApy), 150.4 ppm (DMApy), 107.3 ppm (Ir-
DMApy), 106.5 ppm (DMApy). FT-MS, Calcd: M-, m/z 484.91;
[DMApyH]þ, m/z 123.08. Exptl: m/z 484.91, m/z 123.08. Microana-
lysis: Calcd (þ0.5DMApy) C = 33.2%; H = 3.9%; N = 10.5%. Exptl C =
33.0%; H = 3.9%; N = 10.2%.
’ RESULTS AND DISCUSSION
X-Ray Diffraction. The crystal data and details of data
collection and structure solution and refinement for the crystal
structures of 2-As (CCDC 808951) and 4-As (CCDC 808952)
are summarized in Table 1, while Figure 1 presents the ORTEP
diagrams. Tables 2 and 3 show the most relevant geometrical
parameters and a comparison to the ones obtained by DFT
calculations of the anion. The observation of both structures
allows assurance that the trans position of the complexes is the
preferred one for the substitution. The trans effect exerted by the
CO ligand labilizes the trans chloride in aqueous solution, which
is replaced by a water molecule. If a ligand such as py or 1-MeIm
is present, the water ligand is displaced, and the corresponding
derivatives can be isolated. The most relevant parameters are the
Ir-C and C-O distances. The DFT predicted C-O distance
for free CO by using the present combination of basis sets and
functional is 1.160 Å, while the experimental gas phase value is
1.1282 Å.61 It can be observed that there exists some differences
between the values obtained by X-ray diffraction and the DFT
AsPh4[IrCl4CO(1-MeIm)] (4-As). The solution was heated for 2 h at
80 ꢀC. After this time, 1.2 equivalents of 1-MeIm was added, and the
stirring was continued for another 30 min. Protocol C was followed
using 5 equivalents of AsPh4Cl. The solid was recrystallized using
dichloromethane-ethanol. Yield: 70%. υCO FT-IR = 2052 cm-1
.
Microanalysis: Calcd C = 42.1%; N = 3.4%; H = 3.2%. Exp. C = 42.4%;
N = 3.4%; H = 3.1%. 1H NMR (CDCl3): 8.28 ppm (s, 1H), 7.83 ppm
(tt, 4.1H), 7.76 ppm (m, 8.2H), 7.68 ppm (t, J = 1.4 Hz, 1H), 7.59 ppm
(m, 8.2H), 6.76 (t, J = 1.6 Hz, 0.9H), 3.64 (s, 2.8H). 13C NMR
(CDCl3): 154.4 ppm (CO), 139.1 ppm (Im), 135.0 ppm (AsPh4þ),
132.9 ppm (AsPh4þ), 131.6 ppm (AsPh4þ), 128.5 ppm (Im), 120.3
ppm (AsPh4þ), 119.3 ppm (Im), 34.6 ppm (Im).
DMApyH[IrCl4CO(DMApy)] (5-DMApy). Four equivalents of
DMApy was added, and the solution was stirred overnight at room
temperature. A white-yellowish solid was formed. The solid was
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ARTICLE
Figure 2. Dimeric supramolecular arrangement observed in 2-As: (a) O-H Cl, (b) expanded view, (c) infinite chains are observed for 4-As.
3 3 3
calculated ones. The X-ray values show a slightly shortened bond
for 2-As and an elongated one for 4-As (1.127(6) and 1.139(7)
Å, respectively, versus 1.1282 Å). Comparison of the calculated
C-O bonds of the carbonyls with the one corresponding to free
CO shows a slightly elongated C-O distance for 2-As and for 4-
As (1.167 and 1.165 Å, respectively, versus 1.160 Å for free CO).
Analysis of the Ir-C bonds illustrates that DFT predicts
correctly the slightly shorter Ir-C bond for 2-As as compared
to 4-As. Analyzing the experimental X-ray values, it can be
observed that, to the contrary of what could be expected, upon
elongation of the Ir-C bond (from 2-As to 4-As), the C-O
bond is also elongated. This fact reflects the poor backdonation
from the Ir to the antibonding orbitals of CO. Also, as shown by
the DFT calculations, almost no noticeable change in the C-O
bond length is observed upon the elongation of the Ir-C bond.
Since the effect of the backdonation is to elongate the C-O bond
due to the interaction of metal orbitals with antibonding orbitals
of the ligand, the behavior is in agreement with a CO ligand
interacting mainly as a pure σ donor. Some other Ir(III) carbonyl
compounds show similar distances. For example, Ir(COD)-
(CO)2GePh3 presents Ir-C and C-O distances of 1.91 Å and
1.137 Å, respectively.62 Other Ir(III) complexes such as
[IrCl(CO)5]2þ present elongated distances for Ir-C and shor-
tened ones for C-O: 2.02 Å and 1.08 Å, respectively.63
Expanded views of both structures as well as comple-
mentary crystallographic tables are included in the Supporting
Information.
IR. Figure S1 (Supporting Information) shows a typical IR
spectrum for the presented family. In particular, the spectrum of
5-DMApy is shown. The most important features are the signals
observed below 1500 cm-1, which correspond to the vibrations
of the coordinated DMApy, and the intense band at 2054 cm-1
,
which corresponds to the CO stretching (υCO). This frequency
is in agreement with the values found in terminal carbonyls of
transition metal complexes (1820-2150 cm-1).64-66 As it can
be seen in Table 3, the frequency is modified by changing the
cation. In all cases, only one frequency compatible with CO
stretching was found, confirming that all complexes are mono-
carbonyl. While for [IrCl5CO]2- there are no isomeric structures
present, for the remaining monocarbonyl complexes, both cis and
trans isomers are possible. Using DFT calculations, we discov-
ered, for all complexes, that the trans isomers exhibit υCO 15-
30 cm-1 higher than the cis. In Table 3, we present the calculated
trans frequencies, which are in good agreement with the experi-
mental ones, 1 being the anion with the larger deviation. Taking
into account the X-ray structures for 2-As and 4-As, which turned
out to be the trans isomers, and the experimental and calculated
IR frequencies, we propose for the whole family the trans
configuration. Although the energy differences between both
isomers are not very high, this conclusion is reinforced by the fact
that the calculated stabilities for the trans isomers are higher than
for the cis ones for all of the complexes in the family (7.3 kcal/mol
for 2, 5.4 kcal/mol for 3, 4.8 kcal/mol for 4, and 5.2 kcal/mol for
5). In the following discussion, we will omit the “trans” prefix in
the formulas. All compounds have to be thought of as trans.
NMR. Probably the most important characteristic of these
complexes that can be studied with NMR spectroscopy is the 13C
signal due to CO. Using 1D and 2D experiments, we were able
Analysis of the supramolecular structure of these compounds
shows that while several intermolecular interactions are ob-
served, the CO does not participate directly in any one. In
2-As, O-H Cl hydrogen bonds between both water mole-
3 3 3
cules and the Cl ligands give place to the dimeric supramolecular
motives shown in Figure 2a and b. On the other hand, an infinite
chain as a result of the C-H Cl intermolecular interactions
3 3 3
exhibited in the 4-As anions is observed (Figure 2c). Finally,
some other C-H Cl interactions, between the phenyl rings
3 3 3
from the AsPh4þ and the Cl, are also present in both structures.
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Table 4. Carbonyl 13C NMR Displacements for the Chlor-
ocarbonyliridates Presented in This Work
Hydrolysis of 1-Cs. To study the potential capacity of the
compounds as CORMs, we checked the stability of 1-Cs in
aqueous solutions. Preliminary experiments suggested that 1-Cs
slowly exchanged ligands in aqueous solutions. In particular, the
IR spectra of aqueous solutions showed a υCO shift of ∼10 cm-1
(see Figure S12, Supporting Information). This result showed
that a chloride ligand was replaced by another ligand, probably
H2O. This hypothesis was confirmed by ESI-MS experiments
(data not shown) and, furthermore, by the isolation and char-
acterization of 2 using X-ray diffraction and other techniques.
Regarding these results, similar behavior was previously observed
for [IrCl6]3-, yielding [IrCl5H2O]2- and [IrCl4(H2O)2]-
subsequently.72-74
δ
13C (ppm) CO
solvent
1-As
2-Csa
151.4
144.8
144.6
150.5
151.9
152.3
154.4
156.4
CD3CN
D2O
2-As
CDCl3
D2O
3-Cs
3-As
CDCl3
D2O
4-Cs
4-As
CDCl3
(CD3)2SO
5-DMApy
a The spectrum was recorded upon complete hydrolysis of 1-Cs in D2O.
The proposed reaction can be described as an associative
mechanism:
to determine the 13C NMR chemical shifts for each carbonyl of
the presented complexes. Figure S9 (Supporting Information)
shows a 2D experiment performed on 3-Cs. We employed
external 1D experiments in conjunction with HSQC to highlight
the quaternary and carbonyl C atoms. In the spectrum, it can
be observed that there exists one 13C signal around 150 ppm
which does not correlate with any proton signal. Moreover, the
remaining 13C signals correlate with H signals. These correla-
tions helped to assign the aromatic hydrogens of the pyridine.
Therefore, the noncorrelating signal is assigned to CO. In cases such
as the water derivative, the single 13C signal corresponds to CO. The
results are summarized in Table 4. The 13C NMR signal for the car-
bonyl in these compounds was located between 144 and 157 ppm,
which resulted in particularly low values: terminal transition metal
carbonylsarefoundinthe range 150-220 ppm.64-66 These rather
small differences among the displacements are in agreement with
the also smallrange of observed IRfrequencies. The highυCOand
the low 13C NMR CO chemical shifts observed are compatible
with the poor backdonation present in the compounds.
Electrospray Ionization Mass Spectrometry (ESI-MS). ESI-
MS is a powerful technique used to characterize metal transition
complexes; consequently, we have used it in previous works to
investigate the structures of several classes of such species.66-71
Being a soft ionization technique, it allows the determination of
molecular masses of complex ions and the detection some of the
fragments due to the release of ligands. For the studied carbonyl
complexes, the presence of the moieties IrCl5, IrCl4, and IrCl3 in
the detected signals allows an accurate identification of the cor-
responding fragments due to their specific isotopologue patterns.
The use of high resolution ESI-MS, however, allows unequivocal
identification of a fragment formula from its accurate m/z value.
Figure S10 (Supporting Information) shows a typical ESI-MS
spectrum, in this case for 1. Note the peculiarity of such MS/MS
data where, because of the double charge of the intact parent
anion, its signal appears to the left of the spectrum at a low m/z
values (m/z 198.89 for the main ion) with the characteristic
0.5 m/z separation for the cluster of isotopologue ions. Upon
fragmentation via the loss of a chloride ligand, the [IrCl4CO]- ion
of m/z 360.82 is obtained, which fragments further by CO loss to
form [IrCl4]-, of m/z 332.82 (and respective isotopologue ions).
Note that a further loss of Cl- would produce the uncharged
fragment IrCl3, which is not possible to observe by MS. For all
complexes, a similar fragmentation behavior that is fully consistent
with the proposed structures as well as their ability to liberate CO
was observed, and in addition, the identity of all of the complexes
was confirmed by ESI-MS and ESI-MSMS and/or by high resolu-
tion FT-MS (Table S12, Supporting Information).
2-
2-
½IrCl5COꢁ þ H2O f ½IrCl5ðCOÞH2Oꢁ
ð1Þ
2-
-
½IrCl5ðCOÞH2Oꢁ f ½IrCl4ðCOÞH2Oꢁ þ Cl- ð2Þ
Assuming that eq 1 is the rate determining step, the rate of the
reaction can be written as
v ¼ - k½IrCl5CO2-ꢁ½H2Oꢁ ¼ - k0½IrCl5CO2-
ꢁ
ð3Þ
where k0 = k[H2O] due to the fact that the reaction is carried out
in water. Figure 3 shows a typical kinetic experiment. The
changes can be seen in the spectrum due to the modification
of the coordination sphere. By using factorial analysis techniques,
we obtained from the kinetic experiments the spectra from both
species and the concentration profiles (Figure S13, Supporting
Information), which allowed us to calculate the kinetic constant
at different temperatures. At 298 K, the first order kinetic
constant was (4.28 ( 0.05) ꢀ 10-5 s-1, which is comparable
but higher than for [IrCl6]3- (9.4 ꢀ 10-6 s-1). The effect of the
temperature was analyzed using an Eyring approach. The results
can be observed in Figure S14 (Supporting Information). The
value for the activation energy (17.5 kcal/mol) is smaller than the
one reported for the successive hydrolysis of [IrCl6]3- (30.4,
29.5, and 30.5 kcal/mol, for the first, second, and third chloride
hydrolysis, respectively). The negative value for the activation
entropy (-22 cal k-1 mol-1) is compatible with an associative
process as proposed in eq 1. This result is in agreement with the
fact that Ir(III) compounds exchange solvent by associative
processes.75
Myoglobin Carbonylation Assays. The most popular tech-
nique used to evaluate the potential donation of CO from
complexes employs myoglobin as the CO trapping agent.2 In
the presence of CO, deoxymyoglobin reacts according to
MbðIIÞ þ CO f MbCO
ð4Þ
Deoxymyoglobin yields carboxymyoglobin, which is stable on
the time scale of the experiments. In such experiments, changes
in the Soret and Q bands are observed. Figure 4 shows the typical
plots of CO being released from 2-Cs.
For each compound, several kinetic runs were recorded,
varying the ratio between the complex and the myoglobin. The
formation of MbCO was followed at 423 nm, but in each case, the
whole spectra were also recorded. The initial rates were obtained
by fitting a polynomial function to the first 5% of the trace. For
each experiment, the solutions of Mb were thermostatted to
37 ꢀC. Sodium dithionite was then added to reduce the Mb to
deoxymyoglobin; the complete transformation was evidenced by
the change in the spectrum. Finally, the addition of the carbonyl
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Figure 3. Hydrolysis of 1-Cs at 333 K. The inset presents a detailed 400-500 nm region.
Figure 4. Typical kinetic experiment of CO release (phosphate buffer 0.01 M, pH 7.4, 37 ꢀC) .
complex triggered the reaction. By using the initial rates and
plotting against the concentration of the complex, a first order
kinetic constant for the observed reaction at initial times can be
obtained using linear regression techniques. The same was
repeated for the whole family of compounds. By means of initial
rate experiments, we were able to show that the rate of
carbonylation depends on the CORM concentration (first
order), but it is independent of the Mb concentration (Figures
S2, S3, and S15, Supporting Information). In Figure S2, the effect
on the concentration of the complex is observed. Consequently,
upon increasing the concentration, the rate increases. In the same
way, the modification of the myoglobin concentration does not
affect the initial rate. Besides the completion of the reaction, it
can be observed that the three curves presented in Figure S3 are
almost similar: the initial slopes are identical.
shown. The modification of the rate due to variation of the
complex concentration is linear, suggesting that the reaction is
first order in the complex, at least at initial times. The compared
rates of the complexes can be observed in Figure 5 and Table 5.
By using the initial rate release as being indicative of the overall
capacity to release CO, the fastest release is observed for 5-
DMApy, while the slowest is for 1-Cs. However, if the shapes of
the releasing curves are analyzed in detail, 4-Cs shows a particular
behavior: after a small initial period, the curve flattens, and
eventually, the releasing rate becomes slower than for the
chloride derivative. This regime change could be attributed to
a competition between the CO and imidazole ligand for the
active site of the myoglobin. To test this hypothesis, we repeated
these procedures in the presence of imidazole. The experiments
were carried out using an excess of complex under the same
conditions of pH and temperature of the previous ones. The
addition of imidazole gave place to the disappearance of the
initial fast regime and a diminution of the slope for the slow
The initial rate effect upon the change in the concentration of
the CORM can be analyzed in Figure S15 (Supporting In-
formation), where a log plot of rate versus concentration is
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Figure 5. Comparison of the CO-releasing experiments with initial [complex]/[Mb] = 10 for the five anions investigated in this work. The experimental
conditions are 0.001 M phosphate buffer, ionic strength of KClO4 = 0.08 M, pH 7.35, 36.5 ꢀC, [Mb] approximately 10 μM.
Table 5. Observed kinetic constants (kobs in s-1) for
CO-releasing and initial CO-releasing rates (v0) for
[complex]:[Mb] = 1:1 and [Mb] approx. 10 μM
in these compounds the interaction with the metal is fundamen-
tally σ type (as we discussed in the IR and X-ray sections), there is
no fundamental difference between the O or N σ bond, and
consequently the rates are almost the same. In Table 6, DFT
calculated charges are presented for the metal center and the CO
moiety. The effect of the substitution is better observed on the
charge developed on the carbonyl. As the Ir-CO bond involves
both σ bonding and π backdonation from the metal center to the
carbonyl, a net positive charge over the CO represents that σ
bonding is more important than the backdonation. While in 1 the
net charge is around 0.05e, the remaining compounds show a
higher positive charge. This is in agreement with the diminished
backdonation in the single charged compounds. Using the same
analysis, 2 and its deprotonated derivative can be compared.
The charge on OH- is slightly negative, reinforcing the idea of a
higher backdonation. When comparing 3 and 5, both com-
pounds have similar metal and CO charges. However, upon
protonation of 5, the charge on CO increases, confirming that the
protonation diminishes the backdonation toward the CO, there-
fore weakening the Ir-CO bond.
One of the fastest CORMs described in the literature is
CORM-F10.30 The authors report a 3.4 μM min-1 releasing
rate from a 40 μM solution of the complex in DMSO and 50 μM
of myoglobin. This value corresponds to a t1/2 of ca. 6 min.
However, CORM-3 is faster in plasma.2 Some Mn CORMs with t1/2
under 2 min have also been reported.76 Our fastest complex has a
rate that is approximately 70% of CORM-F10 (extrapolating the
conditions). The remaining complexes show between 5 and 10%
of CORM-F10's releasing rate. Using the kinetic rate constants to
compare with the Mn CORMs, our fastest CORM has a t1/2 of ca.
10 min, and the slowest one is 154 min.
complex
kobs (s-1
)
v0 (μM min-1) complex/Mb ∼ 1:1
1-Cs
(7.5 ( 0.6) ꢀ 10-5
(11.7 ( 0.6) ꢀ 10-5
(19 ( 3) ꢀ 10-5
(26 ( 1) ꢀ 10-5
(110 ( 4) ꢀ 10-5
0.03
0.07
0.10
0.09
0.58
4-Cs
2-Cs
3-Cs
5-DMApy
regime (See Figure S16, Supporting Information). Table 5
presents the initial rates of release for all of the compounds,
calculated as the amount of CO released during the first minute
in a solution containing 10 μM of complex and 10 μM of
myoglobin.
It has to be pointed out that the exchange of the trans chloride
by any of the other ligands produces an increase in the releasing
rate of the compound. We can conclude that the decrease in the
total charge of the complex facilitates the release of CO, probably
due to a decrease in the electronic density available in the metal
center to backdonate to the CO. In the same direction, 5-
DMApy is faster than 2-Cs. The main difference between these
two molecules is the potential protonation of the dimethylamino
group of the DMApy. At the pH of the experiments and taking
into account the fact that upon coordination to a metal center the
pKa of DMApy can be reduced, it is reasonable to suppose that 5-
DMApy is in fact partially or completely protonated. By means of
DFT, we calculated the proton affinity for free and coordinated
DMApy. We found that ΔG for the deprotonation processes
(DMApyHþ þ H2O f DMApy þ H3Oþ) was equal to 41.2
kcal/mol for free DMApyHþ and 13.8 kcal/mol for the coordi-
nated one. This fact is compatible with the observation of a lower
pKa in case of the coordinated species or, in other words, an easier
deprotonation due to coordination. The diminished electronic
density of the iridium center in this case can explain the larger
releasing rate. If we compare 2-Cs with 3-Cs, due to the fact that
Regarding the mechanism of CO release, the results presented
here suggest clearly that the nature of the trans ligand affects the
rate of donation. The initial rate is independent of the myoglobin
concentration and depends linearly on the CORM concentra-
tion. These findings are similar to the ones observed in the
recently reported Re-based compounds of Zobi et al. Modifica-
tions of the trans moiety exerted profound changes in the
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Table 6. Activation Energies for the Ir-CO and Ir-L Bonds of the Complexes, Calculated at the DFT-BPW91 Level in the Gas
Phase and Normal Population Analysis (NPA) Charges for the Ir Atom and CO Moietya
complex
reaction
ΔE (kcal/mol)
NPA qIr (e)
0.550
NPA qCO (e)
0.045
[IrCl5CO]2- f {IrCl4CO----Cl}‡
[IrCl5CO]2- f {IrCl5----CO}‡
[IrCl4CO(H2O)]- f {IrCl4CO----(H2O)}‡
[IrCl4CO(H2O)]- f {IrCl4(H2O)----CO}‡
[IrCl4CO(py)]- f {IrCl4CO----(py)}‡
23.0
67.8
17.2
75.4
28.1
58.1
26.8
61.8
29.1
59.5
1
2
3
4
5
0.561 (0.661)*
0.536
0.177 (-0.030)*
0.187
[IrCl4CO(py)]- f {IrCl4(py)----CO}‡
[IrCl4CO(1-MeIm)]- f {IrCl4CO----(1-MeIm)}‡
[IrCl4CO(1-MeIm)]- f {IrCl4(1-MeIm)----CO}‡
[IrCl4CO(DMApy)]- f {IrCl4CO----(DMApy)}‡
[IrCl4CO(DMApy)]- f {IrCl4(DMApy)----CO}‡
0.554
0.173
0.544 (0.530)#
0.176 (0.231)#
a A / corresponds to the deprotonated species (OH), and # corresponds to the protonated species (DMApyHþ).
Figure 6. Correlation between the activation energy for dissociation (kcal/mol) of the Ir-CO bond versus the Ir-L bond, calculated at the DFT
BPW91 level. The blue line shows the trend.
releasing properties.36 In summary, the Ir-CO cleavage appears
to be the determining step in this type of reaction, at least at initial
times. More complex behaviors are observed as long as the
reaction continues forward, probably due to competition pro-
cesses or saturation.
Dissociation Energies Calculated by DFT. Each one of the
compounds presented above can exchange both the CO and the
trans ligand, a fact exemplified by the hydrolysis and the CO
release of 1. The rates for these two processes at 37 ꢀC are 1.24 ꢀ
10-4 s-1 (trans-Cl- exchange by water) and 7.5 ꢀ 10-5 s-1 (CO
release in the presence of Mb and Cl-). In order to further
explore the influence of the trans ligand, we calculated the energy
required for the dissociation in the gas phase for both ligands:
For all complexes, we calculated the energy changes associated
with reactions 5 and 6. The aim of these calculations is not to
describe explicitly the mechanism in solution, but to understand
the effect of the trans ligand on the CO and vice versa. To
estimate this effect, we chose the gas phase activation energy for
the ligand dissociation. In order to obtain these magnitudes, we
explored the potential energy surface of the dissociation and we
performed the explicit search of transition states. In other words,
we estimated the activation energy in the gas phase for the cases:
n-
‡
½IrCl4COðLÞꢁ f fIrCl4ðLÞ----COg
ð7Þ
ð8Þ
n-
‡
½IrCl4COðLÞꢁ f fIrCl4ðCOÞ----Lg
Table 6 presents the calculated energy changes for reactions 7
and 8. It can be observed that, for all anions, the energy required
for CO dissociation in the gas phase is higher (58.1 to 75.4 kcal/
mol) than for ligand dissociation (17.2 to 29.1 kcal/mol).
n-
n-
½IrCl4COðLÞꢁ f ½IrCl4ðLÞꢁ þ CO
ð5Þ
ð6Þ
n-
m-
½IrCl4COðLÞꢁ f ½IrCl4COꢁ þ Lp-
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Figure 7. Correlation between the activation (dissociation) energy (kcal/mol) of the Ir-CO bond calculated at the DFT BPW91 level versus
the observed kinetic constants for CO release. The red points correspond to H2O and DMApy complexes (2 and 5, respectively). The arrows show the
corresponding displacements for the corresponding OH- and DMApyHþ complexes. The red line shows the qualitative tendency of the points.
Figure 6 presents a correlation between the activation energies
of Table 6 for each one of the complexes. It can be observed that
the dissociation energies of the Ir-CO and Ir-L bonds are
inversely correlated: the complexes with stronger Ir-L bonds
present the weaker Ir-CO bonds, and vice versa. These results
are in agreement with the almost absent backdonation suggested
in these complexes. The particular competition between the trans
ligands (in this case CO and L) causes the presented trend.
So far, we have presented gas phase calculations while the
kinetic measurements were made in aqueous solution. The
reactions in solution are complicated due to the interaction of
the solvent and pH effects among other variables. Despite the
intrinsic nature of the mechanism in solution, we hypothesize
that the relative strength of the Ir-CO bond has to contribute, to
some extent, to the kinetic behavior of the complexes. Taking
into account that the extrapolation from gas phase calculations to
the observed kinetic constants in solution should be taken just as
a qualitative trend, in Figure 7 we plotted the observed first order
rate constants for the releasing compounds (in log scale) versus
the corresponding gas phase activation (dissociation) energy. A
qualitative trend can be observed: the complexes with the higher
dissociation energies are the slower ones. Particularly interesting
is the fact that the two points located far from the trend (in red)
correspond to the aquo and DMApy derivatives, which probably
are the most affected complexes in solution by the acid-base
equilibria of the ligands. If we replace the corresponding com-
plexes by the protonated and deprotonated complexes of each
one (DMApyHþ for DMApy and OH- for H2O), the displace-
ment of their respective points agree with the trend described by
protonated and deprotonated species, which have different
energetics for the CO release. Two important facts can be
extracted from these calculations: (1) the strength of the Ir-
CO bond can be related to the strength of the trans Ir-L bond;
(2) a qualitative correlation of the CO releasing rate can be
obtained from the Ir-CO dissociation energy.
’ CONCLUSIONS
A new family of compounds based on [IrCl4(CO)L]n- was
presented. The compounds can donate CO to myoglobin under
physiological conditions (aqueous solution, pH 7, 37 ꢀC). The
most interesting feature of these species is the poor backdonation
from the iridium center to the CO. This effect can be observed in
the calculated population (NPA) over the CO moiety in each one
of the compounds. The IR and NMR data of the carbonyls spread
in a small range, 144-156 ppm for the NMR signals and 2025-
2085 cm-1 for the IR stretching frequencies. No clear correla-
tions between the stretching frequencies and the NMR signals
were found. However, the donation rate is modulated by the
identity of the sixth ligand trans to CO. The rate is accelerated by
almost 20 times when the Cl- trans to the CO is replaced by
DMApy. All complexes are soluble in water, and the rates of
donation are comparable to other CORMs described in the
literature. An inverse correlation between the Ir-L and Ir-CO
bonds has been found using DFT calculations, which allows (in
principle) one to design in silico new potential compounds with
higher or lower releasing rates using the qualitative trend
observed between the Ir-CO dissociation energy and first order
rate constant for CO release. Due to the versatility of the
[IrCl4(CO)L]n- platform, the extension of this family of com-
pounds is easy. Regarding the toxicity of the compounds, while
no assays were performed so far, the high degree of inertness of
the Ir(III) compounds suggests a low toxicity.
the red line (ΔE DMApyHþ = 55.3 kcal/mol and ΔE OH-
=
66.4 kcal/mol; both dissociations coincide with the activations).
We can hypothesize that due to the observed kinetic constants,
these two complexes are probably in equilibrium between the
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’ AUTHOR INFORMATION
Corresponding Author
*E-mail: doctorovich@qi.fcen.uba.ar.
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