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Photophysical and biological characterization of new cationic cyclometalated M(III) complexes of rhodium and iridium
Accepted Manuscript
Photophysical and Biological Characterization of new cationic cyclometalated M(III)
complexes of rhodium and iridium
Marion Graf , Yvonne Gothe , Nils Metzler-Nolte , Rafał Czerwieniec , Karlheinz
Sünkel
PII:
S0022-328X(14)00213-7
DOI:
10.1016/j.jorganchem.2014.04.031
Reference:
JOM 18566
To appear in:
Journal of Organometallic Chemistry
Received Date: 10 December 2013
Revised Date:
28 April 2014
Accepted Date: 29 April 2014
Please cite this article as: M. Graf, Y. Gothe, N. Metzler-Nolte, R. Czerwieniec, K. Sünkel, Photophysical
and Biological Characterization of new cationic cyclometalated M(III) complexes of rhodium and iridium,
Journal of Organometallic Chemistry (2014), doi: 10.1016/j.jorganchem.2014.04.031.
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Photophysical and Biological Characterization of new cationic
cyclometalated M(III) complexes of rhodium and iridium
Marion Grafa, Yvonne Gotheb, Nils Metzler-Nolteb, Rafał Czerwieniecc
a
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Karlheinz Sünkela*
Department of Chemistry, Ludwig Maximilian University of Munich, Butenandtstraße 5–13,
81377 Munich, Germany
b
Institute of Physical and Theoretical Chemistry Universität Regensburg, Universitätsstraße
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c
Ruhr University Bochum, Universitätsstraße 150, 44801 Bochum, Germany
ABSTRACT
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31, 93053 Regensburg, Germany
Synthesis and characterization of new cyclometalated complex salts [M(ptpy)2(ddmp)]PF6 (M
= Rh, 1; M = Ir, 2; ptpy = 2-(p-tolyl)pyridinato; ddmp = 4,7-dichloro-2,9-dimethyl-1,10phenanthroline) is described. Compounds 1 and 2 were obtained by the reaction of ddmp with
the complexes [{M(µ-Cl)(ptpy)2}2] (M = Rh, Ir) in a mixture of CH2Cl2/MeOH/H2O under
conditions.
The
compounds
1
and
2
crystallized
from
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reflux
dichloromethane/chloroform/hexane in the triclinic space group P 1̄ and their molecular
structures were confirmed by single-crystal X-ray diffraction. Compound 2 exhibits strong
yellow phosphorescence in a polymer matrix and in solution at ambient temperature. Both
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compounds display significant cytotoxicity against human cancer cell lines with the IC50
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values in the high nanomolar range.
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* Corresponding author. Tel.: +49 89218077773; fax: +49 89218077774
E-mail address: suenk@cup.uni-muenchen.de (K. Sünkel)
Dedicated to Prof. Ingo –Peter Lorenz on the occasion of his 70th birthday
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1. Introduction
Bis-cyclometalated Ir(III) complexes play an important role in the development of modern
optoelectronic technologies (e.g. organic light emitting diodes − OLEDs [1] and light-emitting
electrochemical cells − LEECs [2]), (bio-) chemical labels and sensors [3]. In the last years
we described the synthesis and characterisation of several neutral cyclometalated M(III)
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complexes of the elements rhodium and iridium [4], including complexes containing
biomolecules as ancillary ligands [5].
It was found by several groups that for bio-medical diagnostic and therapeutic studies [3c, 69] the use of water-soluble complexes of the type [M(C^N)2(N^N)]+ was particularly
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beneficial. Starting from the long-known compounds with M = Rh [10] and Ir [11], C^N = 2phenylpyridinato (ppy) and N^N = 2,2’-bipyridine (bpy) or phenanthroline (phen), numerous
studies were performed to elucidate the effects of various substituents on the photophysical
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and electrochemical properties of the complexes and how they influence the device
performance in different applications. [12-14]
In this paper we describe the synthesis and characterization of two new cyclometalated
complex salts [M(ptpy)2(ddmp)]PF6 (M = Rh, 1; M = Ir, 2; ptpyH = 2-(p-tolyl)pyridine; ddmp
= 4,7-dichloro-2,9-dimethyl-1,10-phenanthroline). The photophysical studies on the room-
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temperature luminescence of 2 as well as investigations of the cytotoxicity of 1 and 2 towards
the cell lines MCF-7 and HT-29 are presented.
2. Experimental
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2.1. General considerations
All manipulations were performed under an atmosphere of dry nitrogen using
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conventional Schlenk techniques. Solvents and Hptpy were used as received (from Aldrich).
[{M(µ-Cl)(ptpy)2}2] (M = Rh, Ir) were prepared by our published method [4e, 4b]. NMR
spectra were recorded in CD2Cl2 using a Jeol Eclipse 400 instrument operating at 400 MHz
(1H) and 100 MHz (13C) respectively. Chemical shifts are given in ppm, referenced to the
solvent signals at δ = 5.30 (1H) or 53.8 ppm (13C). Assignments of NMR signals refer to
scheme 1. Mass spectra were measured using a Jeol Mstation JMS 700 spectrometer.
Elemental analyses (C, H, N) were performed by the Microanalytical Laboratory of the
Department of Chemistry, LMU Munich, using a Heraeus Elementar Vario El instrument.
Dulbecco’s Modified Eagle’s Medium (DMEM), containing 10% fetal calf serum, 1%
penicillin and streptomycin, was used as growth medium. MCF-7 and HT-29 cells were
detached from the wells with trypsin and EDTA, harvested by centrifugation and resuspended
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again in the cell culture medium. The assays were carried out on 96 well plates with 6000
(3000) cells per well for MCF-7 (HT-29, respectively). After 24 h of incubation at 37°C and
10% CO2, the cells were treated with the compounds 1 and 2 (with DMSO concentrations of
0.5%) with a final volume of 200 µl per well. For a negative control, one series of cells was
left untreated. The cells were incubated for 48 h followed by adding 50 µl MTT (2.5 mg/ml).
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After an incubation time of 2 h, the medium was removed and 200 µl DMSO were added. The
formazan crystals were dissolved and the absorption was measured at 550 nm, using a
reference wavelength of 620 nm. Each test was repeated in quadruplicates in two independent
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experiments for each cell line.
2.2. Synthesis of [Rh(ptpy)2(ddmp)]PF6 (1)
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((scheme 1))
To a solution of [{Rh(µ-Cl)(ptpy)2}2] (142 mg, 0.15 mmol) in 25 mL of a mixture of
CH2Cl2/MeOH/H2O (2:2:1) the ligand 4,7-dichloro-2,9-dimethyl-1,10-phenanthroline (110
mg, 0.4 mmol) was added and the mixture refluxed with stirring for 2 h. After cooling to
room temperature KPF6 (70 mg, 0.4 mmol) was added. The solvent was removed to dryness
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in vacuo and the residue dissolved in dichloromethane and chromatographed on alumina with
CH2Cl2/acetone (9:1) as the eluent. The solution was evaporated to dryness and the residue
was redissolved in 5 ml of dichloromethane and the product was precipitated by slow
diffusion of hexane. X-ray quality crystals were obtained by slow diffusion of hexane into a
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solution of dichloromethane/chloroform of the compound at room temperature. Yield: 130 mg
(50.4 %). Anal. Calc. for C38H30Cl2F6N4PRh: C, 52.98; H, 3.51; N, 6.50. Found: C, 52.94; H,
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3.78; N, 6.63 %. MS (FAB+): m/z = 715.3 [M+] complex cation. 1H NMR: δ= 8.47 (s, 2 H,
Hb), 7.96-7.78 (m, 4 H, H3 and H4), 7.71 (s, 2 H, Hf), 7.59 (d, 8 Hz, 2H, H8), 7.41 (“d”, 2H,
H6), 6.92-6.86 (m, 4H, H5 and H9), 5.98 (s, 2H, H11), 2.15 (s, 6H), 2.05 (s, 6 H). 13C {1H}
NMR: δ= 166.3 (d, 34 Hz, C12), 165.3 (C2), 165.1 (Ce), 149.3 (C6), 147.2 (Ca), 146.0 (Cd),
141.0, 140.9 (C7 and C10), 138.8 (C4), 133.9 (C11), 128.4 (Cf), 127.9 (Cc), 125.0, 124.9,
124.0 (C8, C9 and Cb), 122.9(C5), 120.2 (C3), 27.0 (Cg), 22.0 (C13).
2.3. Synthesis of [Ir(ptpy)2(ddmp)]PF6 (2)
To a solution of [{Ir(µ-Cl)(ptpy)2}2] (169 mg, 0.15 mmol) in 25 mL of a mixture of
CH2Cl2/MeOH/H2O (2:2:1) the ligand 4,7-dichloro-2,9-dimethyl-1,10-phenanthroline (110
mg, 0.4 mmol) was added and the mixture refluxed with stirring for 2 h. After cooling to
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room temperature KPF6 (70 mg, 0.38 mmol) was added. The solvent was removed in vacuo
and the residue was dissolved in dichloromethane and chromatographed on alumina with
CH2Cl2/acetone (9:1) as the eluent. The solution was evaporated to dryness and the residue
redissolved in 5 ml of dichloromethane. The product was precipitated by slow diffusion of
hexane. Suitable crystals for X-ray diffraction were obtained by slow diffusion of hexane into
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a solution of dichloromethane/chloroform at room temperature. Yield: 200 mg (66 %). Anal.
Calc. for C38H30Cl2F6IrN4P x 0.5 CHCl3: C, 45.76; H, 3.04; N, 5.54. Found: C, 46.00; H, 3.13;
N, 5.66 %. MS (FAB+): m/z = 805.4 [M+] complex cation. NMR: δ= 8.49 (s, 2 H, Hb), 7.90
(“d”, 8 Hz, 2 H, H3), 7.76 (“dt”, 2 H, H4), 7.73 (s, 2 H, Hf), 7.57 (“d”, 8 Hz, 2H, H8), 7.43
(“d”, 2H, H6), 6.87 (“dt”, 2H, H5), 6.83 (“dd”, 2H, H9), 5.92 (s, 2H, H11), 2.12 (s, 6H, Hg),
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2.07 (s, 6 H, H13). 13C {1H} NMR: δ= 167.9 (C2), 166.0 (Ce), 149.5 (C6), 149.1 (Ca), 148.2
(C12), 145.9 (Cd), 140.9 (C10), 140.8 (C7), 138.6 (C4), 132.5 (C11), 128.74 (Cf), 128.69 (Cc),
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125.2 (C8), 124.4 (Cb), 124.0 (C9), 122.8 (C5), 119.9 (C3), 27.7 (Cg), 21.9 (C13).
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2.4. X-ray structural determinations
Suitable single crystals of 1 and 2, respectively, were selected by means of a
polarization microscope, mounted on the tip of a glass fiber, and investigated on a BRUKER
D8 Quest diffractometer using Mo Kα radiation (λ = 0.71073 Å). The intensities were
corrected for absorption by the semi-empirical multiscan method (SADABS) [15]. The structure
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was solved by direct methods (SIR 97) and refined by full-matrix least-squares calculations on
F2 (SHELXL-97), as implemented in the software package WINGX.[16] Analysis by the program
PLATON (also implemented in WINGX) showed large voids (33%) in the crystal of the Rh
complex 1, which was handled by implementing the program subroutine
SQUEEZE.
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Anisotropic displacement parameters were refined for all non-hydrogen atoms. Details of the
crystal data, data collection, structure solution, and refinement parameters are summarized in
((Table 1))
2.5. Photophysical Measurements.
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Table 1.
UV-Vis absorption spectra were recorded with a Varian Cary 300 double beam
spectrometer. Luminescence and excitation spectra were measured with a Horiba Jobin Yvon
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Fluorolog 3 steady-state fluorescence spectrometer. For decay time measurements a
PicoQuant LDH-P-C-375 pulsed diode laser (λexc = 372 nm, pulse width 100 ps) was applied
as the excitation source. The emission signal was detected with a cooled photomultiplier
attached to a FAST ComTec multichannel scalar card with a time resolution of 250 ps.
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Photoluminescence quantum yields were determined with a Hamamatsu C9920-02 system
equipped with a Spectralon integrating sphere. Diluted solutions (c ≈ 10−5 M−1) in 2methyltetrahydrofuran (MTHF) were degassed by several freeze-pump-thaw cycles (p =
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1×10−5 mbar). Polymer films containing about 0.1 weight% of the Ir complex 2 were obtained
by dissolving the emitter and poly(methyl methacrylate) (PMMA) in dichloromethane and
spin-coating these solutions onto quartz glass substrates. PMMA films were measured under
continuous flushing with nitrogen.
2.6. Computational Methodology.
Molecular geometry of [It(ptpy)2(ddmp)]+ (2) was optimized using the density
functional theory (DFT) with the hybrid gradient corrected correlation functional B3LYP [17].
Electronic excitations were calculated for the DFT optimized ground-state geometry using the
time-dependent density functional theory (TD-DFT). Six lowest triplet and singlet excitations
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were computed. The Ahlrichs split-valence basis set SVP [18] was applied for atoms C, H, N,
and Cl and the quadruple-dzeta quality basis set QZVP [19] was used for Ir. Inner-core
electrons of Ir were substituted with a relativistic effective core potential. [20] All
computations were carried out using the Gaussian 09 program package. [21]
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3. Results and discussion
3.1. Synthesis and characterization of compounds
The cyclometalating ligand 2-(p-tolyl)pyridine (Hptpy) was used for the synthesis of
the chloro-bridged dimers [{M(µ-Cl)(ptpy)2}2] (M = Rh, Ir) starting from the corresponding
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M(I) complexes [{M(µ-Cl)(coe)2}2] (coe = 1,4-cyclooctadiene) by an oxidative addition
reaction as described previously [2b, 2e]. Subsequently, the preparation of the title complexes
was realized by cleavage of the dimeric compounds to the cationic mononuclear complexes
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using the chelating ligand 4,7-dichloro-2,9-dimethyl-1,10-phenanthroline (ddmp). The
reaction was carried out in a refluxing mixture of dichloromethane/methanol/water for 2 h.
Thus, the complex salts [M(ptpy)2(ddmp)]Cl were formed. The salt metatheses with KPF6
yielded the hexafluorophosphate derivatives 1 and 2 (see Scheme). The complex salts 1 and 2
were obtained as yellow crystals in good yields and were characterized by elemental analyses,
H and 13C NMR spectroscopy, and by single crystal X-ray diffraction studies.
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Due to strong overlap of the signals of the phenanthroline and the phenylpyridine moieties,
both in the 1H- and 13C-NMR spectra, precise assignment of all the NMR signals to individual
protons and carbon atoms in the aromatic region was not possible. The relative intensities of
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((scheme))
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the methyl protons of the ptpy and dmpp ligands being 6:6 prove the proposed stoichiometry.
3.2. Crystal and molecular structure of 1 and 2
Crystals
suitable
for
an
X-ray
diffraction
study
were
grown
from
CH2Cl2/CHCl3/hexane solutions. Crystals of 1 and 2, respectively, belong to the triclinic
space group P 1̄. The Rh compound 1 contains two independent molecules in the unit cell. As
mentioned above, the analysis by the program PLATON showed large voids in the crystal of
1 which make up 33% of the unit cell volume. Since no solvent molecules could be localized,
the program routine SQUEEZE was applied for simulating the missing electron density. This led
to acceptable R1 values of ca. 6%, but left a high wR2 value of ca. 19%. The major difference
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between the two independent molecules is found in the relative orientations of the three
chelate rings: while the interplanar angles between the phenanthroline chelate and the two
cyclometallates are 85±1° at Rh1, they are 80.6±0.8° at Rh2. The Rh-N(tpy) bond lengths are
identical within 2σ, averaging at 2.042(4) Å. The same applies for the Rh-C(tpy) bonds
(average 1.994(5) Å). The Rh-N(phen) bonds are longer at Rh1 (average 2.246(4) Å) than at
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Rh2 (average 2.225(5) Å), which reflects also the difference in the interplanar angles
mentioned above. The N-M-C chelate angles range from 80.5(2)° to 81.6(2)°, while the
N-M-N angle is identical on both Rh atoms within 1σ, averaging at 75.4(1)°. In the related
bipyridine complex [Rh(thpy)2(bpy)]Cl bond lengths of 2.060 Å, 1.989 Å and 2.144 Å are
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found for Rh-N(thpy), Rh-C(thpy) and Rh-N(bpy), respectively[10c]. The chelate angle NRh-N is reported as 76.7(1)°.
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((figure 1))
The Ir complex 2 (figure 1) crystallizes with two molecules of chloroform which could
be localized without any problems. The Ir-N(tpy) bond lengths are identical within 2σ,
averaging at 2.047(5) Å, which is only slightly longer than in the Rh compound. The Ir-C(tpy)
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and Ir-N(ddmp) bond lengths are identical within 1σ, averaging at 2.013(6) and 2.200(5) Å,
respectively. Interestingly, the former bond is longer than in complex 1, while the latter is
shorter. The N-M-C chelate angles average at 80.6(2)° within 1σ, slightly smaller than in the
Rh case, while the N-M-N chelate angle is with 75.9(2)° slightly larger than the Rh analog.
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The interplanar angles between the three chelate planes are identical within 2σ, averaging at
80.3(2)°. In both compounds the cyclometalated rings are close to ideally planar, while the
phenanthroline chelate rings are better described as non-planar “envelopes”. In the related
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complex [Ir(ppy)2(dmdpbpy)][PF6] (dmdpbpy = 6,6'-dimethyl-4,4'-diphenyl- bipyridine)
bond lengths of ca. 2.04 Å, 2.01 Å and 2.21 Å are found for Ir-N(ppy), Ir-C(ppy) and IrN(dmdpbpy), respectively [2b] It was stated that the “ortho” methyl substituents, i.e. methyl
groups in the positions 6 and 6’ of 2,2’-bipyridine and in the positions 2 and 9 of
phenanthroline, lead to lengthening of the Ir-N(bpy) bonds as compared to the unsubstituted
bpy complex. Also in the closely related complex [Ir(ppy)2(phen)][PF6] the Ir-N(ppy), IrC(ppy) and Ir-N(phen) bond lengths of 2.05 Å, 2.01 Å and 2.14 Å were found, respectively.
The latter Ir-N(phen) bonds are
significantly shorter than the Ir-N(ddmp) distances of
2.200(5) Å in compound 2. The bite angles at the cyclometallated ptpy and phenanthroline
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moieties were reported as ca. 80° and 78°, respectively. [2a] Bulky substituents in more
remote positions seemingly have no influence on the Ir-N(phen) bond lengths. [22]
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3.3. Photophysical properties of 1 and 2
Luminescent transition metal (TM) complexes have become recognized as valuable
luminophores for application in biological cell imaging studies. The accumulation of such
bio-imaging agents in particular cell compartments can be monitored through confocal
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luminescence spectroscopy.[23-27] Phosphorescence stemming from the triplet excited state
of a TM complex is distinctly red-shifted relative to the lowest absorption band which arises
from a transition between the singlet ground state and the lowest singlet excited state. Thus, it
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can be easily distinguished from the autogenous cell fluorescence (mostly in the blue spectral
region), which is characterized by relatively small Stokes’ shifts, by wavelength filtering.
Moreover, the relatively long decay times of the TM-complex phosphorescence
(microseconds) differ from the short decay times (nanoseconds) of autogenous fluorescence
by 2 to 4 orders of magnitude. Thus, the emission of a phosphorescent probe can be
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distinguished from the autofluorescence by the time-gated detection methods.[23] For these
reasons we decided to investigate the photophysical properties of the Ir complex 2.
The UV-Vis absorption spectra of 1 and 2 were studied in dichloromethane solution (c
= 0.05 mM) at room temperature. The high-energy part of the spectra (λ ≤ 300 nm) is
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dominated by spin-allowed π → π* transitions of the ptpy and ddmp ligands. These
overlapping ligand-centered transitions give rise to intense absorption bands peaking at λmax =
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272 nm (εmax = 1.8 ×104 M−1cm−1) for 1 and 274 nm (εmax = 5.0 ×104 M−1cm−1) for 2 (Fig. 1),
respectively. In the lower energy region, between ca. 300 and 390 nm for complex 1 and
between 300 and 430 nm for 2, a series of weaker absorption bands (ε ≈ 3 −8 ×103 M−1cm−1)
with much weaker tails (ε < 1000 M−1cm−1) stretching at 390 − 450 nm (compound 1) and
430 − 520 nm (compound 2), respectively, is observed. The red tail of the absorption
spectrum of 2 matches with the lowest-energy signals observed in the excitation spectrum
recorded for this compound in a glassy solution at 77 K (Fig. 2). Since such absorptions are
not present in the spectra of the free ligands ptpyH and ddmp, the long-wavelength absorption
bands of the complexes are assigned to metal-to-ligand charge-transfer (MLCT) transitions
involving the occupied dπ orbitals of the metals (2dπ(Rh) and 3dπ(Ir) in 1 and 2, respectively)
and empty π* orbitals of the ptpy and ddmp ligands, respectively. Similar arguments for the
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assignment of the low-energy absorption bands of related TM-compounds can be found in
numerous studies in the literature.[1c,28,29] The above assignments are further supported by
results of the TD-DFT calculations described below.
((figure 2))
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The Ir complex 2 is strongly luminescent at ambient temperature. For instance,
[Ir(ptpy)2(ddmp)][PF6] (2) doped into PMMA displays yellow luminescence with the
maximum at λmax = 562 nm. The emission band is broad and unstructured (Fig. 3). The
quantum yield φPL amounts to 54 % and the decay time τem is 1.9 µs. Similar τem values in
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order of a few microseconds are frequently found for phosphorescent Ir(III) complexes. [1c,
28,29] Accordingly, the emission of 2 is assigned to the lowest triplet state T1. Results of the
TD-DFT computations point to the T1 excited state being 3MLCT in character with dominant
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contributions from the ddmp ligand. (See below.)
((figure 3))
The emission properties of 2 are modulated by the matrix/solvent used. Thus, solutions
of [Ir(ptpy)2(ddmp)][PF6] (2) in organic solvents show moderately intense orange emission.
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For instance, in 2-methyltetrahydrofuran (MTHF) the luminescence band is centered at λmax =
612 nm. The quantum yield of this emission is 17 % and decay time τem = 0.56 µs (Table 3).
According to the long excited-state lifetime and large diffusion rates in solution the
photoluminescence of 2 is quenched by molecular oxygen. Thus, in air saturated solution the
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quantum yield decreases to 3.5 % and the decay time of τem = 140 ns is 4 times shorter than in
the degassed solution. (Table 2) Nevertheless, the O2-quenching is not complete and the
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luminescence of 2 remains reasonably strong for detection under aerobic conditions.
The observed red-shift of the emission band of 2 from λmax = 526 nm in frozen MTHF
at 77 K to 552 nm in PMMA at room temperature and λmax = 612 nm in the MTHF solution is
conform to the distinct charge-transfer character of the lowest excited state T1 (3MLCT).
Thus, electrostatic interactions of the 3MLCT-excited molecule with the induced dipole
moments in its close surrounding result in an additional stabilization of the excited state and
thus, to a lower energy of the emission. [30] The smaller separation between the emitting state
T1 and the ground state S0 in solution, as compared to the PMMA matrix or the frozen MTHF
glass at 77 K, leads to a stronger vibrational coupling between the T1 and S0 electronic states.
As a result, according to the so-called energy gap law,[31] the non-radiative relaxation of the
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T1 excited state to the electronic ground state S0 is more effective, which manifests itself by
the distinctly lower φPL and τem values in solution.
((Table 2))
3.4. Theoretical calculations
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The B3LYP/[SVP+QZVP(ECP)] DFT calculations were carried out on the
[Ir(ptpy)2(ddmp)]+ ion (2) in order to elucidate the character of the lowest excited states and to
ascertain the role of the particular ligands, ptpy and ddmp, respectively, for the excited-state
properties of the complex. The HOMO and LUMO surfaces are illustrated in Fig. 4 and the
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characters of other spectroscopically relevant molecular orbitals are analysed in Table 3. The
HOMO consists principally from a mixture of Ir-dx2-y2 and phenyl-π orbitals, whereas LUMO
(π*) is mainly localized on the ddmp ligand. Orbitals HOMO – 1 to HOMO – 3 contain
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dominant contributions from the phenyl fragments of the ptpy ligands and HOMO – 4 and
HOMO – 5 represent essentially two 3d(Ir) orbitals. LUMO + 1 is mainly centred on ddmp
and LUMO +2 and LUMO +3 are combined from dominant contributions from the pyridine
rings of the both ptpy ligands.
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((Figure 4))
((Table 3))
The lowest electronic transitions, S0 → T1 and S0 → S1, respectively, are identified as
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MLCT transitions, which originate mainly (98 %) in HOMO → LUMO excitations carrying
distinct 3dx2-y2(Ir)-π*(ddmp) character. The lowest singlet transition at 2.18 eV with the
calculated oscillator strength f of only 0.0001 carries only very little intensity.[32] It
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contributes to the weak red tail of the absorption spectrum. On the other hand, the S0 → S2
transition at 2.47 eV, which stems mainly from the HOMO → LUMO + 1 excitation
(polarized along the C2 axis of symmetry, which intersects the Ir atom and the centre of the
ddmp ligand) is distinctly more intense (f = 0.0025) and, thus, it contributes strongly to the
low-energy part of the absorption spectrum. A similar situation is frequently found in
TM−diimine complexes, e.g. Re(CO)3(bpy)Cl,[33] where the S0 → S1 transition is very weak
and cannot be spectrally resolved from the stronger S0 → S2 MLCT transition.
3.5. Biological activity.
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Ir(III) and Rh(III) complexes have recently gained considerable attention as anti-cancer
agents.[3c, 6b] To obtain an insight into the anti-tumor activity of compounds 1 and 2, their in
vitro toxicity towards the cancer cell lines HT29 (human colon carcinoma) and MCF-7
(human breast carcinoma) has been investigated (Table 4). The cytotoxicity was evaluated
using the MTT assay, which measures the mitochondrial metabolism in the entire cell. For the
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well-established clinical drug cisplatin, IC50 values (half maximal inhibitory concentration) of
7.0 ± 2.0 µM for HT-29 and 2.0 ± 0.3 µM for MCF-7, respectively, were obtained.[34]
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((Table 4))
Compared to cisplatin, the investigated compounds show significantly higher cytotoxicity
towards the cancer cell lines under study. These strong cytotoxic effects are reflected by
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relatively low IC50 values which are in the high nanomolar range. For a comparison, in a
recent publication by Lo et al., IC50 of approximately 4 µM were reported for cyclometallated
Ir compounds with dialkyl-amino substituted phenanthroline ligands [5c].
In general, the MCF-7 cells are more sensitive to the treatment than the HT-29 cells.
Interestingly, the Ir(III) complex shows higher cytotoxicity towards both cell lines compared
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to its Rh(III) analogue. The opposite was reported in a previous work, [11] in which several
Rh(III) and Ir(III) complexes were assayed for their cytotoxic activity. Containing the same
ligand system, the Rh(III) complexes showed higher cytotoxicity than the Ir(III) analogues.
This leads to the assumption that the cytotoxicity is not exclusively related to the metal center
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4. Conclusions
The synthesis of two cationic bis-cyclometalated complexes [M(ptpy)2(ddmp)][PF6] (M =
Rh, 1; M = Ir, 2; ptpy = 2-(p-tolyl)pyridinato, ddmp = 4,7-dichloro-2,9-dimethyl-1,10phenanthroline) is described. These new metallorganic compounds were prepared in good
yields by the bridge-splitting reaction between the dinuclear complexes [{M(µ-Cl)(ptpy)2}2]
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and the chelating diimine ligand ddmp. The X-ray diffraction studies revealed the cationic
molecules of 1 and 2 as mononuclear M(III) complexes and, thus, confirmed the molecular
structures of 1 and 2 inferred from the results of the elemental analyses and the spectroscopic
NMR and MS investigations.
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The iridium complex 2 is strongly luminescent as powder, polymer film, and in solution
at ambient temperature. In PMMA it exhibits intense yellow emission centered at λmax = 562
nm (φPL = 54%). In MTHF solution, this compound displays orange emission at λmax = 612
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nm, which is partly quenched by oxygen in non-degased samples. Nevertheless, even in
aerated samples, the emission is reasonably strong (φPL = 3.5 % and τem = 140 ns) for a non
complicated detection. The photophysical characterisations, supported by the results of the
quantum mechanical computations, lead to the assignment of the observed luminescnce as
stemming from the lowest triplet state T1, which is mainly 3MLCT (d(Ir)-π*(ddmp)) in
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character.
Both compounds under study are capable of penetrating living mammalian cells. In the
human colon carcinoma HT-29 and the breast cancer MCF-7 cell lines strong cytotoxicity
induced by 1 and 2 were observed. The half maximal inhibitory concentrations (IC50) found
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for the both compounds are in the high nanomolar range (200 nM – 1000 nM). The cytotoxic
effects of the iridium complex 2 slightly exceeded that of the rhodium congener 1, i.e. the IC50
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values for 2 were approximately three times smaller than that determined for 1. Remarkably,
the IC50 values of 2 are about one order of magnitude smaller than IC50 exhibited by the
anticancer drug cisplatin under similar conditions against the same cell cultures.
Summing up, the rhodium and iridium complexes reported here are important for future
biological/medicinal investigations making use of the luminescence and cytotoxic properties
of these materials.
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Acknowledgments
The authors are grateful to the Department of Chemistry of the Ludwig Maximilians
University Munich for support. P. Mayer is acknowledged for collecting the X-ray crystal
data data and Prof. Hartmut Yersin (University Regensburg) for inspiring discussions. R.C.
thanks the German Federal Ministry of Education and Research (BMBF) for financial
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support.
Supplementary material
CCDC-975514 (1) and CCDC-975515 (2) contain the supplementary crystallographic
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data for this paper. These data can be obtained free of charge from The Cambridge
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Crystallographic Data Centre via http://www.ccdc.cam.ac.uk/data_request/cif.
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Figure Captions:
Figure 1: Molecular structure of the cation of 2. Thermal ellipsoids at the 30% probability
level.
Figure 2. UV-Vis absorption spectrum of [Ir(ptpy)2(ddmp)][PF6] (2) in CH2Cl2 (c = 0.05
mM) at room temperature (solid line) and 77 K excitation spectrum of 2 recorded in frozen
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MTHF (= 2-methyltetrahydrofuran) solution (dotted line), λdet = 540 nm.
Figure 3. Luminescence spectra of [Ir(ptpy)2(ddmp)][PF6] recorded in poly(methyl
methacrylate) (PMMA, c = 1 weight%) and 2-methyltetrahydrofuran (MTHF, c = 1 × 10−5
M−1) at ambient temperature. λexc = 400 nm.
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Figure 4. Frontier orbitals of [Ir(ptpy)2(ddmp)]+ (2).
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The lowest-energy electronic transitions in [Ir(ptpy)2(ddmp)]+ (molecular symmetry
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group C2) are associated with promotion of an electron from Ir onto the ddmp ligand
along the C2 symmetry axis (= x-axis of coordinates). Thus, they result in a significant
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change of the molecular dipole moment along this axis. In such a situation, the transition
r
matrix element f1 erx f 2 , where f1 and f3 are the molecular wavefunctions of the initial
and the final quantum states, is intuitively expected to be significantly larger than the
r
r
r r
transition matrix elements f1 ery f 2 and f1 erz f 2 orthogonal to the C2 axis. ( erx , e ry ,
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r
erz are the molecular dipole moment components.) HOMO of [Ir(ptpy)2(ddmp)]+ carries
distinct Ir-dx2-y2 character and belongs to the symmetry type a. LUMO is a b type ddmpπ* orbital and LUMO + 1 is an a type ddmp-π* orbital, respectively. In the C2 point
r
group,
f1 erx f 2 elements involving f1 and f3 spanning different irreducible
representations are equal zero. Therefore the HOMO → LUMO transition described by
r
the matrix element a erx b = 0 is expected to carry only very little intensity. On the
r
contrary, the HOMO → LUMO + 1 transition ( a erx a ≠ 0) is expected to be more
intense. Indeed, the oscillator strengths calculated for the HOMO → LUMO and HOMO
→ LUMO + 1 excitations are f = 0.0001 and f = 0.0025, respectively.
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Med. Chem. 51 (2008) 3924
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Table 1: Experimental Data of the Structure determinations
Compound
1
2
C38H30Cl2F6N4PRh
C38H30Cl2F6IrN4P × 2CHCl3
Formula weight
861.44
1189.47
Temperature K
200(2)
200(2)
Crystal system
Triclinic
Triclinic
Space group
P -1
P -1
a [Å]
13.714(7)
10.494(5)
b [Å]
17.332(9)
13.560(6)
c [Å]
22.395(12)
16.705(8)
α
106.308(16)°.
71.398(5)°.
β
99.64(3)°.
81.95(2)°.
107.499(17)°.
γ = 77.448(18)°.
3
Volume [Å ]
4684(4)
Z
2*2
3
Density (calculated) [Mg/m ]
1.222
-1
Absorption coefficient [mm ]
0.564
F(000)
1736
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Unit cell dimensions
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Empirical formula
2195.0(15)
2
1.802
3.630
1164
Crystal size [mm ]
0.215 × 0.102 × 0.062
0.186 × 0.053 × 0.04
Theta range for data collection
2.43 to 25.36°.
2.32 to 25.76°.
-16≤h≤16, -20≤k≤20, -26≤l≤26
-12≤h≤12, -16≤k≤16, -20≤l≤20
85022
39640
17146 [ 0.0497]
8338 [0.0731]
98.5 %
99.0 %
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Index ranges
Reflections collected
Completeness
Absorption correction
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Semi-empirical from equivalents
0.6462 and 0.5878
0.4291 and 0.3523
Data / parameters
17146/ 945
8338 / 545
Goodness-of-fit on F2
0.803
1.037
Final R indices [I>2sigma(I)]
R1 = 0.0571, wR2 = 0.1875
R1 = 0.0415, wR2 = 0.0855
R1 = 0.0771, wR2 = 0.2034
R1 = 0.0669, wR2 = 0.0950
2.232 and -0.887
1.204 and -1.282
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Max. and min. transmission
R indices (all data)
-3
Largest diff. peak and hole [e.A ]
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Table 2. Luminescence properties of [Ir(ptpy)2(ddmp)][PF6] (2).
Emission maximum
λmax
Quantum yield
φPL
Decay time
τem
MTHF [300 K], O2-free a
612 nm
17 %
560 nm
MTHF [300 K], air saturated
612 nm
3.5 %
140 ns
MTHF [77 K]
526 nm b
PMMA [300 K] c
562 nm
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Solvent [Temperature]
7.2 µs
54 %
1.9 µs
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a) The sample was degassed under vacuum by several freeze-pump-thaw cycles; p = 10−5
mbar.
b) The spectrum measured at 77 K is structured with a distinctly resolved shoulder at 560
nm.
c) Measured under N2.
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Table 3. Percent contributions from the Ir atom, ddmp, and ptpy ligands to the highest
occupied orbitals (lying within 1 eV below the HOMO energy) and the lowest virtual orbitals
(lying within 1 eV above the LUMO energy) of [Ir(ptpy)2(ddmp)]+ (2). The Mulliken
population analysis was performed for the ground-state Kohn-Sham orbitals resulting from
the B3LYP/[SVP+QZVP(ECP)] DFT calculations.
Energy
(eV)
Ir (%)
ptpy1 (%)
ptpy2 (%)
ddmp (%)
HOMO – 5
-8.956
66
14
15
6
HOMO – 4
-8.877
59
10
11
21
HOMO – 3
-8.816
1
43
44
11
HOMO – 2
-8.693
11
41
42
6
HOMO – 1
-8.373
1
47
47
5
HOMO
-7.894
29
34
34
3
LUMO
-5.164
3
1
11
85
LUMO + 1
-4.916
1
1
4
95
LUMO + 2
-4.272
5
46
46
3
LUMO + 3
-4.188
5
47
47
1
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Table 4: Cytotoxicity data
Cell line
IC50/µM
[Rh(ptpy)2(dmpp)](PF6) (1)
HT-29
0.5 ± 0.1
MCF-7
1.0 ± 0.3
HT-29
0.2 ± 0.1
MCF-7
0.3 ± 0.1
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[Ir(ptpy)2(dmpp)](PF6) (2)
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Compound
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Cl11
C109
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C104
C103
C110
C105
C108
C106
C102
C132
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Cl12
C136
C107
N101
N104
N102
C112
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C124
C126
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N103
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C114
C138
Ir1
C113
C137
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C111
C125
C139
C140
C143
C127
C131
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HIGHLIGHTS
• new cyclometalated complexes [M(ptpy)2(ddmp)]PF6 (M = Rh, 1; Ir, 2) were prepared
• both molecular structures were confirmed by single-crystal X-ray diffraction.
• 2 phosphoresces yellow in a polymer matrix and in solution at ambient temperature.
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• 1 and 2 show significant cytotoxicity against human cancer cell lines.