The one-pot synthesis and the fluorescence and cytotoxicity studies of chlorotricarbonyl(α-diimine)rhenium(I), fac-(CO)3(α-diimine)ReCl, complexes

Article abstract of DOI:10.1016/j.inoche.2008.05.033

An one-pot reaction of Re₂(CO)₁₀ and an α-diimine (1:2 molar ratio) in refluxed 2-chloroethanol afforded the corresponding chlorotricarbonyl(α-diimine)rhenium(I) complexes, fac-(CO)₃(α-diimine)ReCl, 1-4, in very high yield

Full text of DOI:10.1016/j.inoche.2008.05.033

Inorganic Chemistry Communications 11 (2008) 1054–1056
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Inorganic Chemistry Communications
journal homepage: www.elsevier.com/locate/inoche
The one-pot synthesis and the fluorescence and cytotoxicity studies of
chlorotricarbonyl(a-diimine)rhenium(I), fac-(CO)3(a-diimine)ReCl, complexes
Dejene K. Orsa a, Gregory K. Haynes a, Saroj K. Pramanik b, Maurice O. Iwunze a, George E. Greco c,
Douglas M. Ho d, Jeanette A. Krause e, Dwayne A. Hill b, Richard J. Williams a, Santosh K. Mandal a,
*
a Morgan State University, Department of Chemistry, 1700 E. Cold Spring Lane, Baltimore, MD 21251, United States
b Morgan State University, Department of Biology, 1700 E. Cold Spring Lane, Baltimore, MD 21251, United States
c Goucher College, Department of Chemistry, Baltimore, MD 21204, United States
d Harvard University, Department of Chemistry and Chemical Biology, Cambridge, MA 02138, United States
e University of Cincinnati, Department of Chemistry, Cincinnati, OH 45221-0172, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
An one-pot reaction of Re2(CO)10 and an
a
-diimine (1:2 molar ratio) in refluxed 2-chloroethanol afforded
-diimine)rhenium(I) complexes, fac-(CO)3( -diimine)ReCl, 1-4, in
-diimines in 1-4 are 2,20-bipyridyl, 1,10-phenanthroline, 2,9-dimethyl-1,10-phe-
nanthroline, and 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline, respectively. Alternatively, an one-
pot reaction of Re2(CO)10 and an -diimine (1:2 mole ratio) in refluxed 1-pentanol in the presence of
Received 5 April 2008
Accepted 23 May 2008
Available online 30 June 2008
the corresponding chlorotricarbonyl(
very high yield. The
a
a
a
a
Keywords:
Rhenium
Chloride
Crystal structure
Fluorescence
Cancer cell lines
CO2 and HCl yielded the corresponding chloro complexes, 1-4, in very high yield. 1-4 were characterized
spectroscopically. Additionally, 3 and 4 were characterized through X-ray crystal structure determina-
tions. The chloro complexes, 1-4 exhibit fluorescence both in the solid states and in solutions. Surpris-
ingly, 1-4 are cytotoxic against breast, prostate, and lung cancer cell lines.
Ó 2008 Elsevier B.V. All rights reserved.
Re2ðCOÞ10 þ 2ð
! 2fac-ðCOÞ3ð
þ ClCH2CHOð?Þ þ 4CO
a
-diimineÞ þ 2ClCH2CH2OH
Rhenium tricarbonyl (a-diimine) complexes of the type, fac-
(CO)3(a-diimine)ReX, (where, X is an anionic ligand), are of impor-
tance because most of these complexes exhibit long-lived metal-
to-ligand charge transfer (MLCT) and intra-ligand (IL) excited
states in solutions at room temperature [1]. Additionally, similar
complexes have been reported to be cytotoxic against numerous
cancer cell lines [2]. Among the most frequently studied complexes
a
-diimineÞReCl;1-4 þ CH3CH2OH
ð1Þ
ð2Þ
ðCOÞ10 þ 2ð
a
-diimineÞ þ CH3ðCH2Þ3CH2OH þ 2HCl
! 2fac-ðCOÞ3ð -diimineÞReCl;1-4 þ CH3ðCH2Þ3CHOð?Þ
a
of this type are fac-(CO)3(a-diimine)ReCl because of their unique
photochemical and photophysical properties [3]. Generally these
þ 4CO þ 2H2
complexes are synthesized from the reactions of the corresponding
We did not explore the mechanism of the reactions. It is, however,
possible that ligand substitution reactions yield initially the corre-
sponding dimers, [Re(CO)3(a-diimine)]2 [5]. The reactions of the di-
a-diimine ligands with Re(CO)5Cl, which is either available com-
mercially or synthesized from the reaction of Re2(CO)10 with Cl2.
In this communication, we report the one-pot synthesis and the
mers with 2-chloroethanol or 1-pentanol/CO2/HCl in several steps
afford the corresponding chloro complexes, 1-4. The IR, 1H and
13C NMR spectral data of 1-4 closely match with the published spec-
tral data of 1-4 and similar chloro complexes [6]. Surprisingly, the
13C NMR spectral data of 4 are not available in the literature. The
present study reveals that the 13C NMR spectrum of 4 exhibits
two characteristic and well-resolved resonances at d197 and 189
(intensity ratio of 2:1) due to the three terminal carbonyls. The
molecular structures of 3 and 4 were established through X-ray
crystal structure determinations [7]. The X-ray structures of 1, 2,
and analogous chloro complexes were reported earlier [8]. The
molecular plots of 3 are shown in Fig. 1 and the molecular plots
of 4 are shown in Fig. 2. The rhenium atom in 3 or 4 has distorted
fluorescence and cytotoxicity studies of fac-(CO)3(
a-diimine)ReCl,
1-4, where, the
a
-diimines are 2,20-bipyridyl, 1,10-phenanthroline,
2,9-dimethyl-1,10-phenanthroline and 2,9-dimethyl-4,7-diphenyl-
1,10-phenanthroline, respectively.
The reactions of Re2(CO)10 with corresponding a-diimines in re-
fluxed 2-chloroethanol, or 1-pentanol in the presence of CO2 and
HCl, afford 1-4 in very high yields according to eqs. (1) and (2) [4]:
* Corresponding author. Tel.: +443 885 1665; fax: +443 885 8286.
E-mail address: Santosh.mandal@gmail.com (S.K. Mandal).
1387-7003/$ - see front matter Ó 2008 Elsevier B.V. All rights reserved.
doi:10.1016/j.inoche.2008.05.033

D.K. Orsa et al. / Inorganic Chemistry Communications 11 (2008) 1054–1056
1055
39.0
2
3
26.0
13.0
4
1
0.0
450.00
530.00
610.00
690.00
λ,nm
Fig. 3. Fluorescence spectra of the fac-chlorotricarbonyl(a-diimine)rhenium(I)
Fig. 1. The X-ray crystal structure of 3. Selected bond lengths (Å): Re–C(15),
1.905(4); Re–C(16), 1.916(3); Re–C(17), 1.933(4); Re–N(1), 2.224(3); Re–N(2),
2.211(3); O(15)–C(15), 1.160(5); O(16)–C(16), 1.155(4); O(17)–C(17), 1.128(4); Re–
Cl, 2.4765(9). Selected bond angles (°): C(17)–Re–Cl, 175.56(9); C(16)–Re–Cl,
97.24(11); C(15)–Re–Cl, 91.02(13).
complexes in DMSO (1: 1.9486 x 10ꢁ4 M fac-(CO)3(bipy)ReCl; 2: 2.0590 ꢂ 10ꢁ4
fac-(CO)3(phen)ReCl; 3: 2.1403 ꢂ 10ꢁ4
M
fac-(CO)3(2,9-Me2–phen)ReCl; 4:
1.6513 ꢂ 10ꢁ4 M fac-(CO)3(2,9-Me2–4,7-Ph2–phen)ReCl).
!
ꢀ
ꢁꢀ
ꢁ
1 ꢁ 10ꢁA
1 ꢁ 10ꢁA
Fu
Fs
nu2
ns2
s
s
/u ¼
/
s
octahedron with three terminal CO’s in a facial arrangement, an a-
diimine, and a chloride ligand. There may be a small amount of
trans CO/Cl disorder in 3 as indicated by the shortened C17-O17
bond distance and the more linear Re-C17-O17 bond angle relative
to the other carbonyl groups. This type of disorder is typical for
these complexes [9]. The axial CO and Cl ligands in 4 are disordered
across the equatorial plane.
The UV-visible spectra of 1-4 are very similar to the UV-visible
spectra of 1-4 published earlier by several research groups [6,10].
The fluorescence spectra [11] of 1-4 in DMSO are shown in Fig. 3.
The quantum yields (/) of 1-4 were determined from the following
equation [12] using the solution of equal absorbance (ꢀ0.089) with
crystal violet in methanol as reference standard (/ = 0.54 [13])
The subscripts u and s refers to the unknown and the standard,
respectively, n is the refractive index, and F is the integrated area
of the fluorescence band. Strichler method was used to determine
the fluorescence lifetime [14]:
Z
e
1=s0 ¼ 2:88 ꢂ 10ꢁ9n2mf3
/
ꢁd
m
ꢁ1
ꢀ
ꢀ
m
Table 1
Photophysical parameters of 1-4
Compound
kex (nm)
kem (nm)
e
(ꢂ 103/M-cm)
/
s0 (ns)
1
2
3
4
319
319
319
319
319
576.47
577.19
577.98
578.31
630.21
2.897
4.375
3.259
5.036
–
0.261
0.603
0.483
0.459
0.56
21.0
32.0
38.0
29.0
–
Ref. Sample
DRUG TYPE VS % VIABLE CELLS
100
90
80
70
60
50
40
30
20
10
0
1
2
3
4
CONTROL
DRUG TYPE
Fig. 4. Plot of drug type vs. % viable cells. Brown, pink, and yellow represent breast,
prostate, and lung cancer cell lines, respectively. Green represents control – cells
Fig. 2. The X-ray crystal structure of the major component of 4. Selected bond
lengths (Å): Re(1)–C(1A), 1.902(18); Re(1)–C(2), 1.898(7); Re(1)–C(3), 1.911(6);
Re(1)–Cl(1A), 2.421(3). Selected bond angles (°): C(2)–Re(1)–Cl(1A), 91.9(2); C(1A)–
Re(1)–Cl(!A), 179.6(6); C(3)–Re(1)–Cl(1A), 91.0(2).
exposed to DMSO only. (1) Cancer cells treated with 1
treated with 1 g/mL of 2. (3) Cancer cells treated with 1
treated with 4 g/mL of 4. (For interpretation of the references to colour in this
figure legend, the reader is referred to the web version of this article.)
l
g/mL of 1. (2) Cancer cells
l
l
lg/mL of 3. (4) Cancer cells

1056
D.K. Orsa et al. / Inorganic Chemistry Communications 11 (2008) 1054–1056
filtration. Yields, 78–86%. 1H NMR data for 4 (CDCl3, d): 7.89(s, 2H, phen),
7.69(s, 2H, C6H5), 7.56(m, 6H, C6H5), 7.52(m, 4H, phen), 3.00(m, 6H, CH3). 13C
NMR data for 4 (CDCl3,d): 196.8 (CO), 189.1 (CO), 162.6 (phen), 150.9 (phen),
149.0 (phen), 135.9 (C6H5, 129.6 (C6H5), 129.5 (C6H5), 129.0 (C6H5), 127.3
(phen), 126.4 (phen), 124.3 (phen), 31.3 (CH3).
Table 1 summarizes the photophysical parameters of the chloro
complexes, 1-4. Most importantly, the chloro complexes, 1-4 are
cytotoxic against human breast (MCF 7), prostate (PC3), and lung
(H522) cancer cell lines. The cytotoxicities were studied [15] in
[5] A few years ago we synthesized analogous diphosphine dimers, [M(CO)3(P-
P)]2. See, for example: L.S. O’keiffe, A.C. Mitchell, T.M. Becker, D.M. Ho, S.K.
Mandal, J. Organomet. Chem. 613 (2000) 13;
K. Johnson, T. Frazier, T.M. Becker, K. Miller, D.M. Ho, J. Krause-Bauer, S.K.
Mandal, Inorg. Chem. Com. 4 (2001) 602.
[6] (a) J.V. Caspar, T.J. Meyer, Inorg. Chem. 87 (1983) 952;
(b) D. Beck, J. Brewer, J. Lee, D. McGraw, B.A. DeGraff, J.N. Demas, Coord. Chem.
Rev. 251 (2007) 548;
the concentration range of 0.5–4.0
0.5 g/mL concentration (not shown). However, 1 or 3 are very ac-
tive against lung cancer cell lines in an optimum concentration of
g/mL (Fig. 4). Although 4 is not active in 1 g/mL concentration
(not shown), it is extremely active against all cancer cell lines in an
optimum concentration of 4 g/mL (Fig. 4). Detailed cytotoxicity
lg/mL. 1-4 are barely active in
l
1
l
l
l
(c) See: reference 3a.;
(d) M.K. Itokazu, A.S. Polo, D.L.A. de Faria, C.A. Bignozzi, N.Y.M. Iha, Inorg.
Chim. Acta 313 (2001) 149;
studies using a wide range of concentrations of 1-4 and the mech-
anism of actions of 1-4 are in progress.
(e) J.R. Wagner, D.G. Hendricker, (J. Inorg. Nucl. Chem. 37 (1975) 1375;
(f) A. Juris, S. Campagna, I. Bidd, J.-M. Lehn, R. Ziessel, Inorg. Chem. 27 (1988)
4007;
Acknowledgement
(g) V. Christou, WO 03079737 A2.
This research was supported in part by an appointment to the
US Nuclear Regulatory Commission’s HBCU Faculty Research Par-
ticipation Program administered by the Oak Ridge Institute for Sci-
ence and Education. Crystallographic data for 3 were collected
through the SCrALS (Service Crystallography at Advanced Light
Source) program at the Small-Crystal Crystallography Beamline
11.3.1 at the Advanced Light Source (ALS). The ALS is supported
by the US Department of Energy, Office of Energy Sciences Materi-
als Sciences Division, under contract DE-AC02-05CH11231 at Law-
rence Berkeley National Laboratory. Also this research was
supported in part by the US Department of Energy, under contract
DOE-ER-63580.
[7] X-ray intensity data for 3 were collected on a D8 goniostat equipped with a
Bruker APEXII CCD detector using synchrotron radiation tuned to k = 0.7749 Å.
The data were corrected for absorption and beam corrections. The structure
was solved by a combination of direct methods in SHELXTL v6.14 and the
difference Fourier technique and refined by full-matrix least squares on F2.
Non-hydrogen atoms were refined with anisotropic displacement parameters.
All H-atoms positions were located directly from the difference map and the
coordinates refined. Crystal data for 3: C17H12N2O3ClRe, M = 513.94, yellow
crystals,
0.06 ꢂ 0.03 ꢂ 0.02 mm3,
monoclinic,
space
= 90o, b = 104.516(4)°,
l
= 90°, V = 1575.8(3) Å3, Z = 4, = 9.800 mmꢁ1, h range = 2.06–31.11°, 22561
group
P21/c,
a = 7.8696(9) Å, b = 21.597(3) Å, c = 9.5771(12) Å,
c
a
reflections collected, 3905 (Rint = 0.0654) independent reflections, number of
variables = 253, R = 0.0236, Rw = 0.0579, and goodness-of-fit = 1.035. X-ray
intensity data for 4 were collected on a Bruker SMART APEXII defractometer
equipped with an Oxford Cryosystems 700 Series Cryostream Cooler and Mo
K
a
radiation (k = 0.71073 Å). Unit cell refinement on all observed reflections,
and data reduction with corrections for Lp and decay were performed using
SAINT. Scaling and numerical absorption correction were done using
a
Appendix A. Supplementary material
SADABS. The structure was solved by direct methods and refined by full-
matrix least squares on F2. Non-hydrogen atoms were refined wit anisotropic
displacement coefficients. The H-atoms were assigned isotopic displacement
coefficients and their coordinates were allowed to ride on their respective
CCDC 683150 and CCDC 682962 contain the supplementary
crystallographic data for 3 and 4. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif. Supplementary data associ-
ated with this article can be found, in the online version, at
doi:10.1016/j.inoche.2008.05.033.
carbons. Crystal data for 4:
C29H20N2O3ClRe, M = 666.12, yellow prisms,
0.015 ꢂ 0.050 ꢂ 0.088 mm3, monoclinic, space group P21/c (No. 14),
a = 9.8109(1) Å, b = 7.7000(1) Å, c = 31.9033(5) Å,
a
= 90°, b = 95.317(1)°,
c
= 90°, V = 2399.73(5) Å3, Z = 4, = 5.211 mmꢁ1
l , h range = 2.08–27.50°,
40855 reflections collected, 5511 (Rint = 0.0737) independent reflections,
number of variables = 355, R = 0.0448, Rw = 0.0713, and goodness-of-
fit = 1.284.
[8] (a) P. Kurz, B. Probst, B. Spingler, R. Alberto, Eur. J. Inorg. Chem. 15 (2006)
2966;
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[11] A Steady-state fluorescence experiments were conducted on I-4 using the
Perkin Elmer Luminescence Spectrophotometer, model LS 50B in a quartz
cuvet of 1.0 cm in radiation pathlength. DMSO was used as a solvent.
[12] M. Krieg, M.B. Srichai, R.W. Redmond, Biochem. Biophys. Acta 1151 (1993)
168.
[4] Synthesis of 1-4: Method A: In a typical experiment a mixture of about
1.5 mmol of Re2(CO)10 and 3.0 mmol of an a-diimine was refluxed in 35 mL of
2-chloro ethanol for about 24 h. The mixture was then allowed to cool to room
temperature and finally cooled to ꢁ5 °C. Orange solid of the corresponding
[13] D. Magde, J.H. Branon, T.L. Cremers, J. Olmsted, J. Phys. Chem. 83 (1989)
696.
chlorotricarbonyl(a-diimine) rhenium(I) were separated by filtration. The
filtrate was discarded. The solid was recrystallized in CH2Cl2–hexane at ꢁ5 °C.
Microcrystals of 1-4 were collected by filtration. Yields, 86–93%. Method B: In a
typical experiment a mixture of about 1.5 mmol of Re2(CO)10, 3.0 mmol of an
-diimine, and 3 mmol of HCl was refluxed in 35 mL of 1-pentanol for about
24 h while CO2 was bubbled through the solution. The mixture was cooled to
[14] S.J. Strickler, R.A. Berg, J. Chem. Phys. 37 (1962) 814.
[15] Experimental procedure for cell culture and cell studies has been described in
our earlier publication: see: D.K. Orsa, G.K. Haynes, S.K. Pramanik, M.O.
Iwunze, G.E. Greco, J.A. Krause, D.M. Ho, A.L. Williams, D.A. Hill, S.K. Mandal,
Inorg. Chem. Com. 10 (2007) 821.
a
room temperature and ꢁ5 °C. Microcrystals of 1-4 were collected through