Ruthenium(II) polypyridyl complexes: Potential precursors, metalloligands, and topo II inhibitors

Article abstract of DOI:10.1021/ic701518e

Neutral and cationic mononuclear complexes containing both group 15 and polypyridyl ligands [Ru(κ³-tptz)(PPh₃)-Cl ₂] [1; tptz = 2,4,6-tris(2-pyridyl)-1,3,5-thazine], [Ru(κ³-tptz)(κ²-dppm)CI]BF₄ [2; dppm = bis(diphenylphosphino)-methane], [Ru(κ³-tptz)(PPh ₃)(pa)]Cl (3; pa = phenylalanine), [Ru(κ³-tptz) (PPh₃)(dtc)]Cl (4; dtc = diethyldithiocarbamate), [Ru(κ³-tptz)(PPh₃)(SCN)₂] (5) and [Ru(κ³-tptz)(PPh₃)(N₃)₂] (6) have been synthesized. Complex 1 has been used as a metalloligand in the synthesis of homo- and heterodinuclear complexes [Cl₂(PPh ₃)Ru(μ-tptz)Ru-(η⁶-C₆H ₆)Cl]BF₄ (7), [Cl₂(PPh₃)Ru(μ- tptz)Ru(η⁶-C₁₀H₁₄)Cl]PF₆ (8), and [Cl₂(PPh₃)Ru(μ-tptz)Rh(η⁵-C ₅Me₅)Cl]BF₄ (9). Complexes 7-9 present examples of homo- and heterodinuclear complexes in which a typical organometallic moiety [(η⁶-C₆H₆)RuCl]⁺, [(η⁶-C₁₀H₁₄)RuCl]⁺, or [(η⁵-C₅Me₅)RhCl]⁺ is bonded to a ruthenium(II) polypyridine moiety. The complexes have been fully characterized by elemental analyses, fast-atom-bombardment mass spectroscopy, NMR ( ¹H and ³¹P), and electronic spectral studies. Molecular structures of 1-3, 8, and 9 have been determined by single-crystal X-ray diffraction analyses. Complex 1 functions as a good precursor in the synthesis of other ruthenium-(II) complexes and as a metalloligand. All of the complexes under study exhibit inhibitory effects on the Topoisomerase II-DNA activity of filarial parasite Setaria cervi and β-hematin/hemozoin formation in the presence of Plasmodium yoelii lysate.

Full text of DOI:10.1021/ic701518e

Inorg. Chem. 2008, 47, 1179−1189
Ruthenium(II) Polypyridyl Complexes: Potential Precursors,
Metalloligands, and Topo II Inhibitors
Sanjeev Sharma, Sanjay K. Singh, and Daya S. Pandey*
Department of Chemistry, Faculty of Science, Banaras Hindu UniVersity,
Varanasi 221 005, U.P., India
Received July 31, 2007
Neutral and cationic mononuclear complexes containing both group 15 and polypyridyl ligands [Ru(κ
3-tptz)(PPh3)-
Cl2] [1; tptz
methane], [Ru(
bamate), [Ru(
been used as a metalloligand in the synthesis of homo- and heterodinuclear complexes [Cl2(PPh3)Ru(
6-C6H6)Cl]BF4 (7), [Cl2(PPh3)Ru( 6-C10H14)Cl]PF6 (8), and [Cl2(PPh3)Ru( 5-C5Me5)Cl]BF4 (9).
-tptz)Ru( -tptz)Rh(
Complexes 7 9 present examples of homo- and heterodinuclear complexes in which a typical organometallic moiety
[(
6-C6H6)RuCl]+, [( 6-C10H14)RuCl]+, or [( 5-C5Me5)RhCl]+ is bonded to a ruthenium(II) polypyridine moiety. The
complexes have been fully characterized by elemental analyses, fast-atom-bombardment mass spectroscopy, NMR
(1H and 31P), and electronic spectral studies. Molecular structures of 1
3, 8, and 9 have been determined by
)
2,4,6-tris(2-pyridyl)-1,3,5-triazine], [Ru(
3-tptz)(PPh3)(pa)]Cl (3; pa
phenylalanine), [Ru(
3-tptz)(PPh3)(SCN)2] (5) and [Ru( 3-tptz)(PPh3)(N3)2] (6) have been synthesized. Complex 1 has
-tptz)Ru-
κ
3-tptz)(
κ
2-dppm)Cl]BF4 [2; dppm
3-tptz)(PPh3)(dtc)]Cl (4; dtc
)
bis(diphenylphosphino)-
κ
)
κ
)
diethyldithiocar-
κ
κ
µ
(
η
µ
η
µ
η
−
η
η
η
−
single-crystal X-ray diffraction analyses. Complex 1 functions as a good precursor in the synthesis of other ruthenium-
(II) complexes and as a metalloligand. All of the complexes under study exhibit inhibitory effects on the Topoisomerase
II
−DNA activity of filarial parasite Setaria cervi and
â
-hematin/hemozoin formation in the presence of Plasmodium
yoelii lysate.
Introduction
in determining and eventually improving both the light-
emitting and electron-transfer performances.7 In this direc-
tion, a large number of neutral8 and anionic9 ligands have
been included in the coordination sphere of ruthenium(II)
polypyridyl metal fragments. Among the polypryridyl ligands,
2,4,6-tris(2-pyridyl)-1,3,5-triazine (tptz) has drawn special
attention. In general, tptz functions as a tridentate ligand,
There has been an increasing interest in ruthenium(II)
polypyridine chemistry. The principal reason behind this
surge in research on ruthenium(II) polypyridyl complexes
is their peculiar electrochemical and photophysical proper-
ties.1 These complexes find wide applications in several
research fields such as conversion of solar energy,2 fabrica-
tion of molecular devices,3 DNA intercalation,4 and protein
binding.5 In addition, mono- and dinuclear ruthenium(II)
polypyridyl complexes have been widely used as electro-
chemiluminescence luminophores.6 It has been observed
that the ligand present in such systems plays a crucial role
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* To whom correspondence should be addressed. E-mail: dspbhu@
bhu.ac.in.
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10.1021/ic701518e CCC: $40.75
Published on Web 01/03/2008
© 2008 American Chemical Society
Inorganic Chemistry, Vol. 47, No. 3, 2008 1179

Sharma et al.
forming mononuclear complexes.10 However, in some cases
it simultaneously functions as tridentate and bidentate
ligands.11 Also, there is one report dealing with the trinucle-
ating mode of tptz.12
Although extensive studies have been made on ruthenium
complexes containing polypyridyl ligands, complexes con-
taining both group 15 and polypridyl ligands, wherein group
15 ligands stabilize ruthenium(II) forms, have not been
extensively studied.13 Recently, a series of cationic ruthe-
nium(II) complexes with the formulations [Ru(κ3-L)(EPh3)2-
Cl]+ [L ) tptz or 2,2′:6,6′-terpyridine (tpy); E ) P and As]
and analogous osmium(II) complexes [Os(κ3-tptz)(EPh3)2-
Cl]+ (E ) P and As) containing both group 15 and
polypyridyl ligands were synthesized.14 Various studies
established that the complexes [Ru(κ3-L)(EPh3)2Cl]+ have
the potential to behave as good precursors in the synthesis
of other ruthenium complexes under mild reaction
conditions can act as potential metalloligands in the synthesis
of homo(hetero)di(poly)nuclear complexes and also act as
biocatalysts.14a
In an extension of our earlier studies devoted in this
direction, we have synthesized neutral complex [Ru(κ3-tptz)-
(PPh3)Cl2] from the reactions of [RuCl2(PPh3)3] with tptz in
benzene under refluxing conditions. The neutral complex
[Ru(κ3-tptz)(PPh3)Cl2] also possesses a κ3-bonded tptz,
tertiary phosphine, and labile chloro groups analogous to the
complexes of the series [Ru(κ3-L)(EPh3)2Cl]+. Because of
the presence of the polar chloro groups bound to the
ruthenium center and uncoordinated donor groups on almost
planar tptz, the complexes of this series are expected to
exhibit a rich variety of chemistry, have the potential to
behave as metalloligands, and can act as biocatalysts. We
devoted our efforts in this direction, have isolated complexes
containing both the group 15 and polypyridyl ligands, and
have examined its use as a precursor, metalloligand, and
biocatalyst.
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In this work, we have adopted a multiaspect approach
toward the complex [Ru(κ3-tptz)(PPh3)Cl2] (1) and present
herein its reproducible synthesis, its potential use as a
precursor, and its applicability in the synthesis of homo- and
heterodinuclear complexes. Further, we report herein the
inhibitory effect of the complexes on the DNA-Topoi-
somerase II (Topo II) activity of filarial parasite Setaria cerVi
and on the â-hematin/hemozoin formation in the presence
of Plasmodium yoelii lysate.
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Results and Discussion
Scheme 1 shows the synthetic route for the synthesis of
air-stable neutral complex 1 and its derivatives. Complex 1
was used as a precursor in the synthesis of mononuclear
complexes [Ru(κ3-tptz)(κ2-dppm)Cl]BF4 [2; dppm ) bis-
(diphenylphosphino)methane], [Ru(κ3-tptz)(PPh3)(pa)]Cl (3;
pa ) phenylalanine), [Ru(κ3-tptz)(PPh3)(dtc)]Cl (4; dtc )
diethyldithiocarbamate), [Ru(κ3-tptz)(PPh3)(SCN)2] (5), and
[Ru(κ3-tptz)(PPh3)(N3)2] (6). Complexes 2-6 were obtained
in excellent yield from the reaction of 1 with respective bases
in methanol under refluxing conditions. The formation of
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Chem. 2005, 690, 3105.
1180 Inorganic Chemistry, Vol. 47, No. 3, 2008

Ruthenium(II) Polypyridyl Complexes
Scheme 1
1-3 has been authenticated by single-crystal X-ray diffrac-
tion analyses (vide supra). Complex 4 has also been
synthesized by the reaction of [Ru(κ3-tptz)(PPh3)2Cl]BF4 with
sodium diethyldithiocarbamate in refluxing methanol and has
been structurally characterized.14a
X-ray Crystallography. Molecular structures of 1-3, 8,
and 9 have been determined crystallographically. The
complexes crystallize in P21/c (1), P21/n (2), P1h (3), P121/
n1 (8), and P21 (9) space groups. Details about data collection,
refinement, and structure solution are recorded in Table 1,
and selected geometrical parameters are collected in Table
2. Crystal structures of 1-3, 8, and 9 with atom-numbering
schemes are shown in Figure 2a-e. The coordination
geometry about the ruthenium in the mononuclear complexes
1-3 is distorted octahedral. In complex 1, ruthenium is
bonded with the major coordination sites of tptz through
pyridyl nitrogen atoms N1 and N3 and triazyl nitrogen N2
from the central triazine ring in a κ3 manner, P1 from
triphenylphosphine, and the chloro groups Cl1 and Cl2, while
in complex 2, both of the phosphorus atoms P1 and P2 from
dppm and the chloro group Cl1 are bonded to the ruthenium
center along with tptz through its pyridyl nitrogen atoms (N1
and N3) and central triazyl nitrogen N2 in a κ3 manner. In
complex 3, arrangement of tptz is analogous to that in 1 and
2 and other positions are occupied by phosphorus P1 from
PPh3, amino nitrogen N7, and carboxyl oxygen O1 of the
coordinated pa.
Complex 1 behaves as a metalloligand and reacted with
the chloro-bridged dimeric arene (arene ) benzene and
p-cymene) ruthenium complexes [{(η6-C6H6)Ru(µ-Cl)Cl}2]
and [{(η6-C10H14)Ru(µ-Cl)Cl}2] and isostructural rhodium
complex [{(η5-C5Me5)Rh(µ-Cl)Cl}2] in a 2:1 molar ratio to
afford homo- and heterodinuclear complexes [Cl2(PPh3)Ru-
(µ-tptz)Ru(η6-C6H6)Cl]BF4 (7), [Cl2(PPh3)Ru(µ-tptz)Ru(η6-
C10H14)Cl]PF6 (8), and [Cl2(PPh3)Ru(µ-tptz)Rh(η5-C5Me5)-
Cl]BF4 (9) in pretty good yield. The formation of 8 and 9
has been authenticated crystallographically. Complexes 7-9
present unique examples wherein typical organometallic
fragments, viz., [(η6-C6H6)RuCl]+, [(η6-C10H14)RuCl]+, or
[(η5-C5Me5)RhCl]+, are coordinated to the ruthenium(II)
polypyridine fragment [Ru(κ3-tptz)]. All of the complexes
were characterized by satisfactory elemental analyses. In-
formation about the composition of the complexes was also
obtained from fast-atom-bombardment mass spectroscopy
(FAB-MS). FAB-MS spectra of the representative mono- and
dinuclear complexes 4, 5, 8, and 9 are shown in parts a-d
of Figure 1, and data with the assignments are recorded in
the Experimental Section. The overall fragmentation patterns
and the presence of various peaks in the FAB-MS spectra
strongly supported the formulation of the respective mono-
and dinuclear complexes.
The angles N1-Ru1-N2 and N2-Ru1-N3 in 1 are
essentially equal to 79.02(7) and 78.83(7)°, while in 2 and
3, these are 77.14(15), 76.95(15)° and 78.48(12), 79.02(12)°,
respectively. This suggests inward bending of the coordinated
pyridyl group and may be the reason for the observed
distortion.14a Distortion from the regular octahedral geometry
is further reflected by intraligand trans angles N1-Ru1-
Inorganic Chemistry, Vol. 47, No. 3, 2008 1181

Sharma et al.
complexes.14a,b,16 Uncoordinated pyridyl rings in 1-3 are
inclined at 18.1, 31.6, and 18.6°, respectively, from the
central triazine ring plane.
An interesting structural feature of the homodinuclear
complex 8 and heterodinuclear complex 9 is the coordination
of [(η6-C10H14)RuCl]+ and [(η6-C5Me5)RhCl]+ moieties,
respectively, through the uncoordinated nitrogen atoms N4
and N6 of the tptz bonded to ruthenium in complex 1. The
coordination geometry about Ru1 in both complexes 8 and
9 is the same as that in 1; the only difference lies about Ru2
and Rh1. Ru2 in 8 is bonded through triazine nitrogen N4,
pyridyl nitrogen N6, one chloro group, and the p-cymene
ring (C37-C42) in a η6 manner. Similarly, Rh1 in 9 is
coordinated through triazine nitrogen N4, pyridyl nitrogen
N6 of the tptz in a κ2 manner, one chloro group, and the
pentamethylcyclopentadienyl (Cp*) ring (C37-C41) in a η5
manner. Typical “piano-stool” geometry about Ru2 in 8 and
Rh1 in 9 is maintained. The p-cymene ring in 8 is planar,
the average Ru-C distance is 2.02(8) Å [range 2.176(9)-
2.216(10) Å], and the Ru2 to p-cymene ring centroid bond
distance is 1.685 Å, which is comparable to the distances
reported in other ruthenium p-cymene complexes.17 The Cp*
ring in 9 is planar with an average Rh-C distance of 2.6512
Å, and the Rh center is displaced by 1.785 Å from the
centroid of the Cp* ring. The C-C bond lengths within the
Cp* ring and C-Me distances are normal.18 Rh-N and Rh-
Cl bond lengths are consistent with the values reported in
the literature.18a,19
Crystal structures of 1-3, 8, and 9 revealed the presence
of extensive intra- and intermolecular C-H‚‚‚X (X ) N,
Cl, and F) and C-H‚‚‚π interactions. Matrixes of the
intermolecular interactions for 1-3, 8, and 9 are shown in
Table S1 in the Supporting Information. It is well-established
that these types of interactions play an important role in the
construction of huge supramolecular architectures.20 Weak
interaction studies in 1 show face-to-face C-H‚‚‚π interac-
tions, leading to a single helical motif, which is interlinked
to another helical motif through C-H‚‚‚N interaction, giving
Figure 1. FAB-MS spectra with peak assignments for 4 (a), 5 (b), 8 (c),
and 9 (d).
N3 in 1-3, which are 157.00(7), 154.08(16), and 157.16-
(12)°, respectively. The other two interligand trans angles
Cl1-Ru1-P1 and Cl2-Ru1-N2 are 176.82(2) and 174.22-
(5)° in 1, the angles Cl1-Ru1-P1 and N2-Ru1-P2 are
167.92(5) and 178.05(11)° in 2, and the angles N8-Ru1-
P1 and N2-Ru1-O1 are 172.58(9) and 171.66(5)° in 3,
respectively. The angle Cl2-Ru1-Cl1 in 1 is 90.02(3)°,
which suggested that the chloro groups are cis-disposed. The
Ru-P and Ru-Cl distances are normal and consistent with
the values reported in other related complexes.14a,15 The Ru1
to central triazine nitrogen bond length Ru1-N2 in 1 is
1.9234(17) Å, which is smaller than the Ru1 to coordinated
pyridyl nitrogen bond lengths Ru1-N1 [2.0921(17) Å] and
Ru1-N3 [2.0846(17) Å]. Similarly, the Ru1-N2 bond
distance in 2 is 2.018(4) Å and the Ru1-N1 and Ru1-N3
distances are 2.112(4) and 2.124(4) Å, respectively, while
the Ru1-N2 bond distance in 3 is 1.921(3) Å and the Ru1-
N1 and Ru1-N3 distances are 2.078(3) and 2.103(3) Å. The
Ru-N bond distances are consistent with κ3 coordination
of tptz and comparable to those in other RuIItptz
(16) Paul, P.; Tyagi, B.; Bilakhia, A. K.; Dastidar, P.; Suresh, E. Inorg.
Chem. 2000, 39, 14.
(17) Singh, S. K.; Trivedi, M.; Chandra, M.; Sahay, A. N.; Pandey, D. S.
Inorg. Chem. 2004, 43, 8600 and references cited therein.
(18) (a) Chandra, M.; Sahay, A. N.; Mobin, S. M.; Pandey, D. S. J.
Organomet. Chem. 2005, 690, 3105. (b) Singh, S. K.; Chandra, M.;
Dubey, S. K.; Pandey, D. S. Eur. J. Inorg. Chem. 2006, 3954. (c)
Hughes, R. P.; Lindner, D. C.; Liable-Sands, L. M.; Rheingold, A. L.
Organometallics 2001, 20, 363. (d) Scheiring, T.; Fiedler, J.; Kaim,
W. Organometallics 2001, 20, 1437.
(19) (a) Paul, P.; Tyagi, B.; Bilakhiya, A. K.; Parthsarthi, D.; Bhadbhade,
M. M.; Suresh, E.; Ramchandraiah, G. Inorg. Chem. 1998, 37, 5733.
(b) Aneetha, H.; Zacharias, P. S.; Srinivas, B.; Lee, G. H.; Wang, Y.
Polyhedron 1998, 18, 299.
(20) (a) Braga, D.; Grepioni, F.; Tedesco, E. Organometallics 1998, 17,
2669. (b) Desiraju, G. R.; Steiner, T. Weak Hydrogen Bonds in
Structural Chemistry and Biology; Oxford University Press: Oxford,
U.K., 1999. (c) Steiner, T. Angew. Chem., Int. Ed. 2002, 41, 48. (d)
Hobza, P.; Havlas, Z. Chem. ReV. 2000, 100, 4253. (e) Zhang, J.-P.;
Lin, Y.-Y.; Huang, X.-C.; Chen, X.-M. Inorg. Chem. 2005, 44, 3146.
(f) Desiraju, G. R. J. Chem. Soc., Dalton Trans. 2000, 3745. (g) Lu¨,
X.-Q.; Jiang, J.-J.; Chen, C.-L.; Kang, B.-S.; Su, C.-Y. Inorg. Chem.
2005, 44, 4515. (h) Yin, H.; Lee, G. I.; Park, H. S.; Payne, G. A.;
Rodriguez, J. M.; Sebti, S. M.; Hamilton, A. D. Angew. Chem., Int.
Ed. 2005, 44, 2704. (i) Hirschberg, J. H. K. K.; Brunsveld, L.; Ramzi,
A.; Vekemans, J. A. J. M.; Sijbesma, R. P.; Meijer, E. W. Nature
2000, 407, 167.
(15) (a) Hayashida, T.; Nagashima, H. Organometallics 2002, 21, 3884.
(b) Nishiyama, H.; Konno, M.; Aoki, K.; Davies, H. M. L.; Huw, M.
L. Organometallics 2002, 21, 2536.
1182 Inorganic Chemistry, Vol. 47, No. 3, 2008

Ruthenium(II) Polypyridyl Complexes
Table 1. Crystallographic Data for 1, 2, and 7-9
1
2
3
8
9
chemical formula
fw
C36H27Cl2N6PRu
746.58
blue, block
0.35 × 0.27 × 0.21
P21/c
monoclinic
11.667(3)
14.6718(6)
19.6465(17)
90
105.461(14)
90
3241.3(10)
4
1.530
0.735
C43H34BClF4N6P2Ru
920.03
violet-black, block
0.33 × 0.28 × 0.26
P21/n
monoclinic
12.024(2)
27.0339(12)
13.592(2)
90
104.529(15)
90
4277.1(11)
4
1.429
0.560
C46H39Cl3N7O6.50PRu
1024.27
C46H43Cl3F6N6OP2Ru2
1180.29
blue, block
0.35 × 0.26 × 0.23
P21/n
monoclinic
17.031(3)
18.042(4)
17.038(3)
90
92.20(3)
90
5231.5(18)
4
1.499
0.852
C46H42BCl3F4N6OPRhRu
1122.97
blue, block
0.34 × 0.28 × 0.21
P21
monoclinic
11.4272(4)
15.0419(14)
13.7625(12)
90
98.124(5)
90
2341.9(3)
2
1.593
0.939
color, habbit
cryst size (mm)
space group
cryst syst
a (Å)
violet-black, block
0.33 × 0.26 × 0.21
P1h
triclinic
13.812(2)
14.094(2)
14.2642(18)
61.663(14)
82.940(11)
71.920(13)
2322.3(6)
2
b (Å)
c (Å)
R (deg)
â (deg)
γ (deg)
V (Å3)
Z
D
calc (g cm-3
)
1.476
0.602
293(2)
µ (mm-1
T (K)
)
293(2)
293(2)
293(2)
293(2)
no. of reflns
no. of param
R factor all
5683
415
0.0321
7509
523
0.0954
8156
588
0.0591
9293
598
0.1016
7727
592
0.0491
R factor [I > 2σ(I)]
wR2
0.0240
0.0607
0.0500
0.1328
0.0452
0.1288
0.0776
0.1976
0.0384
0.1064
wR2 [I > 2σ(I)]
GOF
0.0582
1.029
0.1183
0.914
0.1222
1.068
0.1770
1.052
0.0975
1.029
Table 2. Important Bond Parameters for 1, 2, 3, 8 and 9
1
2
3
8
9
Ru1-N1
Ru1-N2
Ru1-N3
Ru1-P1
Ru1-Cl1
Ru1-Cl2
2.0921(17) Ru1-N1
1.9234(17) Ru1-N2
2.0846(17) Ru1-N3
2.112(4)
2.018(4)
2.124(4)
2.2821(14) Ru1-O1
2.3054(14) Ru1-N7
2.4517(14) Ru1-P1
Ru1-N1
Ru1-N2
Ru1-N3
2.103(3)
1.921(3)
2.078(3)
2.119(3)
2.137(3)
Ru1-N1
Ru1-N2
Ru1-N3
Ru1-P1
Ru1-Cl1
2.065(6)
Ru1-N1
2.095(5)
1.925(5)
2.071(5)
2.3140(14)
2.4354(14)
2.4116(16)
2.190(4)
2.091(5)
2.1562(2)
1.785
1.918(5)
2.056(6)
2.335(2)
2.430(2)
Ru1-N2
Ru1-N3
Ru1-P1
Ru1-Cl1
2.3087(7)
2.4457(7)
2.4449(6)
Ru1-P1
Ru1-P2
Ru1-Cl1
2.3186(10) Ru1-Cl2
2.4185(18) Ru1-Cl2
Ru2-N4
2.118(5)
2.083(6)
2.200(9)
1.685
2.394(2)
78.8(2)
158.4(2)
79.6(2)
Rh1-N4
Ru2-N6
Rh1-N6
Ru2-Cav
Rh1-Cav
Ru2-Cct
Rh1-Cct
Ru2-Cl3
Rh1-Cl3
2.4004(17)
79.4(2)
157.68(18)
78.51(19)
N1-Ru1-N2
N1-Ru1-N3
N2-Ru1-N3
79.02(7)
157.00(7)
78.83(7)
N1-Ru1-N2 77.14(15)
N1-Ru1-N2 78.48(12)
N1-Ru1-N2
N1-Ru1-N2
N1-Ru1-N3
N2-Ru1-N3
N1-Ru1-N3 154.08(16) N1-Ru1-N3 157.16(12) N1-Ru1-N3
N2-Ru1-N3 76.95(15) N2-Ru1-N3 79.02(12) N2-Ru1-N3
P1-Ru1-P2 71.83(5)
N2-Ru1-P2 178.05(11) O1-Ru1-N7 78.52(11)
P1-Ru1-Cl1 167.92(5) P1-Ru1-N7 172.58(9)
N2-Ru1-Cl2 174.22(5)
N2-Ru1-O1 171.66(11) N2-Ru1-Cl2 173.83(17) N2-Ru1-Cl2 173.57(16)
Cl1-Ru1-Cl2 90.02(3)
Cl1-Ru1-Cl2 88.17(8)
P1-Ru1-Cl1
N4-Ru2-N6
Cl1-Ru1-Cl2 89.28(6)
P1-Ru1-Cl1
N4-Rh1-N6
P1-Ru1-Cl1
176.82(2)
178.84(8)
76.8(2)
176.37(6)
76.78(18)
a straight chain (Figure S1 in the Supporting Information),
while in 2, C-H‚‚‚F and C-H‚‚‚π interactions lead to an
upstairslike motif (Figure 3).20b In 9, two types of edge-to-
face C-H‚‚‚π interactions have been found, leading to a
single helical motif (Figure S2 in the Supporting Informa-
tion).
and 7.53 (H3) for pendant pyridyl protons of tptz (see Scheme
1 for numbering of the pyridyl protons). The aromatic protons
of PPh3 resonated as a broad multiplet in the region δ 7.36-
1
7.10. The H NMR spectra of 2-6 followed the general
1
trends observed for 1. The main feature of the H NMR
spectra of the dtc-containing complex 4 is the presence of
multiplets in the upshielded side characteristic of methyl and
methylene protons (see the Experimental Section).
1
NMR Studies. H NMR spectral data of the complexes
are recorded in the Experimental Section. The position and
integrated intensity of various signals corresponding to tptz
corroborated well to a system involving coordination of tptz
with the ruthenium in a κ3 manner with two magnetically
equivalent coordinated pyridyl rings and one uncoordinated
However, in the dinuclear complexes 7-9, coordination
of a second metal center splits the equivalency of tptz pyridyl
1
protons. H NMR spectra of 8 show four deshielded peaks
at δ 10.64, 9.41, 8.63, and 8.26 assignable to H1, H4, H2,
and H3, respectively, corresponding to the pyridyl ring
protons of tptz coordinated to [(η6-C10H14)RuCl]+. Also,
chemical shifts for the pyridyl protons, which are in close
proximity to [(η6-C10H14)RuCl]+, exhibited a downfield shift
to a greater extent than the other protons (see the Experi-
mental Section). A similar trend has been observed for 7
and 9 also. Characteristic signals for coordinated benzene
(7), p-cymene (8), and pentamethylcyclopentadienyl (9)
1
pyridyl ring for mononuclear complexes.21 The H NMR
spectrum of 1 displays signals at δ 9.46 (d, 2H, J ) 4.2 Hz,
H1′,1′′), 8.58 (d, 2H, J ) 8.7 Hz, H4′,4′′), 7.86 (t, 2H, J ) 6.9
Hz, H2′,2′′), and 7.58 (m, 3H, H3′,3′′) corresponding to the
protons of coordinated pyridyl rings and δ 8.95 (d, 1H, J )
2.7 Hz, H1), 8.64 (d, 1H, H4) 7.96 (t, 1H, J ) 6.9 Hz, H2),
(21) Chirayil, S.; Hegde, V.; Jahng, Y.; Thummel, R. P. Inorg. Chem. 1991,
30, 2821.
Inorganic Chemistry, Vol. 47, No. 3, 2008 1183

Sharma et al.
Figure 2. Molecular structures of complexes 1 (a), 2 (b), 3 (c), 8 (d), and 9 (e).
1184 Inorganic Chemistry, Vol. 47, No. 3, 2008

Ruthenium(II) Polypyridyl Complexes
Figure 3. Face-to-face π-π and C-H‚‚‚F interaction leading to an upstairs motif in complex 2.
protons appeared at δ 5.82 (s, 6H, C6H6), 5.69 (m, 3H), 5.45
(d, 1H), 2.65 (m, 1H, CH(CH3)2), 2.12 (s, 3H, C-CH3), 1.09
(d, 3H, CH(CH3)2), 0.92 (d, 3H, CH(CH3)2), and 1.45 (s,
15H, C5(CH3)5).17,18b The integrated intensity and position
of the signals are consistent with the formulation of respective
complexes.
Signals associated with the 31P NMR nuclei of the
coordinated PPh3 resonated as sharp singlets in the 31P NMR
spectra of complexes 1 and 3-9 in the range of δ 27.89-
40.77. Complex 2 displayed two doublets at δ 6.64 (d, J )
56.62 Hz) and -11.29 (d, J ) 58.56 Hz) associated with
the 31P NMR nuclei of the coordinated dppm.
UV-Vis Spectroscopy. UV-vis spectra of the complexes
were acquired in dichloromethane, and spectral data are
summarized in the Experimental Section. Electronic spectra
of the mononuclear complexes 1-6 and dinuclear complexes
7-9 are depicted in Figure 4a,b. Ruthenium polyazine
complexes usually show intense peaks in the UV region
corresponding to ligand-based π f π* transitions with
overlapping metal-to-ligand charge-transfer (MLCT) transi-
tions in the visible region.13a An analogous general trend is
observable in the electronic spectra of the complexes under
study. Mononuclear complexes 1-6 displayed intense transi-
tions in the UV-vis region. The lowest-energy absorption
bands in the electronic spectra of 1-6 in the visible region
at ∼478-557 and 374-353 nm (except for complex 2) on
the basis of its intensity and position have been tentatively
assigned to dπRu f π*tptz MLCT transitions. The bands in
the high-energy side at ∼280 nm have been assigned to
ligand-centered π f π*/n f π* transitions.22 The homo/
heterodinuclear complexes 7-9 exhibited similar trends, with
an additional band at ∼405 nm that can be assigned to the
Figure 4. UV-vis spectra of mononuclear complexes 1-6 (a) and
MLCT band due to dπM-arene f π*tptz transitions.18b The
higher-energy MLCT transitions of the dinuclear complexes
exhibited significant red shifts compared to the parent
complex 1, which may be attributed to stabilization of the
lowest unoccupied molecular orbital (LUMO) π* level of
tptz by its coordination to another metal center, leading to
binuclear complexes 7-9 (b) in dichloromethane.
enhanced dπ f π* orbital overlap with a low highest
occupied molecular orbital (HOMO)-LUMO energy gap.23
It is further observed that substitution of the chloro groups
in complex 1 by neutral or ionic bidentate ligands signifi-
cantly destabilizes the π* orbital of tptz, resulting in blue-
shifted dπRu f π*tptz absorption bands. However, substitution
(22) (a) Didier, P.; Ortmans, I.; Mesmaeker, A. K.-D.; Watts, R. J. Inorg.
Chem. 1993, 32, 5239. (b) Sullivan, B. P.; Salmon, D. J.; Meyer, T.
J. Inorg. Chem. 1978, 17, 3334.
(23) Rillema, D. P.; Mack, K. B. Inorg. Chem. 1982, 21, 3849.
Inorganic Chemistry, Vol. 47, No. 3, 2008 1185

Sharma et al.
effect of the metal complexes on the Topo II activity of the
filarial parasite. Gel mobility assays of the mono- and
dinuclear complexes (1, 2, and 5-9) were examined at
various concentration levels. All of the complexes exhibited
DNA binding behavior. An upshift of bound DNA to the
gel origin indicated that these complexes greatly influence
the Topo II-DNA activity by binding to either the Topo
II-DNA complex, DNA, or the enzyme. An appreciable
effect on the DNA activity has been observed upon substitu-
tion of the chloro group in the parent complex 1. Complexes
2 and 6 show complex formation as well as inhibitory activity
at higher concentration levels of 5 µg, where as parent
complex 1 shows inhibitory activity only below 0.2 µg levels
(Figure 5). The homo/heterodinuclear complexes show a
strong ability toward complex formation with the DNA-
Topo II complex even at concentrations lower than 2 µg
(Figure 6). The DNA topoisomerase inhibitory activity of
the complexes under study was found to be concentration-
dependent. At concentrations lower than 0.2 µg (or below
at 0.02 and 0.05 µg levels), the complexes induce relaxation
of the supercoiled DNA, displaying a significant inhibitory
activity of 50-60% as shown in Figure 7. The inhibition
percentage was reduced to ∼40% at 0.02 µg concentration.
However, if the concentration was reduced further, no
inhibitory activity was observed.
Anomalous morphology of Z-DNA and its involvement
in gene expression and recombination has drawn enormous
scientific attention on B-Z transitions.27 The B f Z form
conversion in the presence of the complexes under study was
followed spectrophotometrically. All of the complexes
(except 6) promote conformational changes in the structure
of DNA from B f Z form as evidenced by the observed
change in the A260/A295 ratio from 2.17 for free DNA to 1.32
(1), 1.18 (2), 1.18 (3), 2.61 (6), 1.20 (7), 1.50 (8), and 1.27
(9). Further, condensation of calf thymus (CT) DNA induced
by the complexes was monitored spectroscopically following
the increase in the absorption value at 320 nm.28 All of the
complexes (except 6) were found to cause condensation of
DNA at 10-20 µg concentration. The condensation of DNA
was monitored by measuring the increase in the value of
absorption at 320 nm [0.029 for free DNA to 0.149 (1), 0.123
(2), 0.127 (3), 0.010(6), 0.139 (7), 0.129 (8), and 0.133 (9)]
or a decrease in the absorbance at 260 nm. Complexes 1
and 2 at 10 µg concentration caused condensation of DNA,
while complex 6 was not effective in this process.
Figure 5. Gel mobility shift assay of S. cerVi Topo II by complexes 1, 2,
and 6 (5 µg, lanes 3, 5, and 7; 2 µg, lane 4, 6, and 8). Lane 1: pBR322
(0.25 µg) alone. Lane 2: pBR322 + S. cerVi Topo II. Lanes 3 and 4: 1.
Lanes 5 and 6: 2. Lanes 7 and 8: 6.
Figure 6. Gel mobility shift assay of S. cerVi Topo II by complexes 2, 3,
and 7-9 (2 µg, lanes 3, 5, 7, 9, and 11; 0.2 µg, lanes 4, 6, 8, 10, and 12).
Lane 1: pBR322 (0.25 µg) alone. Lane 2: pBR322 + S. cerVi Topo II.
Lanes 3 and 4: 2. Lanes 5 and 6: 3. Lanes 7 and 8: 7. Lanes 9 and 10:
8. Lanes 11 and 12: 9.
-
of the chloro group by anionic ligands like SCN- or N3
has little influence on the MLCT bands. The complexes
under study are nonluminescent at room temperature.
DNA Interaction Studies. Gel electrophoresis assays were
performed to elucidate direct metal-DNA interaction fol-
lowing a shift in the electrophoretic mobility of the plasmid
DNA on agarose gel. Metal-DNA interaction causes alter-
ation in the structure of DNA, whereupon the mobility of
supercoiled DNA decreases and the migration of open-
circular DNA slightly increases at the comigration junction
of both forms. Further, an essential cellular enzyme Topo II
has been identified as an important biochemical target in
chemotherapy and microbial infections, which is intricately
involved in the topographic structure of DNA transcription
and mitosis.24 Anti-Topo II agents control the Topo II activity
either by trapping the Topo II-DNA complex or by acting
as Topo II inhibitors.25
Ruthenium(II) polypyridyl complexes 1-3 and 6-9 also
displayed a significant inhibitory effect on the heme poly-
meraze activity of P. yoelii lysate, which was studied by
â-hematin formation.29 The parent mononuclear complex 1
showed 94% inhibition of the heme polymerase activity,
while complexes 2, 3, and 6-9 exhibited 71, 38, 23, 45, 34,
and 18% inhibition, respectively. The observed result could
be attributed to an increase in the steric hindrance by
The enzyme-mediated supercoiled pBR322 relaxation
assay was performed to examine the influence of the
complexes on the Topo II-DNA activity of the filarial
parasite S. cerVi.26 Interaction studies exhibited an inhibitory
(24) Wang, J. C. J. Biol. Chem. 1991, 266, 6659.
(25) Morris, R. E.; Aird, R. E.; Murdoch, P. del S.; Chen, H.; Cummings,
J.; Hughes, N. D.; Parsons, S.; Parkin, A.; Boyd, G.; Jodrell, D. I.;
Sadler, P. J. J. Med. Chem. 2001, 44, 3616.
(26) (a) Pandya, U.; Saxena, J. K.; Kaul, S. M.; Murthy, P. K.; Chatterjee,
R. K.; Tripathi, R. P.; Bhaduri, A. P.; Shukla, O. P. Med. Sci. Res.
1999, 27, 103. (b) Tripathi, R. P.; Rastogi, S. K.; Kundu, B.; Saxena,
J. K.; Reddy, V. J. M.; Shrivastav, S. K.; Chandra, S.; Bhaduri, A. P.
Comb. Chem. High Throughput Screening 2001, 4, 237. (c) Burden,
D. A.; Osheroff, N. Biochim. Biophys. Acta 1998, 1400, 139.
(27) (a) Pohl, E. M.; Jovin, T. M. J. Mol. Biol. 1972, 67, 375. (b) Chaires,
J. B. J. Biol. Chem. 1986, 261, 8899 and references cited therein.
(28) (a) Basu, H. S.; Marton, L. J. Biochem. J. 1987, 244, 243. (b) Thomas,
T. J.; Messner, R. P. J. Mol. Biol. 1988, 201, 463.
(29) Pandey, A. V.; Singh, N.; Takwani, B. L.; Puri, S. K.; Chauhan, V.
S. J. Pharm. Biomed. Anal. 1999, 20, 203.
1186 Inorganic Chemistry, Vol. 47, No. 3, 2008

Ruthenium(II) Polypyridyl Complexes
Figure 7. Gel mobility shift assay of S. cerVi Topo II by complexes 1, 2, and 6 (0.2 µg, lanes 3, 6, and 9; 0.05 µg, lanes 4, 7, and 10; 0.02 µg, lanes 5,
8, and 11). Lane 1: pBR322 (0.25 µg) alone. Lane 2: pBR322 + S. cerVi Topo II. Lanes 3-5: 1. Lanes 6-8: 2. Lanes 9-11: 6.
of the complexes were recorded on Shimadzu 8201PC and UV-
subsequent replacement of the chloro group in 1 and
incorporation of another metal center in 7-9 reducing the
free coordination sites.
1
1601 spectrophotometers, respectively. H and 31P NMR spectra
were recorded on a Bruker DRX-300 NMR instrument. Tetram-
ethylsilane and phosphorus trichloride have been used as internal
references for 1H and 31P NMR spectroscopic studies, respectively.
FAB-MS spectra were recorded on a JEOL SX 102/DA 6000 mass
spectrometer using xenon (6 kV, 10 mA) as the FAB gas. The
accelerating voltage was 10 kV, and the spectra were recorded at
room temperature with m-nitrobenzyl alcohol as the matrix.
Synthesis of [Ru(κ3-tptz)(PPh3)Cl2] (1). A suspension of [RuCl2-
(PPh3)3] (0.990 g, 1.0 mmol) in benzene (35 mL) was treated with
tptz (0.312 g, 1.0 mmol), and the resulting solution was heated
under reflux for 4 h, whereupon a microcrystalline product separated
from the blue solution. The microcrystalline product was collected
by filtration, washed repeatedly with benzene and diethyl ether,
and dried under vacuum. Yield: 0.671 g (90%). Anal. Calcd for
C36Cl2H27N6PRu: C, 57.90; H, 3.61; N, 11.26. Found: C, 58.12;
H, 3.40; N, 11.41. FAB-MS (obsd (calcd), rel intens, assign-
ments): m/z 710 (711), 50, [Ru(κ3-tptz)(PPh3)Cl]+; 674 (675), 25,
[Ru(κ3-tptz)(PPh3)]2+; 412 (413), 12, [Ru(κ3-tptz)]2+. 1H NMR (300
MHz, CDCl3): δ 9.46 (d, 2H, J ) 4.2 Hz), 8.95 (d, 1H, J ) 2.7
Hz), 8.61 (dd, 3H, J ) 8.7 Hz), 7.96 (t, 1H, J ) 6.9 Hz), 7.86 (t,
2H, J ) 6.9 Hz), 7.55 (m, 3H), 7.36-7.10 (br m, 15H, PPh3). 31P-
{1H} NMR: δ 36.69 (s). UV-vis [CH2Cl2; λmax, nm (ꢀ, M-1
cm-1)]: 534 (7260), 371 (6360), 288 (26 270).
Synthesis of [Ru(κ3-tptz)(κ2-dppm)Cl]BF4 (2). A suspension
of 1 (0.746 g, 1.0 mmol) in methanol (25 mL) was treated with
dppm (0.384 g, 1.0 mmol) and refluxed for 4 h. The resulting bright-
orange-red solution was filtered to remove any solid impurities,
treated with a saturated solution of NH4BF4 in methanol, and left
for slow crystallization. The orange-red crystalline product was
separated by filtration and washed with methanol and diethyl ether.
Yield: 0.672 g (73%). Anal. Calcd for BC43ClF4H34N6P2Ru: C,
56.08; H, 3.69; N, 9.13. Found: C, 56.39; H, 4.03; N, 9.51. FAB-
MS (obsd (calcd), rel intens, assignments): m/z 833 (833), 75, [Ru-
Conclusion
In this work, we have presented the synthesis and spectral
and structural characterization of some neutral and cationic
ruthenium(II) polypyridyl complexes with multifaceted val-
ues. The complex [Ru(κ3-tptz)(PPh3)Cl2] exhibits a rich
chemistry, serves as a good precursor to form interesting
substitutional products, and acts as a potential metalloligand
in the synthesis of homo- and heterodinuclear complexes.
Further, the complexes exhibit inhibitory activity against the
Topo II-DNA interaction of filarial parasite S. cerVi and
â-hematin/hemozoin formation in the presence of P. yoelii
lysate.
Experimental Section
Reagents. All of the synthetic manipulations were performed
under a nitrogen atmosphere in deaerated solvents. The solvents
were purified rigorously by standard procedures prior to their use.30
Ammonium tetrafluoroborate, triphenylphosphine, bis(diphenylphos-
phino)methane, sodium diethyldithiocarbamate, sodium azide,
potassium thiocyanate, 1,3-cyclohexadiene, R-phellandrene, pen-
tamethylpentacyclodiene, ruthenium(III) chloride hydrate, and rhod-
ium(III) chloride hydrate (all from Aldrich) were used as received
without further purification. Arene ruthenium complexes [{(η6-
C6H6)Ru(µ-Cl)Cl}2] and [{(η6-C10H14)Ru(µ-Cl)Cl}2] and isostruc-
tural rhodium complex [{(η5-C5Me5)Rh(µ-Cl)Cl}2] were prepared
and purified by literature procedures.31 Triply distilled deionized
water was used for the preparation of various buffers. Calf thymus
(CT) DNA and supercoiled pBR322 DNA was procured from
Sigma Chemical Co., St. Louis, MO. Topoisomerase II (Topo II)
from the filarial parasite S. cerVi was partially purified according
to the method by Pandya et al.26
(κ3-tptz)(κ2-dppm)Cl]+; 797 (797), 80, [Ru(κ3-tptz)(κ2-dppm)]2+
;
413 (413), 25, [Ru(κ3-tptz)]2+. H NMR (300 MHz, CDCl3): δ
9.00 (t, 4H, J ) 7.2 Hz), 8.37 (m, 3H), 8.12 (d, 1H, J ) 6.0 Hz),
7.89 (t, 2H, J ) 7.5 Hz), 7.59 (td, 2H, J ) 4.8 Hz), 7.27-6.82
ppm (br m, 20H, dppm), 5.50 (m, 2H of dppm). 31P{1H} NMR: δ
1
General Methods. Elemental analyses were performed by the
Microanalytical Section of the Sophisticated Analytical Instrumen-
tation Centre, Central Drug Research Institute, Lucknow, India. IR
in KBr disks and electronic spectra for a dichloromethane solution
6.64 (d, J ) 56.62 Hz), -11.29 (d, J ) 58.56 Hz). IR (cm-1
,
(30) Perrin, D. D.; Armango, W. L. F.; Perrin, D. R. Purification of
laboratory Chemicals; Pergamon: Oxford, U.K., 1986.
(31) (a) Robertson, D. R.; Robertson, I. W.; Stephenson, T. A. J.
Organomet. Chem. 1980, 202, 309. (b) Bennett, M. A.; Smith, A. K.
J. Chem. Soc., Dalton Trans. 1974, 233. (c) Bennett, M. A.; Huang,
T.-N.; Matheson, T. W.; Smith, A. K. Inorg. Synth. 1982, 21, 74. (d)
White, C.; Yates, A.; Maitilis, P. M. Inorg. Synth. 1992, 29, 228.
Nujol): ν(BF4-) 1060. UV-vis [CH2Cl2; λmax, nm (ꢀ, M-1 cm-1)]:
478 (6970), 295 (27 180).
Alternatively, complex 2 was also prepared by the reaction of
[Ru(κ3-tptz)(PPh3)2Cl]BF4 with dppm in methanol under refluxing
conditions.14a
Inorganic Chemistry, Vol. 47, No. 3, 2008 1187

Sharma et al.
Synthesis of [Ru(κ3-tptz)(PPh3)(pa)]Cl (3). A suspension of 1
(0.746 g, 1.0 mmol) in methanol (25 mL) was treated with a
methanol solution of phenylalanine (pa; 0.165 g, 1.0 mmol) and
KOH (0.056 g, 1.0 mmol) and refluxed for 4 h. The resulting violet-
black solution was filtered while hot to remove any solid impurities
and left for slow crystallization. After a few days, a microcrystalline
product appeared. It was separated by filtration and washed with
diethyl ether. Yield: 0.656 g (75%). Anal. Calcd for C45ClH37N7O2-
PRu: C, 61.71; H, 4.23; N, 11.20. Found: C, 61.49; H, 4.41; N,
(η6-C6H6)Ru(µ-Cl)Cl}2] dissolved and gave a blue-black solution.
The reaction mixture was cooled to room temperature, and a
saturated solution of NH4BF4 in methanol was added and left for
slow crystallization. A blue-black crystalline product was separated
by filtration, washed with diethyl ether, and dried under vacuum.
Yield: 0.734 g (70%). Anal. Calcd for BC42Cl3FH33N6PRu2: C,
48.09; H, 3.14; N, 8.01. Found: C, 47.86; H, 3.51; N, 7.77. FAB-
MS (obsd (calcd), rel intens, assignments): m/z 961 (961), 45, [Cl2-
(PPh3)Ru(µ-tptz)Ru(η6-C6H6)Cl]+; 698 (699), 40, [Cl2Ru(µ-tptz)-
Ru(η6-C6H6)Cl]+. 1H NMR (300 MHz, CDCl3): δ 10.53 (d, 1H, J
) 7.8 Hz), 9.54 (d, 1H, J ) 5.1 Hz), 9.39 (d, 1H, J ) 5.1 Hz),
9.19 (d, 1H, J ) 5.4 Hz), 8.62 (m, 2H), 8.25 (t, 1H, J ) 7.8 Hz),
8.08 (m, 3H), 7.83 (t, 1H, J ) 4.2 Hz), 7.57 (t, 1H, J ) 7.2 Hz),
7.26-7.14 (br m, 15H, PPh3), 5.82 (s, 6H, C6H6). 31P{1H} NMR:
δ 29.91 (s). IR (cm-1, Nujol): ν(BF4-) 1060. UV-vis [CH2Cl2;
1
11.31. H NMR (300 MHz, CDCl3): δ 8.93 (d, 1H, J ) 4.5 Hz),
8.62 (m, 5H), 7.95 (m, 2H), 7.79 (t, 1H, J ) 7.7 Hz), 7.53 (m,
2H), 7.28 (t, 3H, J ) 5.1 Hz), 7.12 (br m for 2H of the Ph ring of
pa and 15H of PPh3), 3.53 (m, 1H), 2.77 (d, 2H, J ) 4.8 Hz).
31P{1H} NMR: δ 40.77 (s). IR (cm-1, Nujol): ν(CO) 1627, 1720.
UV-vis [CH2Cl2; λmax, nm (ꢀ, M-1 cm-1)]: 491 (8840), 355 (7560),
276 (23 340).
λ
max, nm (ꢀ, M-1 cm-1)]: 590 (10 130), 404 (7120), 300 (23 230).
Synthesis of [Cl2(PPh3)Ru(µ-tptz)Ru(η6-C10H14)Cl]PF6 (8).
Synthesis of [Ru(κ3-tptz)(PPh3)(dtc)]Cl (4). A suspension of
1 (0.746 g, 1.0 mmol) and sodium diethyldithiocarbamate (0.224
g, 1.0 mmol) in methanol was refluxed for 6 h. The resulting
solution was completely evaporated to dryness on a water bath.
The solid mass thus obtained was extracted with dichloromethane
and precipitated with diethyl ether. Yield: 0.653 g (76%). Anal.
Calcd for C41ClH37N7PRuS2: C, 57.24; H, 4.30; N, 11.40. Found:
C, 56.98; H, 4.39; N, 11.09. FAB-MS (obsd (calcd); rel intens;
assignment): m/z 824 (823), 75, [Ru(κ3-tptz)(PPh3)(dtc)]+; 561
Complex 8 was prepared by the reaction of 1 with [{(η6-C10H14)-
Ru(µ-Cl)Cl}2] (0.306 g, 0.5 mmol) in methanol according to the
procedure for 7. Yield: 0.872 g (75%). Anal. Calcd for C46-
Cl3F6H41N6PRu2: C, 47.50; H, 3.52; N, 7.22. Found: C, 47.15; H,
3.88; N, 6.97. FAB-MS (obsd (calcd), rel intens, assignments): m/z
1018 (1017), 99, [Cl2(PPh3)Ru(µ-tptz)Ru(η6-C10H14)Cl]+; 755 (755),
60, [Cl2Ru(µ-tptz)Ru(η6-C10H14)Cl]+. 1H NMR (300 MHz,
CDCl3): δ 10.64 (d, 1H, J ) 7.8 Hz), 9.68 (d, 1H, J ) 4.8 Hz),
9.48 (d, 1H, J ) 5.4 Hz), 9.41 (d, 1H, J ) 7.5 Hz), 8.63 (m, 2H),
8.26 (t, 1H, J ) 7.8 Hz), 8.05 (m, 3H), 7.82 (t, 1H, J ) 4.2 Hz),
7.56 (t, 1H, J ) 7.2 Hz), 7.26-7.14 (br m, 15H, PPh3), 5.69 (m,
3H), 5.45 (d, 1H, J ) 5.4 Hz), 2.65 (m, 1H, CH3CHCH3), 2.12 (s,
3H, CCH3), 1.09 (d, 3H, J ) 6.3 Hz, CH(CH3)2), 0.92 (d, 3H, J )
6.6 Hz, CH(CH3)2). 31P{1H} NMR: δ 27.89 (s). IR (cm-1, Nujol):
ν(PF6-) 842. UV-vis [CH2Cl2; λmax, nm (ꢀ, M-1 cm-1): 595
(10 790), 410 (7300), 300 (22 650).
1
(562), 60, [Ru(κ3-tptz)(dtc)]+; 414 (413), 25, [Ru(κ3-tptz)]2+. H
NMR (300 MHz, CDCl3): δ 9.12 (dd, 4H, J ) 5.4 Hz), 8.93 (d,
2H, J ) 5.1 Hz), 8.19 (t, 2H, J ) 5.7 Hz), 7.76 (t, 2H, J ) 6.0
Hz), 6.99 (t, 2H, J ) 9.3 Hz), 7.36-7.10 (br m, 15H, PPh3), 4.11
(q, 2H, J ) 6.9 Hz), 3.59 (q, 2H, J ) 7.2 Hz), 1.52 (t, 3H, J ) 7.2
Hz), 1.12 (t, 3H, J ) 6.9 Hz). 31P{1H} NMR: δ 38.48 (s). IR (cm-1
,
Nujol): ν(CS) 1207. UV-vis [CH2Cl2; λmax, nm (ꢀ, M-1 cm-1):
485 (9580), 353 (9480), 290 (24 980).
Synthesis of [Cl2(PPh3)Ru(µ-tptz)Rh(η5-C5Me5)Cl]BF4 (9).
Complex 9 was prepared by the reaction of 1 with [{(η5-C5Me5)-
Rh(µ-Cl)Cl}2] (0.309 g, 0.5 mmol) in methanol according to the
procedure for 7. Yield: 0.809 g (73%). Anal. Calcd for BC46-
Cl3F4H42N6RuRh: C, 49.86; H, 3.79; N, 7.58. Found: C, 50.01;
H, 4.10; N, 7.46. FAB-MS (obsd (calcd), rel intens, assignments):
m/z 1021 (1020), 80, [Cl2(PPh3)Ru(µ-tptz)Rh(η5-C5Me5)Cl]+; 985
Synthesis of [Ru(κ3-tptz)(PPh3)(SCN)2] (5). It was synthesized
from the reaction of 1 (0.746 g, 1.0 mmol) with a slight excess of
NH4SCN in methanol under refluxing conditions. The reaction
mixture was cooled to room temperature and filtered. The solid
was washed with methanol and diethyl ether. Yield: 0.554 g (70%).
Anal. Calcd for C38H27N8PRuS2: C, 57.64; H, 3.69; N, 9.13.
Found: C, 57.47; H, 4.01; N, 9.50. FAB-MS (obsd (calcd), rel
intens, assignments): m/z 792 (791), 50, [Ru(κ3-tptz)(PPh3)(SCN)2];
734 (733), 95, [Ru(κ3-tptz)(PPh3)(SCN)]+; 675 (675), 25, [Ru(κ3-
tptz)(PPh3)]2+; 413 (413), 20, [Ru(κ3-tptz)]2+. 1H NMR (300 MHz,
CDCl3): δ 9.01 (dd, 2H, J ) 5.7 Hz), 8.62 (dd, 2H, J ) 4.8 Hz),
8.02 (t, 1H, J ) 7.2 Hz), 7.97 (d, 1H, J ) 6.6 Hz), 7.92 (d, 2H, J
) 6.9 Hz), 7.61 (t, 3H, J ) 6.0 Hz), 9.31 (d, 1H, J ) 5.1 Hz),
1
(986), 30, [Cl2(PPh3)Ru(µ-tptz)Rh(η5-C5Me5)]2+. H NMR (300
MHz, CDCl3): δ 10.54 (d, 1H, J ) 7.8 Hz), 9.62 (d, 1H, J ) 5.1
Hz), 9.46 (d, 1H, J ) 5.1 Hz), 9.20 (d, 1H, J ) 5.4 Hz), 9.05 (d,
1H, J ) 7.8 Hz), 8.85 (d, 1H, J ) 7.5 Hz), 8.60 (t, 1H, J ) 7.5
Hz), 8.30 (m, 3H), 8.10 (t, 1H, J ) 5.7 Hz), 7.94 (t, 1H, J ) 5.7
Hz), 7.40-7.34 (br m, 15H, PPh3), 1.45 (s, 15H, C5(CH3)5). 31P-
{1H} NMR: δ 29.81 (s). IR (cm-1, Nujol): ν(BF4-) 1060. UV-
vis [CH2Cl2; λmax, nm (ꢀ, M-1 cm-1)]: 589 (6290), 408 (4550),
293 (19 710).
7.34-7.13 (br m, 15H, PPh3). 31P{1H} NMR: δ 36.84 (s). IR (cm-1
,
Nujol): ν(SCN) 2092. UV-vis [CH2Cl2; λmax, nm (ꢀ, M-1 cm-1)]:
516 (7880), 355 (8260), 274 (30 100).
Crystal Structure Determinations. Crystals suitable for single-
crystal X-ray analyses for complexes 1-3, 8, and 9 were grown
from CH2Cl2/petroleum ether (40-60 °C) at room temperature.
Preliminary data on the space group and unit cell dimensions as
well as intensity data were collected on an Enraf-Nonius MACH3
diffractometer using graphite-monochromatized Mo KR radiation.
The crystal orientation, cell refinement, and intensity measurements
were made using the program CAD-4 PC. The structures were
solved by direct methods and refined by using SHELX-97.32 The
non-hydrogen atoms were refined with anisotropic thermal param-
eters. All of the hydrogen atoms were geometrically fixed and
Synthesis of [Ru(κ3-tptz)(PPh3)(N3)2] (6). Complex 6 was
prepared by the reaction of 1 with a slight excess of sodium azide
in methanol according to the procedure adopted for 5. Yield: 0.577
g (76%). Anal. Calcd for C36H27N12PRu: C, 56.91; H, 3.55; N,
1
22.13. Found: C, 57.11; H, 3.71; N, 21.95. H NMR (300 MHz,
CDCl3): δ 9.47 (d, 2H, J ) 5.4 Hz), 8.96 (d, 1H, J ) 4.2 Hz),
8.59 (dd, 3H, J ) 7.8 Hz), 7.86 (t, 3H, J ) 6.6 Hz), 7.59 (m, 3H),
7.34-7.10 (br m, 15H, PPh3). 31P{1H} NMR: δ 36.20 (s). IR (cm-1
,
Nujol): ν(N3) 2011-2037. UV-vis [CH2Cl2; λmax, nm (ꢀ, M-1
cm-1)]: 558 (5450), 374 (5770), 282 (23 700).
Synthesis of [Cl2(PPh3)Ru(µ-tptz)Ru(η6-C6H6)Cl]BF4 (7). To
a suspension of 1 (0.746 g, 1.0 mmol) in methanol (25 mL) was
added [{(η6-C6H6)Ru(µ-Cl)Cl}2] (0.250 g, 0.5 mmol), and the
resulting suspension was refluxed for 4 h. Slowly the complex [{-
(32) Sheldrick, G. M. SHELX-97: Programme for the solution and
refinement of crystal structures; University of Go¨ttingen: Go¨ttingen,
Germany, 1997.
1188 Inorganic Chemistry, Vol. 47, No. 3, 2008

Ruthenium(II) Polypyridyl Complexes
allowed to refine using a riding model. The computer program
PLATON was used for analyzing the interaction and stacking
distances.33
mL), and 25 µL of P. yoelii enzyme, and the volume was made up
with triple-distilled water. A total of 20 µg of the complexes was
added in the reaction mixture and incubated for 16 h at 37 °C in
an incubator shaker at a speed of 174 rpm. After incubation, the
reaction mixture was centrifuged at 10 000 rpm for 15 min and the
pellets obtained were washed three times with 10 mL of buffer
containing 0.1 M Tris-Cl buffer, pH 7.5, and 2.5% SDS and then
with buffer 2 (0.1 M sodium bicarbonate buffer, pH 9.2, and 2.5%
SDS), followed by distilled water.The semidried pellets were
suspended in 50 µL of 2 N NaOH, and the volume was adjusted to
1 mL with distilled water. The optical density was measured at
400 nm, and the percent inhibition was calculated using the
following formula: % inhibition ) {(1 - o.d. of control)/o.d. of
experimental} × 100.
Gel Mobility Shift Assays. The enzymatic activity of Topo II
was monitored by relaxation of supercoiled pBR322 DNA.26a,c For
relaxation assay, the reaction mixture (20 µL) contained 50 mM
Tris-HCl, pH 7.5, 50 mM KCl, 1 mM MgCl2, 1 mM ATP, 0.1
mM EDTA, 0.5 mM DTT, 30 µg/mL BSA, and enzyme protein.
Supercoiled pBR322 DNA (0.25 µg) was used as the substrate.
The reaction mixture was incubated for 30 min at 37 °C and stopped
by the addition of 5 µL of loading buffer containing 0.25%
bromophenol blue, 1 M sucrose, 1 mM EDTA, and 0.5% SDS.
Samples were applied on horizontal 1% agarose gel in 40 mM Tris-
acetate buffer, pH 8.3, and 1 mM EDTA and run for 10 h at room
temperature at 20 V. The gel was stained with ethidium bromide
(0.5 µg/mL) and photographed in a GDS 7500 UVP (Ultra Violet
Products, Cambridge, U.K.) transilluminator. One unit of topoi-
somerase activity is defined as the amount of enzyme required to
relax 50% of the supercoiled DNA under the standard assay
conditions.
The conformational transition of CT DNA in the presence of
the complexes was determined spectrophotometrically.27a The UV
absorbance ratio of A260/A295 was monitored for conformational
change in the DNA helix from B f Z DNA. Condensation of DNA
was monitored by following the increase in the value of absorbance
at 320 nm (A320) against different complex/DNA ratios, according
to the method of Basu and Marton.28a
Acknowledgment. Thanks are due to the Department of
Science and Technology, Ministry of Science and Technol-
ogy, New Delhi, India (Grant SR/S1/IC-15/2006), for
providing financial assistance and Prof. P. Mathur, In-charge,
National Single-Crystal X-ray Diffraction Facility, Indian
Institute of Technology, Mumbai, India, for providing single-
crystal X-ray data. We also thank Prof. Q. Xu, UBIQUI-
TOUS Division, AIST, Osaka, Japan, and Dr. J. K. Saxena
for their kind help.
Supporting Information Available: Crystallographic data of
complexes 1-3, 8, and 9 in CIF format and relevant matrixes and
figures for weak interactions (Table S1 and Figures S1 and S2,
respectively). This material is available free of charge via the
Internet at http://pubs.acs.org.
Heme Polymerase Assay. Anti-malarial activity of the com-
plexes was studied by the respective inhibition percentage against
â-hematin formation.29 The reaction mixture in 1 mL contained
100 µL of 1 M sodium phosphate buffer, 20 µL of hemin (1.2 mg/
(33) Spek, A. L. Acta Crystallogr. 1990, 46, C31.
IC701518E
Inorganic Chemistry, Vol. 47, No. 3, 2008 1189