Chemistry of HIV-1 virucidal Pt complexes having neglected bidentate sp2 N-donor carrier ligands with linked triazine and pyridine rings. Synthesis, NMR spectral features, structure, and reaction with guanosine

Article abstract of DOI:10.1021/ic060605h

Complexes of the types LPtCl₂ and [L₂Pt]X₂ [L = substituted 3-(pyridin-2′-yl)-1,2,4-triazine] were synthesized and characterized by NMR spectroscopy and, for the first time, by X-ray crystallography in an effort to determine the coordination properties of this novel class of inorganic medicinal agents possessing HIV-1 virucidal activity. The agents containing either one or two sp² N-donor bidentate ligands are referred to as ptt (platinum triazine) agents. The X-ray structures of three LPtCl₂ compounds revealed the expected pseudo-square-planar geometry. The X-ray structure of [(pyPh₂t)₂Pt](BF ₄)₂ [pyPh₂t = 3-(pyridin-2′-yl)-5,6- diphenyl-1,2,4-triazine] has the expected trans relationship of the unsymmetrical L and is essentially planar, an unusual property for a Pt ^II complex with two bidentate sp² N donors. HIV-1 is an RNA virus; the guanosine ribonucleoside (Guo) binds (MepyMe₂t) PtCl₂ at both (inequivalent) available coordination sites to form [(MepyMe₂t)Pt(Guo)₂]²⁺ [MepyMe₂t = 3-(4′-methylpyridin-2′-yl)-5,6-dimethyl-1,2,4-triazine]. This adduct has four nearly equally intense Guo H8 signals attributed to two pairs of head-to-tail (HT) and head-to-head (HH) conformers, which interchange rapidly within each pair. However, equilibration between pairs requires rotation of the Guo cis to the MepyMe₂t pyridyl ring, and the H6′ proton on this ring projects toward the Guo and hinders Guo rotation about the Pt-N7 bond. Thus, the HT/HH pairs do not interchange; such behavior is rare. Guo did not add to [(MepyMe₂t)₂Pt]²⁺, a result suggesting the possibility that the virucidal activity of LPtCl₂ and [L ₂Pt]²⁺ ptt agents arises respectively from covalent and noncovalent (possibly intercalative interactions favored by [L ₂Pt]²⁺ planarity) binding to biomolecular targets.

Full text of DOI:10.1021/ic060605h

Inorg. Chem. 2006, 45, 7182−7190
Chemistry of HIV-1 Virucidal Pt Complexes Having Neglected Bidentate
sp2 N-Donor Carrier Ligands with Linked Triazine and Pyridine Rings.
Synthesis, NMR Spectral Features, Structure, and Reaction with
Guanosine
Vidhi Maheshwari, Debadeep Bhattacharyya, Frank R. Fronczek, Patricia A. Marzilli, and
Luigi G. Marzilli*
Department of Chemistry, Louisiana State UniVersity, Baton Rouge, Louisiana 70803
Received April 10, 2006
Complexes of the types LPtCl2 and [L2Pt]X2 [L
) substituted 3-(pyridin-2′-yl)-1,2,4-triazine] were synthesized and
characterized by NMR spectroscopy and, for the first time, by X-ray crystallography in an effort to determine the
coordination properties of this novel class of inorganic medicinal agents possessing HIV-1 virucidal activity. The
agents containing either one or two sp2 N-donor bidentate ligands are referred to as ptt (platinum triazine) agents.
The X-ray structures of three LPtCl2 compounds revealed the expected pseudo-square-planar geometry. The X-ray
structure of [(pyPh2t)2Pt](BF4)2 [pyPh2t
) 3-(pyridin-2′-yl)-5,6-diphenyl-1,2,4-triazine] has the expected trans
relationship of the unsymmetrical L and is essentially planar, an unusual property for a PtII complex with two
bidentate sp2 N donors. HIV-1 is an RNA virus; the guanosine ribonucleoside (Guo) binds (MepyMe2t)PtCl2 at both
(inequivalent) available coordination sites to form [(MepyMe2t)Pt(Guo)2]2 [MepyMe2t
+
) 3-(4′-methylpyridin-2′-yl)-
5,6-dimethyl-1,2,4-triazine]. This adduct has four nearly equally intense Guo H8 signals attributed to two pairs of
head-to-tail (HT) and head-to-head (HH) conformers, which interchange rapidly within each pair. However, equilibration
between pairs requires rotation of the Guo cis to the MepyMe2t pyridyl ring, and the H6
′
proton on this ring
projects toward the Guo and hinders Guo rotation about the Pt
−N7 bond. Thus, the HT/HH pairs do not interchange;
such behavior is rare. Guo did not add to [(MepyMe2t)2Pt]2+, a result suggesting the possibility that the virucidal
+
activity of LPtCl2 and [L2Pt]2 ptt agents arises respectively from covalent and noncovalent (possibly intercalative
+
interactions favored by [L2Pt]2 planarity) binding to biomolecular targets.
Introduction
more limited soft centers in proteins and nucleic acids. The
nonleaving carrier ligand on Pt can modify binding sites and
thus the activity. Cisplatin [cis-Pt(NH3)2Cl2] and its ana-
logues, cis-PtA2X2 (A2 ) two amines or a diamine), interact
with DNA by forming a 1,2-intrastrand N7-Pt-N7 cross-
link between two adjacent guanines.8 PtII compounds also
have an extensive history of exhibiting antiviral activity
against numerous viruses, including topical antiviral
activity.9-15 In addition, we have clear evidence that the
carrier ligand influences the antiviral activity.13 Structural
In comparison to agents of purely organic molecules,
considerably less effort has been devoted to studying metal-
containing drugs. Pt complexes, which have been found to
be the most promising,1-7 have the advantages of inertness,
low coordination number, and preferential binding to the
* To whom correspondence should be addressed. E-mail: lmarzil@lsu.edu.
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L. G. J. Am. Chem. Soc. 2005, 127, 15833-15842.
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Farrell, N. J. Med. Chem. 2006, 49, 224-231.
(8) Blommaert, F. A.; Van Dijk-Knijnenburg, H. C. M.; Dijt, F. J.; Den
Engelse, L.; Baan, R. A.; Berends, F.; Fichtinger-Schepman, A. M. J.
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2853.
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2000, 5, 575-583.
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7182 Inorganic Chemistry, Vol. 45, No. 18, 2006
10.1021/ic060605h CCC: $33.50
© 2006 American Chemical Society
Published on Web 08/03/2006

Virucidal Platinum Pyridyltriazine Complexes
Scheme 1. Synthesis of
3-(Pyridin-2′-yl)-5,6-disubstituted-1,2,4-triazine (L)
Scheme 2. Synthesis of LPtCl2 and [L2Pt]2+ Complexesa
a Reagents and conditions: (i) A:B ) 1:1, CH3OH, 60 °C, 12 h; (ii)
A:B ) 1:2, CH3OH, 60 °C, 24 h.
(pyPh2t)). The other three ligands contain the 4′-methyl-
pyridin-2′-yl group: 3-(4′-methylpyridin-2′-yl)-5,6-dimethyl-
1,2,4-triazine (MepyMe2t), 3-(4′-methylpyridin-2′-yl)-5-
phenyl-1,2,4-triazine (MepyPht), and 3-(4′-methylpyridin-
2′-yl)-5,6-diphenyl-1,2,4-triazine (MepyPh2t). We describe
here the synthesis of LPtCl2 and [L2Pt]X2 complexes
modifications of the carrier ligand in cisplatin may broaden
the range of antitumor and antiviral activity and may provide
valuable insight into the mechanism of action of the drug.3,16
The development of multipurpose drugs with wider
application is desirable. Numerous Pt coordination com-
pounds have been synthesized and shown to have both
antiviral and antitumor activities.14 Hybrid drugs of the type
cis-[Pt(NH3)2(B)Cl]+, containing a cisplatin-like moiety and
an antiviral Guo-type ligand (B ) acyclovir or penciclo-
vir),14,15 are known. Collaborative studies from this laboratory
have shown that Pt compounds containing one or two
N-donor aromatic 3-(pyridin-2′-yl)-1,2,4-triazine ligands (ptt)
possess great potential as anti-HIV microbicides.13
1
(Scheme 2), along with their characterization by H NMR
spectroscopy and, for selected examples, by single-crystal
X-ray diffraction methods. The pyridyltriazines are relatively
neglected ligands; no crystal structures involving 3-(pyridin-
2′-yl)-1,2,4-triazines with Pt have been reported. However,
crystal structures of pyPh2t complexes of Cu,17 Sn,18 and
Ru19 have been reported. Also known is a crystal structure
of the [Ce(Mebtp)3]3+ [Mebtp ) 2,6-bis(5,6-dimethyl-1,2,4-
triazin-3-yl)-pyridine] complex with the Mebtp tridentate
ligand containing the pyMe2t moiety.20
PtII compounds have a high affinity for reacting with
S-containing biomolecules such as methionine and also with
N7 of purine bases in nucleic acids, but the target for
virucidal activity is not known. Carrier-ligand bulk plays a
role in influencing both biological activity and the properties
of adducts. Because Pt complexes of 3-(pyridin-2′-yl)-1,2,4-
triazines may form 1,2-intrastrand GG cross-links with RNA
in HIV-1 and because the observation of rotamers formed
by restricted rotation about the N7 bonds in Pt(Guo)2 adducts
provides information on ligand steric bulk, we assessed
whether rotamers can be detected for [(MepyMe2t)Pt-
(Guo)2]2+. The carrier ligands in cisplatin and other PtII
anticancer drugs usually are not bulky enough to impede the
rotation of N7-bound guanine about the Pt-N7 bond, but
planar sp2 N-donor ligands such as 5,5′-dimethyl-2,2′-
The [(ferene)PtCl2]2- and [(ferene)2Pt]2- [ferene )
3-(pyridin-2′-yl)-5,6-bis(5-sulfo-2-furyl)-1,2,4-triazine; in
Scheme 1, R2 ) R3 ) 5-sulfo-2-furyl] complexes are among
the most virucidal ptt compounds.13 However, these agents
with sulfonated ring substituents were not isolated as crystals,
1
have very complicated H NMR spectra, and thus were not
well-defined chemically. For example, the triazine ring
binding mode (N2 or N4, Scheme 1), or a mixture of such
binding modes, could not be resolved for the ferene agents.
In this study, we utilize six ligands, L, bearing a 3-(pyridin-
2′-yl)-1,2,4-triazine moiety (Scheme 1). Three ligands contain
the pyridin-2′-yl group: 3-(pyridin-2′-yl)-5,6-dimethyl-1,2,4-
triazine (pyMe2t), 3-(pyridin-2′-yl)-5-phenyl-1,2,4-triazine
(pyPht), and 3-(pyridin-2′-yl)-5,6-diphenyl-1,2,4-triazine
(11) Snyder, M. B.; Saravolatz, L. D.; Markowitz, N.; Pohlod, D.; Taylor,
R. C.; Ward, S. G. J. Antimicrob. Chemother. 1987, 19, 815-
822.
(12) Taylor, R. C.; Ward, S. G.; Schmidt, P. P. U.S. Patent Application,
1986; p 4.
(13) Vzorov, A. N.; Bhattacharyya, D.; Marzilli, L. G.; Compans, R. W.
AntiViral Res. 2005, 65, 57-67.
(14) Balcarova´, Z.; Kasˇpa´rkova´, J.; Zˇa´kovska´, A.; Novaka´va´, O.; Sivo, M.
F.; Natile, G.; Brabec, V. Mol. Pharmacol. 1998, 53, 846-855.
(15) Margiotta, N.; Bergamo, A.; Sava, G.; Padovano, G.; De Clercq, E.;
Natile, G. J. Inorg. Biochem. 2004, 98, 1385-1390.
(16) Fuertes, M. A.; Alonso, C.; Perez, J. M. Chem. ReV. 2003, 103, 645-
662.
(17) Uma, R.; Palaniandavar, M.; Butcher, R. J. J. Chem. Soc., Dalton
Trans. 1996, 10, 2061-2066.
(18) Prasad, L.; Page, L. E.; Smith, F. E. Inorg. Chim. Acta 1983, 68, 45-
49.
(19) Pal, P. K.; Chowdhury, S.; Drew, M. G. B.; Datta, D. New J. Chem.
2000, 24, 931-933.
(20) Iveson, P. B.; Riviere, C.; Guillaneux, D.; Nierlich, M.; Thuery, P.;
Ephritikhine, M.; Madic, C. J. Chem. Soc., Chem. Commun. 2001,
1512-1513.
Inorganic Chemistry, Vol. 45, No. 18, 2006 7183

Maheshwari et al.
bipyridine (5,5′-Me2bipy)21 and 1,10-phenanthroline (phen)22
allow the detection of rotamers on the NMR time scale. The
aromatic portion of the 3-(pyridin-2′-yl)-1,2,4-triazine carrier
ligands in ptt compounds can also possibly intercalate into
nucleic acids.23 Thus, all of these reasons prompted us to
conduct this study of the synthesis and characterization of
ptt compounds related to ptt compounds with ferene that
are known to be HIV-1 virucidal.13
crystals, involved mixing of an acetonitrile solution of cis-Pt(Me2-
SO)2Cl2 (4.22 mg,10 mM in 1 mL) with L (10 mM in 1 mL) and
allowing this mixture to stand at 23 °C. Thin needles of LPtCl2,
varying in color from greenish-yellow to orange, were obtained in
∼15% yield after 24 h.
(pyMe2t)PtCl2 (1). Method A gave a yellow precipitate: yield
) 0.077 g (71%). Method B afforded orange needle-shaped crystals.
1H NMR (ppm) in DMSO-d6: 9.57 (d, H6′), 8.60 (d, H3′), 8.48 (t,
H4′), 8.03 (t, H5′), 2.75 (s, CH3), 2.59 (s, CH3). Anal. Calcd for
C10H10Cl2N4Pt: C, 26.56; H, 2.23; N, 12.39. Found: C, 26.77; H,
2.29; N, 12.37.
Experimental Section
Starting Materials. The starting material, pyridine-2-carbox-
amide hydrazone (2-pyridylamidrazone), was synthesized by a
known method24 (Scheme 1) in yields above 90%. 4′-Methyl-
substituted pyridine-2-carboxamide hydrazone (4′-methyl-2-pyridyl-
amidrazone) was synthesized as described by Case.25 Guanosine
(Guo; Sigma) and pyPh2t (Fluka) were obtained from commercial
sources. cis-Pt(Me2SO)2Cl2 was prepared as described in the
literature.26 Elemental analyses (C, H, and N) were performed by
Atlantic Microlabs, Atlanta, GA.
NMR Measurements. 1H NMR spectra were recorded on Bruker
spectrometers operating at 400 or 500 MHz. We used the values
of 0.00 and 4.78 ppm to reference signals to tetramethylsilane in
deuterated dimethyl sulfoxide (DMSO-d6) solutions and to the
residual HOD signal in deuterated water (D2O)/DMSO-d6 solutions,
respectively. DNO3 and NaOD solutions (0.1 M in D2O) were used
to adjust the pH of D2O/DMSO-d6 solutions. 2D ROESY experi-
ments27 were performed at 25 °C by using a 500-ms mixing time
(128 scans per t1 increment). NMR data were processed with
XWINNMR or Mestre-C software.
Synthesis of L ) 3-(Pyridin-2′-yl)-5,6-disubstituted-1,2,4-
triazine and 3-(4′-Methylpyridin-2′-yl)-5,6-disubstituted-1,2,4-
triazine. The pyMe2t, pyPht, and pyPh2t ligands and their 3-
(4-methylpyridin-2′-yl) analogues, MepyMe2t, MepyPht, and
MepyPh2t, were prepared as described in the literature25,28,29
(Scheme 1), with minor modifications. An ethanol solution (30 mL)
containing 2-pyridylamidrazone, or its 4′-methyl analogue (2.5
mmol), and an R-diketone (2.5 mmol) was heated at reflux for 3 h.
The volume of the solution was reduced to one-fourth by rotary
evaporation. The addition of an excess of hexane afforded the
desired pure crystalline 3-(pyridin-2′-yl)-1,2,4-triazine in 90% yield.
Synthesis of LPtCl2 Complexes. Two methods, A and B, were
employed to obtain LPtCl2 complexes (Scheme 2). Method A
involved heating of a methanol solution (30 mL) of cis-Pt(Me2-
SO)2Cl2 (0.101 g, 0.24 mmol) and L (0.24 mmol) at 60 °C for 12
h. The yellow solid that precipitated was collected, washed with
diethyl ether followed by chloroform, and dried in vacuo. Method
A resulted in high yields of a powdered LPtCl2 product that required
no further purification. Method B, employed to obtain X-ray-quality
(pyPht)PtCl2 (2). Method A gave a yellow powder: yield )
0.084 g (75%). Method B produced yellow-green needles. 1H NMR
(ppm) in DMSO-d6: 10.18 (s, H6), 9.62 (d, H6′), 8.78 (d, H3′),
8.54 (t, H4′), 8.11 (t, H5′), 8.64 (d, o-PhH), 7.85 (t, p-PhH), 7.71
(t, m-PhH). Anal. Calcd for C14H10Cl2N4Pt: C, 33.61; H, 2.01; N,
11.20. Found: C, 33.48; H, 1.95; N, 11.10.
(pyPh2t)PtCl2 (3). Method A gave a yellow solid: yield ) 0.099
1
g (83%). Orange needles were obtained by method B. H NMR
(ppm) in DMSO-d6: 9.63 (d, H6′), 8.62 (d, H3′), 8.53 (t, H4′),
8.09 (t, H5′), 7.38-7.51 (PhH). Anal. Calcd for C20H14Cl2N4Pt:
C, 41.68; H, 2.45; N, 9.72. Found: C, 41.45; H, 2.37; N, 9.80.
(MepyMe2t)PtCl2 (4). Method A resulted in a yellow powder:
yield ) 0.096 g (77%). X-ray-quality crystals in the form of yellow
1
needles were obtained by method B. H NMR (ppm) DMSO-d6:
9.35 (d, H6′), 8.26 (s, H3′), 7.85 (d, H5′), 2.74 (s, CH3), 2.57 (s,
CH3), 2.53 (s, CH3). Anal. Calcd for C11H12Cl2N4Pt: C, 28.34; H,
2.59; N, 12.02. Found: C, 28.32; H, 2.58; N, 11.82.
(MepyPht)PtCl2 (5). The complex was obtained as a yellow
powder by method A: yield ) 0.095 g (68%). 1H NMR (ppm) in
DMSO-d6: 10.15 (s, H6), 9.41 (d, H6′), 8.61 (s, H3′), 7.91 (d,
H5′), 8.65 (d, o-PhH), 7.84 (t, p-PhH), 7.70 (t, m-PhH), 2.59 (s,
CH3). Anal. Calcd for C15H12Cl2N4Pt: C, 35.03; H, 2.35; N, 10.89.
Found: C, 34.81; H, 2.31; N, 10.65.
(MepyPh2t)PtCl2 (6). Method A resulted in a reddish-yellow
precipitate: yield ) 0.112 g (79%). Method B produced yellow
needles. 1H NMR (ppm) in DMSO-d6: 9.44 (d, H6′), 8.49 (s, H3′),
7.93 (d, H5′), 7.75 (d, o-PhH), 7.45-7.63 (m, p-PhH), 2.58 (s, CH3).
Anal. Calcd for C21H16Cl2N4Pt: C, 42.72; H, 2.73; N, 9.49.
Found: C, 42.75, H, 2.58; N, 9.43.
Synthesis of [L2Pt]X2 Salts. cis-Pt(Me2SO)2Cl2 (0.042 g, 0.1
mmol) was added to a methanol solution of L (0.4 mmol, 10 mL),
and the resulting suspension became a solution when stirred at 60
°C for 24 h (Scheme 2). The mixture was allowed to cool to room
temperature. Any precipitate that formed was removed by filtration,
and the clear filtrate was treated with a methanol solution of an
excess of NaBF4 or NaPF6 to precipitate the [L2Pt]X2 salt. The
solid was collected, washed twice with methanol followed by
anhydrous diethyl ether, and allowed to dry in air. Yields of the
1
[L2Pt]X2 salts were 35-45%. The H NMR spectra and shifts for
(21) Bhattacharyya, D.; Marzilli, P. A.; Marzilli, L. G. Inorg. Chem. 2005,
44, 7644-7651.
representative [L2Pt]X2 complexes appear in the Supporting
Information.
(22) Margiotta, N.; Papadia, P.; Fanizzi, F. P.; Natile, G. Eur. J. Inorg.
Chem. 2003, 1136-1144.
[(pyPht)2Pt](PF6)2 (7). The method described above afforded a
yellow solid upon the addition of an excess of NaPF6: yield )
0.30 g (36%). The 1H NMR spectra of the BF4 and PF6 salts were
identical. Anal. Calcd for C28H20N8P2F12Pt: C, 35.27; H, 2.11; N,
11.75. Found: C, 35.54; H, 1.89; N, 11.85.
[(pyPh2t)2Pt](BF4)2 (8). Crystals were obtained by the general
method described above, but by very careful dropwise addition of
a methanol solution of NaBF4 (5 mmol) to the filtrate until the
solution first became cloudy. Thin, yellow, needle-shaped crystals
were obtained by allowing the solution to stand undisturbed for 2
days.
(23) Collins, J. G.; Rixon, R. M.; Wright, J. R. A. Inorg. Chem. 2000, 39,
4377-4379.
(24) Hage, R.; Van Diemen, J. H.; Ehrlich, G.; Haasnoot, J. G.; Stufkens,
D. J.; Snoeck, T. L.; Vos, J. G.; Reedijk, J. Inorg. Chem. 1990, 29,
988-993.
(25) Case, F. H. J. Org. Chem. 1965, 30, 931-933.
(26) Price, J. H.; Williamson, A. N.; Schramm, R. F.; Wayland, B. B. Inorg.
Chem. 1972, 11, 1280-1284.
(27) Sullivan, S. T.; Ciccarese, A.; Fanizzi, F. P.; Marzilli, L. G. J. Am.
Chem. Soc. 2001, 123, 9345-9355.
(28) Hage, R.; Haasnoot, J. G.; Reedijk, J. Inorg. Chim. Acta 1990, 172,
19-23.
(29) Islam, M. A.; Stephen, W. I. Talanta 1992, 39, 1429-1435.
7184 Inorganic Chemistry, Vol. 45, No. 18, 2006

Virucidal Platinum Pyridyltriazine Complexes
Table 1. Crystal Data and Structure Refinement for LPtCl2 [L ) pyMe2t (1), pyPht (2), pyPh2t (3)] and [(pyPh2t)2Pt](BF4)2 (8)
1
2
3
8
empirical formula
fw
C10H10Cl2N4Pt
452.21
C14H10Cl2N4Pt
500.25
C20H14Cl2N4Pt‚CH3CN
617.40
C40H28B2F8N8Pt ‚0.59H2O
1000.00
space group
unit cell dimens
a (Å)
b (Å)
c (Å)
â (deg)
V (Å3)
T (K)
Pbca
P21/c
P21/c
C2/c
7.3055(10)
17.923(4)
17.977(4)
90
2353.8(8)
102
9.236(5)
7.496(4)
19.789(13)
94.312(18)
1366.2(14)
100
10.202(2)
7.4820(10)
27.278(7)
93.513(7)
2078.3(7)
100
35.253(5)
7.8417(15)
13.811(3)
99.270(7)
3768.1(12)
110
Z
F
8
4
4
4
calc (mg/m3)
2.552
12.356
65.2
0.029
0.060
2.432
10.658
55.0
0.062
0.155
1.973
7.029
63.0
0.034
0.059
6483/272
1.763
3.809
56.6
0.033
0.065
4639/275
abs coeff (mm-1
2θmax (deg)
)
R1 indicesa
wR2 [I > 2σ(I)]b
data/param
4267/157
3085/190
a R1 ) (∑||Fï| - |Fc||)/∑|Fï|. b wR2 ) [∑[w(Fï - Fc )2]/∑[w(Fï2)2]]1/2, in which w ) 1/[σ2(Fï2) + (0.0787P)2] and P ) (Fï + 2Fc )/3.
2
2
2
2
Table 2. Selected Bond Distances (Å) and Angles (deg) for LPtCl2
[(MepyPh2t)2Pt](PF6)2 (9). This product was obtained as a
[L ) pyMe2t (1), pyPht (2), pyPh2t (3)] and [(pyPh2t)2Pt](BF4)2 (8)
yellow solid in the same way as 7 was; yield ) 0.041 g (40%).
The 1H NMR spectra of the BF4 and PF6 salts were identical. Anal.
Calcd for C42H32N8P2F12Pt: C, 44.49; H, 2.84; N, 9.88. Found: C,
44.58; H, 2.68; N, 9.94.
1
2
3
8
Bond Distances
1.996(11) 1.996(3)
2.011(11) 2.027(3)
Pt-N1
Pt-N4
Pt-Cl1
Pt-Cl2
2.001(3)
2.020(3)
2.019(3)
2.050(3)
Reaction of ptt’s with Guo. A 14 mM (1.63 mg) solution of
(MepyMe2t)PtCl2 (4) in DMSO-d6 (250 µL) was treated with a
Guo solution (1.98 mg, 15.5 mM in 450 µL of D2O) to give a 1:2
ratio (5 mM to 10 mM ratio) of Pt/Guo, and the solution (pH ∼4.6)
was kept at 25 °C. The mixture of D2O and DMSO-d6 solutions
was used to improve the solubility of 4. The pH of the solution
decreased with time and had to be adjusted to ∼4.6. The solution
2.2969(11) 2.304(4)
2.2899(10) 2.292(4)
2.2920(10) Pt-N4i 2.050(3)
2.2972(10) Pt-N1i 2.019(3)
Bond Angles
N4-Pt-N1 80.33(12)
N1-Pt-Cl1 174.83(9)
N1-Pt-Cl2 96.05(9)
N4-Pt-Cl1 94.50(10)
N4-Pt-Cl2 176.30(9)
Cl2-Pt-Cl1 89.13(3)
C5-C4-C3 123.0(3)
N4-C4-C3 114.1(3)
N3-C3-C4 120.1(3)
N1-C3-C4 114.8(3)
79.8(4)
80.38(11)
174.90(8)
95.86(8)
94.60(8)
176.24(8)
78.68(13)
173.3(3)
96.2(3)
93.8(3)
176.0(3)
90.12(13) 89.16(3)
124.7(13) 122.9(3)
113.6(12) 114.5(3)
119.4(12) 121.0(3)
114.2(11) 115.0(3)
N1-Pt-N1i 180.0
N1-Pt-N4i 101.32(13)
N4-Pt-N1i 101.32(13)
N4-Pt-N4i 180.0
N4i-Pt-N1i 78.68(13)
123.1(4)
1
was monitored for 6 days until the H NMR signals of free Guo
disappeared. However, the reaction was repeated several times, and
to decrease the time for the reaction to reach completion, an excess
of Guo was often employed. A DMSO-d6 solution (250 µL) of
[(MepyMe2t)2Pt](BF4)2 (2.69 mg, 14 mM) was treated with a Guo
(1.98 mg, 15.5 mM) solution in D2O (450 µL) to give a 1:2 ratio
of Pt/Guo, and the solution was maintained at pH ∼4.6 at 25 °C.
114.4(3)
120.6(3)
114.6(3)
and2 and Figures 1 and 2). The atom-numbering systems in
these ORTEP figures are used to discuss only these solid-
state data. A superscript i denotes the atoms of the other
ligand in 8. For all other references to pyridyltriazine ligands
and complexes (e.g., NMR discussion), the atom numbering
in Scheme 1 will be used, and in the text, the number will
be in italics. In some cases, we shall designate the Pt-bound
N’s as N(t) and N(py), in the triazine and pyridine rings,
respectively. The numbering scheme for bipyridines is given
in Figure 3 and for guanosine in Figure 8.
To discuss structural features of the pyridyltriazine ligands,
we shall use some of the terminology employed for the
common symmetrical sp2 N-donor L’s, e.g., 2,2′-bipyridine
(bipy) or phen ligands. The M-N distance for which there
would be no in-plane distortion (Figure 3) has been estimated
to be 2.72 Å.32 Hazell and co-workers concluded that the
stress in coordinated bipy’s caused by the close proximity
of the H atoms on the C atoms ortho to the bridging atoms
is reduced by the twisting of the pyridine rings about the
bond bridging the two pyridine rings and by an in-plane
bending (Figure 3).33 Likewise, in compounds such as
1
The solution was monitored by H NMR spectroscopy, and no
evidence of any reaction was found even after 36 h.
X-ray Data Collection and Structure Determination. Single
crystals were placed in a cooled N2 gas stream at ∼100 K on a
Nonius Kappa CCD diffractometer fitted with an Oxford Cryos-
tream cooler with graphite-monochromated Mo KR (0.710 73 Å)
radiation. Data reduction included absorption corrections by the
multiscan method, with HKL SCALEPACK.30
All X-ray structures were determined by direct methods and
difference Fourier techniques and refined by full-matrix least
squares, using SHELXL97.31 All non-H atoms were refined aniso-
tropically. All H atoms were visible in difference maps but were
placed in idealized positions. A torsional parameter was refined
for each methyl group. For all structures, the maximum residual
densities were located near the Pt positions.
Results and Discussion
X-ray Crystallography. Structures of pseudo-square-
planar complexes reported here include LPtCl2 (L ) pyMe2t,
pyPht, and pyPh2t) and [(pyPh2t)2Pt](BF4)2 (8) (Tables 1
(30) Otwinowski, Z.; Minor, W. Macromolecular Crystallography; New
York Academic Press: New York, 1997; Vol. 276, Part A.
(31) Sheldrick, G. M. SHELXL97, Program for Crystal Structure Solution
and Refinement; University of Go¨ttingen: Go¨ttingen, Germany, 1997.
(32) Hazell, A. Polyhedron 2004, 23, 2081-2083.
(33) Hazell, A.; Simenson, O.; Wernberg, O. Acta Crystallogr. 1986, C42,
1707-1711.
Inorganic Chemistry, Vol. 45, No. 18, 2006 7185

Maheshwari et al.
Figure 1. ORTEP plots of (a) (pyMe2t)PtCl2 (1) and (b) (pyPht)PtCl2
(2). Thermal ellipsoids are drawn with 50% probability.
[(bipy)2Pt]2+, the M-N distance for which there would be
no distortion of the overall coordination environment from
planarity has been estimated to be 2.8 Å.34 Therefore, we
begin our discussion of the structures with bond lengths and
angles involving Pt.
Figure 2. ORTEP plots of (a) (pyPh2t)PtCl2 (3) and (b) [(pyPh2t)2Pt](BF4)2
(8). Thermal ellipsoids are drawn with 50% probability.
Structures of LPtCl2. (a) Coordination Parameters. The
size of the group on the C1 and C2 positions has little effect
on the coordinated bond distances and angles (Table 2). The
Pt-Cl or Pt-N(py) bond distances found for 1-3 are not
significantly different from those in the structure of (4,4′-
Me2bipy)PtCl2 (work in progress). All three LPtCl2 com-
plexes and (4,4′-Me2bipy)PtCl2 have comparable N-Pt-N
bite angles. For 1 and 3, in which the Pt-N distances are
more precisely determined, the Pt-N(py) bond (Pt-N4) is
slightly longer than the Pt-N(t) bond (Pt-N1) (Table 2).
We attribute this apparently slightly smaller Pt-N(t) bond
to an attractive interaction of the positive Pt center with the
lone pair on N2, the triazine N bound to N1. In contrast, the
H on the C8 atom of the pyridine ring (in the position
corresponding to N2) will have a repulsive interaction with
the positive Pt center.
Figure 3. Distortions in bipyridyl ligands: (a) in-plane, (b) twist, and (c)
bowing.
pyridine ring H atom (labeled A, Figure 4). The repulsion
(labeled R, Figure 4) between the lone pair on N2 and the
cis Cl creates a larger than normal N-Pt-Cl angle. The
apparent net effects of the nonbonding interactions involving
the lone pair are a shorter Pt-N(t) bond and a wider cis-
N(t)-Pt-Cl angle.
In 1-3, the cis-N(t)-Pt-Cl2 angle is significantly larger
than the cis-N(py)-Pt-Cl1 angle. There is a slight attractive
interaction between Cl’s cis to a pyridyl ring and the nearby
(b) Bidentate Ligand Parameters. Distortions in the
(34) Rund, J. V. Inorg. Chem. 1967, 7, 24-27.
ligand (Figure 3) will occur if the M-N distance is typical
7186 Inorganic Chemistry, Vol. 45, No. 18, 2006

Virucidal Platinum Pyridyltriazine Complexes
like distorted (Figure 7), while canting of the two ligands
occurs in [(2,2′-bipy)2Pt](NO3)2.33 In contrast, for 8, the Pt
lies on an inversion center, and the coordination geometry
is totally planar and symmetrical (Figure 7). In [(4,4′-
Me2bipy)2Pt](BF4)2, the distances found between H6 (H on
the C ortho to the N; Figure 3) and the opposing C6 of the
other ligand are 2.557 and 2.597 Å. For 8, in contrast, the
distance between the related pyridyl proton (H8; Figure 2)
and the opposing triazine nonbonded N2 of the other ligand
is 2.160 Å. The unusually small distance suggests the
possibility of two weak favorable H‚‚‚N interactions between
the two opposing pyPh2t ligands of 8. Thus, the metal center
exhibits no distortion.
Figure 4. Attractive and repulsive interactions in LPtCl2 and (bipy)PtCl2.
(∼2.0-2.2 Å).33 Because the distances of the C3H and C3′H
atoms of bipyridines (Figure 3) to the C3′ and H3′ atoms
and the C3 and H3 atoms on the other ring, respectively,
are less than the sum of the van der Waals radii,35 it has
been suggested that the resulting repulsive interactions
(labeled R, Figure 4) cause distortions.32,33 The difference
in two exocyclic angles (C5-C4-C3 and N4-C4-C3; see
Figure 2) of the pyridine ring can be used as a simple means
for estimating the in-plane bending (Figure 3).33 The differ-
ences in these two angles for (4,4′-Me2bipy)PtCl2 are
comparable to the differences for LPtCl2 complexes (Table
2), although for LPtCl2 complexes, the H on the pyridyl C
ortho to the bridging C atoms and the lone-pair-bearing
triazine N3 (in 3, Figure 2, the H5-N3 distance ) 2.630 Å
and the C5-N3 distance ) 2.900 Å) should create a slight
favorable attractive interaction (labeled A, Figure 4). There-
fore, any stress due to H3-H3′ repulsion in (4,4′-Me2bipy)-
PtCl2 does not lead to an apparent substantial effect on the
in-plane bending. However, this repulsion could account for
the slight twisting or bowing in (4,4′-Me2bipy)PtCl2 com-
pared to the minimal distortions found for the three LPtCl2
complexes (Figure 5).
Structure of [(pyPh2t)2Pt](BF4)2 (8). (a) Coordination
Parameters. The ORTEP drawing for 8 appears in Figure
2. The Pt-N(py) bond length [2.050(3) Å] in 8 is similar to
the Pt-N(py) bond length [2.032(3) Å] in [(4,4′-Me2bipy)2-
Pt](BF4)2 (work in progress), but it is significantly longer
than the Pt-N(t) bond distance [2.019(3) Å] in 8 (Table 2).
The reason for the shorter Pt-N(t) bond distance was
suggested above. The N-Pt-N bite angle in 8 is similar to
that in [(4,4′-Me2bipy)2Pt](BF4)2. These N-Pt-N bite angles
are slightly smaller than those for LPtCl2 (Table 2). The
Pt-N bond distances in 8 are larger than the corresponding
bond distances in 3.
NMR Spectroscopy. As mentioned, both the reaction of
ferene with cis-Pt(Me2SO)2Cl2 and the resulting products
1
are difficult to assess by H NMR spectroscopy because of
many overlapping signals. Also, simpler 3-(pyridin-2′-yl)-
1,2,4-triazines (L) analogues, which form LPtCl2 and [L2-
Pt]2+ complexes with less complicated spectra, have not been
studied. Hence, we have investigated by 1H NMR spectros-
copy the formation and properties, such as the degree of
solvolysis, of these simpler ptt compounds. We use the
standard numbering system for these L’s (Scheme 1).
Reactions of L (20 mM) with cis-Pt(Me2SO)2Cl2 (5 mM)
in DMSO-d6 were monitored with time until no further
changes were observed. The H6′ doublet was usually
observed between ∼9.3 and 9.6 ppm within ∼1 h of mixing.
After ∼1 day, a weaker doublet appeared farther downfield
(∼10.0-10.2 ppm). (These findings are consistent with the
ferene results: H6′ doublet at ∼9.6 ppm for [(ferene)PtCl2]2-
and at ∼10.7 ppm for [(ferene)2Pt]2-.13) The addition of
[NEt4]Cl caused an increase in the intensity of the doublet
between 9.3 and 9.6 ppm and the disappearance of the more
downfield doublet (∼10-10.2 ppm), indicating that these
are signals of LPtCl2 and [L2Pt]2+, respectively.
For all L’s, [L2Pt]2+ did not form completely and was less
abundant than LPtCl2 in DMSO-d6, even with a 3-fold excess
of L. To form bis-product exclusively, D2O (10 vol %) was
added to a separate solution of L and cis-Pt(Me2SO)2Cl2 (in
a 4:1 ratio). After ∼1 h, the [L2Pt]2+ signals were the only
bound L signals present. The greater solvation of the Cl-
ions in D2O compared to that in DMSO-d6 facilitates the
formation of bis-complexes. The reaction of pyMe2t with
cis-Pt(Me2SO)2Cl2 described in the Supporting Information
provides a detailed set of results that are representative of
studies with other L’s.
[(MepyMe2t)Pt(Guo)2]2+ Characterization. Within 30
min of mixing 4 and Guo in a 1:2 molar ratio in a D2O/
DMSO-d6 solution at pH 4.60 at 25 °C, the [(MepyMe2t)-
Pt(Guo)2]2+ adduct was formed. The adduct has H8 signals
at ∼8.7-8.9 ppm, downfield from the free Guo H8 signal
at 8.11 ppm, indicating that Guo is bound to Pt via N7. Two
guanine base arrangements, HH (head-to-head) and HT
(head-to-tail), are possible for [LPt(Guo)2]2+-type adducts.
Three rotamers (HH, ∆HT, and ΛHT) may be observed when
L ) symmetrical bidentate ligand, whereas four rotamers
(HHa, HHb, ∆HT, and ΛHT) are possible when L )
unsymmetrical bidentate ligand (Figure 8). The symmetry
(b) Relative Bidentate Ligand Relationships. The ligand
distortion due to in-plane bending for 8 was less than that
for [(4,4′-Me2bipy)2Pt](BF4)2 but comparable with those of
LPtCl2 (Table 2). For bipyridine complexes with ∼2-Å M-N
distances, the strain induced by the close approach of the H
atoms of opposing ligands can be reduced by two different
types of distortions. First, a tetrahedral deformation at the
metal can occur, resulting in the ligands being canted relative
to each other (Figure 6). Second, the ligand rings can be
bowed away from the ring directly across (Figure 6).32,33,36
The opposing ligands in [(4,4′-Me2bipy)2Pt](BF4)2 are bow-
(35) Bondi, A. J. Phys. Chem. 1964, 68, 441-451.
(36) Chassot, L.; Muller, E.; Zelewsky, A. V. Inorg. Chem. 1984, 23, 4249-
4253.
Inorganic Chemistry, Vol. 45, No. 18, 2006 7187

Maheshwari et al.
Figure 5. In-plane views of the two rings in bipyPtCl2 (left) and LPtCl2 (right).
suggests the occurrence of a complicated equilibration
process between rotamers and/or an intermediate exchange
rate.
The most likely process accounting for the three signals
is rapid rotation of a Guo in one of the coordination positions
and slow rotation of the other Guo. This situation would give
two pairs of HT and HH conformers that interchange within
the pair but not between pairs. In this case, the presence of
three H8 signals with one large (the upfield H8) signal
requires an overlap of two of the four expected H8 signals.
The upfield Guo H8 signal could not be resolved, even at
-4.0 °C. However, when the pH was raised to 7.75, four
distinct H8 peaks of comparable intensity were observed at
8.88, 8.86, 8.71, and 8.68 ppm (Figure 9). At this pH, the
N1H of coordinated Guo is deprotonated, resulting in greater
dispersion of H8 signals, but less dispersion for the H1′
signals, which all overlap. However, at pH 4.60, there are
two H1′ signals. One H1′ signal (at 6.06 ppm, for one Guo)
is one-third as large as the other overlapped H1′ signal (at
6.04 ppm, for three Guo’s). Thus, results for both H8 and
H1′ signals at both pH’s support the presence of four different
Guo’s in two sets of similarly abundant HT/HH pairs.
Extensive studies in which both the symmetrical carrier
ligand and the guanine derivative (G) were varied systemati-
cally indicate that, for a given adduct, the HT rotamers (in
total) are favored over the HH rotamer(s) (in total).44
Although the reasons for this observation are not fully
understood, the most compelling explanations are that base
dipole-dipole alignment favors the HT over the HH ar-
rangement of guanines and that clashes between the exocyclic
O6 on each guanine in the HH arrangement disfavor the HH
rotamer. When G is a guanosine 5′-monophosphate, ad-
ditional complications arise, increasing the abundance of the
HH form in some cases, but in general Guo adducts have a
particularly low amount of the HH rotamer.21,41,43 In a
previous study of [LPtG2]2+ adducts with an unsymmetrical
L, 2-(aminomethyl)piperidine (pipen), four H8 signals were
observed for each adduct,45,46 as found here. The results were
interpreted as indicating that each pair of H8 signals arose
from a rapidly interchanging pair of conformers, ∆HT/HHa
and ΛHT/HHb (Figure 8), with the HT form dominating. In
Figure 6. Canting (a) and bowing (b) of the two bipyridyl ligands with
respect to each other in [(bipy)2Pt]X2.
of the carrier ligand influences not only the number of
conformers but also the number of sets of Guo signals
detectable for each [LPt(Guo)2]2+ rotamer. For a nonbulky
L, rotation about the Pt-N7 Guo bond is very fast on the
NMR time scale; the rapid equilibration of rotamers in this
case leads to one set or two sets of Guo NMR signals for
[LPt(Guo)2]2+ adducts with symmetrical and unsymmetrical
L, respectively. Bulky carrier ligands restrict the rotation of
Guo about the Pt-N7 bond sufficiently to allow detection
of different rotamers by NMR spectroscopy.21,37-43 Because
the Guo H8 signals are downfield, they can be particularly
informative for assessing the nature and distribution of
rotamers. For an [LPt(Guo)2]2+ adduct with an unsym-
metrical L, the four rotamers should give two and eight H8
signals for rapidly and slowly exchanging conformers,
respectively.
For [(MepyMe2t)Pt(Guo)2]2+, three bound Guo H8 signals
were present (Figure 9): two H8 signals of comparable
intensity at 8.90 and 8.87 ppm (integrating to a total of one
proton) and another larger H8 signal upfield at 8.75 ppm
(integrating to a single proton). The observation of three H8
signals (not two for fast or eight for slow isomerization)
(37) Cramer, R. E.; Dahlstrom, P. L. Inorg. Chem. 1985, 24, 3420-3424.
(38) Cramer, R. E.; Dahlstrom, P. L. J. Am. Chem. Soc. 1979, 101, 3679-
3681.
(39) Xu, Y.; Natile, G.; Intini, F. P.; Marzilli, L. G. J. Am. Chem. Soc.
1990, 112, 8177-8179.
(40) Ano, S. O.; Intini, F. P.; Natile, G.; Marzilli, L. G. Inorg. Chem. 1999,
38, 2989-2999.
(41) Sullivan, S. T.; Ciccarese, A.; Fanizzi, F. P.; Marzilli, L. G. Inorg.
Chem. 2001, 40, 455-462.
(44) Natile, G.; Marzilli, L. G. Coord. Chem. ReV. 2006, 250, 1315-1331.
(45) Wong, H. C.; Coogan, R.; Intini, F. P.; Natile, G.; Marzilli, L. G.
Inorg. Chem. 1999, 38, 777-787.
(46) Wong, H. C.; Intini, F. P.; Natile, G.; Marzilli, L. G. Inorg. Chem.
1999, 38, 1006-1014.
(42) Kiser, D.; Intini, F. P.; Xu, Y.; Natile, G.; Marzilli, L. G. Inorg. Chem.
1994, 33, 4149-4158.
(43) Saad, J. S.; Scarcia, T.; Shinozuka, K.; Natile, G.; Marzilli, L. G. Inorg.
Chem. 2002, 41, 546-557.
7188 Inorganic Chemistry, Vol. 45, No. 18, 2006

Virucidal Platinum Pyridyltriazine Complexes
Figure 7. Side view of [(bipy)2Pt]X2 (left) and [(pyt)2Pt]X2 (right).
Figure 8. Possible base orientations of two cis guanine bases coordinated
to Pt. Each arrow represents a guanine base (bottom). The Pt carrier ligand
is to the rear; when it is unsymmetrical (N1 * N2), there are two HH
conformers. Rotation of one base about the Pt-N7 bond leads to another
conformer, but in each case, the base orientation changes from HT to HH
and vice versa. When the carrier ligand has unsymmetrical bulk, it is possible
that on the NMR time scale the base next to the bulky side of the carrier
ligand does not rotate quickly, whereas the other base rotates rapidly. For
example, the ∆HT conformer would interchange rapidly with the HHa
conformer if the base next to N1 rotated slowly while the base next to N2
rotated readily. In contrast, the ∆HT conformer would form the HHb
conformer only slowly.
Figure 9. Aromatic and H1′ signals of the 1H NMR spectrum of the
[(MepyMe2t)Pt(Guo)2]2+ adduct in a D2O/DMSO-d6 solution at pH 4.60
(top) and pH 7.75 (bottom) at 25 °C. Numbers are taken from the numbering
system in Scheme 1 for L and are shown in Figure 8 for Guo.
NOE cross peaks in the [(MepyMe2t)Pt(Guo)2]2+ ROESY
spectrum between the Guo H8 singlet at 8.86 ppm and the
pyridyl H6′ doublet at 7.96 ppm and between the Guo H8
singlet at 8.88 ppm and the pyridyl H6′ doublet at 7.94 ppm
indicate that the two most downfield H8 signals belong to
the Guo bound cis to the pyridyl ring. The more upfield H8
signals, at 8.71 and 8.68 ppm, belong to the Guo bound cis
to the triazine ring.
Compared to the signals of [(MepyMe2t)Pt(Me2SO-d6)-
Cl]+ in D2O/DMSO-d6 at pH 4.60, the H5′ (7.76 ppm) and
H3′ (8.60 ppm) signals of the [(MepyMe2t)Pt(Guo)2]2+
adduct at pH 4.60 shifted only slightly upfield and downfield,
respectively. In contrast, the H6′ doublets at 8.04 and 8.00
ppm (integrating to a total of one proton) for this adduct
were shifted upfield by ∼1.26 ppm from the H6′ signal at
9.28 ppm of [(MepyMe2t)Pt(Me2SO-d6)Cl]+. The anisotropy
of the cis-coordinated guanine base is responsible for these
large upfield shifts. These shifts and the H8-H6′ NOE cross
peaks leave no doubt that the guanine in the adduct is
positioned very close to H6′. Two considerations [(a) the
pyridyl H6′ proton is known to hinder the rate of rotation
about the Pt-N7 Guo bond21 and (b) two upfield-shifted H6′
signals are resolved for the [(MepyMe2t)Pt(Guo)2]2+ adduct]
leave no doubt that the slowly rotating Guo is cis to the
pyridyl ring and that the Guo cis to the triazine ring is in
fast rotation. Otherwise, the H6′ doublets would probably
be time-averaged.
the pipen case, the amino group allows rapid rotation of the
cis G, whereas the piperidine ring hinders rotation of the
cis G.45,46
The properties of the [(MepyMe2t)Pt(Guo)2]2+ adduct at
pH 7.75 were explored further by using 2D NMR spectros-
copy. An additional 1 equiv of Guo was added to ensure
that all of the Pt compound was consumed prior to a ROESY
experiment, which allows us to probe the exchange processes
and the through-space interactions between Guo and the
MepyMe2t ligand. Neither nuclear Overhauser effect (NOE)
nor exchange spectroscopy cross peaks were observed
between the H8 signals. An HH conformer would give an
H8-H8 NOE cross peak, and even for a rapid HT/HH
equilibrium, a cross peak would be found if either HT/HH
pair had a significant amount of the HH conformer. The four
[(MepyMe2t)Pt(Guo)2]2+ H8 signals thus reflect mainly the
two HT conformers, ∆HT and ΛHT, present in a nearly 1:1
ratio. The H8 NMR signals of the HH conformer were not
detectable, indicating a more rapid rate of rotation about the
Pt-N7 bond for one Guo in [(MepyMe2t)Pt(Guo)2]2+, a
result more similar to that found for (pipen)PtG2 adducts45,46
than for (5,5′-Me2bipy)PtG2 adducts21 and (Me2ppz)PtG2
adducts41 (Me2ppz ) N,N′-dimethylpiperazine).
Inorganic Chemistry, Vol. 45, No. 18, 2006 7189

Maheshwari et al.
Conclusions
Pt-N7 bond, whereas the equivalently placed CH group of
the pyridyl ring does impede rotation. This behavior and the
structural data all point to a lower overall steric effect of
the N2-metal-bound triazine ring compared to the metal-
bound pyridine ring. Dynamic behavior similar to that of
the [(MepyMe2t)Pt(Guo)2]2+ adduct has been well docu-
mented previously only in the case of pipen complexes.45,46
Our result that Guo did not add to [(MepyMe2t)2Pt]2+
suggests the possibility that the virucidal activity of the
LPtCl2 and [L2Pt]2+ ptt agents arises respectively from
covalent and noncovalent (possibly intercalative nucleic acid
interactions favored by [L2Pt]2+ planarity) binding to bio-
molecular targets. These results suggest that the relatively
neglected 3-(2′-pyridyl)-1,2,4-triazine ligands should be
examined more widely in coordination chemistry.
Regardless of the presence of various exocyclic groups,
3-(2′-pyridyl)-1,2,4-triazine ligands are excellent bidentate
sp2 N donors and form both LPtCl2 and [L2Pt]2+ complexes.
The juxtaposition of the pyridyl H6′ proton and the triazine
lone pair of electrons in [L2Pt]X2 allows the formation of a
planar structure. Also, this juxtaposition favors the trans
arrangement of the bidentate ligands in [L2Pt]X2. The ligands
prefer to bind via only the N2 of the triazine ring. No
evidence was found for isomers having N4 coordinated to
Pt. Very likely, this result arises from the effect of the group
ortho to the bound N. For a given bidentate ligand, the
interactions between the juxtaposed groups on the two rings
ortho to the bridging C atoms and on the periphery of the
bidentate ligand are favorable for 3-(2′-pyridyl)-1,2,4-triazine
ligands but unfavorable for bipy’s. This favorable factor
would be present if the triazine ring binds to metals via either
N2 or N4. For N2 binding, the N1 lone pair is readily
accommodated sterically, but the substituent on C5 would
create steric clashes if metal binding were to occur via N4.
Thus, the observation that only N2 binding was detected can
be understood. When combined with the X-ray structural
results, the H6′ NMR spectral shifts of the complexes
containing the L’s examined here establish that the structures
of virucidal ptt compounds containing ferene proposed
earlier were correct.13
Note Added in Proof: A Re complex with the pyPh2t
ligand was recently characterized crystallographically. Das,
S.; Chakravorty, A. Eur. J. Inorg. Chem. 2006, 2285-2291.
Acknowledgment. This work was supported by NIH
Grant GM 29222 (to L.G.M.).
Supporting Information Available: Crystallographic data for
(pyMe2t)PtCl2, (pyPht)PtCl2, (pyPh2t)PtCl2, and [(pyPh2t)2Pt]-
1
(BF4)2 in CIF format, H NMR spectra and chemical shifts for
selected [L2Pt]X2 complexes, and a description of reactions of
pyMe2t with cis-Pt(Me2SO)2Cl2 studied by 1H NMR spectroscopy.
This material is available free of charge via the Internet at
http://pubs.acs.org.
The dynamic properties of the [(MepyMe2t)Pt(Guo)2]2+
adduct indicate that the lone pair on the nonbonded nitrogen,
N1, of the triazine ring is not sterically demanding. This lone
pair does not strongly impede the rotation of Guo about the
IC060605H
7190 Inorganic Chemistry, Vol. 45, No. 18, 2006