Mono- and polynuclear complexes of the model nucleobase 1-methylcytosine. Synthesis and characterization of cis[(PMe2Ph)2Pt{1-MeCy(- H)}]3(NO3)3 and cis-[(PPh3) 2Pt{1-MeCy(-H)}(1-MeCy)]NO3

Article abstract of DOI:10.1021/ic060831r

The hydroxo complex cis-[L₂Pt(μ-OH)]₂(NO ₃)₂ (L = PMe₂Ph), in various solvents, reacts with 1-methylcytosine (1-MeCy) to give as the final product the cyclic species cis-[L₂Pt{1-MeCy(-H),N³N⁴}]₃(NO ₃)₃ (1) in high or quantitative yield. X-ray analysis of 1 evidences a trinuclear species with the NH₂-deprotonated nucleobases bridging symmetrically the metal centers through the N3 and N4 donors. A multinuclear NMR study of the reaction in DMSO-d₆ reveals the initial formation of the dinuclear species cis-[L₂Pt{1-MeCy(-H),N ³N⁴}]₂²⁺ (2), which quantitatively converts into 1 following a first-order kinetic law (at 50°C, t _1/2 = 5 h). In chlorinated solvents, the deprotonation of the nucleobase affords as the major product (60-70%) the linkage isomer of 1, cis-[L₂Pt{1-MeCy(-H)}]₃³⁺ (3), in which three cytosinate ligands bridge unsymmetrically three cis-L₂Pt²⁺ units. In solution, 3 slowly converts quantitatively into the thermodynamically more stable isomer 1. No polynuclear adducts were obtained with the hydroxo complex stabilized by PPh₃. cis-[(PPh₃) ₂Pt(μ-OH)]₂(NO₃)₂ reacts with 1-MeCy, in DMSO or CH₂Cl₂, to give the mononuclear species cis-[(PPh₃)₂Pt{1-MeCy(-H)}(1-MeCy)](NO₃) (4) containing one neutral and one NH₂-deprotonated 1-MeCy molecule, coordinated to the same metal center at the N3 and N4 sites, respectively. X-ray analysis and NMR studies show an intramolecular H bond between the N4 amino group and the uncoordinated N3 atom of the two nucleobases.

Full text of DOI:10.1021/ic060831r

Inorg. Chem. 2006, 45, 8179−8187
Mono- and Polynuclear Complexes of the Model Nucleobase
1-Methylcytosine. Synthesis and Characterization of
cis-[(PMe2Ph)2Pt (1-MeCy( H) ]3(NO3)3 and
cis-[(PPh3)2Pt 1-MeCy( H) (1-MeCy)]NO3
{
− }
{
− }
Bruno Longato,*,†,‡ Diego Montagner,‡ and Ennio Zangrando§
Istituto di Scienze e Tecnologie Molecolari, CNR, c/o Dipartimento di Scienze Chimiche,
UniVersita` di PadoVa, Via Marzolo 1, 35131 PadoVa, Italy, Dipartimento di Scienze Chimiche,
UniVersita` di PadoVa, Via Marzolo 1, 35131 PadoVa, Italy, and Dipartimento di Scienze
Chimiche, UniVersita` di Trieste, Via Giorgieri 1, 34127 Trieste, Italy
Received May 15, 2006
The hydroxo complex cis-[L2Pt(
(1-MeCy) to give as the final product the cyclic species cis-[L2Pt
µ
-OH)]2(NO3)2 (L
)
PMe2Ph), in various solvents, reacts with 1-methylcytosine
1-MeCy( ]3(NO3)3 (1) in high or quantitative
H),N 3N 4
{
−
}
yield. X-ray analysis of 1 evidences a trinuclear species with the NH2-deprotonated nucleobases bridging symmetrically
the metal centers through the N3 and N4 donors. A multinuclear NMR study of the reaction in DMSO-d6 reveals
2
+
the initial formation of the dinuclear species cis-[L2Pt
into 1 following a first-order kinetic law (at 50 C, t1
nucleobase affords as the major product (60
{
1-MeCy(
5 h). In chlorinated solvents, the deprotonation of the
2
−
H),N 3N 4
}
]
(2), which quantitatively converts
2
°
−
)
/
3+
70%) the linkage isomer of 1, cis-[L2Pt
which three cytosinate ligands bridge unsymmetrically three cis-L2Pt2+ units. In solution, 3 slowly converts quantitatively
into the thermodynamically more stable isomer 1. No polynuclear adducts were obtained with the hydroxo complex
{
1-MeCy(
−H)}
]
(3), in
3
stabilized by PPh3. cis-[(PPh3)2Pt( -OH)]2(NO3)2 reacts with 1-MeCy, in DMSO or CH2Cl2, to give the mononuclear
µ
species cis-[(PPh3)2Pt 1-MeCy(−H)}(1-MeCy)](NO3) (4) containing one neutral and one NH2-deprotonated 1-MeCy
{
molecule, coordinated to the same metal center at the N3 and N4 sites, respectively. X-ray analysis and NMR
studies show an intramolecular H bond between the N4 amino group and the uncoordinated N3 atom of the two
nucleobases.
Chart 1
Introduction
Cytosine, as a neutral molecule, can exist in six tautomeric
forms. Structural, spectroscopic, and theoretical studies
indicate that tautomer I (Chart 1, R ) H) is largely the most
dominant.1 Alkylation at N1 reduces the number of possible
tautomers to three (I-III in Chart 1). The basicity of N3
(pKa ) 4.6) favors this cytosine atom as the primary site for
metal coordination.2 However, examples of the rare imino-
* To whom correspondence should be addressed. E-mail:
bruno.longato@unipd.it.
oxo tautomer (II in Chart 1) of 1-methylcytosine, through
N4 coordination to PtIV 3 and PtII,4 are also known.
† Istituto di Scienze e Tecnologie Molecolari, CNR.
‡ Universita` di Padova.
§ Universita` di Trieste.
(1) Taylor, R.; Kennard, O. J. Mol. Struct. 1982, 78, 1. Bandekar, J.;
Zundel, G. Spectrochim. Acta, Part A 1983, 39, 343. Scanlan, M. J.;
Hillier, I. M. J. Am. Chem. Soc. 1984, 106, 3737.
(2) Lippert, B. Prog. Inorg. Chem. 1989, 37, 1.
(3) Lippert, B.; Scho¨llhorn, H.; Thewalt, U. J. Am. Chem. Soc. 1986, 108,
6616.
(4) Pichierri, F.; Holthenrich, D.; Zangrando, E.; Lippert, B.; Randaccio,
L. J. Biol. Inorg. Chem. 1996, 1, 439.
10.1021/ic060831r CCC: $33.50
Published on Web 09/09/2006
© 2006 American Chemical Society
Inorganic Chemistry, Vol. 45, No. 20, 2006 8179

Longato et al.
Chart 2
Chart 3
Deprotonation of the exocyclic NH2 group (pKa ) 16.7)5
leads the anion to behave as mono-, bi-, and tridentate
ligands, as shown in Chart 2, which summarizes the binding
modes of the 1-methylcytosinate ion [1-MeCy(-H)]. The
anion has been found to act as a monodentate ligand through
N4 (A mode), binding metal centers in high oxidation states
such as PtIV 6 and RuIII 7 or, more frequently, as a bidentate
ligand, coordinating the same metal ion in a chelating fashion
(B mode) or bridging two metal centers through N3 and N4
donors (C mode).8 Cytosinate anions have been shown to
act also as tridentate ligands (D mode) in trinuclear PtPd2
and PtAg2 complexes.9
PMe2Ph and PPh3), with 1-MeCy showing that the cytosinate
anion forms trinuclear adducts when L is PMe2Ph. The
thermodynamically stable product is the cyclic species cis-
[(PMe2Ph)2Pt{1-MeCy(-H),N3N4}]33+ (1; Chart 3), charac-
terized by a single-crystal X-ray analysis structurally similar
to that of the PMe3 complex.11 When the condensation
reaction is monitored in DMSO, the cyclic intermediate cis-
[(PMe2Ph)2Pt{1-MeCy(-H),N3N4}]22+ (2) has been identified
and its conversion to 1 investigated. However, when the
condensation reaction is performed in chlorinated solvents,
the main product is the linkage isomer of 1, i.e., the cyclic
We have found that if deprotonation of 1-MeCy is
performed through the hydroxo complex cis-[(PMe3)2Pt(µ-
OH)]22+, the cytosinate ion binds two metal centers exclu-
sively through the N3 and N4 atoms (C mode) to form the
3+
species cis-[(PMe2Ph)2Pt{1-MeCy(-H)}]3 (3; Chart 3),
2+
dinuclear species cis-[(PMe3)2Pt{1-MeCy(-H),N3N4}]2
,
where the bridging nucleobases bind the metal centers
unsymmetrically. A complete characterization of this un-
precedented trinuclear species has been obtained by multi-
nuclear NMR analysis and its stability in solution investi-
gated. Moreover, the extension of this study to the hydroxo
complex stabilized by PPh3 shows that similar polynuclear
complexes of 1-MeCy are unstable. Instead, the mononuclear
bis-adduct cis-[(PPh3)2Pt{1-MeCy(-H)}(1-MeCy)]+ (4) is
formed in high yield. This compound, structurally character-
ized by single-crystal X-ray analysis, represents the first
example of a 1-MeCy complex where one neutral and one
NH2-deprotonated nucleobase are coordinated to the same
metal center.
with the nucleobases bridging the metal centers in a head-
to-tail fashion.10 This complex, in dimethyl sulfoxide (DMSO)
or H2O at 80 °C, converts into the corresponding trinuclear
derivative cis-[(PMe3)2Pt{1-MeCy(-H),N3N4}]33+, in which
the anionic ligands maintain the same head-to-tail arrange-
ment.11 Cyclic trimers of PtII stabilized by phosphines are
rare,12 and this derivative of 1-MeCy appears to be the only
one structurally characterized.13 Very recently, a Pd analogue,
stabilized by N,N,N′,N′-tetramethylethylenediamine, has been
described by Lippert et al.14
In this paper, we report a detailed analysis of the inter-
actions of the hydroxo complexes cis-[L2Pt(µ-OH)]22+ (L )
(5) Lippert, B. Handbook of Nucleobase Complexes; Lusty, J. R., Ed.;
CRC Press: Boca Raton, FL, 1990; Vol. 1, p 9.
(6) Randaccio, L.; Zangrando, E.; Cesa`ro, A.; Holthenrich, D.; Lippert,
B. J. Mol. Struct. 1998, 440, 221.
(7) Graves, B. J.; Hodgson, D. J. J. Am. Chem. Soc. 1979, 101, 5608.
(8) Zangrando, E.; Pichierri, F.; Randaccio, L.; Lippert, B. Coord. Chem.
ReV. 1996, 156, 275.
(9) (a) Holthenrich, D.; Krumm, M.; Zangrando, E.; Pichierri, F.;
Randaccio, L.; Lippert, B. J. Chem. Soc., Dalton Trans. 1995, 3275.
(b) Holthenrich, D.; Zangrando, E.; Chiarparin, E.; Lippert, B.;
Randaccio, L. J. Chem. Soc., Dalton Trans. 1997, 4407.
(10) Trovo`, G.; Bandoli, G.; Casellato, U.; Corain, B.; Nicolini, M.;
Longato, B. Inorg. Chem. 1990, 29, 4616.
(11) Schenetti, L.; Bandoli, G.; Dolmella, A.; Trovo`, G.; Longato, B. Inorg.
Chem. 1994, 33, 3169.
(12) (a) Schweiger, M.; Seidel, S. R.; Arif, A. M.; Stang, P. J. Angew.
Chem., Int. Ed. 2001, 40, 3467. (b) Schweiger, M.; Seidel, S. R.; Arif,
A. M.; Stang, P. J. Inorg. Chem. 2002, 41, 2556. (c) Longato, B.;
Pasquato, L.; Mucci, A.; Schenetti, L.; Zangrando, E. Inorg. Chem.
2003, 42, 7861.
Experimental Section
Instrumentation and Materials. 1H, 13C{1H}, and 31P{1H}
NMR spectra were recorded at 27 °C on a Bruker AVANCE 300
and/or Bruker 600 MHz, while 2D 15N-1H and 31P-1H NMR
spectra were recorded at 27 °C on a Bruker 400 AMX-WB
spectrometer (at 40.56, 75.47, and 161.49 MHz, respectively) and
1
were calibrated against the residual signals of the solvent (for H
and 13C NMR) and external H3PO4 for 31P NMR. The external
references for 195Pt and 15N were Na2PtCl4 in D2O (adjusted to δ
-1628 ppm from Na2PtCl6) and CH3NO2, respectively. Inverse-
detected spectra were obtained through heteronuclear multiple-
quantum or multiple-bond correlation (HMQC or HMBC) experi-
ments, using parameters similar to those previously reported.15
Deuterated solvents (from Aldrich) were used as received. 1-MeCy,16
(13) Randaccio, L.; Zangrando, E. In CisplatinsChemistry and Biochem-
istry of a Leading Anticancer Drug; Lippert, B., Ed.; VHCA: Zu¨rich,
Switzerland, 1999; pp 405-428.
(15) Schenetti, L.; Mucci, A.; Longato, B. J. Chem. Soc., Dalton Trans.
1996, 299.
(16) Kistenmacher, T. J.; Rossi, M.; Caradonna, J. P.; Marzilli, L. G. AdV.
(14) Shen, W.-Z.; Gupta, D.; Lippert, B. Inorg. Chem. 2005, 44, 8249.
Mol. Relax. Interact. Processes 1979, 15, 119.
8180 Inorganic Chemistry, Vol. 45, No. 20, 2006

Complexes of the Model Nucleobase 1-Methylcytosine
cis-[(PMe2Ph)2Pt(µ-OH)]2(NO3)2,17 and cis-[(PPh3)2Pt(µ-OH)]2-
(NO3)2 were synthesized as previously reported.
temperature for ca. 15 h. The resulting solid was recovered by
filtration, washed twice with CHCl3/CH2Cl2 (1:1), and purified by
dissolution in N,N-dimethylformamide (DMF) and precipitation with
Et2O. The yield of the dried solid, having the composition 4‚H2O‚
DMF, was 158 mg (56%). Elem anal. Calcd for C46H43N7O5P2Pt‚
H2O‚DMF: C, 52.45; H, 4.67; N, 9.98. Found: C, 52.73; H, 4.53;
18
Synthetic Work. 1. cis-[(PMe2Ph)2Pt{1-MeCy(-H),N3N4}]3-
(NO3)3 (1). A suspension of cis-[(PMe2Ph)2Pt(µ-OH)]2(NO3)2 (201
mg, 0.183 mmol) and 1-MeCy (45.9 mg, 0.366 mmol) in H2O (5
mL) was stirred at room temperature for ca. 1 h. The resulting
colorless solution, stored overnight at 10 °C, separated a white
amorphous solid, which was recovered by filtration and dissolved
in a mixture of H2O (0.5 mL) and EtOH (1 mL). Slow evaporation
of the solution afforded a crystalline solid, which was recovered
by filtration and dried under vacuum. The elemental analysis and
1H NMR indicate the presence of a molecule of water for each Pt
atom. The yield of 1‚3H2O was 197 mg (55%). Elem anal. Calcd
for C21H28N4O4P2Pt‚H2O: C, 37.34; H, 4.48; N, 8.30. Found: C,
37.70; H, 4.42; N, 8.23. A better yield of 1 was obtained when the
reaction was carried out in acetonitrile as follows. A suspension of
cis-[(PMe2Ph)2Pt(µ-OH)]2(NO3)2 (236 mg, 0.214 mmol) and 1-MeCy
(53.6 mg, 0.428 mmol) in CH3CN (6 mL) was stirred at room
temperature. In a few minutes, a colorless solution was obtained
and was left to stand overnight at room temperature and then filtered
to eliminate trace amounts of Pt. The addition of Et2O afforded a
white solid, which was filtered, washed with Et2O, and dried under
vacuum. Dissolution of the crude product in CH3CN followed by
slow condensation of Et2O vapors afforded a crystalline solid (216
1
N, 10.01. H NMR in DMSO-d6 (δ, ppm): 7.89-7.85 (c.m., 4H,
PPh), 7.64-7.16 (c.m., 11H, PPh and H6 of 1-MeCy(-H)).
3
1-MeCy(-H) resonances: 5.07 (d, JHP ) 4.7 Hz, 1H, NH), 4.98
3
(d, JHH ) 7.3 Hz, 1H, H5), 3.11 (s, 3H, NCH3). 1-MeCy
3
resonances: 10.63 (s, 1H, NH), 8.34 (s, 1H, NH), 6.66 (d, JHH
)
7.3 Hz, 1H, H6), 5.25 (dd, 3JHH ) 7.3 Hz, 5JHP ) 1.6 Hz, 1H, H5),
3.18 (s, 3H, NCH3). {1H}31P NMR in DMSO-d6: AB multiplet at
δ 12.34 (1JPPt ) 3241 Hz) and 0.21 (1JPPt ) 3452 Hz) with 2JPP
)
20.1 Hz. 195Pt (inverse-detected) NMR data in DMSO-d6 (δ,
ppm): -4825 ppm.
1H NMR in DMF-d7 (δ, ppm): 7.789-7.24 (c.m., 31H, PPh
and H6 of 1-MeCy(-H)). 1-MeCy(-H) resonances: 5.15 (d, 3JHH
) 6.8 Hz, 1H, H5), 5.11 (d, 3JHP ) 4.4 Hz, 1H, NH), 3.27 (s, 3H,
NCH3). 1-MeCy resonances: 10.94 (s, 1H, NH), 8.39 (s, 1H, NH),
6.77 (d, 3JHH ) 7.2 Hz, 1H, H6), 5.49 (dd, 3JHH ) 7.2 Hz, 5JHP
)
1.7 Hz, 1H, H5), 3.19 (s, 3H, NCH3). {1H}31P NMR in DMF- d7:
AB multiplet at δ 12.74 (1JPPt ) 3192 Hz) and 0.90 (1JPPt ) 3597
2
Hz) with JPP ) 20.2 Hz.
1
mg, yield 81%) having the composition 1‚H2O‚CH3CN. H and
31P NMR data are collected in Tables 3 and 4, respectively. {1H}13C
NMR (in CDCl3 at 27 °C): 165.94 (d, 3JCP ) 4.5 Hz, C-4), 156.60
4. Kinetic Study of the Conversion of cis-[(PMe2Ph)2Pt{1-
MeCy(-H),N3N4}]2(NO3)2 (2) into 1. A 5-mm NMR tube was
loaded with a solution of cis-[(PMe2Ph)2Pt(µ-OH)]2(NO3)2 (14.2
mg) and 1-MeCy (3.2 mg) in DMSO-d6 (1 mL). The 31P NMR
spectrum, obtained at 27 °C, was similar to that reported in Figure
3a, where the content of 2 was ca. 90%. The temperature of the
sample was then brought to 50 °C, and the 31P NMR spectra (1500
scans) were obtained at intervals of 2-5 h. The relative molar
concentrations of 1 and 2 were measured from the integrals of the
pertinent species. A linear dependence of ln([1]/[2]) vs time was
obtained (see the Supporting Information, Figure S2), and the
calculated value of t1/2 was ca. 5 h.
3
(d, JCP ) 2 Hz, C-2), 143.97 (s, C-6), 133.18-130.17 (complex
set of overlapping doublets, PMe2Ph), 99.35 (s, C-5), 38.90 (s,
NCH3); 15.39 (d, 1JCP ) 42.6 Hz, PMe2Ph), 14.44 (d, 1JCP ) 43.3
1
1
Hz, PMe2Ph), 13.81 (d, JCP ) 41.2 Hz, PMe2Ph), 15.51 (dd, JCP
) 42.5 Hz, JCP ) 1.7 Hz, PMe2Ph). The inverse-detected 195Pt
3
NMR resonance in CDCl3 showed the expected doublet of doublets
1
pattern at δ -4314 ppm, with JPtP values consistent with those
measured in the corresponding 31P NMR spectrum. 15N (inverse-
detected) NMR data in CDCl3 (δ, ppm): -245 N(1); -258 (1JNH
2
) 75 Hz, JNP ) 70 Hz) N(4). [The electrospray ionization (ESI)
spectrum is depicted in the Supporting Information, Figure S1].
2. cis-[(PMe2Ph)2Pt{1-MeCy(-H)}]3 (3). A mixture of cis-
X-ray Structure Determinations. Diffraction data for compound
1 were collected on a Nonius DIP-1030H system equipped with
Mo KR radiation [λ ) 0.710 73 Å; T ) 293(2) K] and those of 4
at the RX diffraction beamline [λ ) 1.000 00 Å; T ) 100(2) K] of
Elettra synchrotron (Trieste, Italy). Cell refinement, indexing, and
scaling of the data sets were carried out using Denzo and
Scalepack.19 Both of the structures were solved by direct method
and subsequent Fourier analyses and refined by the full-matrix least-
squares methods based on F 2 with all observed reflections.20 The
∆F maps evidenced some residuals interpreted as a water O and
an acetonitrile molecule in 1, while the crystal of 4 contained a
water and a DMF molecule per complex unit. The program VOID
(Platon package) evidenced in 1 a residual potential solvent volume
that accounts for the 14.2% of the unit cell. H atoms were located
at geometrical positions; those of cytosine exocyclic amino groups
and of water of 4 were derived from the Fourier map. H atoms of
the disordered solvent species of 1 were not included. All of the
calculations were performed using the WinGX System, version
1.70.05.21 Crystallographic data are collected in Table 1.
3+
[(PMe2Ph)2Pt(µ-OH)]2(NO3)2 (132 mg, 0.12 mmol) and 1-MeCy
(30 mg, 0.24 mmol) in CH2Cl2 (3 mL) was stirred at room
temperature for ca. 1 h at 0 °C. A small amount of the solid phase
was eliminated by filtration, and the addition of Et2O (30 mL)
afforded a white precipitate, which was collected by filtration and
dissolved again in CH2Cl2. Fractional precipitation with Et2O
afforded two portions of precipitate, which were analyzed by 31P
NMR, in fresh prepared CDCl3 solutions. The composition of the
first fraction (ca. 80 mg), expressed as a contribution of the integrals
of each species (see Table 4), was as follows: complex 3 (58%),
complex 1 (32%), unreacted hydroxo complex (2%), and unattrib-
uted resonances (8%). The composition of the second fraction (ca.
50 mg) was as follows: 3 (72%), 1 (14%), unreacted hydroxo
(12%), and unattributed resonaces (2%). This latter sample was
used for the 195Pt (inverse-detected) NMR experiment. (δ, 195Pt):
for PtI, -4320 ppm; for PtII, -4261 ppm.
3. cis-[(PPh3)2Pt{1-MeCy(-H)}(1-MeCy)]NO3 (4). 1-MeCy
(64 mg, 0.51 mmol) was added to a solution of cis-[(PPh3)2Pt(µ-
OH)]2(NO3)2 (204 mg, 0.125 mmol) in a mixture of CH2Cl2 (4 mL)
and CHCl3 (4 mL), and the suspension was stirred at room
(19) Otwinowski, Z.; Minor, W. Processing of X-ray Diffraction Data
Collected in Oscillation Mode. Methods in Enzymology, Volume 276:
Macromolecular Crystallography; Carter, C. W., Jr., Sweet, R. M.,
Eds.; Academic Press: New York, 1997; Part A, pp 307-326.
(20) SHELX97, Programs for Crystal Structure Analysis, release 97-2;
University of Go¨ttingen: Go¨ttingen, Germany, 1998.
(17) Longato, B.; Pasquato, L.; Mucci, A.; Schenetti, L. Eur. J. Inorg. Chem.
2003, 128.
(18) Longato, B.; Montagner, D.; Bandoli, G.; Zangrando, E. Inorg. Chem.
2006, 45, 1805.
(21) Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837.
Inorganic Chemistry, Vol. 45, No. 20, 2006 8181

Longato et al.
Table 1. Crystallographic Data and Details of Structure Refinements
for Compounds 1 and 4
1‚H2O‚CH3CN
4‚H2O‚DMF
formula
Mr
cryst syst
space group
a (Å)
C65H89N13O13P6Pt3
2031.58
triclinic
P1h
14.969(4)
15.766(4)
21.517(5)
74.31(3)
74.71(2)
62.19(2)
4267.4(19)
2
C49H52N8O7P2Pt
1122.02
monoclinic
P21/c
13.190(3)
38.648(5)
9.754(3)
b (Å)
c (Å)
R (deg)
â (deg)
γ (deg)
V (Å3)
Z
110.30(2)
4663.5(19)
4
1.598
4.712
2264
D
calcd (g cm-3
)
1.581
5.078
1996
Mo KR (mm-1
F(000)
)
θ
max (deg)
28.41
26 464
17 974
0.0589
9314
887
0.870
0.0566
31.72
22 826
5073
0.0313
4744
619
reflns collected
unique reflns
Rint
Figure 1. ORTEP drawing (ellipsoid at the 40% probability level) of the
cation of 1. C atoms are not labeled for the sake of clarity.
obsd I > 2σ(I)
no. of param
GOF (F 2)
Table 2. Selected Coordination Bond Distances (Å) and Angles (deg)
for 1
1.070
R1 [I > 2σ(I)]a
wR2a
0.0288
0.0773
0.562, -0.894
Pt1-P1
Pt1-P2
Pt1-N3a
Pt1-N4c
Pt2-P3
Pt2-P4
2.254(3)
2.281(3)
2.093(8)
2.084(7)
2.267(2)
2.259(3)
Pt2-N3b
Pt2-N4a
Pt3-P5
2.108(7)
2.075(8)
2.265(3)
2.266(3)
2.138(7)
2.100(7)
0.1256
1.666, -2.387
residuals (e Å-3
)
a R1 ) ∑||Fo| - |Fc||/∑|Fo|; wR2 ) [∑w(Fo - Fc )2/∑w(Fo )2]1/2
.
2
2
2
Pt3-P6
Pt3-N3c
Pt3-N4b
Results and Discussion
N3a-Pt1-P1
N4c-Pt1-P2
N4a-Pt2-P4
173.1(2)
174.3(3)
173.2(2)
N3b-Pt2-P3
N3c-Pt3-P5
N4b-Pt3-P6
172.6(2)
169.3(2)
172.8(2)
Synthesis and Characterization of cis-[L2Pt{1-MeCy-
(-H),N3N4}]3(NO3)3 (L ) PMe2Ph, 1). The hydroxo
complex cis-[L2Pt(µ-OH)]2(NO3)2 (L ) PMe2Ph) reacts with
1-MeCy, in a variety of solvents, to give the trinuclear species
cis-[L2Pt{1-MeCy(-H),N3N4}]3(NO3)3 (1), according to re-
action 1. In CH3CN at room temperature, the reaction is
their estimated standard deviations [5.308(1) and 5.287(1)
Å, respectively], while Pt1‚‚‚Pt2 appears to be slightly
shorter, at 5.174(2) Å. The whole complex presents structural
features very similar to those of the cis-[(PMe3)2Pt{1-MeCy-
3+
(-H),N3N4}]3 analogue11 and of [(tmeda)Pd{1-MeCy-
3(cis-[L2Pt(µ-OH)]22+) + 6(1-MeCy) f
(-H),N3N4}]33+ (tmeda ) N,N,N′,N′-tetramethylethylenedi-
amine),14 where the mean intermetallic distances are 5.325
and 5.170 Å, respectively.
2(cis-[L2Pt{1-MeCy(-H),N3N4}]33+) + 6H2O (1)
complete in 2-3 h, with 95% yield of 1 (by NMR). In H2O,
DMSO, or chlorinated solvents, a longer reaction time is
required (several hours or days), and the yield is virtually
quantitative.
Crystals separated from CH3CN have the composition 1‚
H2O‚CH3CN. The X-ray structure analysis evidences the
formation of a trinuclear cyclic species of pseudo 3-fold
symmetry, having (PMe2Ph)2Pt units symmetrically bridged
by the cytosinate ligands through the N3 and N4 atoms, thus
forming a 12-membered ring as shown in Figure 1. The
formation of the cyclic cation is attained, for each nucleobase,
through an anti orientation of the metal at N4 with respect
to that bound to N3.
Each Pt atom completes the distorted square-planar
coordination geometry through two phosphine ligands. The
Pt-N3 bond distances [2.093(8), 2.108(7), and 2.138(7) Å]
appear to be slightly longer with respect to the Pt-N4 ones
[2.084(7), 2.075(8), and 2.100(7) Å], while the Pt-P bond
distances fall in the usual range for Pt complexes and vary
from 2.254(3) to 2.281(3) Å (Table 2). The metals outline a
triangle with slightly different edges, with the intermetallic
Pt1‚‚‚Pt3 and Pt2‚‚‚Pt3 distances being comparable within
The pyrimidine rings lie on the same side of the plane
defined by the metals, making dihedral angles with the Pt3
plane of 79.2(1)° (ring a), 66.3(2)° (ring b), and 54.9(1)°
(ring c). Conversely, the N2P2 mean coordination planes of
Pt1, Pt2, and Pt3 are inclined by 51.5(1), 46.5(1), and 38.2-
(1)°, respectively, with respect to the metal plane, and the
cation can be regarded as a double-pinched cone (Figure 2).
The crystal packing evidences a nitrate anion inside the area
delimited by the coordination metal planes on the side of
the P atoms, with an O pointing toward the center of the
complex, interacting with the exocyclic N4 nucleobase atoms.
The N4-ONO2 distances are 3.17, 2.96, and 2.99 Å, with
H atoms (at calculated geometrical positions) of N4 pointing
toward this O. Thus, these complexes act as anion receptors,
and a similar interaction has been detected for the perchlorate
anion in the crystal structures of cis-[(PMe3)2Pt{1-MeCy(-
3+
3+
H)},N3N4]3 and of [(tmeda)Pd{1-MeCy(-H),N3N4}]3
,
where the measured N4-OClO3 mean distances are 3.14 and
3.08 Å, respectively. This feature was also observed in the
two crystallographically independent cations of cis-[(PMePh2)2-
Pt{9-MeAd(-H),N1N6}]33+, where a nitrate was found to
approach each trinuclear complex.12c
8182 Inorganic Chemistry, Vol. 45, No. 20, 2006

Complexes of the Model Nucleobase 1-Methylcytosine
the structurally similar PdII complex.14 We observe, in fact,
that the addition of chloride (as [AsPh4]Cl) to solutions of 1
determines an immediate shift, in opposite directions, of the
31P NMR resonances concomitant with the disappearance of
the N4-H signal (shifted on the phenyl region of PMe2Ph
and [AsPh4]+) and only minor shifts (ca. 0.02 ppm) for H5
and H6 and for methyl resonances of the phosphino ligands.
As an example, a solution of ca. 10-2 M of 1 in DMSO-d6
containing Cl- (molar ratio Cl-/1 ) 2), the observed
chemical shift differences were -0.34 and +0.83 ppm for
the 31P NMR resonances at δ -16.54 and -19.44 ppm,
1
respectively. The fact that the values of JPPt change only a
few hertz upon the addition of Cl- seems to exclude the
coordination of the chloride at the metal center.
Figure 2. View of the nitrate anion interacting with N4-H atoms of the
cation 1 (methyl and phenyl groups at P are not shown for clarity).
Characterization of the Head-to-Tail Dimer 2. Previous
studies showed that the reaction of cis-[(PMe3)2Pt(µ-OH)]2-
(NO3)2 with 1-MeCy, in water or DMSO, affords the
dinuclear complex cis-[(PMe3)2Pt{1-MeCy(-H)N3,N4}]2-
(NO3)2, in which the cytosinate ligands bridge the metal
centers through the N3 and N4 atoms in a head-to-tail
fashion.10 This species, in H2O or DMSO, at 80 °C in several
hours, converts into the corresponding trinuclear derivative,
structurally analogous to 1.11 A similar dimer, 2, is an
intermediate in the formation of 1. The 31P NMR spectrum
of a freshly prepared solution of cis-[(PMe2Ph)2Pt(µ-OH)]2-
(NO3)2 and 1-MeCy in DMSO-d6 is shown in Figure 3a. The
AB multiplet of 2, whose data are collected in Table 4, with
a relative intensity of ca. 90%, is quantitatively replaced by
the resonances of 1 in several days at ambient temperature
(Figure 3b,c). A kinetic study of this transformation, carried
out at ca. 50 °C, indicates a first-order kinetic law, with t1/2
ca. 5 h. In addition, parts a and b of Figure 3 show the
presence of weak resonances [at δ -16.8 (d) and -17.8 ppm
(d, 2JPP ) 22.2 Hz) and δ -18.1 (d) and -20.3 ppm (d, 2JPP
) 24.3 Hz) and apparent singlets at δ -23.7 and -24.16
ppm], whose relative intensities undergo only small changes
during the conversion of 2 into 1. Because these signals
disappear when the conversion of 2 is complete (Figure 3c),
they are attributable to minor species in equilibrium with
the kinetic product 2.
Attempts to obtain a pure sample of 2 were unsuccessful.
The use of CH3CN as a solvent led a mixture of 1-MeCy
and cis-[(PMe2Ph)2Pt(µ-OH)]2(NO3)2 (molar ratio 2:1) to
dissolve in ca. 2 h at ambient conditions. The 31P NMR
spectrum of the resulting solution showed the presence of 1
in a yield of 95%. The remaining resonances were those of
an AB multiplet at δ -18.09 and -19.5 ppm (2JPP ) 27.3
Hz), due to a yet unknown species, not observed after
crystallization of the isolated crude product. Similarly, the
31P NMR spectrum of the mixture obtained a few hours after
mixing the reagents in D2O indicated that complex 1 was
the major component. In addition to the signals of 1 (Table
4), a very complex set of resonances in the range δ -18 to
-24 ppm and an AB multiplet at δ -25.27 and -23.28 ppm
(2JPP ) 25.6 Hz), tentatively attributed to the intermediate
2, were detectable. In a few hours at ambient conditions,
only the resonances of 1 were seen, as a result of the
relatively fast conversion of 2, and of others species in
The trinuclear structure of 1 is maintained in solution, as
indicated by mass spectrometry and multinuclear NMR
analyses (1H, 13C, 31P, and 15N). The ESI spectrum in CH3-
CN (shown in Figure S1 of the Supporting Information)
exhibits a pattern with the corrected isotopic distribution, at
m/z value of 1909, attributable to the monocation {[(PMe2-
Ph)2Pt{1-MeCy(-H)}]3(NO3)2}+. 1H and 31P{1H} NMR data
in various solvents, collected in Tables 3 and 4, respectively,
show the presence of a single species, indicating a high
stability of the trinuclear cation. In the 31P NMR spectra,
the two chemically inequivalent phosphines display an AB
1
pattern with distinct JPPt values, which change only to a
minor extent with the solvent.
In the proton spectra (Table 3), the cytosine ligands exhibit
a doublet of doublets pattern for H5, resulting in a coupling
with H6 (3JHH ) 7.5 Hz) and with one of the 31P nuclei (5JHP
) 1.0-1.6 Hz). 2D 31P-1H NMR experiments in CDCl3
indicate that H5 correlates with the resonance at δ -21.11
ppm, attributable to the phosphine (PB) in the trans position
to the cytosine N3 atom. This attribution stems on the
assumption that the magnetic interaction 1H-31P through five
bonds is favored via the N3 atom rather than the N4 atom.
Consequently, the exocyclic N having a shorter distance (Pt-
N4 ) 2.086 Å, average) is trans to the phosphine that
experiences the lower coupling with the metal (PA, δ -17.83
1
ppm, JPPt ) 3221 Hz).
As expected on the basis of the X-ray structure, the two
methyl groups on the same phosphine exhibit distinct 1H and
13C NMR resonances (see the Experimental Section) because
the coordination planes of the Pt atoms lack any symmetry.
The 2D 31P-1H NMR spectrum, obtained in CDCl3, allows
the assignment of each PMe signal to a specific P atom,
showing that the methyl groups on the same P experience
chemical shift differences up to 0.43 ppm. Moreover, the
magnetic anisotropy due to the presence of phenyl rings
causes a marked deshielding of a methyl group in a
phosphine and an opposite effect in the other one.
From Table 3, it is clear that some resonances of the
nucleobases exhibit a remarkable solvent effect, in particular
for the N4-H proton, observed at δ 6.82 ppm in CDCl3 and
at δ 5.50 ppm in CD3CN. This is likely related to H bond
interactions between the N4-H protons and the counterions,
as shown in the solid state of 1 and as recently reported for
Inorganic Chemistry, Vol. 45, No. 20, 2006 8183

Longato et al.
Table 3. 1H NMR Data (δ in ppm; J in Hz) for Complexes 1-3 in Various Solvents at 27 °C
compd
solvent
H6 (3JHH
)
H5 (3JHH); [5JHP
]
N4-H
NCH3
PMe (2JHP
)
1
1
1
DMSO-d6
CD3CN
CDCl3
a
6.35 dd (7.1); [1.0]
6.93 d (7.5); [1.5]
6.45 dd (7.46); [1.6]
6.63 br s
5.50 br s
6.82 br s
3.22 s
2.56 s
3.42 s
1.87 d (11.5); 1.43 d (11.4); 1.35 d (11.4); 1.16 d (10.8)
1.81 d (11.6); 1.36 d (11.4); 1.36 d (11.4); 1.11 d (10.8)
1.836 d (8.8) and 1.408 d (12.6) (correlate with PB);
1.449 d (12.1) and 1.18 d (10.5) (correlate with PA)
2.003 d (10.5); 1.819 d (11.4); 1.518 d (10.5); 1.426 d (11.4)
7.13 d (7.5)
7.30 d (7.4)
2
3
DMSO-d6
CDCl3
7.20 d (7.3)
7.57b
ca. 5.90 d (7.2)
6.87 dd (ca 7); [1.7]
7.03 br s
6.84 br s
3.12 s
3.32
I
1.868 d (11.2); ca. 1.4 (correlate with PB ); 1.680 d (11.2);
I
1.314 d (10.8) (correlate with PA
)
7.20 d (7.6)
6.79b
ca. 7.5
6.66 br s
6.60
3.36
1.243 d (11.2); 0.977d (11.2) (correlate with PAII);
1.235 d (11.2); ca. 1.18 d (correlate with PB
II
)
7.6b
a
6.89 dd (7.4); [1.4]
6.49 dd (6.49); [1.6]
6.47 dd (8.0); [1.7]
6.53 dd (7.80); [1.5]
3.29
1.768 d (10.4);1.616 d (10.4); 1.599 d (10.8);
III
1.565 d (10.0) (correlate with PAIII and PB
)
3
DMSO-d6
3.16
1.885 d (11.4); 1.834 d (11.4); 1.640 d (11.2); 1.606 d (10.8);
1.549 d (11.4); 1.517 d (10.2)
1.389 d (10.8); 1.177 d (10.8); 1.126 d (11.4); 1.097 d (11.2);
1.050 d (11.4); 0.772 d (11.4)
a
6.33
3.13
a
a
ca. 3.4
a Not attributed. b Values determined through COSY experiments.
1
Table 4. 31P NMR Data (δ, in ppm; J in Hz; JPPt in Parentheses) for
Characterization of the Linkage Isomer of 1, 3. When
the condensation reaction between cis-[(PMe2Ph)2Pt(µ-OH)]2-
(NO3)2 and 1-MeCy is carried out in chlorinated solvents,
the main reaction product is the cyclic trinuclear complex
3, the linkage isomer of 1 depicted in Chart 3. The structure
of 3 has been elucidated through a detailed multinuclear
NMR study, carried out in CDCl3 and DMSO-d6. The
Complexes 1-3 in Various Solvents at 27 °C
complex (solvent)
δ(PA)
δ(PB)
2JPP
1 (DMSO-d6)
1 (CD3CN)
1 (D2O)
1 (CDCl3)
2 (DMSO-d6)
3 (CDCl3)
-16.54 (3226)
-17.48 (3222)
-16.64 (3219)
-17.83 (3221)
-22.80 (3360)
-16.70 (3230) Ia
-19.79 (3164) II
-23.40 (3388) III
-14.7 (3230) Ia
-18.51 (3171) II
-22.70 (3413) III
-19.44 (3327)
-20.46 (3336)
-20.43 (3349)
-21.11 (3334)
-23.56 (3127)
-20.70 (3291)
-20.05 (3164)
-25.70 (3370)
-18.62 (3291)
-18.51 (3171)
-24.13 (3396)
24.8
24.6
24.7
24.7
25.5
24.8
25.8
23.3
25.3
25.8
23.3
1
pertinent H and 31P NMR data are collected in Tables 3
and 4, respectively. At 600 MHz, the cytosinate ligands
exhibit three sets of signals, in agreement with the presence
of a different chemical environment for each nucleobase.
Moreover, the methyl groups of each PMe2Ph ligand show
distinct resonances, giving a total of 12 doublets. As observed
for complex 1, the H5 resonances are characterized by
doublets of doublets, while the N4-H protons show broad
singlets in the range δ 6.6-7.5 ppm. Only one of the H6
3 (DMSO-d6)
a I-III refer to PA and PB in Chart 3.
3
resonances (doublet at δ 7.20 ppm, JHH ) 7.6 Hz) was
directly detectable in the 1D 1H NMR spectrum. The
remaining H6 resonances were obtained through COSY
experiments. The attribution of the N4-H signals has been
obtained on the basis of 15N-1H HMBC experiments (see
the Supporting Information, Figure S3 and S4). Two N4-H
protons (at δ 6.84 and 6.66 ppm, in CDCl3) have chemical
shifts very similar to that found for 1, while the third (at ca.
7.5 ppm, overlapped by the phenyl resonances) appears to
be particularly deshielded.
In the corresponding 31P NMR spectrum, the phosphine
ligands show three AB multiplets, labeled as AIBI, AIIBII,
and AIIIBIII (see Table 4), having the same relative intensities.
2D 31P-1H NMR heterocorrelated experiments indicate that
each 31P nucleus of the AIIIBIII multiplet correlates with a
H5 proton, as shown in Figure 4 for the spectrum obtained
in CDCl3. In particular, the 31P NMR resonances at δ -23.40
and -25.70 ppm correlate with the protons δ 6.79 and 6.87
ppm, respectively, indicating the presence of two nucleobases
bonded at the same metal center, both coordinated at the
N3 site. The remaining H5 proton shows correlation with
Figure 3. 31P{1H} NMR spectra (central part) of cis-[(PMe2Ph)2Pt(µ-
OH)]2(NO3)2 and 1-MeCy (1:2 molar ratio) in DMSO-d6 at 27 °C: (a) fresh
solution; (b) after 45 h; (c) after 3 weeks at room temperature.
equilibrium, into the thermodynamically more stable tri-
nuclear complex.
Although we were unable to obtain a suitable crystal of 2
for X-ray analysis, the comparison of the 31P and 195Pt NMR
data with those of 1, and with those found for the PMe3
analogues,11 strongly supports for 2 a dinuclear nature. As a
matter of fact, the chemical shift difference of the 195Pt NMR
resonances in 1 (δ -4314 ppm) and 2 (δ -4139 ppm) is
very similar to that found in the related PMe3 analogues (∆δ
156 ppm).
I
the resonance at δ -20.70 ppm (PB ). The same results were
II
obtained in DMSO-d6. The two ligands labeled PA PBII (Chart
3), having chemical shifts only slightly different in chlori-
nated solvents (Table 4) or coincident (in DMSO-d6, at 121
8184 Inorganic Chemistry, Vol. 45, No. 20, 2006

Complexes of the Model Nucleobase 1-Methylcytosine
Figure 4. 31P{1H}-1H HMBC spectra (low field) of 3 in CDCl3.
Figure 6. ORTEP drawing (ellipsoid at the 50% probability level) of the
complex cation of 4 showing the intramolecular H bond and π-π ring
interactions.
Table 5. Selected Coordination Bond Distances (Å) and Angles (deg)
for 4
Pt-N3
Pt-N4a
2.100(3)
2.061(4)
Pt-P1
Pt-P2
2.2717(10)
2.2730(14)
N3-Pt-N4a
N3-Pt-P1
N3-Pt-P2
87.51(13)
169.97(10)
89.16(10)
N4a-Pt-P1
N4a-Pt-P2
P1-Pt-P2
84.95(9)
176.48(9)
98.22(4)
appearance of the dinuclear species 2 (not observed in
chlorinated solvents), followed by its slow conversion into
1.
Characterization of the Bis-adduct 4. Unlike the PMe3
and PMe2Ph analogues, the hydroxo complex containing
PPh3 reacts with 1-MeCy, in DMSO and chlorinated solvents,
according to eq 2. The elemental analysis and X-ray structure
Figure 5. 31P{1H} NMR spectra of a solution of [(PMe2Ph)2Pt(µ-OH)]2-
(NO3)2 and 1-MeCy (1:2) in CDCl3 at room temperature: (a) after 50 min;
(b) after 24 h.
cis-[(PPh3)2Pt(µ-OH)]22+ + 4(1-MeCy) f
MHz), exhibit the lowest values of 1JPPt (3164 Hz in CDCl3),
as expected for phosphines in the trans position to N4-
coordinated nucleobases.
2(cis-[(PPh3)2Pt{1-MeCy(-H)}(1-MeCy)]+) + 2H2O (2)
determination of the isolated solid, after crystallization from
DMF, is consistent with the formula cis-[(PPh3)2Pt{1-MeCy-
(-H)}(1-MeCy)]NO3‚H2O‚DMF (4‚H2O‚DMF). The RX
diffraction analysis, performed on a crystal of small dimen-
sions, evidences that compound 4 is comprised of cationic
complexes, NO3- anions, lattice water, and DMF molecules.
The Pt metal exhibits the expected square-planar geometry,
with a cytosine base coordinated through the endocyclic
nitrogen N3 and the other through the deprotonated exocyclic
amino group N4a, as shown in Figure 6 and Table 5. To the
best of our knowledge, this is the first example of a
structurally characterized Pt complex with N3 and N4
coordinated nucleobases in the cis position.22 The Pt-N3
bond length of 2.100(3) Å appears to be significantly longer
than the Pt-N4a one [2.061(4) Å], confirming the trend also
found in the trinuclear complex 1 and in the neutral
complexes trans-[PtX2(1-MeCy,N3)(1-MeCy,N4)] (X ) Cl,
I) recently described. The N3 and N4a coordinated bases
form dihedral angles of 87.66(7) and 76.35(7)°, respectively,
In chlorinated solvents, complex 3 slowly isomerizes to
1. Figure 5a shows the 31P NMR spectrum of the mixture
obtained 50 min after mixing the reagents in CDCl3. The
spectrum of the same solution, obtained after 24 h at ambient
conditions (Figure 5b), shows that the isomerization of 3 is
almost complete. Conversely, if the reaction is carried out
on a larger scale (see the Experimental Section) in CH2Cl2,
followed by the precipitation of the product with the addition
of Et2O, the 31P NMR spectrum of the resulting solid,
dissolved in CDCl3, shows that the rate of conversion of 3
into 1 appears to be much decreased. The removal of water
formed from the condensation reaction (eq 1) determines a
sharp increase on the stability of 3, whose initial concentra-
tion decreased only 15% after 8 days at room temperature.
Because the isomerization of 3 requires dissociation of two
Pt-N bonds (one Pt-N3 and one Pt-N4 bond), it is possible
that in anhydrous solvents such a reaction is prevented.
Moreover, a different pathway for the transformation of 3
into the stable isomer 1 is found in DMSO. In fact, when
the isolated solid containing a mixture of 3 (65%) and 1
(35%) is dissolved in DMSO-d6, we observe the progressive
(22) Miguel, P. J. S.; Lax, P.; Willermann, M.; Lippert, B. Inorg. Chim.
Acta 2004, 357, 4552.
Inorganic Chemistry, Vol. 45, No. 20, 2006 8185

Longato et al.
Figure 8. 15N-1H HMBC spectra (low field) of 4 in DMSO-d6.
Figure 7. Crystal packing with an indication of H bonds (dotted lines)
occurring along and between two arrays of complexes 4 (phosphine phenyl
rings are not depicted for clarity).
with the N4-H proton at δ 5.07 ppm, indicating a trans
configuration of this phosphine with the N4-platinated
nucleobase. As is observed in 1, this ligand is at a lower
with the mean coordination plane N2P2, with the larger tilting
of the second (from the ideal perpendicular position) likely
being assumed in order to favor the intramolecular H bond
(see below).
As is evident from Figure 6, both of the bases are involved
in π-π interaction with an adjacent PPh3 phenyl ring, with
the distances between the ring centroids being 3.347(3) and
3.653(3) Å for the N3 and N4a coordinated bases, respec-
tively. Moreover, the complex appears to be stabilized by
an intramolecular H bond occurring between the N4 amino
group and the uncoordinated nitrogen N3a [N‚‚‚N distance
2.843(6) Å, N-H‚‚‚N 147(4)°].
The crystal packing (Figure 7) shows complexes running
along the a axis and bound by the lattice water molecules
that join carbonyl groups of two consecutive complexes. The
complexes of adjacent arrays are connected through H bonds
occurring via N4-H‚‚‚O2a and through π-π interactions
involving symmetry-related N3 coordinated bases, with the
distance between the ring centroids being 3.619(3) Å. Finally,
N4a acts as a H donor toward the nitrate oxygen O5. The
DMF molecules are far apart and do not interact with the
metal complexes.
1
field and experiences the lower JPPt value.
One of the exocyclic NH2 protons appears particularly
deshielded (δ 10.94 ppm, in DMF-d7) when compared with
the values found for N3-bonded 1-MeCy ligands in the bis-
adducts cis-[L2Pt(1-MeCy)2]2+ (L ) PMe2Ph, δ 7.85 and
8.84 ppm)15 and related complexes.22 This result is in line
with the presence of a strong intramolecular H bond as
observed in the solid state.
No stable polynuclear complexes can be obtained with a
lower nucleobase/Pt ratio. Complex 4, in fact, is the main
component of the reaction mixture even if the molar ratio is
that of eq 1. This is likely due to the higher steric hindrance
of the PPh3 ligands, which prevent the 1-MeCy(-H) anion
from behaving as bridging (or chelating ligand), leaving the
fourth position around the metal ion available for coordina-
tion of a neutral molecule of the nucleobase.
Conclusions
The results here described lead to the conclusion that the
deprotonation of the model nucleobase 1-MeCy promoted
by the hydroxo ligands in cis-[L2Pt(µ-OH)]2(NO3)2 generates
cytosinate ions that behave as mono- or bidentate ligands
toward the metal center, depending on the ancillary ligands
L. The more basic phosphines (PMe3 and PMe2Ph) form
adducts in which the nucleobase acts as a bidentate ligand,
bridiging the metals through the N3 and N4 atoms. The
resulting products are the relatively stable (L ) PMe3) or
scarcely stable (L ) PMe2Ph) head-to-tail dinuclear inter-
Compound 4, virtually insoluble in chlorinated solvents,
1
has been characterized in DMSO-d6 and DMF-d7. The H
NMR spectrum shows two sets of resonances for the
nucleobases: the H5 proton of the N3 platinated molecule
(attributed through the COSY experiment; see the Supporting
Information, Figure S5) exhibits a long-range 1H-31P
coupling (5JHP ) 1.6 Hz) (not observed when the nucleobase
is N4-coordinated), while the exocyclic amino protons appear
as broad singlets at δ 8.34 and 10.63 ppm. Their attribution
stems on the 15N-1H HMBC spectrum, shown in Figure 8,
where these signals show a correlation with the same 15N
2+
mediates cis-[L2Pt{1-MeCy(-H),N3N4}]2 that undergo
rearrangement to the stable trinuclear cyclic analogues cis-
3+
[L2Pt{1-MeCy(-H),N3N4}]3
.
A linkage isomer of these trinuclear cycles has been
characterized when the condensation reaction between the
hydroxo complex stabilized by PMe2Ph and the nucleobase
is carried out in chlorinated solvents. In this case, the fast
self-assembly of the {cis-L2Pt2+} units with the cytosinate
ions leads exclusively to trinuclear cyclic adducts, with the
kinetically favored formation of the unsymmetrical isomer
3. The subsequent quantitative conversion of 3 into the
1
nucleus (at δ -261 ppm, JNH ) ca. 80 Hz). The imino
proton of 1-MeCy(-H), at δ 5.07 ppm, exhibits coupling
with one of the 31P nuclei (3JHP ) 4.7 Hz) and correlates
with the 15N NMR resonance at δ -275 ppm (1JNH and 2JNP
) ca. 85 and 90 Hz, respectively). In the 31P NMR spectrum,
the two phosphines exhibit two well-separated doublets at δ
12.34 and 0.21 ppm, the first of which shows a correlation
8186 Inorganic Chemistry, Vol. 45, No. 20, 2006

Complexes of the Model Nucleobase 1-Methylcytosine
thermodynamically stable isomer 1 is a clear indication of
the more favorable arrangement of the ligands when the
nucleobases bridge the metals symmetrically.
In contrast, the presence of the sterically demanding PPh3
ligands in cis-[L2Pt(µ-OH)]2(NO3)2 favors a monodentate
behavior of the cytosinate ion, which binds the metal at the
N4 site. The concomitant coordination of a second molecule
of cytosine stabilizes the mononuclear adduct cis-[(PPh3)2-
Pt{1-MeCy(-H)}(1-MeCy)]+ through a strong intramolecu-
lar H bond.
Acknowledgment. This work was financially supported
by the Ministero dell’Universita` e della Ricerca Scientifica
e Tecnologica (PRIN 2004). We are indebted to Dr. E.
Marotta for mass spectra.
Supporting Information Available: X-ray crystallographic data
in CIF format, ESI and COSY spectra, and kinetic study of the
conversion of 2 into 1. This material is available free of charge via
the Internet at http://pubs.acs.org.
IC060831R
Inorganic Chemistry, Vol. 45, No. 20, 2006 8187