Synthesis and Characterization of Pt(II) Complexes with Pyridyl Ligands: Elongated Octahedral Ion Pairs and Other Factors Influencing 1H NMR Spectra

Article abstract of DOI:10.1021/acs.inorgchem.7b01294

Our goal is to develop convenient methods for obtaining trans-[Pt^II(4-Xpy)₂Cl₂] complexes applicable to 4-substituted pyridines (4-Xpy) with limited volatility and water solubility, properties typical of 4-Xpy, with X being a moiety targeting drug delivery. Treatment of cis-[Pt^II(DMSO)₂Cl₂] (DMSO = dimethyl sulfoxide) with 4-Xpy in acetonitrile allowed isolation of a new series of simple trans-[Pt^II(4-Xpy)₂Cl₂] complexes. A side product with very downfield H2/6 signals led to our synthesis of a series of new [Pt^II(4-Xpy)₄]Cl₂ salts. For both series in CDCl₃, the size of the H2/6 δ[coordinated minus free 4-Xpy H2/6 shift] decreased as 4-Xpy donor ability increased from 4-CNpy to 4-Me₂Npy. This finding can be attributed to the greater synergistic reduction in the inductive effect of the Pt(II) center with increased 4-Xpy donor ability. The high solubility of [Pt^II(4-Xpy)₄]Cl₂ salts in CDCl₃ (a solvent with low polarity) and the very downfield shift of the [Pt^II(4-Xpy)₄]Cl₂ H2/6 signals for the solutions provide evidence for the presence of strong {[Pt^II(4-Xpy)₄]²⁺,2Cl^-} ion pairs that are stabilized by multiple CH···Cl contacts. This conclusion gains considerable support from [Pt^II(4-Xpy)₄]Cl₂ crystal structures revealing that a chloride anion occupies a pseudoaxial position with nonbonding (py)C-H···Cl contacts (2.4-3.0 ?). Evidence for (py)C-H···Y contacts was obtained in NMR studies of [Pt^II(4-Xpy)₄]Y₂ salts with Y counterions less capable of forming H-bonds than chloride ion. Our synthetic approaches and spectroscopic analysis are clearly applicable to other nonvolatile ligands.

Full text of DOI:10.1021/acs.inorgchem.7b01294

Article
pubs.acs.org/IC
Synthesis and Characterization of Pt(II) Complexes with Pyridyl
Ligands: Elongated Octahedral Ion Pairs and Other Factors
1
Influencing H NMR Spectra
Nerissa A. Lewis, Svetlana Pakhomova, Patricia A. Marzilli, and Luigi G. Marzilli*
Department of Chemistry, Louisiana State University, Baton Rouge, Louisiana 70803, United States
S
* Supporting Information
ABSTRACT: Our goal is to develop convenient methods for obtaining
trans-[PtII(4-Xpy)2Cl2] complexes applicable to 4-substituted pyridines (4-
Xpy) with limited volatility and water solubility, properties typical of 4-Xpy,
with X being a moiety targeting drug delivery. Treatment of cis-
[PtII(DMSO)2Cl2] (DMSO = dimethyl sulfoxide) with 4-Xpy in acetonitrile
allowed isolation of a new series of simple trans-[PtII(4-Xpy)2Cl2] complexes.
A side product with very downfield H2/6 signals led to our synthesis of a
series of new [PtII(4-Xpy)4]Cl2 salts. For both series in CDCl3, the size of the
H2/6 Δδ [coordinated minus “free” 4-Xpy H2/6 shift] decreased as 4-Xpy
donor ability increased from 4-CNpy to 4-Me2Npy. This finding can be
attributed to the greater synergistic reduction in the inductive effect of the
Pt(II) center with increased 4-Xpy donor ability. The high solubility of
[PtII(4-Xpy)4]Cl2 salts in CDCl3 (a solvent with low polarity) and the very
downfield shift of the [PtII(4-Xpy)4]Cl2 H2/6 signals for the solutions
provide evidence for the presence of strong {[PtII(4-Xpy)4]2+,2Cl−} ion pairs that are stabilized by multiple CH···Cl contacts.
This conclusion gains considerable support from [PtII(4-Xpy)4]Cl2 crystal structures revealing that a chloride anion occupies a
pseudoaxial position with nonbonding (py)C−H···Cl contacts (2.4−3.0 Å). Evidence for (py)C−H···Y contacts was obtained in
NMR studies of [PtII(4-Xpy)4]Y2 salts with Y counterions less capable of forming H-bonds than chloride ion. Our synthetic
approaches and spectroscopic analysis are clearly applicable to other nonvolatile ligands.
has been studied most intensively and has demonstrated
significant activity against several cisplatin-resistant tumor cell
lines.9,11,12,18 We propose that, whereas bulky ligands have been
reported to decrease activity of cis bifunctional Pt(II) agents,
bulky ligands are needed to allow trans bifunctional as well as
monofunctional Pt(II) agents to form DNA adducts in which
the DNA structure is distorted in such a way as to lead to
cancer cell cytotoxicity.19−22
Because evidence exists that trans-[PtL2Cl2] complexes with
L = 4-substituted pyridyl ligands (4-Xpy) exhibit cancer cell
cytotoxicity,16,17 we believe that 4-Xpy ligands have sufficient
bulk to cause DNA distortions necessary for anticancer activity.
Thus, we initiated an investigation of the preparation of trans-
[PtII(4-Xpy)2Cl2] complexes containing strongly coordinating
pyridyl ligands such as 4-piperidinopyridine (4-(CH2)5Npy,
Figure 1). Syntheses reported for related complexes often yield
the cis isomer, require harsh conditions (such as 100−150 °C
or the use of concentrated HCl), or depend on using aqueous
conditions or volatile ligands.23−27 Such restrictions are not
amenable to pyridine ligands containing sensitive linking
groups, such as the sulfonamide group that we employ for
bioconjugation.28
INTRODUCTION
■
We have been exploring the metal-binding chemistry of
strongly coordinating pyridyl ligands as one means of
bioconjugation of targeting biological groups to create
complexes with potential therapeutic or diagnostic utility.1
One highly useful synthon for our purposes is the C2-
symmetrical amine, 1-(4-pyridyl)piperazine (pyppzH, Figure
1). The piperazine N attached to the pyridyl ring increases the
donor ability of the pyridyl ring N, whereas the remote
piperazine NH group can be used for linking chemistry. In this
work we pursue fundamental Pt(II) chemistry relevant to the
eventual use of such bioconjugated pyridyl ligands to prepare
complexes having anticancer activity.
Cisplatin, cis-[Pt(NH3)2Cl2], is one of the most effective
chemotherapeutic agents being used in clinical therapy.2,3 Many
closely related cis bifunctional analogues of cisplatin also show
good anticancer activity.2,4−6 In contrast, the inactivity of the
trans-[Pt(NH3)2Cl2] isomer has led to a presumption that trans
compounds are inactive.7−10 Historically, trans-[PtL2Cl2]
complexes have been neglected. In recent years, however,
several types of platinum compounds with trans geometry have
shown promising in vitro activity against several cancer cell
lines, including some that are resistant to cisplatin.7−9,11−17
Among the recently studied trans platinum complexes, the
iminoether complex trans-[Pt(E-HNC(OCH3)CH3)2Cl2]
Received: May 19, 2017
© XXXX American Chemical Society
A
DOI: 10.1021/acs.inorgchem.7b01294
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Inorganic Chemistry
Article
Xpy)4]Cl2 side products. Published NMR data23,27 for [PtII(4-
Xpy)4]Cl2 complexes are limited but are inconsistent with our
results. To gain a comprehensive understanding of the NMR
trends, we prepared a number of new [PtII(4-Xpy)4]Y2
complexes with diverse 4-Xpy ligands and Y counterions.
These NMR studies established that the very downfield shift
position of the H2/6 pyridyl signals reflects the presence of
strong {[PtII(4-Xpy)4]2+,2Cl−} ion pairs in which the H2/6
protons undoubtedly form C−H···Cl contacts. This interpre-
tation gains support from several crystal structures of some new
[PtII(4-Xpy)4]Cl2 complexes. The [PtII(4-Xpy)4]2+ cations in
these crystals form part of elongated pseudo-octahedral
structures with axial chloride ions that have contacts to the
pyridyl ring H2/6 protons consistent with (py)C−H···Cl H-
bonding interactions. The distance of the chloride counterions
to the Pt(II) center is usually a few tenths of an angstrom
longer than the Pt···Cl contact distance of ∼3.5 Å.36,37 Such
elongated pseudo-octahedral ion pairs explain the unusual
NMR features of [PtII(4-Xpy)4]Cl2 complexes, and also the
resulting low charge of the {[PtII(4-Xpy)4]2+,2Cl−} ion pairs is
consistent with the high solubility in CDCl3 of these salts
containing [PtII(4-Xpy)4]2+ cations; such salts are otherwise
expected to be poorly soluble.
Figure 1. Pyridyl ligands (4-Xpy) used to synthesize complexes
studied in the current work organized by donor ability to metals
centers with the weakest donors in upper left and strongest donors in
lower right. Also shown is the pyppzH synthon used in our
bioconjugation approach.1 Bold numbers below the ligands are used
to designate complexes prepared with the ligand having that number.
trans-[PtII(4-Xpy)2Cl2] complexes are designated with these bold
numbers alone, and [PtII(4-Xpy)4]Y2 complexes are designated with
these bold numbers plus a letter that identifies the counterion Y−, as
EXPERIMENTAL SECTION
−
follows: Y− = Cl− (a), PF6 (b), BF4− (c), BPh4− (d), and NO3− (e).
■
For example, [PtII(4-CNpy)4]Cl2 is numbered 1a.
Starting Materials. Pyridine (py), 4-cyanopyridine (4-CNpy), 4-
trifluoromethylpyridine (4-CF3py), 4-acetylpyridine (4-MeCOpy), 4-
methylpyridine (4-Mepy), 4-methoxypyridine (4-MeOpy), 4-
dimethylaminopyridine (4-Me2Npy), 4-piperidinopyridine (4-
(CH2)5Npy), NaPF6, [Et4N]BF4, NaBF4, [Et4N]Cl, and [Et4N]NO3
were obtained from Sigma-Aldrich. cis-[PtII(DMSO)2Cl2] was
prepared by a known method.38
In the present study, we identify versatile approaches for
preparing new trans-[PtII(4-Xpy)2Cl2] complexes. Our syn-
theses do not require high temperatures or rely on using
volatile or water-soluble 4-Xpy. Because the binding of purine
heterocycles to Pt(II) causes ∼1 ppm downfield shift changes,
we expected that large downfield 1H NMR shift changes of the
pyridyl 1H NMR signals on binding to Pt(II) would guide us in
our synthetic work.19−22,29,30 However, in our initial studies we
were surprised to find only an ∼0.1 ppm downfield shift change
of the pyridyl H2/6 signal and even an upfield shift change of
the H3/5 signal (∼0.1 ppm) for ligands such as 4-(CH2)5Npy.
As an aid in improving methods for the synthesis and
characterization of trans-[PtII(4-Xpy)2Cl2] complexes, we
explored fundamental features of the NMR spectra of these
complexes. The relatively few known cis/trans-[Pt(py)2Y2] and
[Pt(Xpy or X2py)4]Y2 complexes (mostly with Y = halide or
NCS− and X = Me) contain ligands such as py, picolines
(Mepy), and lutidines (Me2py) of similar donor ability as
estimated by the respective pKa values of the protonated ligand,
for example, XpyH+, falling within a very limited pKa
range.23,24,26,27,31−35 Also, NMR studies often were reported
in different solvents.17 Thus, the dependence of the NMR
signals on the properties of the complexes, such as the pyridyl
ligand donor ability, was neither well-defined nor understood.
Our use of 4-Xpy ligands with substituents at ring position 4
that vary widely in donor ability (e.g., 4-CNpy and 4-Me2Npy,
Figure 1) minimizes the through-space effect of X on the H2/6
1H NMR signal. This choice allowed us to assess the through-
bond inductive effect passing through the Pt(II) center on the
4-Xpy H2/6 signals for a range of trans-[PtII(4-Xpy)2Cl2]
complexes.
1
NMR Measurements. H NMR spectra were recorded on a 400
MHz Bruker spectrometer or on an Advance-III Prodigy 500 MHz
Bruker spectrometer. Peak positions are relative to 3-(trimethylsilyl)-
propionic-2,2,3,3-d4 acid in D2O, or solvent residual peak (DMSO-d6,
CHD2CN, or CHCl3) with internal tetramethylsilane (TMS) as
reference. All NMR data were processed with TopSpin and
MestReNova software. For specific assignments of signals, please see
Tables 1−3 and Supporting Information.
Mass Spectrometric Measurements. High-resolution mass
spectra recorded on an Agilent 6210 ESI TOF LCMS mass
spectrometer are reported in Supporting Information.
X-ray Data Collection and Structure Determination. Intensity
data were collected at low temperature on a Bruker Kappa Apex-II
Table 1. H2/6 Chemical Shifts (ppm) and Shift Differences
(Δδ, ppm) in CDCl3 at 25 °C for 4-Xpy Ligands (5 mM)
a
Both Free and in trans-[Pt(4-Xpy)2Cl2] Complexes (5 mM)
X
pKa
4-Xpy
trans-[Pt(4-Xpy)2Cl2]
H2/6 Δδ
b
CN
2.10
2.46
3.51
5.98
6.47
9.61
9.60
8.82
8.83
8.82
8.47
8.45
8.22
8.23
9.17
9.18
9.13
8.71
8.69
8.35
8.34
0.35
0.35
0.31
0.24
0.24
0.13
0.11
c
d
f
CF3
MeCO
e
Me
g
h
i
MeO
Me2N
(CH2)5N
a
trans-[Pt(py)2Cl2], this study, 8.92 ppm; reported, 8.91 ppm;23
reported for cis-[Pt(py)2Cl2], 8.74 ppm.23 pKa value from ref 52.
b
c
Estimated from the equation of the line: y = −0.0884x + 9.0472 (see
d
e
During our initial investigation of trans-[Pt(4-Xpy)2Cl2]
preparative procedures, some synthetic conditions gave side
products with unprecedented, unusually downfield signals in
CDCl3. We identified these as H2/6 signals of [PtII(4-
Supporting Information, Figure S2). pKa value from ref 53. Reported
for trans-[Pt(4-Mepy)2Cl2], 8.69 ppm;27 reported for cis-[Pt(4-
Mepy)2Cl2], 8.71 ppm.27 pKa value from ref 54. pKa value from ref
f
g
h
i
55. pKa value from ref 56. pKa value from ref 1.
B
DOI: 10.1021/acs.inorgchem.7b01294
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DUO CCD diffractometer fitted with an Oxford Cryostream cooler
and graphite-monochromated Mo Kα (λ = 0.710 73 Å) radiation from
an IμS microfocus source with multilayer optics. Data reduction
included absorption corrections by the multiscan method, with
SADABS.39 All X-ray structures were determined by direct methods
and difference Fourier techniques and refined by full-matrix least-
squares methods by using SHELXL201440 with H atoms in idealized
positions.
X-ray quality crystals of trans-[PtII(4-Xpy)2Cl2] (X = CF3 (2), MeO
(3), and (CH2)5N (5)) and [PtII(4-Xpy)4]Cl2 (X = MeO (3a), Me2N
(4a), (CH2)5N (5a), and Me (7a)) were obtained by mixing equal
volumes (1 mL) of 4-Xpy and cis-[PtII(DMSO)2Cl2] (5.3 mg, 12.5
mM) in 2:1 or 10:1 (4-Xpy/Pt) molar ratios in acetonitrile and
allowing the mixture to stand at room temperature for 4−24 d. When
this room-temperature procedure was followed with 4-Me2Npy (3.1
mg, 25 mM), the X-ray quality crystals collected after 8 d were the cis-
[PtII(4-Me2Npy)2Cl2] isomer (4′).
General Syntheses of trans-[PtII(4-Xpy)2Y2] and [PtII(4-
Xpy)4]Y2 Complexes. The general synthetic method is illustrated
in Scheme 1, and the numbering key for compounds in this study
appears in Figure 1. Specific details on quantities used, yields, MS data,
etc. can be found in Supporting Information.
The treatment of an aqueous solution (3−5 mL) of [PtII(4-
Xpy)4]Cl2 (X = MeO (3a), Me2N (4a), (CH2)5N (5a), and Me (7a))
(0.1 mmol) with solid NaPF6 (170 mg, 1.0 mmol), [NEt4]BF4 (220
mg, 1.0 mmol), or NaBPh4 (0.342 g, 1.0 mmol) produced the
respective [PtII(4-Xpy)4](PF6)2 (3b−5b and 7b), [PtII(4-Xpy)4]-
(BF4)2 (3c−5c and 7c), or [PtII(4-Xpy)4](BPh4)2 (2d and 4d)
complexes as white solids, which were collected on a filter, washed
with diethyl ether, and dried in air.
Scheme 1. Synthesis of trans-[PtII(4-Xpy)2Cl2] and [PtII(4-
a
Xpy)4]Cl2 Complexes, Showing Numbers for Product
Complexes and the Numbering System for the 4-Xpy
Ligands
Alternate Synthesis of [PtII(4-Xpy)4]Y2 Complexes (X = CN,
CF3, MeCO, MeOpy, or Me2N; Y = NO3−, PF6−, or BF4−). The
general synthetic method for [PtII(4-Xpy)4]Y2 complexes was not
successful with weak donor ligands (4-CNpy, 4-CF3py, and 4-
MeCOpy). The desired [PtII(4-Xpy)4]Y2 complexes were prepared
by an alternate method. Specific details on quantities used, yields, MS
data, etc. can be found in Supporting Information. In this alternate
method, a methanol solution (5 mL) of cis-[PtII(DMSO)2Cl2] (42 mg,
0.1 mmol) was first treated with AgNO3 (29 mg, 0.17 mmol) and then
with 4-CNpy, 4-CF3py, and 4-MeCOpy in a 40:1 (4-Xpy/Pt) molar
ratio. The moderate and strong donor ligands, 4-Mepy, 4-MeOpy, and
4-Me2Npy, were used to prepare [PtII(4-Xpy)4](NO3)2 complexes
(7e, 3e, and 4e) for comparison to the analogues having weak 4-Xpy
donors. The reaction mixture was heated at reflux for 24 h; after ∼10
min a white precipitate (presumed to be AgCl) formed, and the gray
precipitate produced was collected on a filter and then suspended in
acetonitrile (2−4 mL) to dissolve the desired [PtII(4-Xpy)4](NO3)2
salt. The mixture was filtered (to remove AgCl), and ether was added
to the filtrate to the point of cloudiness (∼10−15 mL). The white
precipitate formed {[PtII(4-CNpy)4](NO3)2 (1e), [PtII(4-CF3py)4]-
(NO3)2 (2e), [PtII(4-MeCOpy)4](NO3)2 (6e)} was collected on a
filter, washed with methanol and diethyl ether, and dried in air. For all
a
Complexes that have numbers only are trans-[Pt(4-Xpy)2Cl2]
complexes. Numbers correlate with ligands [X = CN (1); CF3 (2);
MeO (3); Me2N (4); (CH2)5N (5); MeCO (6); and Me (7)].
4-Xpy was added to an acetonitrile or methanol solution of cis-
[PtII(DMSO)2Cl2] (42 mg, 0.1 mmol, in 5 mL) in a 2:1 or 10:1 (4-
Xpy/Pt) molar ratio, and the reaction mixture was heated at reflux for
24 h. The precipitate that formed was collected on a filter, washed with
acetonitrile or methanol and diethyl ether, and dried in air. The
powder collected was then dissolved in CHCl3 (∼1−4 mL), and
diethyl ether (∼10 mL) was added until cloudiness was observed.
After the mixture was left undisturbed (∼10−15 min at room
temperature), yellow or white products were collected on a filter,
washed with diethyl ether, and dried in air. Although three trans-
[PtII(4-Xpy)2Cl2] complexes were previously reported [X = H,23
MeCO,17 and Me24,27], we prepared the three complexes by our
synthetic method. 1H NMR data at 25 °C in CDCl3, CD3CN,
deuterated dimethyl sulfoxide (DMSO-d6), and D2O can be found in
Table 1 and in the Supporting Information.
1
of these products, H NMR spectra (in CD3CN at 25 °C) recorded
both upon dissolution and subsequently contained only one set of
signals.
The treatment of an aqueous solution (3−5 mL) of [PtII(4-
Xpy)4](NO3)2 (X = CN (1e), CF3 (2e), or MeCO (6e)) (0.1 mmol)
with solid NaPF6 (170 mg, 1.0 mmol) or NaBF4 (110 mg, 1.0 mmol)
produced the respective [PtII(4-Xpy)4](PF6)2 (1b, 2b, and 6b) or
[PtII(4-Xpy)4](BF4)2 (1c, 2c, and 6c) as white solids, which were
collected on a filter, washed with water and diethyl ether, and dried in
air. [PtII(4-Xpy)4](PF6)2 and [PtII(4-Xpy)4](BF4)2 [X = MeO (3b and
3c), Me2N (4b and 4c), or Me (7b and 7c)] were prepared as
1
described above by using solid [NEt4]BF4. H NMR data in CDCl3,
Table 2. H2/6 Chemical Shifts (ppm) and Shift Differences (Δδ, ppm) in CDCl3 at 25 °C for 4-Xpy Ligands (5 mM) Both Free
and in [Pt(4-Xpy)4]Y2 Complexes (5 mM)
H2/6
H2/6 Δδ
−
−
−
−
−
−
X/Y
CN
pKa
free
Cl−
NO3
ins
BF4
ins
PF6
Cl−
NO3
ins
BF4
ins
PF6
a
b
b
b
g
g
g
g
b
2.10
2.46
3.51
5.98
6.47
9.61
8.82
8.83
8.82
8.47
8.45
8.22
8.23
10.66
10.74
10.60
10.02
9.93
ins
ins
ins
1.84
1.91
1.78
1.55
1.48
0.85
0.77
ins
c
d
e
f
b
b
g
g
g
g
CF3
9.97
ins
9.76
9.62
9.11
9.04
8.49
8.44
1.14
ins
0.93
0.80
0.64
0.59
0.27
0.21
ins
MeCO
Me
ins
9.36
9.24
8.66
8.86
8.79
8.24
8.22
0.89
0.79
0.44
0.39
0.34
0.02
h
j
MeO
i
Me2N
9.07
k
(CH2)5N
9.601
9.00
−0.01
a
b
c
d
pKa value from ref 52. Contains 50 mM [Et4N]Cl. [Pt(4-CF3py)4](BPh4)2 is insoluble in CDCl3 at 25 °C. Estimated from the equation of the
e
f
g
line: y = −0.0884x + 9.0472 (see Supporting Information, Figure S2). pKa value from ref 53. pKa value from ref 54. Contains 40 mM [Et4N]Cl.
h
i
j
k
pKa value from ref 55. [Pt(4-Me2Npy)4](BPh4)2, 7.28 ppm. pKa value from ref 56. pKa value from ref 1.
C
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Table 3. H2/6 Chemical Shifts (ppm) and Shift Differences (Δδ, ppm) in CD3CN at 25 °C for 4-Xpy Ligands (5 mM) Both
Free and in [Pt(4-Xpy)4]Y2 Complexes (5 mM)
H2/6
NO3
H2/6 Δδ
−
−
−
−
−
−
X/Y
CN
pKa
free
Cl−
BF4
PF6
Cl−
NO3
BF4
PF6
a
b
b
b
g
g
g
g
b
2.10
2.46
3.51
5.98
6.47
9.61
9.60
8.78
8.82
8.77
8.41
8.38
8.13
8.13
10.50
10.59
10.51
9.84
9.31
9.45
9.28
8.63
8.59
8.00
9.01
9.07
8.97
8.50
8.40
7.91
7.88
8.93
9.02
8.95
8.48
8.37
7.90
7.85
1.72
1.77
1.74
1.43
1.45
0.62
0.61
0.53
0.63
0.23
0.25
0.15
0.20
c
d
e
f
b
b
g
g
g
g
CF3
MeCO
Me
0.51
0.20
0.18
0.22
0.09
0.07
h
k
l
MeO
9.83
0.21
0.02
−0.01
−0.23
−0.28
ij
Me2N ,
8.75
−0.13
−0.22
−0.25
(CH2)5N
8.74
a
b
c
d
pKa value from ref 52. Contains 50 mM [Et4N]Cl. [Pt(4-CF3py)4](BPh4)2, 9.01 ppm. Estimated from the equation of the line: y = −0.0884x +
9.0472 (see Supporting Information, Figure S2). pKa value from ref 53. pKa value from ref 54. Contains 40 mM [Et4N]Cl. pKa value from ref 55.
Data collected for [Pt(4-Me2Npy)4]Cl2 (without [Et4N]Cl), 8.42 ppm. [Pt(4-Me2Npy)4](BPh4)2, 7.88 ppm. pKa value from ref 56. pKa value
e
f
g
h
i
j
k
l
from ref 1.
DMSO-d6, D2O, and CD3CN at 25 °C appear in Tables 2 and 3 and in
Supporting Information.
dicationic complexes were very soluble in CDCl3 and exhibited
the unusual, very downfield minor H2/6 NMR signals observed
in reactions with only 2 equiv of 4-Xpy. Factors leading to the
high solubility and very downfield shifts are discussed below.
To expand the range of 4-Xpy basicity and donor ability in
the [PtII(4-Xpy)4]Y2 series, a modified synthetic approach was
employed. When 4-CNpy, 4-CF3py, or MeCO was added to a
methanol solution of cis-[PtII(DMSO)2Cl2] in a 40:1 (4-Xpy/
Pt) molar ratio and the solution heated to reflux in the presence
of AgNO3, the respective [PtII(4-Xpy)4](NO3)2 complexes
were obtained in 68%, 87%, or 76% yields. Aqueous solutions
of [PtII(4-Xpy)4](NO3)2 (X = CN (1e), CF3 (2e), and MeCO
(6e) and [PtII(4-Xpy)4]Cl2 (X = MeO (3a), Me2N (4a),
(CH2)5N (5a), and Me (7a)) (0.1 mmol) were then treated
with solid NaPF6, NaBF4, or [Et4N]BF4 to produce the
respective [PtII(4-Xpy)4](PF6)2 (1b−7b) or [PtII(4-Xpy)4]-
(BF4)2 (1c−7c) complexes.
[Et4N]Cl Addition to [PtII(4-Mepy)4](NO3)2, [PtII(4-Mepy)4]-
(BF4)2, and [PtII(4-Xpy)4](PF6)2 Complexes (X = Me, MeO, Me2N,
and (CH2)5N) in CDCl3 or DMSO-d6. The effect of [Et4N]Cl on a 5
mM solution of the desired [PtII(4-Xpy)4]Y2 complex in CDCl3
(except for [PtII(4-Me2Npy)4](PF6)2, which was poorly soluble) or
DMSO-d6 was studied with a 600 mM stock solution of [Et4N]Cl
prepared from a 5 mM solution of the complex to keep the complex
1
concentration constant throughout the experiment. H NMR spectra
were recorded for each solution (1−125 mM in [Et4N]Cl) after the
addition of each [Et4N]Cl aliquot. As the Cl− concentration was
increased from 0−125 mM, a downfield shift (0.05 ppm) was observed
for the residual CHCl3 signal (from 7.2629 to 7.3080 ppm) relative to
TMS as reference. To account for this shift change, shifts of all peaks
were adjusted accordingly.
[Et4N]Cl Addition to [PtII(4-Xpy)4](NO3)2 in CDCl3 or CD3CN.
NMR tubes containing enough solid [PtII(4-Xpy)4](NO3)2 (X = CN
or CF3) and CDCl3 (600 μL) to make 5 mM solutions in CDCl3 at 25
°C were treated with enough [Et4N]Cl (12.4 mg) to make a 125 mM
Structural Results. Overall Aspects. Crystal data and
details of the structural refinement for complexes 2, 3, 4′, 5,
3a−5a, and 7a are summarized in Supporting Information;
ORTEP plots for these compounds are shown in Figures 2−4,
along with the atom-numbering schemes used to describe the
solid-state data. Selected bond lengths and bond angles are
presented in Tables 4−6. In the trans-[PtII(4-Xpy)2Cl2]
complexes (2, 3, and 5), the PtII metal center has two trans
chloro ligands and two N-bonded pyridyl ligands (Figure 2).
[PtII(4-Xpy)2Cl2] Structures. Even though the 4-Xpy
ligands differ considerably in donor potential, the values of
the Pt−N, Pt−Cl, C1−N1, and C5−N1 bond distances and the
Pt−N−C and C−N−C bond angles for trans-[PtII(4-
Xpy)2Cl2], X = CF3 (2), MeO (3), and (CH2)5N (5) (Table
4) and for cis-[PtII(4-Me2Npy)2Cl2] (4′) (Table 5) are not
significantly different. In addition, no significant differences
were observed in the metrics of the molecular structure of these
new structures with those reported for trans-[PtII(py)2Cl2]41
and cis-[PtII(py)2Cl2]41 or for trans-[PtII(4-Mepy)2Cl2]24 and
cis-[PtII(4-Mepy)2Cl].24 Thus, these structural parameters are
not significantly influenced by either the basicity of 4-Xpy or
the cis or trans geometry of the complex. In the [PtII(4-
Xpy)2Cl2] complexes studied here, the dihedral angle between
the plane of the 4-substituted pyridine ligands and the
coordination plane (a feature we call canting) is ∼50° (see
Supporting Information).
1
solution. The two salts dissolved rapidly, and H NMR spectra were
recorded for each solution within a few minutes and over a period of 9
d. Because of the low solubility of these [PtII(4-Xpy)4](NO3)2 (X =
CN or CF3) salts in CDCl3, we studied them (as well as nitrate salts
having moderate and good donor 4-Xpy ligands) in CD3CN, by
1
recording H NMR spectra soon after and 24 h after addition of 10
molar equiv of [Et4N]Cl (5 mg).
[Et4N]Cl Addition to [PtII(4-Xpy)4]Y2 Complexes in D2O or
DMSO-d6. Solutions (5 mM) of selected [PtII(4-Xpy)4]Y2 complexes
in D2O or DMSO-d6 (600 μL) at 25 °C were treated with 10 molar
equiv of [Et4N]Cl (5 mg) for [PtII(4-Xpy)4](NO3)2 salts or with 8
molar equiv of [Et4N]Cl (4 mg) for [PtII(4-Xpy)4]Cl2 salts; each
1
solution was examined by H NMR spectroscopy.
RESULTS AND DISCUSSION
■
Synthesis. As illustrated in Scheme 1, the treatment of cis-
[PtII(DMSO)2Cl2] in acetonitrile with 2 equiv of 4-Xpy
afforded 26−51% yields of solids containing pure trans-
[PtII(4-Xpy)2Cl2] complexes (X = CN, CF3, MeCO, Me,
MeO, and (CH2)5N). However, when methanol was used as
the solvent, mixtures of cis and trans isomers of [PtII(4-
Xpy)2Cl2] were obtained, as could be deduced from reported
NMR data23,24,27 on a few [PtII(4-Xpy)2Cl2] complexes; in
addition, spectra showed small signals with very downfield
shifts that did not correspond to those in any literature reports.
When a methanol solution of cis-[PtII(DMSO)2Cl2] was
treated instead with 10 equiv of relatively good 4-Xpy donor
ligands (X = Me, MeO, Me2N, and (CH2)5N), [PtII(4-
Xpy)4]Cl2 complexes were formed in 49−84% yields. These
[PtII(4-Xpy)4]Cl2 Structures. ORTEP plots for the cations
of [PtII(4-MeOpy)4]Cl2 (3a), [PtII(4-Me2Npy)4]Cl2 (4a),
[PtII(4-(CH2)5Npy)4]Cl2 (5a), and [PtII(4-Mepy)4]Cl2 (7a)
D
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(X = MeO (3a), Me2N (4a), (CH2)5N (5a), and Me (7a))
(Table 6) compare well with other Pt−N(sp2) bond distances
ranging from 1.99 to 2.08 Å.22,42,43 The canting angle for
[PtII(4-Xpy)4]2+ cations varies from ∼89.2° in 4a to ∼76.4° in
5a, indicating less canting than in trans-[PtII(4-Xpy)2Cl2]
compounds. The large differences in the canting angles indicate
that there is a very low barrier preventing changes in the
dihedral angle.
Pt···Cl and CH···Cl Nonbonded Distances in [PtII(4-
Xpy)4]Cl2 (X = MeO (3a), Me2N (4a), (CH2)5N (5a), or Me
(7a)) Crystals. In almost all cases, the chloride counterions of
the new crystals lie along pseudoaxial sites of the Pt(II) center
but usually at distances that are a few tenths of an angstrom
longer than the Pt···Cl contact distance of ∼3.5 Å.36,37
Including the two counterions and the cation, we can describe
the configuration as resembling an axially elongated octahedron
for both independent molecules in [PtII(4-(CH2)5Npy)4]Cl2·
4H2O (5a) (in which Pt atoms occupy inversion centers with
Pt···Cl distances of 3.885 and 3.912 Å for the A and B
molecules, respectively; see Supporting Information, Table S3)
and Molecule B of [PtII(4-Me2Npy)4]Cl2 (4a) (with the Pt
atom at an inversion center and the Pt···Cl distance = 3.793 Å).
Molecule A of 4a, the Pt atom has an elongated pseudo square
pyramidal arrangement (Pt···Cl distance is 3.675 Å), a structure
serving as a model for {[PtII(4-Xpy)4]2+,Cl−}+ ion pairs with
only one chloride present in solutions made with moderately
polar solvents such as CD3CN (see below). The axially
elongated octahedral arrangement in [PtII(4-Mepy)4]Cl2·H2O
(7a) is less regular and lacks an inversion center; the two Cl−
anions nearest to Pt lie along the twofold rotational axis
perpendicular to the Pt coordination plane, forming a pseudo-
octahedral arrangement with slightly differing Pt···Cl non-
bonded distances of 3.470 Å (Cl1) and 3.690 Å (Cl2) (see
Supporting Information, Table S3). In [PtII(4-MeOpy)4]Cl2
(3a), there are disordered Cl− anions, precluding detailed
geometric comparison of the arrangement of the Cl− anions
relative to the cation; however, the elongated pseudo-
octahedral arrangement appears to be present in this case
also. Finally, although this topic was neither noted nor
discussed in the report of the structure of [PtII(py)4]Cl2 (8a),
the structure does have axially located chlorides (Pt···Cl
distance 3.631 Å).44
Figure 2. ORTEP plots of trans-[Pt(4-CF3py)2Cl2] (2), trans-[Pt(4-
MeOpy)2Cl2] (3), and trans-[Pt(4-(CH2)5Npy)2Cl2] (5). Thermal
ellipsoids are drawn with 50% probability. The asymmetric unit has
only half of each molecule. For the figure, the other half of each
structure was generated by using the inversion center. The
trifluoromethyl group in 2 is disordered over three positions; only
one position is shown for clarity.
In the structures of 4a, 5a·4H2O, and 7a·H2O, the distance
between many of the pyridyl H2/6 protons and the Cl−
counteranions are short enough to be considered as a CH···
Cl intermolecular contact.45 The contacts for 4a are shown in
Figure 5. Although invariably weak, such contacts are known to
exhibit the characteristics of conventional hydrogen bonds,45−47
to occur widely in crystals,46,48 and possibly to extend beyond
the 3.0 Å van der Waals separation.48 The CH···Cl
intermolecular contacts can be described as short (<2.6 Å, (d
≪ ∑vdW), medium (2.6−3.0 Å, (d ≤ ∑vdW), or long (>3.0 Å,
(d > ∑vdW).46
The four nonbonding (py)C−H···Cl distances found in each
structure range from 2.711 to 2.884 Å and from 2.802 to 2.980
Å for molecules A and B, respectively, of 4a, from 2.718 to
3.171 Å and from 2.807 to 3.111 Å for molecules A and B,
respectively, of 5a·4H2O, and from 2.702 to 2.814 Å for 7a·
H2O (see Supporting Information, Table S3). Most of these
contacts are in the medium range. The nonbonding (py)C−
H···Cl distances observed for 7a·H2O (bearing the least basic 4-
Mepy ligand in the structures obtained here) have an average =
2.761 Å, a value which is slightly shorter than the averages for
Figure 3. ORTEP plot of cis-[Pt(4-Me2Npy)2Cl2] (4′). Thermal
ellipsoids are drawn with 50% probability. The asymmetric unit has
only half of a molecule. For the figure, the other half of the structure
was generated by a twofold rotational axis.
are shown in Figure 4. The asymmetric unit of 4a has two
independent molecules (A and B), one of which lies on an
inversion center. Two independent molecules are also found in
the asymmetric unit of 5a, both of them lying on an inversion
center. The molecular structure of 7a has a twofold axis
through the central Pt atom.
The Pt−N and C−N bond distances and the C−N−C, C−
N−Pt, and N−Pt−N bond angles (Table 6) all suggest very
similar binding of the 4-Xpy ligands in the [PtII(4-Xpy)4]2+
cation of 3a, 4a, 5a, and 7a, with N−Pt−N bond angles close to
180°. In general, the Pt−N bond distances for [PtII(4-Xpy)4]2+
E
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Figure 4. ORTEP plots of the cations of [Pt(4-MeOpy)4]Cl2 (3a), [Pt(4-Me2Npy)4]Cl2 (4a), [Pt(4-(CH2)5Npy)4]Cl2 (5a), and [Pt(4-Mepy)4]Cl2
(7a). Thermal ellipsoids are drawn with 50% probability.
Table 4. Selected Bond Distances (Å) and Angles (deg) for trans-[Pt(4-Xpy)2Cl2] [X = CF3 (2), MeO (3), (CH2)5N (5), H, and
Me] Complexes
a
a
a
b
b
CF3
MeO
bond distances
2.0283(13)
(CH2)5N
H
Me
Pt1−N1
Pt1−Cl1
C1−N1
C5−N1
2.0094(19)
2.3005(5)
1.350(3)
2.026(2)
1.977
2.308
1.370
1.408
2.024
2.305
1.333
1.348
2.3000(4)
1.3473(19)
1.351(2)
2.2998(7)
1.335(3)
1.350(3)
1.350(3)
bond angles
N1−Pt1−Cl1
N1−Pt1−Cl1
N1−Pt1−N1
Cl1−Pt1−Cl1
Pt1−N1−C1
Pt1−N1−C5
C1−N1−C5
90.24(5)
89.76(5)
180.0
90.34(4)
89.66(4)
180.0
90.52(7)
89.48(7)
180.0
91.99
89.80
89.80
91.99
180.00
180.00
123.89
120.36
115.50
180.00
180.00
120.00
121.00
118.3(5)
180.0
180.0
180.0
121.12(16)
119.82(16)
119.0(2)
121.71(10)
120.65(10)
117.63(13)
121.03(17)
121.38(18)
117.6(2)
a
b
Pt atom occupies an inversion center (half of the molecule is generated by an inversion center). Data for X = H (refs 24 and 41) and Me (ref 24)
are obtained from the literature, and no standard deviation was obtained from the database.
4a (2.851 Å) and for 5a·4H2O (2.954 Å), the complexes with
the highly basic 4-Me2Npy and 4-(CH2)5Npy ligands,
respectively. This trend is expected and can be attributed to
the higher δ+ charge on the (py)C−H protons of 4-Mepy (7a·
H2O), which leads to stronger CH···Cl intermolecular
interactions and thus shorter (py)C−H···Cl contacts. All of
the [PtII(4-Xpy)4]Cl2 crystals obtained in this study have
relatively good 4-Xpy donors. For the analogues with weaker
F
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Table 5. Selected Bond Distances (Å) and Angles (deg) for
a
cis-[Pt(4-Me2Npy)2Cl2] (4′)
bond distances
Pt1−N1
Pt1−Cl1
C1−N1
C5−N1
2.0217(10)
2.3028(3)
1.3500(15)
1.3569(14)
bond angles
88.47(6)
N1i−Pt1−N1
N1i−Pt1−Cl1i
N1i−Pt1−Cl1
Cl1i−Pt1−Cl1
Pt1−N1−C1
Pt1−N1−C5
C1−N1−C5
178.40(3)
90.26(3)
91.020(17)
122.57(7)
120.41(8)
116.81(10)
a
Symmetry operator (i) = −x + 1, y, −z + 3/2.
Figure 5. Pseudo-elongated octahedral geometry in [Pt(4-Me2Npy)4]-
Cl2 (4a) formed by nonbonding (py)C−H···Cl interactions between
the aromatic protons closest to the platinum atom and the two nearest
Cl− anions.
donor 4-Xpy ligands (X = CN, CF3, and MeCO), the chloride
displaces the 4-Xpy ligand, as discussed below, precluding the
isolation of crystals. However, we expect that the (py)C−H···Cl
contacts for complexes possessing less basic 4-Xpy donors
would be shorter than those observed here for 4a, 5a·4H2O,
and 7a·H2O.
1
downfield) and H3/5 aromatic H NMR signals assigned in
1
NMR Spectroscopy. Selected H NMR spectroscopic data
accordance with the widely observed pattern,1,49 are collected
for 4-Xpy ligands and complexes, including the H2/6 (more
in Tables 1−3 and in the Supporting Information. The atom-
Table 6. Selected Bond Distances (Å) and Angles (deg) for [Pt(4-Xpy)4]Cl2 [X = MeO (3a), Me2N (4a), (CH2)5N (5a), and Me
a
(7a)] Complexes
3a
4a (A)
4a (B)
5a (A)
2.014(2)
5a (B)
2.010(2)
7a
bond distances
Pt1−N1
2.014(8)
2.027(9)
2.026(9)
2.008(9)
2.020(4)
2.011(5)
2.008(5)
2.016(5)
2.033(6)
Pt1−N2
Pt1−N(m)
Pt1−N(n)
a
b
c
b
b
b
d
b
b
d
b
2.016(4)
2.026(4)
2.021(2)
180.0(0)
2.005(2)
180.0(0)
a
c
2.013(5)
bond angles
b
c
b
c
d
d
e
N1−Pt1−N(m)
N2−Pt1−N(n)
N1−Pt1−N2
177.9(3)
179.0(4)
89.8(3)
179.32(17)
178.95(18)
88.12(18)
180.0(0)
179.6(3)
179.3(3)
90.3(2)
b
b
b
b
N1−Pt1−N(m)
N1−Pt1−N(n)
N2−Pt1−N(m)
N(m)−Pt1−N(m)
N1−Pt1−N(m)
N(m)−Pt1−N(n)
C1−N1−C5
92.11(19) , 87.89(19)
92.51(9) , 87.49(9)
91.56(9) , 88.44(9)
c
e
e
91.1(4)
92.23(18)
89.7(2)
b
b
88.3(3)
92.42(18)
b
b
180.0(0)
180.0(0)
b
180.0(0)
bc
,
bc
,
90.8(4)
87.22(18)
117.3(5)
122.0(4)
120.7(4)
118.7(10)
120.4(7)
120.8(8)
118.5(10)
117.5(5)
122.2(4)
120.2(4)
117.3(3)
120.33(19)
122.3(2)
117.4(2)
121.17(19)
121.5(2)
118.6(6)
120.7(5)
120.8(5)
119.1(6)
C1−N1−Pt1
C5−N1−Pt1
C7−N2−C11
C11−N2−C15
C11−N(m)−C15
C7−N2−Pt1
C8−N2−C12
C8−N2−Pt1
C8−N(m)−Pt1
C11−N2−Pt1
C11−N(m)−Pt1
C12−N2−Pt1
C12−N(m)−Pt1
C15−N2−Pt1
C15−N(m)−Pt1
b
b
117.4(2)
116.9(2)
120.6(7)
120.9(7)
120.1(5)
120.8(5)
116.7(5)
120.0(4)
b
121.5(4)
b
b
121.66(19)
121.0(2)
122.8(4)
120.6(4)
b
120.78(19)
122.05(19)
a
b
c
d
e
m and n vary according to the R group. m = 3. n = 4. m = 1. n = 2.
G
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numbering system used in this NMR discussion is shown in
Scheme 1.
CF3py (2) > 4-MeCOpy (6) > 4-Mepy (7) > 4-MeOpy (3) >
4-Me2Npy) (4) ≈ 4-(CH2)5Npy (5). The slightly steeper
negative slope for the complexes than for the free ligand
(Figure 6) can be attributed to the size of the synergistic
decrease of the inductive effect of the Pt(II) metal center
caused by the two mutually trans pyridyl rings. This decrease of
the Pt(II) inductive effect is much smaller when the 4-Xpy
ligand is a poor donor. Thus, H2/6 Δδ is larger. The H2/6 Δδ
values decrease linearly with increasing pKa of 4-Xpy from 0.35
to 0.11 ppm (Table 1 and Figure 7) in the same order as the
plots in Figure 6.
Previous limited NMR studies on cis/trans-[PtII(py)2Cl2] and
cis/trans-[PtII(4-Xpy)2Cl2] complexes employed pyridine-type
ligands having properties in a narrow range.23−25,27,33 In
CDCl3, the H2/6 signal of py in trans-[PtII(py)2Cl2] was shifted
downfield by ∼0.3 ppm as compared to free ligand24 (see
footnotes in Table 1 and Supporting Information, Table S5);
this characteristic downfield chemical shift change giving a
positive value for the parameter Δδ (Δδ = δcomplex − δligand) is
approximately the expected value24 and is usually interpreted as
resulting from the decrease in the electron density of the ligand
upon coordination.17,24,27
In the present study, we first examined relatively basic ligands
that can be used in our bioconjugation approach and found that
the trans-[PtII(4-Xpy)2Cl2] products had rather small H2/6 Δδ
values in CDCl3 (∼0.1 ppm). This H2/6 Δδ value is
comparable to that reported for the [PtII(py)2Cl2] cis isomer
(∼0.1 ppm) as compared to the trans isomer (∼0.3 ppm).23,24
The smaller H2/6 Δδ value for cis-[PtII(py)2Cl2] versus trans-
[PtII(py)2Cl2] was attributed to the mutual anisotropic
shielding effect exerted by adjacent cis anisotropic py
ligands.23,27 Thus, the NMR data do not provide a very useful
guide in synthetic studies of trans-[PtII(4-Xpy)2Cl2] complexes.
In addition, we also observed side products having very
downfield H2/6 signals. Thus, to understand the factors that
influence H2/6 Δδ values, we prepared and examined
complexes of 4-Xpy ligands having a wide range of donor
ability.
1
Figure 7. Change in shift (Δδ, ppm) of the H2/6 H NMR signal in
CDCl3 upon coordination of 4-Xpy to form trans-[Pt(4-Xpy)2Cl2]
(red line; slope = −0.0305, R2 = 0.9858) and [Pt(4-Xpy)4]Cl2 (green
line; slope = −0.1435, R2 = 0.9449) plotted vs the pKa of free 4-Xpy.
Data for “[Pt(4-Xpy)4]Cl2” for X = CN, CF3, and MeCO were
obtained from the nitrate salt as explained in the text.
trans-[PtII(4-Xpy)2Cl2] Complexes. As expected, coordi-
nation of 4-Xpy to form trans-[PtII(4-Xpy)2Cl2] complexes led
to positive Δδ values for the H2/6 signal (Table 1). For both
the free 4-Xpy ligands and the trans-[PtII(4-Xpy)2Cl2]
complexes, the H2/6 and H3/5 signals (in CDCl3) appeared
farther upfield with increasing basicity of the 4-Xpy ligand
(Table 1). This trend can be attributed to the greater electron
richness of the more basic 4-Xpy ligands. Plots of the chemical
shift of the H2/6 signals of 4-Xpy and of trans-[PtII(4-
Xpy)2Cl2] complexes versus the pKa of 4-Xpy are linear and
have a negative slope (Figure 6). For plots of both series of
complexes in Figure 6, the order is as follows: 4-CNpy (1) > 4-
Dependence of NMR Spectra (in CDCl3) of [PtII(4-
Xpy)4]Cl2 Complexes on the Nature of X. As mentioned,
side products having very downfield H2/6 signals found in
early phases of this study were later identified as the [PtII(4-
Xpy)4]Cl2 salts. To obtain related products ([PtII(4-Xpy)4]Y2)
with poor donor 4-Xpy ligands, we used other poorly
coordinating or non-coordinating counterions. Within any
series of [PtII(4-Xpy)4]Y2 complexes regardless of the identity
of the Y counterion, the H2/6 and H3/5 signals appeared
farther upfield with increasing basicity of the 4-Xpy ligands, as
we found for the trans-[PtII(4-Xpy)2Cl2] complexes.
We begin the discussion with the [PtII(4-Xpy)4]Cl2
complexes in CDCl3 (Table 2), because we have the most
extensive solution and structural data for the Y = Cl− complexes
and because Δδ is greater by ∼1 ppm when Y = Cl− than when
Y = other counterions; we conclude with a discussion of other
solvents and [PtII(4-Xpy)4]Y2 complexes with other Y counter-
ions. In plots of the H2/6 shifts of [PtII(4-Xpy)4]Cl2 and trans-
[PtII(4-Xpy)2Cl2] in CDCl3 versus the pKa of 4-Xpy (Figure 6),
the negative slope for the [PtII(4-Xpy)4]Cl2 series is much
steeper than for the trans-[PtII(4-Xpy)2Cl2] series. This
observation can be interpreted as discussed above by noting
that now there are four 4-Xpy ligands synergistically influencing
the inductive effect of the PtII metal center and that the H2/6
shift is sensitive to this inductive effect. As a further illustration
of the synergism, the Δδ values in CDCl3 for [PtII(4-Xpy)4]Cl2
(1.91−0.77 ppm, Table 2) decrease linearly with increasing pKa
of 4-Xpy (Figure 7) to a much greater extent than the trans-
[PtII(4-Xpy)2Cl2] series.
Figure 6. Shifts (ppm) of the H2/6 NMR signals (in CDCl3, 25 °C)
of 4-Xpy both free (5 mM, blue line; slope = −0.0856, R2 = 0.972) and
coordinated in trans-[Pt(4-Xpy)2Cl2] (5 mM, red line; slope =
−0.1165, R2 = 0.9862) and [Pt(4-Xpy)4]Cl2 (5 mM, green line; slope
= −0.2291, R2 = 0.9789) plotted vs the pKa of the free 4-Xpy. Data for
“[Pt(4-Xpy)4]Cl2” for X = CN, CF3, and MeCO were obtained from
the nitrate salt as explained in the text.
H
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1
The H NMR shift data, especially for H2/6 at 8.84 ppm,
already fully formed in the absence of added chloride salt. The
minor upfield shifting is most consistent with salt effects.
A similar [Et4N]Cl salt effect study could not be conducted
for [PtII(4-Xpy)4]Cl2 complexes with the very weak donor 4-
Xpy ligands (X = CN, CF3, and MeCO) because the chloride
salts could not be isolated. However, solutions containing
{[PtII(4-Xpy)4]2+,2Cl−} ion pairs in CDCl3 at 25 °C could be
generated easily by adding [Et4N]Cl to suspensions of [PtII(4-
Xpy)4](NO3)2 [X = CN (1e), CF3 (2e), and MeCO (6e)]
salts, which are insoluble or poorly soluble in CDCl3; shift data
from NMR spectra recorded within ∼5 to 30 min after addition
of [Et4N]Cl can be found in Table 2 and Figures 6 and 7. The
Δδ values found for {[PtII(4-Xpy)4]2+,2Cl−} ion pairs (Table 2)
are ∼1.8 to 1.9 ppm when 4-Xpy is one of these poor ligands, as
compared to Δδ ≈ 1.5 ppm for a medium donor ligand (e.g., X
= Me) and Δδ < 0.9 ppm for the stronger donor ligand (X = 4-
Me2N). These Δδ values are fully consistent with a decrease in
the partial positive charge δ+ of the H2/6 protons with
increasing 4-Xpy pyridyl ring electron richness. A decrease in δ+
of the H2/6 protons in turn diminishes the strength of the
specific H2/6 H-bonding interactions with the chloride ion
within the ion pair.
reported by Pazderski et al.23 [PtII(py)4]Cl2 in CDCl3 do not
agree at all with the H2/6 shifts (∼10 ppm) observed here for
the [PtII(4-Xpy)4]Cl2 complexes with moderate donor 4-Xpy
ligands (Table 2 and Supporting Information, Table S5). To
independently verify the reported preparation23 and character-
ization44 of [PtII(py)4]Cl2 (8a), we prepared [PtII(py)4]Cl2 by
our method and obtained colorless crystals with unit-cell
parameters identical to those reported for [Pt(py)4]Cl2.44 The
H2/6 shift (10.36 ppm) in CDCl3 at 25 °C for our
[Pt(py)4]Cl2 crystals (see Supporting Information, Table S5)
is entirely consistent with the shift value expected from our
data. Concluding that some error was made in the previous
work,23 we turned our attention to elucidating the factors
contributing to the very downfield position of these H2/6
signals.
Cause of the Unusually Large Downfield H2/6 Signals
of [PtII(4-Xpy)4]Cl2 Complexes. Understanding the specific
factors causing the larger Δδ H2/6 values for [PtII(4-Xpy)4]Cl2
salts than for salts with other counterions (Table 2) is an
important goal of our study. Another interesting feature
observed for the [PtII(4-Xpy)4]Cl2 salts is their high solubility
in CDCl3, a solvent of low polarity. We believe that the [PtII(4-
Xpy)4]Cl2 solubility in CDCl3 provides clear evidence that
electrostatic attraction leads to the existence of {[PtII(4-
Xpy)4]2+,2Cl−} ion pairs having overall low charge and
containing multiple stabilizing (py)CH···Cl hydrogen bonds
similar to those found in the solid state (Figure 5 and
Supporting Information, Table S3).
As an aside, as expected, NMR scans of these suspensions
gave no or very weak signals (cf. Figure 8 for X = CN (1e)).
We believe that there can be no doubt that ion pairs between
the [PtII(4-Xpy)4]2+ dication and the various Y anions do exist
in the low-dielectric solvent CDCl3. We hypothesize that in
CDCl3 solutions of [PtII(4-Xpy)4]Cl2 complexes the close
proximity of the Cl− counterion to the H2/6 protons of the
coordinated 4-Xpy pyridyl ring within such ion pairs results in
the formation of multiple CH···Cl contacts between H2/6 and
Cl− and in dynamic ion pairs similar to the elongated pseudo-
octahedrons found in the solid (Figure 5). The formation of
hydrogen bonds is known to lead to downfield shift changes in
the 1H NMR signals.50,51 Thus, the very downfield H2/6
signals for [PtII(4-Xpy)4]Cl2 complexes in CDCl3 are consistent
with the presence of CH···Cl hydrogen bonds, proving beyond
any doubt that specific cation−anion contacts exist within such
dynamic ion pairs in solution is probably not possible, but we
believe that the results of several solution studies to be
described next lead to a very compelling case for the existence
of fully formed {[PtII(4-Xpy)4]2+,2Cl−} ion pairs containing
multiple CH···Cl interactions in CDCl3.
To assess our hypothesis, we first examined the effect of
[Et4N]Cl addition on the H2/6 signals of [PtII(4-Xpy)4]Cl2 in
CDCl3 for X = MeO (3a), Me2N (4a), (CH2)5N (5a), and Me
(7a). If the {[PtII(4-Xpy)4]2+,2Cl−} ion pairs were not fully
formed, the H2/6 signal would shift downfield because the
added chloride would drive the equilibrium toward the
formation of more {[PtII(4-Xpy)4]2+,2Cl−} ion pairs. Downfield
shifts are also expected if the ion pairs have only one chloride
ion, {[PtII(4-Xpy)4]2+,Cl−}+. As the Cl− concentration was
increased, the H2/6 signals shifted slightly upfield by ∼0.02
ppm for 3a and 7a, by 0.17 ppm for 4a, and by 0.18 ppm for 5a
as up to 25 mM [Et4N]Cl was added (see Supporting
Information, Figure S5). The absence of downfield shifts
supports the proposal that {[PtII(4-Xpy)4]2+,2Cl−} ion pairs are
1
Figure 8. Stacked plot of the aromatic region of H NMR spectra (in
CDCl3, 25 °C) for the treatment of [Pt(4-CNpy)4](NO3)2 (1e, 5
mM) with [Et4N]Cl (125 mM). Signals for the trans-[Pt(4-
CNpy)2Cl2] complex are labeled trans. Procedures for obtaining
spectra starting from such nitrate salts are explained in the text.
However, relatively soon after addition of [Et4N]Cl to [PtII(4-
Xpy)4](NO3)2 (X = CN (1e), CF3 (2e), and MeCO (6e))
suspensions in the studies just mentioned above, new signals
corresponding to the free 4-Xpy ligand and to the trans-[PtII(4-
Xpy)2Cl2] complex were detectable (see Figure 8 for X = CN
(1e); also see Supporting Information, Figure S6). Scheme 2
describes the most likely course of the reactions.
Effect of [Et4N]Cl on the H2/6 Signals of [PtII(4-
Xpy)4](PF6)2 and of [PtII(4-Mepy)4]Y2 Complexes in CDCl3
−
−
−
(X = MeO and (CH2)5N, and Y = PF6 , BF4 , and NO3 ). In
our studies of 5 mM solutions of [PtII(4-Xpy)4]Y2 complexes in
various solvents, we ranked the ability of the Y anions both to
form ion pairs and to form hydrogen bonds as follows: Cl− >
NO3− > BF4− ≈ PF6 . We begin by describing results leading to
−
this order with our assessment of the effects of addition of
[Et4N]Cl to CDCl3 solutions of [PtII(4-Xpy)4](PF6)2 [X =
MeO (3b), (CH2)5N (5b), and Me (7b)] complexes. Such an
addition was expected to convert a {[PtII(4-Xpy)4]2+,2PF6 }
−
ion pair to a {[PtII(4-Xpy)4]2+,2Cl−} ion pair. The change of
I
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Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
distances observed for [PtII(4-(CH2)5Npy)4]Cl2 (5a) are
slightly longer than those observed for [PtII(4-Mepy)4]Cl2
(7a) (Supporting Information). These comparative results for
7b and 5b are readily rationalized only if specific contacts occur
between the Cl− anion and the H2/6 protons in the ion pairs.
The curve of the shift changes observed for the H2/6 signal
of [PtII(4-MeOpy)4]PF6 (3b) has a different shape than those
found for 5b and 7b. This different shape was found in a few
cases (Figure 9 and Supporting Information). Both 3b and 7b
have moderately basic 4-Xpy ligands, and the starting and
ending H2/6 shifts are very similar. Likewise, the H2/6 shift
change upon addition of the first aliquot of ∼5 mM Cl− (∼1
equiv of Cl−) is similar for 3b and 7b. However, as more Cl−
was added, the chemical shift of the H2/6 signal of 3b
plateaued and then increased again, and finally plateaued at a
shift similar to that of 7b. Such a finding cannot be easily
explained if there are no specific contacts in the ion pair.
However, if the first equivalent of added Cl− altered the canting
Scheme 2. Species Probably Formed (in CD3CN and CDCl3,
25 °C) after Addition of [Et4N]Cl to [Pt(4-Xpy)4](NO3)2
Complexes in Which 4-Xpy is a Weak Donor Ligand
the counterion in the ion pair caused downfield shift changes of
the H2/6 signals in CDCl3 (Figure 9 and Supporting
Information, Figure S7).
angles within the {[PtII(4-MeOpy)4]2+,Cl−,PF6 } ion pair, a
−
higher amount of Cl− would then be needed for a second Cl−
−
to fully displace the remaining PF6 from this ion pair to form
the {[PtII(4-MeOpy)4]2+,2Cl−} ion pair.
To assess the effect of counterions other than PF6 on Cl−
−
ion-pairing interactions with [PtII(4-Xpy)4]2+, [Et4N]Cl
addition experiments using [PtII(4-Mepy)4](BF4)2 (7c) and
[PtII(4-Mepy)4](NO3)2 (7e) were conducted (Figure 10 and
Figure 9. Shift of the H2/6 signal of [Pt(4-Mepy)4](PF6)2 (7b, 5 mM,
orange), [Pt(4-MeOpy)4](PF6)2 (3b, 5 mM, blue), and [Pt(4-
(CH2)5Npy)4](PF6)2 (5b, 5 mM, green) upon addition of [Et4N]Cl
(0−25 mM) in CDCl3 at 25 °C.
The curves showing the dependence of the downfield shift
changes of H2/6 signals for 7b and 5b on adding [Et4N]Cl
have the smooth shape most often found in our studies (Figure
9 and Supporting Information, Figure S7). For 5b (bearing the
highly basic 4-(CH2)5Npy ligand), the [Et4N]Cl concentration
(Figure 9 and Supporting Information, Figure S7) required to
reach a plateau (∼20 mM) was higher than that for 7b (∼12
mM), as expected, because 4-(CH2)5Npy in 5b is much more
electron-rich than is 4-Mepy in 7b. Thus, the δ+ charge on the
H2/6 protons is relatively smaller, and the CH···Cl interactions
within the ion pair are weaker for 4-(CH2)5Npy in 5b than
those for 4-Mepy in 7b; a higher [Cl−] is therefore required by
5b than by 7b to fully form {[PtII(4-Xpy)4]2+,2Cl−} ion pairs.
The H2/6 signals for 7b and 5b initially at 8.86 and 8.22 ppm
shifted downfield to 10.04 ppm at ∼12 mM [Cl−] and 9.02
ppm at ∼20 mM [Cl−], respectively (Figure 9 and Supporting
Information, Figure S7). The shift change observed for 7b
(∼1.2 ppm) was much larger than for [PtII(4-(CH2)5Npy)4]-
(PF6)2 (5b) (∼0.8 ppm). The smaller H2/6 shift change
observed for 5b, bearing the highly basic 4-(CH2)5Npy ligand,
can be attributed to the electron richness of the pyridyl ring,
which in turn lowers the partial positive charge of the H2/6
protons and diminishes the hydrogen-bonding ability of these
hydrogens. The results for solutions are consistent with the
solid-state data; the average nonbonding (py)C−H···Cl
Figure 10. Shift of the H2/6 signal of [Pt(4-Mepy)4](PF6)2 (7b, 5
mM, red), [Pt(4-Mepy)4](BF4)2 (7c, 5 mM, blue), and [Pt(4-
Mepy)4](NO3)2 (7e, 5 mM, green) upon addition of [Et4N]Cl up to
25 mM in CDCl3 at 25 °C.
Supporting Information, Figure S9). As the [Et4N]Cl
concentration was increased from 0−125 mM, the H2/6
signals for 7c and 7e shifted downfield from 9.11 and 9.39 ppm
to 10.02 and 10.00 ppm, respectively. The shift change of the
H2/6 signal (∼1.2 ppm) observed for [PtII(4-Mepy)4](PF6)2
(7b) was more than that observed for 7c (∼0.9 ppm) and 7e
(∼0.6 ppm, in CDCl3 at 25 °C). The concentration of [Et4N]
Cl required to reach a plateau was much lower (∼13 mM) for
−
7b (with the PF6 anion) than for 7c (∼25 mM) or 7e (∼50
−
−
mM) (with the BF4 or NO3 counterions, respectively). Of
greater interest, the curve for 7c rose sharply to an ∼1:1 ratio of
Cl−, and then rose more gradually. This curve indicates that
very likely a mixed {[PtII(4-Mepy)4]2+,Cl−,BF4 } ion pair forms
−
readily with one Cl− and one BF4 , as proposed above for the
−
{[PtII(4-MeOpy)4]2+,Cl−,PF6 } ion pair. Perhaps the H-
−
−
bonding interactions within the {[PtII(4-Xpy)4]2+,Cl−,BF4 }
ion pair causes changes in the canting of the bound 4-Mepy
ligands. The solid-state structural data show that large changes
in canting are feasible. Such a change in canting could favor H-
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Inorg. Chem. XXXX, XXX, XXX−XXX

Inorganic Chemistry
Article
−
bonding by the tetrahedral BF4 remaining in the mixed ion
donor with low pyridyl-ring electron richness and hence greater
partial positive charge, δ+, on the H2/6 protons. Thus, ion pairs
with specific interactions in CD3CN are similar in nature to
those in CDCl3, although CD3CN is more polar.
−
pair. The BF4 could then be more difficult to substitute from
the mixed ion pair than the octahedral PF6 in the {[PtII(4-
−
Xpy)4]2+,Cl−,PF6 } ion pair. In any case, the shape of the curve
−
is further evidence that there are specific contacts within these
ion pairs. The interaction of the Y anions with the H2/6
protons in {[PtII(4-Xpy)4]2+,2Y−} ion pairs thus decreases in
1H NMR signals of “free” 4-Xpy and trans-[PtII(4-Xpy)2Cl2]
in the first spectrum recorded (∼5 min) after [Et4N]Cl
addition to [PtII(4-CNpy)4](NO3)2 (1e), [PtII(4-CF3py)4]-
(NO3)2 (2e), and [PtII(4-MeCOpy)4](NO3)2 (6e) in CD3CN
at 25 °C (Figure 11 and Supporting Information, Figures S10−
S12). Less time was required for the intensity of the aromatic
signals of [PtII(4-CNpy)4]Cl2 (∼4 h) and [PtII(4-MeCOpy)4]-
Cl2 (∼6 h) to reach the baseline than in the case of [PtII(4-
CF3py)4]Cl2 (∼24 h). Therefore, the donor ability of 4-Xpy
decreases in the order X = CF3 > CN ≈ MeCO. For a detailed
discussion of the spectral changes over time, see Supporting
Information.
−
−
−
the order: Cl− > NO3 > BF4 ≈ PF6 .
Shift of the H2/6 Signals of [PtII(4-Xpy)4](NO3)2 and
Other [PtII(4-Xpy)4]Y2 Complexes in CD3CN. When the
counterion is not chloride, [PtII(4-Xpy)4]Y2 salts are often not
soluble in CDCl3 (cf. Table 2). We decided to conduct broader
studies in the more polar solvents in the hope that we could
obtain data relevant to ion pairing on more [PtII(4-Xpy)4]Y2
compounds in a given solvent. Because D2O and DMSO-d6 are
too polar to allow extensive ion pairing (Supporting
Information), we chose to explore CD3CN. All [PtII(4-
Xpy)4]Y2 complexes prepared in this study were soluble at 5
mM concentration in CD3CN. This solvent was polar enough
to allow NMR spectra to be recorded at 25 °C but was not so
polar as to preclude formation of ion pairs (Tables 3 and S8).
Furthermore, addition of [Et4N]Cl to the chloride salt, [PtII(4-
Me2Npy)4]Cl2 (4a), in CD3CN caused a downfield shift of 0.33
ppm of the H2/6 signal (Table 3). This finding indicates that
the ion pair is not fully formed in CD3CN. In contrast, [Et4N]
Cl addition to 4a and other chloride salts in CDCl3 led to
upfield H2/6 shifts (Figure S5), indicating that the ion pair was
fully formed in the less polar CDCl3 solvent.
CONCLUSIONS
The dependence of the chemical shifts of 4-Xpy H2/6 H
■
1
NMR signals of many new complexes in two series, namely,
trans-[PtII(4-Xpy)2Cl2] and [PtII(4-Xpy)4]Y2, were investigated
by employing 4-Xpy with very diverse donor abilities. For both
series in CDCl3, downfield shift changes (Δδ) were observed
for the H2/6 signals upon coordination of 4-Xpy to form the
respective trans-[PtII(4-Xpy)2Cl2] or [Pt(4-Xpy)4]Cl2 com-
plexes. The size of H2/6 Δδ decreased linearly with increasing
4-Xpy donor ability. The decrease in Δδ was greater for the
[Pt(4-Xpy)4]Cl2 series than for the trans-[PtII(4-Xpy)2Cl2]
series. We conclude that this finding can be attributed to the
synergistic reduction in the inductive effect of the Pt(II) center
by the other three 4-Xpy donor ligands in the [Pt(4-Xpy)4]Cl2
series as compared to only one other 4-Xpy donor ligand in the
trans-[PtII(4-Xpy)2Cl2] series.
1H NMR spectra of [PtII(4-Xpy)4](NO3)2 CD3CN solutions
were recorded ∼5 min after addition of sufficient [Et4N]Cl to
make the solutions 50.0 mM in [Et4N]Cl. For all five
complexes studied, downfield H2/6 shift changes were
observed as expected (Table 3, Figure 11, and Supporting
Solutions of [Pt(4-Xpy)4]Cl2 salts in CDCl3 have very
1
downfield 4-Xpy H2/6 H NMR signals and exhibit much
larger H2/6 Δδ values than those of the corresponding [PtII(4-
Xpy)4]Y2 (Y = PF6, BF4, and NO3) salts. We conclude that
strong ion pairing between Cl− and [PtII(4-Xpy)4]2+ is
facilitated by multiple H2/6···Cl− H-bonding contacts, explain-
ing the large downfield shifts. Also, strong ion pairing explains
the high solubility of the [PtII(4-Xpy)4]Cl2 salts that contain a
[PtII(4-Xpy)4]2+ dication. Other [PtII(4-Xpy)4]Y2 salts were
often much less soluble or even insoluble. Crystal structures
revealed that the chloride counterions occupy axial positions
with nonbonding (py)C−H···Cl distances well within the range
of a typical CH···Cl H-bonding contact (2.4−3.0 Å). Thus, the
crystallographic data confirm our conclusion that the relatively
larger H2/6 Δδ values (in CDCl3 at 25 °C) observed for
[PtII(4-Xpy)4]Cl2 arise from ion pairing, which in turn is
stabilized by multiple (py)C−H···Cl contacts.
1
Several H NMR studies in various solvents allowed us to
Figure 11. Stacked plot of the aromatic region of 1H NMR spectra (in
CD3CN, 25 °C) for the treatment of [Pt(4-CNpy)4](NO3)2 (1e, 5
mM) with [Et4N]Cl (50 mM). Signals for trans-[Pt(4-CNpy)2Cl2] are
labeled trans.
correlate the dependence of the relative stability of the ion pairs
of [PtII(4-Xpy)4]Y2 based on their H-bonding ability as follows:
−
−
−
Cl− > NO3 > BF4 > PF6 . The poor solubility of some
[PtII(4-Xpy)4]Y2 (Y = PF6, BF4, and NO3) complexes as
compared to the [PtII(4-Xpy)4]Cl2 analogues is probably a
result of the weaker ion pairing.
Information, Figures S10−S12). The H2/6 shift changes
observed for [PtII(4-CNpy)4](NO3)2 (∼1.2 ppm), [PtII(4-
CF3py)4](NO3)2 (∼1.1 ppm), [PtII(4-MeCOpy)4](NO3)2
(∼1.2 ppm), and [PtII(4-MeOpy)4](NO3)2 (∼1.2 ppm) were
greater than the 0.75 ppm observed for [PtII(4-Me2Npy)4]-
(NO3)2 (Table 3). Such larger H2/6 shift changes indicate that
H bonding to Cl is better when 4-Xpy is a poor or moderate
Because our procedures for synthesizing model trans-[PtII(4-
Xpy)2Cl2] and [PtII(4-Xpy)4]Y2 complexes do not rely on high
temperatures, water solubility, or Xpy volatility, the methods
are clearly applicable to other nonvolatile monodentate ligands,
such as those bearing biological targeting groups. The NMR
spectroscopic trends we have elucidated can serve as a guide
K
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.7b01294.
■
S
Details of the syntheses and characterization of all
complexes prepared in this study; descriptions and
figures of the effect of [Et4N]Cl addition on H NMR
1
signals of [PtII(4-Xpy)4]Y2 in various solvents; descrip-
tions and figures of replacement of weak 4-Xpy ligands
by chloride upon [Et4N]Cl addition to [PtII(4-Xpy)4]-
(NO3)2 suspensions or solutions; tables of crystallo-
graphic data for complexes 2, 3, 4′, 5, 3a, 4a, 5a, and 7a
in CIF format; tables of selected nonbonding Pt···Cl and
(py)C−H···Cl distances and dihedral angles; tables of 1H
NMR data in CDCl3 for py and various Pt(II) py
complexes and for trans-[Pt(4-Xpy)2Cl2] complexes;
tables of 1H NMR shift data in CDCl3, CD3CN,
DMSO-d6, and D2O for free 4-Xpy and for [Pt(4-
Xpy)4]Y2 complexes both with and without added
[Et4N]Cl; figure showing the orientation of the pyridyl
rings relative to the coordination plane in cis-[Pt(4-
Me2Npy)2Cl2]; plots of 1H NMR data versus pKa for free
ligand and for trans-[Pt(4-Xpy)2Cl2] (including X = H)
in CDCl3 (PDF)
Accession Codes
CCDC 1551057−1551064 contain the supplementary crystal-
lographic data for this paper. These data can be obtained free of
charge via www.ccdc.cam.ac.uk/data_request/cif, or by email-
ing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
*E-mail: lmarzil@lsu.edu.
ORCID
Patricia A. Marzilli: 0000-0002-8103-9606
Luigi G. Marzilli: 0000-0002-0406-0858
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
Upgrade of the diffractometer was made possible through
Grant No. LEQSF(2011-12)-ENH-TR-01, administered by the
Louisiana Board of Regents.
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