Conformational isomerism of trans-[Pt(NH2C6H 11)2I2] and the classical Wernerian chemistry of [Pt(NH2C6H11)4]X2 (X = Cl, Br, I)

Article abstract of DOI:10.1016/j.poly.2012.08.010

X-ray crystallographic analysis of the compound trans-[Pt(NH ₂C₆H₁₁)₂I₂] revealed the presence of two distinct conformers within one crystal lattice. This compound was studied by variable temperature

Full text of DOI:10.1016/j.poly.2012.08.010

Polyhedron 52 (2013) 565–575
Contents lists available at SciVerse ScienceDirect
Polyhedron
journal homepage: www.elsevier.com/locate/poly
Conformational isomerism of trans-[Pt(NH2C6H11)2I2] and the classical Wernerian
chemistry of [Pt(NH2C6H11)4]X2 (X = Cl, Br, I)
⇑
Timothy C. Johnstone, Stephen J. Lippard
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Available online 14 August 2012
X-ray crystallographic analysis of the compound trans-[Pt(NH2C6H11)2I2] revealed the presence of two
distinct conformers within one crystal lattice. This compound was studied by variable temperature
NMR spectroscopy to investigate the dynamic interconversion between these isomers. The results of
this investigation were interpreted using physical (CPK) and computational (molecular mechanics
and density functional theory) models. The conversion of the salts [Pt(NH2C6H11)4]X2 into trans-
[Pt(NH2C6H11)2X2] (X = Cl, Br, I) was also studied and is discussed here with an emphasis on parallels
to the work of Alfred Werner.
Dedicated to the memory of Alfred Werner
on the 100th anniversary of his Nobel Prize
in Chemistry.
Keywords:
Ó 2012 Elsevier Ltd. All rights reserved.
Conformational isomerism
Variable temperature NMR
Molecular mechanics
Density functional theory
Coordination chemistry
Ionization isomerization
Alfred Werner
1. Introduction
the term isomer was later coined by Berzelius to describe
compounds of identical atomic composition but otherwise varying
in properties [7]. Many forms of isomerism are now recognized and
can be largely divided into two categories: structural isomers,
1.1. The past
Alfred Werner is rightly termed the ‘‘Founder of Coordination
Chemistry’’ [1], for it was by his intellectual power that coordina-
tion chemistry, as we know it today, was born. Another title appro-
priately bestowed on Werner is the ‘‘Founder of Inorganic
Stereochemistry’’. Indeed, it was as a result of ‘‘his work on the
linkage of atoms in molecules, by which he has thrown fresh light
on old problems and opened new fields of research, particularly in
inorganic chemistry’’ that the Kungliga Vetenskapsakademien
awarded him the Nobel Prize in 1913 [2]. Given the magnitude
of his impact on the field of inorganic chemistry, it is easy to over-
look the fact that Werner was initially trained as an organic chem-
ist, and his early work on the stereochemistry of nitrogen centers
presaged his later foray into inorganic stereochemistry [3,4]. The
spatial arrangement of atoms featured prominently in Werner’s
work, and it was by the preparation of isomeric, particularly ste-
reoisomeric, species that he firmly established his coordination
theory [5].
which differ in the chemical linkage of atoms, and stereoisomers,
which differ only in the spatial arrangement of similarly bonded
atoms [8].
Stereoisomers typically take front stage in discussions of Wer-
ner’s work, but one form of inorganic stereoisomerism that was
not explicitly treated by Werner is conformational isomerism [9].
Complex isomers of this type share a common atomic connectivity
(i.e. they are not structural isomers) and ligand distribution about
the metal center (i.e. not geometric isomers) but are diastereo-
meric (i.e. not optical isomers). A manner by which this set of cri-
teria can be satisfied is hindered rotation within a molecule [10].
This isomerism was first recognized in coordination compounds
in 1970 during an investigation of two isomeric forms of
[Co(NO2)3NH3(en)] [11]. It was uncovered by X-ray crystallo-
graphic analysis that the two forms were related by rotation
about a single Co–Nnitrite bond [12]. Although the significance of
the discovery was not fully appreciated, Werner may have isolated
these two different forms of the molecule over half a century
earlier [13].
The first report of isomerism, that of isocyanic and fulminic
acid, was recorded by Liebig and Wöhler in the 1820s [6] and
Werner also conducted a large body of work on a host of
structural isomers [9]. One particular form of isomerism in
the Wernerian classification was termed ionization isomerism,
whereby two species sharing the same elemental composition
⇑
Corresponding author. Address: 77 Massachusetts Ave., Building 18, Room 498,
Cambridge, MA 02139, USA. Tel.: +1 617 253 1892; fax: +1 617 258 8150.
E-mail address: lippard@mit.edu (S.J. Lippard).
0277-5387/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.poly.2012.08.010

566
T.C. Johnstone, S.J. Lippard / Polyhedron 52 (2013) 565–575
form different ions upon dissolution. For example, [Co(NH3)4Cl2]Br
and [Co(NH3)4ClBr]Cl constitute a pair of ionization isomers.
Interconversion between these two species is tantamount to ex-
change of an inner sphere for an outer sphere ligand. Variations
on this motif, although not strictly ionization isomerizations, were
critical in preparing the material used by Werner and Jørgensen in
defense of their respective theories of the geometries of transition
metal compounds. For instance, Jørgensen reported that cobalt(III)
chloride can be converted from the luteo to the purpureo form
when heated to temperatures greater than 100 °C [14]. In this
reaction, a chloride ion from the outer sphere of [Co(NH3)6]Cl3
exchanges with an inner sphere ammine ligand to afford
[Co(NH3)5Cl]Cl2.
2.2. Physical measurements
NMR spectral measurements were carried out using a Varian
Inova 500 spectrometer housed in the MIT Department of Chemis-
try Instrumentation Facility (DCIF) and spectra were processed
using Mnova Lite. 1H and 13C{1H} NMR spectra were referenced
to residual internal solvent signals and resonances are reported
in ppm as chemical shifts (d) with respect to tetramethylsilane (d
0 ppm). 195Pt{1H} NMR spectra were referenced externally to a
0.3 M solution of K2PtCl4 in D2O (d ꢀ1628 ppm) and resonances
are reported in ppm referenced to K2PtCl6 in D2O (d 0 ppm). FTIR
spectra were collected on a ThermoNicolet Avatar 360 spectropho-
tometer using the OMNIC software. Samples were prepared as KBr
pellets. Melting points were obtained using a Mel-temp electro-
thermal melting point apparatus. ESI-MS measurements were per-
formed on an Agilent Technologies 1100 series LC/MSD ion trap. A
commercial analytical laboratory performed the elemental
analyses.
1.2. The present
During the course of an investigation of the chemistry of an
intermediate in the synthesis of the anticancer agent satraplatin
[15], cis,cis,trans-[Pt(NH3)(NH2C6H11)Cl2(OOCCH3)2], we obtained
the crystal structure of trans-[Pt(NH2C6H11)2I2]. In a single crystal
2.3. Synthesis of [Pt(NH2C6H11)4]Cl2 (1)
of this compound, there is a pair of conformational isomers having
both syn and anti disposition of the cyclohexylamine rings with re-
spect to the plane containing platinum and its four bonded atoms.
We were therefore interested to determine whether the two
isomers could be resolved and whether it might be possible to
observe dynamic exchange between them. When preparing trans-
A red solution of potassium tetrachloroplatinate(II) (200 mg,
0.48 mmol) in 4 mL of water was treated with cyclohexylamine
(1 mL, 8.7 mmol) and heated to 100°C in the dark. After 30 min
at reflux, the reaction mixture, a suspension of a white solid in a
colorless solution, was removed from heat, cooled to room tem-
perature, and then further cooled in an ice bath for 4 h. After this
time, the mixture was filtered and the filtrate was collected for
crystallization (vide infra). The off-white precipitate isolated was
washed with cold water, cold ethanol, and diethyl ether to provide
a white solid. The solid was dried in a dessicator. Yield: 184 mg,
58%. M.p. 226–227°C (decomposition to black solid). The reaction
product has low solubility in water and common organic solvents
but it dissolves in DMF at temperatures above 50°C, resulting in a
chemical transformation of the compound as described in Sec-
tion 2.5. With gentle heating (not above 50°C) enough material
dissolved to allow for characterization by mass spectrometry.
ESI-MS (positive mode): m/z = 100.1 ([NH3C6H11]+, Calc. 100.1),
[Pt(NH2C6H11 2 2
) I ], we encountered reactivity paralleling that of the
aforementioned conversion of luteo to purpureo cobalt(III) ammine
chlorides, whereby the halide salts of the [Pt(NH2C6H11)4]2+ cation,
[Pt(NH2C6H11)4]X2, converted to trans-[Pt(NH2C6H11)2X2] upon
heating (Scheme 1). This chemistry, together with model studies
ranging from hand-held CPK representations, to molecular
mechanics (MM), to density functional theory (DFT) calculations
are reported herein.
2. Experimental
2.1. General methods and materials
295.8 ([M]2+
,
Calc. 295.7), 392.2 ([Mꢀ(NH2C6H11)2-H]+, Calc.
392.2), 528.4 ([Mꢀ(NH2C6H11)+Cl]+, Calc. 528.1), 590.3 ([MꢀH]+,
Calc. 590.4). IR (KBr pellet, cmꢀ1): 3177 s, 3110 s, 3041 m, 2929
s, 2853 s, 1640 m, 1578 m, 1452 m, 1384 m, 1242 m, 1158 m,
1054 m, 956 w, 896 w, 846 w, 806 w, 767 w, 458 w. Anal. Calc.
for C24H52Cl2N4Pt: C, 43.50; H, 7.91; N, 8.45. Found: C, 43.25; H,
8.31; N, 8.34%.
Potassium tetrachloroplatinate(II) was purchased from Strem
Chemicals and used as received. Cyclohexylamine was used as re-
ceived from Sigma–Aldrich. Potassium halide salts were obtained
from Mallinckrodt and used as received. Reactions were carried
out under normal atmospheric conditions, although care was taken
to avoid excessive exposure of the platinum complexes to light,
particularly when heated in solution.
2.4. Synthesis of trans-[Pt(NH2C6H11)2I2] (6) using HI(aq)
To a suspension of compound 1 (80 mg, 0.12 mmol) in 3 mL of
water was added 7 M hydriodic acid (2 mL, 14 mmol). No reaction
was evident until the mixture was heated to 90 °C. At this
temperature, the suspended solid gradually turned yellow. After
6 h, the reaction was removed from the heat, cooled to room
temperature, and the yellow precipitate was collected by filtra-
tion. The yellow solid was washed with water and then dried.
Yield: 71 mg, 92%. M.p. 206–208 °C (decomposition to a black liquid).
1H NMR (DMF-d7, 500 MHz): d 4.24 (s, 2H), 3.01 (s, 1H), 2.29 (s,
2H), 1.69 (s, 2H), 1.54 (d, 6 Hz, 1H), 1.22 (m, 9 Hz, 4H), 1.11
(s, 1H). 13C{1H} NMR (DMF-d7, 125 MHz): d 58.34, 35.54, 26.40,
25.83. 195Pt{1H} (DMF-d7, 107 MHz): ꢀ3331. IR (KBr pellet,
cmꢀ1): 3274 m, 3243 m, 3196 m, 3113 w, 2930 vs, 2855 s,
1565 s, 1446 m, 1385 m, 1230 m, 1195 m, 1052 m, 1038 w,
893 w. ESI-MS (negative mode) m/z = ꢀ773.9 ([M+I]ꢀ, Calc.
ꢀ773.9). Anal. Calc. for C12H26I2N2Pt: C, 22.27; H, 4.05; N, 4.33.
Found: C, 22.45; H, 3.69; N, 4.18%.
Scheme 1. The compounds and reaction investigated in this study. Compound 6
can also be prepared as indicated in Scheme 2.

T.C. Johnstone, S.J. Lippard / Polyhedron 52 (2013) 565–575
567
2.5. Reaction observed upon heating 1
(DMF-d7, 500 MHz): d 4.26 (s, 2H), 2.88 (s, 1H), 2.33 (d, J = 9.5 Hz,
2H), 1.69 (d, J = 11 Hz, 2H), 1.54 (d, 13.5 Hz, 1H), 1.26 (m, 4H),
1.10 (s, 1H). 13C{1H} NMR (DMF-d7, 125 MHz): d 56.55, 35.14,
26.49, 25.80. 195Pt{1H} (DMF-d7, 107 MHz): ꢀ2584. IR (KBr pellet,
cmꢀ1): 3228 s, 3203 s, 3130 m, 2927 s, 2856 s, 1576 m, 1449 m,
1393 m, 1340 m, 1243 m, 1201 m, 1160 m, 1057 m, 1045 m, 963
w, 893 m, 846 w, 793 w, 737 w. ESI-MS (negative mode) m/
z = ꢀ633.0 ([M+Br]ꢀ, Calc. ꢀ632.9). Anal. Calc. for C12H26Br2N2Pt:
C, 26.05; H, 4.74; N, 5.06. Found: C, 26.45; H, 4.46; N, 4.94%.
In order to characterize the solid obtained in the above-de-
scribed synthesis of 1 (Section 2.3), attempts were made to dis-
solve the solid in a variety of solvents, but no appreciable
dissolution occurred. We did observe, however, that when the col-
orless solid was heated in DMF, the powder was consumed and the
solution acquired a yellow color. The solution was analyzed by ESI-
MS (positive mode) m/z = 527.5 ([1-(NH2C6H11)+Cl]+, Calc. 527.2).
After cooling to room temperature, yellow prisms deposited and
were analyzed by X-ray crystallography as described in
Section 2.11.2.
2.9. Synthesis of [Pt(NH2C6H11)4]I2 (5)
The reaction was carried out on the same scale as described
above for the synthesis of 3, using potassium iodide (3.2 g,
19.27 mmol) instead of potassium bromide. The product was iso-
lated as a colorless solid. Yield: 384 mg, 94%. M.p. 177–180 °C
(decomposition to orange liquid, slight yellowing of the solid ob-
served beginning at 167 °C). Unlike 1 and 3, 5 is readily soluble
in DMF at room temperature. 1H NMR (DMF-d7, 500 MHz): d 5.24
(s, 8H), 2.81 (s, 4H), 2.47 (d, J = 11 Hz, 8H), 1.74 (d, J = 14 Hz, 8H),
1.60 (d, 13 Hz, 4H), 1.47 (q, J = 12 Hz, 8H), 1.32 (q, 13 Hz, 8H),
1.09 (q, 13 Hz, 4H). 13C{1H} NMR (DMF-d7, 125 MHz): d 56.69,
34.80, 26.26, 26.02. IR (KBr pellet, cmꢀ1): 3192 s, 3108 s, 3038 s,
2933 s, 2853 s, 1596 m, 1564 m, 1450 m, 1264 m, 1165 m, 1059
m, 1045 m, 895 m, 752 m, 458 w. ESI-MS (positive mode) m/
z = 295.7 ([M]2+, Calc. 295.7), 392.2 ([Mꢀ(NH2C6H11)2ꢀH]+, Calc.
392.2), 590.4 ([MꢀH]+, Calc. 590.4), 619.2 ([Mꢀ(NH2C6H11)+I]+,
Calc. 619.2). Anal. Calc. for C24H52I2N4Pt: C, 34.09; H, 6.20; N,
6.63. Found: C, 34.23; H, 5.54; N, 6.49%.
2.6. Synthesis of trans-[Pt(NH2C6H11)2Cl2] (2)
Compound 1 (121 mg, 0.18 mmol) was suspended in DMF
(15 mL). The mixture was sonicated to disperse the solid and
heated to 120 °C for 3 h. After this time, the reaction mixture
was a homogenous yellow solution. The solution was concentrated
to dryness and the remaining residue was dissolved in a minimal
amount of hot CH2Cl2. Addition of hot hexanes followed by cooling
to ꢀ40 °C induced crystallization. The off-white crystalline solid
was collected by filtration and washed with hexanes and diethyl
ether. Yield: 64 mg, 75%. M.p. 244–245 °C (decomposition to black
solid). 1H NMR (DMF-d7, 500 MHz): d 4.29 (s, 2H), 2.80 (s, 1H), 2.34
(d, J = 11 Hz, 2H), 1.70 (b, J = 12 Hz, 2H), 1.54 (d, J = 12 Hz, 1H), 1.22
(m, 4H), 1.11 (m, 1H). 13C{1H} NMR (DMF-d7, 125 MHz): d 55.64,
34.86, 26.51, 25.82. 195Pt{1H} (DMF-d7, 107 MHz): ꢀ2214. IR (KBr
pellet, cmꢀ1): 3231 s, 3204 s, 3135 m, 2929 s, 2855 s, 1582 m,
1450 m, 1247 m, 1202 m, 1162 m, 1057 m, 895 w, 847 w. ESI-
MS (negative mode) m/z = ꢀ499.1 ([M+Cl]ꢀ, Calc. ꢀ499.1). Anal.
Calc. for C12H26Cl2N2Pt: C, 31.64; H, 5.64; N, 6.03. Found: C,
32.03; H, 5.48; N, 6.03%.
2.10. Synthesis of trans-[Pt(NH2C6H11)2I2] (6)
The reaction was carried out as described above for the synthe-
ses of 2 and 4 except that 359 mg (0.42 mmol) of 5 were used. The
product was isolated as a yellow crystalline solid. Yield: 151 mg,
55%. M.p. 206–208 °C (decomposition to black liquid). The charac-
terization is identical to that reported in Section 2.4 for the synthe-
2.7. Synthesis of [Pt(NH2C6H11)4]Br2 (3)
Potassium tetrachloroplatinate(II) (200 mg, 0.48 mmol) was
dissolved in water (5 mL) and to the resulting red solution was
added potassium bromide (2.3 g, 19.27 mmol). After heating to
100 °C for 1 h, the solution became a deep orange color, signifying
the formation of the tetrabromoplatinate(II) anion. Cyclohexyl-
amine (1 mL, 8.7 mmol) was added to the hot solution and a yellow
solid immediately began to precipitate. The mixture was stirred at
100 °C for 1 h, after which time the reaction mixture comprised a
white precipitate suspended in a colorless solution. The mixture
was removed from heat and cooled to 4 °C overnight. The off-white
solid was collected by filtration and washed with cold water and
cold ethanol to afford a white solid. Yield: 299 mg, 83%. M.p.
205–207 °C (decomposition to black solid). As with compound 1,
the solid is insoluble, precluding NMR characterization. With gen-
tle heating (not above 50 °C) enough material dissolved to allow
for characterization by mass spectrometry without substantial
conversion to 4. ESI-MS (positive mode) m/z = 100.1 ([NH3C6H11]+,
Calc. 100.1), 295.7 ([M]2+, Calc. 295.7), 392.2 ([Mꢀ(NH2C6H11)2ꢀH]+,
Calc. 392.2), 572.3 ([Mꢀ(NH2C6H11)+Br]+, Calc. 572.2). IR (KBr
pellet, cmꢀ1): 3194 s, 3110 s, 3037 s, 2939 s, 2849 s, 1600 m,
1544 m, 1455 m, 1263 m, 1169 m, 1059 m, 1045 m, 895 m, 452
w. Anal. Calc. for C24H52Br2N4Pt: C, 38.35; H, 6.97; N, 7.45. Found:
C, 38.48; H, 6.85; N, 7.33%.
sis of 6 via reaction of 1 with HI(aq)
.
2.11. X-ray crystallography
Single crystals were grown as described below, mounted on a
nylon cryoloop in Paratone oil, and cooled to 100 K under a stream
of nitrogen. A Bruker APEX CCD X-ray diffractometer controlled by
the APEX2 software [16] was used to collect the diffraction of graph-
ite-monochromated Mo K
a radiation (k = 0.71073 Å) from the
crystal. The data were integrated with SAINT [17] and absorption,
Lorentz, and polarization corrections were calculated by SADABS
[18]. Space group determination was carried out by analyzing the
metric symmetry and systematic absences of the diffraction pat-
tern with XPREP [19]. Using the SHELXTL-97 software package
[20,21], structures were solved by either Patterson or direct meth-
ods and refined against F2. Refinement was carried out using stan-
dard procedures [22]. All atoms, including hydrogen, were located
in the difference Fourier map during refinement. Hydrogen atoms
were placed at calculated positions and refined with their isotropic
displacement parameters (Uiso) set equal to 1.5, for terminal CH3
groups, or 1.2, for secondary and tertiary carbons and nitrogens,
times the Uiso of the atom to which they are attached. Specific
refinement details are reported below and CIF data are provided
for all structures in the Supplementary data along with tables of
bond lengths and angles. All structures have been deposited in
the Cambridge Structural Database. Pertinent crystallographic
parameters are collected in Table 1. All structures were checked
for missed higher symmetry and twinning with PLATON [23] and
2.8. Synthesis of trans-[Pt(NH2C6H11)2Br2] (4)
The reaction was carried out as described above for the synthe-
sis of 2 except that 290 mg (0.39 mmol) of 3 were used. The prod-
uct was isolated as a pale yellow crystalline solid. Yield: 114 mg,
54%. M.p. 224–225 °C (decomposition to black liquid). 1H NMR
were further validated using CHECKCIF
.

568
T.C. Johnstone, S.J. Lippard / Polyhedron 52 (2013) 565–575
Table 1
Crystallographic parameters for 1, 2ꢁ2DMF, 3, 4, 5, and 6.
1
2ꢁ2DMF
3
4
5
6
Formula
Formula weight
Space group
a (Å)
b (Å)
c (Å)
C
24H52Cl2N4Pt
C18H40Cl2N4O2Pt
610.52
P1
C24H52Br2N4Pt
751.61
P1
C12H26Br2N2Pt
553.26
P21/c
6.1614(5)
8.6696(7)
15.2029(12)
C24H52I2N4Pt
845.59
P1
C12H26I2N2Pt
647.24
P1
662.68
P21/c
12.7318(17)
10.7966(14)
11.6467(16)
ꢀ
ꢀ
ꢀ
ꢀ
6.1518(6)
8.0596(8)
12.6037(12)
76.2260(10)
76.2260(10)
89.3090(10)
588.11(10)
1
6.3395(7)
10.3789(12)
12.3584(14)
110.489(2)
102.599(2)
97.082(2)
725.42(14)
1
6.7701(5)
10.4276(7)
12.2655(8)
110.2170(10)
101.5970(10)
98.6220(10)
772.96(9)
1
9.4215(8)
11.2597(10)
12.6232(11)
105.3630(10)
92.6850(10)
98.4830(10)
1271.94(19)
3
a
(°)
b (°)
111.360(2)
96.8440(10)
c
(°)
V (Å3)
Z
1491.0(3)
2
806.30(11)
2
T (K)
100(2)
4.897
1.72–28.76
29730
3869
142
99.7
1.17
2.75
100(2)
6.196
1.72–28.80
10483
3037
126
99.1
1.27
3.05
100(2)
7.608
1.83–27.04
13197
3173
142
99.7
1.92
4.60
100(2)
13.641
2.70–28.39
15547
2025
79
99.9
1.44
3.47
100(2)
6.552
1.84–28.33
15245
3806
142
99.2
1.40
3.31
100(2)
11.900
1.68–27.92
24450
6046
232
99.2
2.53
4.45
l(Mo K
a
) (mmꢀ1
)
h range (°)
Total number of data
Number of unique data
Number of parameters
Completeness to h (%)
a
R1 (%)
b
wR2 (%)
GOFc
1.055
0.85 and ꢀ0.68
1.033
1.01 and ꢀ0.73
1.029
1.97 and ꢀ0.82
1.110
1.01 and ꢀ1.25
1.049
1.09 and ꢀ0.71
0.994
1.29 and ꢀ0.80
Maximum and minimum peaks (e Åꢀ3
)
a
b
c
R1
wR2 = {
GOF = {
=
R
||Fo| ꢀ |Fc||/
R|Fo|.
[w(Fo ꢀ Fc2)2]/
R .
[w(Fo2)2]}1/2
2
R
[w(Fo ꢀ Fc2)2]/(n ꢀ p)}1/2, where n is the number of data and p is the number of refined parameters.
2
R
2.11.1. Structural analysis of [Pt(NH2C6H11)4]Cl2 (1)
tron density peak (1.97 e Åꢀ3) and hole (ꢀ0.82 e Åꢀ3) were located
0.83 Å and 0.55 Å from the platinum and bromine atoms,
respectively.
Vapor diffusion of ethanol into the aqueous filtrate of the reac-
tion mixture that yielded 1 afforded colorless blocks. The asym-
metric unit contained a chloride ion and half of the complex
cation of 1. The platinum sits on an inversion center, the action
of which generates the full molecule. No solvent co-crystallizes
with the complex and the chloride counterions act as hydrogen
bond acceptors for the amine donors. No disorder was present in
the structure and the largest residual electron density peak
2.11.4. Structural analysis of trans-[Pt(NH2C6H11)2Br2] (4)
Large yellow prisms were obtained by slow evaporation of an
acetone solution of 4. A fragment was broken off from a larger crys-
tal and mounted on the diffractometer. The asymmetric unit of the
crystal contained half of a molecule of 4 with the platinum atom
sitting on an inversion center. The full molecule is therefore pres-
ent in the anti conformation. This structure is isomorphous with
one previously reported in the literature [25]. In this previous
study, the collection was carried out at room temperature and
the hydrogen atoms were not included in the model. No disorder
was present in the structure reported here and the largest residual
electron density peak (1.01 e Åꢀ3) and hole (ꢀ1.25 e Åꢀ3) were lo-
cated 0.74 Å and 0.77 Å from the platinum atom, respectively.
(0.85 e Åꢀ3
)
and hole (ꢀ0.68 e Åꢀ3
) were located 0.80 Å and
0.76 Å from the platinum atom, respectively.
2.11.2. Structural analysis of trans-[Pt(NH2C6H11)2Cl2]ꢁ2DMF
(2ꢁ2DMF)
As described in Section 2.5, when 1 is suspended in DMF and
heated, the solid dissolves and produces a yellow solution. When
this solution is allowed to stand at room temperature overnight,
yellow prisms form. The prisms formed in this manner generated
a diffraction pattern with split spots. A fragment was broken off
of a prismatic crystal and appeared to contain a single domain.
Although the metric parameters of the crystal approximate those
of a monoclinic system, a satisfactory refinement could only be ob-
2.11.5. Structural analysis of [Pt(NH2C6H11)4]I2 (5)
Colorless needles of 5 were grown by slow evaporation of a
DMF solution. The asymmetric unit comprises one half of the cat-
ion of 5 and an iodide counterion. The platinum complex sits on an
inversion center generating the full molecule. No solvent was pres-
ent in the lattice and there was no evidence of twinning or disor-
der. The largest residual electron density peak (1.02 e Åꢀ3) and
hole (ꢀ0.71 e Åꢀ3) were located 0.81 Å and 0.84 Å from the plati-
num and bromine atoms, respectively.
ꢀ
tained in space group P1. The asymmetric unit of the crystal con-
tained half of a molecule of 2 and a molecule of DMF. The
platinum atom sits on an inversion center and application of this
symmetry operation generates the full molecule in the anti confor-
mation. This structure is the DMF solvate of a structure previously
reported in the literature [24]. No disorder was present in the
structure and the largest residual electron density peak
2.11.6. Structural analysis of trans-[Pt(NH2C6H11)2I2] (6)
Yellow needles were consistently obtained when attempting to
grow crystals of the iodo-bridged complex [Pt(NH2C6H11)I(l-I)]2.
(1.01 e Åꢀ3
)
and hole (ꢀ0.73 e Åꢀ3
) were located 0.87 Å and
0.79 Å from the platinum atom, respectively.
This compound was prepared as described previously [26]. A crys-
2.11.3. Structural analysis of [Pt(NH2C6H11)4]Br2 (3)
tal was selected from a crop of needles grown by slow evaporation
Colorless prisms of 3 were grown by slow evaporation of a DMF
solution. To obtain a clean sample, we broke off a fragment from a
larger crystal. The asymmetric unit contains one half of the cation
of 3 and a bromide counterion. The platinum complex sits on an
inversion center. No solvent was present in the lattice and there
was no evidence of twinning or disorder. The largest residual elec-
of a DMF solution of [Pt(NH2C6H11)I(l-I)]2. The asymmetric unit
contained 1.5 molecules of 6. The full molecule in the asymmetric
unit is present in the syn conformation and the inversion center
generates the anti conformation from the half-molecule that sits
on this special position. No solvent molecules were present in
the structure and no disorder was detected. The largest residual

T.C. Johnstone, S.J. Lippard / Polyhedron 52 (2013) 565–575
569
electron density peak (1.29 e Åꢀ3) and hole (ꢀ0.80 e Åꢀ3) were lo-
cated 0.86 Å and 0.66 Å from Pt2 and I12, respectively (a complete
atom-labeling scheme is depicted in Fig. 1).
the input geometry following normalization of the C–H and N–H
bond lengths to 1.089 Å and 1.015 Å, respectively. This process
was carried out with the program Mercury to account for the
well-established fact that X-ray diffraction analysis underesti-
mates the length of bonds involving hydrogen atoms. A rigid sur-
face scan was carried out along the linear combination of
internal coordinates corresponding to rotation of one of the cyclo-
hexylamine ligands about the Pt–N bond. This scan was accom-
plished by simultaneously incrementing all the I–Pt–N–X
dihedral angles, where X represents each atom of one of the cyclo-
hexylamine ligands. That is, at each step of the rigid surface scan,
all I–Pt–N–X dihedral angles were increased by a fixed amount
(2°) and at each of these geometries a single point energy calcula-
tion was carried out. The maximum along this scan was used as an
initial guess at the transition state in subsequent DFT calculations.
The coordinates of this maximum are tabulated in the Supplemen-
tary data. As a practical note, we mention here that due to the ini-
tialization procedure of GAUSSIAN 03, despite the fact that MM
calculations do not employ basis sets, basis sets need to be defined
for all atoms in the calculation. The default basis set that is used by
GAUSSIAN 03, should no basis set be indicated in the input file, is
undefined for Pt and causes the calculation to fail. We have circum-
vented this difficulty by placing a dummy atom, for which the de-
fault basis set is defined, at the position of the platinum and
parameterizing it with the UFF parameters for platinum. We have
verified that the element chosen for the dummy atom does not af-
fect the outcome of the calculations as long as it is correctly param-
eterized as a Pt. We chose to use Pd so that the graphics generated
have a coloring scheme similar to that expected for Pt.
2.12. Variable temperature (VT) NMR
To interrogate the potential dynamic conversion between the
syn and anti conformers of 6, the NMR spectrum of this compound
was acquired at low temperature. In DMF-d7, the solution could be
cooled to ꢀ55 °C, before reaching the solvent freezing point. At this
temperature, no de-coalescence was observed. Dichlorofluorome-
thane (DCFM, prepared as described in [27]), a solvent that can
be super-cooled to ꢀ150 °C, was used to access lower tempera-
tures. Solutions of 6 in DCFM-d were cooled to ꢀ113 °C, but still
no de-coalescence was observed. There was, however, a systematic
change in the chemical shift of the signal arising from the amine
protons over the range 0 °C to ꢀ113 °C, which allowed for the
determination of the thermodynamic parameters describing the
isomerization. The NMR spectrum in DMF-d7 was also recorded
at temperatures as high as 60 °C with no significant observed
change in the lineshapes of the resonances. At each temperature,
the sample was allowed to equilibrate for an additional 2 min fol-
lowing a stable thermostat reading, re-locked, shimmed, and then
analyzed.
2.13. CPK models
Physical models of compounds 2, 4, and 6 were constructed
using standard CPK plastic models in which the radius of the plas-
tic sphere is proportional to the van der Waals radius of a given
atom [28,29]. A generic ‘‘metal’’ sphere was used for the central
platinum atom.
2.15. Density functional theory (DFT) calculations
DFT calculations were also carried out using GAUSSIAN 03. The
geometries of the syn and anti conformations of 6 were optimized
in the gas phase using the hybrid functional PBE0 [32], Ahlrichs’
TZVP basis set for C, H, and N, and the LANL2DZ effective core
potentials for I and Pt [33,34]. The atomic coordinates of the
respective conformers from the X-ray structure of 6 were used as
input for the geometry optimizations. Frequency calculations were
performed to confirm that the converged structures were local
minima on the potential energy surface (PES) and to provide
zero-point energy (ZPE) corrections. A transition state search was
performed using the quadratic synchronous transit-guided quasi-
Newton (STQN) method, which uses as input the coordinates of
the initial and final states of the isomerization and an initial guess
for the transition state [35,36]. The optimized geometries of the
anti and syn conformations were used as the start and end struc-
tures, respectively, and the coordinates from the maximum of
the MM rigid surface scan were used as the initial guess for the
transition state. The search converged on a transition state that ap-
peared reasonable in that it corresponded qualitatively with that
predicted by the physical CPK models and the MM calculations. A
frequency calculation was carried out to confirm that the structure
corresponds to a first order saddle point on the PES and to provide
a ZPE correction to the total energy. Results were visualized with
GAUSSVIEW. The coordinates of the DFT optimized structures of the
anti and syn conformations as well as the transition state are tab-
ulated in the Supplementary data.
2.14. Molecular mechanics (MM) calculations
MM calculations were performed on GAUSSIAN 03 [30] using the
universal force field (UFF) and the corresponding UFF parameters
for all atoms [31]. The atomic coordinates of 6 in the anti confor-
mation, as determined by X-ray crystallography, were used as
3. Results and discussion
3.1. Crystallization of 6
One route to the platinum(IV) prodrug satraplatin involves
the preparation of an iodo-bridged platinum(II) dimer,
Fig. 1. The syn and anti conformers of 6 as present in the crystal structure.
Ellipsoids are drawn at the 50% probability level.

570
T.C. Johnstone, S.J. Lippard / Polyhedron 52 (2013) 565–575
[Pt(NH2C6H11)I(
l
-I)]2. Cleavage of the iodo bridges affords the
coalescence was observed in the 1H, 13C, or 195Pt NMR spectra re-
corded at temperatures (ꢀ55 °C) just above the freezing point of
DMF, nor when a DCFM-d solution of 6 was cooled to ꢀ113 °C.
Over the course of cooling the solution, a systematic trend in the
chemical shift of the amine protons was observed, however, as de-
picted in Fig. 2.
mixed cis-(cyclohexylamine)(ammine)platinum(II) core present in
satraplatin [37]. While attempting to crystallographically deter-
mine the structure of the iodo-bridged dimer, yellow needles were
obtained from a DMF solution. X-ray diffraction analysis revealed
these crystals to be composed of trans-[Pt(NH2C6H11 2 2
) I ] (6). As
described in Section 2.11.6 and depicted in Fig. 1, within the crystal
lattice, 6 is present in both syn and anti conformations. The
presence of both conformers in the solid state structure might
indicate that a high barrier to rotation is present, resulting in stable
isomeric species that simply happen to co-crystallize. Alterna-
tively, a lower barrier could be present, with the crystallization
process trapping out the two dynamically interconverting isomers.
A plot of the chemical shift of the amine peak versus tempera-
ture reveals a sigmoidal relationship (Fig. 3). This behavior reflects
the change in equilibrium distribution of the syn and anti species
with changing temperature. The exchange is occurring on the
sub-millisecond time scale as evidenced by the single, averaged
signal that results. This signal represents the weighted average of
signals arising from the two isomers. The observed chemical shift
is related to the ratio of the two isomers by Eq. (1):
3.2. Preparation of 6
K
eqdanti þ dsyn
1 þ Keq
d ¼
ð1Þ
The possibility that compound 6 might exist as two stable con-
formers prompted the independent synthesis of this molecule.
Simple diam(m)nedihaloplatinum(II) species such as 6 are among
the oldest known coordination compounds, and the existence of
both cis and trans geometric isomers was used by Werner as evi-
dence to support his coordination theory [38]. The classical prepa-
ration of the trans isomer, initially known as Jørgensen’s reaction,
involves treatment of the tetraam(m)ineplatinum(II) cation with
hydrohalic acid or heating the halide salt of the cation [39]. This
reactivity was initially viewed as standing in contrast to Peyrone’s
reaction, in which the cis isomer can be prepared by treatment of
the tetrahaloplatinate(II) anion with ammonia/amine [40]. It was
not until the work of Chernyaev on the trans effect that these
two reactions were understood to be different manifestations of
the same basic principle [41,42]. Compound 6 was prepared by
treatment of 1, itself readily prepared by refluxing K2PtCl4 with
cyclohexylamine [43], with aqueous hydriodic acid (Scheme 2).
The desired product can be obtained but the reaction proceeds
sluggishly. Moreover, the endpoint is difficult to ascertain because,
at the start of the reaction, the material is a white suspension and
at the end of the reaction the product is a suspension of yellow so-
lid. Furthermore, compound 1 does not readily dissolve in aqueous
solutions, most likely due to the hydrophobicity of the cyclohexyl-
amine ligands, which hampers smooth progression of the reaction.
By substituting the known dependence of the equilibrium constant
on the standard free energy of reaction and the dependence of this
parameter in turn on the standard enthalpy and entropy of reaction,
we arrive at Eq. (2). This expression assumes that there is no tem-
perature dependence of the chemical shifts of the NH resonances
for both presumed conformers.
T
D
Sꢂꢀ
D
Hꢂ
expð
Þdanti þ dsyn
RT
RT
d ¼
ð2Þ
T
D
Sꢂꢀ
D
Hꢂ
1 þ expð
Þ
A least-squares fit of the data to this equation (Fig. 3) pro-
vides values of danti = 3.605 ppm, dsyn = 3.330 ppm, H° = 30.127
kJ molꢀ1, and S° = 139.6 J molꢀ1 Kꢀ1. The assignment of the anti
D
D
conformer to the limiting signal at 3.605 ppm and the syn
conformer to the signal at 3.330 ppm is based on the computa-
tional data – and chemical intuition – that suggest the anti
conformation to be slightly lower in energy than the syn. These
parameters can be used to calculate the standard Gibbs free
energy of isomerization,
in Section 3.4, DFT calculations provide an estimate of
D
G°298.15 = ꢀ11.5 kJ molꢀ1. As described
DG°298.15 =
ꢀ2.01 kJ molꢀ1. Although the calculated value is only 18% of the
experimentally determined one, the absolute difference between
the two is <10 kJ molꢀ1
.
To rule out the possibility that the shift in the amine proton res-
onance arises from some sort of aggregation phenomenon, the VT
NMR study was conducted at a series of different concentrations.
Over the range of 3.3–10 mM, no deviation in the chemical shifts
of the signals was observed. Representative spectra at different
concentrations and temperatures are reported in the Supplemen-
tary data. The lack of a concentration dependence indicates that
the process being observed is most likely not an aggregation phe-
nomenon. Although the computational results presented here sup-
port the assignment of the signal shift as arising from changes in
the syn–anti equilibrium, we cannot definitively rule out the pos-
sibility that some other process might be causing the observed
NMR phenomenon.
3.3. VT NMR spectral study of 6
Multinuclear (1H, 13C, and 195Pt) NMR spectroscopic character-
ization of the reaction product showed no evidence for the pres-
ence of two distinct conformers of 6, a result consistent with
earlier characterization data for this compound [43]. The possibil-
ity remained, however, that the two conformers might be dynam-
ically interconverting in solution. Variable temperature NMR
studies were carried out to investigate this possibility but no de-
The failure of the two resonances to separate, even at tempera-
tures as low as ꢀ113 °C, highlights the low barrier to interconver-
sion between these two species. The height of this barrier was
estimated in modeling studies described in the next section.
3.4. Modeling
3.4.1. Physical models
In order to probe the magnitude of the barrier to rotation and to
corroborate the thermodynamic parameters determined above,
modeling was carried out at various levels. The first step taken
was to build a physical model of the compound. Although rudi-
mentary and highly simplified, this construction process provides
Scheme 2. Preparation of 6 according to Jørgensen’s rule.

T.C. Johnstone, S.J. Lippard / Polyhedron 52 (2013) 565–575
571
Fig. 2. VT NMR of 6 in DCFM-d. The shift in the amine peak is highlighted with dashed lines. The signal between 2.9 and 3.1 ppm arises from the CH group directly attached to
the amine nitrogen. All other signals arise from cyclohexyl ring protons or solvent as indicated in the Supplementary data (Fig. S1).
is more readily photographed. Models were built with bromide and
iodide ligands as well and similar qualitative conclusions can be
drawn. Manual rotation about the Pt–N bond results in a steric
clash between a ring C–H group and the halide ligand, as high-
lighted in the middle of Fig. 4. Starting from the anti conformation,
manual forcing across this barrier provides access to the syn
conformation.
3.4.2. Molecular mechanics
Given that the bond between the Pt and the N is a simple
r
-type dative coordinate bond, a significant electronic barrier to
rotation is not expected. Moreover, the CPK models suggested that
direct steric interactions between the cyclohexyl ring and the
halide ligand provide the kinetic barrier to isomerization. These
facts suggest that a purely mechanical model of the rotation may
provide meaningful insight into the process. Molecular mechanics
(MM) calculations can provide such information. In fact, one of the
first uses of MM was to study the hindered internal rotation of
biphenyls [45,46]. MM calculations are also computationally inex-
pensive, allowing for a relatively large number of geometries to be
probed at low cost. The universal force field (UFF) was employed
because it has been parameterized for all elements of the periodic
table. Although more exact results could be obtained by explicitly
parameterizing the force field for the molecule under investigation,
the goal of the MM calculations here is only to provide a qualitative
description of the rotation process and to gain insight into a poten-
tial transition state for the isomerization. Higher level calculations
have been used to provide an estimate into the magnitude of the
rotational barrier.
Fig. 3. Plot of amine chemical shift against temperature. The theoretical curve was
fit according to Eq. (2) with danti = 3.605 ppm, dsyn = 3.330 ppm,
H° = 30.127 kJ molꢀ1, and S° = 139.6 J molꢀ1 Kꢀ1
D
D
.
a very real and tactile sense of the relative dimensions within the
molecule that is not as readily conveyed in computer simulations.
Indeed, there is no substitute to ‘‘running one’s hands over a
molecular model and experiencing the visual–tactile link that is
so important for establishing three-dimensionality in our minds
[44].’’ In Fig. 4 is shown a photo of the CPK model of 2. This chlo-
ride-containing complex was chosen for illustration because the
smaller halide ligand shows the steric hindrance in a manner that
The results of a rigid surface scan are presented in Fig. 5. As the
cyclohexylamine group is rotated about the Pt–N bond, the energy
rises. In contrast to ab initio calculations, which calculate energies
with respect to the energies of the constituent nuclei and electrons
at infinite separation, the energies calculated in MM are reported

572
T.C. Johnstone, S.J. Lippard / Polyhedron 52 (2013) 565–575
Fig. 4. CPK models of the anti (left) and syn (right) conformers of 2 with corresponding line diagrams below. Manual rotation from one conformer to the other causes a clash
between a ring hydrogen atom and the halide ligand, as shown in the middle.
Given the size and flexibility of the molecule under investiga-
tion, it is possible that errors in the computed thermochemical
parameters may arise from incorrect partitioning of internal rota-
tions as vibrations in the gas phase statistical mechanical calcula-
tions [47]. Indeed, the output from the GAUSSIAN 03 calculations
contains a warning indicating that some of the low energy vibra-
tions modeled as harmonic oscillations may instead correspond
to internal rotations. Although it can be difficult to correct the par-
tition functions without a suitable expression for the variation in
energy along the coordinate of the internal rotation [48], if a calcu-
lated vibrational mode were indeed a hindered internal rotation,
then there exists a relationship (Eq. (3)) between the height of
the rotational barrier and the harmonic oscillator frequency (
m),
the periodicity of the rotation (
r), and the reduced rotational mo-
ment of inertia (Ir) [49].
8p
2m2lr
Fig. 5. MM rigid surface scan about the Pt–N bond. Structures are shown of the anti
(left) and syn (right) conformers as well as the maximum along the PES (middle).
The red ellipse highlights the steric interaction between the H and I atoms. (Color
online.)
V0
¼
ð3Þ
r2
The lowest energy vibrations calculated for both the syn and
anti conformations correspond to rotation about the Pt–N bond.
The barrier to that internal rotation is therefore the barrier to the
rotation in which we are interested. The details of the determina-
with respect to a hypothetically unstrained molecule. The geome-
try of the maximum along this PES scan occurs, much as one might
expect, when the ligand is halfway through the rotation. Specifi-
cally, we can see that a cyclohexyl hydrogen, highlighted with a
red ellipse in Fig. 5, has been brought in close proximity to a halide
ligand, as was seen with the CPK models (Fig. 4).
tion of Ir, m, and the barrier height are presented in the Supplemen-
tary data. The rotational barrier estimated in this manner is
24.0 kJ molꢀ1, a value that compares favorably with one deter-
mined as the difference between the ZPE corrected energies of
the ground and transition states, determined below
(25.6 kJ molꢀ1). This correspondence indicates that, although inter-
nal rotations may have been incorrectly partitioned as harmonic
oscillator vibrations, the error introduced appears to be small.
A transition state search was carried out and the optimized
geometry of the transition state corresponds to an intuitively rea-
sonable structure with one cyclohexyl ring positioned over a halide
ligand. The frequency calculation revealed that there is only one
vibration with an imaginary frequency, confirming that the struc-
ture is located on a first order saddle point on the PES. Importantly,
this vibration corresponds to an internal rotation about the Pt–N
bond, which is in agreement with the expectation that the reaction
coordinate that passes through the transition state should be the
rotation of the cyclohexylamine ligand. The difference in ZPE cor-
rected Gibbs free energies of the anti conformer and the transition
state was found to be 25.6 kJ molꢀ1. The difference in energy
3.4.3. DFT studies
DFT calculations were carried out to more accurately estimate
the energies of the isomers and the magnitude of the barrier to
their interconversion. The geometries of syn and anti conformers
were optimized in the gas phase and found to agree well with
those from the crystal structure. The absence of vibrations with
imaginary frequencies indicates that there are no negative ele-
ments in the respective Hessians of the two structures and con-
firms that they are mimina on their respective PESs. The ZPE
corrected difference in free energy between the anti and syn con-
formers was found to be ꢀ2.01 kJ molꢀ1, with the anti being more
stable. As described in Section 3.3, this result supports the assign-
ment of the different conformers to their respective chemical
shifts.

T.C. Johnstone, S.J. Lippard / Polyhedron 52 (2013) 565–575
573
between these species is depicted in Fig. 6, along with a molecular
3.6. Characterization of 2, 4, and 6
diagram of the transition state. The arrows in the diagram of the
transition state represent the vibrational motion of the individual
atoms along the vibrational mode calculated to have an imaginary
frequency. In Fig. 6, it can be appreciated that the general form of
this vibration is an internal rotation of one of the cyclohexylamine
ligands about the Pt–N bond. That is, the vibrational vectors lay
tangent to circles described by the rotation of the ligand. The cal-
culated rotational barrier approaches the limit of processes that
can be detected by dynamic NMR spectroscopy. Using the chemical
shifts determined in Section 3.3 as those of the isomers, a rough
calculation [50], the details of which are provided in the Supple-
mentary data, reveals that de-coalescence is only expected to occur
at temperatures below ꢀ150 °C. This result explains why no split-
ting of the resonances was observed in the VT NMR experiments.
These three compounds display spectroscopic properties con-
sistent with their formulations as well as the trends expected by
systematic alteration of the halide. For instance, the 195Pt NMR
chemical shifts of compounds 2, 4, and 6 are ꢀ2214, ꢀ2584, and
ꢀ3331 ppm, respectively. This progression is consistent with the
greater degree of covalent character expected in the Pt–X bond
as we move down the halogens, owing to the decrease in halide
hardness, particularly in light of the soft [52], or class b [53], char-
acter of Pt(II). This trend also parallels that expected from the var-
iation in electronegativity as we move up the halogen family. As
the elements become more electronegative, they donate less elec-
tron density to the metal center and shift the 195Pt NMR signal
downfield. The lack of a significant effect of the halide on the 1H
NMR chemical shifts of the amine protons is consistent with the
trans geometry of these compounds. The IR data are consistent
with the presence of amine groups and aliphatic C–C and C–H
groups [43], but the diagnostic bands arising from Pt–X (X = halide)
vibrations occur at energies lower than we could probe experimen-
tally in this study.
Crystal structures were previously reported for compounds 2
and 4 [24,25]. We collected a new data set for an identical poly-
morph of 4 at low temperature and obtained a higher resolution
structure. The structure of 2 reported here is a solvate [54] of the
previously reported structure and again the newly collected low
temperature data set refined to a generate a more accurate struc-
ture than previously reported. In both structures, the bond lengths
and angles are as would be expected for square-planar platinum(II)
complexes. In both instances, the platinum complex sits on an
inversion center in the crystal lattice and necessarily assumes the
anti conformation (Fig. 7). The interatomic distances and angles
of the newly reported structure of 6 are also as expected, but in this
structure the complex has crystallized in both the syn and anti
conformers. In all three complexes, including both conformations
of 6, the amine groups ligated to the platinum centers are at equa-
torial positions on the cyclohexane rings. This conformation is ex-
pected, given the lesser degree of steric hindrance experienced by
substituents at these positions. As opposed to rotation about the
Pt–N bond, which the dynamic NMR experiments reported here
have indicated is a rather facile and rapid process, flipping of the
cyclohexane ring is expected to be unfavorable with such a bulky
substituent. The NMR spectra indicate that the axial and equatorial
protons do not exchange, even upon heating to 60 °C.
3.5. Further reactivity of 1
In the process of characterizing compound 1, it was observed
that heating the colorless solid in DMF caused it to dissolve, afford-
ing a bright yellow solution. The color change indicated the occur-
rence of a reaction, and mass spectrometric analysis of the solution
showed it to contain the [Pt(NH2C6H11)3Cl]+ cation. Moreover,
when the solution was allowed to stand at room temperature over-
night, yellow prisms formed. Single crystal X-ray diffraction analy-
sis of these prisms showed them to contain compound 2. This
small-scale experiment indicated that, on heating, the outer sphere
chloride ligands exchange with the inner sphere cyclohexylamine
ligands. This reactivity parallels some of the earliest reactions car-
ried out by Werner and Jørgensen as they developed systematic
series of compounds in support of their respective theories on
the structures of transition metal complexes [5].
We verified that the conversion of 1 to 2 in this manner can oc-
cur on a bulk scale as had previously been reported for the conver-
sion of 5 to 6 under different reaction conditions [43,51]. Moreover,
we found that the method here is generalizable to the bromide and
iodide salts of [Pt(NH2C6H11)4]2+, compounds 3 and 5, respectively,
affording compounds 4 and 6. Complexes 2, 4, and 6 are readily
purified by recrystallization from hot CH2Cl2/hexanes. The com-
pounds become increasing soluble in CH2Cl2 as we proceed from
2 to 6, undoubtedly due to the increase in polarizability of the ha-
lide ligand.
3.7. Characterization of 1, 3, and 5
The tetraammineplatinum(II) halide salts 1, 3, and 5 are all
readily prepared by reaction of the corresponding tetrahaloplati-
nates (prepared in situ) with cyclohexylamine. Only the iodide salt
5 could be spectroscopically studied because it could be dissolved
without chemical modification. The chloro and bromo complexes
require heating to dissolve in DMF, a process that invariably results
in partial decomposition to form species in which coordinated
cyclohexylamine ligands are replaced by halide ions. These species
are evidenced by coloration of the solution and are detected by ESI-
MS. In the gas phase, the complex cation appears to degrade read-
ily, even under the relatively gentle ESI conditions, as indicated by
the appearance of [NH3C6H11]+, [Mꢀ(NH2C6H11)2ꢀH]+, and
[Mꢀ(NH2C6H11)+X]+ signals in ESI-MS measurements of 1, 3, and
5. The conversion from 1, 3, and 5 to 2, 4, and 6, respectively,
may be facilitated by the bulkiness of the ligands, which serves
to destabilize the tetraamineplatinum(II) cation.
Fig. 6. Energy level diagram from gas phase DFT calculations. The molecular
diagram depicts the calculated transition state and the vectors represent the single
vibrational mode (rotation about the Pt–N bond) calculated to have an imaginary
frequency.
The crystal structures of 1, 3, and 5 show the cation to have
bond distances and angles as expected for a Pt(II) complex. An
interesting aspect of all of these structures is that, as we proceed

574
T.C. Johnstone, S.J. Lippard / Polyhedron 52 (2013) 565–575
Fig. 7. Molecular diagrams of 2 (left) and 4 (right). Ellipsoids are drawn at the 50% probability level.
about the platinum center, the rings of the cyclohexylamine li-
gands are oriented up–up–down–down as opposed to the less ste-
rically encumbering up–down–up–down conformation (Fig. 8).
There appears to be no significant drive to favor one conformation
over the other apart from steric repulsion, and so this particular
arrangement of the ligands is most likely induced by crystal pack-
ing forces. The lattice is held together by hydrogen bonds between
the amine hydrogen atoms and the halide counterions as well as
close contacts between the cyclohexyl rings.
the attention and imagination of experienced and neophyte inor-
ganic chemists alike, and work in this field is still vibrant today.
Here we have reported an investigation into the dynamic confor-
mational isomerization of trans-[Pt(NH2C6H11 2 2
) I ], spurred by a
chance crystallographic finding. The inability to spectroscopically
observe the two distinct isomers under the conditions employed
has been rationalized through the use of physical models and com-
putational chemistry. These computational models were also used
to evaluate the validity of the thermodynamic parameters of the
isomerization that were extracted from the VT NMR data.
While exploring this isomerism, the thermal instability of
[Pt(NH2C6H11)4]X2 (X = Cl, Br, I) was observed and exploited in the
preparation of the corresponding series trans-[Pt(NH2C6H11)2X2].
This chemistry was found to parallel some of the earliest reactions
used to prepare compounds to support the development of
Werner’s coordination theory.
4. Conclusion
A century has passed since Alfred Werner was awarded the No-
bel Prize for his foundation of coordination theory and the field
may in some ways be considered a mature branch of inorganic
chemistry. The powerful notions of structure and symmetry
embodied in coordination chemistry, however, continue to capture
Acknowledgments
This work was supported by Grant CA034992 from the National
Cancer Institute. Spectroscopic instrumentation at the MIT DCIF is
maintained with funding from NIH Grant 1S10RR13886-01. T.C.J.
has received partial funding from the Harvard/MIT CCNE, NIH
Grant 5-U54-CA151884. Justin J. Wilson is gratefully acknowl-
edged for helpful discussions and for assistance with the prepara-
tion of the manuscript.
Appendix A. Supplementary data
CCDC 882679–882684 contain the supplementary crystallo-
graphic data for 1–6, respectively. These data can be obtained free
of charge via http://www.ccdc.cam.ac.uk/conts/retrieving.html, or
from the Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: (+44) 1223-336-033; or e-mail: de-
posit@ccdc.cam.ac.uk. Supplementary data associated with this
article can be found, in the online version, at http://dx.doi.org/
10.1016/j.poly.2012.08.010.
References
[1] G.B. Kauffman, Alfred Werner Founder of Coordination Chemistry, Springer-
Verlag, Berlin, New York, 1966.
[2] Nobelstiftelsen, Chemistry, Published for the Nobel Foundation by Elsevier
Pub. Co., Amsterdam, New York, 1964.
Fig. 8. Thermal ellipsoid plot of the complex cation of 1. Ellipsoids are drawn at the
50% probability level.

T.C. Johnstone, S.J. Lippard / Polyhedron 52 (2013) 565–575
575
[3] A. Hantzsch, A. Werner, Ber. Dtsch. Chem. Ges. 23 (1890) 11.
[4] G.B. Kauffman, J. Chem. Educ. 43 (1966) 155.
[5] G.B. Kauffman, Classics in Coordination Chemistry. Part 1: The Selected Papers
of Alfred Werner, Dover Publications, New York, 1968.
[6] S. Esteban, J. Chem. Educ. 85 (2008) 1201.
[7] J.J. Berzelius, Ann. Chim. Phys. 46 (1831) 113.
[8] G.P. Moss, Pure Appl. Chem. 68 (1996) 2193.
[9] G.B. Kauffman, Coord. Chem. Rev. 11 (1973) 161.
[10] K.S. Pitzer, J. Chem. Phys. 5 (1937) 469.
[11] T.E. MacDermott, S. Barfoed, Acta Chem. Scand. 24 (1970) 924.
[12] K.G. Jensen, H. Soling, N. Thorup, Acta Chem. Scand. 24 (1970) 908.
[13] A. Werner, A. Grün, Ber. Dtsch. Chem. Ges. 38 (1905) 4033.
[14] S.M. Jørgensen, Z. Anorg. Chem. 19 (1899) 78.
Yazyev, A.J. Austin, R. Cammi, C. Pomelli, J.W. Ochterski, P.Y. Ayala, K.
Morokuma, G.A. Voth, P. Salvador, J.J. Dannenberg, V.G. Zakrzewski, S.
Dapprich, A.D. Daniels, M.C. Strain, O. Farkas, D.K. Malick, A.D. Rabuck, K.
Raghavachari, J.B. Foresman, J.V. Ortiz, Q. Cui, A.G. Baboul, S. Clifford, J.
Cioslowski, B.B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I. Komaromi, R.L.
Martin, D.J. Fox, T. Keith, M.A. Al-Laham, C.Y. Peng, A. Nanayakkara, M.
Challacombe, P.M.W. Gill, B. Johnson, W. Chen, M.W. Wong, C. Gonzalez, J.A.
Pople, Gaussian 03, Revision B.02, Gaussian, Inc., Pittsburgh, PA, 2003.
[31] A.K. Rappe, C.J. Casewit, K.S. Colwell, W.A. Goddard, W.M. Skiff, J. Am. Chem.
Soc. 114 (1992) 10024.
[32] C. Adamo, V. Barone, J. Chem. Phys. 110 (1999) 6158.
[33] P.J. Hay, W.R. Wadt, J. Chem. Phys. 82 (1985) 270.
[34] P.J. Hay, W.R. Wadt, J. Chem. Phys. 82 (1985) 299.
[15] L.R. Kelland, G. Abel, M.J. McKeage, M. Jones, P.M. Goddard, M. Valenti, B.A.
Murrer, K.R. Harrap, Cancer Res. 53 (1993) 2581.
[16] APEX2, 2008-4.0, Bruker AXS, Inc., Madison, WI, 2008.
[17] SAINT, SAX Area-Detector Integration Program, 2008/1, University of Göttingen,
Göttingen, Germany, 2008.
[35] C.Y. Peng, H.B. Schlegel, Isr. J. Chem. 33 (1993) 449.
[36] C.Y. Peng, P.Y. Ayala, H.B. Schlegel, M.J. Frisch, J. Comput. Chem. 17 (1996) 49.
[37] A.R. Khokhar, Y.J. Deng, S. Albaker, M. Yoshida, Z.H. Siddik, J. Inorg. Biochem. 51
(1993) 677.
[38] A. Werner, Z. Anorg. Chem. 3 (1893) 267.
[18] G.M. Sheldrick, SADABS: Area-Detector Absorption Correction, University of
Gottingen, Gottingen, Germany, 2008.
[39] S.M. Jørgensen, J. Prakt. Chem. 33 (1886) 489.
[40] M. Peyrone, Liebigs Ann. 51 (1844) 1.
[19] XPREP, 2008/2, Bruker AXS, Madison, WI, 2008.
[41] I.I. Chernyaev, Ann. Inst. Platine (USSR) 4 (1926) 243.
[42] G.B. Kauffman, J. Chem. Educ. 54 (1977) 86.
[20] G.M. Sheldrick, SHELXTL-97, University of Göttingen, Göttingen, Germany, 2000.
[21] G.M. Sheldrick, Acta Crystallogr., Sect. A 64 (2008) 112.
[22] P. Müller, Crystallogr. Rev. 15 (2009) 57.
[23] A.L. Spek, PLATON, A Multipurpose Crystallographic Tool, Utrecht University,
Utrecht, The Netherlands, 2008.
[43] F.D. Rochon, V. Buculei, Inorg. Chim. Acta 358 (2005) 2040.
[44] R. Hoffmann, Personal communication to E.G. Lewars in 2009. Recorded in
Computational Chemistry, Chapter 5: Ab Initio Calculations, p. 365.
[45] F.H. Westheimer, J.E. Mayer, J. Chem. Phys. 14 (1946) 733.
[46] T.L. Hill, J. Chem. Phys. 14 (1946) 465.
[47] R.B. McClurg, R.C. Flagan, W.A. Goddard, J. Chem. Phys. 106 (1997) 6675.
[48] D.G. Truhlar, J. Comput. Chem. 12 (1991) 266.
[49] P.Y. Ayala, H.B. Schlegel, J. Chem. Phys. 108 (1998) 2314.
[50] L.M. Jackman, F.A. Cotton, R.D. Adams, Dynamic Nuclear Magnetic Resonance
Spectroscopy, Academic Press, New York, 1975.
[51] J.P. Souchard, F.L. Wimmer, T.T.B. Ha, N.P. Johnson, J. Chem. Soc., Dalton Trans.
(1990) 307.
[52] R.G. Pearson, J. Am. Chem. Soc. 85 (1963) 3533.
[53] S. Ahrland, J. Chatt, N.R. Davies, Q. Rev. Chem. Soc. 12 (1958) 265.
[54] J. Bernstein, Polymorphism in Molecular Crystals, Clarendon Press, Oxford,
2002.
[24] G. Zanotti, A. Delpra, G. Bombieri, A.M. Tamburro, Acta Crystallogr., Sect. B 34
(1978) 2138.
[25] C.J.L. Lock, M. Zvagulis, Acta Crystallogr., Sect. B 36 (1980) 2140.
[26] F.D. Rochon, P.C. Kong, Can. J. Chem. 64 (1986) 1894.
[27] J.S. Siegel, F.A.L. Anet, J. Org. Chem. 53 (1988) 2629.
[28] R.B. Corey, L. Pauling, Rev. Sci. Instrum. 24 (1953) 621.
[29] W.L. Koltun, Biopolymers 3 (1965) 665.
[30] M.J. Frisch, G.W. Trucks, H.B. Schlegel, G.E. Scuseria, M.A. Robb, J.R. Cheeseman,
J.A. Montgomery Jr., T. Vreven, K.N. Kudin, J.C. Burant, J.M. Millam, S.S. Iyengar,
J. Tomasi, V. Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G.A.
Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R. Fukuda, J. Hasegawa,
M. Ishida, T. Nakajima, Y. Honda, O. Kitao, H. Nakai, M. Klene, X. Li, J.E. Knox,
H.P. Hratchian, J.B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R.E. Stratmann, O.