Design and controlled emission properties of bioorganometallic compounds composed of uracils and organoplatinum(ii) moieties

Article abstract of DOI:10.1039/c2dt30533j

The bioorganometallic platinum(ii) compounds PtU6 and PtU5 were designed by the conjugation of the corresponding uracil derivative and the organoplatinum(ii) compound [4-octyloxy-(C^N^N)PtCl]. The single crystal X-ray structure determination of PtU6 revealed the formation of the dimeric structure through intermolecular hydrogen bonds between the uracil moieties of two independent molecules, wherein each hydrogen-bonded dimer was connected through Pt(ii)-Pt(ii) and π-π interactions. The tuning of the emission properties of the organoplatinum(ii) compounds was achieved by changing the direction of hydrogen bonding sites and the molecular scaffold having two 2,6-dihexamidopyridine moieties as a complementary hydrogen bonding site for the uracil moiety, which depends on the regulation of the aggregated structures, to induce the Pt(ii)-Pt(ii) and π-π interactions.

Full text of DOI:10.1039/c2dt30533j

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Dalton
Transactions
An international journal of inorganic chemistry
www.rsc.org/dalton
Volume 41 | Number 28 | 28 July 2012 | Pages 8479–8730
ISSN 1477-9226
COVER ARTICLE
Moriuchi, Hirao et al.
Design and controlled emission properties of bioorganometallic compounds
composed of uracils and organoplatinum(II) moieties

Dynamic ArtVicielweALritnicklesOnline
Dalton
Transactions
Cite this: Dalton Trans., 2012, 41, 8524
www.rsc.org/dalton
PAPER
Design and controlled emission properties of bioorganometallic compounds
composed of uracils and organoplatinum(II) moieties†
Toshiyuki Moriuchi,*a Yuki Sakamoto,a Shunichi Noguchi,a Takashi Fujiwara,a Shigehisa Akine,b
Tatsuya Nabeshimab and Toshikazu Hirao*a
Received 6th March 2012, Accepted 2nd May 2012
DOI: 10.1039/c2dt30533j
The bioorganometallic platinum(II) compounds PtU6 and PtU5 were designed by the conjugation of
the corresponding uracil derivative and the organoplatinum(II) compound [4-octyloxy-(C^N^N)PtCl].
The single crystal X-ray structure determination of PtU6 revealed the formation of the dimeric structure
through intermolecular hydrogen bonds between the uracil moieties of two independent molecules,
wherein each hydrogen-bonded dimer was connected through Pt(II)–Pt(II) and π–π interactions. The
tuning of the emission properties of the organoplatinum(II) compounds was achieved by changing the
direction of hydrogen bonding sites and the molecular scaffold having two 2,6-dihexamidopyridine
moieties as a complementary hydrogen bonding site for the uracil moiety, which depends on the
regulation of the aggregated structures, to induce the Pt(II)–Pt(II) and π–π interactions.
The utilization of self-assembling properties of nucleobases in
bio-inspired systems offers the flexibility of exploiting four
Introduction
Highly-ordered molecular assemblies are constructed in bio-
systems to fulfill unique functions as observed in enzymes,
receptors, etc. The introduction of functional complexes into
highly-ordered biomolecules is considered to be a convenient
approach to design novel biomaterials and bio-inspired systems,
etc. Recently, the field of bioorganometallic chemistry has drawn
great attention and undergone rapid development.1 The conju-
gation of organometallic compounds with biomolecules such as
peptides and nucleobases is predicted to afford such bioconju-
gates. The architectural control of molecular self-organization is
of importance for the development of functional materials2 and
non-covalent bonding is a powerful tool in the construction of
architectural molecular assemblies. The regulation of hydrogen
bonding is a key factor in the design of various molecular assem-
blies by virtue of its directionality and specificity.3 The reversi-
bility and tunable nature of hydrogen bonding is also of
fundamental importance in the chemical and/or physical proper-
ties of molecular assemblies. The double helical DNA is created
by A–T and G–C base pairs, which are mainly controlled by
hydrogen bonds, π–π interactions, and hydrophobic effects.4
different binding motifs. A variety of metal-modified nucleo-
bases have been designed to demonstrate molecular architecture
through hydrogen bonds.5 On the other hand, square-planar d8
transition metal complexes possess intriguing photophysical and
photochemical properties. In particular, luminescent platinum(II)
complexes with oligopyridine and cyclometalating ligands have
attracted much attention because of their interesting lumine-
scence properties based on the metallophilic interaction through
2
dZ ⋯dZ2 and/or π–π interactions.6 A combination of nucleobases
with luminescent platinum(II) complexes has allowed the design
of novel bioconjugates. From these points of view, we herein
report the design of the bioorganometallic compounds composed
of uracils and organoplatinum(II) compounds and the controlled
emission properties based on the regulation of aggregation
(Fig. 1).
Results and discussion
The bioorganometallic platinum(II) compounds PtU6 and PtU5
were prepared by the reaction of [4-octyloxy-(C^N^N)PtCl] (2),
which was obtained from the reaction of 6-(4-octyloxyphenyl)-
2,2′-bipyridine (1) and K2PtCl4, with 6-ethynyl-1-octyluracil or
5-ethynyl-1-octyluracil, respectively (Scheme 1). Further struc-
tural information was obtained by single-crystal X-ray structure
determination (Table 1). The X-ray crystal structure of PtU6
revealed the formation of dimeric structure through intermole-
cular hydrogen bonds between the uracil moieties of two
independent molecules (Fig. 2a and Table 2). Selected bond
distances and angles of PtU6 are reported in Table 3. The
[4-octyloxy-(C^N^N)Pt] moiety is nearly parallel to the uracil
aDepartment of Applied Chemistry, Graduate School of Engineering,
Osaka University, Yamada-oka, Suita, Osaka 565-0871, Japan.
E-mail: moriuchi@chem.eng.osaka-u.ac.jp, hirao@chem.eng.osaka-u.ac.jp;
Fax: +81-6-6879-7415; Tel: +81-6-6879-7413
bFaculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1
Tennodai, Tsukuba, Ibaraki 305-8571, Japan.
E-mail: akine@chem.tsukuba.ac.jp, nabesima@chem.tsukuba.ac.jp;
Fax: +81-29-853-4507; Tel: +81-29-853-4507
†Electronic supplementary information (ESI) available: 1H NMR
spectra for Job’s plots. CCDC reference number 851423 for PtU6. For
ESI and crystallographic data in CIF or other electronic format see DOI:
10.1039/c2dt30533j
8524 | Dalton Trans., 2012, 41, 8524–8531
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moiety, probably due to the d,π-conjugation; the dihedral angles
between the least squares plane of the [4-octyloxy-(C^N^N)Pt]
and the uracil moieties are 19.8(3) and 14.8(3)°. Furthermore,
each hydrogen-bonded dimer was connected through π–π inter-
actions between the [4-octyloxy-(C^N^N)Pt] ligands as well as
the uracil moieties to form π-stacks in a crystal packing, wherein
Pt(II)–Pt(II) interaction (the intermolecular Pt–Pt distance is
ca. 3.3 Å) was observed, as shown in Fig. 2b. These π–π and
Pt(II)–Pt(II) interactions might require the orientation of the
[4-octyloxy-(C^N^N)Pt] moiety within
a limited range of
locations parallel to the uracil moiety. In fact, the platinum(II)
complex PtU6 exhibited an emission band around 720 nm,
derived from the triplet metal–metal-to-ligand charge transfer
(3MMLCT) excited state resulting from Pt(II)–Pt(II) and π–π inter-
actions in the solid state (Fig. 3). In contrast, the platinum(II)
complex PtU5, wherein the direction of hydrogen bonding sites
of the uracil moieties is different from PtU6, showed an emission
band based on the metal-to-ligand charge transfer (MLCT) and/
or ligand-to-ligand charge transfer (LLCT) transition. The syner-
gistic effects of emission properties are considered to depend on
the aggregation properties of the platinum(II) complexes.
Table 1 Crystallographic data for PtU6
PtU6
Formula
Formula weight
Crystal system
Space group
a, Å
b, Å
c, Å
C38.5H47N4O3Pt1Cl
844.36
Triclinic
ˉ
P1 (No. 2)
12.1080(4)
14.5494(5)
20.4353(7)
89.7533(9)
88.4541(9)
83.7668(9)
3577.4(2)
4
1.568
40.236
−150
0.71075
0.065
α, °
β, °
γ, °
V, Å3
Z
dcalcd, g cm-3
μ(Mo Kα), cm-1
T, °C
λ(Mo Kα), Å
a
R1
b
wR2
0.214
2 2
2 2 1/2
a R1 = ∑kFo| − |Fck/∑Fo|. b wR2 = [∑w(Fo2 − Fc ) /∑w(Fo ) ]
.
Fig. 1 Design of the bioorganometallic compounds composed of
uracils and organoplatinum(II) complexes, and molecular scaffolds.
Scheme 1 Synthesis of the bioorganometallic platinum(II) compounds PtU6 and PtU5.
This journal is © The Royal Society of Chemistry 2012 Dalton Trans., 2012, 41, 8524–8531 | 8525

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Table 3 Selected bond distances (Å) and angles (°) for PtU6
PtU6a
Bond distances (Å)
Pt(1)–N(1)
Pt(1)–N(2)
2.112(9)
1.983(8)
2.141(9)
1.985(8)
Pt(1)–C(16)
Pt(1)–C(25)
C(25)–C(26)
C(26)–C(27)
C(27)–C(30)
N(3)–C(27)
N(3)–C(28)
N(4)–C(28)
N(4)–C(29)
C(29)–C(30)
O(2)–C(28)
O(3)–C(29)
2.010(11)
1.949(9)
2.010(9)
1.931(9)
1.211(13)
1.437(13)
1.340(14)
1.390(13)
1.399(12)
1.358(13)
1.389(12)
1.433(12)
1.234(12)
1.234(12)
1.220(13)
1.419(13)
1.344(14)
1.394(13)
1.397(12)
1.373(13)
1.371(13)
1.409(13)
1.225(12)
1.259(12)
Bond angles (°)
N(1)–Pt(1)–N(2)
N(1)–Pt(1)–C(16)
N(1)–Pt(1)–C(25)
N(2)–Pt(1)–C(16)
N(2)–Pt(1)–C(25)
C(16)–Pt(1)–C(25)
C(27)–N(3)–C(28)
N(3)–C(28)–N(4)
C(28)–N(4)–C(29)
N(4)–C(29)–C(30)
77.8(4)
160.3(4)
101.2(4)
82.5(4)
176.3(4)
98.4(4)
121.0(8)
116.3(9)
125.9(8)
114.7(8)
79.1(4)
160.7(4)
99.8(4)
81.7(4)
178.8(4)
99.5(4)
122.1(8)
114.7(8)
126.7(8)
114.8(9)
Fig. 2 (a) A hydrogen-bonded dimer through intermolecular hydrogen
bonds between the uracil moieties and (b) a portion of a layer containing
the π-stacked molecular assembly through π–π interactions between the
[4-octyloxy-(C^N^N)Pt] ligands as well as uracil moieties in a crystal
packing of PtU6.
a Two independent molecules exist in the asymmetric unit.
Table 2 Intermolecular hydrogen bonds for PtU6a
Donor
Acceptor
D⋯A (Å)
D–H⋯A (°)
N(4)
O(23)b
O(3)
2.787(10)
2.819(10)
2.819(10)
2.787(10)
175(5)
170(4)
170(4)
175(5)
N(24)b
N(24)
N(4)b
O(3)b
O(23)
a Two independent molecules exist in the asymmetric unit. b −X + 2, −Y,
−Z + 1.
Fig. 3 Emission spectra (λex = 470 nm) of PtU6 and PtU5 in the solid
state at 298 K.
To control the aggregate of the organoplatinum(II) complexes
with uracil moieties, molecular scaffolds ND and AD composed
of the aromatic rigid naphthalene and anthracene frameworks
with two 2,6-dihexamidopyridine moieties as a complementary
hydrogen bonding site for the uracil moiety were designed and
synthesized according to the synthetic routes shown in
Scheme 2.7 The molecular scaffold ND was prepared by the
coupling reaction of 1,8-diiodonaphthalene and 2,6-dihexamido-
4-ethynylpyridine (7) using the palladium-catalyzed Sonogashira
coupling procedure in 40% yield. The coupling reaction of 1,8-
diethynylanthracene and 4-(2,6-dihexamidopyridyl) trifluoro-
methanesulfonate (5) led to the formation of the molecular scaf-
fold AD in 28% yield. The appearance of a new shoulder band
at around 500 nm was observed after the addition of 0.5 molar
equiv. amount of ND to a dichloromethane solution of PtU6 in
the UV-vis spectrum, as shown in Fig. 4a. The absorption at
around 500 nm is probably assignable to the MMLCT transition
based on the ND-induced aggregation of PtU6 through comp-
lementary hydrogen bonding. Only PtU6 in dichloromethane
showed an emission band at 590 nm, which is ascribed to a
3MLCT and/or 3LLCT emission (Fig. 4b). Interestingly, PtU6
exhibited a new emission band based on a synergistic effect
around 730 nm with
a concomitant decrease of the
3MLCT–3LLCT emission in the presence of the molecular scaf-
fold ND (Fig. 4b). This emission band is assignable to a
3MMLCT emission based on Pt(II)–Pt(II) and π–π interactions
between the [4-octyloxy-(C^N^N)Pt] and uracil moieties, as
shown in Fig. 4b. The molecular scaffold ND was found to play
an important role in the aggregation of PtU6 through comp-
lementary hydrogen bonding and π–π interactions between the
ligands in a solution state. The 1 : 2 stoichiometry of ND–PtU6
was confirmed by Job’s plots (Fig. 5a). The stepwise association
constants (K1 and K2 in M−1) were evaluated to be log K1 =
8526 | Dalton Trans., 2012, 41, 8524–8531
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3.7(3) and log K2 = 4.1(2), respectively, for a 1 : 2 complexation
of ND with PtU6.8 The value for the ratio 4K2/K1 ≈ 16 clearly
indicates the positive homotropic cooperative nature of this com-
plexation. The metallophilic and π–π interactions are likely to
induce the positive cooperative effect. Such absorption and emis-
sion resulting from Pt(II)–Pt(II) and π–π interactions were hardly
observed in the case of PtU5 (Fig. 4c and d), although a 1 : 2
complexation of ND with PtU5 was confirmed by Job’s plots
(Fig. 5b). A decrease in K values (log K1 = 2.95(2) and log K2 =
2.82(9)) between ND and PtU5 was observed.8 These results
suggest the importance of the direction of hydrogen bonding
sites in arranging the [4-octyloxy-(C^N^N)Pt] moieties
regularly.
An interbase distance is considered to affect the Pt(II)–Pt(II)
and π–π interactions in aggregated complexes, which might be
reflected in their absorption and emission properties. The
molecular scaffold AD was also confirmed to form the 1 : 2
complex with PtU6 by Job’s plots (Fig. 5c), wherein the stepwise
association constants (K1 and K2) were calculated to be log
K1 = 5.05(4) and log K2 = 4.189(6), respectively.8 The addition
of 0.5 molar equiv. amount of AD composed of anthracene to a
dichloromethane solution of PtU6 caused a new shoulder band
around 500 nm assignable to the MMLCT transition based on
Pt(II)–Pt(II) and π–π interactions in the UV-vis spectrum
(Fig. 6a). The increase of the 3MMLCT emission at around
730 nm based on its synergistic effect and the decrease of the
3MLCT–3LLCT emission were also observed in the emission
spectrum by the addition of 0.5 molar equiv. amount of AD, as
shown in Fig. 6b. In comparison to the emission with the
molecular scaffold ND composed of naphthalene, the low intensity
3
3
of the MMLCT emission and the high intensity of the MLCT
emission observed with the AD aggregate were probably due to
the weak Pt(II)–Pt(II) and π–π interactions based on the longer
interbase distance (Fig. 7). The emission properties of PtU6
were found to be controllable by changing the molecular scaffold
size.
Conclusions
Scheme 2 Synthesis of the molecular scaffolds ND and AD composed
of the aromatic rigid frameworks naphthalene and anthracene, respec-
tively, with two 2,6-dihexamidopyridine moieties as a complementary
hydrogen bonding sites for the uracil moiety.
In conclusion, bioorganometallic compounds were synthesized
to conjugate uracils and organoplatinum(II) compounds. The
designed bioorganometallic platinum(II) compound PtU6 was
Fig. 4 (a) UV-vis spectra of ND, PtU6, and ND–PtU6 (1 : 2) in dichloromethane ([ND] = 0.5 × 10−3 M, [PtU6] = 1.0 × 10−3 M) at 298 K, (b) emis-
sion spectra (λex = 530 nm) of PtU6 and ND–PtU6 (1 : 2) in dichloromethane ([ND] = 0.5 × 10−3 M, [PtU6] = 1.0 × 10−3 M) at 298 K, (c) UV-vis
spectra of ND, PtU5, and ND–PtU5 (1 : 2) in dichloromethane ([ND] = 0.5 × 10−3 M, [PtU5] = 1.0 × 10−3 M) at 298 K and (d) emission spectra
(λex = 530 nm) of PtU5 and ND–PtU5 (1 : 2) in dichloromethane ([ND] = 0.5 × 10−3 M, [PtU5] = 1.0 × 10−3 M) at 298 K.
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Fig. 5 (a) Job’s plots for the complexation of ND with PtU6, where Δδ× [ND] was plotted against [ND]/([ND] + [PtU6]) at an invariant total con-
centration of 2.0 × 10−3 M in CD2Cl2 at 295 K, (b) Job’s plots for the complexation of ND with PtU5, where Δδ × [ND] was plotted against [ND]/
([ND] + [PtU5]) at an invariant total concentration of 2.0 × 10−3 M in CD2Cl2 at 295 K and (c) Job’s plots for the complexation of AD with PtU6,
where Δδ × [AD] was plotted against [AD]/([AD] + [PtU6]) at an invariant total concentration of 2.0 × 10−3 M in CD2Cl2 at 295 K.
spectrometer with tetramethylsilane as an internal standard.
Mass spectra were run on a JEOL JMS DX-303 spectrometer.
6-Ethynyl-1-octyluracil,9 5-ethynyl-1-octyluracil,7 4-benzyl-
oxy-2,6-pyridinediamine,10 1,8-diiodonaphthalene11 and 1,8-
diethynylanthracene12 were prepared by the methods described
in the literature.
Synthesis of 6-(4-octyloxyphenyl)-2,2′-bipyridine (1)
A
mixture of N-(2-pyridacyl)pyridinium iodide (3.4 g,
10 mmol), 3-dimethylamino-1-(4-octyloxyphenyl)propan-1-one
hydrochloride (3.3 g, 10 mmol), and NH4OAc (17 g, 0.22 mol)
in glacial acetic acid (40 mL) was refluxed under Ar for 3 days.
After the addition of water and dichloromethane to the resulting
mixture, the organic phase was washed in saturated NaHCO3
aqueous solution and brine, and then dried over Na2SO4. The
solvent was evaporated in vacuo and the residue was chromato-
graphed on a silica-gel column (eluent, CH2Cl2–EtOAc 49 : 1) to
give the desired 6-(4-octyloxyphenyl)-2,2′-bipyridine (1) (2.0 g,
5.5 mmol) as a white solid.
Fig. 6 (a) UV-vis spectra of AD, PtU6, and AD–PtU6 (1 : 2) in
dichloromethane ([AD] = 0.5 × 10−3 M, [PtU6] = 1.0 × 10−3 M) at
298 K and (b) emission spectra (λex = 530 nm) of PtU6 and AD–PtU6
(1 : 2) in dichloromethane ([AD] = 0.5 × 10−3 M, [PtU6] = 1.0 ×
10−3 M) at 298 K.
found to form a dimeric structure through intermolecular hydro-
gen bonds between the uracil moieties of two independent mo-
lecules, wherein each hydrogen-bonded dimer was connected
through Pt(II)–Pt(II) and π–π interactions. The tuning of the emis-
sion properties of the bioorganometallic platinum(II) compounds
was achieved by changing the direction of hydrogen bonding
sites and the molecular scaffold size, which depends on the regu-
lation of the aggregated structures, to induce Pt(II)–Pt(II) and π–π
interactions. The architectural control of molecular assemblies
using pre-organized molecular scaffolds is predicted to be a
useful approach to artificial highly-ordered systems without
chemical synthesis. Studies on their application to functional
materials and catalysts are now in progress.
1: Yield 55%; mp 61–62 °C; IR (KBr) 3279, 3048, 2917,
2850, 1607, 1582, 1561, 1516, 1455, 1434, 1249, 1182,
1
1017 cm−1; H NMR (400 MHz, CDCl3, 1.0 × 10−2 M) δ 8.69
(d, 1H, J = 4.0 Hz), 8.63 (d, 1H, J = 8.0 Hz), 8.31 (d, 1H, J =
8.0 Hz), 8.10 (d, 1H, J = 8.8 Hz), 7.90–7.80 (m, 2H), 7.71 (d,
1H, J = 8.0 Hz), 7.32 (dd, 1H, J = 8.0, 4.0 Hz), 7.02 (d, 1H, J =
8.8 Hz), 4.04 (t, 2H, J = 6.4 Hz), 1.86–1.79 (m, 2H), 1.52–1.45
(m, 2H), 1.42–1.26 (m, 8H), 0.90 (t, 3H, J = 6.8 Hz); 13C NMR
(100 MHz, CDCl3, 1.0 × 10−2 M) 160.1, 156.5, 156.2, 155.5,
149.0, 137.6, 136.9, 131.7, 128.2, 123.7, 121.3, 119.5, 118.6,
114.7, 68.1, 31.8, 29.4, 29.3, 26.1, 22.7, 14.1 ppm; HRMS
(FAB) m/z Calcd for C24H29N2O (M+), 361.2274; Found,
361.2281; Anal. Calcd for C24H28N2O: C, 79.96; H, 7.83; N,
7.77. Found: C, 79.94; H, 7.82; N, 7.67.
Experimental
General methods
All the reagents and solvents were purchased from commercial
sources and were further purified by the standard methods,
where necessary. All manipulations were carried out under Ar.
Melting points were determined on a Yanagimoto Micromelting
Point Apparatus and were uncorrected. Infrared spectra were
Synthesis of the platinum(II) complex 2
A mixture of 1 (100 mg, 0.28 mmol) and K2PtCl4 (165 mg,
0.40 mol) in acetonitrile–water (8.0 : 8.0 mL) was refluxed under
Ar for 42 h and the solvent was evaporated. The product was
extracted with dichloromethane. The solvent was evaporated
1
obtained with a JASCO FT/IR-480 Plus spectrometer. H NMR
spectra were recorded on a JEOL JNM-ECS 400 (400 MHz)
8528 | Dalton Trans., 2012, 41, 8524–8531
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Fig. 7 Schematic representation of the controlled aggregation of the bioorganometallic platinum(II) compound PtU6 by using molecular scaffolds.
in vacuo and the residue was washed with methanol to give the
desired platinum(II) complex 2 (138 mg, 0.23 mmol) as an
orange solid.
Calcd for C38H46N4O3Pt1·0.5H2O: C, 56.28; H, 5.84; N, 6.91.
Found: C, 56.47; H, 5.53; N, 6.96.
2: Yield 84%; mp 153–154 °C (decomp.); IR (KBr) 3052,
Synthesis of the bioorganometallic platinum(II) complex PtU5
2925, 2853, 1591, 1544, 1435, 1263, 1203, 1034 cm−1 1H
;
NMR (400 MHz, CDCl3, 1.0 × 10−2 M) δ 8.99 (d, 1H, J = 5.6,
1.6 Hz), 8.05 (dt, 1H, J = 8.0, 1.6 Hz), 7.90 (d, 1H, J = 8.0 Hz),
7.75 (t, 1H, J = 8.0 Hz), 7.62 (dd, 1H, J = 8.0, 5.6 Hz), 7.47 (d,
1H, J = 8.0 Hz), 7.35 (d, 1H, J = 8.0 Hz), 7.28 (d, 1H, J =
8.8 Hz), 7.13 (d, 1H, J = 2.8 Hz), 6.61 (dd, 1H, J = 8.8, 2.8 Hz),
4.03 (t, 2H, J = 6.4 Hz), 1.82–1.75 (m, 2H), 1.52–1.44 (m, 2H),
1.41–1.26 (m, 8H), 0.90 (t, 3H, J = 6.8 Hz); 13C NMR
(100 MHz, CDCl3, 1.0 × 10−2 M) 166.8, 161.6, 157.8, 154.7,
149.3, 145.4, 139.8, 139.1, 138.7, 127.8, 126.5, 122.8, 119.7,
118.4, 117.0, 111.1, 68.3, 32.3, 29.8, 29.7, 26.5, 23.1, 14.3 ppm;
HRMS (FAB) m/z Calcd for C24H27ClN2OPt (M+), 589.1454;
Found, 589.1456; Anal. Calcd for C24H27ClN2OPt·0.5H2O: C,
48.12; H, 4.71; N, 4.68. Found: C, 48.29; H, 4.44; N, 4.58.
To a dichloromethane (4.0 mL) solution of 5-ethynyl-1-octyluracil
(75 mg, 0.30 mmol), 2 (89 mg, 0.15 mmol), and CuI (1.8 mg,
9.5 μmol) was added triethylamine (1.8 mL, 13 mmol) under Ar
at room temperature in the dark. The resulting mixture was
stirred at room temperature for 14 h and the solvent was evapor-
ated. The product was extracted with dichloromethane. After
evaporation of the solution, the bioorganometallic platinum(II)
complex PtU5 was isolated as an orange solid (73 mg, 91 μmol)
by reprecipitation from dichloromethane and ether.
PtU5: yield 61%; mp 197–199 °C (decomp.); IR (KBr) 3088,
3039, 2928, 2852, 2106, 1695, 1659, 1581, 1547, 1435, 1351,
1225, 1173 cm−1; 1H NMR (400 MHz, CDCl3, 2.5 × 10−2 M) δ
9.36 (d, 1H, J = 5.2 Hz), 8.32 (s, 1H), 8.07 (t, 1H, J = 7.6 Hz),
7.94 (d, 1H, J = 7.6 Hz), 7.80 (t, 1H, J = 8.0 HzH), 7.63 (dd,
1H, J = 7.6, 5.2 Hz), 7.58 (d, 1H, J = 8.0 Hz), 7.48 (d, 1H, J =
8.0 Hz), 7.44 (s, 1H), 7.39 (d, 1H, J = 2.4 Hz), 7.37 (d, 1H, J =
8.4 Hz), 6.60 (dd, 1H, J = 8.4, 2.4 Hz), 4.07 (t, 2H, J = 6.4 Hz),
3.72 (t, 2H, J = 7.2 Hz), 1.83–1.68 (m, 4H), 1.52–1.25
(m, 20H), 0.91–0.87 (m, 6H); 13C NMR (100 MHz, CD2Cl2,
2.0 × 10−3 M) 165.7, 163.4, 162.1, 158.7, 154.9, 152.5, 150.2,
144.8, 143.7, 139.6, 139.4, 139.3, 128.2, 126.6, 124.0, 122.9,
118.4, 116.9, 112.6, 110.3, 104.8, 94.7, 68.3, 49.1, 32.3, 32.2,
29.9, 29.8, 29.7, 29.6, 29.5, 26.9, 26.5, 23.1, 23.0, 14.3,
14.2 ppm; HRMS (FAB) m/z Calcd for C38H47N4O3Pt194 (M+),
801.3275; Found, 801.3267; Anal. Calcd for C38H46N4O3Pt1·
0.5H2O: C, 56.28; H, 5.84; N, 6.91. Found: C, 56.49; H, 5.55;
N, 6.98.
Synthesis of the bioorganometallic platinum(II) complex PtU6
To a dichloromethane (3.0 mL) solution of 6-ethynyl-1-octyluracil
(50 mg, 0.20 mmol), 2 (59 mg, 0.10 mmol), and CuI (1.5 mg,
7.9 μmol) was added triethylamine (1.2 mL, 8.6 mmol) under
Ar at room temperature in the dark. The resulting mixture was
stirred at room temperature for 23 h and the solvent was evapor-
ated. The residue was washed with methanol, and the bioorgano-
metallic platinum(II) complex PtU6 was isolated as a dark red
solid (76 mg, 95 μmol) by recrystalization from dichloromethane
and methanol.
PtU6: yield 95%; mp 240–241 °C (decomp.); IR (KBr) 3427,
2925, 2853, 2089, 1696, 1651, 1561, 1456, 1435, 1262, 1202,
1
1041 cm−1; H NMR (400 MHz, CD2Cl2, 2.0 × 10−3 M) δ 8.97
(dd, 1H, J = 5.2, 1.6 Hz), 8.28 (br, 1H), 8.11 (td, 1H, J = 7.6,
1.6 Hz), 7.95 (d, 1H, J = 7.6 Hz), 7.84 (t, 1H, J = 8.0 Hz),
7.63–7.57 (m, 2H), 7.52 (d, 1H, J = 8.0 Hz), 7.37 (d, 1H, J =
8.4 Hz), 7.18 (d, 1H, J = 2.4 Hz), 6.62 (dd, 1H, J = 8.4, 2.4 Hz),
5.83 (s, 1H), 4.22 (t, 2H, J = 7.6 Hz), 4.00 (t, 2H, J = 6.4 Hz),
1.87–1.75 (m, 4H), 1.50–1.11 (m, 20H), 0.89 (t, 3H, J =
6.8 Hz), 0.77 (t, 3H, J = 6.8 Hz); 13C NMR (100 MHz, CD2Cl2,
2.0 × 10−3 M) 165.7, 163.2, 162.1, 158.6, 154.7, 152.1, 151.5,
143.6, 142.7, 140.0, 139.9, 139.4, 128.2, 126.9, 124.2, 123.3,
118.7, 117.0, 110.5, 103.2, 97.2, 68.3, 46.7, 32.3, 29.8, 29.7,
29.3, 27.3, 26.5, 23.1, 23.0, 14.3 ppm; HRMS (FAB) m/z Calcd
for C38H47N4O3Pt194 (M+), 801.3275; Found, 801.3268; Anal.
Synthesis of 2,6-dihexamido-4-ethynylpyridine (7)
2,6-Dihexamido-4-ethynylpyridine (7) was synthesized from
4-benzyloxy-2,6-pyridinediamine in 5 steps. To a dichloro-
methane (100 mL) solution of 4-benzyloxy-2,6-pyridinediamine
(2.2 g, 10 mmol) and triethylamine (5.6 mL, 40 mmol) was
added a dichloromethane (50 mL) solution of heptanoylchloride
(3.3 mL, 21 mmol) dropwise under Ar at 0 °C. The resulting
mixture was stirred at room temperature for 12 h. The resulting
mixture was diluted with dichloromethane, washed with satu-
rated NaHCO3 aqueous solution and brine, and then dried over
Na2SO4. The solvent was evaporated in vacuo and the residue
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was chromatographed on a silica-gel column (eluent, CH2Cl2) to
give 3 (3.3 g, 7.6 mmol).
A mixture of 6 (1.6 g, 3.7 mmol) and KOH (0.41 g,
7.3 mmol) in methanol (55 mL) was stirred at room temperature
under Ar for 4 h. The resulting mixture was diluted with ethyl
acetate, washed with water and brine, and then dried over
Na2SO4. The ethyl acetate extract was evaporated in vacuo and
the residue was chromatographed on a silica-gel column (eluent,
CH2Cl2–EtOAc 9 : 1) to give 7 (0.98 g, 2.7 mmol).
3: Yield 76%; mp 54–56 °C; IR (KBr) 3424, 3325, 2953,
2926, 2860, 2367, 1692, 1673, 1583, 1541, 1503, 1440 cm−1
;
1H NMR (400 MHz, CD2Cl2, 5.0 × 10−2 M) δ 7.66 (s, 2H),
7.61 (s, 2H), 7.46–7.32 (m, 5H), 5.14 (s, 2H), 2.33 (t, J = 7.5
Hz, 4H), 1.70–1.63 (m, 4H), 1.38–1.28 (m, 12H), 0.89 (t, J =
7.0 Hz, 6H); 13C NMR (100 MHz, CD2Cl2, 5.0 × 10−2 M)
172.0, 168.8, 151.3, 136.5, 128.9, 128.5, 128.1, 96.2, 70.5,
38.1, 31.9, 29.2, 25.6, 22.9, 14.2 ppm; HRMS (FAB) m/z Calcd
for C26H38N3O3 (M+), 440.2908; Found, 440.2924.
7: Yield 73%; mp 45–47 °C; IR (KBr) 3566, 3402, 3278,
2955, 2927, 2857, 2116, 1672, 1613, 1557, 1507, 1419,
1
1212 cm−1; H NMR (400 MHz, CD2Cl2, 5.0 × 10−2 M) δ 7.97
(s, 2H), 7.67 (s, 2H), 3.31 (s, 1H), 2.35 (t, J = 7.6 Hz, 4H),
1.72–1.64 (m, 4H), 1.38–1.29 (m, 12H), 0.89 (t, J = 7.0 Hz,
6H); 13C NMR (100 MHz, CD2Cl2, 5.0 × 10−2 M) 171.9, 150.4,
134.7, 111.9, 81.8, 81.5, 38.1, 31.9, 29.2, 25.6, 22.9, 14.2 ppm;
HRMS (FAB) m/z Calcd for C21H32N3O2 (M+), 358.2489;
Found, 358.2499; Anal. Calcd for C21H31N3O2·0.5H2O: C,
68.82; H, 8.80; N, 11.47. Found: C, 68.78; H, 8.76; N, 11.19.
Benzyl ether 3 (5.6 g, 13 mmol) was dissolved in a mixture of
ethanol (60 mL). Pd/C (10 wt%, 0.59 g) was added and the reac-
tion mixture was placed under H2, stirred at room temperature
for 18 h and filtered through celite. The solvent was evaporated
in vacuo and the residue was chromatographed on a silica-gel
column (eluent, EtOAc) to give 4 (4.0 g, 12 mmol).
4: Yield 90%; mp 80–82 °C; IR (KBr) 3271, 2956, 2929,
2858, 1657, 1597, 1464, 1435, 1230 cm−1; 1H NMR (400 MHz,
CDCl3, 1.0 × 10−2 M) δ 10.03 (s, 1H), 7.67 (s, 2H), 7.55 (s,
2H), 2.38 (t, J = 7.6 Hz, 4H), 1.75–1.68 (m, 4H), 1.41–1.25 (m,
12H), 0.89 (t, J = 6.4 Hz, 6H); 13C NMR (100 MHz, CDCl3,
1.0 × 10−2 M) 172.6, 168.0, 150.1, 98.0, 38.1, 31.5, 28.8, 25.4,
22.5, 14.0 ppm; HRMS (FAB) m/z Calcd for C19H32N3O3 (M+),
350.2438; Found,350.2454; Anal. Calcd for C19H31N3O3: C,
65.30; H, 8.94; N, 12.02. Found: C, 65.05; H, 8.94; N, 11.84.
To a pyridine (6.5 mL, 80 mmol) solution of 4 (700 mg,
2.0 mmol) was added trifluoromethanesulfonic anhydride
(0.5 mL, 3.0 mmol) dropwise under Ar at 0 °C. The reaction
mixture was stirred at room temperature for 3 h. After removal of
the solvent, the residue was poured into water and extracted with
ether. The ether extract was evaporated in vacuo and the residue
was chromatographed on a silica-gel column (eluent, hexane–
EtOAc 4 : 1) to give 5 (810 mg, 1.7 mmol).
Synthesis of the molecular scaffold ND
To a DMF (7.5 mL) solution of 1,8-diiodonaphthalene (92 mg,
0.24 mmol), 7 (0.26 g, 0.72 mmol), PdCl2(Ph3P)2 (15 mg,
20 μmol) and CuI (4.8 mg, 25 μmol) was added triethylamine
(2.5 mL, 18 mmol) at room temperature. The resulting mixture
was stirred under Ar at 55 °C for 21 h. The resulting mixture
was diluted with dichloromethane, washed with water and brine,
and then dried over Na2SO4. The solvent was evaporated
in vacuo and the residue was chromatographed on a silica-gel
column (eluent, CHCl3–EtOAc 19 : 1) to give ND (79 mg,
95 μmol) as a white solid.
ND: yield 40%; mp 178–180 °C; IR (KBr) 3296, 3050, 2954,
2928, 2856, 2211, 1703, 1672, 1610, 1555, 1420, 1260, 1213,
1168 cm−1 1H NMR (400 MHz, CDCl3, 5.0 × 10−3 M) δ
;
7.95–7.91 (m, 4H), 7.77 (s, 4H), 7.55–7.52 (m, 6H), 2.30 (t, 8H,
J = 7.7 Hz, Hm), 1.65(q, J = 7.7 Hz, 8H), 1.39–1.28 (m, 24H),
0.90 (t, J = 7.0 Hz, 12H); 13C NMR (100 MHz, CDCl3, 5.0 ×
10−3 M) 171.3, 149.8, 136.1, 135.9, 134.4, 131.7, 130.9, 126.2,
120.0, 111.5, 95.1, 93.9, 37.9, 32.0, 29.3, 25.6, 22.9, 14.2 ppm;
HRMS (FAB) m/z Calcd for C53H67N6O4 (M+), 839.5218;
Found, 839.5220; Anal. Calcd for C52H66N6O4·H2O: C, 72.87;
H, 8.00; N, 9.80. Found: C, 73.14; H, 7.78; N, 9.69.
5: Yield 84%; mp 49–51 °C; IR (KBr) 3396, 3261, 3120,
3040, 2958, 2931, 2862, 2362, 1686, 1605, 1523, 1433,
1
1212 cm−1; H NMR (400 MHz, CD2Cl2, 5.0 × 10−2 M) δ 7.93
(s, 2H), 7.80 (s, 2H), 2.38 (t, J = 7.7 Hz, 4H), 1.73–1.64 (m,
4H), 1.40–1.29 (m, 12H), 0.89 (t, J = 7.0 Hz, 6H); 13C NMR
(100 MHz, CD2Cl2, 5.0 × 10−2 M) 172.2, 159.0, 151.8, 119.0,
101.9, 38.0, 31.9, 29.2, 25.4, 22.9, 14.2 ppm; HRMS (FAB) m/z
Calcd for C20H31F3N3O5S (M+), 482.1931; Found, 482.1949.
To a triethylamine (24 mL) solution of 5 (1.9 g, 4.0 mmol),
PdCl2(Ph3P)2 (0.14 g, 0.20 mmol), and CuI (19 mg, 0.10 mmol)
was added trimethylsilylacetylene (2.8 mL, 20 mmol) under Ar
at room temperature. The reaction mixture was stirred at 50 °C
for 14 h. After removal of the solvent, the residue was poured
into water and extracted with dichloromethane. The dichloro-
methane extract was evaporated in vacuo and the residue was
chromatographed on a silica-gel column (eluent, CH2Cl2) to give
6 (1.7 g, 3.9 mmol).
6: Yield 98%; IR (KBr) 3282, 2958, 2947, 2858, 2168, 1675,
1609, 1557, 1419, 1211 cm−1; 1H NMR (400 MHz, CD2Cl2, 5.0
× 10−2 M) δ 7.93 (s, 2H), 7.86 (s, 2H), 2.34 (t, J = 7.6 Hz, 4H),
1.70–1.62 (m, 4H), 1.36–1.27 (m, 12H), 0.88 (t, J = 7.0 Hz,
6H), 0.24 (s, 9H); 13C NMR (100 MHz, CD2Cl2, 5.0 × 10−2 M)
172.0, 150.3, 135.6, 111.6, 102.8, 99.7, 38.0, 31.9, 29.2, 25.6,
22.9, 14.2, −0.3 ppm; HRMS (FAB) m/z Calcd for
C24H40N3O2Si (M+), 430.2884; Found, 430.2899.
Synthesis of the molecular scaffold AD
To a tetrahydrofuran (3.5 mL) solution of 1,8-diethynylanthra-
cene (91 mg, 0.40 mmol), 5 (0.48 g, 1.0 mmol), PdCl2(Ph3P)2
(8.4 mg, 12 μmol), and CuI (2.3 mg, 12 μmol) was added tri-
ethylamine (1.5 mL, 11 mmol) at room temperature. The
mixture was stirred under Ar at 50 °C for 17 h. The resulting
mixture was diluted with dichloromethane, washed with water
and brine, and then dried over Na2SO4. The solvent was evapo-
rated in vacuo and the residue was chromatographed on a silica-
gel column (eluent, CH2Cl2–MeOH 19 : 1) to give AD (98 mg,
0.11 mmol) as a pale yellow solid.
AD: Yield 28%; mp 213–215 °C; IR (KBr) 3057, 2955, 2927,
2856, 2208, 1708, 1609, 1556, 1501, 1418, 1264, 1212,
1
1166 cm−1; H NMR (400 MHz, CD2Cl2, 5.0 × 10−3 M) δ 9.56
(s, 1H), 8.56 (s, 1H), 8.12 (d, J = 8.8 Hz, 2H), 7.98 (s, 4H),
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7.88 (d, J = 6.8 Hz, 2H), 7.55 (dd, J = 8.8, 6.8 Hz, 2H), 2.27
(t, J = 7.6 Hz, 8H), 1.65–1.56 (m, 8H), 1.37–1.26 (m, 24H),
0.91 (t, J = 6.8 Hz, 12H); 13C NMR (100 MHz, CD2Cl2, 5.0 ×
10−3 M) 171.4, 150.1, 135.8, 132.0, 131.9, 131.8, 130.3, 128.2,
125.7, 124.3, 120.9, 111.6, 93.7, 91.9, 37.9, 32.0, 29.4, 25.5,
23.0, 14.2 ppm; HRMS (FAB) m/z Calcd for C56H69N6O4 (M+),
889.5375; Found, 889.5370.
Acknowledgements
This work was supported by Grant-in-Aids for Science Research
on Priority Areas (No. 20036034) and Innovative Areas (No.
22108516) from the Ministry of Education, Culture, Sports,
Science and Technology, Japan. Thanks are also due to the
Analytical Center, Graduate School of Engineering, Osaka
University.
Physical measurements
Notes and references
UV-vis spectra were obtained using a Hitachi U-3500 spectro-
photometer in a deaerated dichloromethane solution under nitro-
gen at 298 K. Emission spectra were collected using a Shimadzu
RF-5300PC spectrofluorophotometer in a deaerated dichloro-
methane solution under nitrogen at 298 K.
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1H NMR titrations
The CD2Cl2 solution of ND or AD with a concentration
0.5 × 10−3 M containing various amounts of PtU6 or PtU5 was
prepared and 1H NMR spectra were measured at 295 K. The
changes in chemical shift of ND or AD signals as a function of
PtU6 or PtU5 were then analyzed. The titration data for three
different signals were used to determine the association constant
in each experiment.
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8 Self-association constants (Kdim) of PtU6 and PtU5 were calculated to be
less than 20 M−1, suggesting that self-association would not interfere
with aggregation of the organoplatinum(II) compounds to the molecular
scaffolds.
9 T. Moriuchi, S. Noguchi, Y. Sakamoto and T. Hirao, J. Organomet.
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14 CrystalStructure 4.0: Crystal Structure Analysis Package, Rigaku Corpor-
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Job’s plots
For each component of the complex, 5.0 mL CD2Cl2 solutions of
accurately measured and identical concentrations (2.0 × 10−3 M)
were prepared. The two solutions were then combined to give a
series of samples of identical total concentration (2.0 × 10−3 M)
containing different mole fractions of the two components. The
1H NMR spectrum of each sample was then measured at 295 K,
and these spectra were used to produce a graph of Δδ × [H]
against [H]/([H] + [G]) shown as the Job’s plots.†
X-Ray structure analysis
All the measurements for PtU6 were made on a Rigaku R-AXIS
RAPID diffractometer using graphite monochromated Mo Kα
radiation. The structure of PtU6 was solved by direct methods13
and expanded using Fourier techniques. All the calculations
were performed using the Crystal Structure crystallographic soft-
ware package14 except for the refinement, which was performed
using SHELXL-97.15 The non-hydrogen atoms were refined an-
isotropically. The H atoms involved in hydrogen bonding were
located in electron density maps. The remainder of the H atoms
were placed in idealized positions and allowed to ride with the
C atoms to which each was bonded. Crystallographic details are
given in Table 1. Crystallographic data (excluding structure
factors) for the structures reported in this paper have been
deposited with the Cambridge Crystallographic Data Centre as
supplementary publication no. CCDC 851423 for PtU6.†
15 G. M. Sheldrick, Acta Crystallogr., 2008, A64, 112.
This journal is © The Royal Society of Chemistry 2012
Dalton Trans., 2012, 41, 8524–8531 | 8531