Synthesis and assembling properties of bioorganometallic cyclometalated Au(III) alkynyls bearing guanosine moieties

Article abstract of DOI:10.1039/c1ob05842h

A guanosine-based Au(III) compound was demonstrated to serve as a versatile bioorganometallic conjugate, which could form a variety of aggregates in the absence and presence of KPF₆via self-assembly of the guanosine moiety.

Full text of DOI:10.1039/c1ob05842h

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COMMUNICATION
Synthesis and assembling properties of bioorganometallic cyclometalated
Au(III) alkynyls bearing guanosine moieties†
Xiangtai Meng,a Toshiyuki Moriuchi,*a Norimitsu Tohnai,b Mikiji Miyata,b Masatoshi Kawahata,c
Kentaro Yamaguchic and Toshikazu Hirao*a
Received 27th May 2011, Accepted 13th June 2011
DOI: 10.1039/c1ob05842h
A guanosine-based Au(III) compound was demonstrated to
serve as a versatile bioorganometallic conjugate, which could
form a variety of aggregates in the absence and presence of
KPF6 via self-assembly of the guanosine moiety.
expand the Hoogsteen edge of dG and stabilize G-quadruplexes.4
Attachment of oligo(p-phenylene-vinylene) (OPV) to yield 8-OPV-
G is demonstrated to form p-conjugated organic nanoparticles
via G-quadruplex self-assembling.5 Moreover, 8-(pyren-1-yl)-dG
represents an optical label for DNA analytical and electron
transfer studies.6 On the other hand, there has been a growing
interest in luminescent transition metal complexes owing to their
application to organic light-emitting devices.7 Luminescent Au(III)
compounds have not been investigated so much in contrast
to isoelectronic platinum(II) compounds.8 To the best of our
knowledge, the synthesis and study of the assembling properties
of bioorganometallic Au(III) alkynyl complexes bearing guanosine
moieties have not been reported so far. Herein, we report the
synthesis of two Au(III) complexes 1 and 2 possessing guanosine
moieties to study their assembling properties.
Bioorganometallic chemistry is a rapidly growing research field at
the interface of various disciplines.1 Conjugation of organometal-
lic compounds with biomolecules such as DNA, amino acids,
and peptides is envisioned to provide novel systems depending on
the properties of both components. Nucleobases of DNA possess
acceptors and donors for hydrogen bonding, which permits self-
association into various nano-architectures. A variety of modified
nucleobases with fluorescent, electrical, magnetic, and metal ion
binding properties have been reported to expand the scope of their
applications.2 A typical example is the assembly of guanosines and
their derivatives to octameric or polymeric species in the presence
and absence of a cation (Fig. 1).3 For example, Rivera et al.
developed a series of 8-aryl-2¢-deoxyguanosine derivatives which
The synthetic routes to 1 and 2 are outlined in Scheme 1.
The Stille cross-coupling reaction of the 8-bromoguanosine 3
with the tin compound 4 afforded the protected guanosine 5,9
which was followed by deprotection with K2CO3 to give the 8-
ethynylguanosine 6. The structure of 5 was confirmed by single-
crystal X-ray analysis.† An intramolecular hydrogen bond was
˚
found between N(1) and O(6) (N(1)–O(6), 2.651(7) A; N(1)–H–
O(6), 129 (3)◦). In the crystal packing structure, an intermolecular
hydrogen bonding network was observed (Fig. 2).10 As the final key
step, the coupling of 6 or 7 with the cyclometallic Au(III) complex 8,
was carried out using the copper-catalyzed Sonogashira procedure
under an argon atmosphere to give the expected Au(III) compound
2 or 1, respectively. Interestingly, the solubility of both Au(III)
complexes is different. Bioorganometallic compound1 is soluble in
chlorinated solvents at room temperature, and very easily soluble
in THF even at a low temperature. However, bioorganometallic
compound 2 shows poor solubility, being slightly soluble in
chlorinated solvents and soluble in THF at room temperature.
Therefore, in this communication, we only study the assembling
properties of 1. Additionally, bioorganometallic compound 1
Fig. 1 Assembly types of guanosine derivatives.
aDepartment of Applied Chemistry, Graduate School of Engineer-
ing, 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
bDepartment of Material and Life Science, Graduate School of Engineering,
Osaka University, Yamada-oka, Suita, Osaka 565-0871, Japan. E-mail:
tohnai@mls.eng.osaka-u.ac.jp
1
was fully characterized by H, 13C, 2D NMR, IR, and HRMS
techniques (ESI†).
cPharmaceutical Sciences at Kagawa Campus, Tokushima Bunri University,
1314-1 Shido, Sanuki, Kagawa 769-2193, Japan. E-mail: yamaguchi@
kph.bunri-u.ac.jp; Fax: +81-87-894-0181; Tel: +81-87-894-5111
The assembling properties of 1 were studied by 1H NMR
spectroscopy. As shown in Fig. 3a, the amino protons (NH2) are
equivalent as a sharp singlet at 6.33 ppm in DMSO-d6 while the
amide proton (NH) resonates at 10.78 ppm. These chemical shifts
indicate that 1 is mostly present in a monomeric species (Fig. 3b).
† Electronic supplementary information (ESI) available: Experimental
procedures and characterization data for all new compounds. CCDC
reference number 822824. For ESI and crystallographic data in CIF or
other electronic format see DOI: 10.1039/c1ob05842h
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Scheme 1 Synthesis of the bioorganometallic compounds 1 and 2.
Fig. 2 Crystal structure (left) and packing structure (right) of 5.
-25 ◦C, the amide signal became sharper and downfield-shifted
(12.70 ppm). Simultaneously, two new signals appeared at 9.63
and 4.76 ppm, which correspond to hydrogen-bonded (NH2b) and
non-hydrogen-bonded (NH2f) amino protons, respectively. A 2D
NOESY experiment yielded a cross-peak between NH2b and H3
(ESI, Figure S1†). These chemical shifts are in agreement with
an empty G-quartet structure even without assistance of a cation
(Fig. 3b).5,12
When 0.25 equivalents of KPF6 were added to a THF-d8
solution of 1, the 1H NMR spectrum changed, with disappearance
of both the amino and amide signals at 25 ◦C (Fig. 4). Lowering
the temperature to -15 ◦C, a new sharp signal was observed at
12.39 ppm. At a lower temperature, -30 ◦C, another new set
of amide signal gradually appeared at around 12.59 ppm. The
ratio of these two signals is 1 : 2. At the same time, two new sets
of signals appeared at 9.50 and 6.80 ppm with the same ratio.
The downfield signal (9.50 ppm) may be assigned to a hydrogen-
bonded amino proton and the other signal (6.80 ppm) can be
assigned to a non-hydrogen-bonded amino proton. In order to
assign these two sets of signals, the assembling properties of 1
were studied in the presence of 0.125 and 0.5 equivalents of KPF6
in THF at various temperatures. Addition of 0.125 equivalents
of KPF6 resulted in only one main set of the sharp signal at
12.39 ppm above -30 ◦C, and the amino signals split into two
Fig. 3 1H NMR spectra of 1 in the absence of KPF6.
In contrast, when CD2Cl2 was used as a solvent, the amino signal
became unobservably broad at room temperature with a downfield
shift of the amide signal to 12.58 ppm. These findings suggest
that 1 assembles into a mixture of oligomeric species even in
the absence of an alkaline cation.11 Lowering the temperature to
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The assembling properties were also studied by CD, absorption,
and emission techniques. As shown in Fig. 6a, upon addition of
KPF6 a drop in intensity was observed with the absorption band
at 248–326 nm, accompanied by the concomitant growth of a
new low-energy shoulder in the region of 380–450 nm. Moreover,
as shown in Fig. 6b, the CD spectrum changed dramatically
after addition of KPF6. These observations indicate a change in
the confirmation and/or secondary structure of 1, namely, from
oligomers to an octamer or polymeric columnar aggregate.
Fig. 4 1H NMR spectra of 1 in the presence of 0.25 eq. of KPF6 in
THF-d8 at various temperatures.
broad bands at 9.50 and 6.80 ppm (Fig. 5a). From the ratio of
the guanosine : KPF6 (8 : 1), this species might be assigned to an
octamer (Fig. 5b). In addition, analysis of the sample by CSI-
TOF MS resulted in a spectra showing a peak m/z = 4626 which
matches the mass [18+2Na]2+ in THF (ESI, Figure S2†). This is
because the alkali metal-mediated gas-phase binding of the G-
quadruplex occurs in the order Na+ > K+, in contrast to the
stabilizing order in solution.13 After adding 0.5 equivalents of
KPF6 at -30 ◦C, the amide proton was mainly observed as a broad
signal around 12.59 ppm (Fig. 5a). Lowering the temperature
to -60 ◦C made the amide proton signal sharper and the more
major signal (Fig. 5a). This set of signals was not assigned to a
hexadecamer because amide protons of the hexadecamer display
at least two sharp signals. With the increased amount of potassium
ion and at the lower temperature, the species with the broad signal
(12.59 ppm) became the major one. These findings suggest that this
set of signals might be assigned to a polymeric columnar aggregate
(Fig. 5b).14
Fig. 6 (a) UV–vis spectra and (b) CD spectra of 1 in the absence (red
line) and presence (blue line) of KPF6 (0.25 eq.) in CH2Cl2 (1.0 ¥ 10-4 M).
The chloro precursor [Au(CŸNŸC)Cl] has been reported to be
emissive only at a low temperature, but not at room temperature.15
However, bioorganometallic compound 1 showed luminescence at
400–700 nm in solution at room temperature because the strong d-
donating alkynyl ligand is considered to enhance the luminescence
properties by increasing the d-d splitting. This emission band
might have originated from a metal-perturbed IL3[p–p] state of
the tridentate CŸNŸC ligand. An increased intensity was observed
after addition of KPF6 at room temperature (Fig. 7a), probably
due to the rigidity after the formation of the G-quadruplex. No
p–p interaction between CŸNŸC ligands was observed at room
temperature. However, lowering the temperature to a freezing
point, a new intense band appeared at 540 nm (Fig. 7b), which
is probably due to a p–p interaction between the CŸNŸC ligands.
The 1H NMR also suggests a p–p interaction between the CŸNŸC
1
ligands. After addition of KPF6, at the low temperature, the H
NMR chemical shift of the CŸNŸC group was changed (ca. Dd ª
0.1 ppm) (Fig. 8). These changes also suggest a tighter assembling
aggregate at the lower temperature. A similar p–p interaction was
also observed in the absence of KPF6 at the lower temperature,
because 1 forms an empty G-quartet at a low temperature. The
empty G-quartet was able to stack with each other as indicated
Fig. 7 Emission spectra of 1 (lex = 390) in the presence (blue line)/absence
(red line) of KPF6 (0.25 eq.) in CH2Cl2 (1.0 ¥ 10-4 M) at (a) 25 ◦C and (b)
frozen.
Fig. 5 1H NMR spectra of 1 in the presence of different amounts of KPF6
in THF-d8.
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Notes and references
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Fig. 8 The aromatic part of the 1H NMR spectrum of 1 in THF-d8.
1
by H NMR, although the arrangement and distance might be
different in the presence of KPF6. A small change (ca. Dd ª 0.03
ppm) in the chemical shift was observed for the CŸNŸC group at
the lower temperature (ESI, Figure S3†).
In conclusion, new type of bioorganometallic conjugates, 1
and 2, consisting of the guanosine and cyclometalated Au(III)
moieties were synthesized. The bioorganometallic conjugate 1
was demonstrated to form the empty quartet, octamer, and
polymeric columnar aggregate depending on the presence of
KPF6. Furthermore, the formation of the G-quadruplex via
self-assembly was found to induce a p–p interaction. Studies
on the application of the G-quadruplex induced metal ion
aggregates to functional materials and catalysts are now in
progress.
Acknowledgements
The author X. M. expresses special thanks for the Global COE
(center of excellence) Program “Global Education and Research
Center for Bio-Environmental Chemistry” of Osaka University.
This work was supported by Grant-in-Aids for Science Research
on Innovative Areas (No. 22108516 and 23111711) 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.
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