Metal array fabrication based on ultrasound-induced self-assembly of metalated dipeptides

Article abstract of DOI:10.1039/c3dt51696b

Pd- and Pt-bound bis-metalated peptides were synthesised by the condensation of Pd- or Pt-aldimine-complex-bound glutamic acids to afford the four possible metal isomers of bis-Pd and bis-Pt-homometalated dipeptides and PdPt- and PtPd-heterometalated dipeptides without metal disproportionation. Ultrasound-induced self-assembly of these bis-metalated peptides proceeded effectively to afford supramolecular gels that displayed well-ordered metal arrays. The formation of parallel β-sheet type aggregates through interpeptide amide-amide hydrogen bonding was confirmed by IR, scanning electron microscopy (SEM), and synchrotron X-ray diffraction analyses (WAXS and SAXS). The mechanism of the ultrasound-induced self-assembly of the metalated dipeptides was elucidated via kinetic and association experiments by ¹H NMR, in which ultrasound-triggered dissociation of intramolecular hydrogen bonds between the chloride ligands of the Pd- and Pt-complexes and amides initially occurred. This was followed by the formation of intermolecular amide-amide hydrogen bonds, which afforded the corresponding oligomeric peptide self-assembly as the nucleus for supramolecular aggregation. The observed first-order relationship of the gelation rate versus the sonication frequency suggested that the microcavitation generated under sonication conditions acted as a crucial trigger and provided a reaction field for efficient self-assembly.

Full text of DOI:10.1039/c3dt51696b

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Dalton
Transactions
Volume 42 | Number 45 | 7 December 2013 | Pages 15807–16232
Metal array fabrication based on ultrasound-induced
self-assembly of metalated dipeptides
An international journal of inorganic chemistry
www.rsc.org/dalton
Programmable 3D metal array fabrication was achieved through
ultrasound-induced self-assembly of Pd- and Pt-bound dipeptides.
An interchanging gimmick of intra-/intermolecular hydrogen
bonding triggered by ultrasound microcavitation was found to
afford the β-sheet-templated well-ordered Pd- and Pt-array.
Themed issue: Coordination Programming: Science of Molecular Superstructures Towards Chemical Devices
ISSN 1477-9226
COVER ARTICLE
Tatsuma et al.
presence of ligands
2
Plasmon-induced oxidation of gold nanoparticles on TiO in the
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Metal array fabrication based on ultrasound-induced
self-assembly of metalated dipeptides†
Cite this: Dalton Trans., 2013, 42, 15953
a,b,c
a
b
a
Katsuhiro Isozaki,*
Hikaru Takaya*
Yusuke Haga, Kazuki Ogata, Takeshi Naota* and
a,b,d
Pd- and Pt-bound bis-metalated peptides were synthesised by the condensation of Pd- or Pt-aldimine-
complex-bound glutamic acids to afford the four possible metal isomers of bis-Pd and bis-Pt-homometa-
lated dipeptides and PdPt- and PtPd-heterometalated dipeptides without metal disproportionation.
Ultrasound-induced self-assembly of these bis-metalated peptides proceeded effectively to afford supra-
molecular gels that displayed well-ordered metal arrays. The formation of parallel β-sheet type aggre-
gates through interpeptide amide–amide hydrogen bonding was confirmed by IR, scanning electron
microscopy (SEM), and synchrotron X-ray diffraction analyses (WAXS and SAXS). The mechanism of the
ultrasound-induced self-assembly of the metalated dipeptides was elucidated via kinetic and association
1
experiments by H NMR, in which ultrasound-triggered dissociation of intramolecular hydrogen bonds
between the chloride ligands of the Pd- and Pt-complexes and amides initially occurred. This was fol-
lowed by the formation of intermolecular amide–amide hydrogen bonds, which afforded the corres-
ponding oligomeric peptide self-assembly as the nucleus for supramolecular aggregation. The observed
first-order relationship of the gelation rate versus the sonication frequency suggested that the microcavi-
tation generated under sonication conditions acted as a crucial trigger and provided a reaction field for
efficient self-assembly.
Received 25th June 2013,
Accepted 22nd July 2013
DOI: 10.1039/c3dt51696b
www.rsc.org/dalton
Well-ordered nanostructured metal arrays based on the higher achieved the facile synthesis of multi-Pd-bound peptides from
5
order self-assembly of bioorganometallics show great promise Pd-bound glutamic acids. Metal array fabrication based on
in the development of new types of nanomaterials. The ability the self-assembly of the Pd-bound dipeptides, as well as the
6
of peptides to “program” in sequentially and dimensionally related Pt-bound glutamic acid derivatives, was demonstrated,
controlled higher-order hierarchical structures such as α-helix affording high ordering and three dimensional control. These
and β-sheet enables rational control of the spatial positioning findings led us to further exploit the programmable fabrication
and configurations of metals conjugated within their of heterometallic arrays based on Pd- and Pt-bound hetero-
sequences. This feature of peptides makes metalated peptides metalated peptides.
one of the most useful and attractive platforms for the
The reported synthetic methods for metalated peptides can
peptide-based fabrication of functional organometallic be roughly categorised into three types (Scheme 1). In the
materials. Unsurprisingly, there have been many reports of Type 1 approach, the desired metals are directly introduced
1
peptide-based organometallics, which have been used in bio- into coordination sites on the synthesised peptide, in which
2
3,4
labeling and peptide self-assembly;
however, the prepa- strong coordinating ligands have been furnished on the α-side
ration of multimetal arrays based on the self-assembly of meta- chains. Strong chelating ligands such as oligopyridines, poly-
lated peptides is a nearly untouched subject. Recently, we carboxylates, and cyclams have been utilized as these metal
7
binding sites. Although many examples of mono-metalated
peptides have been reported, the multimetalated peptides are
still limited. Tanaka and Shionoya reported Pt-terpyridine-
a
Department of Chemistry, Graduate School of Engineering Science, Osaka
University, Machikaneyama, Toyonaka, Osaka 560-8531, Japan
b
complex-bound cysteine cyclooligopeptides which acted as
International Research Center for Elements Science, Institute for Chemical Research,
8
positively charged anion receptors, and also recently reported
Kyoto University, Uji, Kyoto 611-0011, Japan
c
Polymer Materials Unit, National Institute for Materials Science, Tsukuba, Ibaraki
Pt-ethylenediamine-complex-bound peptides bearing alter-
9
3
d
05-0044, Japan
nately arranged Pt(II) and Pt(IV) ions. Fairlie synthesised Pd-
PREST, Japan Science and Technology Agency, Japan
Electronic supplementary information (ESI) available. CCDC 947371 and
50317. For ESI and crystallographic data in CIF or other electronic format see
bound multiple cyclic peptides as models to investigate metal-
†
4
c
induced helix formation in metalloprotein folding. Kimura
reported a self-assembled Cu-terpyridine-complex-bound cyclic
9
DOI: 10.1039/c3dt51696b
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coupling of the corresponding metalated amino acids. Despite
this advantage, a limited number of syntheses of multimeta-
lated peptides have been reported, because undesirable metal
detachment occurs under acidic/basic deprotection con-
ditions, upon condensation with heat, and also during oxi-
dative/reductive cleavage from polymer supports. Therefore,
the appropriate choice of metal complexes and molecular
design to ensure sufficient robustness is key to programmable
metal array fabrication based on a Type 3 approach. Over the
last ten years, several metalated amino acids have been
applied in Type 3 syntheses to afford the corresponding multi-
1
5
metalated peptides. Condensations of ferrocene-, metallo-
1
6
17
porphyrin-,
terpyridine complex-,
and phenanthroline
1
8
complex -bound amino acids, including our Pd-aldimine-
complex-bound glutamic acid and NCN-pincer Pd-complex-
bound norvalines, were successfully demonstrated. Also, Zn-
and Mg-porphyrin-bound heterometalated peptides were first
reported by Solladié,
Pt-NCN pincer complex-bound norvaline peptides and Ru-,
Rh-, and Pt-terpyridine-complex-bound tyrosine peptides
were established.
5
1
9
1
6a
and recently, the syntheses of Pd- and
2
0
1
7,18
As mentioned above, we found that the Pd-aldimine-
complex-bound glutamic acids were sufficiently robust to form
the corresponding multi-Pd-bound peptides and undergo
ultrasound-induced self-assembly without detaching the Pd
5
center. The corresponding Pt-aldimine-complex-bound gluta-
Scheme 1 Synthesis of metalated peptides.
mic acid was also sufficiently robust toward the various N- and
C-terminus conversions and ultrasound-induced self-assembly.
glutamine tripeptide. Yamamura demonstrated that Zn-por- These Pd- and Pt-bound glutamic acids enabled us to prepare
1
0
phyrin-bound tyrosine peptides showed light-harvesting pro- homo- and heterometalated Pd- and Pt-bound dipeptides 1
1
1
perties. Another type of tyrosine-based metalated peptide without metal redistribution (Fig. 1), and further, to fabricate
1
2
was developed by Hamachi for fluorescence bio-imaging.
Pd,Pt-metal arrays through ultrasound-induced self-assembly.
The second method (Type 2) is based on the conjugation of
metal units with peptide side chains, in which metal com-
plexes bearing appropriate linkers such as succinimidyl
1
3
14
esters and halobenzyl groups were coupled with peptide
side chain functionalities such as amines and hydroxyl
groups. To the best of our knowledge, the synthesis of multi-
metalated peptides by the Type 2 method has not been
reported. With these two approaches, a diverse range of metals
can be introduced because the incorporation of metals into
the peptide scaffolds is performed at the last stage of the syn-
thesis, and tolerates undesirable decomplexation or decompo-
sition of the metal units during peptide synthesis. However,
these approaches hardly allow the selective synthesis of a par-
ticular sequence in the heterometalated peptide because the
metal coordination proceeds under the thermodynamically
controlled diffusion process and/or association/dissociation
processes. This complicates selective metal introduction and
affords mixtures of metal-sequenced isomers.
The Type 3 method, a stepwise coupling of metalated
amino acids, is considered promising in terms of the sequence
control of the metal arrays, because the order of the metals on
the peptide can be simply determined by the chronological
sequence of amino acids condensation. One can obtain any
ordering of heterometalated peptides exclusively by the simple Fig. 1 Pd,Pt bis-metalated glutamic acid dipeptides.
1
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Herein, the synthesis and characterisation of these metalated amino amides 4a and 4b. Condensation of 4 with the activated
peptides and the metal array fabrication based on ultrasound- C-ester prepared from 2a or 2b gave four possible metal
induced self-assembly are fully discussed based on precise isomers of the Pd,Pt-bound homo- and heterometalated gluta-
5
analytical and structural studies with the support of wide mic acid dipeptides, 1PdPd, 1PtPd, 1PdPt, and 1PtPt in moderate
angle and small angle X-ray scattering (WAXS and SAXS, yields. All products were adequately characterised by high-
1
respectively) using synchrotron radiation.
resolution NMR (920 MHz for H) and high-resolution
mass spectroscopy after purification, as shown in the experi-
mental section. To exclude the possibility of metal exchange,
we carried out a control experiment. Upon refluxing a
Results and discussion
Synthesis of Pd,Pt-metalated dipeptides
1
: 5 mixture of 2a and 2b in toluene for 1 week, neither
metal exchange nor metal leaching was detected by H NMR
1
Pd- and Pt-bound amino acids were synthesised according to observation. This result clearly exhibited the robust nature of
5
,6
the previous methods. Deprotection of the N- and C-termini both the Pd- and Pt-aldimine-complexed amino acids and
of the metalated amino acids was efficiently performed peptides.
without leaching metals by conventional methods for peptide
synthesis. The C-terminal allyl esters of the Pd- and Pt-bound
Gelation properties
amino acids 2a and 2b were deprotected by a palladium-cata-
The Pd,Pt-bis-metalated peptides 1PdPd, 1PtPd, 1PdPt, and 1PtPt
lysed deallylation reaction in the presence of α,γ-diketone com-
2
1
underwent ultrasound-induced self-assembly to form organo-
gels from homogeneous solutions of EtOAc or chlorobenzene.
pounds.
Condensation of the resulting activated ester
intermediate of 2 with n-butylamine was performed in situ by
the addition of the coupling agent 1-(3-dimethylaminopropyl)-
−
2
In a typical procedure, ultrasound irradiation (0.45 W cm
,
3.5 kHz, 3.0 min) of a homogeneous 1.50 × 10− M solution
2
4
3
-ethylcarbodiimide hydrochloride (EDCl), affording the
of dipeptide 1PtPt in EtOAc turned the stable pale yellow solu-
tion to a stable opaque gel (Fig. 2). Gelation was observed
exclusively when ultrasound was used as an external stimulus;
spontaneous gelation under a heating–cooling cycle did not
occur. When non-sonicated samples were cooled and left to
stand for extended periods, the precipitation of small amounts
of an amorphous powder and crystals was observed. The
resulting supramolecular gels of 1 were stable but were readily
converted to the original solutions upon heating, suggesting
that this gelation was a non-covalent interaction-based self-
assembly.
desired C-n-butylamido derivatives 3a in 68% and 3b in 69%
yields (Scheme 2). The N-terminal Fmoc protecting groups of 3
could be deprotected quantitatively in the presence of excess
piperidine to afford the corresponding Pd- and Pt-bound free
The minimum gelation concentrations of dipeptides 1PdPd
,
1
PtPd, 1PdPt, and 1PtPt were estimated in EtOAc and chloro-
benzene (Table 1). The observed ultrasound-induced gelation
proceeded only in EtOAc and chlorobenzene among the sol-
vents tested; benzene, toluene, acetone, and acetonitrile did
not afford a gel irrespective of concentration and sonication
conditions. As shown in Table 1, the minimum gelation con-
centration of the metalated dipeptides increased linearly from
7.00 for 1PdPd, 12.5 for 1PtPd, and 13.0 for 1PdPt, to 17.5 of 1PtPt,
paralleling the increase in the amount of Pt in the peptides. In
our previous paper, detailed kinetic experiments under various
sonication conditions showed that switching ligand chloride–
2
2,23
amide hydrogen intramolecular hydrogen bonds
of
Scheme 2 Synthesis of Pd,Pt-bound glutamic acid dipeptides. (i) Pd(PPh
cat.), dimedone, EDCl, CH Cl , rt, 0.5 h; (ii) n-BuNH , rt, 12 h; (iii) piperidine,
CH CN, rt, 0.5 h; (iv) Pd(PPh (cat.), dimedone, EDCl, CH Cl , rt, 12 h.
3 4
)
2
(
2
2
2
Fig. 2 Ultrasound-induced gelation and precipitation of a 1.50 × 10− M solu-
3
3
)
4
2
2
tion of 1PtPt in EtOAc at 25 °C.
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Table 1 Minimum gelation concentration of homo- and heterometalated pep- were shifted the farthest downfield of all the peptides. With
a
tides (mM)
the replacement of a Pd atom by Pt, the chemical shifts of the
amide protons NH gradually shifted upfield, from 7.17 ppm
2
Solvent
1
PdPd
1
PtPd
1
PdPt
1
PtPt
of 1PdPd to 7.16 ppm of 1PtPd, 7.15 ppm of 1PdPt, and 7.15 ppm
17.50 of 1PtPt (Fig. 3c). This trend was also observed for the amide
8.50
EtOAC
7.00
6.25
12.50
8.50
13.00
10.00
Chlorobenzene
1
protons NH , from 5.83 ppm of 1PdPd to 5.82 ppm of 1PtPd
,
a
After sonication (0.45 W cm−2, 40 kHz, 3.0 min) in the designated
5.78 ppm of 1PdPt, and 5.77 ppm of 1PtPt (Fig. 3d). The down-
solvent at 25 °C.
field shifts of the protons correlated strongly with the equili-
brium rate of the association/dissociation constant of
M–Cl⋯H–N hydrogen bonds. The same orders of hydrogen
Pd–Cl⋯H–N to intermolecular amide–amide hydrogen bonds
triggered self-assembly to form β-sheet supramolecular aggre-
gates (Scheme 3). On the basis of this result, the observed
1
bonding stability observed by H NMR and of the minimum
gelation concentration shown in Table 1 were in satisfactory
agreement with the fact that M–Cl⋯H–N hydrogen bonds were
the key factors in the ultrasound-induced self-assembly of
dipeptide 1. Further investigation of the proposed M–Cl⋯H–N
5
order of minimum gelation concentrations can be rationalised
by assuming a mechanism in which the efficiency of gelation
depends on the binding energy of M–Cl⋯H–N hydrogen
bonds (vide infra). Interestingly, in chlorobenzene, no large
differences among the minimum gelation concentrations of
the dipeptides were exhibited. This result indicates that coordi-
nation of the chlorine atoms in chlorobenzene potently
affected the formation and disruption of M–Cl⋯H–N hydrogen
bonds, which are considered to be critical factors in the self-
assembly process of metalated dipeptides.
intramolecular hydrogen bond interaction was carried out by
1
the variable-concentration H NMR analysis of 1
in CDCl3,
PdPd
in which downfield shifts of amide and imine protons due to
hydrogen bond formation were observed in the concentration
range 3.13–12.5 mM (Fig. S1†), which was consistent with the
results obtained at a minimum gelation concentration of
7.0 mM of 1PdPd. This result suggests that the hydrogen bonding
changes from intramolecular to intermolecular to afford the
peptide self-assembly. Dissociation of these M–Cl⋯H–N hydro-
gen bonds was verified in the variable-temperature H NMR
experiment performed on 1PdPd in a 3.0 mM diluted AcOEt-d8
solution (Fig. S2†). The corresponding upfield shifts of amide
and imine protons were clearly observed by elevating the temp-
erature from 298 to 343 K.
1
H NMR study of the intramolecular hydrogen bonding of
1
amide protons in the metalated peptides
The 1H NMR spectra in CDCl3 showed the typically shifted
imine and amide protons of the dipeptides 1PdPd, 1PtPd, 1PdPt
,
and 1PtPt (Fig. 3a). The imine protons of the N- and C-terminal
Pt-benzaldimine moieties of 1PtPt were observed at 8.37 and
Association experiments of PdCl- and PtCl-benzaldimine
complexes with N-methylacetamide
8
.35 ppm (Fig. 3b). The imine protons of the N- and C-terminal
Pd-benzaldimine moieties of 1PdPd were observed at 8.17 and
.16 ppm. The downfield shifts of the N-terminal imine
8
To clarify the M–Cl⋯H–N (M = Pd and Pt) hydrogen bonding
interactions of compound 1, association experiments were
carried out using nonpeptidyl model complexes, chloro-
protons indicate that the intensities of their M–Cl⋯H–N intra-
molecular hydrogen bonds were higher than those of the
C-terminal ones due to the influence of the electron deficient
amide N–H of the carbamate N-Boc-terminus. Almost the
same downfield shifts were observed on the imine protons of
[
2-[(butylimino-κN)methyl]phenyl-κC](triphenylphosphine)pal-
1
ladium (5a) and platinum (5b). H NMR titration experiments
were performed on these complexes and N-methylacetamide
1
2
Pt in 1PtPd and Pt in 1PdPt (8.37 and 8.35 ppm) and the
protons of Pd in 1
(NMA) in CDCl in the presence of excess amounts of 5a and
3
1
2
and Pd in 1
(8.17 and 8.16 ppm), in
PdPt
PtPd
5b (Fig. 4). As the concentration of the complexes increased,
comparison with those in the case of 1PdPd and 1PtPt. Higher
stabilities of the hydrogen bonds in Pd–Cl⋯H–N compared to
Pt–Cl⋯H–N can be assumed by the downfield shifts of the
amide protons (Fig. 3c and d). The amide protons of 1PdPd
the NMA N–H chemical shifts shifted downfield. Benesi–
Hildebrand plots from the titration of both 5a and 5b showed
linear relationships between 1/Δδ and 1/[M], unambiguously
indicating 1 : 1 complex formation. The association constants
a
K between complexes 5a and 5b with NMA were calculated to
−1
be 3.51 and 1.51 M , respectively. The higher association con-
stant of the Pd complex 5a clearly demonstrated the higher
hydrogen bonding stability of Pd–Cl⋯H–N versus Pt–Cl⋯H–N.
Evaluation of hydrogen bond acceptor abilities of Pd- and Pt-
aldimine complexes
As shown in Fig. 5, we succeeded in performing single crystal
X-ray analysis for the Pd- and Pt-aldimine complexes, chloro-
[
2-[(2-hydroxyethylimino-κN)methyl]phenyl-κC](triphenylphos-
5
6
phine)palladium (6a) and -platinum (6b). With these X-ray
Scheme 3 Ultrasound-induced hydrogen bond switching.
structures providing the initial coordinates of the molecular
1
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1
2
1
Fig. 3 (a) H NMR spectra of 1PdPd (blue), 1PtPd (green), 1PdPt (purple), and 1PtPt (red) in CDCl
3
. Expanded spectra of (b) imine, (c) amide NH , and (d) amide NH
proton regions.
Fig. 5 ORTEP drawings for (a) Pd complex 6a and (b) Pt complex 6b. Thermal
ellipsoids are drawn at the 50% probability level, and H atoms are omitted for
clarity.
indicated that the atomic charges on Pd and Cl were 0.501 and
−0.652 in the case of 6a, and 0.448 and −0.629 in the case of
6b (Fig. 6). The M–Cl dipole moment arising from the calcu-
lated charge delocalization illustrated the higher hydrogen
bond acceptor ability of Pd–Cl than that of Pt–Cl, which well
explains the resulting order of the minimum gelation concen-
Fig. 4 Benesi–Hildebrand plots of association experiments between 5a (circle),
b (diamond) and NMA.
5
1
trations (Table 1), the H NMR downfield shifts (Fig. 3) among
geometries, density functional theory (DFT) studies were the metal dipeptide isomers 1, and the differences in the
carried out at the B3LYP/LanL2DZ level to estimate the hydro- association constants of 5a and 5b. It is noteworthy that
1
gen bond acceptor abilities of the Pd–Cl and Pt–Cl moieties.
H NMR signals of α-imino hydrogen of 6 showed similar
Charge delocalization on the Pd, Pt, and Cl atoms was ana- downfield shifts related to the intramolecular hydrogen bond
lysed using natural bonding orbital (NBO) analysis, which of M–Cl⋯H–N (Fig. S5†).
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Fig. 6 NBO charges of Cl, Pd, and Pt atoms calculated by DFT (B3LYP/LanL2DZ
level) from crystal structures of complexes 6a and 6b. Light blue: Pd; yellow: Pt;
green: Cl.
Fig. 8 WAXS spectra of gel samples of peptide 1 prepared from a EtOAc solu-
tion (2.5 × 10− M). Blue: 1PdPd; purple: 1PtPd; green: 1PdPt; red: 1PtPt
2
.
in the IR spectra of these peptides supported the corres-
ponding hydrogen-bond formation of the β-sheet-type self-
assembly. The increasing sharp reflections in the Pt-bound
dipeptides 1PdPt, 1PtPd, and 1PtPt suggested that the mono-
disperse character of the fibrous aggregates increased with
crystallinity, and smaller aggregates would form in comparison
with the non-Pt-bearing dipeptide 1PdPd. The higher minimum
gelation concentrations of Pt-bound dipeptides (Table 1) can
be explained by the defective development of entangled fibre
networks due to the smaller and less flexible fibrous aggre-
gates of Pt-bound dipeptides.
Fig. 7 SEM images of Pt-coated xerogel samples of 1PtPt prepared from (a)
EtOAc and (b) chlorobenzene solutions.
Scanning electron microscopy (SEM) observations of
supramolecular gel fibres
SAXS analysis of supramolecular gels
For further structural study of the self-assembly of the meta-
lated dipeptides, small angle X-ray scattering (SAXS) analysis
was carried out at the BL40B2 beam line of SPring-8. As
The structural characterisation of the supramolecular aggre-
gates of the metalated peptides 1PdPd, 1PdPt, 1PtPd, and 1PtPt
was performed by SEM observations. Xerogel samples of the
metalated peptides were prepared by dispersing EtOAc gels
into excess hexane, spin-coating onto silicon wafers, and
drying under vacuum. SEM images of the metalated peptides
depicted in Fig. 9a, SAXS spectra of the EtOAc gels of 1PdPd
,
1PtPd, 1PdPt, and 1PtPt seemed to present a mixture of two struc-
tures because two sets of peaks appeared in all regions of
reflection. One set of peaks had values nearly equal to those of
the chlorobenzene gels (Fig. 9b), as indicated by blue dotted
lines. Two possible modes for dipeptide self-assembly can be
considered—the parallel and antiparallel β-sheets, as shown in
Fig. 10. Molecular modelling studies at the PM-3 level of calcu-
lations provided molecular lengths of 2.14 and 2.28 nm along
the N- to C-peptide axes of the parallel and antiparallel
β-sheets, respectively. These two values were in good accord-
ance with the assigned SAXS peaks of reflections at 2.19 and
1
PdPt, 1PtPd, and 1PtPt exhibited micrometer-scale fibrous belt-
5
like aggregates, similar to that of 1PdPd. As shown in Fig. 7,
the fibrous aggregates of 1PtPt prepared from a chlorobenzene
solution were shorter and thinner, with narrower distributions
of length and thickness, compared to the EtOAc gel. As will be
discussed later, we believe that the chlorine–amide hydrogen
bonds between chlorobenzene and the peptides are formed
during the self-assembly of 1, and this hydrogen bond for-
mation reduces the activation energy required to generate the
oligomeric intermediates that initiate gelation. The relatively
lower minimum gelation concentrations in chlorobenzene
2.24 nm in Fig. 9a, and could be reasonable for a mixture of
parallel and antiparallel β-sheet aggregates. In contrast to the
SAXS spectra of the EtOAc gels, the chlorobenzene gels
revealed simple SAXS peaks without shoulders. The reflections
at 2.17 nm were close to the width calculated for the parallel
β-sheet structure (2.14 nm), which was also supported by the
amide I and II bands in the IR spectrum. The reflections of
(Table 1) agreed with the reduction in the activation energy for
the self-assembly process of 1.
WAXS analysis of supramolecular gels
To investigate the nanostructures of the supramolecular gel the chlorobenzene gel at 1.29, 1.84, 2.05, and 2.17 nm in
fibres of 1, WAXS analysis was carried out using synchrotron Fig. 9a were comparable to the set of peaks at 1.28, 1.80, 2.06,
radiation at the BL19B2 beam line of SPring-8. As shown in and 2.19 nm, which are supposed to be the reflections from
Fig. 8, the WAXS spectra of peptides 1PdPd, 1PdPt, 1PtPd, and parallel β-sheet self-assemblies of 1. Fig. 11a shows the pro-
1
PtPt showed broad reflection at 2θ = 20.1°, indicating a typical posed parallel β-sheet type self-assembled structure of 1, in
interstrand distance of β-sheets of 0.46 nm. The observed which π–π stacking interactions of the Fmoc protecting groups
amide CvO and N–H stretching bands at 1652 and 3350 cm−1 are found to stabilise the β-sheet assembly. Variable-
1
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Fig. 9 SAXS spectra of dipeptide gels of 1 prepared from (a) EtOAc and (b)
chlorobenzene solutions (2.5 × 10− M). Blue: 1PdPd; purple: 1PtPd; green: 1PdPt
2
;
red: 1PtPt
.
Fig. 11 Self-assembly structures in supramolecular gels of 1: (a) parallel
β-sheet assembly and (b) parallel β-sheet lamellar aggregate structure.
Fig. 12 3D-controlled metal array fabrication through parallel β-sheet self-
assembly of heterometalated dipeptides: (a) Pd,Pt-bound peptide-based parallel
β-sheet monolayer and (b) Pd,Pt-bound peptide-based antiparallel β-sheet
monolayer.
more favorable in terms of lower steric repulsion. The prospec-
tive architecture of the parallel β-sheet assembly of 1 is
depicted in Fig. 11b. As this multilamellar β-sheet structure
illustrates, the reflections at 4.10, 2.05, and 1.30 nm in the
chlorobenzene gels could be assigned as the diagonal length
Fig. 10 Illustration of (a) parallel and (b) antiparallel β-sheet structures of 1.
concentration UV-vis experiment performed on 1
showed of the dipeptides and its lamellar reflections, and the 1.84 nm
PdPd
1
9
intense hypochromic behavior in the region of 215–256 nm, reflection was assignable to four times the interstrand dis-
which lets us attribute the tight π-stacking of the Fmoc groups tances of the β-sheet. As we reported in our previous paper,
to the formation of the proposed parallel β-sheet assembly. this type of β-sheet formation provides an efficient method for
5
,6
Additionally, a molecular modelling study demonstrated that the fabrication of well-ordered metal arrays. Fig. 12 shows
the parallel β-sheet accumulation of metal complex moieties is the parallel and antiparallel β-sheet monolayers derived from
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PdPt or 1PtPd dipeptides. In the case of the parallel β-sheet
Dalton Transactions
1
assembly, the Pd and Pt complexes aligned along the same
side and with the same orientations, thus confirming three-
dimensional control of the metal array fabrication through the
β-sheet self-assembly of one-dimensionally controlled metal
arrays of heterometalated peptides.
Effect of ultrasound frequency for gelation
In the self-assembly of the metalated peptides, ultrasound
plays a key role because gelation does not proceed in its
absence. Instead, the formation of an amorphous powder or
microcrystals was observed. Previously, we revealed that the
gelation rate of the bis-Pd-bound dipeptide 1PdPd clearly
5
exhibited a first order dependence on the sonication time.
These results strongly suggested that the ultrasound-induced
gelation of 1PdPd consisted of a sonication-induced initiation
step and a subsequent propagation step. In this context, we
measured differential scanning calorimetry (DSC) profiles of
the supramolecular gel of 1
to estimate the gel fibre granu-
PdPd
5
larity. The results revealed a dependence on sonication dur-
ation; the gels prepared at longer sonication times tended to
show higher temperature shifts of the endothermic peaks. The
observed sonication time-dependent thermal properties and
kinetics with induction period can be ascribed to the soni-
cation-induced formation of initial nucleic domains for self-
Fig. 13 Effect of ultrasound frequency for gelation of 1PdPd: (a) normalised
gelation rate to ultrasound frequency and (b) relative intensity of cavitation to
assembly, which afford microscopic aggregates via further various ultrasound frequencies.
propagation association. Prolonged ultrasound irradiation
would provide a greater amount of the initiator and a more
well-developed fibrous network.
Plausible mechanism for ultrasound-induced self-assembly
Recently, various sonication-induced phenomena such as The ultrasound-induced self-assembly mechanism is proposed
2
4
25,26
sonoluminescence, sonochemical reactions,
and surface as depicted in Fig. 14. First, the extremely high temperature
2
7
cleaning and degradation of organic contaminants have and pressure conditions within the microcavitation bubbles
been investigated in relation to microcavitation. These studies dissociate the intramolecular hydrogen bonds in the self-
demonstrated that implosion of the sonication-induced locked metalated dipeptides to afford unlocked metastable
micron-sized cavity generates a large amount of energy at the intermediates. Evaporation inside the microcavitation bubbles
implosion sites, where the lower the frequency, the larger is leads to supersaturation that accelerates association and
the cavity generated and the higher is the implosion energy. results in interlocked metastable intermediates, and ulti-
Therefore, we investigated the effect of the ultrasound fre- mately, metastable oligomers. Importantly, such high energy,
quency on the gelation rate of 1PdPd. Fig. 13a plots the gelation high concentration conditions cannot be accessed by conven-
rate normalised by the cavitation energy for three ultrasound tional thermal processes (i.e., without sonication), which is the
frequencies, and Fig. 13b depicts the relative intensity of cavi- reason that only amorphous precipitates were formed with a
tation to various ultrasound frequencies. The relationship heating–cooling process. After implosion of the microbubbles,
suggests that ultrasound-induced microcavitation is a key insoluble, well-grown metastable oligomers act as nuclei for
factor in the ultrasound-induced self-assembly of metalated further spontaneous propagation, giving β-sheet supramole-
dipeptides. The exponentially decayed dependence of gelation cular aggregates. In contrast, the primitive, small oligomers
rates on the energy of microcavitation was roughly fitted with readily dissolve in the mother solution to afford the starting
the profile of the relative energy of microcavitation. As self-locked dipeptide. A similar sonication-induced nucleation
described above, microcavitation caused by ultrasound upon amyloid fibril growth has been reported as a sonication-
2
8
irradiation generates high-energy-density sites with extremely specific self-assembly process.
high temperature, pressure, and supersaturation around the
We believe that the initial step that generates oligomers
cavities. As Fig. 13a shows, the gelation rate increases with inside the microcavity proceeds under kinetic control, and that
decreasing frequencies because lower-frequency ultrasound the propagation step for the spontaneous growth of gel fibrils
irradiation generates larger bubbles with higher energy, and after cavitation collapse is a thermodynamically controlled
higher-frequency ultrasound generates smaller bubbles with process (Fig. 15). The high energy conditions inside the micro-
lower energy.
cavitation bubble cleave the M–Cl⋯H–N intramolecular
1
5960 | Dalton Trans., 2013, 42, 15953–15966
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Dalton Transactions
Paper
Fig. 14 Mechanism for ultrasound-induced supramolecular gelation of metalated dipeptides.
Pt–Cl, the stabilisation order of the oligomeric intermediates
would be 1PdPd > 1PtPd = 1PdPt > 1PtPt, as in the case of inter-
locked dimer intermediates, because of the more stable
Pd–Cl⋯H–N hydrogen bond than that of Pt–Cl⋯H–N (Fig. 15,
inset). The order of minimum gelation concentrations
observed in EtOAc solution, 1PdPd < 1PtPd ≈ 1PdPt < 1PtPt, was
also well explained due to the higher degree of stabilisation of
the intermediates and the lower activation energy in the gela-
tion of the Pd-bound dipeptides. In the case of chlorobenzene
gelation, the hydrogen bonding interaction between the excess
amounts of chlorobenzene solvent and the amide hydrogens
stabilises the unlocked metastable intermediates and dramati-
cally decreases the activation energy, to tolerate the stability
differences between the interlocked oligomeric intermediates
of 1PdPd, 1PtPd, 1PdPt, and 1PtPt (Fig. 15, inset). This, then,
results in the similar minimum gelation concentrations shown
in Table 1. The chlorobenzene gelation process would proceed
under more thermodynamic than kinetic control, forming the
thermodynamically more stable parallel-type β-sheet aggre-
gates with Fmoc π–π stacking stabilisation and a sterically
favoured metal configuration (Fig. 11a). Thus, the parallel
β-sheet seems to be the thermodynamically more stable struc-
ture in the self-assembly into supramolecular aggregates.
Fig. 15 Plausible energy diagram for the self-assembly process of metalated
dipeptides. Blue and yellow balls show Pd and Pt moieties, and red and blue
dotted lines show the intra- and intermolecular hydrogen bonds, respectively.
The inset shows the thermal stabilities of the interlocked intermediates of 1PdPd
,
1PtPd/1PdPt, and 1PtPt.
hydrogen bonds to give the “unlocked” metastable monomers,
which then form metastable oligomeric interlocked intermedi-
ates. In this process, intermolecular M–Cl⋯H–N hydrogen
bonds stabilise and lower the activation energy to give larger
metastable/stable oligomers. This mechanism well explains
our results: no gelation occurred with metalated peptides
having weaker or no intramolecular M–Cl⋯H–N hydrogen
Conclusions
bonds, even at higher concentration or with longer soni- We synthesised Pd,Pt-bound bis-metalated dipeptides by the
5
cation. From the calculated hydrogen bond acceptor abilities condensation of robust Pd- and Pt-aldimine-complex-bound
of M–Cl, where Pd–Cl shows a more potent ability compared to glutamic acids. The four possible metal-sequenced isomeric
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Dalton Transactions
dipeptides were fully characterised, and the absence of metal Gelation test
leaching or redistribution during the peptide synthesis was
A mixture of metalated peptides 1PdPd, 1PtPd, 1PdPt, 1PtPt and
confirmed. The ultrasound-induced gelation properties of the
metalated dipeptides were evaluated in order to fabricate well-
ordered metal arrays. The precise self-assembled structures of
the supramolecular gels were elucidated by means of SEM,
WAXS, and SAXS analyses, which revealed the formation of
multilamellar β-sheet aggregates. Selective parallel β-sheet for-
mation was accomplished in chlorobenzene solution,
affording 3D controlled metal arrays. These results clearly
demonstrated the potential utility of metal array fabrication
using metalated peptides, because the facile peptide synthesis
protocol enabled complete control of the 1D sequence in the
metal array and selective formation of the 3D metal arrange-
ment through the one-pot self-assembly process. The evalu-
solvents were charged with a glass test tube (50.0 mm ×
10.0 mm, thickness: 1.00 mm). The test tube was capped
and heated until the complex was completely dissolved into
the solvent. The resulting solution was cooled for 1 min
with the help of a water bath after standing at room tempera-
ture for 30 min to confirm the stable solution state at room
temperature, the solutions were sonicated for 3 min using a
−2
sonoreactor (0.45 W cm , 40 kHz). The states of the phase
were confirmed if these two criteria were met: (1) by visual
observation; (2) when inverted, sample did not flow
perceptibly.
1
XRD analysis
ation of the minimum gelation concentration, the H NMR
association experiment using model complexes, and the DFT The gel samples for XRD analysis were prepared by sonication
calculations based on the X-ray structures of the Pd- and (0.45 W cm− , 40.0 kHz) of a solution of 1.5 × 10 M of 1PdPd
2
−2
,
Pt-aldimine complexes revealed the hydrogen bonding abilities PtPd, 1PdPt, and 1PtPt in EtOAc or chlorobenzene in a glass
1
of the Pd–Cl and Pt–Cl moieties, which are the key factors in capillary (8.4 mm × 0.9 mm, thickness 0.02 mm) at room
the ultrasound-induced gelation. Kinetics experiments on this temperature. The WAXS and SAXS analyses were performed
gelation process at various ultrasound frequencies clearly using BL19B2 and BL40B2 beam lines at SPring-8.
showed that ultrasound-induced microcavitation promoted
and accelerated the self-assembly of the metalated dipeptides.
Synthesis of Fmoc-L-Glu(O[Pt])-OAll {[Pt]v(–(CH ) NvCH–
2 2
C H )Pt(Cl)(PPh )} (2b). Compound 6b (0.840 g, 1.31 mmol),
6 4 3
The mechanistic investigation of the ultrasound-induced self- Fmoc-L-Glu(OH)-OAll (0.455 g, 1.11 mmol), EDCl (0.379 g,
assembly of the metalated peptides with an energy diagram 1.97 mmol), and DMAP (0.0220 g, 0.180 mmol) were
revealed the key feature of the ultrasound-mediated gelation: added to CH Cl (13.0 mL), stirred at room temperature for
2 2
the high-energy microcavitation environment controls the 6 h. The mixture solution was washed with water (25.0 mL × 2)
switching of the intra- and intermolecular hydrogen bonds of and brine (25.0 mL), dried over Na SO . The solvent
2
4
the metalated dipeptides. Based on this mechanistic investi- was removed under vacuum to give yellow product. The
gation, the further exploitation of metal array fabrication will resulting product was purified by SiO column chromato-
be attempted using longer heterometalated peptides, directed graphy eluting with EtOAc–Hexane (1/2) to afford a yellow solid
2
1
toward the preparation of functional nanomaterials bearing of 2b (1.07 g, 94%). H NMR (CDCl
3
, 500 MHz): δ 1.93–2.00 (m,
CO–), 2.20–2.27 (m, 1H, –CHCH CH CO–),
.34–2.47 (m, 2H, –CHCH CH COO–), 4.21 (t, J = 7.0 Hz, 1H,
unique photo- and electronic properties.
1H, –CHCH CH
2 2
2
2
2
2
2
(
1
4
C
6
H
4
)
2
CH–), 4.30–4.36 (m, 2H, –OCH
H, FmocNHCH–), 4.42 (d, J = 6.5 Hz, 2H, (C
.53–4.61 (m, 2H, –OCH CH Nv), 4.63 (d, J = 6.0 Hz, 2H,
2
CH
2
Nv), 4.38–4.46 (m,
6
H
4
)
2
CHCH –),
2
Experimental
2
2
General
–
–
–
OCH
COOCH
2
CHvCH
2
), 5.25 (dd, 10.5, 1.0 Hz, 1H,
J
=
1
13
31
H, C and P NMR spectra were recorded on JEOL JNM-AL400,
2
CHvCH
2
), 5.33 (dd, J = 17.5, 1.0 Hz, 1H,
Varian Unity-500 and JEOL JNM-ECA 920 spectrometers. High
resolution mass spectra were obtained on a Bruker Daltonics
solariX Fourier transform ion cyclotron mass spectrometer
COOCH CHvCH ), 5.41 (d, J = 8.5 Hz, 1H, FmocNH–), 5.89
2
2
(
ddd, J = 17.0, 10.0, 6.5 Hz, 1H, –COOCH
2
CHvCH
Pt–), 6.55 (ddd, J = 7.0,
.5, 1.0 Hz, 1H, C H Pt–), 6.86 (ddd, J = 7.5, 7.0, 0.5 Hz, 1H,
2
), 6.52 (ddd,
JH–H = 7.0, 1.0 Hz, JP–H = 2.5 Hz, 1H, C H
6 4
(FT-ICR-MS). Optical rotation was measured on a JASCO DIP-370
6
6
4
digital polarimeter. Ultrasound irradiation was performed on a
Honda HSR-301 sonoreactor equipped with ultrasound synthesi-
zer. SEM images were obtained on Hitachi S-5000L. Single
crystal X-ray diffraction analyses were employed using Rigaku
AFC-10R with Saturn 724+ detector for 6a and BL02B1 at SPring-
C
6
H
4
Pt–), 7.28 (dd, J = 7.5, 1.0 Hz, 1H, C
CH–), 7.33–7.39 (m, 6H, –P(C
.37–7.44 (m, 5H, (C H ) CH–, –P(C H ) ), 7.58 (d, J = 7.5 Hz,
6
H
4
Pt–), 7.31 (ddd, J =
7
7
1
.5, 7.5, 1.0 Hz, 2H, (C
6
H
4
)
2
6 5 3
H ) ),
6
4 2
6 5 3
H, (C
H )
6 4 2
CH–), 7.59 (d, J = 7.5 Hz, 1H, (C
CH–, –P(C ), 8.30 (d, JP–H = 9.5 Hz, JPt–H
1.0 Hz, 1H, CHvN–). C NMR (CDCl , 125 MHz): δ 28.6, 30.1,
6 4 2
H ) CH–), 7.72–7.76
(
m, 8H, (C
H )
6 4 2
H )
6 5 3
=
1
3
8
with Mercury detector for 6b. XRD measurements were per-
8
4
1
1
3
formed using beam lines BL19B2 and BL40B2 at SPring-8.
7.1, 53.3, 56.9, 63.6, 66.2, 67.0, 119.2, 120.0, 122.9, 125.0,
27.1, 127.77, 127.9, 128.4, 129.9, 130.8, 131.3, 131.8, 135.4,
37.05, 137.10, 141.27, 141.29, 143.6, 143.8, 145.44, 145.49,
Materials
3
1
Palladium-bound amino acids 2a, 3a, 4a, dipeptide 1PdPd, N- 146.2, 156.0, 171.5, 172.4, 179.6. P NMR (CDCl
3
, 202.3 MHz): δ
benzylidenebutylamine, and Pt{C –CHvN(CH OH}(Cl)– 22.949 (s, JPt–P = 4222.2 Hz, 1P, PtPPh ). FT-ICR-MS (ESI): m/z
6
H
4
2
)
2
3
5
,6
+
(
PPh ) were synthesized according to the previous reports.
calcd for C H N O PPt [M − Cl] 996.27402, found 996.27194.
3
50 46
2
6
1
5962 | Dalton Trans., 2013, 42, 15953–15966
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Dalton Transactions
Synthesis of Fmoc-L-Glu(O[Pt]n=2)-NHBu {[Pt]n=2v(–(CH
Paper
2
)
2
-
(50.2 mg, 0.0293 mmol, 26%). IR (KBr): 3367 (N–H), 1733
NvCHC H )Pt(Cl)(PPh )} (3b). Platinated amino acid 2b (CvO), 1663 (CvO), 1618 (CvN) cm−
1
.
1
H NMR (CDCl3,
CH CH ), 1.28 (qt,
), 1.43 (tt, J = 7.4, 7.4 Hz,
2H, –CH CH CH CH ), 1.90–1.95 (m, 2H, –CHCH CH CO–),
6
4
3
(
0.205 g, 0.198 mmol), Pd(PPh
dimethylcyclohexan-1,3-dione (dimedone, 0.0333 g, 0.238 mmol), J = 7.4, 7.4 Hz, 2H, –CH
and EDCl (0.0775 g, 0.404 mmol) were added into CH Cl
3
)
4
(0.0273 g, 0.0236 mmol), 5,5- 920 MHz): δ 0.86 (t, J = 7.4 Hz, 3H, –CH
2
CH
2
2
3
2
CH CH CH
2
2
3
2
2
2
2
2
3
2
2
(
2.5 mL), and the solution was stirred for 0.5 h at room temp- 2.09–2.13 (m, 2H, –CHCH
erature. The solution was added to n-butylamine (0.0220 mL, –CHCH CH COO–), 2.44–2.49 (m, 1H, –CHCH
.222 mmol) and stirred 12 h at room temperature. The 2.48–2.53 (m, 1H, –CHCH CH COO–), 3.14–3.21 (m, 2H,
2
CH
2
CO–), 2.36–2.41 (m, 2H,
2
2
2
CH COO–),
2
0
2
2
solvent was removed under vacuum to give a yellow orange –CONHCH
product. The resulting product was purified by SiO column 4.19 (t, J = 7.5 Hz, 1H, (C
chromatography eluting with EtOAc–Hexane (1/1) to afford a –OCH CH Nv), 4.26–4.28 (m, 1H, –OCH CH Nv), 4.34–4.37
2
CH
2
CH
2
CH
3
), 4.13–4.16 (m, 1H, FmocNHCH–),
2
6 4 2
H )
CH–), 4.18–4.22 (m, 2H,
2
2
2
2
yellow solid of 3b (0.144 g, 69%). IR (KBr): 3409 (N–H), 1725 (m, 2H, –CONHCHCONH–, –OCH
2
CH
–), 4.53–4.60 (m, 4H, –OCH
00 MHz): δ 0.91 (t, J = 7.5 Hz, 3H, –CH CH CH CH ), 1.32 (qt, (d, J = 6.4 Hz, 1H, FmocNHCH–), 6.38 (dd, J = 6.4, 6.4 Hz, 1H,
2
Nv), 4.39 (d, J = 6.5 Hz,
−1
1
(CvO), 1664 (CvO), 1616 (CvN) cm
.
H NMR (CDCl
3
,
2H, (C
6
H
4
)
2
CHCH
2
2
CH Nv), 5.75
2
5
2
2
2
3
J = 7.5, 7.5 Hz, 2H, –CH
2
CH
), 1.86–1.93 (m, 1H, –CHCH
.07–2.17 (m, 1H, –CHCH CH CO–), 2.35–2.42 (m, 1H, C H Pd–, C H Pt–), 6.84 (dd, J = 7.4, 6.4 Hz, 1H, C H –), 6.87
2
CH
2
CH
3
), 1.46 (tt, J = 7.5, 7.5 Hz,
C
6
H
4
Pd–), 6.45 (t, J = 5.5 Hz, 1H, –CONHBu), 6.49 (dd, J = 8.3,
2H, –CH CH CH CH
2 2 2 3
2
CH CO–), 1.8 Hz, 1H, C
2
6 4
H
Pt–), 6.52, 6.53 (ddd, J = 7.4, 7.4, 1.8 Hz, 2H,
2
2
2
6
4
6
4
6 4
–
CHCH
2
CH
2
COO–), 2.50–2.58 (m, 1H, –CHCH
2
CH
), 4.14–4.20 (m, 1H, –CONHCHCONH–), 7.27–7.31 (m, 4H, (C
7.5 Hz, 1H, (C H ) CH–), C H Pd–), 7.32–7.34 (m, 14H, (C H ) CH–, –P(C H ) ),
2
COO–), (ddd, J = 8.3, 7.4, 0.9 Hz, 1H, C
6
H
4
–), 7.11 (d, J = 8.3 Hz 1H,
3
.19–3.25 (m, 2H, –CONHCH
2
CH CH CH
2 2 3
=
6
H
4
)
2
CH–, C Pt–,
6 4
H
FmocNHCHCO–), 4.21 (t,
.25–4.31 (m, 1H, –OCH CH
CHCH –), 4.40–4.46
.52–4.58 (m, 1H, –OCH CH Nv), 4.63–4.68 (br, 1H, (m, 14H, (C H ) CH–, –P(C H ) ), 8.16 (d, J
J
6
4 2
6
4
6
4 2
6 5 3
4
2
2
Nv), 4.39 (d, J = 6.5 Hz, 2H, 7.38–7.41 (m, 6H, –P(C
6 5 3
H ) ), 7.56 (d, J = 7.4 Hz, 1H,
(C
H )
6 4 2
2
(m, 1H, –OCH CH Nv), (C CH–), 7.58 (d, J = 7.4 Hz, 1H, (C
2
2
6
H
4
)
2
6
H
4
)
2
CH–), 7.70–7.74
4
= 7.4 Hz, 1H,
2
2
6
4 2
6
5 3
P–H
1
3
–
OCH
CONHBu), 6.42–6.58 (m, 2H, C
.5 Hz, 1H, C H Pt–), 7.28 (dd, J = 7.5, 1.0 Hz, 1H, C H Pt–), 7.31 47.1, 52.8, 54.9, 56.7, 57.5, 63.8, 64.0, 67.2, 120.0, 123.0, 124.1,
2
CH
2
Nv), 5.65 (d, J = 8.0 Hz, 1H, FmocNH–), 6.12 (br, 1H, CHvNPd–), 8.35 (d, JP–H = 8.3 Hz, 1H, CHvNPt–). C NMR
–
6 4
H Pt–), 6.82 (ddd, J = 7.5, 7.0, (CDCl , 125 MHz): δ 13.7, 20.0, 27.5, 30.4, 30.6, 31.4, 39.4,
3
0
6
4
6 4
(
ddd, J = 7.5, 7.5, 1.0 Hz, 2H, (C
), 7.39–7.44 (m, 5H, (C
.0 Hz, 1H, (C H ) CH–), 7.59 (d, J = 7.0 Hz, 1H, (C H ) CH–), 138.24, 141.25, 141.27, 143.55, 143.73, 145.37, 146.2, 147.9,
6
H
4
)
2
CH–), 7.33–7.39 (m, 6H, –P 125.1, 127.2, 127.8, 127.9, 128.1, 128.4, 128.6, 129.95, 130.52,
(C
H )
6 5 3
6
H
4
)
2
CH–, –P(C ), 7.58 (d, J = 130.87, 130.8, 131.82, 135.39, 135.42, 137.01, 137.06, 138.16,
6 5 3
H )
7
7
6
4 2
6 4 2
3
1
.72–7.77 (m, 8H, (C
6
H
4
)
2
CH–, –P(C
6
H
5
)
3
), 8.38 (d, JP–H = 9.0 Hz, 156.4, 158.3, 170.4, 171.2, 173.1, 173.7, 177.7, 180.0. P NMR
, 125 MHz): δ 13.7, (CDCl , 202.3 MHz): δ 22.939 (s, JPt–P = 4216.0 Hz, 1P, PtPPh ),
0.0, 28.9, 30.4, 31.5, 39.4, 47.1, 54.0, 57.0, 63.7, 67.1, 120.0, 43.206 (s, 1P, PdPPh ). FT-ICR-MS (ESI): m/z calcd for
13
JPt–H = 88.5 Hz, 1H, CHvN–). C NMR (CDCl
3
3
3
2
1
1
1
3
+
22.9, 125.1, 127.12, 127.78, 127.9, 128.5, 130.0, 130.8, 131.7,
35.4, 137.03, 137.08, 141.29, 143.6, 143.8, 145.40, 145.45, 146.3, [α]
56.3, 170.8, 173.3, 179.8. P NMR (CDCl , 202.3 MHz): δ 22.921
C
83
H
81ClN
5
O
8
P
2
PdPt [M − Cl] 1674.39446, found 1674.40746.
+15.8 (c 0.54, CHCl ).
Synthesis of Fmoc-L-Glu(O[Pt]n=2)-L-Glu(O[Pd]n=2)-NHBu
). FT-ICR-MS (ESI): m/z calcd for {[Pt]n=2v(–CH CH NvCHC )Pt(PPh )(Cl)}, {[Pd]n=2v(–CH CH
)Pd(PPh )(Cl)} (1PtPd). Palladated amino acid 3a
(0.192 g, 0.200 mmol) was dissolved into acetonitrile (10.0 mL)
Synthesis of Fmoc-L-Glu(O[Pd]n=2)-L-Glu(O[Pt]n=2)-NHBu and piperidine (210 μL) was added, stirred for 30 min at room
[Pd]n=2v(–(CH NvCHC )Pd(Cl)(PPh ), [Pt]n=2v(–(CH temperature. The reaction mixture was washed with hexane
NvCHC H )Pt(Cl)(PPh )} (1PdPt). Piperidine (0.120 mL) was (10.0 mL × 5) and evaporated to afford a yellow solid. The
2
2
D
3
31
3
(s, JPt–P = 4218.3 Hz, 1P, PtPPh
3
2
2
6
H
4
3
2
2
-
+
27
D
C
+
H N O
51 51 3 5
PPt [M − Cl] 1011.32127, found 1011.31784. [α]
NvCHC
6
H
4
3
5.1 (c 0.31, CHCl3).
{
2
)
2
6
H
4
3
2 2
) -
6
4
3
added to a stirred solution of platinated amino acid 3b yellow solid was dissolved into CH
0.121 g, 0.115 mmol) in acetonitrile (6.00 mL). The solution the CH Cl (2.00 mL) solution of platinated amino acid 2b
was stirred for 0.5 h at room temperature. The mixture solu- (0.207 g, 0.200 mmol), Pd(PPh ) (23.2 mg, 20.0 μmol), dime-
2 2
Cl (2.00 mL) and added to
(
2
2
3
4
tion was washed with hexane (10.0 mL × 5) and evaporated to done (30.8 mg, 0.220 mmol), and EDCl (76.6 mg, 0.400 mmol)
afford a yellow oil. The yellow oil was dissolved into CH
2
Cl
2
which had been stirred for 30 min at room temperature before-
(
5.00 mL), and added to the CH Cl (10.0 mL) solution of pal- hand. The reaction mixture was stirred for 12 h at room temp-
2
2
ladium amino acid 2a (0.102 g, 0.115 mmol), Pd(PPh
3
)
4
2
erature. The residue was chromatographed on SiO , where a
(14.0 mg, 0.0120 mmol), dimedone (20.6 mg, 0.147 mmol), major fraction was collected and evaporated to give a yellow
and EDCl (46.2 mg, 0.241 mmol) which had been stirred solid of 1PtPd. Further purification was carried out using recy-
for 0.5 h at room temperature beforehand. The reaction cling gel permeating chromatography to afford pure 1PtPd
1
mixture was stirred for 12 h at room temperature. The (0.113 g, 33%). H NMR (CDCl
3
, 920 MHz): δ 0.85 (t, J = 7.4 Hz,
residue was purified by SiO2 column chromatography 3H, –CH CH ), 1.27 (qt, J = 7.4, 7.4 Hz, 2H, –CH CH CH ),
2
3
2
2
3
eluting with EtOAc–Hexane (3/1) to afford a yellow solid 1.40–1.46 (m, 2H, –CH
of 1PdPt. Further purification was carried out using recycling 2.08–2.16 (m, 2H, –CHCH
gel permeating chromatography to afford pure 1PdPt –CH CH CO–), 2.45 (ddd, J = 17.5, 7.4, 6.4 Hz, 1H, –CH CH CO–),
2
CH
2
CH
2
–), 1.92 (br, 2H, –CHCH
2
CH
2
–),
2 2
CH –), 2.36–2.41 (m, 2H,
2
2
2
2
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Paper
Dalton Transactions
2
.50 (ddd, J = 16.7, 8.0, 5.5 Hz, 1H, –CH
2
CH
2
CO–), 3.15 (ddt, J = –OCH
2
CH
2
Nv),
4.34–4.38
(m,
3H,
2 2
–OCH CH Nv,
1
3.2, 7.3, 5.3 Hz, 1H, –NHCH CH –), 3.19 (ddt, J = 13.2, 7.3, –CONHCHCONH–), 4.39 (d, J = 6.4 Hz, 2H, (C H ) CHCH –),
2
2
6
4 2
2
5
.3 Hz, 1H, –NHCH
J = 7.4, 7.4, 5.6 Hz, 1H, –NHCHCO–), 4.18 (t, J = 7.2 Hz, 1H, FmocNHCH–), 6.44 (t, J = 5.5 Hz, 1H, –CONHBu), 6.49 (dd, J = 8.3,
C H ) CHCH –), 4.22 (br, 1H, –CH CH N–), 4.29 (br, 1H, 1.8 Hz, 2H, C H Pt–), 6.53 (ddd, J = 7.4, 7.4, 1.8 Hz, 2H, C H Pt–),
2 2 2 2 2 2
CH –), 4.12 (br, 1H, –CH CH N–), 4.14 (ddd, 4.54–4.58 (m, 4H, –OCH CH Nv), 5.74 (d, J = 5.5 Hz, 1H,
(
6
4 2
2
2
2
6
4
6 4
–
OCH
.2 Hz, 2H, (C
CH CH N–), 4.58 (br, 2H, –OCH CH –, –CH CH N–), 5.81 (d, J = 7.27–7.31 (m, 4H, (C H ) CH–, C H Pt–), 7.32–7.34 (m, 14H,
2
CH
2
–), 4.34 (br, 2H, –OCH
2
CH
2
–, –NHCHCO–), 4.39 (d, J = 6.84 (dd, J = 7.4, 6.4 Hz, 1H, C
6 4
H Pt–), 6.87 (ddd, J = 7.4, 7.4, 0.9
7
–
6
H
4
)
2
CHCH O–), 4.52–4.57 (m, 2H, –OCH
2
2
CH –, Hz, 1H, C Pt–), 7.12 (d, J = 7.4 Hz 1H, –CONHCHCONH–),
2
6 4
H
2
2
2
2
2
2
6
4 2
6 4
6
1
7
.2 Hz, 1H, FmocNHCH–), 6.37 (dd, JH–H = 7.2 Hz, JP–H = 6.5 Hz, (C
H, –C Pd–), 6.48 (t, J = 5.3 Hz, 1H, –CHNHBu), 6.50 (dd, J = 7.4 Hz, 1H, (C
.5, 1.5 Hz, 1H, –C H Pt–), 6.52 (ddd, J = 7.5, 7.5, 1.5 Hz, 1H, 7.70–7.73 (m, 14H, (C H ) CH–, –P(C H ) ), 8.34 (d, J
6 4 2 6 5 3 6 5 3
H ) CH–, –P(C H ) ), 7.38–7.41 (m, 6H, –P(C H ) ), 7.56 (d, J =
6
H
4
6
H
4
)
2
CH–), 7.58 (d, J = 7.4 Hz, 1H, (C
6
H
4
)
2
CH–),
= 9.2 Hz,
6
4
6
4 2
6
5 3
P–H
13
–
C
6
H
4
Pd–), 6.53 (dd, J = 7.5, 7.5 Hz, 1H, –C
.5, 7.5 Hz, 1H, –C Pd–), 6.87 (ddd, J = 7.5, 7.5, 1.5 Hz, 1H, (CDCl
C H Pt–), 7.14 (d, J = 7.5 Hz, 1H, –CONHCH–), 7.27 (dd, J = 7.5, 52.8, 54.8, 56.69, 57.79, 63.77, 63.81, 67.2, 120.0, 122.98, 123.04,
6 4
H Pt–), 6.84 (dd, J = 1H, CHvN–), 8.35 (d, JP–H = 9.2 Hz, 1H, CHvN–). C NMR
7
–
6
H
4
3
, 125 MHz): δ 13.7, 20.0, 27.5, 30.4, 30.6, 31.4, 39.4, 47.1,
6
4
1
7
7
.5 Hz, –C
.30 (dd, J = 7.5, 1.5 Hz, 1H, –C
.5, 1.5 Hz, JP–H = 7.5 Hz, 12H, –P(C H ) ), 7.36 (ddd, J = 7.5, 7.5, 143.54, 143.73, 145.29, 145.36, 145.36, 145.42, 146.24, 146.30,
6
H
4
Pt–), 7.29 (ddd, J = 7.5, 7.5, 1.5 Hz, 2H, (C
6 4 2
H ) CH–), 125.1, 127.2, 127.8, 127.9, 128.62, 128.65, 129.94, 129.97, 130.8,
6 4
H Pd–), 7.33 (dddd, JH–H = 7.5, 131.76, 131.81, 135.37, 135.39, 136.99, 137.04, 141.24, 141.25,
6
5 3
31
1
6
.5 Hz, 2H, (C
H, –P(C ), 7.57 (d, J = 7.5 Hz, 1H, (C
Hz, 1H, (C H ) CH–), 7.70–7.76 (m, 14H, –P(C H ) , (C H ) CH–), FT-ICR-MS (ESI): m/z calcd for C H ClN O P Pt [M − Cl]
6
H
4
)
2
CH–), 7.40 (tdd, JH–H = 7.5, 1.5, JP–H = 7.5 Hz, 156.4, 170.4, 171.2, 173.1, 173.6, 179.98, 180.00. P NMR (CDCl
3
,
6
H
5
)
3
6
H
4
)
2
CH–), 7.58 (d, J = 7.5 202.3 MHz): δ 22.884, 22.949 (s, JPt–P = 4231.5 Hz, 2P, PtPPh ).
3
+
6
4 2
6
5 3
6
4 2
83 81
5
8
2
2
2
4
8.15 (d, JP–H = 7.8 Hz, 1H, –CHNPd–), 8.36 (d, JP–H = 9.0 Hz, 1H, 1763.45457, found 1763.46586. [α]
D
+16.0 (c 0.53, CHCl
3
).
1
3
–CHNPt–). C NMR (CDCl
3
, 125 MHz): δ 13.7, 19.9, 27.5, 29.2,
Synthesis of Pt{C
6
H
4
–CHvN(CH CH }(Cl)(PPh
2
)
3
3
3
) (5b). N-
3
0.4, 30.6, 31.3, 31.7, 39.3, 47.1, 52.9, 53.7, 54.8, 56.8, 57.3, 63.7, Benzylidenebutylamine (2.43 g, 15.1 mmol) and K [PtCl ] (2.14 g,
2
4
6
1
1
4.0, 67.2, 120.0, 122.9, 124.1, 125.1, 127.1, 127.7, 127.8, 127.9, 5.16 mmol) were added to acetic acid (200 mL). The solution was
28.0, 128.1, 128.5, 128.6, 129.7, 130.2, 130.6, 130.7, 130.8, 131.0, stirred for 24 h at 70 °C under argon atmosphere. After cooling to
35.3, 135.4, 137.0, 138.1, 138.2, 141.2, 143.5, 143.7, 145.4, 146.3, room temperature, PPh (1.36 g, 5.17 mmol) was added to the
3
1
47.8, 156.4, 158.2, 170.4, 171.2, 173.1, 173.7, 177.7, 180.0. mixture, and then stirred for 3 h. The mixture was filtered through
P NMR (CDCl , 202.3 MHz): δ 23.02 (s, JPt–P = 4206.6 Hz, celite and the solvent was removed under vacuum to afford a
3
3
1
PtPPh ), 43.19 (s, PdPPh ). FT-ICR-MS (ESI): m/z calcd for yellow product. The resulting product was purified by SiO column
3
3
2
+
C
83
H
81ClN
Synthesis
[Pt]n=2v(–(CH ) NvCHC H )Pt}(Cl)(PPh )} (1PtPt). Piperidine the desired complex as a yellow solid of 5b (0.293 g, 9%). IR (KBr):
0.600 mL) was added to a stirred solution of platinated amino 1617 (CvN) cm . H NMR (CDCl
acid 3b (0.669 g, 0.643 mmol) in acetonitrile (20.0 mL). The 7.5 Hz, 3H, –CH CH CH CH ), 1.40 (qt, J = 7.5, 7.5 Hz, 2H,
solution was stirred for 0.5 h at room temperature. The –CH CH CH CH ), 1.87 (tt, J = 7.5, 7.5 Hz, 2H, –CH CH CH CH ),
5
O
8
P
2
PdPt [M − Cl] 1673.39463, found 1673.41035.
chromatography eluted with EtOAc–Hexane (1/3) to afford a yellow
of
2 2
Fmoc-L-Glu(O[Pt]n=2)-L-Glu(O[Pt]n=2)-NHBu mixture. The mixture reprecipitated from CH Cl –Hexane to give
{
(
2 2
6
4
3
−
1 1
3
, 500 MHz): δ 0.95 (t, J =
2
2
2
3
2
2
2
3
2
2
2
3
mixture solution was washed with hexane (60.0 mL × 5) and 3.61 (td, J = 7.0, 4.5 Hz, 2H, vNCH
2
CH
2
CH
2
CH
3
), 6.50 (ddd,
Pt–), 6.54
evaporated to afford a yellow oil. The yellow oil was dissolved H–H = 6.5, 1.5 Hz, JP–H = 2.5 Hz, JPt–H = 43.0 Hz, 1H, C H
J
6 4
into CH Cl (10.0 mL), and added to the CH Cl (20.0 mL) (ddd, J = 8.0, 7.0, 1.5 Hz, 1H, C H Pt–), 6.90 (ddd, J = 7.5, 7.0, 1.5 Hz,
2
2
2
2
6 4
solution of 2b (0.692 g, 0.670 mmol), Pd(PPh
3
)
4
(82.8 mg, 1H, C
6
H
4
Pt–), 7.26 (dd, J = 7.5, 1.0 Hz, 1H, C
), 7.40–7.44 (m, 3H, –P(C
EDCl (0.296 g, 1.54 mmol) which had been stirred for 0.5 h at 6H, –P(C H ) ), 8.27 (d, J = 9.5 Hz, JPt–H = 91.0 Hz, 1H,
6
H
4
Pt–), 7.34–7.38
0
.0717 mmol), dimedone (0.108 g, 0.768 mmol), and (m, 6H, –P(C
6
H
5
)
3
H ) ), 7.72–7.77 (m,
6 5 3
6
5 3
P–H
1
3
room temperature beforehand. The reaction mixture CHvN–). C NMR (CDCl
3
, 125 MHz): δ 13.8, 19.9, 32.9, 58.4,
was stirred for 12 h at room temperature. The residue was 122.8, 127.6, 127.8, 130.2, 130.7, 131.15, 131.17, 135.4, 137.05,
31
purified by SiO2 column chromatography eluting with 137.10, 144.97, 145.02, 146.6, 177.1. P NMR (CDCl , 202.3 MHz):
3
EtOAc–Hexane (3/1) to afford a yellow solid of 1PtPt. Further δ 23.113 (s, JPt–P = 4183.2 Hz, 1P, PtPPh
3
). FT-ICR-MS (ESI): m/z
+
purification was carried out using recycling gel permeating calcd for C29H29NPPt [M − Cl] 617.16827, found 617.16872.
chromatography to afford pure 1PtPt (0.454 g, 0.252 mmol, 39%).
X-ray crystallographic analysis of 6a and 6b
IR (KBr): 3398 (N–H), 1733 (CvO), 1669 (CvO), 1616 (CvN)
−1
1
cm . H NMR (CDCl
3
, 920 MHz): δ 0.86 (t, J = 7.4 Hz, 3H, Crystal of 6a and 6b suitable for X-ray diffraction study was
–
CH CH CH CH ), 1.28 (qt, J = 7.4, 7.4 Hz, 2H, –CH CH CH CH ), obtained from CHCl and EtOAc solution, respectively. Inten-
2
2
2
3
2
2
2
3
3
1
–
.43 (tt, J = 7.4, 7.4 Hz, 2H, –CH
CHCH CH CO–), 2.08–2.13 (m, 2H, –CHCH
m, 2H, –CHCH CH COO–), 2.44–2.49 (m, 1H, –CHCH CH COO–), 0.71070 Å) and Saturn724+ detector with synchrotron radiation
2
CH
2
CH
2
CH
3
), 1.91–1.95 (m, 2H, sity data were corrected on a Rigaku Saturn AFC-10R diffract-
2
2
2
CH CO–), 2.36–2.41 ometer with graphite monochromated Mo-Kα radiation (λ =
2
(
2
2
2
2
2
.49–2.53 (m, 1H, –CHCH
2 2
CH COO–), 3.14–3.21 (m, 2H, (λ = 0.69980 Å). The structures of 6a and 6b were solved by
–
CONHCH CH CH CH ), 4.13–4.15 (m, 1H, FmocNHCHCO–), direct methods and refined by the full-matrix least-squares
2
2
2
3
4
.18 (t, J = 7.4 Hz, 1H, (C H ) CH–), 4.25–4.30 (m, 2H, methods using SHELX-97.
6
4 2
1
5964 | Dalton Trans., 2013, 42, 15953–15966
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Dalton Transactions
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9
K. Tanaka, K. Kaneko, Y. Watanabe and M. Shionoya,
Dalton Trans., 2007, 5369.
Acknowledgements
This work was supported by Grant-in-Aid for Scientific 10 F. Fujimura and S. Kimura, Org. Lett., 2007, 9, 793.
Research (22550099) and Grant-in-Aid for Scientific Research 11 T. Yamamura, S. Suzuki, T. Taguchi, A. Onoda, T. Kamachi
on Innovative Areas, The Coordination Programming–Science
and I. Okura, J. Am. Chem. Soc., 2009, 131, 11719.
of Super-molecular Structure and Creation of Chemical 12 (a) A. Ojida, K. Honda, D. Shinmi, S. Kiyonaka, Y. Mori and
Elements (24108719) from the Ministry of Education, Culture,
Sports, Science and Technology (MEXT), PREST (07051361)
programs from Japan Science and Technology Agency (JST).
I. Hamachi, J. Am. Chem. Soc., 2006, 128, 10452; (b) A. Ojida,
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I. Hamachi, Chem.–Asian. J., 2010, 5, 877.
The synchrotron radiation experiments were performed at the 13 (a) B. M. J. M. Suijkerbuijk, M. Q. Slagt, R. J. M.
2
9
SPring-8 (BL02B1:
2
2013A1661, BL19B2: 2009A1805;
K. Gebbink, M. Lutz, A. L. Spek and G. van Koten, Tetra-
hedron Lett., 2002, 43, 6565; (b) B. Geißer and R. Alsfasser,
Inorg. Chim. Acta, 2003, 348, 179; (c) M. Salman, M. Gunn,
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K.I. expresses his special thanks to the MEXT project “inte-
grated research on chemical synthesis”. K.O. expresses his
special thanks to the Global COE program “International
Center for Integrated Research and Advanced Education in
Materials Science” for financial support. All the authors thank
Prof. Masaharu Nakamura for his conduct, helpful discussion, 14 (a) A. Fedorova, A. Chaudhari and M. Y. Ogawa, J. Am. Chem.
and commitment to all of us. The authors also thank Ms
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This journal is © The Royal Society of Chemistry 2013
Dalton Trans., 2013, 42, 15953–15966 | 15965

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Paper
Dalton Transactions
2
2 For examples of Pd–Cl⋯H–N hydrogen bonds in the
crystalline state, see: (a) O. Baldovino-Pantaleón,
D. Morales-Morales, S. Hernández-Ortega, R. A. Toscano
c2cs35463b; (b) M. M. Caruso, D. A. Davis, Q. Shen,
S. A. Odom, N. R. Sottos, S. R. White and J. S. Moore,
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