Cooperative complexation of amino acid derivatives to platinum acetylide-based bolaamphiphile

Article abstract of DOI:10.1021/ol500752b

A platinum(II) acetylide-based bolaamphiphile equipped with two peripheral B18C6 moieties has been successfully prepared, which demonstrates cooperative recognition behavior toward l-alanine ester salt in chloroform. In a polar methanol/chloroform (3/1, v/v) medium, the amino acid additives influence the aggregation of the bolaamphiphile significantly, leading to the morphological transition from nanospherical to disordered structures. The adaptive properties of the current host-guest binary system will benefit the development of stimuli-responsive supramolecular materials.

Full text of DOI:10.1021/ol500752b

Letter
pubs.acs.org/OrgLett
Cooperative Complexation of Amino Acid Derivatives to Platinum
Acetylide-Based Bolaamphiphile
Yu-Jing Tian,†,‡ En-Tai Shi,‡ Yu-Kui Tian,‡ Ri-Sheng Yao,*,† and Feng Wang*,‡
†School of Medical Engineering, Hefei University of Technology, Hefei, Anhui 230009, P. R. China
‡Key Laboratory of Soft Matter Chemistry, Department of Polymer Science and Engineering, University of Science and Technology
of China, Hefei, Anhui 230026, P. R. China
S
* Supporting Information
ABSTRACT: A platinum(II) acetylide-based bolaamphiphile
equipped with two peripheral B18C6 moieties has been
successfully prepared, which demonstrates cooperative recog-
nition behavior toward L-alanine ester salt in chloroform. In a
polar methanol/chloroform (3/1, v/v) medium, the amino
acid additives influence the aggregation of the bolaamphiphile
significantly, leading to the morphological transition from
nanospherical to disordered structures. The adaptive proper-
ties of the current host−guest binary system will benefit the development of stimuli-responsive supramolecular materials.
Scheme 1. Synthetic Route to the Platinum(II) Acetylide-
Based Bolaamphiphile 1 and Schematic Representation for
the Complexation of L-Alanine Ester Salt 2 with 1 To Afford
the Host−Guest Paired Structure 3
ntegration of biomolecules such as amino acids and peptides
Iinto π-conjugated chromophores represents an efficient
strategy to realize biological−synthetic hybrid materials with
tailored chemical and physical properties.1 Much effort has
been devoted to the covalent linkage of amino acid derivatives
to the π-conjugated molecules.2 In contrast, incorporation of
these bioactive ligands to the π-conjugated assemblies via a
molecular recognition process has been far less exploited. Such
a noncovalent strategy could realize the fine-tuning of solubility
as well as electrical and optical properties for the resulting
supramolecular assemblies.3 More importantly, it commonly
involves complex recognition events, serving as a feasible
platform to mimic biological systems which take advantage of
multivalency and cooperativity principles to achieve enhanced
binding efficiency.4
We endeavor to construct platinum(II)-containing π-
conjugated supramolecular assemblies and examine their
recognition properties toward amino acid additives. Due to
the presence of d8 transition metal ion Pt2+ with square planar
geometry, platinum(II) acetylide complexes have exhibited
interesting self-assembly properties.5,6 For example, we have
recently demonstrated that rod-like platinum(II) acetylide
complexes show the propensity to undergo cooperative
supramolecular polymerization in apolar methylcyclohexane
solution.5d Herein, bolaamphiphilic monomer 1 is designed
which bears two benzo-18-crown-6-ether (B18C6) moieties on
both sides of the rod-like platinum(II) acetylide core (Scheme
1). Considering that the appending B18C6 units act as
solvophilic groups and provide appreciable solubility, bolaam-
phiphile 1 is expected to assemble spontaneously in polar
environments. Meanwhile, since B18C6 is a versatile receptor
for a variety of ammonium cations,7 the homoditopic monomer
1 could associate with amino acid derivatives such as L-alanine
ester salt 2 to achieve host−guest paired structure 3 (Scheme
1). When combining the above two self-assembly processes
together, noncovalent decoration of L-alanine ester salt 2 to the
multivalent self-assembling nanostructures would be realized,
which is advantageous for the development of supramolecular
sensing and chiroptical materials.8
The synthetic route toward the targeted monomer 1 is quite
straightforward (Scheme 1). Reaction of B18C6 acid 4 with 4-
ethynylaniline in the presence of EDC·HCl and DMAP yielded
the amide 5. Further treatment of 5 with trans-[Pt(PEt3)2Cl2]
in the presence of diisopropylamine and copper(I) iodide
afforded bolaamphiphile 1, which was characterized by
multinuclear NMR (1H, 13C, 31P) and ESI-MS spectroscopies
Received: March 11, 2014
© XXXX American Chemical Society
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(Figures S4−S7). The 31P NMR spectrum of 1 displays one
signal at 7.22 ppm in d-chloroform (Figure S6), suggesting the
equivalence of the two phosphorus atoms and validating the
trans configuration for the two triethylphosphine units.
Since chloroform is a solvent that limits aggregation of
chromophores, the maxima UV−Vis absorption band of 1
located at 354 nm in chloroform is assigned to the long-axis
polarized π−π* and Pt−π* transitions from the molecularly
dissolved platinum(II) acetylide unit (Figure 1a, black line).
bolaamphiphile 1, significant downfield shifts are observed for
the amide protons, indicating the formation of intermolecular
hydrogen bonding arrays between the amide groups (Figure
S8). It should be noted that the resonance of the amide protons
disappears in d4-methanol/d-chloroform (3/1, v/v) (Figure
S9), as a consequence of the H/D exchange with the solvent. In
the meantime, no obvious changes occur for the ethyleneoxy
protons on the B18C6 moiety, reflecting the negligible
hydrogen bonding interaction between the ethyleneoxy oxygen
atoms on the B18C6 unit and the amide groups. Therefore,
such phenomena suggest that, in a polar medium, hydrogen
bonding is still maintained between the intermolecular amide
groups, which results in the tight packing of the solvophobic
segments, thereby making significant contributions for the self-
assembly process.9
Detailed microscopic measurements were then performed to
investigate the morphology of the resulting assemblies derived
from 1. Atomic force microscopy (AFM) reveals the presence
of spherical structures for a 10−4 M solution of 1 in methanol/
chloroform (3/1, v/v) (Figure 1c), for which the horizontal
distances of the individual spheres have an average diameter of
220 nm. The size is similar to the hydrodynamic diameter of
the aggregates measured by dynamic light scattering (DLS)
(248 nm, Figure 1b), indicating that the nanospheres do not
spread in the AFM sample preparation. In contrast, based on
DLS measurement, very small aggregates (hydrodynamic
diameter ≈ 5 nm) are detected for a 10−4 M solution of 1 in
chloroform (Figure S13), highlighting the effect of solvent
polarity on the assembling size of the platinum acetylide-based
oligomers. It should be noted that the resulting spherical
structures in polar solvent tend to aggregate together on the
surface, which is supported by transmission electron micros-
copy (TEM) (Figure 1d) and field emission scanning electron
microscopy (FE-SEM) (Figure 1e) measurements. Such
phenomena could be ascribed to the existence of molecule−
surface interactions when depositing the aggregates on the solid
support.10
Figure 1. (a) Changes in absorption spectra of 1 in CHCl3/MeOH
solutions of different solvent compositions (from 100% CHCl3 (black
line) to 5% chloroform in methanol (red line)); (b) hydrodynamic
size distributions of a 10−4 M solution of 1 in MeOH/CHCl3 (3/1, v/
v) measured by DLS at 25 °C; (c) spherical aggregates prepared by
drop-casting a 10−4 M solution of 1 in MeOH/CHCl3 (3/1, v/v) on
mica substrate, as imaged by tapping mode AFM; (d) TEM images of
1 recorded on a copper grid; (e) FE-SEM images of 1 recorded on
silicon wafer; (f) FE-SEM images of a 1:2 mixture of 1 and 2 recorded
by drop-casting of the MeOH/CHCl3 (3/1, v/v) solution on silicon
wafer.
Next, host−guest paired structure 3 resulting from the
association between bolaamphiphile 1 and L-alanine methyl
ester salt 2 was examined in chloroform, which remains the
monomeric state for the platinum(II) acetylide chromophore.
The spectrum of a 1:2 mixture of 1 and 2 displays only one set
of peaks (Figure 2), suggesting fast-exchange complexation
1
between B18C6 and ammonium cations on the H NMR time
scale. After complexation, a significant downfield shift is
observed for the amide protons NH on 1 from 7.69 to 9.42
ppm. Moreover, peaks corresponding to H1, H3, H5, and H6 of
1 move downfield, while CH and CH3 protons of 2 exhibit
upfield shifts due to the shielding effect of the electron-rich
B18C6 macrocyclic ring. In addition, protons H6 of 1 are split
into two signals locating at 4.48 and 4.22 ppm, respectively,
attributing to the different chemical environments. The
apparent proton shifting and splitting phenomena illustrate
The evolution from the monomeric to self-assembled state of
bolaamphiphile 1 is probed by varying the chloroform−
methanol compositions, while keeping the concentration of 1
at 10−4 M. Specifically, increasing the amount of methanol in a
molecularly dissolved solution of 1 in chloroform leads to a
remarkable blue shift of the maxima absorption spectra (348
nm for 1 in methanol/chloroform (19/1, v/v), Figure 1a, red
line), indicating the overlapping of platinum(II) acetylide
chromophores to form H-type aggregates.
For a deeper understanding of the noncovalent forces driving
the self-assembly process, 1H NMR measurements were
investigated for bolaamphiphile 1 in deuterated solvents of
different polarities (d-chloroform and d4-methanol/d-chloro-
form (3/1, v/v)) (Figures S8−S9). For both experiments, the
aromatic protons shield slightly upfield at high monomer
concentration, thus suggesting the involvement of weak
aromatic π−π stacking interactions for the aggregation process.
In d-chloroform, upon increasing the concentration of
+
that the NH3 recognition site forms an edge-to-face
orientation with B18C6 cavities.7c
Further experiments were carried out to determine the
complexation stoichiometry between 1 and 2. Electrospray
ionization mass spectrometry characterization (ESI-MS) was
performed for a mixture solution of 1 and 2 under mild
conditions, which displays two intense peaks locating at m/z
722.7 (100%) and 774.2 (76%), corresponding to [1·2 − Cl −
H]2+ and [1·22 − 2Cl]2+, respectively (Figure S10). Proton
NMR titration experiments were also performed, for which the
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B18C6/NH3+ recognition motif exhibits weaker binding affinity
in methanol/chloroform (3/1, v/v) than that in pure
chloroform (manifested by the slight upfield shifts for protons
H
1−5 in 1H NMR spectra, Figure S14), the amino acid additive
exerts a significant influence on the morphology of the resulting
supramolecular assemblies. Specifically, upon adding 2 equiv of
2 to 1 in methanol/chloroform (3/1, v/v), FE-SEM reveals the
transition from the original spherical structures (Figure 1e) to
disordered and coagulated aggregates (Figure 1f). We
speculated that, to form the desired edge-to-face host−guest
+
complexes between B18C6 and NH3 units, more steric
hindrance and electrostatic repulsion could be imparted to
the periphery of bolaamphiphile 1 (Scheme 2). As a result, the
Scheme 2. Schematic Representation for the Morphological
Transition of Bolaamphiphile 1 in Response to L-Alanine
Ester Salt Additives 2
1
Figure 2. (a) Partial H NMR spectra (300 MHz, d-chloroform, 25
°C): (a) 4.00 mM 2; (b) a 1:2 mixture of 1 and 2 ([1] = 2 mM, [2] =
4 mM); (c) 2.00 mM 1. Signals affiliated with solvents are denoted by
star symbols.
initial concentration of 1 was kept constant at 2.00 mM while
the concentration of 2 was systematically varied (Figure S11).
Based on the molar ratio plot, the complexation stoichiometry
between 1 and 2 is determined to be 1:2 at room temperature
(Figure 3a).
original particle’s radius of curvature increases to accommodate
additional strain, resulting in the coacervate of the nanospheres
to form disordered aggregates.13
Figure 3. (a) Mole ratio plot for 1 and 2; (b) Scatchard plot for the
complexation between 1 and 2. P = fraction of L-alanine ester salt 2
units complexed. The titration experiments were performed in d-
chloroform at 25 °C.
In summary, we have demonstrated that platinum(II)
acetylide bolaamphiphile 1, equipped with two solvophilic
B18C6 moieties on the periphery, exhibits a strong tendency to
form spherical aggregates in a polar methanol/chloroform (3/1,
v/v) solution. High-affinity host−guest molecular recognition
leads to the cooperative complexation behaviors between L-
alanine ester salt 2 and the homoditopic platinum(II) acetylide
bolaamphiphile 1. Notably, upon addition of 2 to 1, the
disappearance of nanospheres derived from bolaamphiphile 1
could be visualized, accompanied by the formation of
disordered coagulated assemblies. Therefore, the current
study provides an example for morphological transition in
response to amino acid additives, which serves as a potential
candidate for the development of intelligent materials for
controlled release, biosensing, and optical resolution.
The Δ0 value of amide protons NH on 1, representing the
chemical shift difference between the uncomplexed and fully
complexed species, was determined to be 1.58 ppm (Figure
S12). The extent of complexation, p, of the B18C6 unit can be
subsequently calculated from p = Δ/Δ0 (Δ: chemical shift
difference for NH between the uncomplexed and partially
complexed species). The Scatchard plot (Figure 3b) is
nonlinear and exhibits a maximum value, indicating that the
two B18C6 units of 1 associate with 2 in a cooperative manner.
From the slope and the intercept of the Scatchard plot, K1 was
estimated to be 382 M−1 and K2 was determined to be 549
M−1. The cooperative complexation between 1 and 2 is
confirmed by the K2/K1 ratio (1.4), which is higher than the
value of 0.25 expected for statistical complexation.11 The arising
cooperative complexation could be mainly attributed to the
electrostatic repulsion effect.12 Briefly, the 1:1 complex 1·2
leads to the redistribution of the electron density along the π-
conjugated platinum(II) acetylide rod, which facilitates
complexation for the second L-alanine ester salt to form the
1·22 structure. Meanwhile, allosteric changes could also be
involved after formation of the 1:1 complex 1·2.
ASSOCIATED CONTENT
* Supporting Information
■
S
1
Synthetic route to the bolaamphiphile 1, characterizations, H
NMR titration between 1 and 2, and the corresponding
Benesi−Hildebrand plot. This material is available free of
charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Authors
■
Finally, we turned to investigate the complexation behavior
between 1 and 2 in polar solvent. Although the noncovalent
*E-mail: Rishengyao@163.com.
*E-mail: drfwang@ustc.edu.cn.
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Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This work was supported by the National Natural Science
Foundation of China (21274139, 91227119), Anhui Provincial
Natural Science Foundation (1208085QB22).
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