Hierarchical Self-Assembly of a Water-Soluble Organoplatinum(II) Metallacycle into Well-Defined Nanostructures

Article abstract of DOI:10.1021/acs.orglett.8b02925

A water-soluble metallosupramolecular hexagon containing pendant methyl viologen (MV) and trimethylammonium units at the vertices has been synthesized via an organoplatinum(II) pyridyl coordination-driven self-assembly reaction. The MV units of the metallacycle were further utilized in the formation of a heteroternary complex with cucurbit[8]uril and a galactose-functionalized naphthalene derivative, yielding a metallacycle-cored carbohydrate cluster that was subsequently ordered into nanospheres and tapes, depending upon the concentration.

Full text of DOI:10.1021/acs.orglett.8b02925

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Hierarchical Self-Assembly of a Water-Soluble Organoplatinum(II)
Metallacycle into Well-Defined Nanostructures
Sougata Datta,*,† Manik Lal Saha,*,† Nabajit Lahiri,† Guocan Yu,‡ Janis Louie,*,†
and Peter J. Stang*,†
†Department of Chemistry, University of Utah, 315 South 1400 East, Room 2020, Salt Lake City, Utah 84112, United States
‡State Key Laboratory of Chemical Engineering, Center for Chemistry of High-Performance & Novel Materials, Department of
Chemistry, Zhejiang University, Hangzhou 310027, P. R. China
S
* Supporting Information
ABSTRACT: A water-soluble metallosupramolecular hexagon
containing pendant methyl viologen (MV) and trimethylammo-
nium units at the vertices has been synthesized via an
organoplatinum(II) ← pyridyl coordination-driven self-assem-
bly reaction. The MV units of the metallacycle were further
utilized in the formation of a heteroternary complex with
cucurbit[8]uril and a galactose-functionalized naphthalene
derivative, yielding a metallacycle-cored carbohydrate cluster
that was subsequently ordered into nanospheres and tapes,
depending upon the concentration.
arbohydrates play crucial roles in various biological
Cucurbit[n]urils (CB[n], n = 5−8, 10, 14) are a family of
Cprocesses: bacterial or viral infection, fertilization, pumpkin-shaped macrocyclic cavitands, having repetitive
glycoluril units interconnected by methylene groups.8 Among
immune response, tumor-cell metastasis, etc., via enabling
the CB[n] homologues, CB[8] is capable of accommodating
two identical or different small guest molecules in its cavity in
water.9 For example, amino acids and peptides form non-
covalent homodimers (1:2) with CB[8], while heterodimeriza-
tions (1:1:1) were observed with dicationic species such as
methyl viologen (MV) and 2,7-dimethyldiazaphenanthrenium
and electron-rich aromatic molecules such as naphthalene,
indole, etc. (Ka ≥ 1011 M−2).10 This unique property of CB[8]
has been utilized for the preparation of microcapsules for on-
demand release, tunable emission, supramolecular polymer-
ization, catalysis, protein dimerization, enzymatic activity,
etc.11
specific recognition interactions between a glyco cluster and a
protein.1 Given these intricate functions, various synthetic
carbohydrate-containing functional scaffolds including glyco-
proteins, polymers, dendrimers, carbon nanomaterials, calixar-
enes, pillararenes, etc. have been prepared via covalent
synthesis.2 In contrast to the tedious covalent approach,
supramolecular chemistry, in particular coordination-driven
self-assembly via metal−ligand bonding, is a viable strategy,
whereby a fast and efficient one-pot synthesis of diverse
supramolecular coordination complexes (SCCs) can be
accomplished.3 Due to their well-defined shapes and sizes,
SCCs are excellent platforms to install functional units either
on the periphery or at the vertices, resulting in functional
systems, such as sensors and catalysts, etc.4 Functionalized
SCCs are currently synthesized from appropriate prefunction-
alized precursors whose preparations involve some additional
covalent synthesis of organic ligands or metal acceptors.5
Recently, hierarchical self-assembly techniques have emerged
as a new strategy, wherein multiple orthogonal interactions
between molecular precursors can produce functional
structures while keeping the synthetic steps at a minimum.
For example, a precise unification of coordination-driven self-
assembly with crown ether based host−guest interactions leads
to the formation of robust metallacycle-cored supramolecular
polymer gels in organic solvents.6 The hierarchical approach is,
however, much less explored in aqueous medium due to the
intrinsic hydrophobicity of SCCs, restricting the implementa-
tion of biologically relevant functionalities, such as sugars, into
the SCC platforms.7
Herein, we combine the organoplatinum(II) ← pyridyl
coordination-driven self-assembly with CB[8]-mediated host−
guest interactions to report the synthesis of a metallacycle-
cored carbohydrate cluster (Scheme 1) that subsequently
formed various nanostructures, such as nanospheres and tapes,
depending upon the concentration. In these hierarchical
nanostructures, the metal−ligand coordination provides the
first level of organization, while host−guest interaction and
hydrogen bonding derived from CB[8] and sugar units enable
the higher-order organizations. The approach described herein
provides a facile strategy to prepare carbohydrate functional
materials that can be useful for biomedical research. As shown
in Scheme 1, the synthesis of hexagon 1 requires a 120°
−
dipyridyl donor 2·2PF6 and a 120° organoplatinum acceptor
Received: September 12, 2018
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.8b02925
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
Scheme 1. Preparation of Discrete Metallacyclic Hexagon 1 and Cartoon Representation of the Formation of Heteroternary
Host−Guest Complex 5 from 1, CB[8], and NG
3. The former was prepared by a 1-ethyl-3-(3-
(dimethylamino)propyl)carbodiimide hydrochloride (EDC·
HCl) mediated amidation reaction between 612 and 713 in
70% yield (Scheme 2A). While the multistep synthesis of the
new metal acceptor 3 commenced with a nucleophilic
substitution reaction that transformed 814 into 9 (Scheme
2B), a palladium-catalyzed Sonogashira reaction of 9 with
(trimethylsilyl)acetylene delivered a trimethylsilyl-protected
acetylene derivative that provided precursor 10 after hydrolysis
(65% isolated yield). Compound 10 was then reacted with 4
equiv of trans-PtI2(PEt3)2 to prepare 11, which upon reaction
with methyl iodide, followed by anion metathesis with AgNO3,
resulted in 3 in good yield. Subsequently, the self-assembled [3
+ 3] hexagon 1 was obtained by stirring a mixture of MV-
The formation of 1 was further supported by electrospray
ionization time-of-flight mass spectrometry (ESI-TOF-MS). In
the mass spectrum of 1, two peaks were identified that support
the formation of a [3 + 3] assembly: m/z = 1387.51 Da for [M
− 4ONO2]4+ and m/z = 1097.61 Da for [M − 5ONO2]5+.
Both peaks were isotopically resolved and matched well with
their calculated theoretical distributions (Figure S26, Support-
ing Information (SI)). All attempts to grow X-ray single
crystals of 1 have thus far proven unsuccessful, likely due to the
flexibility of the alkyl chains. PM6 semiempirical computations
of 1 (Figure S27, SI) featured a planar hexagonal ring at the
core with an internal diameter of 2.80 nm. The ring is
surrounded by three MV units and three trimethylammonium
(TMA) groups alternatively at the vertices. The host−guest
1
complexation between 1 and CB[8] was studied by H NMR
−
functionalized 120° dipyridyl donor, 2·2PF6 , and 120°
experiments in D2O (Figure S29, SI). The signal at 9.05 and
9.15 ppm of 1 was assigned to the H1 and H4 protons of the
MV units (Figures S28 and S29A, SI). They shifted upfield in
4[1·(CB[8])3], merged with the peak of pyridyl H8 protons,
and appeared as a broad peak at 8.8 ppm due to host−guest
complexation (Figure S29B, SI). Upon subsequent hetero-
ternary host−guest complexation with 3 equiv of NG, this peak
of 4 split into two sets and appeared at 8.4 and 8.8 ppm, where
the former was assigned to the H1 and H4 protons of the MV
units and the latter was assigned to the pyridyl H8 protons.
(Figure S29C, SI). At the same time, the NG protons appeared
in the range of 7.4−8.0 ppm and experienced a significant
upfield shift in 5[4·(NG)3] (Figures S29C and D, SI).
organoplatinum(II) acceptor 3 in a 1:1 stoichiometry in
H2O/acetone (1:2 v/v) at room temperature for 12 h,
followed by anion exchange using tetrabutylammonium nitrate
(Scheme 1). The resulting hexagon 1 is water soluble, although
−
the corresponding precursors 2·2PF6 and 3 are water
insoluble.
1
In the H NMR spectrum of 1 (Figure 1A), the pyridyl
protons H8 and H7 of 2 showed downfield shifts (Δδ[H8] =
0.24 ppm; Δδ[H7] = 0.28 ppm) with reference to those of the
−
free 2·2NO3 (Figure 1B) due to the coordination of the
pyridyl N atoms to the Pt centers. Likewise, the 31P{1H} NMR
spectrum of 1 revealed a single sharp singlet at ∼16.97 ppm
with concomitant 195Pt satellites (JPt−P = 2303 Hz), consistent
with a single phosphorus environment (Figure 1D). This signal
shifted upfield by 4.49 ppm relative to that of acceptor 3
(Figure 1E). The decrease in the coupling of 195Pt satellites
(ca. ΔJ = 99 Hz) in 1 relative to that of 3 is consistent with the
electron backdonation from the platinum centers.
1
These upfield shifts in the H NMR spectra are diagnostic for
the heteroternary complexation.15 The presence of galactose
units does not interfere with such heteroternary complexation
(Figure S30, Supporting Information).
The morphologies of the self-assembled aggregates of 1, 4,
and 5 in water were examined using transmission electron
B
DOI: 10.1021/acs.orglett.8b02925
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Scheme 2. Synthesis of (A) MV-Functionalized Dipyridyl
Donor 2·2PF6− and (B) TMA-Pendent Organoplatinum(II)
a
Acceptor 3
a
Conditions: (i) EDC·HCl, DMAP, DMF, 48 h, room temperature,
70%; (ii) aq. Me2NH, K2CO3, THF, 6 h, 60 °C (90%); (iii) and (iv)
(trimethylsilyl)acetylene, Pd(PPh3)4, CuI, Et3N, THF, 24 h, 60 °C;
KOH, methanol, 24 h, room temperature, (95%); (v) trans-
PtI2(PEt3)2, CuI, Et2NH, toluene, room temperature, 16 h (57%);
(vi) and (vii) MeI, CH2Cl2, reflux, 24 h; AgNO3, CH2Cl2, room
temperature, 12 h (90%).
1
Figure 1. (A−C) Partial H and (D, E) 31P NMR spectra (CD3OD,
25 °C) of (A,D) hexagonal metallacycle 1, (B) donor 2·2NO3−, and
(C,E) acceptor 3.
microscopy (TEM). Spherical nanoparticles with a diameter of
ca. 14 nm were formed by 1 at a concentration of 17 μM
(Figure S31A, SI). A dynamic light scattering (DLS)
experiment performed with a 17 μM aqueous solution of 1
showed a narrow size distribution (Figure S33A, SI). The
average hydrodynamic diameter (Dh) of 1 was observed to be
15 nm in good accordance with the TEM results. The host−
guest complex 4 formed globular aggregates with an average
size of 100 nm (Figures S31B and S33B, SI). The
heteroternary complex 5 showed tape-like morphology with
widths of about 30−200 nm at a concentration of 17 μM
(Figure S31C, SI). However, it is evident from the TEM image
that the tape-like structure is not well developed (Figure S31C,
SI). Nicely formed tapes with widths of about 200−300 nm
were obtained after keeping the aqueous solution of 5 (17 μM)
at room temperature for 1 week (Figure 2A).
At a concentration of 3.4 μM, 5 exhibited lump-like
aggregates (Figure S31D, SI) which transformed into nano-
spheres with diameters of 80−200 nm upon standing of the
aqueous solution at room temperature for 1 week (Figure 2B).
DLS data revealed the average size of the nanospheres to be ca.
140 nm (Figure S33C, SI), which is consistent with the TEM
result (Figure 2B). Likewise, Yan et al. observed morphological
Figure 2. TEM images of the aggregates obtained from the aqueous
solutions of 5 after standing for 1 week at concentrations of (A) 17
and (B) 3.4 μM, respectively.
transition from sphere-to-fiber/ribbon upon increasing the
concentration of organoplatinum rhomboids having hydro-
philic PEG groups at the vertices.16 Additionally, STEM-EDS
(STEM, scanning transmission electron microscopy; EDS,
energy-dispersive spectroscopy) spectra of the above samples
further confirmed the presence of carbon, nitrogen, oxygen,
phosphorus, and platinum in the aggregates (Figure S32, SI).
We further investigated the effect of adding an excess of 2-
naphthol to 5. Lump-like aggregates of 5 were still observed
after addition of 3 equiv (with respect to 1) of 2-naphthol
C
DOI: 10.1021/acs.orglett.8b02925
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In summary, a multicationic organoplatinum(II) hexagon 1
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studied by H NMR spectroscopy, TEM, and DLS experi-
ments. The heteroternary complex 5 resulted in a tape-like
morphology after its aqueous solution was kept at room
temperature for 1 week. The galactose units at the surface of
the tape-like structures may endow them with interesting
biofunction. Exploration of biological applications of these
nanostructures is underway in our laboratory.
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.8b02925.
Experimental details, NMR spectra, and other materials
(PDF)
AUTHOR INFORMATION
Corresponding Authors
(9) Assaf, K. I.; Nau, W. M. Chem. Soc. Rev. 2015, 44, 394−418.
(10) (a) Datta, S.; Misra, S. K.; Saha, M. L.; Lahiri, N.; Louie, J.;
Pan, D.; Stang, P. J. Proc. Natl. Acad. Sci. U. S. A. 2018, 115, 8087−
8092. (b) Barrow, S. J.; Kasera, S.; Rowland, M. J.; del Barrio, J.;
Scherman, O. A. Chem. Rev. 2015, 115, 12320−12406.
■
*E-mail: sougata.datta@utah.edu.
*E-mail: manik.saha@utah.edu.
*E-mail: louie@chem.utah.edu.
*E-mail: stang@chem.utah.edu.
(11) (a) Liu, J.; Lan, Y.; Yu, Z.; Tan, C. S. Y.; Parker, R. M.; Abell,
C.; Scherman, O. A. Acc. Chem. Res. 2017, 50, 208−217. (b) Ni, X.-L.;
Chen, S.; Yang, Y.; Tao, Z. J. Am. Chem. Soc. 2016, 138, 6177−6183.
(c) Zheng, L.; Sonzini, S.; Ambarwati, M.; Rosta, E.; Scherman, O. A.;
Herrmann, A. Angew. Chem., Int. Ed. 2015, 54, 13007−13011.
(d) Huang, Z.; Yang, L.; Liu, Y.; Wang, Z.; Scherman, O. A.; Zhang,
X. Angew. Chem., Int. Ed. 2014, 53, 5351−5355. (e) Zhang, K.-D.;
Tian, J.; Hanifi, D.; Zhang, Y.; Sue, A. C.-H.; Zhou, T.-Y.; Zhang, L.;
Zhao, X.; Liu, Y.; Li, Z.-T. J. Am. Chem. Soc. 2013, 135, 17913−
17918. (f) Dang, D. T.; Nguyen, H. D.; Merkx, M.; Brunsveld, L.
Angew. Chem., Int. Ed. 2013, 52, 2915−2919. (g) Reczek, J. J.;
Kennedy, A. A.; Halbert, B. T.; Urbach, A. R. J. Am. Chem. Soc. 2009,
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ORCID
Manik Lal Saha: 0000-0003-2242-3007
Janis Louie: 0000-0003-3569-1967
Peter J. Stang: 0000-0002-2307-0576
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
P.J.S. and S.D., respectively, thank the NIH (R01-CA215157)
and SERB Indo-U.S. Postdoctoral fellowship for financial
support.
(12) Pollock, J. B.; Cook, T. R.; Stang, P. J. J. Am. Chem. Soc. 2012,
134, 10607−10620.
(13) Yamaguchi, H.; Harada, A. Biomacromolecules 2002, 3, 1163−
1169.
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DOI: 10.1021/acs.orglett.8b02925
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