Extending the limits of precision polymer synthesis: Giant polyphenylene dendrimers in the megadalton mass range approaching structural perfection

Article abstract of DOI:10.1021/ja311430r

The catalyst-free Diels-Alder synthesis of polyphenylene dendrimers with a chromophore core has now been demonstrated to achieve the seventh to ninth generations upon divergent growth. Since standard analytical tools such as size-exclusion chromatography do not provide realistic molecular weights, MALDI-TOF mass spectrometry was applied to characterize the complete series of nine generations. Perfection and monodispersity were thus elucidated at such high masses. Transmission electron microscopy imaging was used to determine the size of these molecularly defined nanosized particles with diameters of up to 33 nm.

Full text of DOI:10.1021/ja311430r

Communication
pubs.acs.org/JACS
Extending the Limits of Precision Polymer Synthesis: Giant
Polyphenylene Dendrimers in the Megadalton Mass Range
Approaching Structural Perfection
Thi-Thanh-Tam Nguyen,† Martin Baumgarten, Ali Rouhanipour, Hans Joachim Rader, Ingo Lieberwirth,
̈
and Klaus Mullen*
̈
Max Planck Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany
S
* Supporting Information
a
Scheme 1. Synthesis of the Masked AB2 Building Block 5
ABSTRACT: The catalyst-free Diels−Alder synthesis of
polyphenylene dendrimers with a chromophore core has
now been demonstrated to achieve the seventh to ninth
generations upon divergent growth. Since standard
analytical tools such as size-exclusion chromatography do
not provide realistic molecular weights, MALDI-TOF mass
spectrometry was applied to characterize the complete
series of nine generations. Perfection and monodispersity
were thus elucidated at such high masses. Transmission
electron microscopy imaging was used to determine the
size of these molecularly defined nanosized “particles” with
diameters of up to 33 nm.
a
Reagents and conditions: (a) TIPS-acetylene, [PdCl2(PPh3)2], CuI,
PPh3, TEA/toluene (2:1), 0 °C → r.t., 20 h, 70%. (b) 4-
(Trimethylsilyl)phenylboronic acid, K2CO3, tetra-n-butylammonium
bromide (TBAB), [Pd(PPh3)4], toluene/water (2:1), 80 °C, 36 h,
66%. (c) (i) BBr3, dry CH2Cl2, 0 °C → r.t., 3 h; (ii) pinacol, EtOAc,
77% for two steps. (d) K2CO3, TBAB, [Pd(PPh3)4], toluene/water
(4:1), 80 °C, 20 h, 50%.
mong the different synthetic macromolecules in the
Amegadalton mass range that can be prepared on a laboratory
or industrial scale, high-generation dendrimers stand out for their
well-defined shapes, monodispersity, and structural perfection.1
Nevertheless, there exist only a few literature reports dealing with
the synthesis of very large dendrimers, and many of the reported
compounds have not been thoroughly characterized.2,3 This
shortcoming has so far hampered a discussion whether
dendrimers are suitable test cases for precision synthesis of
high-molecular-weight polymers.
dendrimers are the biggest and best-characterized dendrimers
known to date. Theoretically, G9 has a diameter of ∼33 nm and a
molecular mass approaching 1.9 MDa. Unlike any other reported
large dendrimers,2c,3c,4,8 those described in this paper (i) are
bigger in size; (ii) are almost free of structural defects; (iii)
possess a highly luminescent PDI chromophore in the center;
and (iv) most importantly, can be isolated and characterized by a
series of analytical techniques, including H and 13C NMR,
1
Two problems are commonly encountered during the
synthesis of high-generation dendrimers: (i) the occurrence of
structural defects and (ii) dendrimer aggregation by interdigita-
tion of dendrimer arms.4 In regard the first issue, defects in the
dendritic structure can arise through incomplete reactions
brought about by steric congestion at the periphery,5 reactions
with yields below unity,2c,3d,6 or backfolding of flexible dendritic
branches, which hides their functional groups.3c,7 The aim of this
work was to prepare defect-free polyphenylene dendrimers
(PPDs) with diameters of up to 33 nm using a simplified and
scalable synthetic procedure. Pushing the limits of polymer
chemistry with PPDs as models is a matter of not only
redesigning the dendrimer architecture and improving the
synthetic techniques applied but also making physical methods
of structure proof applicable.
FTIR, UV−vis absorption, and luminescence spectroscopy as
well as size-exclusion chromatography (SEC) and, as the most
powerful tool, matrix-assisted laser desorption ionization mass
spectrometry (MALDI-TOF MS). The presence of the PDI core,
in addition to allowing optical detection of the dendrimers, is
instrumental in the MS detection.
To push the limits of polymer synthesis, PPDs are ideal objects
because (i) the reactive groups on the surfaces are sterically
accessible as a result of the lack of backfolding of the dendrimer
arms and (ii) our repetitive Diels−Alder cycloaddition method
for divergent dendrimer growth is high-yielding and irreversible
as a result of the extrusion of CO. While this is analogous to that
of the parent PPDs,2a two key ingredients are now needed: the
multiethynyl-functionalized PDI chromophore core 6 (see
Scheme 2) and the AB2 building block 5 with extended arms.
In principle, one could have considered even more “exploded”
AB2 reagents for faster dendrimer growth, but the efficient
Our approach utilized an easily accessible building block (5;
Scheme 1) and a large perylenediimide (PDI) core in a repetitive
Diels−Alder cycloaddition (Scheme 2). This strategy enabled us
for the first time to synthesize and characterize PPDs up to the
ninth generation. To the best of our knowledge, these
Received: November 21, 2012
Published: March 1, 2013
© 2013 American Chemical Society
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Communication
a
organic solvents (except for alcohols and alkanes). All of the
intermediates and final products could thus be characterized
completely. Full synthetic details and analytical data for all of the
reported compounds can be found in the Supporting
Information (SI).
Scheme 2. Synthesis of the G1 through G9 Dendrimers
Successful purification of the dendrimers after each synthetic
step enabled us to isolate the single dendrimers, as reflected in
the relatively well-resolved peaks in the 1H NMR spectra shown
in Figure 1. The aromatic resonances from the third- to the ninth-
Figure 1. 300 MHz 1H NMR spectra of G1 and G2 and 500 MHz 1H
NMR spectra of G3−G9 in CD2Cl2 at 298 K.
generation dendrimers, however, were virtually identical, as the
peaks for the protons from the PDI core (around 8.22 ppm) were
1
“diluted”. All of the H NMR spectra showed relative signal
intensities of aromatic and TIPS protons in agreement with the
structural formula. Moreover, no signal at 3.15 ppm originating
from unreacted ethynyl groups could be detected after each
Diels−Alder cycloaddition providing additional proof that the
reactions were quantitative.
Sharp, narrow SEC traces of all nine dendrimer generations
after a second purification by analytical SEC were observed
(Figure 2A). Such sharp SEC traces have not been achieved
previously for high-generation dendrimers; instead, all of the
reported large dendrimers exhibited only very broad peaks. Not
surprisingly, the SEC data can be interpreted only qualitatively
because linear polystyrene (PS) standards were used. Figure 2B
shows a semilogarithmic plot of molecular mass versus elution
volume for both the PS standards and dendrimers G1−G9. The
curve for the PS standards is a relatively straight line, whereas that
of the dendrimers is linear only up to G3, after which the slope
starts to increase as a function of the dendrimer size. This
increase indicates that bigger dendrimers are delayed longer than
expected during SEC elution.
MS analysis was employed to detect the molecular weight and
possible structural defects of this dendrimer series. Because of the
outstanding purity of the SEC-fractionated dendrimers and the
high fragmentation stability of the PDI core upon UV laser
irradiation during MALDI analysis, MS could be applied to the
whole series. This enabled the first successful analysis of “real”
synthetic polymers up to the megadalton range beyond PS
standards9 and dendrimer clusters.4
a
Reagents and conditions: o-Xylene, 145 °C, and tetracyclone 5 for
(i), (iii), (v), (vii), (ix), (xi), (xiii), (xv), and (xvii); TBAF, THF, r.t.
for (ii), (iv), (vi), (viii), (x), (xii), (xiv), and (xvi). Yields: (i) 95.8%;
(ii) 90%; (iii) 91.9%; (iv) 90.5%; (v) 95.4%; (vi) 93.9%; (vii) 95.0%;
(viii) 75.0%; (ix) 81.3%; (x) 88.5%; (xi) 82.1%; (xii) 87.3%; (xiii)
85.7%; (xiv) 95.0%; (xv) 78.0%; (xvi) 92.0%; (xvii) 75.3%.
synthesis of 5 in only four steps (Scheme 1) was essential for
achieving sufficient amounts of ultrahigh-molecular-weight
products. Fourfold Diels−Alder cycloaddition of 5 to 6 afforded
the first-generation dendrimer 7 bearing eight triisopropylsilyl
(TIPS)-protected ethynyl chain ends. Deprotection of the
ethynyl groups was achieved with tetrabutylammonium fluoride
trihydrate (TBAF), quantitatively affording pure deprotected
dendrimers G1 (8). The reaction cycle was repeated throughout
eight generations, and the final coupling yielded the G9
dendrimer with 2048 TIPS-protected ethynyl chain ends and
18 402 benzene rings! On the experimental side, making such
large PPDs accessible required significant improvements over the
established techniques. Thus, an additional purification step
involving analytical SEC proved to be essential for high-
generation dendrimers. Furthermore, to avoid side reactions,
the deprotected dendrimers after desilylation had to be kept in
the dark at temperatures below 40 °C. Because of the large
dihedral angles between adjacent phenyl rings in the semirigid
PPDs, all of the synthesized dendrimers, in spite of their high
molecular weights, showed good solubility in most common
The determined molecular weights of our dendrimers were in
perfect agreement with the theoretical values up to G4. Slight
deviations of the measured values from the calculated ones
commenced at G5 and increased incrementally from one
generation to the next. As representative for the higher
generations, Figure 3 shows the baseline-corrected mass
spectrum of G7. The signals can be assigned to dendrimers
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from 15% for the singly charged molecules to only 10% for the
species with a charge of 5+. It also follows that the multiply
charged molecules provide a more exact molecular weight
measurement than the singly charged species because of their
higher detection efficiency. For this reason, the measured values
in SI Table 2 summarizing the mass spectrometric results (see
the SI) were calculated using the highest charge states available
and serve as best approximations to the real molecular weights. A
similar phenomenon was observed previously for high-mass PS
samples. An interpretation of this finding is still missing, most
probably because of missing evidence for the exact “true”
molecular weights.10
The evidence for structural imperfections with an onset at G5,
corresponding to a molecular weight already above 100 kDa,
should not be understood as downgrading the structural purity of
our dendrimers. On the contrary, they own superior perfection in
comparison with other systems, as otherwise they could not be
analyzed by mass spectrometry at all because of the well-known
restrictions for polymers with broad molecular weight
distributions.11 Astruc and co-workers, for example, reported
the synthesis of nine successive generations of flexible organo-
silicon dendrimers, but MALDI-TOF mass spectra could be
recorded only up to the fourth generation, and defects were
found to be present proceeding from the second generation.3c
It should be emphasized that the polydispersity of the whole
dendrimer series did not exceed a value of 1.005, which still
corresponds to a very narrow molecular weight distribution and
affirms the extremely high structural perfection of these giant
PPDs. Such findings could not be elucidated with comparable
exactness by MS previously. For traditional characterization
methods such as SEC, NMR spectroscopy, and viscometry, such
details are not visible, and the dendrimers would appear as
virtually perfect systems.
Figure 2. (A) SEC traces obtained for different dendrimer generations
G1−G9. (B) Semilogarithmic plot of average molecular mass vs SEC
elution volume for the linear polystyrene standards compared with the
theoretical molecular masses of the dendrimers plotted vs their
experimental SEC elution volumes. Conditions: THF, 1 mL/min; 500
Å, 104 Å, 106 Å SDV (Polymer Standard Service Mainz) columns (0.8
cm × 30 cm); ambient temperature.
To obtain direct information on the size of the dendrimers,
transmission electron microscopy (TEM) was employed. The
samples were obtained by drop-casting of dilute dendrimer
solutions [10−9 M in tetrahydrofuran (THF)] onto thin carbon
substrates (Figure 4). The TEM micrographs of G8 and G9
Figure 3. MALDI-TOF mass spectrum of G7 measured with DCTB as
the matrix (smoothed and baseline-corrected).
carrying charges of up to 5+, with a peak maximum of the singly
charged molecules at 400 kDa and a peak width of ∼100 kDa.
The mass deviation of 15% relative to the theoretical value, as
well as the fact that the peak width is significantly beyond a mass
spectrometric peak broadening, could be interpreted as a mass
distribution resulting from a slight chemical heterogeneity. Since
the detected mass is lower than the theoretical mass, we conclude
that the differences observed above G4 are generally due missing
branches with increasing generation number. The deviation
between the experimental and theoretical masses (SI Table 2),
however, can only partially be attributed to structural defects
because there was also a systematic error during the measure-
ments. Recalculations for the more highly charged states
generally provided a smaller deviation with increasing charge
size. This suggests that the MS method, which to date is the most
precise tool for molecular weight determinations, also reaches its
limit, which is most probably due to the very low but detectable
polydispersity. In the case of G7, the deviation is thus reduced
Figure 4. TEM micrographs of (A) G8 and (B) G9 dendrimers on
carbon substrates.
yielded diameters between 23 and 33 nm, in close agreement
with the lengths extracted from modeling of linear polypheny-
lene chains. Thus, the rigid pentaphenylbenzene branching units
provide conformational stiffness and directionality to the chain
ends similar to that of the nonexpanded PPDs without
backfolding.
In conclusion, we have successfully synthesized and
comprehensively characterized a series of giant fluorescent
polyphenylene dendrimers with hitherto unsurpassed structural
perfection. The largest member of this series is the ninth-
generation dendrimer (G9), with an expected molecular mass of
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Germany, 2002. (e) Vogtle, F.; Richardt, G.; Werner, N. Dendrimer
̈
up to 1.9 MDa and a longest-extension diameter of up to 33 nm,
as firmly established by TEM imaging. G9 contains as many as
18 402 benzene rings and an amazing 2048 chain ends. We have
thus pushed the synthetic limit, as G9 represents the biggest
aromatic dendrimer reported to date. The entire series of nine
rigorously purified dendrimer generations exhibited sharp,
narrow SEC traces and could even be characterized by
MALDI-TOF mass spectrometry, confirming the structural
perfection up to G4 and indicating a slight increase of chemical
heterogeneity from G5 on. Although it seems to be a
contradiction, it can be assumed that MALDI MS could detect
these slight structural imperfections at high molecular weights
only because of the outstanding structural perfection not
obtained previously. The reason that polystyrene was to date
the only example of synthetic polymers in the megadalton range
to which MS had been applied is an unbeatable structural
perfection and polydispersity that to date has been achievable
only by anionic polymerization. The fact that our dendrimers can
now compete with PS standards can be considered as a
breakthrough of our repetitive Diels−Alder cycloaddition
reaction and justifies the nomenclature “precision polymers”.
The success of our divergent dendrimer synthesis up to these
high generations and extremely large molecular sizes relied on
three significant improvements: (i) the use of an easily accessible
extended dendritic branching unit in combination with a
relatively voluminous PDI scaffold; (ii) the careful three-step
purification of each; and especially (iii) keeping the deprotected
dendrimer solution at low temperature and in the dark while
gradually removing the solvent. Because of the fluorescent PDI
core, fluorescence correlation spectroscopy could also be applied
to obtain size information on the basis of diffusion coefficients.
This is particularly important since one and the same PDI
chromophore is now encapsulated in shells of widely different
thicknesses. All of these optical properties will be reported in a
forthcoming paper.
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ASSOCIATED CONTENT
■
S
* Supporting Information
Synthetic details and characterization data. This material is
available free of charge via the Internet at http://pubs.acs.org.
(4) Clark, C. G.; Wenzel, R. J.; Andreitchenko, E. V.; Steffen, W.;
AUTHOR INFORMATION
Corresponding Author
muellen@mpip-mainz.mpg.de
■
Zenobi, R.; Mullen, K. J. Am. Chem. Soc. 2007, 129, 3292.
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(5) deGennes, P. G.; Hervet, H. J. Phys., Lett. 1983, 44, 351.
(6) Baumgarten, M.; Qin, T.; Mullen, K. Shape Persistent
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Present Address
Polyphenylene-Based Dendrimers. In Designing Dendrimers;
Campagna, S., Ceroni, P., Puntoriero, F.; Eds.; Wiley: Hoboken, NJ,
2012; pp 121−159.
†T.-T.-T.N.: Institut Charles Sadron, 23 rue du Loess, BP 84047,
67034 Strasbourg Cedex 2, France.
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(8) (a) Andreitchenko, E. V.; Clark, C. G.; Bauer, R. E.; Lieser, G.;
Notes
The authors declare no competing financial interest.
Mullen, K. Angew. Chem., Int. Ed. 2005, 44, 6348. (b) Jackson, C. L.;
̈
ACKNOWLEDGMENTS
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The authors thank Dr. Karel Goossens for English checking, Ms.
Sandra Seywald for SEC measurements and SEC fractionation,
Dr. Tianshi Qin for support, and Dr. Manfred Wagner for NMR
measurements.
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