L-lysine dendronized polystyrene

Article abstract of DOI:10.1021/ma047621n

This paper reports the synthesis and characterization of a novel class of dendronized polymers which are based on styrene functionalized dendritic L-lysine macromonomers. Free radical polymerization of zeroth and first generation macromonomers afforded de

Full text of DOI:10.1021/ma047621n

2064
Macromolecules 2005, 38, 2064-2071
L-Lysine Dendronized Polystyrene
Anke Lu1 bbert,† Tuan Q. Nguyen,‡ Frank Sun,§ Sergei S. Sheiko,§ and
Harm-Anton Klok*,‡
Max Planck Institute for Polymer Research, Ackermannweg 10, D-55128 Mainz, Germany;
EÄ cole Polytechnique Fe´de´rale de Lausanne (EPFL), Institut des Mate´riaux, Laboratoire des Polyme`res,
Baˆtiment MX-D, CH-1015 Lausanne, Switzerland; and Department of Chemistry, CB# 3290,
University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599-3290
Received November 18, 2004; Revised Manuscript Received January 3, 2005
ABSTRACT: This paper reports the synthesis and characterization of a novel class of dendronized
polymers which are based on styrene functionalized dendritic L-lysine macromonomers. Free radical
polymerization of zeroth and first generation macromonomers afforded dendronized polymers with number-
average degrees of polymerization (DP) between 50 and 240, corresponding to number-average molecular
weights between 50 × 103 and 240 × 103 g/mol. In contrast, only short oligomers (DP ) 5-15) were
obtained on polymerization of the second generation dendritic L-lysine macromonomers. Molecularly
resolved AFM images allowed first insight into the structure of these peptide dendronized polymers.
Depending on the degree of polymerization, either rods, short rods, or globular structures were found.
Introduction
This contribution reports the synthesis and charac-
terization of a novel class of peptide-based dendronized
polymers, which were obtained by polymerization of
styrene functionalized L-lysine dendrons. Dendrimers
and linear dendritic block copolymers based on L-lysine
have attracted interest, e.g., for the development of
multiple antigen peptides8 or as vectors for gene deliv-
ery.9 The L-lysine dendronized polystyrenes that will be
discussed in this contribution add to these existing
classes of branched L-lysine-based polymer architectures
and may possess interesting properties for similar
applications.
Dendronized polymers are polymers that contain
dendritic fragments attached to a polymer backbone.1
One of the most intriguing features of these macromol-
ecules is that their overall structure can be controlled
by the degree of polymerization of the backbone and the
size and shape of the dendritic substituents. Percec et
al. found that dendronized polymers based on styrene
or methacrylate functionalized conical dendrons form
spherical objects with a random coil backbone confor-
mation at low degrees of polymerization. Increasing the
degree of polymerization, however, was found to result
in the formation of a cylindrical-shaped polymer with a
relatively extended backbone conformation.2 Because of
the size of the dendritic substituents, such cylindrical
polymers may have diameters of several nanometers.
Furthermore, the dendritic groups generate a densely
packed surface, which can suppress interlocking of
individual dendronized macromolecules. As a result,
appropriately designed dendronized polymers can be
regarded as individual molecular objects, which could
be interesting building blocks to construct larger archi-
tectures.
The chemical structure of the dendritic substituents
that have been appended to polymer backbones varies
widely, from Fre´chet-type benzyl ether dendrons3 to
phenylacetylene-based structures.4 A class of dendrons,
however, which has only received very little attention
are dendrons based on amino acids. An exception is the
work by Ritter and Niggemann, who reported the
synthesis and polymerization of methacrylate function-
alized L-aspartic acid dendrons.5,6 These authors, how-
ever, could not obtain molecular weight data of their
products5 and only found evidence for the formation of
low molecular weight oligomers.6 In a more recent series
of articles, the synthesis and properties of various
polyacrylates substituted with L-aspartic acid and L-
glutamic acid dendrons were described.7
Experimental Section
Abbreviations. DIPEA, N,N-diisopropylethylamine; DMF,
N,N-dimethylformamide; FD, field desorption; Fmoc, 9-fluo-
renylmethoxycarbonyl; HBTU, O-benzotriazole-N,N,N′,N′-tet-
ramethyluronium hexafluorophosphate; HOBt, N-hydroxy-
benzotriazole; MALDI-TOF, matrix-assisted laser desorption-
ionization time-of-flight; MS, mass spectrometry; NMP,
N-methyl-2-pyrrolidone; SPPS, solid-phase peptide synthesis;
TFA, trifluoroacetic acid or trifluoroacetamide; VBA, 4-vinyl-
benzylamine; Z, benzyloxycarbonyl.
ꢀ
Materials. NR,N -di-TFA-L-lysine (9)10 and 4-vinylbenzyl-
amine (1)11 were prepared according to literature procedures.
NMP and DMF were dried over molecular sieves (4 Å). All
other solvents and chemicals were purchased from commercial
suppliers and used as received.
Analytical Methods. 1H and 13C NMR spectra were
recorded on Bruker AMX300, DRX 500, and DPX700 spec-
trometers. The residual proton or carbon signal of the deu-
terated solvent was used as internal standard. Chemical shifts
are reported in parts per million (ppm), and peak multiplicities
are described using the following abbreviations: bs, broad
singlet; m: multiplet; s: singlet; d: doublet; t: triplet; q:
quartet; qC: quaternary carbon. Mass spectra were recorded
on a VG ZAB 2-SE-FPD instrument (field desorption, FD) or
a Bruker Reflex II MALDI-TOF mass spectrometer. Dithranol
was used as the matrix, and samples were prepared either
with DMSO as the solvent or without solvent following the
solid-state procedure. In some cases, sodium trifluoracetate
was added to facilitate ionization. Gel permeation chromatog-
raphy (GPC) was performed on a Waters 150CV modified for
on-line differential viscometry. All analyses were carried out
at 60 °C using two TSK-Gel Alpha columns (3000 + 4000) in
series and DMF + 1 g/L LiBr as the eluent. Elution times were
† Max Planck Institute for Polymer Research.
‡ EÄ cole Polytechnique Fe´de´rale de Lausanne (EPFL).
§ University of North Carolina at Chapel Hill.
* Corresponding author: e-mail harm-anton.klok@epfl.ch; Fax
++ 41 21 693 5650.
10.1021/ma047621n CCC: $30.25 © 2005 American Chemical Society
Published on Web 02/12/2005

Macromolecules, Vol. 38, No. 6, 2005
L-Lysine Dendronized Polystyrene 2065
converted into absolute molecular weights using the “universal
calibration” curve, which was constructed using anionically
prepared poly(methyl methacrylate) standards, in combination
with the information obtained from the refractive index and
differential viscometer detectors. Intrinsic viscosities were
obtained in similar fashion by combination of the signals from
the two detectors. Tapping mode AFM images were collected
using a multimode atomic force microscope (Veeco Metrology
Group) equipped with a Nanoscope IIIa controller. NSC-14 Si
cantilevers (Mikromash USA) with a resonance frequency of
about 160 kHz and a spring constant of about 5 N/m were used.
The radius of the probe was less than 10 nm. High-resolution
images of single molecules were obtained using DP-14 Hi’Res
probes possessing ultra-sharp whiskers with a radius below
3.5 nm.
CO-O); 172.82 (RCH-CO); 173.96 (COOH). MS (FD): m/z )
486.1 (100% [M]+); 508.1 (92% [M-Na]+); 524 (12% [M-K]+);
993.2 (80% [2M]+); 1477.9 (7% [3M]+).
1
2b: Yield: 2.59 (6,2 mmol, 99%) of a white solid. H NMR
(250 MHz, DMSO, 298 K): δ (ppm) ) 1.25 (m, 2H, RCHCH2-
CH2); 1.44 (m, 2H, RCH-CH2); 1.67 (q, 2H, RCH(CH2)2-CH2);
2.38 (t, 2H, HOCO-CH2); 3.20 (m, 2H, RCH(CH2)3-CH2); 3.28
ꢀ
(m, 2H, HOOCCH2-CH2); 4.23 (q, 1H, RCH); 8.20 (t, 1H, N -
NH); 9.40 (t, 1H, RCHCO-NH); 9.49 (d, 1H, RCH-NH); 12.72
(bs, 1H, COOH). 13C NMR (75 MHz, DMSO, 298 K): δ (ppm)
) 23.67 (CH2); 28.73 (CH2); 31.66 (CH2); 34.62 (CH2); 35.75,
35.87 (CH2); 39.82, 39.94 (CH2); 54.12, 54.21 (RCH); 111.10,
114.91, 118.73, 122.55 (NR-CF3); 111.23, 115.04, 118.86,
ꢀ
122.68 (N -CF3); 156.43, 156.53, 156.61, 156.83, 156.91,
157.01, 157.10, 157.30, 157.38, 157.50, 157.58, 157.78, 157.86,
157.99, 158.06 (CO-CF3); 171.08 (RCH-CO); 173.72 (COOH).
19F NMR (282 MHz, DMSO, 298 K): δ (ppm) ) -73.93, -73.96
Procedures. Preparation of the Zeroth Generation
Nr,NE-Diprotected tert-Butyl Ester Dendrons. General
ꢀ
ꢀ
procedure: the appropriate NR,N -diprotected L-lysine deriva-
(NR-CF3); -74.46, -74.49 (N -CF3). MS (FD): m/z ) 410.3
tive was dissolved in dry DMF (∼0.2 M) together with 2 equiv
of HBTU, 2 equiv of HOBt, and 3 equiv of DIPEA. After 5-10
min, 1.5 equiv of â-alanine-tert-butyl ester hydrochloride was
added, and the reaction mixture was stirred at room temper-
ature. After 16 h, the reaction was quenched by adding the
reaction mixture to a 20-fold excess of water. The precipitate
was filtered, washed extensively with water, and vacuum-
dried.
(100% [M]+); 819.6 (9% [2M]+).
First and Second Generation Dendrons. First genera-
tion dendrons were prepared on a 4-hydroxymethyl-3-meth-
oxyphenoxybutyric (HMPB)-BHA-resin (loading: 0.61 mmol/
g). The synthesis of the second generation dendrons was
performed on a Tentagel S AC-resin (loading: 0.24 mmol/g).
The L-lysine dendrons were prepared using standard Fmoc
SPPS protocols.12 Peptide bond formation was facilitated by
the use of HBTU/HOBt. The first two amino acids were
coupled to the resin using an automated peptide synthesizer
(Applied Biosystems ABI 433A). After that, the resin was
taken from the synthesizer, and the preparation of the first
and second generation dendrons was completed manually. In
the case of the first generation dendrons, the resin-bound
dipeptide swollen in NMP was treated with 2.5 equiv of the
appropriate amino acid derivative, 5 equiv of HBTU/HOBt,
and 7 equiv of DIPEA and gently shaken for 16 h at room
temperature. In the last coupling step for the preparation of
the second generation dendrons, 1 equiv of resin-bound amine
groups was treated with 4 equiv of the appropriate amino acid,
8 equiv of HBTU/HOBt, and 12 equiv of DIPEA and gently
shaken for 9 h at room temperature. The dendrons were
cleaved from the support by treating the resin-bound product
three times for a period of 30 min with a 3% (v/v) of TFA in
CH2Cl2. Subsequently, the combined washings were evapo-
rated under vacuum, and the residual solid was triturated with
water to afford a fine powder, which was filtered and vacuum-
dried. Dendron 3b, after evaporation of TFA/CH2Cl2, however,
was dissolved in acetone and precipitated in a 20-fold excess
of n-hexane.
Zeroth-Generation Nr,NE-Di-Z-Protected tert-Butyl Es-
ter Dendron. Yield: 98% of a white solid. 1H NMR (300 MHz,
DMSO, rt): δ (ppm) ) 1.17-1.59 (m, 15H, tBu + RCH-(CH2)3);
2.34 (t, 2H, tBuOCO-CH2); 2.95 (q, 2H, RCH(CH2)3-CH2); 3.21
t
(m, 2H, BuOOCCH2-CH2); 3.89 (q, 1H, RCH); 4.99 (s, 2H, Z
CH2); 7.24 (t, 1H, NH); 7.33 (m, 11H, arom CH + RCH-NH);
7.94 (t, 1H, NH). 13C NMR (75 MHz, DMSO, 298 K): δ (ppm)
) 23.23 (CH2); 28.20 (CH2); 29.56 (CH2); 32.13 (CH2); 35.30
(CH2); 55.13 (RCH); 65.58 (CH2); 65 83 (arom CH); 80.35 (qC);
ꢀ
128.19 (N -Z arom CH); 128.81 (NR-Z arom CH); 137.5, 137.76
(Z arom qC); 156.39 (CO); 156.54 (CO); 171.05 (RCH-CO);
172.39 (CO). MS (FD): m/z ) 543 (100% [M]+); 1085 (15%
[2M]+).
Zeroth Generation Nr,NE-Di-TFA-Protected tert-Butyl
1
Ester Dendron. Yield: 98% of a white solid. H NMR (300
MHz, DMSO, rt): δ (ppm) ) 1.23 (m, 2H, RCHCH2-CH2); 1.39
(m, 11H, tBu + RCH-CH2); 1.66 (q, 2H, RCH(CH2)2-CH2); 2.35
(t, 2H, tBuOCO-CH2); 3.14 (m, 2H, RCH(CH2)3-CH2); 3.25 (m,
t
2H, BuOOCCH2-CH2); 4.22 (t, 1H, RCH); 8.19 (t, 1H, NH);
9.4 (t, 1H, NH); 9.5 (d, 1H, RCH-NH). 13C NMR (75 MHz,
DMSO, 298 K): δ (ppm) ) 23.63, 23.76 (CH2); 28.59 (CH2);
28.63 (CH3); 30.34 (CH2); 31.67 (CH2) 35.74, 35.89 (CH2); 39.71
(CH2); 53.42, 54.18 (RCH); 80.84 (qC); 111.06, 114.88, 118.69,
3a: Yield: 79% of a beige solid. 1H NMR (300 MHz, DMSO,
298 K): δ (ppm) ) 1.1-1.7 (m, 18H, RCH-(CH2)3); 2.35 (t,
2H, HOOC-CH2); 2.95 (m, 6H, RCH(CH2)3-CH2); 3.89, 3.97
(m, 2H, outer RCH); 4.15 (m, 1H, inner RCH); 5.01 (m, 8H, Z
CH2) 7.23 (t, NH); 7.34 (m, 20H, arom CH); 7.85 (d, NH); 7.95
(t, NH). 13C NMR (75 MHz, DMSO, 298 K): δ (ppm) ) 23.47,
23.73 (CH2); 29.66, 29.97 (CH2); 32.41, 32.63, 32.79 (CH2);
34.69 (CH2); 35.60, 35.72 (CH2); 39.36 (CH2); 53.20 (outer
ꢀ
122.51 (NR-CF3); 111.19, 115.00, 118.82, 122.64 (N -CF3);
156.78, 156.82, 157.01, 157.26, 157.35, 157.50, 157.75, 157.82
(CO-CF3); 171.01, 171.43 (RCH-CO); 172.87 (CO). 19F NMR
(282 MHz, DMSO, 298 K): δ (ppm) ) -73.91, 73.95, -74.12,
ꢀ
-74.16 (NR-CF3); -74.44, -74.47 (N -CF3). MS (FD): m/z )
466.6 (100% [M]+); 932.8 (21% [2M]+).
Preparation of the Zeroth Generation Nr,NE-Dipro-
tected Carboxylic Acid Dendrons (2a,b). General proce-
ꢀ
RCH); 55.62 (inner RCH); 66.01 (N Z-CH2); 66.26, 66.30 (NRZ-
dure: ∼3 g of the appropriate zeroth generation NR,N -
CH2) 128.57, 128.61 (N Z arom CH); 129.23 (NRZ arom CH);
ꢀ
ꢀ
diprotected tert-butyl ester dendron was dissolved in as little
as possible of a 50/50 (v/v) mixture of CH2Cl2 and TFA and
stirred at room temperature for 2 h. After that, solvents were
removed at the rotary evaporator, and the residue was
triturated with water (2a) or ice-cold diethyl ether (2b).
Finally, the solids were isolated by filtration and vacuum-
dried.
137.92, 137.96, 138.19 (arom qC); 156.78, 156.83, 156.91,
156.97 (Z-CO); 172.27, 172.35, 172.55, 172.62 (CO); 173.69
(COOH). MS (MALDI-TOF, dithranol, DMSO): m/z ) 1032
(50% [M + Na]+); 1048 (39% [M + K]+).
3b: Yield: 91% of a beige solid. 1H NMR (300 MHz, DMSO,
298 K): δ (ppm) ) 1.24 (bs, 6H, RCHCH2-CH2); 1.47 (bs, 6H,
RCH-CH2), 1.69 (m, 6H, RCH(CH2)2-CH2); 2.37 (m, 2H,
HOOC-CH2); 3.01, 3.15 (s, 2H, RCH(CH2)3-CH2); 3.24 (m, 2H,
HOOCCH2-CH2); 4.20 (m, 2H, outer RCH); 4.35 (m, 1H, inner
RCH); 7.98 (t, NH); 8.07 (t, NH); 8.12 (d, NH); 8.29 (d, NH);
9.38 (t, NH); 9.47 (m, 2NH); 12.21 (bs, 1H, COOH). 13C NMR
(75 MHz, DMSO, 298 K): δ (ppm) ) 23.65 (CH2); 28.68, 29.50,
29.60, 31.51, 31.67, 31.75, 32.72, 32.78, 34.60, 35.75, 39.40,
39.50 (CH2); 53.20, 53.50 (outer RCH); 54.24 (inner RCH);
111.06, 114.87, 118.69, 122.51 (NR-CF3) 111.18, 115.00,
1
2a: 2.64 g (5.5 mmol, 98%) of a white solid. H NMR (300
MHz, DMSO, rt): δ (ppm) ) 1.14-1.67 (m, 6H, RCH-(CH2)3);
2.38 (t, 2H, HOCO-CH2); 2.96 (q, 2H, RCH(CH2)3-CH2-); 3.23
(m, 2H, HOOCCH2-CH2); 3.90 (m, 1H, RCH); 5.01 (m, 4H, Z
CH2); 7.26 (t, 1NH, RCH-NH); 7.36 (m, 11H, arom CH +
RCH-NH); 7.96 (t, 1NH, RCHCO-NH). 13C NMR (75 MHz,
DMSO, 298 K): δ (ppm) ) 23.7 (CH2); 30.01 (CH2); 32.59 (CH2);
34.90 (CH2); 35.74, 35.85 (CH2); 40.91 (CH2) 55.49 (RCH);
66.05, 66.31 (CH2); 128.67 (NR-Z arom CH); 129.28 (NR-Z
arom qC); 137.99, 138.22 (Z arom qC); 156.87, 156.87 (NH-
ꢀ
118.82, 122.64 (N -CF3); 156.38, 156.86, 157.33, 157.81 (NR-
ꢀ
CF3-CO); 156.56, 157.04, 157.53, 158.01 (N -CF3-CO); 170.67,

2066 Lu¨bbert et al.
Macromolecules, Vol. 38, No. 6, 2005
170.75, 170.86, 170.94, 172.08, 172.18, 172.28, 173.63, 173. 71
CH2); 4.21 (s, 1H, RCH); 4.25 (d, 2H, VBA CH2); 5.22 (dd, 1H,
CHdCH2); 5.79 (dd, 1H, CHdCH2); 6.71 (q, 1H, CHdCH2); 7.22
(d, 2H, VBA arom CH); 7.41 (d, 2H, VBA arom CH); 8.2 (t,
NH); 8.38 (t, TFA-NH); 9.40 (t, NH); 9.47 (d, 1H, RCH-NH).
13C NMR (75 MHz, DMSO, 298 K): δ (ppm) ) 23.18 (CH2);
28.21 (CH2); 31.14 (CH2); 33.53 (CH2); 35.86 (CH2); 39.32 (CH2);
42.26 (CH2); 53.62 (RCH); 114.28 (CHdCH2); 126.51, 127.93
(VBA arom CH); 136.16 (CHdCH2); 136.83 (VBA arom qC);
139.69 (VBA arom qC); 170.50 (CO); 170.65 (CO). 19F NMR
(282 MHz, DMSO, 298 K): δ (ppm) ) -73.83 (NR-CF3);
(CO + COOH). 19F NMR (282 MHz, DMSO, rt): δ (ppm) )
ꢀ
-73.86, -73.88, 73.90 (NR-CF3), -74.40, -74.41 (N -CF3). MS
(MALDI-TOF, solid state, Na): m/z ) 841 (8% ([M+ - OH]);
880 (90% [M + Na]+); 896 (14% [M + K]+); 902 (59% [M +
2Na]+); 918 (7% [M + Na + K]+); 924 (7% [M + 3Na]+).
4a: Yield: 65% of a beige solid. 1H NMR (300 MHz, DMSO,
298 K): δ (ppm) ) 1.08-1.74 (m, 42H, RCH-(CH2)3); 2.36 (t,
2H, HOOC-CH2); 2.95 (bs, 14H, RCH(CH2)3-CH2); 3.24 (m,
2H, HOOCCH2-CH2); 3.93 (m, 4H, outer RCH); 4.19 (m, 3H,
inner RCH); 5.0 (m, 16H, Z CH2); 7.33 (m, 40H, arom. CH +
7NH); 7.73-8.02 (m, 8NH); 12.13 (COOH). 13C NMR (75 MHz,
DMSO, 298 K): δ (ppm) ) 23.55, 23.72 (CH2); 29.67, 29.97
(CH2); 32.41, 32.63 (CH2); 34.61 (CH2); 35.67 (CH2); 39.39
ꢀ
-74.37 (N -CF3). MS (FD): m/z ) 525.0 (71% [M]+); 547.1
(100% [M + Na]+), 563.1 (18% [M+ K]+).
6a: Reaction conditions: 3a:1:HBTU:HOBt:DIPEA ) 1:2:
2:2:3; 8 mL of NMP; reaction time: 16 h. Yield: 1.57 g (1.4
ꢀ
1
(CH2); 53.26 (outer RCH); 55.62 (inner RCH); 66.02 (N -Z
mmol, 94%) of a beige solid. H NMR (300 MHz, DMSO, 298
ꢀ
CH2), 66.27 (NR-Z CH2); 128.60 (N -Z arom); 129.22 (NR-Z
K): δ (ppm) ) 1.07-1.73 (m, 18H, RCH-(CH2)3); 2.31 (t, 2H,
VBA-CO-CH2); 2.96 (bs, 6H, RCH(CH2)3-CH2); 3.27 (m, 2H,
VBA-COCH2-CH2); 3.89, 3.98 (2m, 2H, outer RCH); 4.17 (m,
1H, inner RCH); 4.25 (d, 2H, VBA CH2); 5.0 (m, 8H, Z CH2);
5.21 (dd, 1H, CHdCH2); 5.78 (dd, 1H, CHdCH2); 6.7 (q, 1H,
CHdCH2); 7.21 (d, 2H, VBA arom CH); 7.33 (m, 20H, Z arom
CH + 3NH); 7.4 (d, 2H, VBA arom CH); 7.84 (d, 3H, NH); 7.95
(t, 1H, NH); 8.36 (t, 1H, NH). 13C NMR (75 MHz, DMSO, 298
K): δ (ppm) ) 23.49, 23.73 (CH2); 29.67, 29.98 (CH2); 32.41,
32.65, 32.81 (CH2); 36.04, 36.23 (CH2); 39.37 (CH2); 42.61,
42.72 (CH2); 49.39 (VBA CH2) 53.26 (outer RCH); 55.62 (inner
ꢀ
arom); 137.89, 137.94 (NR-Z arom qC); 138.17 (N -Z arom qC);
156.83, 156.91, 156.97 (Z CO); 172.09, 172.23, 172.28, 172.54,
172.62, 172.87 (CO); 173.66 (COOH). MS (MALDI-TOF,
dithranol, DMSO): m/z ) 2083 (46% [M + Na]+), 2099 (21%
[M + K]+).
4c: Yield: 74% of a beige solid. 1H NMR (300 MHz, DMSO,
298 K): δ (ppm) ) 0.99-1.80 (m, 42H, RCH-(CH2)3); 2.95 (bs,
14H, RCH(CH2)3-CH2); 3.89, 3.97 (m, 4H, outer RCH); 4.14
(m, 2H, middle RCH); 4.27 (m, 1H, inner RCH); 4.99 (m, 16H,
Z CH2); 7.21 (t, NH); 7.33 (m, 40H, arom CH); 7.83 (t, NH);
8.08 (d, NH); 12.55 (COOH). 13C NMR (75 MHz, DMSO, 298
K): δ (ppm) ) 23.40, 23.54, 23.72 (CH2); 29.65, 29.96 (CH2);
32.39, 32.61, 32.77 (CH2); 39.26, 39.37, 39.45 (CH2); 52.72,
ꢀ
RCH); 66.02 (N -Z-CH2); 66.27 (NR-Z-CH2); 114.70 (CHd
CH2); 126.95, 128.37 (VBA arom CH); 128.61 (NR-Z arom CH);
ꢀ
129.23 (N -Z arom CH); 136.60 (VBA arom qC); 137.28 (CHd
ꢀ
52.97, 53.23 (inner RCH); 55.61 (outer RCH); 66.02 (N -Z CH2),
CH2); 137.91, 137.95 (Z arom qC); 138.17 (VBA arom qC);
156.84, 156.91, 156.98 (Z CO); 171.07, 171.15, 172.22, 172.30,
172.55, 172.64 (CO). MS (MALDI-TOF, dithranol, DMSO):
m/z ) 1148 (100% [M + Na]+).
ꢀ
66.27 (NR-Z CH2); 128.60 (N -Z arom CH); 129.22 (NR-Z
ꢀ
arom CH); 137.90, 137.94 (NR-Z arom qC); 138.17 (N -Z arom
qC); 156.82, 156.86, 156.92, 156.97 (Z-CO); 172.10, 172.53,
(CO); 174.31 (COOH). MS (MALDI-TOF, dithranol, DMSO):
m/z ) (13% [M - 1Z]+); 2012 (31% [M + Na]+); 2028 (64% [M
+ K]+).
6b: Reaction conditions: 3b:1:HBTU:HOBt:DIPEA ) 1:6:
3:3:4.5; 12 mL of NMP; reaction time: 8 h. Yield: 1.45 g (1.5
1
mmol, 85%) of a white solid. H NMR (300 MHz, DMSO, 298
Nr,NE-Diprotected L-Lysine Dendronized Styrene Mac-
K): δ (ppm) ) 1.24 (q, 2H, RCHCH2-CH2); 1.47 (q, 2H, RCH-
CH2); 1.69 (q, 2H, RCH(CH2)2-CH2); 2.32 (t, 2H, VBA-CO-
CH2); 3.15 (q, 2H, RCH(CH2)3-CH2); 3.3 (2H, VBA-CO-
CH2CH2); 4.18 (m, 2H, outer RCH); 4.25 (d, 2H, VBA CH2);
4.35 (m, 1H, inner RCH); 5.21 (dd, 1H, CHdCH2); 5.79 (dd,
1H, CHdCH2); 6.70 (q, 1H, CHdCH2); 7.21 (d, 2H, VBA-CH);
7.41 (d, 2H, VBA arom CH); 8.29 (t, NH); 8.38 (t, TFA-NH);
9.38 (t, NH); 9.47 (d, 1H, RCH-NH). 13C NMR (75 MHz,
DMSO, 298 K): δ (ppm) ) 23.73 (CH2); 28.68 (CH2); 31.47,
31.64, 31.78 (CH2); 36.06 (CH2); 36.08 (CH2); 39.48 (CH2); 42.71
(CH2); 53.19 (inner RCH); 54.20 (outer RCH); 111.03, 114.84,
ꢀ
romonomers. General procedure: the appropriate NR,N -
diprotected L-lysine dendron was dissolved in dry NMP,
together with HBTU, HOBt, and DIPEA. After 5-10 min, 1
was added, and the reaction mixture was stirred at room
temperature. The relative amounts of dendron, 1, HBTU,
HOBt, and DIPEA as well as the amounts of solvent and the
reactions time are listed below for each of the dendronized
macromonomers. The reaction was quenched by addition of a
20-fold excess of bidistilled water. To remove excess and
unreacted 1, the pH of the aqueous phase was adjusted to pH
7, and subsequently the solid residue was excessively washed
with bidistilled water. In the case of macromonomer 6b, the
solid obtained after the addition of water was dissolved in
acetone and subsequently precipitated in n-hexane.
ꢀ
118.66, 122.48 (NR-CF3); 111.14, 114.96, 118.78, 122.60 (N -
CF3) 114.69 (CHdCH2); 126.95, 128.37 (VBA arom CH); 136.60
(VBA arom qC); 137.28 (CHdCH2); 140.12 (VBA arom qC);
156.33, 156.81, 157.28, 157.76 (NR-CF3-CO); 156.51, 157.00,
ꢀ
5a: Reaction conditions: 2a:1:HBTU:HOBt:DIPEA ) 1:2:
2:2:3; 28 mL of NMP; reaction time: 16 h. Yield: 3.61 g (6
157.48, 157.97 (N -CF3-CO) 170.71, 170.87, 170.91, 171.06,
171.17 (CO); 172.10, 172.16 (CO). 19F NMR (282 MHz, DMSO,
mmol, 97%) of a white solid. H NMR (300 MHz, DMSO, 298
rt): δ (ppm) ) -73.86, -73.88, 73.89 (NR-CF3), -74.40,
1
ꢀ
K): δ (ppm) ) 1.23-1.53 (m, 6H, RCH-(CH2)3); 2.32 (t, 2H,
VBA-CO-CH2); 2.95 (q, 2H, RCH(CH2)3-CH2); 3.27 (q, 2H,
VBA-COCH2-CH2); 3.90 (m, 1H, RCH); 4.25 (d, 2H, VBA
CH2); 5.00 (m, 4H, Z-CH2); 5.21 (d, 1H, CHdCH2); 5.78 (d, 1H,
CHdCH2); 6.70 (dd, 1H, CHdCH2); 7.21 (d, 2H, VBA arom
CH); 7.32 (m, 7H, Z arom CH + 2NH); 7.41 (d, 2H, VBA arom
CH); 7.97 (t, NH); 8.38 (t, NH). 13C NMR (75 MHz, DMSO,
298 K): δ (ppm) ) 23.71 (CH2); 30.01 (CH2); 32.56 (CH2); 36.10
(CH2); 36.24 (CH2); 40.44 (CH2); 42.71 (CH2); 55.61 (RCH);
66.03, 66.29 (Z-CH2); 114.72 (CHdCH2); 126.98 (VBA arom
CH); 126.98 (VBA arom CH); 128.39 (NR-Z arom CH); 128.64
-74.41 (N -CF3). MS (FD): m/z ) 995 (100% [M + Na]+), 1017
(6% [M + 2Na]+).
7a: Reaction conditions: 4a:1:HBTU:HOBt:DIPEA ) 1:3:
3:2.5:4; 15 mL of NMP; reaction time: 16 h. Yield: 1.81 g (0.83
1
mmol, 95%) of a beige solid. H NMR (300 MHz, DMSO, 298
K): δ (ppm) ) 1.06-1.73 (m, 42H, RCH-(CH2)3); 2.31 (t, 2H,
VBA-CO-CH2); 2.96 (bs, 14H, RCH(CH2)3-CH2); 3.3 (m, 2H,
VBA-COCH2-CH2); 3.89, 3.97 (2m, 4H, outer RCH); 4.16 (m,
3H; inner RCH); 4.25 (bs, 2H, VBA CH2); 5.0 (m, 16H, Z CH2);
5.21 (d, 1H, CHdCH2); 5.78 (d, 1H, CHdCH2); 6.69 (q, 1H,
CH-CH2); 7.2 (d, 2H, VBA arom CH); 7.33 (m, 40H, Z arom
CH + 7NH); 7.39 (d, 2H, VBA arom CH); 7.84 (bs, 7NH); 7.93
(bs, 1NH); 8.36 (t, 1NH). 13C NMR (75 MHz, DMSO, 298 K):
δ (ppm) ) 23.58, 23.73 (CH2); 29.67, 29.97 (CH2); 32.14, 31.60,
32.82 (CH2); 36.05, 36.25 (CH2); 39.39 (CH2); 42.63, 42.71
(CH2); 49.40 (VBA CH2); 53.26 (outer RCH); 55.61 (inner RCH),
ꢀ
(N -Z arom CH); 129.26 (VBA arom CH); 136.61 (VBA arom
ꢀ
qC); 137.31 (CHdCH2); 137.96 (NR-Z arom qC); 138.19, (N -Z
arom qC); 140.16 (VBA arom qC); 156.85, 157.0 (Z-CO);
171.24 (CO); 172.81 (CO). MS (FD): m/z ) 601.8 (100% [M]+).
5b: Reaction conditions: 2b:1:HBTU:HOBt:DIPEA ) 1:2:
2:2:3; 35 mL of NMP; reaction time: 16 h. Yield: 3.75 g (7.2
ꢀ
66.02 (N -Z-CH2); 66.27 (NR-Z-CH2); 114.72 (CHdCH2);
1
mmol, 98%) of a white solid. H NMR (300 MHz, DMSO, 298
126.98 (VBA arom CH); 128.36 (VBA arom CH); 128.60 (NR-Z
ꢀ
K): δ (ppm) ) 1.29 (q, 2H, RCHCH2-CH2); 1.43 (q, 2H, RCH-
CH2); 1.67 (q, 2H, RCH(CH2)2-CH2); 2.33 (t, 2H, VBA-CO-
CH2); 3.15 (q, 2H, RCH(CH2)3-CH2); 3.26, (m VBA-COCH2-
arom CH); 129.23 (N -Z arom CH); 136.58, 137.88, 137.94 (Z
arom qC); 137.27 (CHdCH2); 138.17 (VBA arom qC) 140.11
(VBA arom qC); 156.83, 156.92, 156.98 (Z CO); 171.08, 171.16,

Macromolecules, Vol. 38, No. 6, 2005
L-Lysine Dendronized Polystyrene 2067
Scheme 1
172.14, 172.22, 172.56 (CO). MS (MALDI-TOF, dithranol,
DMSO): m/z ) 2198 (100% [M + Na]+).
RCH(CH2)3-CH2); 4.25-4.67 (n*5H, RCH + VBA CH2); 6.10-
7.24 (n*4H, VBA arom CH); 8.03-8.55 (n*NH); 9.37 (n*NH).
7c: Yield: 1.28 g (0.61 mmol, 93%) of a beige solid. 1H NMR
(300 MHz, DMSO, 298 K): δ (ppm) ) 1.02-1.81 (m, 42H,
RCH-(CH2)3); 2.96 (bs, 14H, RCH(CH2)3-CH2); 3.89-4.06 (2m,
4H, outer RCH); 4.1-4.38 (m, 5H; inner RCH + VBA CH2);
5.0 (m, 16H, Z C 2); 5.19 (dd, 1H, CHdCH2); 5.77 (dd, 1H, CHd
CH2); 6.6-6.76 (m, 1H, CH-CH2); 6.82-7.52 (m, arom CH);
7.71, 8.00, 8.20, 8.37 (NH). 13C NMR (75 MHz, DMSO, 298
K): δ (ppm) ) 23.55, 23.72 (CH2); 29.67, 29.97 (CH2); 32.39,
32.64, 32.82 (CH2); 39.37 (CH2); 42.72 (VBA CH2) 53.25, 53.53
Results and Discussion
Styrene functionalized L-lysine dendrons of three
different generations (5-7) were prepared by solution
coupling of 4-vinylbenzylamine (1) with the appropriate
ꢀ
NR,N -diprotected L-lysine dendron (2-4) under stan-
dard peptide coupling conditions (Scheme 1). The syn-
thesis of the dendronized macromonomers was per-
formed with an excess of 1 to drive the reaction to
completion. The L-lysine functionalized macromonomers
not only differed in generation but also in the chemical
nature of the N-terminal protective groups. Two differ-
ent protective groups were explored: the benzyloxycar-
bonyl (Z) and trifluoroacetyl (TFA) groups, which differ
in size, polarity, and the conditions under which they
can be removed. The zeroth generation dendrons (2a,b)
were prepared via solution coupling of â-alanine-tert-
ꢀ
(inner RCH); 55.61 (outer RCH), 66.02 (N -Z-CH2), 66.27
(NR-Z-CH2); 114.70 (CHdCH2); 126.90 (VBA arom CH);
ꢀ
128.22 (VBA arom CH); 128.60 (NR-Z arom CH); 129.22 (N -Z
arom CH); 136.53, 136.59 (Z arom qC); 137.25 (CHdCH2);
137.89 (VBA arom qC) 137.94 (VBA arom qC); 156.82, 156.97
(Z-CO); 172.09, 172.35, 172.54, 172.61, 173.21 (CO). MS
(MALDI-TOF, dithranol, DMSO): m/z ) 2128 (100% [M +
Na]+).
Polymerization Experiments. Polymerizations were per-
formed in Schlenk tubes, which were charged with the ap-
propriate amounts of macromonomer, solvent, and initiator
(AIBN, 1 mol %). After three “freeze-pump-thaw” cycles, the
Schlenk tube was heated to 70 °C under an argon atmosphere,
and the polymerization was allowed to proceed for 3 days. After
that, the polymers were precipitated in water (Z-protected
dendronized polystyrenes) or diethyl ether (TFA-protected
dendronized polystyrenes), filtered, and vacuum-dried. After
determination of the conversion via 1H NMR spectroscopy,
unconverted macromonomer was removed via dialysis.
Polymer from 5a: 1H NMR (500 MHz, DMSO, 302 K): δ
(ppm) ) 1.08-1.68 (n*9H, [-CH-CH2-] + RCH-(CH2)3); 2.32
(n*2H, VBA-CO-CH2); 2.93 (n*2H, RCH(CH2)3-CH2); 3.92
(n*1H, RCH); 4.18 (n*2H, VBA CH2); 4.96 (n*4H, Z CH2);
5.97-7.05 (n*4H, VBA arom CH); 7.17 (n*2NH); 7.28 (n*10H,
Z arom CH); 7.95 (n*1NH); 8.29 (n*1NH).
Polymer from 5b: 1H NMR (300 MHz, DMF, 298 K): δ
(ppm) ) 1.12-2.01 (n*6H, RCH-(CH2)3; 2.54 (n*2H, VBA-
CO-CH2); 3.32 (n*2H, RCH(CH2)3-CH2); 4.15-4.58 (n*3H,
RCH + VBA CH2); 6.17-7.31 (n*4H, VBA arom CH); 8.31
(n*1NH); 9.42 (n*1NH).
Polymer from 6a: 1H NMR (700 MHz, DMSO, 333 K): δ
(ppm) ) 1.01-1.76 (n*21H, [-CH-CH2-] + RCH-(CH2)3);
2.33 (n*2H, VBA-CO-CH2); 2.96 (n*6H, RCH(CH2)3-CH2);
3.93, 4.00 (n*2H, outer RCH); 4.23 (n*3H, VBA-CH2 + inner
RCH); 4.99 (n*8H, Z CH2); 6.04-6.99 (n*(4H + 3NH), VBA
arom CH + NH); 7.12-7.55 (n*20H, Z CH2); 7.60-7.87
(n*3NH); 8.11 (n*1NH).
Polymer from 6b: 1H NMR (300 MHz, DMF, 298 K): δ
(ppm) ) 1.18-2.13 (n*18H, RCH-(CH2)3; 2.49 (n*2H, VBA-
CO-CH2); 3.15 (N + 2H, VBA-COCH2-CH2); 3.31 (n*6H,
butyl ester hydrochloride with the appropriate NR,N -
ꢀ
diprotected L-lysine derivative followed by removal of
the tert-butyl ester protective group. Higher generation
dendrons were obtained via Fmoc solid-phase peptide
synthesis. While most of the macromonomers contain
â-alanine as a spacer between the styrene moiety and
the peptide dendron, one homologue of macromonomer
7a was prepared (7c) in which 1 was directly coupled
to a second generation Z-protected dendron without a
â-alanine spacer (4c).
The dendronized macromonomers were characterized
by means of 1H and 13C NMR spectroscopy and MALDI-
TOF mass spectrometry. Figure 1 shows MALDI-TOF
mass spectra of the first and second generation Z-
protected L-lysine dendronized macromonomers (6a and
7a, respectively). Each of the mass spectra only shows
a single peak with a mass corresponding to the sodium-
labeled species. In the mass spectra, there are no
indications for the presence of defects in the L-lysine
dendron or for incomplete coupling of 1 to the dendron.
Figure 2 shows the 1H NMR spectrum of the first
generation Z-protected L-lysine dendronized macromono-
mer (6a). Comparison of the integrals of the signals of
the styrene moiety with those of the amino acid residues
also indicates that the coupling reaction proceeded to
completion and proves the absence of residual unreacted
dendron or 1. The inset in Figure 2 shows part of the
1H NMR spectrum of a batch of the same macromono-

2068 Lu¨bbert et al.
Macromolecules, Vol. 38, No. 6, 2005
erization of the dendronized polymers on the initial
monomer concentration.13 For this reason, attempts
were made to investigate the polymerization of mac-
romonomers 5-7 over a broad range of concentrations
between 0.1 and 1.0 M. Of the Z-protected macromono-
mers 5a, 6a, 7a, and 7c only the zeroth-generation
monomer (5a) was soluble in DMF at all concentrations.
The first-generation monomer (6a) could not be com-
pletely dissolved in DMF at concentrations above 0.5
mol/L, and for the second-generation macromonomer 7a
a homogeneous solution was obtained only at a concen-
tration of 0.1 mol/L. Once the monomers were dissolved
in DMF, the reaction mixture remained homogeneous
throughout the course of the polymerization, and no
precipitation was observed. In contrast to the Z-pro-
tected macromonomers, the TFA-protected macromono-
mers 5b and 6b were completely soluble in DMF at all
the investigated concentrations. After a reaction time
of 3 days, the polymerization mixture was precipitated
in water (Z-protected L-lysine dendronized polystyrenes)
or diethyl ether (TFA-protected L-lysine dendronized
polystyrenes). Conversions were calculated from the 1H
NMR spectra of the crude reaction products by com-
parison of the integrals of the vinyl group of the styrene
moiety with those of the amino acid residues in the
L-lysine dendron (Tables 1 and 2). Subsequently, re-
sidual monomer was removed via dialysis in DMF. The
purified L-lysine dendronized polymers were analyzed
with 1H NMR spectroscopy and GPC. The results of
Figure 1. MALDI-TOF mass spectra of macromonomers 6a
(left, m/z ) 1148) and 7a (right, m/z ) 2199).
mer that was recorded prior to the washing step to
remove excess and unreacted 1. In this inset, the vinyl
and methylene protons of unreacted and residual 1
appear as small peaks that are slightly shifted downfield
with respect to the corresponding signals of the mac-
romonomer.
ꢀ
Polymerization experiments with the NR,N -dipro-
tected L-lysine dendronized macromonomers were car-
ried out in DMF using 1 mol % 2,2′-azobis(isobutyroni-
trile) (AIBN) as the initiator. Earlier reports have
described a strong dependence of the degree of polym-
Figure 2. 1H NMR spectrum of macromonomer 6a (300 MHz, DMSO-d6, 298 K). The inset shows part of the 1H NMR spectrum
of the same macromonomer prior to purification.

Macromolecules, Vol. 38, No. 6, 2005
L-Lysine Dendronized Polystyrene 2069
Table 1. Reaction Conditions for the Polymerization of the Z-Protected Dendronized Macromonomers and GPC Results
Obtained from the Corresponding Polymers
a
a
c
cmonomer
cmonomer
[wt %]
Mn (×10-3
)
c
c
c
c
expt
monomer
[mol/L]
convb [%]
[g/mol]
DPn
Mw/Mn
KMHKS × 10-3
aMHKS
1
2
5a
0.1
0.3
0.5
0.7
1
0.1
0.3
0.5
0.1
0.1
6.0
16.0
24.1
30.7
38.8
10.6
26.3
37.3
18.7
17.4
71
85
88
91
90
44
62
58
11
10
65.5
53.4
92.6
96.1
93.8
60.1
61.5
104.4
11.9
25.3
109
89
2.04
2.73
2.27
2.51
2.41
1.88
2.62
3.57
2.62
1.53
13.19
9.53
9.71
11.23
10.43
74.32
12.53
25.42
9553.2
122.3
0.561
0.598
0.597
0.593
0.594
0.381
0.571
0.495
0.061
0.365
3
154
160
156
53
4
5
6
6a
7
55
8
93
9
7a
7c
5
10
13
a Initial macromonomer concentration. b Determined by 1H NMR. c Number-average molecular weight (Mn), number-average degree of
polymerization (DPn), polydispersity (Mw/Mn), and Mark-Houwink-Kuhn-Sakurada (MHKS) coefficients K and a determined from
GPC.
Table 2. Reaction Conditions for the Polymerization of the TFA-Protected Dendronized Macromonomers and GPC
Results Obtained from the Corresponding Polymers
a
a
c
cmonomer
cmonomer
[wt %]
Mn(×10-3
)
c
c
c
c
expt
monomer
[mol/L]
convb [%]
[g/mol]
DPn
Mw/Mn
KMHKS × 10-3
aMHKS
11
12
13
14
15
16
17
18
19
20
5b
0.1
0.3
0.5
0.7
1
0.1
0.3
0.5
0.7
1
5.2
14.2
21.7
27.9
35.6
9.3
23.6
33.9
41.8
50.7
91
97
98
99
99
57
78
82
96
93
33.3
45.4
63
87
107
149
128
65
152
187
222
242
2.25
1.86
1.77
1.61
1.88
1.71
1.8
1.75
2.54
1.98
8.786
6.061
5.398
2.215
0.919
18.33
1.708
0.625
1.774
1.329
0.604
0.644
0.644
0.729
0.784
0.512
0.701
0.785
0.714
0.738
55.9
77.9
67.2
6b
63.3
147.4
181.6
215.8
235.8
a Initial macromonomer concentration. b Determined by 1H NMR. c Number-average molecular weight (Mn), number-average degree of
polymerization (DPn), polydispersity (Mw/Mn), and Mark-Houwink-Kuhn-Sakurada (MHKS) coefficients K and a determined from GPC.
with increasing dendron size, which is in agreement
with earlier reports on other dendronized macromono-
mers.1c While most polymerization experiments yielded
dendronized polymers with reasonable degrees of po-
lymerization, the second-generation Z-protected mac-
romonomer 7a only afforded oligomers with a number-
average degree of polymerization according to GPC of
∼5. Attempts to obtain higher molecular weight den-
dronized polymers from 7a, e.g., by increasing the
reaction time, were unsuccessful.
In addition to polymer molecular weight, the GPC
experiments can also provide insight into the hydrody-
namic properties of the dendronized polymers. The on-
line coupling of a viscometer detector allows the deter-
mination of the Mark-Houwink-Kuhn-Sakurada
(MHKS) coefficients K and a, which are also included
in Tables 1 and 2. The MHKS coefficient a is most
interesting, since its value depends on the polymer
conformation. Except for the polymer obtained from 7a,
the MHKS a coefficients are all in the range 0.5-0.8,
indicative for a random coil backbone conformation.14
The polymer prepared from macromonomer 7a has a
very low MHKS a coefficient of 0.061, which is in the
range expected for a compact sphere.14 The GPC experi-
ments, thus, suggest that at least in dilute DMF
solution the zeroth and first generation dendrons are
not sufficiently sterically demanding to cause stretching
of the polymer backbone, and the dendronized polymers
appear to adopt a random coil conformation. The very
small MHKS coefficient a for the polymer obtained from
7a is probably related to the very small degree of
polymerization of this polymer. It is also difficult to
evaluate the effect of the introduction of the â-alanine
spacer on the backbone conformation of the dendronized
polymers. The difference in the MHKS coefficient a
Figure 3. Monomer conversion vs initial monomer concentra-
tion for the Z-protected L-lysine-based dendronized mac-
romonomers 5a, 6a, and 7a.
these experiments are listed in Tables 1 and 2 for the
Z-protected and the TFA-protected dendronized poly-
styrenes, respectively. Figure 3 plots monomer conver-
sion vs monomer concentration in the polymerization
mixture for the Z-protected L-lysine-based macromono-
mers (5a, 6a, 7a).
The data in Table 1, Table 2, and Figure 3 show that
monomer conversion and polymer molecular weight
depend on the initial monomer concentration in the
reaction medium. The effects, however, are by far not
as dramatic as those reported for the polymerization of
several other dendronized macromonomers.13 Even at
low monomer concentrations, dendronized polymers
with reasonable molecular weights were obtained. Mono-
mer conversion and polymer molecular weight decrease

2070 Lu¨bbert et al.
Macromolecules, Vol. 38, No. 6, 2005
Figure 4. (a) TEM micrograph of an ultrasharp Hi’Res AFM tip with a radius <3 nm. (b-e) AFM images of dendronized polymers
obtained by polymerization of macromonomer 6a at a concentration of 0.1 mol/L (b), macromonomer 6a at a concentration of 0.5
mol/L (c, e), and macromonomer 7a (d). Samples were prepared by spin-casting onto mica substrates.
between samples 7a and 7c cannot be directly at-
tributed to the presence/absence of the â-alanine spacer
since the two polymers have significantly different
molecular weights.
unit and an almost extended backbone conformation.
However, since the diameter of the rods is ∼6.6 nm, the
aspect ratio of the objects is relatively small, and the
hydrodynamic behavior of the molecules may rather
approximate that of a compact sphere or ellipsoid
instead of a rod.
In an attempt to obtain additional insight into the
structure of the dendronized polymers, AFM experi-
ments were performed on thin films, which were spin-
cast from DMF on mica substrates. Obtaining high-
resolution images of the samples proved difficult and
took significant effort; however, using ultrasharp tips,
single molecule resolution could be achieved. So far, only
images from dendronized polymers based on mac-
romonomers 6a and 7a could be obtained. Figure 4
shows images obtained from dendronized polymers
prepared by polymerization of 6a at concentrations of
0.1 and 0.5 mol/L and 7a at 0.1 mol/L. The image with
the highest resolution is Figure 4c, which shows rodlike
objects. Analysis of an ensemble of 100 molecules in
Figure 4c revealed an average length of 15 ( 7 nm and
an average diameter of 6.6 ( 1.3 nm. The length of the
rods is close to that expected for an extended backbone
conformation assuming a length of 0.25 nm per styrene
repeat unit and a degree of polymerization of ∼90.
Although the resolution is not as good as in Figure 4c,
the images in Figure 4b and Figure 4d reveal short
rodlike objects and globular structures, respectively.
Since the samples imaged in Figure 4b and Figure 4d
have degrees of polymerization of ∼50 and ∼5, which
is much smaller than that of the sample shown in
Figure 4c, this illustrates the effect of the degree of
polymerization on the single molecule structure of these
peptide dendronized polymers.
At a first glance, the results from the GPC experi-
ments and the AFM images seem contradictionary.
While the MHKS a coefficients suggest a random coil
backbone conformation, the AFM images reveal rodlike
structures for the polymers prepared from macromono-
mer 6a. One explanation for this discrepancy may be
the moderate degrees of polymerization of the den-
dronized polymers. The polymer obtained from 6a at a
monomer concentration of 0.5 mol/L has a number-
average degree of polymerization of ∼90, which is in
good agreement with the observed rod length of ∼15 (
7 nm, assuming a length of 0.25 nm per styrene repeat
Conclusions
In this contribution, we have described the synthesis
of a new class of peptide dendronized polymers, which
were obtained via free radical polymerization of styrene
functionalized L-lysine dendrons. While the dendronized
macromonomers of the zeroth and first generation
generally afforded high molecular weight dendronized
polymers (number-average degree of polymerization
(DP): 50-240), only short oligomers (DP ) 5-10) were
obtained for the second generation macromonomers.
First AFM experiments illustrated the effect of the
degree of polymerization on the single molecule archi-
tecture; with decreasing degree of polymerization, the
structure of the dendronized polymers changes from
rods to short rods to globules. Extensive studies to
elucidate the structure of the materials are underway
and will be reported elsewhere.
Acknowledgment. This work was partially sup-
ported by the Deutsche Forschungsgemeinschaft (Emmy
Noether Program).
References and Notes
(1) See e.g.: (a) Frey, H. Angew. Chem., Int. Ed. 1998, 37, 2193.
(b) Schlu¨ter, A. D.; Rabe, J. P. Angew. Chem., Int. Ed. 2000,
39, 864. (c) Zhang, A.; Shu, L.; Bo, Z.; Schlu¨ter, A. D.
Macromol. Chem. Phys. 2003, 204, 328.
(2) Percec, V.; Ahn, C.-H.; Ungar, G.; Yeardly, D. J. P.; Mo¨ller,
M.; Sheiko, S. S. Nature (London) 1998, 391, 161.
(3) See e.g.: (a) Chen, Y. M.; Chen, C. F.; Liu, W. H.; Xi, F.
Macromol. Rapid Commun. 1996, 47, 401. (b) Neubert, I.;
Amoulong-Kirstein, E.; Schlu¨ter, A. D.; Dautzenberg, H.
Macromol. Rapid Commun. 1996, 47, 517.
(4) See e.g.: Kaneko, T.; Horie, T.; Asano, M.; Aoki, T.; Oikawa,
E. Macromolecules 1997, 30, 3118.
(5) Niggemann, M.; Ritter, H. Acta Polym. 1996, 47, 351.
(6) Niggemann, M.; Ritter, H. J. Macromol. Sci., Pure Appl.
Chem. 1997, A34, 1325.

Macromolecules, Vol. 38, No. 6, 2005
L-Lysine Dendronized Polystyrene 2071
(7) (a) Bushin, S. V.; Girbasova, N. V.; Belyaeva, E. V.; Bezruk-
ova, M. A.; Andreeva, L. N.; Bilibin, A. Yu. J. Polym. Sci.,
Ser. A 2002, 44, 632. (b) Girbasova, N. V.; Migunova, I. I.;
Raspopova, I. R.; Bilibin, A. Yu. J. Polym. Sci., Ser. A 2003,
45, 320. (c) Girbasova, N.; Aseyev, V.; Saratovsky, S.;
Moukhina, I. Tenhu, H. Bilibin, A. Macromol. Chem. Phys.
2003, 204, 2258. (d) Bilibin, A.; Zorin, I.; Saratovsky, S.;
Moukhina, I.; Egorova, G.; Girbasova, N. Macromol. Symp.
2003, 199, 197. (e) Bilibin, A. Yu.; Egorova, G. G.; Girbasova,
N. V.; Saratoskii, S. V.; Mukhina, I. V. J. Polym. Sci., Ser. A
2004, 46, 89.
(b) Choi, J. S.; Joo, D. K.; Kim, C. H.; Kim, K.; Park, J. S. J.
Am. Chem. Soc. 2000, 122, 474.
(10) Weygand, F.; Geiger, R. Chem. Ber.-Rec. 1956, 89, 647.
(11) Charreyre, M. T.; Razafindrakoto, V.; Veron, L.; Delair, T.;
Pichot, C. Macromol. Chem. Phys. 1994, 195, 2141.
(12) (a) Fields, G. B.; Noble, R. L. Int. J. Peptide Protein Res. 1990,
35, 161. (b) Fmoc Solid Phase Peptide SynthesissA Practical
Approach; Chan, W. C., White, P. D., Eds.; Oxford University
Press: New York, 2000.
(13) See e.g.: Shu, L.; Schlu¨ter, A. D. Macromol. Chem. Phys.
2000, 201, 239.
(8) See e.g.: (a) Tam, J. P.; Spetzler, J. C. Methods Enzymol.
1997, 289, 612. (b) Tam, J. P. J. Immunol. Methods 1996,
196, 17.
(14) Harding, S. E. Prog. Biophys. Mol. Biol. 1997, 68, 207.
(9) See e.g.: (a) Ohsaki, M.; Okuda, T.; Wada, A.; Hirayama, T.;
Niidome, T.; Aoyagi, H. Bioconjugate Chem. 2002, 13, 510.
MA047621N