Table 1 Summary of conversion, molecular weight and polydispersity data for homopolymerization of ABA using various initiators in protic
media at 20 uCa
Molecular weight
d
Initiator type
Solvent H2O : MeOH
Time/h
Conversion (%)b
Mn(theory)c
Mn(GPC)d
Mn(exp)
Mw/Mn
1
1
1
2
2
2
3
3
3
a
100 : 0
100 : 0
60 : 40
60 : 40
60 : 40
60 : 40
100 : 0
60 : 40
60 : 40
4
4
18
6
6
18
4
97
92
95
90
92
92
97
93
82
8260
11 540
11 900
7500
11 300
11 300
7980
13 300
—
9880
7900e
8990e
1.16
—
17 800d,f
12 300d,f
15 900d,f
15 900d,f
10 000b
9230b
1.22
1.22
1.21
1.20
1.16
1.13
1.25
9970
12 300
12 500
11 700
11 600
10 200
18
18
7660
10 100
11 700b
b
Synthesis conditions: [ABA] 5 1.747 M. The molar ratio of initiator : CuBr : bpy was 2 : 2 : 5 in all experiments. Determined from 1H
c
d
NMR. Calculated from the following equation: Mn(theory) 5 143.1([ABA]0/[initator]) 6 %Conversion/100 + Mw(initiator). Determined by
GPC analysis [THF containing 0.25 wt% tetrabutylammonium bromide, PSt standards, RI, UV, TALS (two angle light scattering) detectors]
after PABA was converted into its methyl ester form. PABA homopolymer was treated with diazomethane, which was generated from diazald
reacted with KOH in water–ethanol solution at 65 uC, to obtain partially esterified products, having solubility in THF for Mw determination
e
f
(see ref. 18). Mw determined from the multi-angle light scattering (MALS) detector in water at 20 uC. Determined from TALS (15u and 90u)
detector with a 680 nm laser and a refractive index detector.
To terminate the polymerization, the dark brown solution
was bubbled with oxygen gas, diluted with water, and acidified
with a solution of concentrated HCl (37%). The spent ATRP
catalyst was removed by treatment with silica gel, followed by
dialysis against deionized water for 48 h with periodic bath
changes to remove unreacted monomers. The dialysis products
were freeze-dried.
The monomer consumption was monitored by 1H NMR
spectroscopy as a function of time. The signal from methine
protons of the polymer backbone at 1–2 ppm increased gradually,
together with the reduction of the vinyl peaks at 6.09 and 5.62 ppm,
which were ascribed to the ABA monomer (see ESI{). Like
the ATRP of other hydrophilic monomers reported elsewhere,10
high conversions were achieved in short times in protic media
at 20 uC for the ATRP of ABA, which means that the rate
of polymerization is extremely fast under remarkably mild
conditions.
1H NMR spectroscopy was also used to determine the number
average molecular weight of the purified PABA prepared using
initiator 3 by comparing the intensity of the aromatic protons at
7.8 and 7.2 ppm of the initiator with that due to the methylene
protons of the PABA residues at 2.5 ppm. Good agreement of
Mn(NMR) and Mn(theory) shows that the molecular weight of
PABA could be controlled by the monomer : initiator molar
ratio, which is supporting evidence for a living polymerization
(see ESI{ and Table 1). The molecular weights of the polymers
increased with conversion, as expected for a living polymerization,
but the plots were not strictly linear. This supports the earlier
report by Armes et al. that the kinetics for ATRP of acidic
monomers is complex.11 It was impossible to determine Mn of
polymers prepared using initiators 1 and 2 by NMR calculations
due to the overlapping peaks of initiator and PABA residues.
Table 1 summarizes molecular weights, polydispersities, and
conversion data for homopolymers. GPC analysis indicates that
the homopolymerization of ABA using the three different
initiators afforded relatively narrow, monomodal peaks with
polydispersities of around 1.13 to 1.25 and proceeded to high
conversions (.90%) in either water or a 60 : 40 water–methanol
mixture (ESI and Table 1). Some deviations between the
molecular weights determined by GPC and theoretical Mn
were found, which may be due to the difference in the
hydrodynamic volumes of the polystyrene standard and the
resulting polymers.
Static light scattering from some polymers was also measured to
obtain weight average molecular weights. The specific refractive
index increments (dn/dc) of PABA in water at 20 uC and in THF
at 40 uC were determined using a refractive index detector (Wyatt
OPTILAB DSP). A detailed experimental protocol is available as
Supporting Information.{ The measured dn/dc values at 690 nm
were 0.1572 ml g21 in water for PABA and 0.101 ml g21 in THF
for methylated PABA. The molecular weights of PABA obtained
by this method, especially by MALS, are in good agreement with
the theoretical molecular weights (see Table 1).
In summary, well-defined, potentially biocompatible natural
amino acid-based polymers, PABA, were synthesized by ATRP in
aqueous media under conditions very close to physiological
conditions, potentially facilitating functionalization of proteins or
biomaterials that cannot be functionalized in organic solvents.
High monomer conversions under mild conditions (20 uC) and
narrow polydispersities of the resulting PABA are clear indications
of a controlled polymerization mechanism. All three of the
initiator systems used afforded good results, but the ethylene
glycol-based initiator may be preferred over the other initiators
based on biocompatibility considerations. Future studies will focus
on the use of ATRP to synthesize amino acid-based di- and tri-
block amphiphilic copolymers, which may have use in biotech-
nology applications by fabricating self-assembled biocompatible
micelles for hydrophobic drug delivery. We will also explore
polymerization of other amino acids in order to determine how
general this procedure is for producing well-defined amino acid-
based polymers.
Research sponsored by the ORNL Laboratory Director’s
Research and Development Program, US Department of
Energy, under contract No. DE-AC05-00OR22725 with Oak
Ridge National Laboratory, managed and operated by UT-
Battelle, LLC.
This journal is ß The Royal Society of Chemistry 2005
Chem. Commun., 2005, 1046–1048 | 1047
Chung, Il-Doo
