Synthesis and characterization of well-defined optically active methacrylic diblock copolymers

Article abstract of DOI:10.1002/pola.26223

A new, simple, and cost-effective approach toward the development of well-defined optically active diblock copolymers based on methacrylate monomers is described for the first time. Starting from the low-cost optically active (S)-(-)-2-methyl-1-butanol, a new optically active methacrylic monomer, namely, (S)-(+)-2-methyl-1-butyl methacrylate [(S)-(+)-MBuMA], was synthesized. Reversible addition fragmentation chain transfer polymerization was then used for preparing well-defined poly[(S)-(+)-MBuMA] homopolymers and water-soluble diblock copolymers based on [(S)-(+)-MBuMA] and the hydrophilic and ionizable monomer 2-(dimethyl amino)ethyl methacrylate (DMAEMA). The respective homopolymers and diblock copolymers were characterized in terms of their molecular weights, polydispersity indices, and compositions by size exclusion chromatography and ¹H NMR spectroscopy. Polarimetry measurements were used to determine the specific optical rotations of these systems. The structural and compositional characteristics of micellar nanostructures possessing an optically active core generated by p((S)-(+)-MBuMA)-b-p(DMAEMA) chains characterized by predetermined molecular characteristics may be easily tuned to match biological constructs. Consequently, the aggregation behavior of the p[(S)-(+)-MBuMA]-b-p[DMAEMA] diblock copolymers was investigated in aqueous media by means of dynamic light scattering and atomic force microscopy, which revealed the formation of micelles in neutral and acidified aqueous solutions.

Full text of DOI:10.1002/pola.26223

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Synthesis and Characterization of Well-Defined Optically Active
Methacrylic Diblock Copolymers
Mariliz Achilleos,1 Demetris Kafouris,2 Simon J. Holder,3 Theodora Krasia-Christoforou1
1Department of Mechanical and Manufacturing Engineering, University of Cyprus, P.O. Box 20537, 1678 Nicosia, Cyprus
2Department of Chemistry, University of Cyprus, P.O. Box 20537, 1678 Nicosia, Cyprus
3Functional Materials Group, School of Physical Sciences, University of Kent, Canterbury, Kent CT2 7NH, United Kingdom
Correspondence to: M. Achilleos (E-mail: achilleos.mariliz@ucy.ac.cy) or T. Krasia-Christoforou (E-mail: krasia@ucy.ac.cy)
Received 18 April 2012; accepted 13 June 2012; published online
DOI: 10.1002/pola.26223
ABSTRACT: A new, simple, and cost-effective approach toward
the development of well-defined optically active diblock
copolymers based on methacrylate monomers is described for
the first time. Starting from the low-cost optically active (S)-
etry measurements were used to determine the specific optical
rotations of these systems. The structural and compositional
characteristics of micellar nanostructures possessing an opti-
cally active core generated by p((S)-(þ)-MBuMA)-b-p(DMAEMA)
chains characterized by predetermined molecular characteris-
tics may be easily tuned to match biological constructs. Conse-
quently, the aggregation behavior of the p[(S)-(þ)-MBuMA]-b-
p[DMAEMA] diblock copolymers was investigated in aqueous
media by means of dynamic light scattering and atomic force
(ꢀ)-2-methyl-1-butanol,
a new optically active methacrylic
monomer, namely, (S)-(þ)-2-methyl-1-butyl methacrylate [(S)-
(þ)-MBuMA], was synthesized. Reversible addition fragmenta-
tion chain transfer polymerization was then used for preparing
well-defined poly[(S)-(þ)-MBuMA] homopolymers and water-
soluble diblock copolymers based on [(S)-(þ)-MBuMA] and the
hydrophilic and ionizable monomer 2-(dimethyl amino)ethyl
methacrylate (DMAEMA). The respective homopolymers and
diblock copolymers were characterized in terms of their molec-
ular weights, polydispersity indices, and compositions by size
exclusion chromatography and 1H NMR spectroscopy. Polarim-
microscopy, which revealed the formation of micelles in neu-
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tral and acidified aqueous solutions.
2012 Wiley Periodicals,
Inc. J Polym Sci Part A: Polym Chem 000: 000–000, 2012
KEYWORDS: block copolymers; chiral; micelles; reversible addi-
tion fragmentation chain transfer (RAFT)
INTRODUCTION Nature routinely uses optically active mole-
cules such as D-sugars and L-amino acids to build up chiral
biopolymers such as proteins and DNA.1,2 The specific chiral
configuration of such macromolecules imparts unique prop-
erties to these materials such as molecular recognition capa-
bility and highly efficient catalytic action toward asymmetric
catalysis.2 The significance of the aforementioned chiral
biopolymers in biological processes such as self-replication,
protein synthesis, regulation, and gene expression cannot be
understated,3–6 and in contrary, racemic molecules have
been proved to be inefficient in these processes.
of reports appear in the literature dealing with the synthesis
of well-defined optically active polymers characterized by
predetermined molecular weights (MWs) and narrow molec-
ular weight distributions (MWDs).23–31 The aforementioned
characteristics are highly desirable, as they allow for their
structural characteristics to be correlated to the properties
of the materials.
As far as methacrylate-based polymers are concerned, rela-
tively complex functional moieties such as amino acids,32
1,10-binaphthyl,33 urea,34 cyclic pyrrolidinyl moieties or suc-
cinimide35 and cholesteryl groups36 have been introduced as
side chains to induce optical activity. The synthesis of opti-
cally active methacrylic monomers characterized by struc-
tural simplicity has not yet been reported.
Inspired by naturally occurring optically active polymers, chi-
ral polymeric materials obtained synthetically7–11 have been
of particular interest in the area of modern polymer science
because of their fascinating applicability in chiral and
molecular recognition,12–14 enantiomeric separation,15,16 chi-
roptical switching,17,18 nonlinear optics,19,20 circular photolu-
minescence and electroluminescence,21,22 and so forth. How-
ever, most of the developed systems are characterized by
structural complexity and/or demanding synthetic methodo-
logies toward their preparation. Moreover, a limited number
Herein, we report for the first time the synthesis of a new,
simple, and optically active methacrylic monomer by follow-
ing an easy and cost-effective synthetic approach, that is, by
using a cheap optically active methacrylic alcohol as a start-
ing material. For the synthesis of the respective homopoly-
mers, reversible addition fragmentation chain transfer
(RAFT) polymerization was used, which is
a versatile
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SCHEME 1 One-step synthetic methodology followed for the preparation of (S)-(þ)-MBuMA optically active monomer.
polymerization technique, allowing for the preparation of
well-defined polymers of various architectures such as block
copolymers, star polymers, graft polymers, hyperbranched
polymers, and polymer (co)networks.37,38
propyl benzodithioate (CPDTB, CTA 2), with 2,20-azobis(iso-
butylnitrile) (AIBN) serving as the radical source. All poly-
mers were obtained as pink gum-like solids, which are solu-
ble in most common organic solvents used to dissolve n-
butyl methacrylate such as tetrahydrofuran (THF), benzene,
ethyl acetate, and toluene. To demonstrate the controlled
character of the RAFT process in the polymerization of the
(S)-(þ)-MBuMA, p((S)-(þ)-MBuMA) homopolymers were
prepared in the presence (RAFT polymerization) and ab-
sence (conventional free radical polymerization) of a CTA
under identical experimental conditions (entries 1 and 6 in
Table 1). The SEC traces of the two homopolymers prepared
by RAFT and conventional free radical polymerization are
plotted in Figure 1. The RAFT homopolymer was character-
ized by low polydispersity index (PDI ¼ 1.16) and unimodal
MWD, whereas the homopolymer prepared via the conven-
tional free radical process exhibited broad MWD (2.0).
The RAFT process was readily used to prepare well-defined
poly((S)-(þ)-2-methyl-1-butyl
methacrylate)
p((S)-(+)-
MBuMA) homopolymers as well as diblock copolymers with
the water-soluble and ionizable 2-(dimethyl amino)ethyl
methacrylate (DMAEMA) on sequential chain growth, using
p((S)-(þ)-MBuMA) as the macro-chain transfer agents
(macro-CTAs). The molecular and compositional characteris-
tics of the resulting homopolymers and diblock copolymers
were determined by size exclusion chromatography (SEC)
1
and H NMR spectroscopy, respectively.
The aggregation behavior of the p((S)-(þ)-MBuMA)-b-
p(DMAEMA) diblock copolymers was investigated by
dynamic light scattering (DLS). In aqueous media, micelles
are generated consisting of a hydrophobic, optically active
core comprised of p((S)-(þ)-MBuMA) chains and a hydro-
philic, ionizable (depending on the pH) p(DMAEMA) corona.
Micellization of diblock copolymers possessing an optically
active block segment may lead to nanoparticles with size
and shape that can be tuned to match biological con-
structs.39 They may also have applications in the selective
uptake of chiral molecules for enantiomeric separations.
Hence, the preparation and characterization of optically
active methacrylate-based micelles consisting of simple opti-
cally active methacrylates as well as their evaluation as effec-
tive chiral recognition systems will be a highly promising
research direction.
The MW parameters (number-average MWs and PDIs) along
with the polymerization yield of the synthesized homopoly-
mers are summarized in Table 1. As can be seen from the ta-
ble, all polymers synthesized by RAFT were characterized by
unimodal, narrow MWDs and low PDIs (<1.25).
Even though in the literature it is reported that there is no
difference in the effectiveness and reactivity of the CDTB and
CPDTB toward methacrylate-based monomers,38 in our case,
the latter was proved to be more effective in terms of poly-
merization yield by following exactly the same experimental
conditions (i.e., reaction time, solution concentration, and
temperature), as p(S)-(þ)-MBuMA) homopolymers synthe-
sized using CTA 2 (CPDTB) were obtained in a much higher
yield (ꢁ65%) when compared with those obtained in the
presence of CTA 1 (CDTB; ꢁ35%).
RESULTS AND DISCUSSION
Poly((S)-(1)-MBuMA) Homopolymers
In this work, for the first time, a new optically active mono-
mer, namely, (S)-(þ)-MBuMA, was synthesized via a typical
esterification methodology reported in the literature,40
involving the reaction of the low-cost optically active (S)-
(ꢀ)-2-methyl-1-butanol with methacryloyl chloride in the
presence of triethylamine, as illustrated in Scheme 1.
RAFT polymerization was then used to prepare a series of
well-defined optically active p((S)-(þ)-MBuMA) homopoly-
mers, as shown in Scheme 2.
SCHEME 2 RAFT-controlled radical polymerization of (S)-(þ)-
MBuMA carried out in solution in the presence of either CDTB
or CPDTB and AIBN.
Two monofunctional CTAs were used in polymer synthesis,
namely, cumyl dithiobenzoate (CDTB, CTA 1) and 2-cyano-2-
2
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TABLE 1 Yield and Molecular Weight Parameters of Homopolymers Based on (S)-(1)-MBuMA
Obtained by RAFT and FRP
SEC Results
Yield
(%)
Theoretical Molecular
Weight (g molꢀ1 b
Entry
Experimental Structurea
)
Mn
PDI
1
2
3
4
5
6
a
(S)-(þ)-MBuMA55 (CDTB)
(S)-(þ)-MBuMA85 (CDTB)
(S)-(þ)-MBuMA55 (CDTB)
(S)-(þ)-MBuMA70 (CPDTB)
(S)-(þ)-MBuMA75 (CPDTB)
(S)-(þ)-MBuMA100 (FRP)
35
30
33
65
68
95
5,750
8,135
1.16
1.25
1.12
1.13
1.15
2.00
9,650
12,600
8,800
5,450
15,500
16,150
15,600
11,000
11,750
14,750
Determined by SEC.
b
[(g monomer)/(mol RAFT agent)] ꢃ (polymerization yield) þ MW of CTA; Mn, number-average molecular
weight; PDI, polydispersity index; (S)-(þ)-MBuMA, (S)-(þ)-2-methyl-1-butyl methacrylate; CDTB, cumyl
dithiobenzoate; CPDTB, 2-cyano-2-propyl benzodithioate; FRP, free radical polymerization.
Optical rotation measurements were carried out in chloro-
form for the (S)-(þ)-MBuMA monomer and two p((S)-(þ)-
MBuMA) homopolymers characterized by different average
MWs. More precisely, the specific optical rotation value
obtained for the (S)-(þ)-MBuMA monomer was [a]2D1 (ꢂ)
þ3.17 6 0.1. The optical rotation values for the (S)-(þ)-
MBuMA55 (Mn ¼ 5,750 g molꢀ1; entry 1 in Table 1) and the
(S)-(þ)-MBuMA70 (Mn ¼ 15,500 g molꢀ1; entry 4 in Table 1)
homopolymers were determined to be [a]2D4 (ꢂ) þ3.3 6 1.6
and [a]2D4 (ꢂ) þ3.4 6 0.75, respectively. Even though the
aforementioned homopolymers were characterized by differ-
ent MW parameters, no significant variations in the values of
the specific optical rotations were observed, demonstrating
the independency of the latter on the molecular weight. This
result is in agreement with previously reported work by
Skey and O’Reilly23 and Endo and coworkers.41 Moreover,
the similarity of the optical rotation values of the two homo-
polymers to that of the monomer suggests that no coopera-
tive effect exists between the polymer units within the
homopolymers (i.e., no helix formation).
Unfortunately, attempts to record circular dichroism (CD)
spectra were hampered by the ester chromophore transitions
having absorptions in the far-UV region and small extinction
coefficients; typically for esters, these can be expected to be
kmax ¼ 190–215 nm and e ¼ 50–500 molꢀ1 dmꢀ3 cmꢀ1. The
far-UV region is notoriously difficult to access for weak chro-
mophores because of the limited range of solvents with no
significant absorption in this range. Homopolymer 4 was not
soluble in pentane, acetonitrile, water, or trifluoroethanol or
mixtures of these solvents. A 2:1 ratio of cyclohexane and
propanol did dissolve the polymer though significant absorp-
tion for the solvent was observed from 240 nm and lower.
Therefore, no absolutely distinct Cotton effects could be
observed in the range of 200–300 nm. As can be seen from
Figure 2, weak possible Cotton effects were visible in the CD
spectrum in the region 200–300 nm that overlap with
absorptions visible in the UV–vis spectra. The far-UV absorp-
tions in the UV spectrum (Fig. 2) could be deconvolved into
three major peaks at 209, 224, and 255 nm, tentatively
assigned to the p–p* and n–p* transitions of the carbonyl
FIGURE 1 SEC traces of the p((S)-(þ)-MBuMA) homopolymer
synthesized by RAFT polymerization and the respective one
synthesized by conventional free radical polymerization.
FIGURE 2 UV–vis absorption spectrum (upper line) and circular
dichroism spectrum (lower line) of homopolymer 4 in cyclo-
hexane:1-propanol (2:1) at 21 ꢂC.
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TABLE 2 Yield and Molecular Weight Parameters of p((S)-(1)-MBuMA)-b-p(DMAEMA)
Copolymers
SEC Results
Yield
(%)
Theoretical Molecular
Weight (g molꢀ1 b
Mn
(g molꢀ1
Entry
Experimental Structurea
)
)
PDI
1
2
3
a
(S)-(þ)-MBuMA55-b-DMAEMA104
(S)-(þ)-MBuMA55-b-DMAEMA230
(S)-(þ)-MBuMA55-b-DMAEMA475
65
72
60
23,500
37,100
56,000
24,500
45,000
83,500
1.15
1.15
1.35
Determined by SEC and 1H NMR.
b
[(g monomer)/(mol RAFT agent)] ꢃ (polymerization yield) þ Mn of macro-CTA 1; Mn, number-average
molecular weight; PDI, polydispersity index; (S)-(þ)-MBuMA, (S)-(þ)-2-methyl-1-butyl methacrylate;
DMAEMA, 2-(dimethyl amino)ethyl methacrylate.
and the p–p* transition of the aromatic chain ends from the
CTDB. It is apparent that better solvent systems and possibly
synchrotron CD measurements will be necessary to conclu-
sively observe the electronic optical activity of these polymers.
diameters (DH) of the resulting macromolecular aggregates
were determined by DLS and atomic force microscopy (AFM).
The experimental DH values for the p((S)-(þ)-MBuMA)-b-
p(DMAEMA) micelles generated in water at pH ¼ 2.54 and 5.5
are summarized in Table 3. From the obtained data, it can be
clearly seen that under acidified conditions, the hydrodynamic
diameter or the micellar aggregates increases as expected,
because on protonation of the DMAEMA units found on the
micellar exterior, chain extension is caused through electro-
static repulsion.44,45 At a pH of 2.54, the DMAEMA block can
be considered fully charged (a ꢄ 1),46 and dramatic expan-
sions in the size micelles with poly(DMAEMA) coronae have
been previously recorded on decreasing the pH to similar val-
ues.47,48 In some cases, the obtained DHs values exceed the
maximum theoretical micelle diameters calculated assuming
spherical morphology and fully extended chains (see Table 3),
suggesting the presence of micellar aggregates in solution.
p((S)-(1)-MBuMA)-b-p(DMAEMA) Diblock Copolymers
Amphiphilic diblock copolymers were synthesized through
chain growth of the p((S)-(þ)-MBuMA) (macro-CTA 1) via
the addition of the hydrophilic and ionizable DMAEMA. The
degree of polymerization (DP) of the presynthesized p((S)-
(þ)-MBuMA) was 55 in all cases, whereas the DP of the
DMAEMA block segment varied (104, 230, and 475; entries
1–3 in Table 2). The polymerization yield, the theoretical
and experimental MWs, and the PDIs of the obtained p((S)-
(þ)-MBuMA)-b-p(DMAEMA) diblock copolymers are sum-
marized in Table 2.
All diblock copolymers received as orange solids were
obtained in good yield (60–72%). The PDIs were relatively
low (1.15–1.35), with the highest value corresponding to the
(S)-(þ)-MBuMA55-b-DMAEMA475 having the highest MW.
Moreover, the MWD of the diblock copolymers is shifted to-
ward higher MWs when compared with that of the (S)-(þ)-
MBuMA55 homopolymer (Fig. 3), demonstrating the block ef-
ficiency from homopolymer to block copolymer42,43 and thus
providing further evidence for the ‘‘living’’ nature of the poly-
merization under these conditions.23,38
Figure 4 illustrates sample AFM micrographs of spherical
block copolymer micelles of (a) (S)-(þ)-MBuMA55-b-
DMAEMA104 and (b) (S)-(þ)-MBuMA55-b-DMAEMA230 gener-
ated in water at pH 2.54 and 5.5, respectively. It is notewor-
thy that the DH values from the AFM measurements are in
The specific optical rotation of (S)-(þ)-MBuMA55-b-
DMAEMA475 (Mn ¼ 83,500 g molꢀ1; entry 3 in Table 2) in
chloroform was determined to be [a]2D1 (ꢂ) þ5.1 6 0.6, dem-
onstrating the preservation of optical activity of the (S)-(þ)-
MBuMA units in the block copolymer structure.
Aggregation Behavior in Aqueous Media
Because of their amphiphilic character, the p((S)-(þ)-
MBuMA)-b-p(DMAEMA) diblock copolymers are expected to
self-assemble in selective for one of the block solvents
generating well-organized nanomorphologies in solution.
The aggregation behavior of the p((S)-(þ)-MBuMA)-b-
p(DMAEMA) diblock copolymers was investigated in aqueous
media. Water is a good solvent for the p(DMAEMA) block
segment, and therefore, micelles are generated in aqueous
solutions consisting of a p(DMAEMA) solvating corona and a
p((S)-(þ)-MBuMA) optically active core. The hydrodynamic
FIGURE 3 SEC traces of the (S)-(þ)-MBuMA55 homopolymer
and the corresponding (S)-(þ)-MBuMA55-b-DMAEMA104 and
(S)-(þ)-MBuMA55-b-DMAEMA230 diblock copolymers prepared
via chain growth of the former with DMAEMA.
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TABLE 3 Experimental Hydrodynamic Diameters (DHs) Obtained by DLS for the p((S)-(1)-MBuMA)-b-p(DMAEMA) Diblock
Copolymer Micelles Formed in Aqueous Solutions at Different pH
DH (Theoretical)
(nm)b
DH (DLS)
Polydispersity
(DLS)
DH (AFM)
Entry
Experimental Structurea
pH
(nm)
(nm)
1
2
3
4
5
6
a
(S)-(þ)-MBuMA55-b-DMAEMA104
(S)-(þ)-MBuMA55-b-DMAEMA104
(S)-(þ)-MBuMA55-b-DMAEMA230
(S)-(þ)-MBuMA55-b-DMAEMA230
(S)-(þ)-MBuMA55-b-DMAEMA475
(S)-(þ)-MBuMA55-b-DMAEMA475
5.5
80
N.D.
68
N.D.
N.D.
74
2.54
5.5
80
0.323
0.210
0.282
0.333
0.361
144
144
267
267
70
98
2.54
5.5
199
116
300
122
137
230
2.54
Determined by SEC and 1H NMR.
b
Calculated assuming a spherical morphology and fully extended chains; (S)-(þ)-MBuMA, (S)-(þ)-2-methyl-1-butyl methacrylate; DMAEMA, 2-(di-
methyl amino)ethyl methacrylate.
closer agreement with the DH values from DLS in pH 5.5 sol-
utions; this is a result of AFM measurement of the largely
dehydrated micelles with collapsed coronae.
under anhydrous MgSO4 (98%; Scharlau), followed by filtra-
tion before use. AIBN (95%; Sigma-Aldrich) was recrystal-
lized twice from ethanol. (S)-(ꢀ)-2-Methyl-1-butanol (99%;
Sigma-Aldrich), methacryloyl chloride (97%; Fluka), metha-
nol (99.9%; Scharlau), ethanol (99.9%; Scharlau), and n-hex-
ane (96%; Scharlau) were used as received.
As seen from the images, spherical micelles are present in
both cases, whereas the existence of micellar aggregates is
suggested for the sample from the pH 2.54 solution. The lat-
ter supports the supposition from the DLS data that some
micellar aggregation occurs for the pH 2.54 solutions.
Syntheses
Synthesis of CDTB
EXPERIMENTAL
Materials and Methods
CDTB was synthesized in two steps, following a procedure
reported by Rizzardo et al.49 Briefly, the first step involved
the preparation of dithiobenzoic acid via the reaction of sul-
fur, sodium methoxide, and benzyl chloride in methanol at
room temperature for 18 h. Subsequently, dithiobenzoic acid
was left to react with a-methylstyrene in carbon tetrachlo-
ride at 70 ꢂC for 18 h to obtain CDTB in 19.3% yield
after purification by column chromatography (silica gel)
using n-hexane as solvent.
THF (HPLC grade; Scharlau) and benzene (99%; Fluka) were
stored over CaH2 before distillation under reduced pressure
immediately prior to the reactions. DMAEMA (99%; Merck)
was passed through basic alumina column (Activated, basic,
Brockmann I, ꢁ150 mesh, pore size ¼ 58 Å), stored over
CaH2 (99.99%; Aldrich), followed by distillation under
reduced pressure, and storage under nitrogen atmosphere
before use. Triethylamine (99.5%; Scharlau) was stored
FIGURE 4 AFM (topography/derivative) images of the diblock copolymer micelles formed in aqueous media: (a) (S)-(þ)-MBuMA55
-
b-DMAEMA104 at pH ¼ 2.54 and (b) (S)-(þ)-MBuMA55-b-DMAEMA230 at pH ¼ 5.5. Scale: 5 lm ꢃ 5 lm.
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1H NMR (300 MHz, CDCl3): d (ppm): 7.87 (d, 2H), 7.58–7.22
(m, 8H), 2.01 (s, ACH3).
uate-thaw cycles, and heated at 65 C for 20 h. The polymer-
ꢂ
ization was terminated by cooling the reaction mixture to
room temperature. The produced p((S)-(þ)-MBuMA) was
retrieved by precipitation in methanol (5 mL).
Synthesis of (S)-(þ)-2-MBuMA
A typical procedure for the synthesis of the (S)-(þ)-2-
MBuMA is described.38 To a round-bottomed flask (100 mL)
equipped with an egg-shaped polytetrafluoroethylene (PTFE)
stirring bar, methacryloyl chloride (3.5 g, 35.5 mmol) was
added dropwise into a mixture of (S)-(ꢀ)-2-methyl-1-butanol
(2.46 g, 27.9 mmol) and triethylamine (19.4 mL) in freshly
distilled THF (19 mL) at 0 ꢂC. After the addition was com-
pleted, the mixture was left to stir for 1 h until it reached
room temperature. The whole mixture was then placed in
the refrigerator (to assist precipitation of the reaction
byproduct, namely, triethylamine hydrochloride salt) for 1
day. The mixture was then left to reach room temperature
followed by filtration to remove the salt. Subsequently, basic
alumina was added into the filtrate and left to stir at room
temperature for 1 h. The basic alumina was then filtered off,
and the filtrate was passed through a basic alumina column
followed by washing of the latter with THF. The volatiles
were removed under vacuum with the aid of a rotary evapo-
rator, and the product was further dried in the vacuum oven
at room temperature for 1 day. Yield: 30% wt.
Synthesis of p((S)-(þ)-MBuMA)-b-p(DMAEMA) Block
Copolymer
A typical procedure for the synthesis of the p((S)-(þ)-
MBuMA)-b-p(DMAEMA) diblock copolymer is described. To a
round-bottomed flask (25 mL) equipped with an egg-shaped
PTFE stirring bar and maintained under nitrogen atmos-
phere, p((S)-(þ)-MBuMA) (Mn ¼ 8135 g molꢀ1, 0.1103 g,
0.0136 mmol of the macro-CTA) and DMAEMA (0.32 g, 2.04
mmol) were added using Schlenk-line techniques. AIBN
(0.0013 g, 0.00816 mmol) was dissolved in benzene (0.7
mL) and was added into the reactor via the aid of a syringe.
The reaction mixture was stirred rapidly at room tempera-
ture, degassed by three freeze-evacuate-thaw cycles, and
ꢂ
heated at 65 C for 20 h. The polymerization was terminated
by cooling the reaction mixture to room temperature. The
produced p((S)-(þ)-MBuMA)-b-p(DMAEMA) was retrieved
by precipitation in n-hexane (10 mL).
1H NMR (CDCl3): d (ppm): 4.05 (CH2AO), 1.91 (CHACH2ACH3),
1.81 (CH2AC), 1.25 (CH3AC and CHACH2ACH3), 1.024
(CHACH3), 0.90 (CHACH2ACH3), 2.60 (CH2AN), 2.06
(CH3ANACH3).
1H NMR (CDCl3): d (ppm): 1.96 (CH3AC), 5.52 and 6.07
(CH¼¼CH), respectively, 4.11 (CH2AO), 2.02 (CHACH3), 1.09
(CHACH3), 1.31 (CH2ACH), 0.88 (CH2ACH3).
Micellization
Micellar solutions of the p((S)-(þ)-MBuMA)-b-p(DMAEMA)
block copolymers were prepared in aqueous media. Each
block copolymer was placed in water and stirred at room
temperature until complete dissolution. In the case of the
acidified solutions, the pH was adjusted on adding one drop
of HCl (10% w/w).
Synthesis of p((S)-(þ)-MBuMA) by RAFT Polymerization
A typical procedure for the synthesis of the p((S)-(þ)-
MBuMA) is described. To a round-bottomed flask (25 mL)
equipped with an egg-shaped PTFE stirring bar and main-
tained under nitrogen atmosphere, (S)-(þ)-2-MBuMA (1.5 g,
10 mmol) was added using Schlenk-line techniques. CDTB
(0.027 g, 0.1 mmol) and AIBN (0.01 g, 0.06 mmol) were dis-
solved in benzene (1.7 mL), and the monomer was added
via the aid of a syringe. The reaction mixture was stirred
rapidly at room temperature, degassed by three freeze-evac-
Characterization
NMR spectra were recorded in CDCl3 with tetramethylsilane
used as an internal standard using an Avance Brucker 300
MHz spectrometer equipped with an Ultrashield magnet. The
MWs and PDIs of the polymers were determined by SEC
using equipment supplied by Polymer Standards Service
(PSS). All measurements were carried out at room tempera-
ture using Styragel HR 3 and Styragel HR 4 columns. The
mobile phase was THF delivered at a flow rate of 1 mLminꢀ1
using a Waters 515 isocratic pump. The refractive index was
measured with a Waters 2414 refractive index detector sup-
plied by PSS. The instrumentation was calibrated using
poly(methyl methacrylate) standards with low PDI [MWs of
739,000, 446,000, 270,000, 126,000, 65,000, 31,000, 14,400,
4200, 1580, 670, 450, and 102 (methyl isobutyrate)
g molꢀ1] supplied by PSS.
ꢂ
uate-thaw cycles, and heated at 65 C for 20 h. The polymer-
ization was terminated by cooling the reaction mixture to
room temperature. The produced p((S)-(þ)-MBuMA) was
retrieved by precipitation in methanol (10 mL).
1H NMR (CDCl3): d (ppm): 3.95 (CH2AO), 1.91 (CHACH2ACH3),
1.81 (CH2AC), 1.25 (CH3AC and CHACH2ACH3), 1.024
(CHACH3), 0.90 (CHACH2ACH3) [tacticity (calculated based on
ACH3 backbone protons): 75% rr, syndiotactic (d ꢁ 0.8 ppm);
14% mr, heterotactic (d ꢁ 1.0 ppm); 11% mm, isotactic (d ꢁ
1.2 ppm)].
Synthesis of p((S)-(þ)-MBuMA) by Free
Radical Polymerization
The specific optical rotation of the monomer (S)-(þ)-MBuMA
and of the homopolymers 4 and 5 in chloroform (AR) solu-
tions were recorded in a 5-cm sample tube on an Optical Ac-
tivity AA-5 polarimeter at 21 and 24 ꢂC, respectively, with
the instrument zeroed with the chloroform solvent.
To a round-bottomed flask (25 mL) equipped with an egg-
shaped PTFE stirring bar and maintained under nitrogen
atmosphere, (S)-(þ)-2-MBuMA (1 g, 6.4 mmol) was added
using Schlenk-line techniques. AIBN (0.01 g, 0.064 mmol)
was dissolved in benzene and was added to the monomer
with the aid of a syringe. The reaction mixture was stirred
rapidly at room temperature, degassed by three freeze-evac-
CD spectra were recorded on a JASCO J-715 Spectropolarime-
ter with a PTC-4235/15 Peltier heating attachment. The final
6
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CD spectrum obtained from a solution of homopolymer 4 in
cyclohexane/1-propanol (2:1) at 20 ꢂC was the average of
three separate measurements of 32 accumulations each, with
the cyclohexane/propanol solvent subtracted.
terms of size, morphology, hydrophobic/hydrophilic content,
and charge combined with the MEKC method will lead to the
development of highly efficient optically active polymeric
materials with potential use in chiral separation processes.
The UV–vis spectrum was recorded on a Unicam UV-500 UV–
Visible Spectrometer and obtained from homopolymer 4 in a
cyclohexane:1-propanol (2:1) solution with the solvent as
the baseline.
ACKNOWLEDGMENTS
This work was financially supported by the University of
Cyprus. The authors are grateful to Costas S. Patrickios for
providing access to the DLS and AFM apparatus. They also
thank the A. G. Leventis Foundation for a generous donation
that enabled the purchase of the NMR spectrometer of the
University of Cyprus.
DLS measurements were carried out using a 90Plus Broo-
khaven DLS spectrometer equipped with a 30-mW laser
operating at 633 nm. DLS experiments were performed at
90ꢂ scattering angle. Solution concentrations were main-
tained at ꢁ0.1 g Lꢀ1. The high quality of the scattering
curves was ensured by repeating the measurements several
times. All polymer solutions were filtered through cellulose
acetate microfilters (pore size: 0.45 lm) prior to the
measurements.
REFERENCES AND NOTES
1 Fujiki, M. Macromol. Rapid Commun. 2001, 22, 539–563.
2 Berova, N.; Nakanishi, K.; Woody, R. W. Circular Dichroism:
Principles and Applications, 2nd ed.; Wiley-VCH: New York,
2000.
AFM measurements were performed on a PicoPlus scanning
probe microscope from Molecular Imaging (Agilent) using a
cantilever (length: 125 mm; width: 45 mm; resonant fre-
quency: 200–400 kHz; force constant: 25–75 N mꢀ1; tip ra-
dius <10 nm, height: 12–16 mm; Applied Nanostructures).
Dilute solutions of the p((S)-(þ)-2-MBuMA)-b-p(DMAEMA)
diblock copolymers (0.1 g Lꢀ1) prepared in aqueous media
(at pH 2.54 and 5.5) were spin coated on a mica substrate
and visualized by AFM. All measurements were carried out
with tapping mode at room temperature in the air.
3 Mason, S. F. Nature 1984, 311, 19–23.
4 Bonner, W. A. Chirality 2000, 12, 114–126.
5 Avalos, M. A.; Babiano, R.; Cintas, P.; Jimenez, J. L.; Palacios,
J. C. Chem. Rev. 1998, 98, 2391–2404.
6 Avalos, M. A.; Babiano, R.; Cintas, P.; Jimenez, J. L.; Palacios,
J. C. Chem. Commun. 2000, 887–892.
7 Kane-Maguire, L. A. P.; Wallace, G. G. Chem. Soc. Rev. 2010,
39, 2545–2576.
8 Mallakpour, S.; Zadehnazari, A. Express Polym. Lett. 2011, 5,
142–181.
9 Fujiki, M.; Koe, J. R.; Terao, K.; Sato, T.; Teramoto, A.; Wata-
nabe, J. Polym. J. 2003, 35, 297–344.
CONCLUSIONS
10 Mayer, S.; Zentel, R. Prog. Polym. Sci. 2001, 26, 1973–2013.
Conclusively, we have presented for the first time the synthe-
sis of a new, simple, and optically active methacrylic mono-
mer (S)-(þ)-2-MBuMA by following an easy and cost-effec-
tive synthetic methodology, thus creating a straightforward
and undemanding approach toward the design and synthesis
of optically active monomers characterized by structural
simplicity.
11 Cornelissen, J. J. L. M.; Rowan, A. E.; Nolte, R. J. M.; Som-
merdijk, N. A. J. M. Chem. Rev. 2001, 101, 4039–4070.
12 Meng, J.; Wei, G.; Huang, X. B.; Dong, Y.; Cheng, Y. X.;
Zhu, C. J. Polymer 2011, 52, 363–367.
13 Sanda, F.; Fujii, T.; Tabei, J.; Shiotsuki, M.; Masuda, T. Mac-
romol. Chem. Phys. 2008, 209, 112–118.
14 Yoshida, M.; Hatate, Y.; Uezu, K.; Goto, M.; Furusaki, S. Col-
loid Surf A 2000, 169, 259–269.
RAFT-controlled radical polymerization has been successfully
used for the preparation of well-defined homopolymers and
water-soluble diblock copolymers based on this monomer.
The latter demonstrated the ability to self-organize in
aqueous solutions creating well-defined macromolecular
aggregates (i.e., micelles) of tunable diameters possessing a
hydrophilic and ionizable corona and an optically active
hydrophobic core. Such optically active micellar nanostruc-
tures are expected to act as effective chiral recognition sys-
tems. Future work involves the evaluation of the p((S)-(þ)-
2-MBuMA)-b-p(DMAEMA) diblock copolymer micelles for the
separation of enantiomeric molecules by using the micellar
electrokinetic chromatography (MEKC) technique. The latter
is the second most commonly used capillary electrochroma-
tography method, in which the separation mechanism is
based on the electrophoretic mobility and the partitioning of
the analytes between the mobile phase and the micellar
aggregates that are present, acting as a moving stationary
phase or else a pseudo-stationary phase. It is expected that
the tunable design of the aforementioned micellar systems in
15 Okamoto, Y.; Hatada, K. J. Liq. Chromatogr. 1986, 9,
369–384.
16 Yoshida, M.; Uezu, K.; Goto, M.; Furusaki, S. J. Appl. Polym.
Sci. 2000, 78, 695–703.
17 Fujiki, M. J. Am. Chem. Soc. 2000, 122, 3336–3343.
18 Ohira, A.; Okoshi, K.; Fujiki, M.; Kunitake, M.; Naito, M.;
Hagihara, T. Adv. Mater. 2004, 16, 1645–1650.
19 Winoto, D.; Carr, S. H. Polymer 1995, 36, 4561–4566.
20 Philip, B.; Sreekumar, K. J. Polym. Mater. 2001, 18, 365–369.
21 Tanga, H.-Z.; Fujikia, M.; Motonaga, M. Polymer 2002, 43,
6213–6220.
22 Gomez, R.; Segura, J. L.; Martın, N. Chem. Commun. 1999,
619–620.
23 Skey, J.; O’Reilly, R. K. J. Polym. Sci. Part A: Polym. Chem.
2008, 46, 3690–3702.
24 Wang, J.; Zhu, X. L.; Cheng, Z. P.; Zhang, Z. B. J. Polym.
Sci. Part A: Polym. Chem. 2007, 45, 3788–3797.
25 Wang, J.; Xu, W. L.; Cheng, Z. P.; Zhu, X. L.; Zhang, Z. B.;
Zhu, J.; Zhang, W. J. Polym. Sci. Part A: Polym. Chem. 2008,
46, 7690–7701.
WWW.MATERIALSVIEWS.COM
JOURNAL OF POLYMER SCIENCE PART A: POLYMER CHEMISTRY 2012, 000, 000–000
7

JOURNAL OF
POLYMER SCIENCE
ARTICLE
WWW.POLYMERCHEMISTRY.ORG
26 Yu, L. P.; Zhang, Z. B.; Chen, X. R.; Zhang, W.; Wu, Z. H.;
Cheng, Z. P.; Zhu, J.; Zhu, X. L. J. Polym. Sci. Part A: Polym.
Chem. 2008, 46, 682–691.
Moad, G.; Rizzardo, E.; Thang, S. H. Macromolecules 1998, 31,
5559–5562.
38 Moad, G.; Rizzardo, E.; Thang, S. H. Aust. J. Chem. 2009,
62, 1402–1472.
27 Angiolini, L.; Benelli, T.; Giorgini, L.; Salatelli, E. Macromole-
cules 2006, 39, 3731–3737.
39 Holder, S. J.; Sommerdijk, N. A. J. M. Polym. Chem. 2011,
2, 1018–1028.
28 Xu, W. J.; Zhu, X. L.; Zhu, J.; Cheng, Z. P. J. Polym. Sci.
Part A: Polym. Chem. 2006, 44, 1502–1513.
40 Keams, J. E.; MacLean, C. D.; Solomon, D. H. J. Macromol.
Sci. Part A 1974, 4, 673–685.
29 Angiolini, L.; Benelli, T.; Giorgini, L.; Salatelli, E. Polymer
2005, 46, 2424–2432.
41 Sanda, F.; Endo, T. Macromol. Chem. Phys. 1999, 200,
30 Nagai, A.; Ochiai, B.; Endo, T. Chem. Commun. 2003,
2651–2661.
3018–3019.
42 Demetriou, M.; Krasia-Christoforou, T. J. Polym. Sci. Part A:
Polym. Chem. 2008, 46, 5442–5451.
31 Skey, J.; Willcock, H.; Lammens, M.; Du Prez, F.; O’ Reilly,
R. K. Macromolecules 2010, 43, 5949–5955.
43 Achilleos, M.; Krasia-Christoforou, T.; Patrickios, C. S. Mac-
romolecules 2007, 40, 5575–5581.
32 Angiolini, L.; Caretti, D.; Giorgini, L.; Salatelli, E.; Altomate,
A.; Carlini, C.; Solaro, R. Polymer 2000, 41, 4767–4780.
44 Mao, B. W.; Gan, L. H.; Gan, Y. Y.; Tam, K. C.; Tan, O. K.
Polymer 2005, 46, 10045–10055.
33 Xue, H.; Xu, Y. A.; Song, N. H.; Gao, L. X.; Ding, M. X.
Polym. Int. 2003, 52, 1321–1325.
45 Riess, G. Prog. Polym. Sci. 2003, 28, 1107–1170.
34 Lee, Y. K.; Nakashima, Y.; Onimura, K.; Tsutsumi, H.; Oishi,
T. J. Appl. Polym. Sci. 2003, 90, 1018–1025.
46 Lee, A. S.; Gast, A. P.; Butun, V.; Armes, S. P. Macromole-
cules 1999, 32, 4302–4310.
35 Angiolini, L.; Benelli, T.; Giorgini, L.; Golemme, A.; Maur-
iello, F.; Salatelli, E.; Termine, R. Macromol. Chem. Phys. 2008,
209, 944–956.
47 Lee, A. S.; Butun, V.; Vamvakaki, M.; Armes, S. P.; Pople, J.
A.; Gast, A. P. Macromolecules 2002, 35, 8540–8551.
48 Tan, B. H.; Gudipati, C. S.; Hussain, H.; He, C. B.; Liu, Y.;
Davis, T. P. Macromol. Rapid Commun. 2009, 30, 1002–1008.
36 Lee, Y. K.; Onimura, K.; Tsutsumi, H.; Oishi, T. J. Polym.
Sci. Part A: Polym. Chem. 2000, 38, 4315–4325.
49 Le, T. P. T.; Moad, G.; Rizzardo, E. Thang, S. H. PCT. Int.
Appl. WO 9,801,478-A1-980,115 [Chem. Abstr. 1998, 128,
115390].
37 Chiefari, J.; Chong, Y. K.; Ercole, F.; Krstina, J.; Jeffery, J.;
Le, T. P. T.; Mayadunne, R. T. A.; Meijs, G. F.; Moad, C. L.;
8
JOURNAL OF POLYMER SCIENCE PART A: POLYMER CHEMISTRY 2012, 000, 000–000