Chiral Coalition in Helical Sense Enhancement of Copolymers: The Role of the Absolute Configuration of Comonomers

Article abstract of DOI:10.1021/jacs.7b09965

Both the role of the absolute configuration and the tendency of a chiral monomer to promote a certain helical scaffold in a poly(phenylacetylene) (PPA) have been evaluated to study the communication between two chiral monomers within a copolymer chain. Nineteen different PPA copolymer series - 47 helical copolymers altogether - were prepared to explore the existence of a chiral-to-chiral communication mechanism. From the data obtained, we found that communication between two different chiral monomers emerges when both exhibit two special features: (a) a different conformational composition - one must exist in a single low-energy conformation ( chiral Sergeant ) and the other must present two conformers ( chiral Soldier ) - and (b) the induction of a similar scaffold in the PPA, either cis-cisoidal or cis-transoidal. In the selected systems, the chiral Soldier includes the 4-ethynylanilide (para position) of either (R)- or (S)-2-methoxy-2-phenylacetic acid pendants characterized by their conformational flexibility (equilibrium between synperiplanar and antiperiplanar conformations). The chiral Sergeant contains the same chiral groups but linked to the backbone in meta position [3-ethynylanilide of (R)- or (S)-2-methoxy-2-phenylacetic acid] and is selected on the basis of its restricted antiperiplanar conformation. Incorporation of a very small amount (1%) of the Sergeant into a chain composed of just the Soldier transforms the originally axially racemic chain into a helix with strong sense preference (either M or P) that is determined by the absolute configuration of the Soldier.

Full text of DOI:10.1021/jacs.7b09965

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Article
Chiral Coalition in Helical Sense Enhancement of Copolymers:
the Role of the Absolute Configuration of Comonomers
Sandra Arias, Rafael Rodríguez, Emilio Quiñoá, Ricardo Riguera, and Felix Freire
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b09965 • Publication Date (Web): 14 Dec 2017
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Chiral Coalition in Helical Sense Enhancement of Copol-
ymers: the Role of the Absolute Configuration of Comon-
omers
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Sandra Arias‡, Rafael Rodríguez‡, Emilio Quiñoá, Ricardo Riguera* and Félix Freire*
Centro Singular de investigación en Química Biolóxica e Materiais Moleculares (CIQUS) and Departamento de Química
Orgánica, Universidade de Santiago de Compostela, E-15782 Santiago de Compostela, Spain.
Chiral Communication, Helical Polymers, Poly(phenylacetylene)s, Sergeants and Soldiers effect, Chiral Amplification.
ABSTRACT:!Both the role of the absolute configuration and the tendency of a chiral monomer to promote a certain helical scaffold
in a polyphenylacetylene (PPA) have been evaluated to study the communication between two chiral monomers within a copolymer
chain. 19 different PPA copolymer series —47 helical copolymers altogether— were prepared to explore the existence of a chiral to
chiral communication mechanism. From the data obtained, we found that communication between two different chiral monomers
emerge when both exhibit two special features: (a) a different conformational composition —one must exist in a single low energy
conformation ("chiral Sergeant") and the other must present two conformers ("chiral Soldier")—, and (b) the induction of a similar
scaffold in the PPA, either cis-cisoidal or cis-transoidal. In the selected systems, the chiral Soldier includes the 4-ethynylanilide (para
position) of either (R)- or (S)-2-methoxy-2-phenylacetic acid pendants characterized by their conformational flexibility (equilibri-
um between synperiplanar and antiperiplanar conformations). The chiral Sergeant contains the same chiral groups but linked to the
backbone in meta position [3-ethynylanilide of (R)- or (S)-2-methoxy-2-phenylacetic acid] and is selected on the basis of its re-
stricted antiperiplanar conformation. Incorporation of a very small amount (1%) of the Sergeant to a chain composed just by the
Soldier transforms the originally axially racemic chain into a helix with strong sense preference (either M or P) that is determined
by
the
absolute
configuration
of
the
Soldier.
nomenon known as the Majority rule.6b,6d,6f,6h It means that
the major enantiomer determines the final helical sense.
INTRODUCTION
The helical structure adopted by many biomolecules and its
relationship with their function1 has inspired the scientific
community to develop new non natural helical materials
such as foldamers,2 supramolecular helices3 or helical pol-
ymers.4
The above mechanisms are based on the interaction be-
tween a chiral monomer and an achiral one (Sergeants and
Soldiers effect) or between two chiral monomers that are
enantiomers (Majority rule). Another case of chiral com-
munication named Chiral Conflict5g was described in co-
polymers formed by two chiral components that induce
opposite helical sense and are in close ratio, resulting in an
axially racemic structure.
Studies on the folding of these helical materials have lead
to the identification of the most relevant parameters that
determine the formation of a helix and allowed the formu-
lation of several mechanisms that explain the chiral ampli-
fication observed. Among them, the Sergeants and Soldiers
effect,5 the Majority rule6 or the Domino effect7 are particu-
larly important.
Herein we described a novel helical enhancement mecha-
nism based on the interaction between two non-
enantiomeric chiral monomers, where a chiral monomer
(chiral Sergeant) will induce a preferred conformation on
the other chiral monomer (chiral Soldier) resulting in a
helical sense enhancement of the copolymer. This outcome
is opposite to that originated from Chiral Conflict, where
no interaction between the different chiral monomers is
observed.
The Sergeants and Soldiers effect, first described in polyi-
socyanates,5d-e,5g-k shows that the introduction of a small
amount of a chiral monomer (Sergeant) within a polymer
formed by an achiral monomer (Soldier) is able to induce
an excess of the screw sense in the copolymer chain that
depends on the R/S configuration of the Sergeant. It was
also found that when the two monomers forming the copol-
ymer are enantiomers in a 1/1 ratio, the copolymer is —as
expected— axially racemic. However, the presence of a
slight excess of one of the enantiomers [e.g., 51% (R) mon-
omer and 49 % (S) or vice versa] produces the adoption of
a single handed helical structure in the whole chain, a phe-
We will show in this paper that this chiral to chiral Ser-
geants and Soldiers effect allows the conversion of a chiral
polymer with very low helical sense preference [poly-(R)-
1] into a strongly biased one by introduction in the chain of
a small amount [i.e., <10%] of a selected chiral monomer
[(R)-2], where the parent homopolymers (poly-1 and poly-
1
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Page 2 of 9
Figure 1. (a) Structures of poly-(R)-1 and poly-(R)-2 homopoly-
2, Figure 1a) promote similar helical structures —both 3/1,
cis-cisoidal; although poly-1 yields an axially racemic
chain (no helical sense preference) while poly-2 induces a
strong helical sense—.8
1
2
3
mers. (b) Schematic illustration of the chiral amplification process
of a helical polymer based on a chiral to chiral Sergeants and
Soldiers effect vs. the amplification based on external stimuli.
4
5
6
7
8
9
This internal doping of the helically “poor” polymer with a
tiny amount of the chiral Sergeant should be useful to op-
timize materials and chemical processes where the helical
sense preference is directly related to its function, such as
applications in chiral stationary phases,9 asymmetric syn-
thesis10 or chiral recognition.11 An additional advantage of
this approach is that there is no need to resort to external
stimuli (e.g., pH, solvents, temperature) and therefore no
interferences with the application are expected (Figure 1b).
a)
n
n
H
H
N
H
O
O
N
H
MeO
poly-(R)-2
OMe
poly-(R)-1
10
11
12
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3/1, cis-cisoidal, left-handed helix
(strong helical sense preference)
3/1, cis-cisoidal, axially racemic helix
(no helical sense preference)
b)
Chiral Amplification via
External Stimuli
Environmental Changes
RESULTS AND DISCUSSION
99 %
monomer A
20
Mn+
For the study of the helical sense enhancement based on
chiral to chiral communication mechanism between chiral
monomers, we prepared a series of PPA type copolymers
composed by the combination of two chiral units in differ-
ent ratios.
100 %
monomer A
10
solvent
0
-10
-20
1 % Dopant
chiral
additives
T
Chiral
Amplification
-30
pH
One of the monomeric components is formed by monomer
(R)-1, which contains (R)-2-methoxy-2-phenylacetic acid
[(R)-MPA] bonded to the PPA backbone in para-position
[or its enantiomeric form (S)-1].
-40
300
400
500
null or low right-
handed sense
enhanced
right-handed helix
Wavelength [nm]
Chiral Amplification via
Internal Stimuli
No Environmental Changes
chiral to achiral interaction
a)
chiral to chiral interaction
Chiral Soldiers
(they produce optically
unactive homopolymers)
Chiral Sergeants
Achiral Dopants
(they produce optically active homopolymers) (they produce axially racemic helical polymers)
O
O
O
O
O
O
NH
O
NH
O
NH
NH
NH
(S)-2
(R)-2
12
13
(R)-1
O
O
O
O
NH
O
O
O
NH
NH
CF3
NH
NH HN
O
O
O
(S)-1
(R)-3
(R)-4
14
15
O
O
O
O
NH
O
HN
HN
HN
NH
O
O
O
O
O
O
(S)-5
(S)-6
(S)-7
16
O
17
O
O
O
O
NH
O
NH
HN
HN
N
H
O
O
O
O
O
O
O
(S)-8
(S)-9
(S)-10
18
19
b)
Two possible scenarios
c)
Poly-[(S)-1-co-X]
Poly-[(R)-1-co-X]
X
O
O
O
O
X
H
NH
NH
H
1-r
r
R
r
n
1-r
H
H
n
NO
COMMUNICATION
O
O
COMMUNICATION
N
R
H
N
H
H
O
chiral or achiral
H
X = monomers 2-19
O
Figure 2. (a) Structure of monomers used as chiral Soldiers, chiral Sergeants and achiral dopants. (b) Presence or absence of chiral to chiral
communication in helical copolymers. (c) Copolymer series poly-[(R)-1-co-X] and poly-[(S)-1-co-X], where X are monomers 2-19 used as
chiral Sergeants and achiral doping agents.
2
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Journal of the American Chemical Society
This monomer, although chiral, produces a cis-cisoidal
10)= cis-transoidal), showed a decrease in the CD signal
when the amount of Sergeant component (3-10) is reduced
within the copolymer series —see Figure 4b for poly-[(R)-
1r-co-(S)-71-r], and SI (S18 to S45) for the series involving
monomer (R)-1 and monomers 3-6, 8-10—, proving that no
helical amplification is present, and therefore the absence
of an efficient communication between chiral monomers 3-
10 and chiral monomer 1.
1
2
3
4
5
6
7
8
axially racemic helix (mixture of left and right-handed
helices originated by its conformational composition) and
where any helical amplification can be easily detected
(active CD, Figure 2a). For these reasons, this monomer
was selected as the chiral Soldier.12
The other chiral component was selected taking into ac-
count both the conformational behavior of the monomers
and the dynamic helical behavior of the corresponding
homopolymers. Monomers (2-10) with a preponderant
conformer in their structure are known to produce polymers
with a defined helical structure, and therefore it was ex-
pected that they should work well as chiral Sergeants.[7,12]
Moreover, two main groups can be distinguished in 2-10,
attending to the secondary structure adopted by the corre-
sponding homopolymers:
In addition, in order to demonstrate that the helical sense
enhancement shown in poly-[(R)-1r-co-(R)-21-r] and poly-
[(S)-1r-co-(R)-21-r] is due to a chiral to chiral communica-
tion within a stereoregular cis-cisoidal copolymer chain
(poly-1 and poly-2), we prepared a series of cis-cisoidal
stereoregular PPA type copolymers [poly-[(R)-1r-co-(R)-
X1-r], X= 12 to 19 (a total of 34), composed by the combi-
nation of the chiral Soldier [(R)-MPA] and an achiral mon-
omer (monomers 12-19) in different ratios (Figure 2).5a,c
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
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60
a) Monomer 2 generates a cis-cisoidal helical scaffold
similar in elongation to poly-1.
CD experiments on poly-[(R)-1-co-X] and poly-[(S)-1-co-
X], X= 12-19] (0.3 mg/mL in THF) showed a null CD and
therefore the presence of an axially racemic helix, which
indicates that there is no communication between those
monomeric units —see Figure 4c for poly-[(R)-1r-co-(S)-
131-r] series and SI (S52) for those copolymer series involv-
ing monomer (R)-1 and monomers 12, 14-15—.
b) Monomers 3 to 10 produce cis-transoidal helical scaf-
folds that are more stretched than the one obtained from
poly-1.
In this way, a series of PPA copolymers —i.e., poly-[(R)-
1r-co-(R)-X1-r] and poly-[(S)-1r-co-(R)-X1-r] X= 2 to 10, a
total of 34—, containing both enantiomers of chiral Soldier
1, were prepared using a rhodium (I) catalyst (Figure 2).
Ten chiral homopolymers [poly-(1-10), Figure 1a and Fig-
ure 3] were also prepared and used as references.[14], [15]
10
CHIRAL TO CHIRAL
COMMUNICATION
a)
30
0
O
O
left-handed
8
6
4
2
NH
(R)-1
-30
-60
-90
-120
-150
Poly-(R)-2
n
n
Chiral to Chiral
communication
mechanism
Poly[(R)-10.20-co-(R)-20.80
Poly[(R)-10.40-co-(R)-20.60
Poly[(R)-10.60-co-(R)-20.40
]
O
]
H
H
MeO
N
HN
(R)-2
]
H
Poly[(R)-10.80-co-(R)-20.20
]
O
O
H
n
N
H
N
O
O
H
OMe
O
left-handed
poly-[(R)-1-co-(R)-2]
OMe
CF3
300
400
500
Wavelength [nm]
poly-(R)-3
poly-(R)-4
poly-(S)-5
80
6
4
2
b)
NO CHIRAL TO
CHIRAL
COMMUNICATION
O
O
left-and
right handed
50%-50%
40
0
n
n
n
NH
O
N
O
N
H
H
H
-40
Me
(R)-1
H
Poly-(S)-7
-80
Poly[(R)-10.20-co-(S)-70.80
Poly[(R)-10.40-co-(S)-70.60
Poly[(R)-10.60-co-(S)-70.40
Poly[(R)-10.80-co-(S)-70.20
)
)
)
)
N
O
NO chiral to chiral
communication
mechanism
H
OMe
H
OMe
O
O
O
-120
-160
-200
Me
OMe
O
poly-(S)-6
poly-(S)-7
poly-(S)-8
HN
left-handed
O
n
n
(S)-7
300
400
500
O
O
N
Wavelength [nm]
H
H
poly-[(R)-1-co-(S)-7]
20
5
H
N
O
H
OMe
NO CHIRAL -ACHIRAL
COMMUNICATION
c)
left-and
right handed
50%-50%
10
0
O
O
O
O
4
3
2
1
OMe
NH
Poly[(R)-10.20-co-130.80
Poly[(R)-10.40-co-130.60
Poly[(R)-10.60-co-130.40
Poly[(R)-10.80-co-130.20
]
poly-(S)-9
poly-(S)-10
]
]
]
-10
-20
-30
-40
-50
(R)-1
NO chiral to
achiral
communication
mechanism
Figure 3. Additional chiral homopolymers employed in this
study.
O
HN
13
left-and
right handed
50%-50%
O
CD studies of the different copolymer series (0.3 mg/mL in
THF) revealed that only poly-[(R)-1r-co-(R)-21-r] and poly-
[(S)-1r-co-(R)-21-r], both made from monomers that gener-
ate cis-cisoidal homopolymers (poly-1 and poly-2, Figure
1a) showed helical sense amplification, associated to the
interaction between monomers 1 and 2 (Figure 4a).
250 300 350 400 450 500
Wavelength [nm]
poly-[(R)-1-co-13]
Figure 4. (a) Helical sense enhancement in poly-[(R)-1r-co-(R)-21-
r] series. (b) Helical sense decay in poly-[(R)-1r-co-(S)-71-r] series.
(c) Macroscopically racemic poly-[(R)-1r-co-13] series.
On the contrary, the other copolymer series —poly-[(R)-1r-
co-(R)-X1-r] X= 3 to 10—, made from monomers producing
different helical scaffolds (poly-1= cis-cisoidal; poly-(3-
Summing up, these studies indicate that a chiral to chiral
communication mechanism is observed only in PPA copol-
3
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Page 4 of 9
ymers comprising two features: a) the comonomers must
to the chiral Soldiers [(R)-1],11e promoting the synperipla-
nar (sp) conformation of the pendants and, as a conse-
quence, the expected helical inversion (see 71 for detailed
explanation).
1
2
3
4
5
6
7
8
display different dynamic conformational behaviors —e.g.,
monomer 1 with different conformers in equilibrium
(sp/ap) and monomer 2 with a preferred single confor-
mation (ap)— and b) that the homopolymers arising from
those comonomers must show similar helical scaffolds
(e.g., cis-cisoidal).
r = 0.1
100% CD Signal
a)
b)
c)
e)
10
100
50
0
THF 25ºC
0.3 mg/mL
r = 0.01
35% CD Signal
0
-10
-20
-30
-40
-50
In order to better analyze this communication mechanism,
we decided to study the different copolymer series resulting
from all the combinations between monomers [(R)-1/(S)-1
and [(R)-2/(S)-2), namely [poly-[(R)-1r-co-(R)-21-r], [poly-
[(S)-1r-co-(R)-21-r], [poly-[(R)-1r-co-(S)-21-r] and [poly-[(S)-
1r-co-(S)-21-r].
poly-(R)-2
poly[(R)-10.10-co-(R)-20.90
poly[(R)-10.20-co-(R)-20.80
poly[(R)-10.30-co-(R)-20.70
]
]
]
]
]
]
]
]
]
90
95
100
9
% (R)-1
poly[(R)-10.40-co-(R)-20.60
poly[(R)-10.50-co-(R)-20.50
poly[(R)-10.60-co-(R)-20.40
poly[(R)-10.70-co-(R)-20.30
poly[(R)-10.80-co-(R)-20.20
poly[(R)-10.90-co-(R)-20.10
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
100% CD Signal -10ºC
3
2
1
r = 0.01
70% CD Signal
T= -10ºC
100% CD Signal 25ºC
The results from the poly-[(R)-1r-co-(R)-21-r] and poly-[(S)-
1r-co-(R)-21-r] series are describe next, while those on the
complementary poly-[(R)-1r-co-(S)-21-r] and poly-[(S)-1r-
co-(S)-21-r] series can be found in S66.
r = 0.01
35% CD Signal
T= 25ºC
300
400
500
Wavelength [nm]
90
95
100
% (R)-1
d)
r = 0.1
THF 25ºC 0.3 mg/mL
10
100% CD Signal
100
50
0
8
6
4
2
r = 0.01
60% CD Signal
The CD spectra of poly-[(R)-1r-co-(R)-21-r] series (0.3
mg/mL THF) (Figure 5a) show for all those copolymers the
same left-handed helical sense associated to a negative first
Cotton effect. It is remarkable that the intensity of the band
—and therefore the excess of left-handed sense— is quite
similar in all the series independently of monomer ratios.
This indicates that a very effective chiral amplification
phenomenon is in operation with remarkably small
amounts of the chiral Sergeant [(R)-2].
0
-10
-20
-30
-40
-50
-60
poly-(R)-2
poly[(S)-10.10-co-(R)-20.90
]
]
]
]
]
]
]
]
]
poly[(S)-10.20-co-(R)-20.80
poly[(S)-10.30-co-(R)-20.70
poly[(S)-10.40-co-(R)-20.60
poly[(S)-10.50-co-(R)-20.50
poly[(S)-10.60-co-(R)-20.40
poly[(S)-10.70-co-(R)-20.30
poly[(S)-10.80-co-(R)-20.20
poly[(S)-10.90-co-(R)-20.10
90
95
100
% (S)-1
f)
100% CD Signal -10ºC
r = 0.01
70% CD Signal
T= -10ºC
300
400
500
100% CD Signal 25ºC
Wavelength [nm]
r = 0.01
60% CD Signal
T= 25ºC
100
More precisely, the presence of just 1% of (R)-2 in the
copolymer is enough to get 35% of the maximum helicity
(Figure 5b), while incorporation of 10% of (R)-2 —i.e.,
poly-[(R)-10.90-co-(R)-20.10]— induces the same helicity in
the copolymer as that of the pure homopolymer [poly-(R)-
2] (Figure 5a). Moreover, if the CD spectra are measured at
-10°C, this helical amplification is even better and 1% of
(R)-2 is enough to make the whole copolymer chain to
attain 70% of the maximum helicity (Figure 5c). The high
effectiveness of this communication between Sergeants and
Soldiers is related to the structure of (R)-1 and (R)-2 and
their mutual interactions within the chain.
90
95
% (S)-1
g)
pendant
"clockwise"
3.2 nm
backbone
"clockwise"
60º
3.2 nm
60º
An explanation of those results can be envisioned consider-
ing the role played by the conformation of the pendants in
the helical structure of the parent homopolymers [poly-(R)-
1 and poly-(R)-2], and their response to the addition of
mono and divalent ions.16a-b
cis-cisoidal,
3 residues per turn
poly-[(S)-10.90-co-(R)-20.10
]
Figure 5. (a) CD studies for poly-[(R)-1r-co-(R)-21-r] copolymer
series. (b) Plot of g-values for poly-[(R)-1r-co-(R)-21-r] in a range
of 90 to 99%. (c) Plot of g-values at room temperature and -10ºC.
(d) CD studies for [poly-[(S)-1r-co-(R)-21-r] copolymer series. (e)
Plot of g-values for poly-[(S)-1r-co-(R)-21-r] in a range of 90 to
99%. (f) Plot of g-values at room temperature and -10ºC. (g) AFM
images and 3D-models of poly-[(S)10.90-co-(R)-20.10].
In poly-(R)-2, the pendants adopt a preferred antiperiplanar
conformation —ap, between carbonyl and methoxy
groups— responsible for inducing a left-handed helix in the
polyene backbone. For its part, poly-(R)-1 exhibits an axi-
ally racemic helix associated to 1:1 anti- and synperiplanar
conformations in the pendant groups.7, 13e, 16b
Thus, in the poly-[(R)-1r-co-(R)-21-r] series, the virtually
static Sergeant [(R)-2] adopts a fixed ap conformation —
virtually identical to the one in poly-(R)-2— and com-
mands the highly dynamic Soldier [(R)-1] to adopt an ap
conformation, promoting a left-handed helical structure
similar to the one in the poly-(R)-2 homopolymer (see S76
and S77 in SI for structural studies).
In order to further examine the role of the chirality in the
communication, we carried out analogous studies on the
diastereomeric copolymer series, poly-[(S)-1r-co-(R)-21-r]
where the (R)-1 chiral Soldier was replaced by its (S)-1
enantiomer. CD spectra of poly-[(S)-1r-co-(R)-21-r] series
are shown in Figure 5d. As before, all the copolymers are
CD active, and the intensity of the bands prove that chiral
amplification processes are in action. Intriguingly, a signal
inversion from negative (left-handed helix) to positive
This hypothesis is verified by addition of divalent metal
ions (i.e., Ba2+) to poly-[(R)-1r-co-(R)-21-r]. The ions chelate
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(right-handed helix) is observed within the copolymer the same helix in the copolymer (see S69 and S70 in SI for
1
2
3
4
5
6
7
8
detailed explanation).
series when the amount of the Sergeant [(R)-2] decreases
until reaching a value close to 40%, where the CD signal is
almost null. The other copolymers (in this series) contain-
ing the Sergeant in a ratio lower than 40% show a helix
inversion with respect to the CD signal of poly-(R)-2 (Fig-
ure 5d). This effect indicates that the Sergeant and the
chiral Soldier [(S)-1] induce opposite helical senses, and
therefore they follow the ”abnormal” Sergeants and Sol-
diers effect.17
The chiral communication mechanism between chiral
monomers was quantified using Sato´s theory, a variation
of the Ising model developed by Green, which takes into
account also the “classical”5 and the “abnormal”17 Ser-
geants and Soldiers effect. This model considers that the
degree and direction of the helical sense induction depend
on the nature of the neighboring monomer units.
9
Thus, two different energy preferences (!Gh) are consid-
ered related to the presence of a chiral sergeant followed in
sequence either by another chiral Sergeant (!GSS) or by a
chiral Soldier, which can be introduced in either (R)- or (S)-
absolute configuration (!GSs-(R) o (!GSs-(S)):
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16
17
18
19
20
21
22
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40
41
42
43
44
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47
48
49
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59
60
This suggests that the chiral Sergeant [(R)-2] shifts the
original 1:1 sp/ap equilibrium in the chiral Soldier [(S)-1]
to a preferred ap conformation that favors the right-handed
helical sense and triggers the helical inversion as the Ser-
geant ratio diminishes in the copolymer series.
gabs= tanh (-N!Gh/RT) . gmax
(1)
More precisely, the CD traces are negative (dominant left-
handed helix) at high percentages of (R)-2 and positive
(dominant right-handed helix) at low (R)-2 ratios, indicat-
ing that the Sergeant commands the Soldiers to adopt the
opposite helical sense [Sergeants= left-handed, Soldiers=
right-handed]. From a quantitative point of view, the chiral
amplification is better in poly-[(S)-1r-co-(R)-21-r] than in
poly-[(R)1r-co-(R)-21-r]. In fact, the maximum helicity is
now obtained with just 10% of the chiral (R)-2 Sergeant,
while 1% of the chiral (S)-1 Soldier is enough to obtain a
60% of the maximum helicity (Figures 5d,e). Moreover,
these values are improved at low temperature: at -10°C, 1%
of (R)-2 is enough to get 71% of the maximum helicity
(Figure 5f).
!Gh= x2. !Gh,SS + x(1-x). !Gh,Ss (2)
The gabs obtained at 20°C was plotted against the mole
fraction of the chiral Sergeant monomer and subjected to a
nonlinear, least-squares fitting of the parameters !Gh,SS
,
!Gh,Ss and gmax using equations 1 and 2 (Figures 6a and
6b).18 The parameters could be converged successfully
affording !Gh,SS and !Gh,Ss values.19
In the poly-[(R)-1r-co-(R)-21-r] copolymer series, which
follows the “classical” Sergeants and Soldiers effect, posi-
tive values of !Gh,SS +0.37 and !Gh,Ss-(R) +0.50 kJ/mol indi-
cate that the same left-handed helical structure (M helix) is
induced by both, the chiral Sergeant [(R)-2] and chiral
Soldier [(R)-1] once is activated (Figure 6a).
As above, CD studies with the poly-[(S)-1r-co-(R)-21-r]
series showed that the (S)-1 pendant is in ap conformation.
Addition divalent metal ions produced helical inversion —
due to the ap to sp conformational change— confirming
that in this series the (S)-1 chiral Soldier adopts a favored
ap conformation when is commanded by the (R)-2 Sergeant
(see S72 in SI for detailed explanation).
a)
b)
5!10-3
1!10-2
5!10-3
0
"Gh,SS
"Gh,Ss
"Gh,SS
"Gh,Ss-(S)
0.37 (M) KJ/mol
0.50 (M) Kj/mol
0.19 (M) KJ/mol
-0.36 (P) Kj/mol
0
Experimental Data
Calculated Line
THF 20ºC
!= 385nm
As a result, a left-handed helix can be induced in the axial-
ly racemic poly-(R)-1 by synthetizing a copolymer with a
very small amount of either (R)-2 [e.g., poly-[(R)-1r-co-(R)-
21-r] (r> 0.9)] or (S)-2 [e.g., poly-[(R)-1r-co-(S)-21-r] (r>
0.9)].
-5!10-3
-1!10-2
THF 20ºC
!= 385nm
-5!10-3
-1!10-2
Experimental Data
Calculated Line
0.0
0.5
1.0
0.0
0.5
1.0
Mole Fraction of (R)-2
Mole Fraction of (R)-2
Alternatively, the axially racemic poly-(S)-1 can be com-
pelled to adopt a right-handed helix by doping the polymer
with (R)-2 or (S)-2 [e.g., right-handed helix in poly-[(S)-1r-
co-(R)-21-r] (r> 0.9) and poly-[(S)-1r-co-(S)-21-r] (r> 0.9)].
Figure 6. (a) Plots of gabs values at indicated wavelength of poly-
[(R)-1r-co-(R)-21-r] copolymer series against copolymer composi-
tion and their corresponding curve fitting based on equations (1)
and (2) to obtain the free energy parameters !Gh,SS and !Gh,Ss-(R)
(b) Idem for poly-[(R)-1r-co-(R)-21-r] copolymer series.
.
The secondary structure of the chiral amplified poly-[(S)-
10.90-co-(R)-20.10] was analyzed in the solid state. Thus, a
dilute solution of poly-[(S)-10.90-co-(R)-20.10] was spin coat-
ed onto a HOPG substrate and submitted to AFM stud-
ies.[14] The high resolution images obtained from the well-
ordered monolayers allowed us to measure the helical pitch
(3.2 nm), packing angle (60°) and helical sense described
by the pendants (right-handed), indicating that the copoly-
mer displays a cis-cisoidal helix (Figure 5g).
On the contrary, opposite sign values of !Gh,SS and
!Gh,Ss-(S) (i.e., +0.19 and -0.36) were obtained for the poly-
[(S)1r-co-(R)-21-r] copolymer series, indicating that the
chiral Soldier [(S)-1] tends to induce the opposite P helix
once is activated by the chiral Sergeant [(R)-2], which
induces a M helix in the copolymer (Figure 6b). This poly-
[(S)-1r-co-(R)-21-r] copolymer series follows the “abnor-
mal” Sergeants and Soldiers effect. Low temperature stud-
ies (i.e., -10ºC) can be found in the SI showing stronger
effects (see S61).
These data are in very good agreement with those found
when poly-(S)-1 homopolymer is amplified towards a right-
handed helix by addition of a monovalent metal ion (exter-
nal stimulus),13d indicating that the internal doping leads to
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Page 6 of 9
Majority Rules Studies between
enantiomers: no communication
a)
Finally, to fulfill the chiral to chiral communication studies
of this work, we checked the presence/absence of the Ma-
jority rules phenomenon in these systems. In this regard,
poly-[(R)-1r-co-(S)-11-r] and poly-[(R)-2r-co-(S)-21-r] copol-
ymer series composed by enantiomers (i.e., neither Ser-
geants nor Soldiers) were prepared. CD experiments indi-
cated that Majority rules are not operative in these systems
[i.e., there is not communication between enantiomers; see
full details in SI (S16) and Figure 7a].
1
2
3
4
5
6
7
8
poly-[(R)-2r-co-(S)-2(1-r)
]
poly-[(R)-1r-co-(S)-1(1-r)
]
O
O
O
NH
HN
(R)-2
O
(R)-1
X
X
Enantiomers
Enantiomers
O
O
NH
O
HN
9
The lack of majority rules allows us to propose a particular-
ly interesting case, represented by copolymers where one
monomer is racemic —(R/S)-2 (the Sergeant)— and the
other is chiral —(R)-1 (the Soldier)—. From the studies
detailed above, we knew that both Sergeants, (R)- and (S)-
2, induce the same ap conformation in the chiral Soldier
[(R)-1]. As a result, copolymers with a large ratio of mon-
omer (R)-1 adopt a left-handed helix. Thus, all copolymers
with a [poly-[(R)-1>0.8-co-(R/S)-2<0.2] composition should
adopt the same left-handed helical structure (Figure 7b). In
fact, CD spectra of poly-[(R)-1>0.8-co-(R/S)-2<0.2] copolymer
series showed as expected a negative Cotton effect (Figure
7c) similar to the one obtained for poly-[(R)-1>0.8-co-(R)-
2<0.2] (Figure 5a) and poly-[(R)-1>0.8-co-(S)-2<0.2] (Figure
5d), indicating that both enantiomers of monomer 2 give
the same order to monomer (R)-1, i.e., the adoption of a
preferred ap conformation.
(S)-1
O
10
11
12
13
14
15
16
17
18
19
20
21
22
23
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60
No Majority Rules
No Majority Rules
b)
Chiral Sergeants and Chiral Soldiers effect:
effective communication
poly-[(R)-1r-co-(R)-2(1-r)
]
poly-[(S)-1r-co-(R)-2(1-r)
]
O
O
O
O
(R)-1
(S)-1
NH
NH
No
Enantiomers
No
Enantiomers
O
O
HN
Ph
HN
Ph
H
O
H
O
Chiral Amplification
Chiral Amplification
c)
ap
20
10
CHIRAL TO CHIRAL
COMMUNICATION
O
6
4
2
NH
O
0
(R)-1
With this CD data on hand, we carried out the theoretical
evaluation of the contribution of the Soldier to the CD
spectra (gmax_Soldier (R) or (S)). In this special case, gmax_Sergeant is
null due to the presence of a racemic mixture of the Ser-
geant and therefore gabs is proportional to the gmax_Soldier
(equation 3).
-10
-20
-30
-40
-50
-60
O
O
ap
NH
(S)-2
Poly(R/S)-2
Poly[(R)-10.20-co-(R/S)-20.80)]
Poly[(R)-10.40-co-(R/S)-20.60)]
Poly[(R)-10.60-co-(R/S-2)0.40)]
Poly[(R)-10.80-co-(R/S)-20.20)]
O
HN
(R)-2
O
300
400
500
poly-[(R)-1-co-(R/S)-2]
g
abs = x . gmax_Soldier + (1-x) gmax_Sergeant = x . gmax_Soldier (3)
Wavelength [nm]
d)
e)
Thus, plotting gabs against the mole fraction of the chiral
Sergeant monomer should produce (after linear regression)
the gmax_Soldier value. The values obtained (gmax_s-(R)= -0.012)
for the poly-[(R)-1>0.8-co-(R/S)-2<0.2] series (Figure 7d), fit
perfectly on the equation of a straight line, indicating that
the CD contribution of the chiral Soldier is always the same
due to the adoption of a specific conformation (ap) once
the Sergeant is introduced within the copolymer chain.
1.5!10-2
1.0!10-2
5.0!10-3
0.0
0.10
0.08
0.06
0.04
0.02
0.00
gmax_Ss-(R)
!Gh,Ss-(R)
0.01224
-0.51 Kj/mol (M)
0.0
0.5
1.0
0.0 0.2 0.4 0.6 0.8 1.0
Mole Fraction of rac-2
Mole Fraction of (R)-1
For its part, !Gh depends only on !Gh,Ss, (!Gh,SS is null,
racemic Sergeant). Combination of equations (2) and (3)
should allow to obtain !Gh,Ss by plotting gabs/gmax against the
mole fraction of (R)-1. The value obtained (!GhSs= +0.51
KJ/mol; Figure 7e) shows that in poly-[(R)-1r-co-(R/S)-21-r],
the M-helix is more favorite by just +0.51 KJ/mol when a
chiral Sergeant (R or S)-2 is adjoined by a chiral Soldier
[(R)-1].
Figure 7. (a) Schematic representation indicating the absence of
Majority Rules in poly-[(R)-1r-co-(S)-11-r] and poly-[(R)-2r-co-(S)-
1-r] series (no communication). (b) Idem showing the presence of
2
chiral to chiral communication in the poly-[(R)-1r-co-(R)-21-r] and
poly-[(S)-1r-co-(R)-21-r]. For poly-[(S)-1r-co-(S)-21-r] and poly-
[(R)-1r-co-(S)-21-r] series the same effect is observed (see S78 and
S68 respectively in SI). (c) Helical sense enhancement of a macro-
scopically racemic polymer [(R)-1] by a racemic mixture of a
chiral Sergeant [(R/S)-2]. (d) Plots of gabs values at indicated wave-
length of poly-[(R)-1r-co-(R/S)-21-r] against copolymer composi-
tion in THF at -10°C, and their corresponding regressions to
obtain gmax. (e) Plots of gabs/gmax values at indicated wavelength of
poly-[(R)-1r-co-(R/S)-21-r] against copolymer composition in THF
at -10°C, and their corresponding regression to obtain the free
CONCLUSIONS
In summary, we report here a chiral amplification proce-
dure based on chiral Sergeant to chiral Soldier communica-
tion. Using this novel approach is possible to induce a
single handed helical structure on a dynamic axially race-
mic polyphenylacetylene by doping the chain with a very
small amount (1-10%) of an adequately selected chiral
monomer (that acts as Sergeant) (Figure 8).
energy parameters !Gh,Ss-(R)
.
In our examples, the chiral Sergeant has a fairly restricted
conformation mobility that fixes a preferred conformation
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Supporting Information
on the highly dynamic chiral Soldier independently on the
1
2
3
4
5
6
7
8
absolute configuration of the Sergeant, although the extent
of this communication is different in both copolymer series,
indicating the importance of the chirality of the two coun-
terparts in this chiral to chiral communication mechanism.
Moreover, both the chiral Sergeant and the chiral Soldier
should produce a similar helical scaffold in their corre-
sponding homopolymers (e.g., cis-cisoidal) to transmit the
order between monomers more effectively. Thus, either M
or P helical senses can be induced depending on the abso-
lute configuration of the chiral Soldier (Figure 8).
Materials and methods, synthesis and characterization of mono-
mers and copolymers, conformational studies, AFM studies,
nanostructuration studies and supporting references.
The Supporting Information is available free of charge on the ACS
Publications website.
AUTHOR INFORMATION
Corresponding Author
9
ricardo.riguera@usc.es, felix.freire@usc.es.
10
11
12
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14
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17
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21
22
23
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49
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53
54
55
56
57
58
59
60
Author Contributions
CD Active, right-handed helix
90-99 % (R)-1
Poly-[(S)-1r-co-(R)-21-r
Poly-[(S)-1r-co-(S)-21-r
]
All authors have given approval to the final version of the manu-
script. ‡These authors contributed equally.
]
O
90-99 % (S)-1
NH
O
Copolymerization
ACKNOWLEDGMENT
O
(R)-1
(S)-1
1-10 % (R)-2
or
1-10 % (S)-2
NH
O
O
We thank Servicio de Nanotecnología y Análisis de Superficies
(CACTI, UVIGO) and Servicio de Microscopía Electrónica
(RIAIDT, USC). We also thank the Ministerio de Ciencia e Inno-
vación ([CTQ2014-61470-EXP, FPI (R. Rodríguez)], Fundación
Gil Dávila fellowship (S. Arias.), Xunta de Galicia (Centro Singu-
lar de Investigación de Galicia accreditation 2016-2019,
GRC2014/040) and the European Union (European Regional
Development Fund-ERDF) for financial support.
HN
R1
R2
O
O
O
Copolymerization
1-10 % (R)- or (S)-2
HN
R1
R2
Poly-[(R)-1r-co-(R)-21-r
Poly-[(R)-1r-co-(S)-21-r
CD Active, left-handed Helix
]
1-10 % (R)-2
or
1-10 % (S)-2
]
1-10 % (R)- or (S)-2
Figure 8. Chiral amplification of a chiral helical polymer with low
screw sense excess by copolymerization with the two enantiomers
of an appropriate chiral doping agent.
ABBREVIATIONS
PPA, poly(phenylacetylene); AFM, Atomic Force Microscopy;
CD, Circular Dichroism; MPA, methoxyphenylacetic acid
Thus, a M helical sense will be induced in both poly-[(R)-
1r-co-(R)-21-r] and poly-[(R)-1r-co-(S)-21-r] copolymer se-
ries, because the two different configurations of the Ser-
geant command the same conformation on the chiral Sol-
dier [(R)-1]. The same effect is observed in the poly-[(S)-
1r-co-(R)-21-r] and poly-[(S)-1-co-(S)-21-r] copolymer series,
although the helical sense induced in the copolymer is the
P helix due to the enantiomeric configuration of the chiral
Soldier [(S)-1].
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In addition to this remarkable chiral enhancement, the
resulting well-ordered polymer maintains its dynamic char-
acter and tunability. So, when submitted to appropriate
stimuli (e.g., metal coordination), it can undergo further
helical inversion or nanostructuration (see S78 in SI).
Moreover, it is also important to emphasize that the phe-
nomenon here reported (chiral to chiral Sergeants and Sol-
diers effect) is very different —both from the structural and
from the chiral amplification points of view— from the
other phenomena of communication between comonomers
in polymers described in the literature and mentioned
above —i.e., "“classical”" Sergeants and Soldiers (between
chiral and achiral comonomers), Majority Rule (between
enantiomeric comonomers) and Chiral Conflict (nullifica-
tion of axiality)—.
We think this approach can open new perspectives in the
preparation of functional polymers with precise stereo-
chemical characteristics and suggests that polymers now
considered useless as macroscopically helical materials,
because of their low sense preference, could be improved
by this procedure to form a single preponderant P/M helix.
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(18) In the equations, gabs represents Kuhn´s dissymmetry factor
(=[θ]/3300/") and gmax correspond to the gabs of the optically active
parent homopolymer. !Gh is the free energy difference per monomeric
unit between both possible helical senses adopted by the polyene
backbone (P/M). !Gh,SS correspond to the !Gh of a chiral Sergeant
(Sergeant= S) interacting with another chiral Sergeant followed in
sequence along the polymer chain, while !Gh,Ss denotes the free energy
of a chiral Sergeant interacting with a neighboring in sequence chiral
Soldier [Soldier= s; Soldier with (R) configuration= s-(R); Soldier with
(S) configuration= s-(S)]. !Gh,SS and !Gh,Ss are, in accordance to Sato´s
model, competing energy contributions that determine the adoption
of a preferred handed helical structure.
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ACS Macro Lett. 2012, 1, 261. (c) Megens, R. P.; Roelfes, G. Chem.
Eur. J. 2011, 17, 8514.
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rea Polym J. 1996, 4, 139. (b) Yuki, H.; Okamoto, Y.; Okamoto, I. J.
Am. Chem. Soc. 1980, 102, 6356. (c) Okamoto, Y.; Hatada, K. In
Chromatographic Chiral Separations; Zief, M.; Crane, L. J. Eds.; Mar-
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(19) Curve fitting shown in Figure 6 for poly-[(S)-1r-co-(R)-21-r
]
and poly-[(R)-1r-co-(R)-21-r] display deviations that can be attributed
to the measurement of the CD signal at a certain wavelength (#= 385
nm). This measurement has an inevitable intrinsic error due to the
small shifting undergone by the maximum absorbance when the ratio
of monomer composition varies (i.e., meta and para monomers show
maxima at different wavelengths). Also, other undetected measure-
ment errors when performing the experiments might contribute to
those deviations.
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90-99 % (R)-1
O
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NH
O
O
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90-99 % (R)-1
NH
O
Homopolymer-(R)-1
Copolymerization
macroscopically racemic
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chiral
coalition
R1
R2
1-10 % (R)-2
O
O
HN
HN
R1
R2
1-10 % (R)-2
O
O
Homopolymer-(R)-2
helical sense enhacement
single handed helix (dopant)
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