Chiral-to-Chiral Communication in Polymers: A Unique Approach to Control Both Helical Sense and Chirality at the Periphery

Article abstract of DOI:10.1021/jacs.8b07782

A novel approach to the classical Sergeants and Soldiers effect, using chiral Sergeants and chiral Soldiers, allows control over both helical and external chirality in helical polymers. In the systems reported here, it is possible to induce the same helic

Full text of DOI:10.1021/jacs.8b07782

Subscriber access provided by University of South Dakota
Article
Chiral-to-Chiral Communication in Polymers: A Unique Approach
to Control both Helical Sense and Chirality at the Periphery
Katherine Cobos, Emilio Quiñoá, Ricardo Riguera, and Félix Freire
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.8b07782 • Publication Date (Web): 29 Aug 2018
Downloaded from http://pubs.acs.org on August 30, 2018
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a service to the research community to expedite the dissemination
of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in
full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully
peer reviewed, but should not be considered the official version of record. They are citable by the
Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore,
the “Just Accepted” Web site may not include all articles that will be published in the journal. After
a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web
site and published as an ASAP article. Note that technical editing may introduce minor changes
to the manuscript text and/or graphics which could affect content, and all legal disclaimers and
ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or
consequences arising from the use of information contained in these “Just Accepted” manuscripts.
is published by the American Chemical Society. 1155 Sixteenth Street N.W.,
Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 9
Journal of the American Chemical Society
1
2
3
4
5
6
7
8
9
Chiral-to-Chiral Communication in Polymers: A Unique Ap-
proach to Control both Helical Sense and Chirality at the
Periphery
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
Katherine Cobos, Emilio Quiñoá, Ricardo Riguera,* Félix Freire*
Centro Singular de investigación en Química Biolóxica e Materiais Moleculares (CiQUS) and Departamento de Química Orgáni-
ca, Universidade de Santiago de Compostela, E-15782 Santiago de Compostela, Spain
Supporting Information Placeholder
component). This chiral amplification phenomena is denot-
ed as the “Sergeants and Soldiers effect”2 and in practical
terms, it means that the introduction of a small amount of a
chiral unit (“Sergeant”) within a polymer formed by achiral
monomers ("Soldiers") will produce the formation of either
P or M helices in the resulting copolymer chain depending
on the chirality of the Sergeant used. This approach is very
convenient to obtain functional helical polymers folded into
a single handed P or M helix, because doping an inexpensive
achiral chain with a small amount of an expensive chiral
monomer provides the functional helicity —helices acting as
chiral stationary phases,3 chiral catalysts,4 chiral nanocon-
tainers5— that otherwise would be produced from a more
expensive fully chiral homopolymer.
ABSTRACT: A novel approach to the classical Sergeants and
Soldiers effect, using chiral Sergeants and chiral Soldiers,
allow controlling both helical and external chirality in helical
polymers. In the systems here reported it is possible to in-
duce the same helical sense (M or P) from any of the two
enantiomers of a chiral pendant group ["chiral Soldier", ma-
jor component; i.e., (R)- or (S)-1] when they face a single
enantiomer of an appropriate "chiral Sergeant" [minor com-
ponent; i.e., (S)-2]. For instance, copolymer series poly-
[(R)-1r-co-(S)-2(1-r)], poly-[(S)-1r-co-(S)-2(1-r)] and poly-
[(rac)-1r-co-(S)-2(1-r)] adopt the same P helix despite the
major component shows opposite absolute configurations.
This chiral to chiral communication effect is transmitted by
the stabilization of different conformations in each enantio-
meric form of the Soldier. As a result, this groundbreaking
approximation to the Sergeants and Soldiers effect allows
preparing a single-handed helix —which only depends on
the Sergeant's configuration— with different chiralities on
the helix periphery. Thus, a P helix can be decorated with the
(R)-, (S)- or even a racemic mixture of the chiral Soldier.
Changes on the absolute configuration of the Sergeant will
permit to obtain the opposite M helix, which can also be
decorated with the (R)-, (S)- or the racemic mixture of the
chiral Soldier.
In our group, we became interested on the possibility to
extend and also improve the helical function of
a
poly(phenylacetylene) (PPA) not only by controlling the
helicity of the polymer (P/M) but also by taming simultane-
ously the chiral pendants used as Soldiers.2a Thus, while the
helical sense of the polymer will be commanded by the chi-
rality of the Sergeant, the chirality on the periphery of the
helix will depend on the intrinsic chirality of the Soldier.
In this way, four different diastereoisomeric copolymers
could be prepared from a chiral Sergeant (Sgt.) and a chiral
Soldier
(Sold.)
—[poly-[(R/S)-Sergeant-co-(R/S)-
Soldier]—. In these copolymers, the helical sense will be
defined by the chirality of the Sergeant, while the chirality on
the surface of the helix will depend on the chirality of the
Soldier. For instance, if the (R)-Sgt. commands a left handed
(M)-helix, both the (R)- and (S)- enantiomers of the Soldier
will adopt the same M helix although their intrinsic chiralities
are the opposite (Figure 1a). Similar situation should be
founded if the enantiomeric form of the Sergeant [i.e. (S)-
Sgt.] is used to induce a single-handed helix, although in this
case a P helix should be generated (Figure 1b).
INTRODUCTION
The secondary structure of a helical polymer is related to
the interactions between the monomers that constitute the
polymeric chain.1 In the case of copolymers formed by the
combination of chiral and achiral monomers, this interaction
may occur through a conformational communication mech-
anism resulting in a chiral amplification phenomenon. In
such a case, it is found that the presence of a small amount of
the chiral monomer (minor component) is capable of domi-
nating the secondary structure of the whole copolymer chain
by inducing a certain orientation in the achiral units (major
ACS Paragon Plus Environment

Journal of the American Chemical Society
Sgtminor/(R)-Soldmajor ]— and P helices are commanded by the
poly-[(S)-Sgt-co-(R)-Sold]
Page 2 of 9
a)
b)
1
2
3
4
5
6
poly-[(R)-Sgt-co-(R)-Sold]
enantiomeric form [(S)-] of the Soldier —Phelix1 [(R)-
Sgtminor/(S)-Soldmajor; Phelix2 [(S)-Sgtminor/(S)-Soldmajor]—. As a
result, two helices are obtained according to the absolute
configuration of the major component: the Soldier ("chiral
coalition effect", Figure 2).
(S)-Sold.
(R)-Sold.
(R)-Sgt.
(S)-Sold.
(R)-Sold.
(S)-Sgt.
(R)-Sgt.
(S)-Sgt.
7
8
9
chiral Sergeant
chiral Sergeant
(R)-, (S)- or (R/S)-
(R)-, (S)- or (R/S)-
(R)-Sold.
(R)-Sold.
(S)-Sold.
(S)-Sold.
(S)-Sold.
(R)-Sold.
(R)-Sold.
(S)-Sold
(R)-Sold
Rh(I)
Rh(I)
(S)-Sold.
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
(R)-1
(R)
(S)-1
(S)
(R)-, (S)-
or (R/S)-Sgt
(R)-, (S)-
or (R/S)-Sgt
copolymerization
copolymerization
poly-[(S)-Sgt.-co-(S)-Sold]
poly-[(R)-Sgt.-co-(S)-Sold]
(R)-Sgt. = comands M helix
Both (R)-Sold. and (S)-Sold. adopt M helix
(S)-Sgt. = comands P helix
Both (R)-Sold. and (S)-Sold. adopt P helix
chiral Soldier
chiral Soldier
Chiral Coalition
Helical sense enhacement defined by the Soldier’s chirality
M helix
P helix
Identical helical sense with different
chirality on the periphery
Identical helical sense with different
chirality on the periphery
Figure 2. Schematic representation of the chiral coalition effect.
Figure 1. Conceptual representation of the chiral to chiral Ser-
geants and Soldiers effect using a Sergeant with either the (a)
(R)- or (b) (S)-configuration. [Sgt = Sergeant, Sold = Soldier]
Herein, we will shown a chiral PPA copolymer that follows
the “classical” Sergeant and Soldier effect and fulfill our ex-
pectations: its P/M helical sense is exclusively determined by
the chirality of the Sergeant, independently of the chirality of
the Soldier, which will determine the chirality of the helix
periphery—(R)-, (S)-, while the chirality at periphery of the
helix is determined by the (R)- or (S)- absolute configura-
tion of the Soldier. Moreover, modulation of the confor-
mation of the Soldier by the presence of external stimuli —
e.g., metal ions— will allow us to perform helix inversion
between helical enhanced copolymers without changing the
absolute configuration of the Sergeant.
Thus, our approach focuses on the preparation of PPAs
formed by two chiral components that establish communica-
tion between them. One is designed to control the helical
sense (P/M) while the other is selected to tune the [(R)-
/(S)-] configuration at the periphery of the helix.
In a first attempt, we explored the chiral-to-chiral commu-
nication mechanism in some PPAs copolymers.2a Those
initial studies allowed us to elucidate the communication
pathway between the two monomers, and the role played by
their absolute configuration in the process of helical sense
enhancement. As a result, we found that in order to have an
effective (chiral) Sergeant to (chiral) Soldier effect, the two
monomeric units must comprise the following requirements:
a) the corresponding homopolymers must present similar
helical scaffolds (i.e., cis-cisoidal or cis-transoidal), b) the
Soldier must be conformationally flexible (i.e., homopolymer
with weak polyenic band in CD), and c) the Sergeant must
have a clearly predominant conformation (i.e., homopolymer
with strong polyenic CD signature).2a
RESULTS AND DISCUSSION
To perform these studies we selected as chiral Soldiers the
4-ethynylanilides of (R)- or (S)-α-methoxy-α-phenylacetic
acid (MPA) [monomers (R)- or (S)-1] (Figure 3),2a, 7 and as
chiral Sergeant the 4-ethynylanilide of the (S)-α-9-anthryl-
α-methoxyacetic acid (9-AMA) [monomer (S)-2], that
differs from monomer 1 in the replacement of the phenyl
ring by an anthryl group (Figure 3a).
Monomer 1 [(R)- or (S)-] is known to be constituted by
an equilibrium of two conformations at the O=C-C-O bond
—ap/sp— in a 1:1 ratio (Figure 3b).7e In the corresponding
polymers [i.e., poly-(R)-1 and poly-(S)-1], the pendants
adopt the same conformational equilibrium and therefore,
equal amounts of the induced right- and left-handed helices.
As a result, poly-(R)-1 and poly-(S)-1 adopt a cis-cisoidal
helix, which are optically inactive (null CD) and, in spite of
their stereogenic carbon centre. Therefore, these polymers
behave as helical racemic from a macroscopic point of view7e
(Figure 3c).
Nevertheless, although PPA copolymers prepared in ac-
cordance with those conditions showed high chiral amplifi-
cation via the Sergeant and Soldier effect, the amplification
phenomena observed follows an “abnormal” effect.2a, 2d, 6 In
the copolymer series studied, we observed that the Soldier
—not the Sergeant!— was the component commanding the
helical sense of the copolymer. Thus, the Sergeant, acting as a
"chiral dopant", is used to trigger the Soldier, which is activat-
ed in the same way (identical conformation activated in all
cases) independently on the absolute configuration of the
Sergeant—[(R)-, (S)-]—, but producing opposite helical
senses following the Soldier´s absolute configuration.2a
Therefore, in those copolymer series, the chirality of the
Soldier is the one that commands the helical sense of the
copolymer. For instance, M helices are commanded by the
(R)-Sold. —Mhelix1 [(R)-Sgtminor/(R)-Soldmajor]; Mhelix2 [(S)-
ACS Paragon Plus Environment

Page 3 of 9
Journal of the American Chemical Society
a)
b)
a)
O
O
R2
R1
O
1
X RAY
R2
R1
O
N
N
N
2
O
R1
H
H
H
O
O
R2
3
4
5
6
7
8
9
N
H
(R)-1, R1= Ph R2= H
(S)-1, R1= H R2= Ph
(R)-2, R1= 9-Anthryl R2= H
(S)-2, R1= H R2= 9-Anthryl
sp conformation
ap conformation
H
O
(S)-2
ap conformation
c)
O
b)
THF
c)
CHCl3
DCM
NH O
n
n
ap conformation
P helix
H
H
O
O
O
O
HN
HN
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
NH
Ant
O
O
sp conformation
M helix
Poly-(S)-1
Poly-(S)-2
nm
d)
Figure 3. a) Structure of monomers (R)-1, (S)-1, (R)-2 and
(S)-2. b) Conformational equilibrium between ap and sp con-
formations. c) Structure of poly-(S)-1 showing the presence of
two different conformers at the MPA moieties responsible for
the coexistence of the two helical senses in the polymer.
Poly (S)-2
Poly (S)-2 + Ba2+
Ba2+
O
Ant
H
O
N
O
H
Ant
H
N
O
ap
H
Ba(ClO4)2
On the other hand, the amides of 9-ΑΜΑ (monomers 2)
are known to adopt a preferred ap conformation at the O=C-
C-O bond (Figure 4a), both in solution and in solid state as
confirmed by CD, NMR and X-ray8 (Figure 4a and SI).
sp
sp conformation
ap conformation
Figure 4. a) Chemical structure and X-ray of (S)-2. b) Chemi-
cal structure of poly-(S)-2. c) CD spectra of poly-(S)-2 in dif-
ferent solvents. d) Conformational ap/sp switch of poly-(S)-2
induced by Ba2+ (external stimulus) and corresponding CD
spectra in CHCl3.
Synthesis, structure and properties of poly-2
Polymerization of monomer (S)-2 with a Rh(I) catalyst,
[{Rh(nbd)Cl}2 (nbd=2,5-norbonadiene)], afforded poly-
(S)-2 in good yield (> 90%) and with a high cis content of
Wavelength [nm]
1
double bonds as determined by H NMR and Raman (vinyl
b)
a)
T= 243.0 ºC
protons at δ= 5.8–6.2 ppm in NMR; Raman bands at 1576,
1345, 1023 cm-1).9, 10 CD spectra of poly-(S)-2 measured in
different solvents (polar/non polar) indicated that poly-(S)-
2 adopts a preferred helical sense which is directly related to
the presence of the major ap conformation at the pendant
group (Figures 4b, c).
c-c
t-t
c)
THF
CHCl3
DCM
2.5 nm
65º
The presence of the major ap conformer in poly-(R)-2 and
poly-(S)-2, was confirmed by the helical inversion observed
after addition of Ba(ClO4)2 to a chloroform solution of the
polymer (chelation with M2+ favors the sp conformation,
Figure 4d), and by the helical enhancement observed after
addition of salts of monovalent metal ions such as LiClO4
that favor the ap conformation8 (see SI for details).
cis-cisoidal
3:1 helix
pendant
"clockwise"
backbone
"clockwise"
Figure 5. a) 3D structure and AFM image of poly-(S)-2 show-
ing a Pint/Pext helix. b) DSC thermogram of poly-(S)-2 showing a
typical cis-cisoidal trace. c) CD studies of poly-(S)-2 showing a
positive Cotton effect at the vinylic region.
Next, structural studies —CD, Raman, DSC and AFM—
were performed to obtain the secondary structure of these
polymers (Figure 5).11 High resolution AFM images of a
well-ordered monolayer of poly-(S)-2 revealed the presence
of well-packed polymer chains aligned parallel to each other.
From these images, the helical pitch (2.5 nm), packing angle
(65º) and the sense of the external part of the helix (Pext)
were determined (Figure 5a). These data are in full agree-
ment with a cis-cisoidal backbone that was further confirmed
by DSC studies (Figure 5b).
Moreover, the presence of a positive Cotton effect at the
vinylic region indicates also a P sense for the internal helix of
the polymer in agreement with the presence of a cis-cisoidal
polyene backbone12 (Figure 5c). Hence, from these structur-
al studies, we can conclude that poly-(S)-2 adopts a cis-
cisoidal polyene backbone (ω1= 65º) with the internal and
the external helices rotating in the same direction [i.e.,
clockwise (Pint/Pext)].
In summary, the homopolymers derived from monomers 1
and 2 present the same type of helical scaffold (cis-cisoidal,
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 4 of 9
(S)-2(1-r)] series showed, for all of them, CD curves analo-
ω1= 65º), although with different dynamic behavior: poly-1
series are helical racemic due to a rapid equilibrium between
the two helical senses, while poly-2 presents clearly a preva-
lent helical sense, which can be tuned by the action of metal
ions as external stimuli.
1
2
3
4
5
6
7
8
gous to that obtained from the poly-(S)-2 homopolymer
(Figure 7). In quantitative terms, the amount of Sergeant
needed to induce a single-handed helix in the copolymer —
maximum CD signal at the vinylic region— is close to 33%,
meaning that each Sergeant unit is able to fix the confor-
mation of two Soldiers.
The similarity between the helical structures of poly-1 and
poly-2 suggests2a that a copolymer formed by both mono-1
and mono-2 should constitute a good model to analyze the
chiral communication through a fully chiral Sergeants and
Soldiers effect, where the Sergeant can control the helical
sense of the copolymer, independent of the (R/S)-Soldier
chirality.
poly[(S)-1r-co-(S)-21-r
poly[(S)-2
]
a)
9
poly[(S)-10.10-co-(S)-20.90
poly[(S)-10.20-co-(S)-20.80
]
]
poly[(S)-10.30-co-(S)-20.70]
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
poly[(S)-1r-co-(S)-21-r]
poly[(S)-10.40-co-(S)-20.60
poly[(S)-10.50-co-(S)-20.50
poly[(S)-10.60-co-(S)-20.40
poly[(S)-10.63-co-(S)-20.37
poly[(S)-10.65-co-(S)-20.35
poly[(S)-10.67-co-(S)-20.33
poly[(S)-10.70-co-(S)-20.30
poly[(S)-10.80-co-(S)-20.20
poly[(S)-10.90-co-(S)-20.10
]
]
]
]
]
]
]
]
]
r = 0.3
100% CD Signal
Chiral-to-chiral communication studies
Different
copolymers
—poly[(S)-1r-co-(S)-2(1-r)],
poly[(R)-1r-co-(S)-2(1-r)] and poly[(rac)-1r-co-(S)-2(1-r)], r=
0.9-0.1— were prepared by polymerization of mixtures of
the chiral Soldiers [(S)-1, (R)-1, (rac)-1] and the chiral
Sergeant [(S)-2] with [(Rh(nbd)Cl)2] in different ratios
(Figure 6).
% (S)-2
Wavelength [nm]
poly[(R)-1r-co-(S)-21-r
poly[(S)-2
b)
]
poly[(R)-10.10-co-(S)-20.90
poly[(R)-10.20-co-(S)-20.80
]
]
poly[(R)-10.30-co-(S)-20.70]
poly[(R)-1r-co-(S)-21-r]
poly[(R)-10.40-co-(S)-20.60
poly[(R)-10.50-co-(S)-20.50
poly[(R)-10.60-co-(S)-20.40
poly[(R)-10.63-co-(S)-20.37
poly[(R)-10.65-co-(S)-20.35
poly[(R)-10.67-co-(S)-20.33
poly[(R)-10.70-co-(S)-20.30
poly[(R)-10.80-co-(S)-20.20
poly[(R)-10.90-co-(S)-20.10
]
]
]
]
]
]
]
]
]
r = 0.3
100 % CD Signal
O
O
HN
(S)-Sgt
Chiral Sergeant
(S)-2
H
[Rh(nbd)Cl]2
Et3N / THF
+
% (S)-2
Chiral Soldiers
r
H
1-r
n
(R)-1, (S)-1 and (rac)-1
Wavelength [nm]
poly[(rac)-1r-co-(S)-21-r
poly[(S)-2
O
c)
]
Copolymer series
R1
NH
poly[(rac)-10.10-co-(S)-20.90
poly[(rac)-10.20-co-(S)-20.80
]
]
Poly-[(R)-1-co-(S)-2]
R2
poly[(rac)-10.30-co-(S)-20.70]
O
R1= Ph, R2= H
poly[(rac)-10.33-co-(S)-20.67
poly[(rac)-10.35-co-(S)-20.65
poly[(rac)-10.37-co-(S)-20.63
poly[(rac)-10.40-co-(S)-20.60
poly[(rac)-10.50-co-(S)-20.50
poly[(rac)-10.60-co-(S)-20.40
poly[(rac)-10.70-co-(S)-20.30
poly[(rac)-10.80-co-(S)-20.20
poly[(rac)-10.90-co-(S)-20.10
]
]
]
]
]
]
]
]
]
poly[(rac)-1r-co-(S)-21-r
]
Poly-[(S)-1-co-(S)-2]
(R)-, (S)- and
rac-Sold
R1= H, R2= Ph
r = 0.3
100% CD Signal
Poly-[(rac)-1-co-(S)-2]
R1= H/Ph, R2= Ph/H
Figure 6. Monomer and copolymer structures used in this
study.
All the copolymers showed by NMR (vinyl protons, δ =
5.7– 5.8 ppm) and Raman (1567, 1335, 1003 cm-1) to posses
% (S)-2
10
a cis polyene backbone.9, Moreover, the DSC traces re-
Wavelength [nm]
Figure 7. CD spectra and r values of the different copolymer
series: (a) poly-[(S)-1r-co-(S)-2(1-r)], (b) poly-[(R)-1r-co-(S)-
vealed as expected the presence of cis-cisoidal polyene back-
bones.13 Their molecular weights were estimated by GPC
(THF as eluent with polystyrene standards as calibrants; see
SI for details) to be between Mn= 8000 and 12000 with
Mn/Mw values around 1.5– 2.5.
2
(1-r)] and (c) poly-[(rac)-1r-co-(S)-2(1-r)].
Moreover, from these studies we may highlight that these
copolymers respond to the classical Sergeant and Soldier
effect but in a fully chiral system, where the chiral Sergeant
[(S)-2] commands the chiral Soldier [(S)-1, (R)-1, (rac)-1]
within the chain to adopt the right-handed P helix inde-
pendently of the absolute configuration of the latter.
The chiral Soldier/chiral Sergeant monomer ratios in the
copolymers were shown by NMR to be coincident with the
feeding mixtures (see SI). Also, their random distribution
within the chain was demonstrated by the Kelen-Tüdos
method using varied monomer feed ratios and termination at
low conversions14 (see SI).
These results must follow different chiral to chiral com-
munication mechanisms between the Sergeant and then two
enantiomeric forms of the Soldier units. Thus, for instance, if
the (S)-Sergeant [(S)-2] induces a certain preferred confor-
The CD spectra (0.3 mg/mL in THF) of poly-[(S)-1r-co-
(S)-2(1-r)], poly-[(R)-1r-co-(S)-2(1-r)] and poly-[(rac)-1r-co-
ACS Paragon Plus Environment

Page 5 of 9
Journal of the American Chemical Society
mation (conformation 1) into the (S)-Soldier [(S)-1], origi-
1
2
3
4
5
6
7
8
nating the P helical sense in the chain, a different confor-
mation (conformation 2) has to be induced in the enantio-
meric Soldier [(R)-1] to promote the same P helix. Moreo-
ver, when the Soldier is racemic [(rac)-1] the Sergeant should
be able to command selectively two different conformations
of the Soldier to promote a single handed helical structure
into the copolymer —i.e., the Sergeant commands confor-
mation 1 to the (S)-Soldier, while conformation 2 is induced
in the (R)-Soldier—.
Li+
Ba2+
O
O
O
N
H
H
N
H
H
O
sp conformation
ap conformation
a)
b)
poly-[(S)-10.60-co-(S)-20.40](mru) /
Li+ = 1/3 (mol/mol)
9
poly-[(S)-10.60-co-(S)-20.40
poly-[(S)-10.60-co-(S)-20.40
]
]
/ (mru)/Ba2+ = 1/3 (mol/mol)
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
without Ba2+
Important information related to these aspects was ob-
tained from the interaction of the copolymers with metal
ions. In poly-1 homopolymers, containing MPA as pendant,
it is well known that the 1:1 sp/ap conformational equilibri-
um of the chiral Soldier unit can be selectively shifted to
either the ap or sp conformations by addition of monovalent
and divalent metal ions respectively.7 Those changes in the
conformation of the pendants are transmitted to the helical
backbone and can be monitored by CD studies through
either inversion or amplification of the CD traces.
with Li+
without Li+
with Ba2+
poly-[(S)-10.60-co-(S)-20.40]
Wavelength [nm]
d)
c)
without Ba2+
with Ba2+
without Li+
Hence, we test these experiments in the different copoly-
mer series. When LiClO4 was added to a THF solution of
copolymer poly-[(S)-10.60-co-(S)-20.40], a slight chiral ampli-
fication was observed, while addition of Ba(ClO4)2 produced
a helical inversion (Figures 8a,b). This fact indicates that the
chiral Soldier [(S)-1] in the native copolymer (Figure 9a)
adopts an ap conformation, slightly improved by complexa-
tion with Li+ but switched to the sp form by chelation with
Ba2+.7
with Li+
poly-[(R)-10.60-co-(S)-20.40
poly-[(R)-10.60-co-(S)-20.40
(mru)/Li+ = 1/3 (mol/mol)
]
]
poly-[(R)-10.60-co-(S)-20.40
poly-[(R)-10.60-co-(S)-20.40
(mru)/Li+ = 1/3 (mol/mol)
]
]
Wavelength [nm]
Wavelength [nm]
Figure 8. CD spectra of copolymer poly-[(S)-10.6-co-(S)-20.4
]
Analogous experiments on poly-[(R)-10.60-co-(S)-20.40
]
before and after the addition of (a) LiClO4 and (b) Ba(ClO4)2.
CD spectra of copolymer poly-[(R)-10.6-co-(S)-20.4] before and
after the addition of (c) LiClO4 and (d) Ba(ClO4)2.
showed that LiClO4 produced a helix inversion in the copol-
ymer, while the addition of Ba(ClO4)2 produced a slight
helical enhancement (Figures 8c,d). Thus, in poly-[(R)-1r-
co-(S)-21-r], the chiral Soldier [(R)-1] adopts a preferred sp
conformation (Figure 9b).7
Thus, two different energy preferences (ΔGh) are consid-
ered related to the presence of a chiral Sergeant followed in
sequence by another chiral Sergeant (ΔGSS) or by a chiral
Soldier (ΔGSs)
Finally, in the poly-[(rac)-1r-co-(S)-2(1-r)] series, the (R)-1
Soldiers have to adopt a sp conformation, while an ap con-
formation must be induced for the (S)-1 ones to produce a
helical enhancement in the copolymer (Figure 9c).
gabs = tanh(−NΔGh/RT)gmax
ΔGh = x2ΔGh,SS + x(1 − x)ΔGh,Ss (2)
(1)
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 ΔGh,SS
ΔGh,Ss, and gmax using eqs 1 and 2 (Figure 10). The parame-
ters could be converged successfully, affording ΔGh,SS and
ΔGh,Ss values.
From a mechanistic point of view, we think that the effec-
tiveness of the chiral Sergeant [(S)-2], inducing preferred
and different conformations on each of the two possible
absolute configurations of the chiral Soldier [(R)-1 and (S)-
1] is related to the ability of the anthryl group to gener-
ate π− π stabilizing interactions with the Soldiers in either ap
or sp forms (Figure 9).
,
In the poly-[(S)-1r-co-(S)-21−r] copolymer series, negative
values of ΔGh,SS= -2.97 and ΔGh, Ss= -0.24 kJ/mol were ob-
tained indicating that the same right-handed helical structure
(P helix) is induced by the chiral Sergeant [(S)-2] and chiral
Soldier [(S)-1] (Figure 10). In the case of the poly-[(R)-1r-
co-(S)-21−r] copolymer series, negative values of ΔGh,SS= -
2.60 and ΔGh,Ss= -0.17 kJ/mol were obtained indicating again
that the same right-handed helical structure (P helix) is in-
Additionally, we decided to quantify this chiral to chiral
Sergeant and Soldiers effect in the three different copolymer
series studied —i.e., poly-[(S)-1r-co-(S)-2(1-r)], poly-[(R)-1r-
co-(S)-2(1-r)] and poly-[(rac)-1r-co-(S)-2(1-r)]— using Sato´s
theory, which considers that the degree and direction of the
helical sense induction depends on the nature of the neigh-
boring monomer units.15, 16
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 6 of 9
poly[(S)-1r-co-(S)-21-r
]
poly[(R)-1r-co-(S)-21-r
]
duced although is less energetically favored than in the poly-
[(S)-1r-co-(S)-21−r] copolymer series (Figure 10).
1
2
ΔGh,SS
ΔGh,Ss
ΔGh,SS
ΔGh,Ss
-0.24 (P) Kj/mol
-2.97 (P) Kj/mol
-2.60 (P) Kj/mol
-0.17 (P) Kj/mol
3
4
Experimental data
Calculated line
Experimental data
Calculated line
a)
(S)-2 ap
5
6
THF, 20ºC
THF, 20ºC
λ=402 nm
λ=402 nm
7
8
9
(S)-1 ap
(S)-2 ap
poly[(rac)-1r-co-(S)-21-r
]
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
ΔGh,SS
ΔGh,Ss
-2.58 (P) Kj/mol
-0.19 (P) Kj/mol
Experimental data
Calculated line
(S)-1 ap
THF, 20ºC
λ=402 nm
(S)-2 ap
b)
Figure 10. Plots of gabs values at indicated wavelength of poly-
[(S)-1r-co-(S)-21−r], poly-[(R)-1r-co-(S)-21−r] and poly-[(rac)-
1r-co-(S)-21−r] copolymer series against copolymer composition
and their corresponding curve fitting based on eqs 1 and 2 to
(R)-1 sp
(R)-1 sp
obtain the free energy parameters ΔGh,SS and ΔGh,Ss
.
(S)-2 ap
(S)-1 ap
Finally, it is important to point out that all these copolymers
series maintain intact their capacity to originate nanostructu-
ration via helical polymer-metal complexes (HPMCs).7d For
instance, poly-[(rac)-10.67-co-(S)-20.33] (conc= 0.3 mg/mL in
CHCl3) originated stable and well-defined spherical particles
when treated with Ba2+ and Ag+. Both the divalent and monova-
lent cations were added as perchlorates in MeOH (mru/Mn+=
1.0/0.2 mol/mol) and the resulting tunable nanospheres
showed very good sizes and PDI values (61 nm, 0.071 and 74
nm and 0.067 respectively) (Figure S17) and preserved the
encapsulating properties of these systems.7d
c)
(S)-2 ap
(R)-1 sp
(S)-1 ap
CONCLUSIONS
(S)-2 ap
In conclusion, we have describe six helical copolymer se-
ries constituted by two chiral components that respond to
the classical Sergeants and Soldiers effect and where ten
different helices can be prepared from four different stereo-
chemical combinations: P/M helical sense of the backbone
and R/S chirality of the groups at the periphery (Figure 11).
The helical sense is exclusively determined by the absolute
configuration of the Sergeant (minor component) while the
chirality at the periphery is determined by the absolute con-
figuration of the Soldier (major component). In addition, the
helical sense of four of these six helical copolymers can be
selectively inverted or enhanced by the addition of metal ions
as external stimuli (Figure 11). In this way, helical polymers
with clockwise (or counterclockwise) helical sense and (R)-
or (S)-chirality at the external part can be produced and the
helix inverted to the opposite counterclockwise (or clock-
wise) sense while maintaining the chiral decoration at the
surface. From a structural point of view, this helical induction
Figure 9. 3D model of the helical structures adopted by (a)
poly-[(S)-1r-co-(S)-2(1-r)], (b) poly-[(R)-1r-co-(S)-2(1-r)] and (c)
poly-[(rac)-1r-co-(S)-2(1-r)], highlighting the conformational
composition of the pendant groups.
Finally, the calculations on the poly-[(rac)-1r-co-(S)-21−r],
gave similar results to the previous case, ΔGh,SS= -2.58 and
ΔGh,Ss= -0.19 kJ/mol, indicating that the P helical sense is
also favored in these copolymer series but in a less effective
way when compared to poly-[(S)-1r-co-(S)-21−r] (Figure 10).
These energy values are in good agreement with the r-
values obtained for the Sergeants and Soldier effect in the
copolymers —i.e., poly-[(S)-1r-co-(S)-21−r] r= 0.3, poly-[(R-
1r-co-(S)-21−r] r= 0.3 and poly-[(rac)-1r-co-(S)-21−r] r= 0.3—
indicating that the Soldier with (S) configuration is the most
"obedient" one.
ACS Paragon Plus Environment

Page 7 of 9
Journal of the American Chemical Society
is due to the unique interactions between the large anthryl
a)
P helix commanded by the Sergeant (S)-2
1
2
3
4
5
6
7
8
groups of the Sergeants and the vicinal Soldier units that shift
their conformation to favor π−π stacking that stabilize the
helix. Additionally, these chiral copolymers form HPMCs
that originate nanospheres with encapsulating properties
when treated with appropriate metal salts.
poly[(S)-1r-co-(S)-21-r
]
]
poly[(R/S)-1r-co-(S)-21-r
]
poly[(R)-1r-co-(S)-21-r
S
S
R
R
S
R
3
2
1
S
S
R
S
According with our results, the design of a copolymer with
this behavior requires: i) Sergeant and Soldier producing
homopolymers with resembled scaffolds, i.e., similar dihedral
angles for conjugated double bonds; ii) a Sergeant with a
preferred single conformation and a highly extended aro-
matic ring, and finally iii) a Soldier with a highly dynamic
conformational equilibrium between two conformations.
R
R
9
P
P
P
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
chirality on the periphery defined by the Soldiers [(R)-1; (S)-1]
Metal
S
S
S
R
R
R
Metal
This novel approach to helical structures with controlled
helicity (P or M) even after changes on the chirality of the
major component of the copolymer [(R)-, (S)- or rac-Sold.],
will open new avenues towards the rational design and pro-
duction of new chiroptical materials, where the role of the
helix and the role of the chirality at the pendant groups could
be explored independently.
helix
inversion
helix
inversion
8
7
S
R
M
M
poly[(S)-1r-co-(S)-21-r] / Metal
Complex
poly[(R)-1r-co-(S)-21-r] / Metal
Complex
M helix commanded by the Sergeant (R)-2
b)
poly[(R)-1r-co-(R)-21-r
]
poly[(S)-1r-co-(R)-21-r]
ASSOCIATED CONTENT
poly[(R/S)-1r-co-(R)-21-r]
Supporting Information.
S
R
S
S
R
R
Materials and methods, synthesis and characterization of mon-
omers, synthesis and characterization copolymers, conforma-
tional studies, AFM studies, nanostructuration studies and
supporting references.
6
5
4
S
R
S
R
R
S
The Supporting Information is available free of charge on the
ACS Publications website.
M
M
M
chirality on the periphery defined by the Soldiers [(R)-1; (S)-1]
AUTHOR INFORMATION
Corresponding Author
R
R
R
R
Metal
Metal
S
S
S
helix
inversion
helix
inversion
ricardo.riguera@usc.es, felix.freire@usc.es
9
10
Funding Sources
S
No competing financial interests have been declared.
P
P
ACKNOWLEDGMENT
poly[(R)-1r-co-(R)-21-r] / Metal
Complex
poly[(S)-1r-co-(R)-21-r] / Metal
Complex
Financial support from MINECO (CTQ2014-61470-EXP,
CTQ2015-70519-P), Xunta de Galicia (GRC2014/040, Centro
singular de investigación de Galicia accreditation 2016-2019,
ED431G/09) and the European Regional Development Fund
(ERDF) is gratefully acknowledged. We also thank Servicio de
Nanotecnología y Análisis de Supeficies (CACTI, UVIGO).
Figure 11. (a) Graphical illustration of the helical structures of
poly-[(R)-1r-co-(S)-2(1-r)] (1), poly-[(rac)-1r-co-(S)-2(1-r)] (2)
and poly-[(S)-1r-co-(S)-2(1-r)] (3) showing identical scaffold
and helical sense (P helix) but different composition at the
periphery. The M helices obtained by helical inversion are also
shown (7 and 8). (b) Idem for poly-[(R)-1r-co-(R)-2(1-r)] (4),
poly-[(rac)-1r-co-(R)-2(1-r)] (5) and poly-[(S)-1r-co-(R)-2(1-r)
]
(6) showing identical scaffold and helical sense (M helix) but
different composition at the periphery. The P helices obtained
by helical inversion are also shown (9 and 10).
REFERENCES
(1) (a) Xu, A.; Masuda, T.; Zhang, A. Polym. Rev. 2017, 57, 138. (b)
Yashima, E.; Ousaka, N.; Taura, D.; Shimomura, K.; Ikai, T.; Maeda, K.
Chem. Rev. 2016, 116, 13752. (c) Freire, F.; Quiñoá, E.; Riguera, R. Chem.
ACS Paragon Plus Environment

Journal of the American Chemical Society
Page 8 of 9
Rev. 2016, 116, 1242. (d) Yashima, E.; Maeda, K.; Lida, H.; Furusho, Y.;
(11) (a) F. Freire, E. Quiñoá, R. Riguera, Chem. Commun., 2017, 53,
481. (b) R. Rodríguez, J. Ignés-Mullol, F. Sagués, E. Quiñoá, R. Riguera, F.
Freire, Nanoscale, 2016, 8, 3362. (c) S. I. Sakurai, S. Ohsawa, K. Nagai, K.
Okoshi, J. Kumaki, E. Yashima, E. Angew. Chem., Int. Ed., 2007, 46, 7605.
(12) Fernández, B.; Rodríguez, R.; Rizzo, A.; Quiñoá, E.; Riguera, R.;
Freire, F. Angew. Chem. Int. Ed. 2018, 57, 3666.
(13) Liu, L.; Namikoshi, T.; Zang, Y.; Aoki, T.; Hadano, S.; Abe, Y.;
Wasuzu, I.; Tsutsuba, T.; Teraguchi, M.; Kaneko, T. J. Am. Chem.
Soc. 2013, 135, 602.
(14) (a) K. Maeda, M. Muto, T. Sato, E. Yashima, Macromolecules,
2011, 44, 8343. (b) T. Kelen, F. Tüd.s, J. Macromol. Sci. Chem.,1975, 9, 1.
(15) Lifson S.; Andreola, C.; Peterson, N. C.; Green, M. M. J. Am.
Chem. Soc. 1989, 111, 8850.
(16) (a) F. Takei, K. Onitsuka, S.Takahashi, K. Terao, T. Sato, Macro-
molecules 2007, 40, 5245. (b) J. Tabei, M. Shiotsuki, T. Sato, F. Sanda, T.
Masuda, Chem. Eur. J. 2005, 11, 3591.
Nagai, K. Chem. Rev. 2009, 109, 6102. (e) Liu, J.; Lam, J. W. Y.; Tang, B. Z.
Chem. Rev. 2009, 109, 5799. (f) Yashima, E.; Maeda, K.; Furusho, Y. Acc.
Chem. Res. 2008, 41, 1166. (g) Rudick, J. G.; Percec, V. Acc. Chem. Res.
2008, 41, 1641. (h) Yashima, E.; Maeda, K. Macromolecules 2008, 41, 3.
(i) Yashima, E.; Maeda, K. Helically Folding Polymers in Foldamers:
Structure Properties and Applications; Eds: Hecht, S.; Huc, I. WILEY-
VCH, Weiheim, 2007, pp 331. (j) Maeda, K.; Yashima, E. Top. Curr.
Chem. 2006, 265, 47.
(2) (a) Arias, S.; Rodríguez, R., Quiñoá, E., Riguera, R., Freire, F. J. Am.
Chem. Soc. 2018, 140, 667. (b) Arias, S.; Bergueiro, J.; F. Freire, Quiñoá,
E.; Riguera, R. Small, 2016, 12, 238. (c) Nagata, Y.; Nishikawa, T.;
Suginome, M. ACS Macro Lett., 2016, 5, 519. (d) Nagata, Y.; Nishikawa,
T.; Suginome, J. Am. Chem. Soc., 2015, 137, 4070. (e) Bergueiro, J.; Freire,
F.; Wendler, E. P.; Seco, J. M.; Quiñoá, E.; Riguera, R. Chem. Sci. 2014, 5,
2170. (f) Jain, V.; Cheon, K.-S.; Tang, K.; Jha, S.; Green, M. M. Isr. J.
Chem. 2011, 51, 1067. (g) Jain, V.; Cheo, K. –S.; Tang, Jha, S.; Green M.
M. Angew. Chem., Int. Ed. 2011, 51, 1067. (h) Mateos-Timoneda, M. A.;
Crego-Calama, M.; Reinhoud, D. N. Chem. Soc. Rev., 2004, 33, 363. (i)
Tang, K.; Green, M. M.; Cheon, K. S.; Selinger, J. V.; Garetz, B. A. J. Am.
Chem. Soc., 2003, 125, 7313. (j) Green, M. M.; Park, J. W.; Sato, T.; Tera-
moto, A.; Lifson, S.; Selinger, R. L.; Selinger, J. V. Angew. Chem., Int. Ed.
1999, 38, 3139. (k) Gu, H.; Nakamura, Y.; Sato, T.; Teramoto, A.; Green,
M. M.; Jha, S. K.; Andreola, C.; Reidy, M. P. Macromolecules 1998, 31,
6362. (l) Green, M. M.; Peterson, N. C.; Sato, T.; Teramoto, A.; Cook, R.;
Lifson, S. Science 1995, 268, 1860. (m) Green, M. M.; Reidy, M. P.; John-
son, R. D.; Darling, G.; O’Leary, D. J.; Willson, G. J. Am. Chem. Soc. 1989,
111, 6452.
(3) (a) Maeda, K.; Hirose, D.; Okoshi, N.; Shimomura, K.; Wada, Y.,
Ikai, T.; Kanoh, S.; Yashima, E. J. Am. Chem. Soc. 2018, 140, 3270. (b)
Shimomura, K.; Ikai, T.; Kanoh, S.; Yashima, E.; Maeda, K. Nat. Chem.
2014, 6, 429.
(4) (a) Ke, Y.-Z.; Nagata, Y.; Yamada, T.; Suginome, M. Angew. Chem.
Int. Ed. 2015, 54, 9333. (a) Yamamoto, T.; Yamada, T.; Nagata, Y.;
Suginome, M. J. Am. Chem. Soc. 2010, 132, 789.
(5) (a) Zhao, B.; Chen, C.; Huang, H.; Deng, J. Colloid. Polym. Sci.
2015, 293, 349. (b) Zhang, H.; Song, J.; Deng, J. Macromol. Rapid Com-
mun. 2014, 35, 1216.
(6) (a) Takei, F.; Onitsuka, K.; Takahashi, S.; Terao, K.; Sato, T. Mac-
romolecules 2007, 40, 5245. (b) Tabei, J.; Shiotsuki, M.; Sato, T.; Sanda,
F.; Masuda, T. Chem. Eur. J. 2005, 11, 3591. (c) Deng, J. P.; Tabei, J.;
Shiotsuki, M.; Sanda, F.; Masuda, T. Macromolecules 2004, 37, 9715. (d)
Morino, K.; Maeda, K.; Okamoto, Y.; Yashima, E.; Sato, T. Chem. Eur. J.
2002, 8, 5112. (e) Koe, J. R.; Fujiki, M.; Motonaga, M.; Nakashima, H.
Macromolecules 2001, 34, 1082. (f) Maeda, K.; Okamoto, Y. Macromole-
cules 1999, 32, 974.
(7) (a) Rodríguez, R.; Arias, S.; Quiñoá, E.; Riguera, R.; Freire, F. Na-
noscale, 2017, 9, 17752. (b) Arias, S.; Freire, F.; Quiñoá, E.; Riguera, R.
Polym. Chem. 2015, 6, 4725. (c) Arias, S.; Freire, F.; Quiñoá, E.; Riguera,
R. Angew. Chem., Int. Ed. 2014, 53, 13720. (d) Freire, F.; Seco, J. M.;
Quiñoá, E.; Riguera, R. J. Am. Chem. Soc. 2012, 134, 19374. (e) Freire, F.;
Seco, J. M.; Quiñoá, E.; Riguera, R. Angew. Chem., Int. Ed. 2011, 50,
11692.
1
2
3
4
5
6
7
8
9
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
(8) (a) Freire, F., Seco, J. M.; Quiñoá, E., Riguera, R. Org.
Lett., 2010, 12, 208. (b) Freire, F., Quiñoá, E., Riguera, R. Chem. Com-
mun. 2007, 14, 1456.
(9) (a) Li, B. S.; Lam, J. W. Y.; Yu , Z.-Q.; Tang, B. Z. Langmuir 2012,
28, 5770. (b) Louzao, I.; Seco, J. M.; Quiñoá, E.; Riguera, R. Angew. Chem.
Int. Ed. 2010, 49, 1430. (c) Sakurai, S. I.; Okoshi, K.; Kumaki, J.; Yashima,
E. Angew. Chem., Int. Ed. 2006, 45, 1245. (d) Li, B. S.; Kang, S. Z.; Cheuk,
K. K. L.; Wan, L.; Ling, L.; Bai, C.; Tang, B. Z. Langmuir 2004, 20, 7598.
(10) (a) Cheuk, K. K. L.; Li, B. S.; Lam, J. W. Y.; Xie, Y.; Tang, B. Z.
Macromolecules 2008, 41, 5997. (b) Mayershofer, M. G.; Nuyken, O. J.
Polym. Sci., Part A: Polym. Chem. 2005, 43, 5723. (c) Li, B. S.; Cheuk, K.
K. L.; Ling, L.; Chen, J. X. X.; Baiand, C.; Tang, B. Z. Macromolecules
2003, 36, 77. (d) Cheuk, K. K. L.; Lam, J. W. Y.; Lai, L. M.; Dongand, Y.;
Tang, B. Z. Macromolecules 2003, 36, 9752.
ACS Paragon Plus Environment

Page 9 of 9
Journal of the American Chemical Society
1
2
3
4
5
TOC
M-helix
M-helix
6
7
8
9
(R)
Sgt
(S)
(R)
Sgt
Sgt
Sgt
Sgt
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
Sgt
(R)
(S)
(S)
poly-(Sgt)
poly-(Sgt)-co-(R)
poly-(Sgt)-co-(S)
poly-(Sgt)-co-(rac)
ACS Paragon Plus Environment