From Sergeants and Soldiers to Chiral Conflict Effects in Helical Polymers by Acting on the Conformational Composition of the Comonomers

Article abstract of DOI:10.1002/anie.202009215

Different communication mechanisms can be switched within a copolymer by acting on the conformational composition of the components and their chirality. Thus, a sergeant and soldiers effect is produced in two diastereomeric copolymer series, poly[(S)-1

Full text of DOI:10.1002/anie.202009215

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
www.angewandte.org
Accepted Article
Title: From Sergeants and Soldiers to Chiral Conflict Effects in Helical
Polymers by Acting on the Conformational Composition of the
Comonomers
Authors: Felix Freire, Katherine Cobos, Rafael Rodríguez, Emilio
Quiñoá, and Ricardo Riguera
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.202009215
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10.1002/anie.202009215
Angewandte Chemie International Edition
RESEARCH ARTICLE
From Sergeants and Soldiers to Chiral Conflict Effects in Helical
Polymers by Acting on the Conformational Composition of the
Comonomers
Katherine Cobos,‡[a] Rafael Rodríguez,‡[a] Emilio Quiñoá,[a] Ricardo Riguera,[a] Félix Freire*[a]
[a]
Dr. K. Cobos, Dr. R. Rodríguez, Prof. E. Quiñoá, Prof. R. Riguera, Prof. F. 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
E-mail: felix.freire@usc.es
Supporting information for this article is given via a link at the end of the document.
Abstract: Different communication mechanisms can be switched
within a copolymer by acting on the conformational composition of the
components and their chirality. Thus, a Sergeant and Soldiers effect
is produced in two diastereomeric copolymer series —poly[(S)-1r-co-
(S)-2(1-r)] and poly[(R)-1r-co-(S)-2(1-r)]— due to the presence in
chloroform of a preferred conformation in (S)-2, and a conformational
equilibrium in 1, where a P helix is induced independently of the
absolute configuration of the Soldier. In THF, the presence of a
conformational equilibrium at the pendants of the two components
produces a reciprocal chiral enhancement effect by copolymerization
of the two monomers, while in DMF, a third chiral to chiral
communication switch is produced due to the presence of a single
conformer at the pendant group of the two components. In such case,
a Chiral Conflict or Chiral Accord effect is produced depending if the
two components induce the same or the opposite helical sense.
selective interconversion of a copolymer into its M or P helices by
the action of external stimuli operating on the Sergeant moiety,
which commands the Soldiers to adopt one helicity or the other.[30]
Thus, doping the achiral homopolymer with a small amount of an
adequate chiral Sergeant is a very convenient way for the
preparation of single-handed helical structures, with applications
in fields such as sensing,[33-34] chiral stationary phases[35-36] or
asymmetric synthesis[37-38] among others.
A step forward in the study of communication mechanisms along
polymeric chains arises from the copolymerization of two chiral
monomers. The resulting copolymer allows us to explore not only
which monomer rules the helix, but also how their absolute
configurations affect the final helical structure. Our group has
recently found that when a chiral monomer with no conformational
preference —chiral Soldier— is copolymerized with another chiral
monomer that exhibits a preferred conformational composition —
chiral Sergeant— (Figure 1), the resulting copolymer is governed
by the classical Sergeants and Soldiers effect.[39-40]
In this way, this “chiral-to-chiral Sergeants and Soldiers effect”
allows the preparation of four diastereomeric copolymers from
chiral Sergeant (Sgt.)/chiral Soldier (Sold.) pairs —[poly-[(R/S)-
Sergeant-co-(R/S)-Soldier]—. In each copolymer, the helical
sense is defined by the chirality of the Sergeant, while the chirality
on the “surface” of the helix depends on the chirality of the Soldier
exclusively. For instance, if the (R)-Sgt. commands a left-handed
(M)-helix, both (R)- and (S)-enantiomers of the Soldier adopt that
(M)-helix although their intrinsic chiralities are the opposite
(Figure 1b). However, if the enantiomeric form of the Sergeant —
(S)-Sgt.— is used, a (P)-helix is induced with either of the
Soldier's two enantiomeric forms —(R)- and (S)-Sold.— (Figure
1).[39]
In addition to the chiral-to-chiral Sergeants and Soldiers effect,
our group has also described a new chiral communication
phenomenon different from the classical Sergeants and Soldiers
effect.[38-41] In the copolymers in which this phenomenon occurs,
the two enantiomeric forms of the Sergeant activate the same
conformation in the chiral Soldier and as a result, the helix is ruled
by the absolute configuration of the Soldier and not by the
Introduction
Dynamic helical polymers, such as poly(phenylacetylene)s
(PPAs), are a fascinating family of long chain macromolecules
whose helical scaffold (sense and/or elongation) can be modified
by the action of different external stimuli.[1-10] This phenomenon
has been shown to allow the selective conversion of axially
racemic polymers —composed by chiral or achiral monomers—
into either of its two helical sense stereoisomers (M or P) by the
action of solvents —polarity and donor parameters—, metal ions,
chiral molecules, temperature or pH.[11-20] On the other hand, if the
starting polymer adopts a preferred M or P helix once is prepared,
those stimuli can be used to produce structural modifications such
as screw sense enhancement or helical inversion.[1-20]
An alternative way to induce a single-handed helical structure in
an axially racemic polymer without altering the environmental
conditions was described by Green and coworkers and denoted
as Sergeants and Soldiers effect.[21-26] They copolymerized an
achiral monomer (Soldier, major component) with a small amount
of a chiral monomer (Sergeant, minor component), and found that
the M or P helical sense of the copolymer was determined
exclusively by the (R)- or (S)- chirality of the Sergeant.[21-32] In the
Sergeants and Soldiers effect, the origin of the helical induction
lies on the conformational restriction suffered by the Soldiers as a
result of the preferred conformation adopted by the Sergeants. In
addition, the combination of the Sergeants and Soldiers effect
with the dynamic behavior of helical polymers makes possible the
enantiomeric form of the Sergeant. For instance, according to this
[40]
mechanism, denoted as Chiral Coalition effect,
all the
copolymers made by the same (S)-Sold. —in the example shown
in Figure 2— show an M helix regardless of the (R)- or (S)-chirality
of the Sergeant. To prepare the opposite P sense in the helix of
1
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10.1002/anie.202009215
Angewandte Chemie International Edition
RESEARCH ARTICLE
the copolymer, the enantiomeric Soldier has to be used,
independently of the absolute configuration of the Sergeant.[40]
Figure 2. (a) Conceptual representation of the Chiral Coalition effect using
Sergeants with either (R)- or (b) (S)-configurations. The same (S)-configuration
of the Soldier is employed in both cases and (M)-helices are obtained. (P)-
helical senses arise when the (R)-Soldier is employed with those same
enantiomeric Sergeants. [Sgt.= Sergeant, Sold.= Soldier].
Results and Discussion
To perform these studies, the 4-ethynylanilides of (R)- or (S)--
methoxy--phenylacetic acid (MPA) were chosen as chiral
Soldiers [monomers (R)- or (S)-1] (Figure 3),[42-47] while the 4-
ethynylanilide of the (S)-mandelic acid (MA) was selected as
chiral Sergeant [monomer (S)-2].[48] The difference between these
two monomers is one substituent at the chiral carbon. Thus, while
monomer 1 bears a methoxy group, monomer 2 possess a
hydroxyl group (Figure 3a and 3b). However, this only apparently
small difference between the two monomers produces a large
difference in the dynamic behavior of the corresponding
monomers and homopolymers.[48]
Monomer 1 [(R)- or (S)-Sold.] is known to have two main
conformations at the (O=)C-C(-O) bond in low polarity solvents:
one with an antiperiplanar (ap) orientation and the other with a
synperiplanar (sp) orientation between the carbonyl and methoxy
groups, in a ratio close to 1:1 (Figure 3a).[46]
Figure 1. (a) Axially racemic polymer obtained from a chiral monomer —m-(S)-
1— that is used as Soldier in the copolymers. M and P helices arise from two
different conformations of the chiral monomer. (b) Conceptual representation of
the chiral-to-chiral Sergeants and Soldiers effect using Sergeants with either
(R)- or (c) (S)-configurations. In the last two cases the same (S)-configuration
of the Soldier is employed. Those same helical senses are obtained when the
(R)-Soldier is employed with those same enantiomeric Sergeants. [Sgt.=
Sergeant, Sold.= Soldier].
The combination of the classical Sergeants and Soldiers effect
(chiral Sgt./achiral Sold.) with external stimuli has proven to be
very useful to make copolymers with P or M senses.[30] However,
this helix inversion process does not work well in copolymers
where the two comonomers are chiral because once an external
stimulus is added, the chiral-to-chiral communication is disrupted,
decreasing the screw sense preference in the copolymer.[39] As a
consequence, it is not possible to obtain the two P and M helical
senses from the same copolymer. To that end and to date, it is
necessary to prepare two different copolymers with opposite
configurations at the Sergeant.
Herein, we will show that different chiral-to-chiral communication
mechanisms can be activated within a chiral copolymer chain by
acting on the conformational composition of the co-monomer
used as chiral Sgt. Moreover, the chiral enhancement effect
induced in the copolymer will also depend on the relative absolute
configurations between the Sergeant and the Soldier. As a result,
for a single chiral Sgt./chiral Sold. pair, it is possible to activate a
complete set of communication mechanisms: Chiral-to-Chiral
Sergeants and Soldiers effect, Chiral Coalition, Chiral Conflict,
Chiral Accord and also a synergistic chiral enhancement effect.
This conformational equilibrium is also present in their
corresponding homopolymers [poly-(R)-1 and poly-(S)-1],
producing in each of them equal amounts of cis-cisoidal P and M
helices. As a result, axially racemic and optically inactive (null CD)
materials are generated despite the configuration of their
stereogenic carbon centers[46] (Figure 3c). On the other hand, in
polar solvents, the equilibrium is shifted towards
a sp
conformation which induces a screw sense excess towards an M
helix for poly-(R)-1 and a P helix for poly-(S)-1. These polymers
can be transformed into chiral materials by the action of external
stimuli such as monovalent or divalent metal ions, which
selectively induce P or M helices in poly-1 by fixing either ap
(monovalent metal ions) or sp (divalent ones) conformations in
the pendants.[46]
On the other hand, monomer 2 [(R)- or (S)-Sgt.] has a major ap
conformation at the (O=)C-C(-O) bond (Figure 3b), which can be
shifted to sp by adding stimuli such as Ba(ClO4)2.[48] The
homopolymer —poly-(R)-2— has a cis-cisoidal structure with a
preferred M helical sense in low polarity solvents — ap pendant—,
while a P helicity is induced in polar solvents due to the presence
of major sp conformations at the pendants (Figure 3d). In poly-
2
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10.1002/anie.202009215
Angewandte Chemie International Edition
RESEARCH ARTICLE
(S)-2, and due to its enantiomeric relationship with poly-(R)-2, a P
helix is induced in low polarity solvents while an M helix appears
in polar solvents (Figure 3d).
O
OH
HN
CHIRAL SERGEANT
(S)-Sgt.
(S)-2
Similar to what happens with the corresponding monomers, a
conformational switch can be produced in the pendant groups by
adding metal ions such as Li+ or Ba2+, which generate either a
chiral amplification or a helix inversion in poly-2.
H
[Rh(nbd)Cl]2
Et3N / THF
+
CHIRAL SOLDIERS
r
1-r
H
n
(R)-1, (S)-1
O
Copolymer series
These two monomers
1 and 2 meet all the necessary
R1
NH
Poly-[(R)-1r-co-(S)-2(1-r)
R1= Ph, R2= H
Poly-[(S)-1r-co-(S)-2(1-r)
]
requirements to show an effective chiral communication
mechanism along a copolymer chain as found in our previous
studies:[37,39-41] 1) similar scaffolds for the parent homopolymers
—i.e., cis-cisoidal—; 2) conformational flexibility at the Soldier —
highly dynamic poly-1—; 3) the presence of a preferred
conformation at the Sergeant —screw sense excess in poly-2—;
4) the same functional group used as connector between the
pendant and the backbone in both Sergeant and Soldier —i.e.,
anilide—.
R2
O
(R)-, (S)- Sold.
]
R1= H, R2= Ph
Figure 4. Monomer and copolymer structures used in this study.
NMR (vinyl protons, = 5.7– 5.8 ppm) and Raman (c.a. 1575,
1340, 1004 cm-1) spectra indicated in all cases the presence of
cis polyene backbones (see SI).[49-51] In addition, DSC
measurements showed traces typical for cis-cisoidal polyene
backbones (see SI).[53]
NMR studies also indicated that chiral Soldier/chiral Sergeant
monomer ratios in the copolymers were coincident with the
feeding mixtures (see SI). Moreover, their random distribution
within the copolymer chain was demonstrated by using the Kelen-
Tüdos[54-55] approach (see SI).
The molecular weights of the copolymers were estimated by GPC
(THF as eluent with polystyrene standards as calibrants; see SI
for details) to be between Mn= 10000 and 40000 with Mw/Mn
values in a 1.2-2.7 range.
Chiral-to-chiral communication mechanisms in the poly-[(S)-
1r-co-(S)-2(1-r)] copolymer series
CD spectra of the poly-[(S)-1r-co-(S)-2(1-r ] copolymer series in
)
several solvents showed the existence of different chiral
communication mechanisms between the two monomers, which
depend on the individual dynamic behavior observed in the
homopolymers of the two copolymer components (Figure 5 and
SI).
In this way, homopolymers poly-(S)-1 and poly-(S)-2 show in
chloroform the formation of an axially racemic helix and a well
folded P helix respectively (Figure 5a).[56-58] CD spectra of the
poly-[(S)-1r-co-(S)-2(1-r)] copolymer series show in this solvent the
classical Sergeants and Soldiers effect, where the chiral Sergeant
[(S)-2] is able to induce a P helix in the chiral Soldier [(S)-1] in a
very effective way —just 3% of the chiral Sergeant [(S)-2] is
enough to induce the maximum helical preference (CD signature
at the vinylic region) in the copolymer chain, r= 0.03— (Figure
5b).[55-56] From the mechanistic point of view, in chloroform this
process is originated by the ap conformation of the Sergeant [(S)-
2] (Figure 5b),[48] which commands the Soldier [(S)-1] to adopt an
ap conformation that in turn induces the same P helix orientation
in the copolymer chain. The conformational composition at the
pendants was determined by fixing their ap or sp conformations
Figure 3. Figure 3. Structure and conformational equilibrium between ap and
sp conformations for monomers (a) (R)- and (S)-1 and (b) (R)- and (S)-2. (c)
Structure of poly-(R)- and poly-(S)-1 and 2. (d) Schematic illustration of the
helical structures adopted by the enantiomeric forms of poly-1 and poly-2 in low
polarity solvents.
by addition of either monovalent or divalent metal ions (see SI).[46-
Next, copolymer series poly[(S)-1r-co-(S)-2(1-r ] and poly[(R)-1r-co-
)
48]
(S)-2(1-r ] (r= 0.9-0.1) were prepared by polymerizing mixtures of
)
In THF, homopolymers poly-(S)-1 and poly-(S)-2 show CD traces
indicative of a screw sense excess towards the P helices [ CD380
(+)] (Figure 5a), [56-58] although their magnitude is moderate. This
fact indicates a slight screw sense excess towards a P helix in
the chiral Sergeant [(S)-2] and the chiral Soldiers [(S)-1 and (R)-
1] in different ratios with [(Rh(nbd)Cl)2] (Figure 4). The other two
diastereomeric copolymer series —poly[(R)-1r-co-(R)-2(1-r ] and
)
poly[(S)-1r-co-(R)-2(1-r
]
)
(r= 0.9-0.1)— bearing the (R)-
both polymers. CD studies for the poly-[(S)-1r-co-(S)-2(1-r
copolymer series in this solvent show that all the copolymers
adopt a preferred P helix, although the magnitude of the CD
]
)
configuration of the Sergeant [(R)-2] were also synthetized
yielding opposite helical senses due to their enantiomeric
relationship (See Figure S19).
3
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10.1002/anie.202009215
Angewandte Chemie International Edition
RESEARCH ARTICLE
spectra is approximately twice that of the original homopolymers
(Figure 5c).
This chiral enhancement effect is observed in all the poly-[(S)-1r-
Finally, analogous studies were carried out in polar solvents such
as DMF or DMSO. In these solvents, homopolymers poly-(S)-1
and poly-(S)-2 adopt helical structures with an M screw sense
preference. Interestingly, in this solvent the magnitude of the CD
spectra is greater for poly-(S)-1 than for poly-(S)-2, which
indicates better folding for the first one.
co-(S)-2(1-r copolymer series, independently of the copolymer
)
composition, which indicates that an effective chiral
communication mechanism is being produced within the
copolymer chain. In this way, a synergistic chiral enhancement
arises due to a reciprocal stabilization of the ap conformers in both
monomer repeating units —(S)-1 and (S)-2— once they are
copolymerized.
CD studies of the poly-[(S)-1r-co-(S)-2(1-r ] copolymer series in
)
DFM show a lack of communication between the two components
of the copolymer. The CD spectra of the different copolymers
along the series vary with the copolymer composition and agree
with the magnitude of the parent homopolymers. This lack of
communication between chiral monomers that promote the same
helical sense into the copolymers is denoted as Chiral Accord.[59]
Thus, within a single chiral copolymer series, three different chiral
communication mechanism are observed —Chiral-to-Chiral
Sergeants and Soldiers effect, Reciprocal Chiral Enhancement
and Chiral Accord—, which are activated depending on the
conformational composition at the pendant groups.
a)
Poly-(S)-1 (Sold.)
10
5
(low polar solvents)
O
(CHCl3, axially racemic)
(THF, P helix)
MeO
O
N
0
N
OMe
H
H
sp
(polar solvents)
-5
ap
sp
(DMF, M helix)
Poly-(S)-1
-10
-15
-20
OMe
O
N
H
Mhelix
Poly-(S)-2 (Sgt.)
Axially Racemic or
300
400
500
2.2. Chiral-to-chiral communication mechanisms in the poly-
slight P helix excess
Wavelength [nm]
[(R)-1r-co-(S)-2( )] copolymer series
1-r
Poly-(S)-2
— (THF, Phelix
)
HO
O
N
CD spectra of the diastereomeric poly-[(R)-1r-co-(S)-2(1-r ] series
O
)
- - (CHCl3, Phelix
)
5
0
N
OH
showed again the existence of different chiral communication
mechanisms between the two monomers in solvents with different
polarity and donor ability such as CHCl3, THF or DMF (Figure 6
and SI). Interestingly, the chiral communication mechanisms that
arise between the two comonomers —(R)-1 and (S)-2— depends
again on their conformational composition in the corresponding
homopolymers.
Thus, in chloroform, poly-(R)-1 is formed by a mixture of P or M
helices in an equal population due to the existence of an
equilibrium between two different conformers in the pendant
group (sp/ap), that induce opposite helical sense in the PPA
(Figure 6a).[46] On the other hand, poly-(S)-2 adopts in chloroform
a screw sense excess towards a P helix due to the presence of a
preferred ap conformer at the pendant (Figure 6a).[48]
H
H
sp
ap
(polar solvents)
(low polar solvents)
-5
Mhelix
Phelix
Poly-(S)-2 (DMF, Mhelix
300 350 400 450
Wavelength [nm]
)
b)
LOW POLAR SOLVENTS : CHCl3
10
Poly-(S)-
Poly[(R)-10.2-co-(S)-20.8
Poly[(R)-10.4-co-(S)-20.6
2
)
]
r = 0.03
Poly[(S)-1r-co-(S)-2(1-r)
]
6
4
2
0
400
5
0
Poly-(S)-
2
O
Poly[(R)-
1r-co-(S)-
21-r] Series
Chiral
Enhancement
O HN
Poly-(S)-
1
300
200
100
0
(S)-1
-5
ap conformation
O
-10
-15
-20
-25
Phelix
Poly[(R)-10.6-co-(S)-20.4
Poly[(R)-10.8-co-(S)-20.2
)
)
NH OH
Poly[(R)-10.93-co-(S)-20.07
Poly[(R)-10.95-co-(S)-20.05
Poly[(R)-10.97-co-(S)-20.03
)
)
)
Phelix
(S)-2
Poly-(R)-
1
ap conformation
100 80 60 40 20
% (S)-2
0
Phelix
300
400
500
Phelix
Wavelength [nm]
“Chiral to Chiral Sergeants and Soldiers”
c)
LOW POLAR SOLVENTS : THF
15
10
5
CD studies of the corresponding poly-[(R)-1r-co-(S)-2(1-r ] series in
Poly-(S)-2
Poly[(S)-10.1-co-(S)-20.9
)
]
Poly[(S)-1r-co-(S)-2(1-r)
]
Poly[(S)-10.2-co-(S)-20.8
Poly[(S)-10.3-co-(S)-20.7
Poly[(S)-10.4-co-(S)-20.6
]
]
6
4
2
chloroform show the activation of the Sergeants and Soldiers
effect and that the chiral Sergeant [(S)-2] is able to induce a P
helix [CD380(+)] in the chiral Soldier [(R)-1] in a very effective way
(r= 0.03). From a mechanistic point of view, Sergeant [(S)-2],
which adopts a preferred ap conformation at the pendant and
induces a P helix on the copolymer, is able to command a sp
conformation on the Soldiers [(R)-1] that also induce the same P
helix on the helix (Figure 6b).
On the other hand, in THF, homopolymers poly-(R)-1 and poly-
(S)-2 show CD traces indicative of screw sense excesses with
opposite helicities —poly-(R)-1 M helix [ CD380 (-)]; poly-(S)-2 P
helix [ CD380 (+)] (Figure 6a)—. The helix induction in both
homopolymers, poly-(R)-1 and poly-(S)-2, is modest, indicating a
low excess of the ap conformer at the pendant group. CD studies
]
]
O
Poly[(S)-10.5-co-(S)-20.5
Chiral
Enhancement
Poly[(S)-10.6-co-(S)-20.4
]
300
200
100
0
O HN
Poly-(S)-2
Poly[(R)-1r-co-(S)-21-r] Series
(S)-1
Poly-(S)-1
ap conformation
O
0
Phelix
NH OH
Poly[(S)-10.7-co-(S)-20.3
Poly[(S)-10.8-co-(S)-20.2
Poly[(S)-10.9-co-(S)-20.1
Poly[(S)-10.93-co-(S)-20.07
Poly[(S)-10.97-co-(S)-20.03
Poly[(S)-10.95-co-(S)-20.05
Poly-(S)-1
]
]
]
-5
(S)-2
Chiral
]
]
]
ap conformation
Enhancement
-10
-15
Phelix
Phelix
“Reciprocal Chiral Enhancement”
0
300
400
500
100 80 60 40 20
% (S)-2
0
Wavelength [nm]
Poly[(S)-1r-co-(S)-2(1-r)
]
d)
POLAR SOLVENTS: DMF
Poly-(S)-2
Poly[(S)-10.1-co-(S)-20.9
Poly[(S)-10.2-co-(S)-20.8
Poly[(S)-10.3-co-(S)-20.7
Poly[(S)-10.4-co-(S)-20.6
]
]
]
]
5
0
Poly[(S)-1r-co-(S)-2(1-r)
]
6
4
2
180
160
140
120
100
80
O
O
Poly[(S)-10.5-co-(S)-20.5
]
Poly-(S)-
Poly[(R)-1r-co-(S)-21-r] Series
Poly-(S)-
2
HN
1
(S)-1
sp conformation
-5
M helix
Poly[(S)-10.7-co-(S)-20.3
Poly[(S)-10.8-co-(S)-20.2
Poly[(S)-10.9-co-(S)-20.1
]
]
]
O
OH
-10
-15
-20
Poly-(S)-
1
NH
(S)-2
sp conformation
0
500
Mhelix
Mhelix
100 80 60 40 20
% (S)-2
0
300
400
Wavelength [nm]
of the poly-[(R)-1r-co-(S)-2(1-r ] series in this solvent reveal that
)
“Chiral Accord”
different communication mechanism have been triggered
depending on the monomer ratios within the copolymer chain,
resulting in the magnification of the CD trace towards either a P
or M helices (Figure 6c). For instance, all the copolymers in a the
poly-[(R)-1<0.3-co-(S)-2>0.7] range adopt a helical structure with a
preferred P sense commanded by monomer (S)-2 and where the
folding of the parent poly-(S)-2 can be improved in the order of
200-300% by doping it with monomer (R)-1. On the other hand,
those copolymers containing monomer (R)-1 in a ratio higher than
Figure 5. a) CD spectra, helical sense and major conformations at the pendants
for poly-(S)-1 and poly-(S)-2 in low polar (THF and CHCl3) and polar solvents
(DMF). CD studies of the poly-[(S)-1r-co-(S)-2(1-r)] series in (b) low polar (CHCl3),
(c) low polar (THF) and (d) polar (DMF) solvents highlighting the conformational
composition of the copolymer components. ECD and UV-Vis measurements
were performed in a 1 mm quartz cuvette. Concentration of homopolymers and
copolymers = 0.3 mg/mL.
90% —poly-[(R)-1>0.9-co-(S)-2<0.1]— produce an
M
helix
4
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10.1002/anie.202009215
Angewandte Chemie International Edition
RESEARCH ARTICLE
commanded by monomer (R)-1, and where the folding of the
parent poly-(R)-1 can be improved in by 200% by doping it with a
small amount of monomer (S)-2 (3-5 %) (Figure 6c). This fact
indicates that a large chiral enhancement towards the P or M
helical senses in THF can be activated throughout the poly-[(R)-
opposite helical senses —e.g., poly-[(R)-1r-co-(S)-2(1-r)], poly-(R)-
1 M helix and poly-(S)-2 P helix—.
Therefore, it can be concluded that playing with the
conformational composition of the two chiral components of a
copolymer series, it is possible to activate/deactivate different
chiral communication effects along polymer chains, which will
allow us to enhance or decrease their folding at our convenience
and depending on the potential application sought for the material.
1r-co-(S)-2(1-r ] series by playing with the monomer ratios.
)
Finally, CD studies of the poly-[(R)-1r-co-(S)-2(1-r ] series were
)
carried out in DMF. In this solvent, the corresponding
homopolymers show well-folded helical structures with opposite
helical senses and similar magnitude —poly-(R)-1 P helix [ CD380
(+)]; poly-(S)-2 M helix [ CD380 (-)] (Figure 6a)—. This fact
indicates that the conformational preferences in both
homopolymers are similar and therefore also means that the
strength of the two monomers within the copolymer chain should
be similar.
a)
Poly-(R)-1 (Soldier)
20
15
10
5
(low polar solvents)
Poly-(R)-1
6
4
2
OMe
O
N
MeO
O
N
(DMF, P helix)
H
H
sp
ap
sp
(polar solvents)
0
O
N
(THF, M helix)
(CHCl3, axially racemic)
-5
OMe
CD studies of the poly-[(R)-1r-co-(S)-2(1-r ] copolymer series in
H
)
Axially Racemic or
slight M helix excess
-10
0
Phelix
300
400
500
DMF show the absence of chiral communication between the two
monomers (Figure 6d). In this case, a Chiral Conflict emerged,[41]
where the two monomers forming the copolymer induce opposite
helical senses within the copolymer chain and identical to those
that they induce in the corresponding homopolymers —monomer
(R)-1 induces a P helix, while monomer (S)-2 induces an M
helix—, which shows the lack of communication between
comonomers along the copolymer chain.
Wavelength [nm]
Poly-(S)-2 (Sergeant)
Poly-(S)-2
5
0
HO
O
N
— (THF, Phelix)
- - (CHCl3, Phelix
O
)
N
OH
H
H
sp
ap
(polar solvents)
(low polar solvents)
-5
Poly-(S)-2 (DMF, Mhelix
300 350 400 450
Wavelength [nm]
)
Mhelix
Phelix
b)
Therefore, we could observe again along this copolymer series —
LOW POLAR SOLVENTS: CHCl3
Poly[(R)-10.97-co-(S)-20.03
]
Poly[(R)-1r-co-(S)-2(1-r)
]
poly-[(R)-1r-co-(S)-2(1-r ]—, how different chiral communication
)
Poly[(R)-1r-co-(S)-2(1-r)
]
r = 0.03
25
20
15
10
5
Poly[(R)-10.97-co-(S)-20.03
]
800
600
400
200
0
Poly[(R)-10.8-co-(S)-20.2
Poly[(R)-10.6-co-(S)-20.4
Poly[(R)-10.4-co-(S)-20.6
Poly[(R)-10.2-co-(S)-20.8
]
]
]
]
effects —Sergeants and Soldiers, Chiral Enhancement or Chiral
Conflict— can be activated depending on the conformational
composition at the pendant groups.
O
O
6
4
2
0
Chiral
enhancement
HN
(R)-1
sp conformation
Poly[(R)-1r-co-
(S)-21-r] Series
O
Phelix
0
Poly-(S)-2
Poly-(R)-1
NH OH
Poly-(R)-
Poly-(S)-
1
-5
Phelix
(S)-2
2
-10
-15
-20
ap conformation
Phelix
100 80
60
40
20
0
“Chiral to Chiral
Sergeants and Soldiers”
300
400
500
Conclusion
% (S)-2 (Sgt.)
Wavelength [nm]
Poly-(R)-1
c)
LOW POLAR SOLVENTS : THF
In conclusion, we have demonstrated that different chiral-to-chiral
communication mechanisms can be activated in a copolymer by
playing with the conformational composition of the two
Poly[(R)-1<0.3-co-(S)-2>0.7
]
O
O
Chiral
enhancement
“Chiral to Chiral
Sergeants and
Soldiers”
HN
(R)-1
Poly[(R)-1<0.7-co-(S)-2>0.3
Sergeants and Soldiers effect
Poly[(S)-1x-co-(S)-21-x
]
400
200
0
Sold. = (R)-1
O
components. Thus, if one monomer shows
a preferred
]
(S)-2
sp conformation
NH OH
Phelix
Poly[(R)-1r-co-(S)-2(1-r)
]
THF
conformation in one solvent [m-(S)-2], while the other [m-(R) or
m-(S)-1] shows an equilibrium between different conformers, a
Sergeants and Soldiers effect emerges and all the copolymers of
the two possible copolymer series —poly-[(R)-1r-co-(S)-2(1-r)] or
poly-[(S)-1r-co-(S)-2(1-r)]— adopt the same P helical structure,
independently on the absolute configuration of the Soldier [m-(R)-
or m-(S)-1].
Poly(10.6-co-20.4
Poly(10.7-co-20.3
Poly(10.4-co-20.6
)
)
)
Sgt. = (S)-2
ap conformation
10
6
Phelix
Phelix
5
0
Poly-(S)-2
Poly-(R)-1
20
4
2
0
100 80
60
40
0
Poly-(R)-1
-5
% (S)-2 (Sgt.)
Poly[(R)-1<0.7
co-(S)-2>0.3
-
Mhelix
]
O
-10
-15
Chiral
enhancement
Poly[(R)-10.8-co-(S)-20.2
Poly[(R)-10.9-co-(S)-20.1
Poly[(R)-10.95-co-(S)-20.05
)
)
O HN
(R)-1
-200
Chiral
coalition
Poly-(S)-2
ap conformation
Poly[(R)-1<0.1-co-(S)-2>0.9
]
O
Mhelix
300
400
500
Wavelength [nm]
NH OH
On the other hand, if the copolymer is made by monomers that do
not produce well folded homopolymers, e.g., poly-1 and poly-2 in
THF, copolymerization of those two monomers can result in a
Reciprocal Chiral Enhancement effect. For instance,
homopolymers poly-(S)-1 and poly-(S)-2 produced helical
structures with poor P helical sense excesses in THF, which can
be increased by 200% by copolymerization of the two monomers.
On the other hand, if m-(R)-1 and m-(S)-2, which induce opposite
helical senses, are copolymerized, the Chiral Enhancement can
be produced in both directions, either P or M, depending on the
monomer ratios within the copolymer.
(S)-2
“Chiral Coalition
or Abnormal Sergeants
and Soldiers effect”
ap conformation
Phelix
Poly[(R)-1>0.9-co-(S)-2<0.1
]
d)
POLAR SOLVENTS: DMF
Poly[(R)-1r-co-(S)-2(1-r)
]
Poly[(R)-1r-co-(S)-2(1-r)
]
O
O
20
15
10
5
Poly-(R)-1
Poly[(R)-10.9-co-(S)-20.1
Poly[(R)-10.7-co-(S)-20.3
Poly[(R)-10.5-co-(S)-20.5
(R)-1
)
)
)
Chiral Conflict
HN
6
4
2
Phelix
Poly[(R)-1r-co-(S)-2(1-r)
Poly-(R)-
1
sp conformation
100
0
Poly-(S)-
2
Phelix
0
O
OH
-5
NH
-10
-15
-20
-25
Mhelix
Poly[(R)-10.3-co-(S)-20.7
Poly[(R)-10.1-co-(S)-20.9
Poly-(S)-2
)
)
100 80 60 40 20
0
(S)-2
% (S)-2 (Sgt.)
sp conformation
-100
Mhelix
300
400
500
Wavelength [nm]
“chiral conflict”
Finally, it was found that if the two monomers that form the
copolymer are well folded, e.g., poly-1 and poly-2 in DMF, a lack
of communication between monomers is observed producing a
Chiral Accord when the two components induce the same helical
sense —e.g., poly-[(S)-1r-co-(S)-2(1-r)], poly-(S)-1 and poly-(S)-2
M helix — or a Chiral Conflict when the two components induce
Figure 6. a) CD spectra, helical sense and major conformations at the pendants
for poly-(R)-1 and poly-(S)-2 in low polar (THF and CHCl3) and polar solvents
(DMF). CD studies of the poly-[(R)-1r-co-(S)-2(1-r)] series in (b) low polar (CHCl3),
(c) low polar (THF) and (d) polar (DMF) solvents highlighting the conformational
composition of the copolymer components. ECD and UV-Vis measurements
5
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10.1002/anie.202009215
Angewandte Chemie International Edition
RESEARCH ARTICLE
were performed in a 1 mm quartz cuvette. Concentration of homopolymers and
copolymers= 0.3 mg/mL.
[29] Y. Nagata, T. Nishikawa, M. Suginome, J. Am. Chem. Soc., 2015, 137,
4070-4073.
[30] J. Bergueiro, F. Freire, E. P. Wendler, J. M. Seco, E. Quiñoá, R. Riguera,
Chem. Sci. 2014, 5, 2170-2176.
[31] Z. Yan, S. Cai, Y. Tan, J. Zhang, C. Yan, T. Xu, X. Wan, ACS Macro Lett.
2019, 8, 789-794.
Acknowledgements
[32] M. A. Mateos-Timoneda, M. Crego-Calama, D. N. Reinhoud, Chem. Soc.
Rev., 2004, 33, 363-372.
Financial support from MINECO (CTQ2015-70519-P), Xunta de
Galicia (ED431C 2018/30, Centro singular de investigación de
Galicia accreditation 2019-2022, ED431G 2019/03, and
postdoctoral fellowship to R. R.) and the European Union
(European Regional Development Fund - ERDF) is gratefully
acknowledged. ‡ K. Cobos and R. Rodríguez contributed equally
to this work.
[33] H. Iida, M. Miki, S. Iwahana, E. Yashima, Chem. Eur. J. 2014, 20, 4257-
4262.
[34] R. Rodríguez, E. Quiñoá, R. Riguera, F. Freire, Chem. Mater. 2018, 30,
2493-2497.
[35] K. Shimomura, T. Ikai, S. Kanoh, E. Yashima, K. Maeda, Nat. Chem.,
2014, 6, 429-434.
[36] D. Hirose, A. Isobe, E. Quiñoá, F. Freire, K. Maeda. J. Am. Chem. Soc.
2019, 141, 8592-8598.
[37] H. Iida, Z. Tang, E. Yashima, J. Polym. Sci., Part A: Polym. Chem. 2013,
51, 2869-2879.
Keywords: Chiral Communication • Poly(phenylacetylene) •
Sergeants and Soldiers • Chiral Coalition • Chiral Conflict
[38] Z. Tang, H. Iida, H.-Y. Hu, E. Yashima, ACS Macro Lett. 2012, 1, 261-
265.
[1]
[2]
[1]
A. Xu, T. Masuda, A. Zhang, Polym. Rev. 2017, 57, 138-158.
[39] K. Cobos, E. Quiñoá, R. Riguera, F. Freire, J. Am. Chem. Soc. 2018, 140,
12239-12246.
E. Yashima, N. Ousaka, D. Taura, K. Shimomura, T. Ikai, K. Maeda,
Chem. Rev. 2016, 116, 13752-13990
[40] S. Arias, R. Rodríguez, E. Quiñoá, R. Riguera, F. Freire, J. Am. Chem.
Soc. 2018, 140, 667-674
[3]
[4]
F. Freire, E. Quiñoá, R. Riguera, Chem. Rev. 2016, 116, 1242-1271.
E. Yashima, K. Maeda, H. Lida, Y. Furusho, K. Nagai, Chem. Rev. 2009,
109, 6102-6211.
[41] M. Alzubi, S. Arias, R. Rodríguez, E. Quiñoá, R. Riguera, F. Freire,
Angew. Chem. Int. Ed. 2019, 58, 13365-13369
[5]
[6]
J. Liu, J. W. Y. Lam, B. Z. Tang, Chem. Rev. 2009, 109, 5799-5867.
E. Yashima, K. Maeda, Y. Furusho, Acc. Chem. Res. 2008, 41, 1166-
1180.
[42] R. Rodríguez, S. Arias, E. Quiñoá, R. Riguera, F. Freire, Nanoscale,
2017, 9, 17752-17757.
[43] S. Arias, F. Freire, E. Quiñoá, R. Riguera, Polym. Chem. 2015, 6, 4725-
4733.
[7]
[8]
[9]
J. G. Rudick, V. Percec, Acc. Chem. Res. 2008, 41, 1641-1652
E. Yashima, K. Maeda, Macromolecules, 2008, 41, 3-12.
E. Yashima, K. Maeda, Helically in Foldamers: structure, properties, and
applications, (Eds: Hecht, S.; Huc, I). Wiley-VCH, Weinheim, Germany
2007, Ch. 11.
[44] S. Arias, F. Freire, E. Quiñoá, R. Riguera, Angew. Chem., Int. Ed. 2014,
53, 13720-13724.
[45] F. Freire, J. M. Seco, E. Quiñoá, R. Riguera, J. Am. Chem. Soc. 2012,
134, 19374-19383.
[10] K. Maeda, E. Yashima, Top. Curr. Chem. 2006, 265, 47-88.
[11] R. Ishidate, A. J. Markvoort, K. Maeda, E. Yashima, J. Am. Chem. Soc.
2019,141, 7605-7614.
[46] F. Freire, J. M. Seco, E. Quiñoá, R. Riguera, Angew. Chem., Int. Ed.
2011, 50, 11692-11696.
[47] J. Bergueiro, M. Núñez-Martínez, E. Quiñoá, R. Riguera, F. Freire,
Nanoscale Horiz., 2020, 5, 495-500.
[12] T. Ikai, R. Ishidate, K. Inoue, K. Kaygisiz, K. Maeda, E. Yashima,
Macromolecules 2020, 53, 973-981
[48] K. Cobos, R. Rodríguez, O. Domarco, E. Quiñoá, R. Riguera, F. Freire,
Macromolecules, 2020, 53, 3182-3193.
[13] S. Leiras, F. Freire, J. M. Seco, E. Quiñoá, R. Riguera, Chem. Sci. 2013,
4, 2735-2743.
[49] K. K. L. Cheuk, B. S. Li, J. W. Y. Lam, Y. Xie, B. Z. Tang, Macromolecules,
2008, 41, 5997-6005.
[14] E. Yashima, K. Maeda, O. Sato, J. Am. Chem Soc., 2001, 123, 8159-
8160.
[50] M. G. Mayershofer, O. Nuyken, J. Polym. Sci., Part A: Polym. Chem.,
2005, 43, 5723-5747.
[15] R. Rodríguez, E. Quiñoá, R. Riguera, F. Freire, Chem. Mater. 2018, 30,
2493-2497.
[51] B. S. Li, K. K. L. Cheuk, L. Ling, J. X. X. Chen, C. Baiand, B. Z. Tang,
Macromolecules, 2003, 36, 77-85.
[16] E. Suárez-Picado, E. Quiñoá, R. Riguera, F. Freire, Chem. Mater. 2018,
30, 6908-6914.
[52] K. K. L. Cheuk, J. W. Y. Lam, L. M. Lai, Y. Dongand, B. Z. Tang,
Macromolecules, 2003, 36, 9752.
[17] E. Suárez-Picado, E. Quiñoá, R. Riguera, F. Freire, Angew. Chem. Int.
Ed., 2020, 59, 4537-4543
[53] L. Liu, T. Namikoshi, Y. Zang, T. Aoki, S. Hadano, Y. Abe, I. Wasuzu, T.
Tsutsuba, M. Teraguchi, T. Kaneko, J. Am. Chem. Soc. 2013, 135, 602-
605.
[18] R. Rodríguez, E. Suárez-Picado, E. Quiñoá, R. Riguera, F. Freire,
Angew. Chem. Int. Ed., 2020, 59, 8616-8622.
[19] R. Rodríguez, E. Quiñoá, R. Riguera, F. Freire, Small, 2019, 15, 1970070.
[20] M. Fukuda, R. Rodríguez, Z. Fernández, T. Nishimura, D. Hirose, G.
Watanabe, E. Quiñoá, F. Freire, Chem. Commun., 2019, 55, 7906-7909
[21] M. M. Green, J. W. Park, T. Sato, A. Teramoto, S. Lifson, R. L. Selinger,
J. V. Selinger, Angew. Chem., Int. Ed. 1999, 38, 3138-3154.
[22] H. Gu, Y. Nakamura, T. Sato, A. Teramoto, M. M. Green, S. K. Jha, C.
Andreola, M. P. Reidy, Macromolecules 1998, 31, 6362-6368.
[23] M. M. Green, N. C. Peterson, T. Sato, A. Teramoto, R. Cook, S. A. Lifson,
Science 1995, 268, 1860-1866.
[54] K. Maeda, M. Muto, T. Sato, E. Yashima, Macromolecules, 2011, 44,
8343-8349.
[55] T. Kelen, F. Tüdös, J. Macromol. Sci. Chem., 1975, 9, 1-27.
[56] B. Fernández, R. Rodríguez, A. Rizzo, E. Quiñoá, R. Riguera, F. Freire,
Angew. Chem., Int. Ed. 2018, 57, 3666.
[57] B. Fernández, R. Rodríguez, E. Quiñoá, R. Riguera, F. Freire, ACS
Omega, 2019, 4, 5233-5240.
[58] L. Palomo, R. Rodríguez, S. Medina, E. Quiñoá, J. Casado, F. Freire, F.
J: Ramírez, Angew. Chem. Int. Ed., 2020, 59, 9080-9087.
[59] S. Sforza, T. Tedeschi, R. Corradini, R. Marcheli, Eur. J. Org. Chem.
2007, 5879–5885.
[24] M. M, Green, M. P. Reidy, R. D. Johnson, G. Darling, D. J. O’Leary, G.
Willson, J. Am. Chem. Soc. 1989, 111, 6452-6454.
[25] Y. Liu, Ch. Chen, T. Wang, M. Liu, Langmuir 2016, 32, 322-328.
[26] V. Jain, K.-S. Cheon, K. Tang, S. Jha, M. M. Green, Isr. J. Chem. 2011,
51, 1067-1074.
[27] S. Arias, J. Bergueiro, F. Freire, E. Quiñoá, R. Riguera, Small, 2016, 12,
238-244.
[28] Y. Nagata, T. Nishikawa, M. Suginome, ACS Macro Lett., 2016, 5, 519-
522.
6
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10.1002/anie.202009215
Angewandte Chemie International Edition
RESEARCH ARTICLE
Entry for the Table of Contents
O
O
O
HN
Chiral
Amplification
Chiral
Amplification
NH
O
(S) -1
(S)-1
Phelix,
O
(THF)
O
OH
5
0
HO HN
NH
(S) -2
-5
(S) -2
97% Soldier
3% Sergeant
-10
-15
-20
Mhelix,
(DMF)
97% Soldier
3% Sergeant
Mhelix
DMF
Phelix
THF
A complete set of Communication Mechanisms —Chiral-to-Chiral Sergeants and Soldiers effect, Chiral Coalition, Chiral Conflict,
Chiral Accord and also a synergistic chiral enhancement effect— can be activated in a chiral copolymer by acting on the
conformational composition and the absolute configuration of the components.
Institute and/or researcher Twitter usernames: @ciqususc, @felixfreirelab
7
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