A Stimuli-Responsive Macromolecular Gear: Interlocking Dynamic Helical Polymers with Foldamers

Article abstract of DOI:10.1002/anie.201915488

Herein, macromolecular gears composed of helical poly(phenylacetylenes) (PPAs) bearing short oligopeptides as pendant groups are described, in which the two structural motifs (framework and substituents) are combined. These gears are obtained by polymerization of the acetylene groups introduced at the C-terminus of short oligopeptides formed by achiral (Aib)_n units (n=1–3) derivatized at the N-terminus by a single enantiomer (R or S) of α-methoxy-α-trifluoromethylphenylacetic acid (MTPA, Mosher's reagent). The chiral information of the MTPA is transmitted to the achiral Aib fragments and, through either chiral tele-induction and/or chiral harvesting mechanisms, is further transferred to the polyene backbones, which adopt preferentially P or M helical senses. Moreover, these materials also show dynamic behavior and respond to the action of external stimuli by either inverting the P/M sense and/or modifying the elongation in fully reversible processes.

Full text of DOI:10.1002/anie.201915488

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
International Edition
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Accepted Article
Title: Stimuli-responsive Macromolecular Gear: Interlocking Dynamic
Helical Polymers with Foldamers
Authors: Felix Freire, Rafael Rodríguez, Esteban Suárez-Picado,
Emilio Quiñoá, and Ricardo Riguera
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201915488
Angew. Chem. 10.1002/ange.201915488
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http://dx.doi.org/10.1002/ange.201915488

10.1002/anie.201915488
Angewandte Chemie International Edition
RESEARCH ARTICLE
Stimuli-responsive Macromolecular Gear: Interlocking Dynamic
Helical Polymers with Foldamers
Rafael Rodríguez‡, Esteban Suárez-Picado‡, Emilio Quiñoá, Ricardo Riguera, 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
felix.freire@usc.es
Supporting information for this article is given via a link at the end of the document
Abstract:
Macromolecular
gears
composed
by
helical
stereochemistry of the copolymer components determines the
helical sense of the polymer chain.
poly(phenylacetylenes) (PPAs) bearing short oligopeptides as
pendant groups are described, where the two structural motifs
(framework and substituents) are combined. These gears are
obtained by polymerization of the acetylene groups introduced at the
C-terminus of short oligopeptides formed by achiral (Aib)n units (n=1-
3) derivatized at the N-terminus by a single enantiomer (R or S) of -
methoxy--trifluoromethylphenylacetic acid, (MTPA, Mosher´s
reagent). The chiral information of the MTPA is transmitted to the
achiral Aib fragments and, through either chiral teleinduction and/or
chiral harvesting mechanisms, is further transferred to the polyene
backbones, which adopt preferentially P or M helical senses.
Moreover, these materials also show dynamic behavior and respond
to the action of external stimuli by either inverting the P/M sense
and/or modifying the elongation in fully reversible processes.
Peptidomimetics are oligomers formed by either non-natural
amino acids or combinations of natural and non-natural amino
acids that fold into helical structures mimicking natural
peptides.[10] Achiral residues can be used as building blocks, and
the selective induction of the P/M helical senses is achieved by
linking (covalent or supramolecular interactions) a chiral amino
acid at one of the two edges —N or C terminus. This phenomenon
named as “domino effect” [11] was described by Inai in oligomers
formed
by
-aminoisobutyric
acid
(Aib)
and
-
and
didehydrophenylalanine.[11]
Toniolo,[11]
Yashima[12]
Clayden[13] have done a great contribution in this field studying the
folding of oligopeptides constituted mainly by achiral 1-
aminocyclohexanecarboxylic acid (ACHC), Aib or Aib/glycine
residues. In these oligopeptides, the screw sense induction is
produced by a chiral amino acid placed at the N or C-termini of
the sequence, whose stereochemistry determines the helical
sense adopted by the foldamer.[10]-[13] Additionally, changes on the
foldamer screw sense can be also obtained by manipulation of
the hydrogen bonds of the helical scaffold, or by using pH or
photochemistry as external stimuli. As a result, frequently, the
changes of helical sense of the oligopeptide requires either
changes on the absolute configuration of the peptide or on the net
number of atoms in the foldamer.[10]-[13]
Introduction
Helical structures are structural motifs frequently observed in
nature that are closely related to the function of molecules.
Classical examples are the -helix in peptides and proteins, the
helices found in polysaccharides or the DNA double helix.[1]
The structure/function relationship found in biomacromolecules is
the main reason for the development during the last decades of
new molecular systems folded into helical structures such as
foldamers or helical polymers, which can act as new biomimetic
functional materials.[2]-[3]
In natural peptides or DNA, the presence of chiral monomers
restricts the possibility of switching their helical sense due to the
different stability of the two possible diastereomeric helices. This
problem can be surpassed using polymers or foldamers
constructed by non-chiral units, which show a low energy barrier
between the two (P/M) helical senses and therefore allowing the
helical inversion by external stimuli.[3] For instance, a preferred
helical sense can be induced in polymers made by achiral
monomers, by using a chiral additive,[4] or by the classical
Sergeants and Soldiers effect.[5]
In previous works, achiral spacers consisting on a glycine or
diglycine fragments were used to explore chiral teleinduction in
poly(phenylacetylene)s (PPAs). In those systems it was found
that by increasing the number of glycine residues from 1 to 2, the
teleinduction decreases dramatically.[14]
Herein we want to demonstrate that it is possible to induce a
screw sense preference in PPAs using achiral spacers that follow
other chiral information transmission mechanism, such as chiral
information harvesting. [15]
Thus, we will show that introduction of the (R)- or (S)--methoxy-
-trifluoromethylphenylacetic acid (MTPA, Mosher reagent) —at
the N-terminus of an achiral Aib oligopeptide— will generate a
twisted structure with a preferred orientation.[16]
In addition, the introduction of a 4-ethynylaniline group at the C-
terminus of these peptides, followed by polymerization of the
alkyne group will produce the corresponding PPAs[17] behaving as
macromolecular gears. In these systems, the chiral MTPA residue
is expected to induce a major P/M orientation in the achiral
oligopeptide, which through either teleinduction and/or chiral
information harvesting mechanisms will result in the adoption of a
preferred P/M screw sense in the polyene main chains (Scheme
In the case of dynamic helical polymers made by chiral monomers,
the helical sense enhancement[6] or inversion[7] can be induced by
external stimuli (e.g.; temperature, solvents, metal ions, etc.),
which act on the conformational composition of the monomer-
repeating unit. An alternative way is to introduce a small amount
of a chiral dopant into the polymer sequence —chiral coalition[8]
and chiral Sergeants and Soldiers effect[9]—, where the
1
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10.1002/anie.201915488
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RESEARCH ARTICLE
1). Moreover, changes in solvent polarity could produce
modifications in the ensemble of the MTPA-(Aib)n conformations,
which should be further transmitted to the PPA as changes on the
elongation and/or sense of the helix. [15], [18]
X-ray studies of (R)-MTPA-(Aib)1-PA crystals obtained from
DCM/hexane solutions revealed the presence of an M twisted
structure stabilized by the presence of an antiperiplanar
conformation between the carbonyl and methoxy group (apOMe) of
the (R)-MTPA residue (Figures 2a and S14-16).
CD studies of (R)-MTPA-(Aib)1-PA in low polar solvents such as
chloroform, show a positive Cotton band that correlates with the
M oriented twisted structure obtained from X-ray studies as
inferred from theoretical studies [TD-DFT (CAM-B3LYP)/3-21G]
Chiral Information
Harvesting
ECD/UV-vis
PPA Output
[19]
(Figure 2a). Additional CD studies in more polar solvents
Screw Sense
Induction
reveal the dynamic character of this monomer, where a CD trace
with a first negative band is obtained (Figure 2b). This structural
change must be produced by a conformational alteration on the
MTPA moiety, which inverts the screw sense of the Aib turn.
Calculated
Chiral
group
X-ray structure
a)
Experimental
PPA main
f (i+1)= 56º
y (i+1) = 39º
chain
MTPA
apOMe
(Aib)n oligomer (n = 1, 2, 3)
M turn,
CHCl3
Scheme 1. Conceptual illustration of the chiral information harvesting
mechanism in a PPA bearing a chiral N-terminal Aib oligomer as pendant group.
torsion: M
(R)-MTPA-(Aib)1-PA
240 260 280 300 320
Wavelength [nm]
Dynamic behavior
Results and Discussion
b)
f (i+1)= - 56º
Calculated
To create a macromolecular gear, first it is necessary to design
and test its different components. Our gear was planned to be
formed by a helically tunable poly(phenylacetylene) skeleton, with
achiral Aib oligopeptides as pendants and possessing at the N-
Experimental
y (i+1)= - 39º
torsion: P
MTPA
terminus
a
switchable chiral fragment (-methoxy-
P turn,
THF
apCF
3
trifluoromethylphenylacetic acid, MTPA) (Figure 1). This chiral
element was chosen because once is directly linked to a PPA, it
responds to polarity changes.[18] As a result, in our gear design,
MTPA should induce a preferred conformation at the Aib
oligopeptides —known to adopt twisted structures such as -turns
or 310 helices[13]— that should work as chiral harvesting promoters.
Thus, we prepared three different H-(Aib)n-COOH oligomers (n=
1, 2, 3) capped at the N-terminus with the chiral (R)-MTPA unit
and at the C-terminus with a 4-ethynilaniline [(R)-MTPA-(Aib)n-
PA] (See SI for synthetic details).
(R)-MTPA-(Aib)1-PA
250
300
350
Wavelength [nm]
Figure 2. a) X-ray structure of (R)-MTPA-(Aib)1-PA and comparison of the
experimental and calculated ECD spectra in CHCl3. b) P twisted structure of
(R)-MTPA-(Aib)1-PA whose calculated ECD trace matches the experimental
one in THF.
Thus, computational studies —[TD-DFT (CAM-B3LYP)/3-21G —
were carried out for a P oriented twist of (R)-MTPA-(Aib)1-PA,
which possess an antiperiplanar conformation between the
carbonyl and the CF3 groups. The (i+1) and (i+1) dihedral
angles were introduced with the same values as those obtained
from the crystal structure but with opposite signs (Figure 2b). The
experimental and the theoretical ECD studies show a very good
match.
2D-NMR (NOESY) showed the presence of sequential NH-NH
cross peaks in polar and low-polar solvents confirming the
presence of twisted structures. Other long-distance NOEs gave
further evidence of predominant peptide conformations (see SI for
full details).
In the case of the oligomer containing two Aib residues —(R)-
MTPA-(Aib)2-PA—, X-ray diffraction showed two different twisted
structures that resemble a -turn —(R)-MTPA-(Aib)2-PA (1) and
(R)-MTPA-(Aib)2-PA (2)— (Figure 3). The two structures are
stabilized by intramolecular hydrogen bonds between i and i+3
residues (Figures 3a) and with antiperiplanar orientations
Figure 1. (a) (R)-MTPA-(Aib)n-PA (n= 1, 2, 3) monomers. (b) (R)-MTPA-(Aib)n-
PPAs (n= 1, 2, 3).
2
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10.1002/anie.201915488
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RESEARCH ARTICLE
a)
between the carbonyl and methoxy groups of the (R)-MTPA
moieties, although the orientation of the twisted (Aib)2 spacers
show opposite P and M directions in both scaffolds ——(R)-
MTPA-(Aib)2-PA (1), M turn and (R)-MTPA-(Aib)2-PA (2), P turn—
(Figure 3a).
X-ray structures
f (i+2) = -57º
y (i+1) = -48º
y (i+2) = -37º
y (i+1) = 45º f (i+2) = 56º
y (i+2) = 41º
f (i+1)= 48º
f (i+1)= -54º
MTPA
apOMe
CD studies of (R)-MTPA-(Aib)2-PA in chloroform (low-polar) and
methanol (polar) show different CD traces, which confirm the
b
-turn: P
dynamic behavior of this monomer. Computational studies[19]
—
b
-turn: M
MTPA
apOMe
TD-DFT (CAM-B3LYP)/3-21G— on the X-ray structure of (R)-
MTPA-(Aib)2-PA (1) —M -turn— showed a good match between
the calculated and the experimental ECD spectra in chloroform
(Figures 3 a,b).
(R)-MTPA-(Aib)2-PA (1)
(R)-MTPA-(Aib)2-PA (2)
b)
Calculated
Experimental
However, the calculated CD trace obtained from (R)-MTPA-
(Aib)2-PA (2) —P -turn— does not match the experimental CDs
obtained in low-polar or polar solvents (Figure 3a). This fact
suggests that this structure is not abundant in solution.
In order to explain which structure contributes to the CD spectrum
obtained in polar solvents, we carried out computational studies
on R)-MTPA-(Aib)2-PA (3) (Figure 3c), which was built from (R)-
MTPA-(Aib)2-PA (1) by changing the -turn from M to P orientation.
Moreover, the MTPA was introduced in antiperiplanar
conformation between the carbonyl and the CF3 (Figure 3c). In this
case, a good match between the experimental and the theoretical
data was obtained (Figure 3c).
2D-NMR (NOESY) showed the presence of sequential NH-NH
cross peaks in polar and low-polar solvents, confirming the
presence of twisted structures. Other long-distance NOEs gave
further evidence of predominant peptide conformations (see SI for
full details).
Calculated
Lowpolarsolvent
Polarsolvent
(R)-MTPA-(Aib)2-PA (2)
(R)-MTPA-(Aib)2-PA (1)
200
250
300
350
200
250
300
350
Wavelength [nm]
Wavelength [nm]
c)
y (i+2) = - 41º
f (i+2) = - 56º
Calculated
Experimental
b
-turn: P
y (i+1) = - 45º
f (i+1)= - 48º
MTPA
apCF
(R)-MTPA-(Aib)2-PA (3)
3
(R)-MTPA-(Aib)2-PA (3)
200
250
300
350
Wavelength [nm]
Interestingly, in the case of (R)-MTPA-(Aib)3-PA, X-ray studies
showed the coexistence in the same crystal unit of two structures
with the two helical senses —P and M— that resemble 310 helices,
stabilized by two consecutive i, i+3 hydrogen bonds (Figures 4a,b).
These two helices are defined by different conformations at the
MTPA moiety: i) (R)-MTPA-(Aib)3-PA (1), antiperiplanar
Figure 3. a) X-ray structures obtained for (R)-MTPA-(Aib)2-PA. b) Comparison
of the experimental ECD spectra obtained in low-polar and polar solvents with
those calculated for (R)-MTPA-(Aib)2-PA (1) and (R)-MTPA-(Aib)2-PA (2). c)
Comparison between theoretical and experimental ECD spectra obtained for
(R)-MTPA-(Aib)2-PA (3).
conformation between the carbonyl and methoxy group (apOMe
associated to the right-handed twist (P) in the oligomer (Figure
4a); ii) (R)-MTPA-(Aib)3-PA (2), antiperiplanar conformation
)
a)
b)
y (i+3) = 54º
MTPA
apCF3
f (i+3)= 52º
f (i+3)= -50º
y (i+3) = -40º
y (i+2)
= 33º
MTPA
apOME
f (i+2)
= -60º
between the carbonyl and the trifluoromethyl group (apCF3
)
responsible for the adoption of a left-handed screw sense (M)
(Figure 4b).
f (i+2)
= 59º
f (i+1)= 52º
y (i+2)
= -30º
y (i+1) = -48º
y (i+1) = 54º
f (i+1)= -54º
Computational studies[19] —TD-DFT (CAM-B3LYP)/3-21G—
(R)-MTPA-(Aib)3-PA (2)
(R)-MTPA-(Aib)3-PA (1)
(P) 310 helix
showed
a good match between the calculated and the
(M) 310 helix
experimental ECD spectrum obtained for (R)-MTPA-(Aib)3-PA (1)
(P helix, apOMe) in chloroform (Figure 4a,c).
c)
d)
Calculated
Calculated
In the case of (R)-MTPA-(Aib)3-PA (2) (M helix, apCF3), also a good
match was observed for the theoretical and the experimental ECD
spectra measured in dichloromethane (Figure 4b, d). Only the first
Cotton effect showed opposite signs —positive in the calculated
and negative in the experimental spectrum—.
Experimental
Experimental
(CHCl3)
(CH2Cl2)
This Cotton band is associated to the MTPA conformational
composition, which can be positive or negative depending on the
relative orientation of the aryl ring respect to the carbonyl group
of the chiral MTPA.[16] Therefore, the MTPA can interfere with the
CD trace associated to the Aib foldamer. This effect has been
previously reported by Clayden´s group in other Aib oligomers.[20]
2D-NMR (NOESY) experiments showed the presence of
sequential NH-NH cross peaks in addition to other long-distance
NOEs, which gave further evidence of the existence of
predominant well-folded peptide conformations in solution (see SI
for full details).
200
250
300
200
250
300
Wavelength [nm]
Wavelength [nm]
Figure 4. X-ray structures of the (a) P and (b) M orientation for (R)-MTPA-(Aib)3-
PA. c) Comparison of the experimental ECD spectra obtained in chloroform with
the one calculated for (R)-MTPA-(Aib)3-PA (1). d) Idem for (R)-MTPA-(Aib)2-PA
(2) in dichloromethane.
3
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RESEARCH ARTICLE
Moreover, Raman studies showed —in the case of (R)-MTPA-
(Aib)3-PA— a band at 1670 cm-1 considered as a 310 helix
marker[21] (see Figure S24).
The construction of the second element of the gear —the polyenic
chain— was addressed by rhodium catalyzed polymerization of
the terminal alkyne contained in the C-terminus of the
monomers.[22]
40
30
20
10
0
a) (R)-MTPA-Aib-PPA
Pendant
(P turn)
b)
(R)-MTPA-Aib-PPA
CHCl3
THF
NMP
Helix inversion
and
elongation
changes
Pendant Screw
Sense Switch
Pendant
(M turn)
-10
-20
Thus, (R)-MTPA-(Aib)n-PA (n= 1, 2, 3) were polymerized into the
corresponding poly(phenylacetylene)s (PPAs) by using a Rh(I)
catalyst. Polymers, (R)-MTPA-(Aib)n-PPA (n= 1, 2, 3) were
obtained in good yields, with high contents of cis double bonds as
300
400
500
PPA (P helix)
low polar solvents
PPA (M helix)
polar solvents
Wavelength [nm]
20
10
0
c) (R)-MTPA-(Aib)2-PPA
d)
= Solvent
Molecules
CHCl3
DMSO
1
inferred by H NMR spectra and Raman (See SI). The number-
Elongation
changes
average molecular weight (Mn) and distribution (Mn/Mw) of the
oligomers was determined by size exclusion chromatography
(SEC) —34525, 2.25; 35660, 2.02; 39980, 2.11 for (R)-MTPA-
-10
-20
Aib-PPA,
(R)-MTPA-Aib2-PPA
and
(R)-MTPA-Aib3-PPA
300
400
500
respectively—.
PPA (M helix)
low polar solvents
PPA (M helix)
polar solvents
Wavelength [nm]
Next, CD studies of (R)-MTPA-(Aib)n-PPA (n=1, 2, 3) were carried
out and showed traces typical for PPA helical structures,[1]
confirming the presence of an effective chiral information
transmission mechanism from the chiral MTPA moiety to the
polyene backbone (Figure 5). This mechanism varies from a chiral
teleinduction to a chiral harvesting process depending on the
length of the achiral spacer. Based on the structural information
obtained from X-ray studies of the monomers (see above),
teleinduction should be active mainly in (R)-MTPA-(Aib)1-PPA
due to the close location of the chiral MTPA towards the polyene
backbone, while chiral harvesting should occur mainly in (R)-
MTPA-(Aib)3-PPA, where the chiral center is placed far away from
the polyene. In the case of (R)-MTPA-(Aib)2-PPA, both
mechanisms could be operative.
Moreover, CD studies showed that (R)-MTPA-(Aib)1-PPA
undergoes a helix inversion accompanied with an elongation of
the polyene by solvent polarity changes (Figures 5a, b). However,
(R)-MTPA-(Aib)2-PPA and (R)-MTPA-(Aib)3-PPA just showed
variations on the stretching of their helical scaffolds with
increasing polarity, maintaining the same helical sense
preference (Figures 5c-f).[23[
e) (R)-MTPA-(Aib)3-PPA
f)
f)
10
3
2
1
CHCl3
THF
DMF
= Solvent
5
0
Molecules
Elongation
changes
-5
CHCl3
THF
DMF
-10
-15
-20
PPA (P helix)
low polar solvents
PPA (P helix and planar)
polar solvents
300
400
500
600
Wavelength [nm]
g)
h)
Elongation changes
CHCl3
DMF
StructuralSwitchinTheSolidState
Non-Polar Polar
CHCl3
CHCl3 /DMF (80:20)
CHCl3 /DMF (60:40)
CHCl3 /DMF (40:60)
CHCl3 /DMF (20:80)
DMF
400
500
Wavelength [nm]
600
Figure 5. (a) Conceptual illustration of the helix inversion and stretching process
of (R)-MTPA-(Aib)1-PPA; (b) CD/Uv-vis spectra depicting inversion/stretching
process. (c) Conceptual illustration of the stretching process of the (R)-MTPA-
(Aib)2-PPA. (d) CD/Uv-vis spectra depicting the helix stretching process. (e)
Schematic illustration of the stretching process of (R)-MTPA-(Aib)3-PPA. (f)
CD/UV-Vis spectra of (R)-MTPA-(Aib)3-PPA in different solvents showing the
three different helical states with different elongation degrees. (g) UV-Vis
experiment and inset picture of the colorimetric change throughout the titration
from compressed to stretched structure (CHCl3 to DMF) of (R)-MTPA-(Aib)3-
PPA. (h) Images of (R)-MTPA-(Aib)3-PPA depicting the structural switch from
compressed to stretched structure in the solid state.
STD 2D-NMR at different mixing times gave us information about
the spatial proximity between functional groups at the pendants.
Similar pattern of cross peaks as those obtained from the
monomers were found in the case of of (R)-MTPA-(Aib)n-PPA (n=
1, 2, 3). These results are in agreement with a stereoregular
structure adopted by the PPA, from which those cross peaks are
also expected.[24]
Finally, while the helix inversion of (R)-MTPA-(Aib)1-PPA by
polarity changes is commanded by conformational changes at the
MTPA moiety, the helical stretching observed in all the polyene
backbones can arise from other phenomena.
Interestingly, although these Aib oligomer-polar solvent
interactions affect the elongation of the PPAs, active CD spectra
are still observed in most cases. Hence, the increase of solvent
polarity produces changes in the ensemble of Aib oligomer
conformations, which include the presence of some unfolding
states. However, the overall orientation of the achiral spacer —
Aib oligomer— is still biased into a preferred screw sense due to
the presence of the (R)-MTPA moiety placed at the N-terminus.
All these structural changes are fully reversible and are also
operative in the solid state. For instance, the yellow to red change
observed for (R)-MTPA-(Aib)3-PPA when the polarity increased is
observed in both the liquid and solid stated (Figures 5g, h). The
latter transformation takes place under different solvent
atmospheres.
Six different PPAs were designed and synthetized to clarify this
point. Two of them contain a racemic mixture of MTPA —(rac)-
MTPA-(Aib)n-PPA (n= 2, 3), two contain an amino water-soluble
group at the N-terminus of the Aib oligomer —H2N-(Aib)n-PPA (n=
2, 3), and other two are the H2N-(Aib)n-PPA (n= 2, 3) oligomers
N-capped with dodecanoyl chloride —12C-(Aib)n-PPA (n= 2, 3)—.
In all cases, the CD spectra were null as expected, and UV-Vis
studies revealed a bathochromic shift of the polyene backbone
when the polarity increased (Figure S33). Therefore, this fact
indicated that the interaction of the polar solvents with the Aib
residues is the phenomenon responsible of the helical stretching
observed in all Aib containing PPAs.
4
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Conclusion
Keywords: Chiral Harvesting • Helical Polymer • Screw Sense
Control • Chiral Teleinduction • Poly(phenylacetylene)s
We have demonstrated that the introduction of a single MTPA
enantiomer at the N-terminus of short Aib oligomers, capped at
the C-terminus with a 4-ethynilaniline —(R)-MTPA-(Aib)n-PA—,
results in the formation of twisted structures with a preferred
screw sense confirmed by X-ray, 2D-NMR, CD studies and TD-
DFT calculations. This helical sense excess can be altered —
reduced or inverted— by the action of solvents used as external
stimuli, which modify the conformational composition at the
MTPA-(Aib)n moiety.
Polymerization of these MTPA-(Aib)n-PA oligomers yielded the
corresponding helical poly(phenylacetylene)s (PPAs) with a
preferred screw sense. Depending on the size of the achiral Aib
spacer, two different mechanism of chiral information
transmission are envisioned: 1) Chiral teleinduction. This chiral
transmission mechanism emerges in PPAs containing a short Aib
oligomer —MTPA-(Aib)1-PPA—. In this polymer, the spatial
location of the aryl ring of the MTPA moiety is the one that induces
a helical sense excess in the PPA backbone due to the proximity
between the chiral residue and the polyene. 2) Chiral harvesting.
This mechanism is produced in PPAs bearing larger Aib
oligomers used as spacers —MTPA-(Aib)3-PPA—. In this polymer,
the chiral MTPA fragment is placed in a remote position and
therefore, the helix induction via chiral teleinduction is negligible.
Hence, the helix induction is produced via a two-step process,
where the chiral information of the MTPA is transmitted to the
achiral Aib fragment and harvested by the polyene backbone,
which adopts preferentially a P or M helical scaffold.
Interestingly, in the case of MTPA-(Aib)2-PPA, the two helical
induction mechanisms —teleinduction and harvesting— can act
simultaneously due to the size of the achiral spacer.
Moreover, different dynamic behavior was observed for the three
(R)-MTPA-(Aib)n-PPA (n= 1, 2, 3). While (R)-MTPA-(Aib)1-PPA
can invert its helical sense when the solvent polarity increases,
(R)-MTPA-(Aib)2-PPA and (R)-MTPA-(Aib)3-PPA just show a
decrease in the screw sense excess, probably due to the increase
of unfolded structures at the Aib moiety.
This helix inversion or decrease in the screw sense excess is
always accompanied with an elongation change at the polyene
backbone. This variation on the helical stretching is not related to
conformational changes at the MTPA moiety but produced by
interactions between the solvent and the Aib oligomers as inferred
from achiral Aib containing PPAs.
These studies confirm that chiral harvesting approaches can be
useful tools to control the structure of helical polymers and related
macromolecules with potential applications in fields such as
sensing, asymmetric catalysis, chiral stationary phases among
others.
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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 the
European Regional Development Fund (ERDF) is gratefully
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Entry for the Table of Contents
Chiral Information Harvesting
2
2
Chiral Group
Screw Sense
Induction
1
1
ECD/UV-vis
PPA Output
Macromolecular gear. Long-range chiral induction is produced in poly(phenylacetylene)s (PPAs) that bear achiral Aib oligomers
capped at the N-termini with a chiral acid (Mosher’s reagent). The chiral residue induces screw sense preferences into the different Aib
oligomers which are harvested by the PPAs adopting an excess of a single-handed helical structure.
Institute and/or researcher Twitter usernames: @ciqususc, @felixfreirelab,
7
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