# Light- and Temperature-Controlled Hybridization, Chiral Induction and Handedness of Helical Foldamers

Youssef Aidibi, Soussana Azar, Louis Hardoin, Marie Voltz, Sébastien Goeb, Magali M Allain, Marc Sallé, Romain Costil, Denis D Jacquemin, Ben Feringa, et al.

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## ► To cite this version:

Youssef Aidibi, Soussana Azar, Louis Hardoin, Marie Voltz, Sébastien Goeb, et al. Light- and Temperature-Controlled Hybridization, Chiral Induction and Handedness of Helical Foldamers. Angewandte Chemie International Edition, 2024, 64 (1), pp.e202413629. 10.1002/anie.202413629. hal-05100475

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Submitted on 6 Jun 2025

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# Light- and Temperature-Controlled Hybridization, Chiral Induction and Handedness of Helical Foldamers

Youssef Aidibi, Soussana Azar, Louis Hardoin, Marie Voltz, Sébastien Goeb, Magali Allain, Marc Sallé, Romain Costil, Denis Jacquemin,* Ben Feringa,* and David Canevet*

**Abstract:** Helical foldamers have attracted much attention over the last decades given their resemblance to certain biomacromolecules and their potential in domains as different as pharmaceutics, catalysis and photonics. Various research groups have successfully controlled the right- or left- handedness of these oligomers by introducing stereogenic centers through covalent or non-covalent chemistry. However, developing helical structures whose handedness can be reversibly switched remains a major challenge for chemists. To date, such an achievement has been reported with light-responsive single-stranded foldamers only. Herein, we demonstrate that grafting a unidirectional motor onto foldamer strands constitutes a relevant strategy to i) control the single or double helical state of a foldamer, ii) switch on the chiral induction process from the motor to the helical strands and iii) select the handedness of double helical structures through photochemical and thermal stimulations.

## Introduction

Foldamers constitute a class of synthetic oligomers that are designed to fold into well-defined conformations through noncovalent interactions.[1,2] Among the wide diversity of foldamers, helical structures have been the focus of a growing interest in the scientific community,[3-5] which is notably inspired by the naturally occurring helical structures observed both in nucleic acids and proteins. This particular attention also stems from the singular features of helices, which structure may be tuned in terms of diameter, length, pitch (i.e. vertical distance between consecutive turns), and handedness.[6,7] Helical foldamers are indeed chiral molecular architectures, which display either right- or left-handed conformations.

Since the chiral nature of polyisocyanides was described by Millich and co-workers in 1969,[8] these appealing helical structures have been applied in research fields as different as pharmaceutics,[9] catalysis,[10,11] sensors,[12] or linear and nonlinear optics.[13-15] Over the last decades, this potential prompted various research groups to make extensive efforts to develop hundreds of chiral foldamers derived from either biotic or abiotic monomers.[4] As far as geometrical attributes of helices are concerned, another remarkable trait of helical foldamers lies on the possible association of single helices to form multi-stranded structures.[16] This phenomenon, often named hybridization,[17] has allowed for important achievements in host-guest chemistry,[18] molecular machinery,[19] or self-assembled materials.[20]

In solution, the behavior of helical foldamers is largely governed by supramolecular interactions, explaining why it is strongly influenced by the chemical environment and why their stimuli-responsive nature has been explored in different ways. Varying the solvent composition, the temperature or the concentration constituted the first strategies to control foldamers in solution.[21,17] These parameters were shown to be relevant to drive folding-unfolding processes,[22-24] tune the molar fractions of single and multiple helices[16,25] or to induce a preferential handedness in the case of chiral solvents.[26-28] More recently, similar achievements were also reported through acid-base reactions[24,29-33] or by introducing well-suited guests.[34-41]

To overcome the limitations of these strategies, be that in terms of reversibility or kinetics, current efforts are dedicated to the development of stimuli-responsive helical foldamers that can be addressed through electro-[12,42] or photochemical stimulations. Regarding the latter, various research teams have reported that the folding process of

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<footnote>[*] Dr. Y. Aidibi, S. Azar, L. Hardoin, M. Voltz, Dr. S. Goeb, M. Allain, Prof. M. Sallé, Prof. D. Canevet
Univ Angers, CNRS, MOLTECH-ANJOU, F-49000 Angers, France
E-mail: david.canevet@univ-angers.fr

Dr. R. Costil, Prof. B. Feringa
Stratingh Institute for Chemistry, Zernike Institute for Advanced Materials
University of Groningen, Nijenborgh 49747 AG Groningen, Netherlands
E-mail: b.l.feringa@rug.nl

Prof. D. Jacquemin
Nantes Université, CNRS, CEISAM UMR 6230, 44000, Nantes, France
E-mail: denis.jacquemin@univ-nantes.fr

Prof. D. Jacquemin
Institut Universitaire de France (IUF), 75005, Paris, France</footnote>

<footnote>© 2024 The Author(s). Angewandte Chemie International Edition published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution Non-Commercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.</footnote>
foldamers into helical conformations can be driven through
light irradiation, provided the insertion of photoresponsive
units within the foldamer backbone.[43-54] For instance, Flood
and collaborators have demonstrated that the azobenzene
photoswitch is valuable to govern the double helix formation
of foldamers and hence, their anion recognition
properties.[55-57] Given the importance of chiral species, it is
not surprising that researchers have also recently started
developing helical foldamers with photocontrolled handed-
ness. In this context, Clayden, Moretto and their teams have
notably designed oligomers grafted with a photoisomerisable
maleamide/fumaramide unit, which allowed for controlling
an intramolecular chiral induction process[58] or the catalytic
activity of single-stranded foldamers.[59] In the same vein,
Huc and co-workers showed in 2021 that the handedness of
a supramolecular assembly made up of a single-stranded

dithienylethene-containing foldamer and a carbohydrate
could be inverted through photocyclization.[60]

In this context, we decided to explore the concept
represented in Figure 1 with helical oligomers that hybridize
to form duplexes connected to a unidirectional rotary
motor[61-64] acting both as chiral inducer and hybridization
switch. Thanks to the light- and temperature-controlled
configurational and conformational isomerism of the motor,
we demonstrate here that it is possible i) to control the
single or double helical state of foldamer strands, ii) to
switch on the chiral induction process from the motor to the
foldamer skeleton through *trans*-to-*cis* photoisomerization,
and iii) to reversibly control the (*P*',*P*') or (*M*',*M*') double
helix handedness both photochemically and thermally.

**Results and Discussion**

Design and Synthesis

To this end, we selected the first-generation unidirectional
rotary motor (Scheme 1) described by some of us since it is
fully controlled photochemically and thermally, potentially
providing access to four distinct states differing by their *cis*
or *trans* configurations and their (*P*,*P*) or (*M*,*M*) chirality
(Figure 1). On the other hand, the oligopyridine dicarbox-
amide skeleton (Scheme 1) was selected since i) it displays a
stable helical conformation in most organic solvents thanks
to a collection of hydrogen bonds and aromatic interactions,
ii) it forms double helices with moderate equilibrium
constants, iii) relatively long oligomers can be synthesized
according to reliable synthetic pathways, iv) different func-
tional groups can be grafted at both extremities in a
straightforward manner thanks to orthogonal protecting
groups. In this framework, an oligomer including eight

<figure><img src="image_5.png" /><figcaption>**Figure 1.** Schematic representation of the explored concept with (M,M)-trans 1 and (P,P)-cis 1. The M and P configurations correspond to the handednesses of the motor unit (—C=C—C=CH₃ sequences). The configurations of the foldamer helices will be denoted *P'* and *M'*. The asymmetric carbon atoms display S configurations, making the (S,S,P,P,cis) and the (S,S,M,M,cis) pseudo-enantiomers.</figcaption></figure>

<figure><img src="image_6.png" /><figcaption>**Scheme 1.** Synthesis of foldamer-motor conjugates (M,M)-trans 1, mono-(M,M)-trans 1' and (M,M)-cis 1 through copper-catalyzed azide-alkyne cycloaddition.</figcaption></figure>
pyridyl rings (alkyne **2**, Scheme 1) was designed to ensure the formation of two loops. In addition, a strategy based on the copper-assisted azide-alkyne cycloaddition (CuAAC) was set up to efficiently graft foldamer chains on the motor unit. Alkyne **2** was synthesized according to a twelve-step procedure with an overall yield of 43% (Scheme S1). In parallel, the carboxylic acid functions of the motor moiety,[65] in the *cis* or in the *trans* configuration, were activated with oxalyl chloride in the presence of a catalytic amount of dimethylformamide to synthesize diazides **3** and **4** with good yields (Scheme S2).[66] Once the different precursors were isolated, the final steps were carried out in standard CuAAC conditions. This led to the target foldamer-motor conjugates (*M*,*M*)-trans **1** and (*M*,*M*)-cis **1** with 84 and 73% yields, respectively. We underline that both derivatives were purified by recycling size-exclusion chromatography (eluent: chloroform) to reach high purities. This purification process also allowed the isolation of **mono-**( *M*,*M*)-trans **1'** (12% — Scheme 1), which served as a reference to understand these sophisticated systems. Along the different synthetic steps, single crystals of intermediates **4** and **11**, as well as foldamer **2**, were obtained and studied by X-ray diffraction (Figures 2, S1 and S2, Table S1).[67] Apart from confirming the chemical structures of both derivatives, these analyses did show the formation of two-loop helices in the case of foldamer **2** in the solid state and confirmed the (*M*,*M*) helical configuration of the motor unit in **4**.

<figure><img src="image_7.png" /><figcaption>**Figure 2.** Crystallographic structure of foldamer **2**. A single handedness (*P*) is presented but both helicities are observed in the crystal structure (centrosymmetric space group *P*2₁/*n*).</figcaption></figure>

<figure><img src="image_8.png" /><figcaption>**Figure 3.** ¹H NMR spectra of foldamer (*M*,*M*)-trans **1**, **mono-**(*M*,*M*)-trans **1'** and foldamer (*M*,*M*)-cis **1** (*C* = 3.4 mM, CDCl₃, 298 K, 300 MHz).</figcaption></figure>

**¹H and DOSY NMR Spectroscopy**

Dimethylsulfoxide-d₆ constitutes a particularly valuable solvent to study oligopyridine dicarboxamide foldamers, since it is known for impeding double helix formation. This facilitated the initial characterizations of (*M*,*M*)-trans **1**, (*M*,*M*)-cis **1** and **mono-**( *M*,*M*)-trans **1'** and showed that all three derivatives were obtained (see Figure S3 and experimental details in the Supporting Information file).

In chloroform-*d* (C=3.4 mM, 298 K, 300 MHz—Figures 3 and S4), the situation proved different. **Mono-**( *M*,*M*)-trans **1'**, which cannot form an intramolecular duplex, exhibits a single set of signals beyond 10.2 ppm for amide protons, characteristic of a single helical state for such foldamer strands.[68] On the other hand, the ¹H NMR spectrum of (*M*,*M*)-trans **1** recorded under the same conditions shows two significant differences: the spectrum has low resolution, and appears more complex with the presence of additional low-intensity signals (e.g. δ= 10.2 ppm). In order to assign the latter, variable concentration ¹H NMR experiments were conducted (Figure S5). These experiments revealed that these signals disappear at low concentrations, suggesting the formation of a supramolecular polymer through foldamer strand hybridization at high concentrations. This was further confirmed by DOSY NMR spectroscopy (Figures S6–S8), which evidenced an increase of the diffusion coefficient upon diluting solutions of (*M*,*M*)-trans **1** in chloroform-*d* (from 11.0 to 1.0 mM).

In the case of (*M*,*M*)-cis **1**, a slow exchange at the NMR timescale was observed as well (Figures 3, S4 and S9). One set of signals can clearly be assigned to foldamer strands in their single helical state, since it displays downfield-shifted signals and poor resolution, as observed for **mono-**( *M*,*M*)-trans **1'**. In contrast, the second well-resolved set appears at lower chemical shifts, which is typical of hybridized foldamers.[25] Variable-concentration NMR experiments (Figure S9) proved again valuable, since these showed that the characteristic signals of the double helix consistently and distinctly appeared, even at concentrations as low as 2.5×10⁻⁴ M, and that no significant variation of integrations occurs along this experiment. Thereby, (*M*,*M*)-cis **1** appears to undergo a conformational equilibrium in chloroform, which involves an intramolecular single-to-double helix interconversion with relatively slow kinetics of exchange.

In our exploration of the concept sketched in Figure 1, it appeared relevant to shift this equilibrium towards a fully hybridized state. This was performed by preparing solutions of (*M*,*M*)-cis **1** in mixtures of chloroform and acetonitrile. As reported earlier[42] and shown in Figure S10, increasing the ratio of acetonitrile up to 1/1 leads to the progressive and complete disappearance of the single helices (δ > 10.2 ppm), including at concentrations as low as 5×10⁻⁴ mol.L⁻¹ (Figure S11).[69] In addition, similar experiments were performed with (*M*,*M*)-trans **1** in a chloroform-acetonitrile (1/1 *v*/*v*) mixture. The corresponding ¹H NMR spectra display a poor resolution (Figure S13), suggesting the formation of aggregates. DOSY NMR spectroscopy (Figure S14) showed that higher diffusion coefficients are
measured at lower concentrations (from 11.2 to 1.0 mM) and hence, that intermolecular interactions also take place in this solvent mixture with the *trans* derivative.

## UV Absorption, Circular Dichroism and Theoretical Calculations

Absorption in the UV range and chiral induction from the motor to the foldamer strands constitute a requisite for the proposed concept. This is why (M,M)-trans **1**, (M,M)-cis **1**, alkyne **2** and diazides **3** and **4** were first studied by UV absorption and circular dichroism spectroscopies at concentrations excluding intermolecular duplex formation (below 10⁻⁵ mol.L⁻¹). All derivatives display broad absorption bands between 280 and 380 nm (Figure S15). The UV absorption spectra of foldamer-containing derivatives display similar shapes, which is reasonable considering the relatively high absorption ability of oligopyridine dicarboxamide strands in comparison with the motor unit. Nevertheless, we note that a subtle shoulder is observed in the case of (M,M)-cis **1** (λ≈330 nm), which is consistent with the slightly red-shifted absorption of the motor unit in its cis configuration.[⁶⁵]

While absorption measurements provided little information, circular dichroism analyses afforded valuable insights. The ECD spectra of diazide **3**, (M,M)-trans **1**, and mono-(M,M)-trans **1'** showed similar shapes (Figure S16), indicating that no chiral induction process from the motor to the foldamer strand is at play when the motor is in the *trans* configuration. In contrast, their *cis* analogues—diazide **4**, (M,M)-cis **1** and the photo- and thermally generated mono-(M,M)-cis **1'**—displayed different ECD signatures (Figure 4). Diazide **4** and mono-(M,M)-cis **1'** display similar chiroptical features, indicating that the helical state of the foldamer is not affected by the presence of the chiral motor and hence, that chiral induction does not occur. Conversely, a strong negative Cotton effect was observed at λ=330 nm

for (M,M)-cis **1**. Since this spectral feature cannot be attributed to electronic transitions centered on the motor (see CD spectrum of **4** on Figure 4), and given the UV absorption spectrum of alkyne **2** (Figure S15), this signal can only be ascribed to the foldamer backbone, adopting a preferential helical chirality. In short, a clear phenomenon of chiral induction is observed when the motor presents a *cis* configuration and both foldamer strands are oriented towards the same direction and hybridize. This result is in sharp contrast with the previously reported behavior of motor-helicate conjugates.[⁶⁵] To identify the preferential helicity of the foldamer strands in (M,M)-cis **1**, quantum chemical calculations were led on that system in addition to the corresponding (P,P)-cis **1**. In more details, the ground state geometries (Figure S17) were optimized through Density Functional Theory (B3LYP-D3BJ/def2-SVP) and the spectral features were simulated according to time-dependent calculations (PCM-B3LYP/6-31+G(d)). A clear agreement was found between simulated and experimental data, be that in terms of peak position and molar circular dichroism Δε intensity. These calculations demonstrate that the main electronic circular dichroism band is composed of a very large number of excited states, almost all of them being related to cumbersome molecular orbitals combos. For (M,M)-cis **1**, theory predicts an ECD band peaking at ca. 340 nm with a Δε of −128 L.mol⁻¹.cm⁻¹ (Figure S10) in good agreement with the measured values (Figure 4) and in the same range as those for previously reported examples.[³²,⁷⁰] Thereby, a (M',M') configuration could be assigned to the helical foldamer strands in (M,M)-cis **1**. Noteworthily, the simulated molar circular dichroism values, which are calculated for the enantiopure structure, correspond to 66% of the experimental one, suggesting that the chiral induction process from the motor part to the foldamer duplex is efficient.

## Behaviour under Photochemical & Thermal Stimulation

Considering that our main objective consisted in controlling the double helix handedness of a foldamer-motor conjugate, our attention mostly focused on the photochemical and thermal inter-conversion of (M,M)-cis **1** into its (P,P)-cis **1** analogue. (M,M)-trans **1** was used as a reference whereas (P,P)-trans **1**, a metastable compound at room temperature, was not characterized. At this stage, we underline that irradiating (M,M)-cis **1** at room temperature should directly lead to the (P,P)-cis **1** analogue, since the (P,P)-trans motor obtained after Step **1** is not stable at this temperature and undergoes a conformational change (Step **2**) to reach the (M,M)-trans configuration, which is finally photo-converted into the (P,P)-cis **1** isomer (Step **3**).

With this in mind, photochemical stimulations (λ<sub>exc</sub> = 313 nm) of (M,M)-trans **1** (step 3) and (M,M)-cis **1** (steps 1, 2 and 3) were performed (C = 8.7×10⁻⁶ M in CHCl₃/CH₃CN (1/1 v/v)) and similar evolutions of the UV absorption spectra were noticed (Figures 5 and S18). The absorption band centered at 310 nm decreased, while a shoulder appeared at lower energies. The UV-visible absorption

<figure><img src="image_9.png" /><figcaption>**Figure 4.** CD Spectra of (M,M)-cis **1** (8.7×10⁻⁶ mol.L⁻¹), (M,M)-cis diazide **4** (4.0×10⁻⁵ mol.L⁻¹) and mono-(M,M)-cis **1'** (obtained after irradiation and heating of mono-(M,M)-trans **1'**, 8.5×10⁻⁶ mol.L⁻¹) recorded in CHCl₃/CH₃CN (1/1, v/v).</figcaption></figure>
<figure><img src="image_10.png" /><figcaption>**Figure 5.** Evolution of the UV/Visible absorption spectrum of a solution of</figcaption></figure>

spectra obtained after irradiation of solutions of (M,M)-
**trans** 1 and (M,M)-**cis** 1 do overlap, suggesting that the same
isomer is obtained irrespective of the configuration of the
starting material (Figure S19).

In this context, CD spectroscopy provides an unambig-
uous identification of the obtained stereoisomer formed
upon stimulation of the unidirectional rotary motor. When
considering solutions of (M,M)-cis 1, comparing the CD
spectra before and after excitation clearly demonstrates an
inversion of the foldamer helicity (Figure 6): the (P,P)-cis
analogue is generated in such conditions, which leads to a
light-promoted double helix inversion and hence, to a (P',P')
duplex configuration. At this stage, one can note that the
CD spectra presented in Figure 6 are not mirror images,
because both derivatives are actually pseudo-enantiomers:
(S,S,M,M,M',M') for (M,M)-cis 1 and (S,S,P,P,P',P') for
(P,P)-cis 1. In this regard, comparing the CD signatures of
reference compound 5 (or diazide 4) in its (P,P) and its
(M,M) configurations proves relevant (Figure 7): one can

<figure><img src="image_11.png" /><figcaption>**Figure 7.** a) Chemical structure of reference compound **5**. b) Evolution of the CD spectrum of a solution of diazide **4** (8.5×10⁻⁶ mol·L⁻¹, CHCl₃/CH₃CN (1/1, ν/ν)) under irradiation (λ=313 nm). c) Evolution of the CD spectrum of a solution of (M,M)-**cis** **5** in the same conditions. d) Photoconversions as a function of the time of irradiation for (M,M)-**cis** **1**, diazide **4** and (M,M)-**cis** **5** in the same conditions.</figcaption></figure>

observe that (M,M)-cis derivatives display a molar circular
dichroism Δε close to 0 L.mol⁻¹.cm⁻¹ at λ=330 nm, while
their photogenerated (P,P)-cis analogues show negative Δε
values inferior to −20 L.mol⁻¹.cm⁻¹. Thereby, the positive
CD response of the (P',P') double helical foldamer structure
in (P,P)-cis 1 is partially compensated by the negative
dichroic effect of the motor in its (P,P)-cis configuration at
this wavelength.

In order to get insight into the impact of foldamer
strands on the kinetics of handedness inversion, photo-
isomerization experiments (Figure 7) were performed in the
same conditions (concentration, source, position, orientation
and temperature) with (M,M)-cis 1, diazide 4 and reference
(M,M)-cis 5 (Figure 7a). Following the evolution of the
photoconversions as a function of time (Figures 6 and 7b-d)
showed that both diazide 4 and (M,M)-cis 5 reached the
photostationary state in about 200 s. Interestingly, this was
only achieved after 1200 s in the case of (M,M)-cis 1,
highlighting the slower dynamics of this system. Different
hypotheses can be formulated to explain this behavior: the
higher steric hindrance and the stabilization of double
helices through aromatic interactions could result in a higher
energetical barrier, thus slowing down the double helix
inversion; alternatively, energy transfer processes from the
motor to the foldamer strand could also lead to a decrease
of the photoisomerization quantum yield.

As mentioned above, no chiral induction from the motor
to the foldamer is observed in the *trans* configuration, when
foldamer strands are in the single helical state. This actually
opens the possibility to switch on the chiral induction
process from the motor to the foldamer strands by photo-
converting (M,M)-*trans* **1** into the corresponding (P,P)-*cis* **1**
stereoisomer. As a matter of fact, a strong positive Cotton
effect did appear at 330 nm (Figures 8 and S20a) upon
irradiation of (M,M)-*trans* **1** at λ<sub>exc</sub>=313 nm. The corre-
sponding CD spectrum nicely overlays with the one of

<figure><img src="image_12.png" /><figcaption>**Figure 6.** Evolution of the CD spectrum upon photoconversion of (M,M)-cis 1 into (P,P)-cis 1 (8.5×10⁻⁶ mol·L⁻¹) in CHCl₃/CH₃CN (1/1, ν/ν).</figcaption></figure>
<figure><img src="image_13.png" /><figcaption>**Figure 8.** CD Spectra of (M,M)-trans **1**, (P,P)-cis **1** (obtained by irradiation of (M,M)-trans **1**) at λ = 313 nm and (M,M)-cis (obtained by heating the solution of (P,P)-cis at 55 °C during 6 hours) in CHCl₃/CH₃CN (1/1, ν/ν).</figcaption></figure>

<figure><img src="image_14.png" /><figcaption>**Figure 9.** Evolution of the CD spectra of solutions of a) (P,P)-cis **1**, b) (P,P)-cis **4** and c) (P,P)-cis **5** upon heating at 55 °C (C = 8.5×10⁻⁶ mol·L⁻¹, CHCl₃/CH₃CN (1/1, ν/ν)). d) Evolutions of the conversions as a function of time.</figcaption></figure>

(P,P)-cis **1** (Figure S21), obtained after photoexcitation of (M,M)-cis **1** (Figure 6), which definitely demonstrates both the formation of a double helical structure and its (P',P') configuration. Noticeably, under the same conditions, the photostationary state was reached in about 240 s, i.e., significantly faster than in the case of (M,M)-cis **1** (Figure S20b).

To come full circle (Figure 1), solutions of photogener-
ated (P,P)-cis 1 were heated up to 55°C during few hours,
which induced a clear inversion of the CD spectrum (Fig-
ure 8). The corresponding CD spectra, obtained after
irradiation and heating of (M,M)-trans 1 on one hand, and
as synthesized (M,M)-cis 1 on the other hand, are similar,
which indicates that the thermal isomerization of (P,P)-cis 1
leads to the regeneration of (M,M)-cis 1 upon simple
warming (Figure S22). In other words, these experiments
demonstrate that the handedness of a double helical
foldamer can be reversibly switched through photochemical
and thermal processes. To our knowledge, this constitutes
an unprecedented achievement.

Eventually, since foldamer strands affected the kinetics
of photoisomerization, it appeared relevant to assess their
impact over the thermal conversion from the (P,P)-cis
configuration to the (M,M)-cis one in the case of 4, 5, and 1
(Figure 9). Full conversions were reached within 150, 230,
and 420 min, respectively, highlighting the occurrence of
interactions between motor substituents. These observations
appear logical, since weaker thermal conversion efficiencies
are associated to more sterically demanding fragments,
which are furthermore prone to interact together through
noncovalent interactions.

Conclusion

Helical foldamers have been recently in the limelight of the
scientific community. In particular, their chirality makes

them promising architectures in various fields such as host-
guest chemistry, optoelectronics and catalysis. Therefore,
being able to control their handedness in a reversible
manner and thanks to a stimulus as simple as light appears
particularly appealing. To tackle this demanding objective,
we designed and synthesized a foldamer-motor conjugate
and explored its stereochemistry.

Likewise, we demonstrated that double helix formation
is necessary to observe chiral induction from the motor to
the helical strands, and that it is possible to switch on the
chiral induction of the motor to the foldamer, by promoting
the *trans* to *cis* configurational change of the motor unit.
More importantly, UV/Visible absorption and circular
dichroism spectroscopies show that the chirality of a double
helical foldamer can be reversibly controlled through photo-
chemical and thermal stimulations. We believe that this
proof-of-principle constitutes an important step forward in
the field of chiral recognition and towards applications in
the field of luminescent materials.

**Supporting Information**

The authors have cited additional references within the
Supporting Information.[42,71–76]

Acknowledgements

This work was supported by the Pays-de-la-Loire region (ARDENT project) and the French National Research Agency (project n°ANR-19-CE06-0008 and ANR-18-EURE-0012). DC thanks the Centre National de la Recherche Scientifique and the University of Angers for research leaves. The University of Angers is also acknowledged for a MIR funding. The authors are also thankful to the SCIAM platform (Benjamin Siegler for NMR spectroscopy and Ingrid Freuze for mass spectrometry analyses)
and the SFR Matrix. This work used the computational ressources of the GliCID/CCIPL computational center installed in Nantes. BLF acknowledges the Ministry of Education, Culture and Science of the Netherlands (Gravitation Program No. 024.001.035 to B.L.F.).

## Conflict of Interest

The authors declare no conflict of interest.

## Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.

**Keywords:** Foldamers • Chirality • Photoswitch • Hybridization • Chiral induction

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Manuscript received: July 19, 2024

Accepted manuscript online: September 3, 2024

Version of record online: October 31, 2024