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\DOI{10.5802/crchim.423}
\datereceived{2025-07-11}
\daterevised{2025-07-16}
\dateaccepted{2025-09-12}
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\dateposted{2025-11-24}
\begin{document}

\begin{noXML}

\CDRsetmeta{articletype}{clarification}

\title{Shaping the 3D architecture of [2.2]paracyclophanes: from
selective functionalization to functional luminophores}

\alttitle{Modeler l'architecture 3D des [2.2]paracyclophanes : de la
fonctionnalisation s\'{e}lective \`{a} la conception de luminophores
fonctionnels}

\author{\firstname{Laurent} \lastname{Micouin}\CDRorcid{0000-0003-1080-8591}}
\address{Universit\'{e} Paris Cit\'{e}, CNRS, Laboratoire de Chimie et
de Biochimie Pharmacologiques et Toxicologiques, F-75006 Paris, France}
\email[L. Micouin]{laurent.micouin@u-paris.fr}

\author{\firstname{Erica} \lastname{Benedetti}\CDRorcid{0000-0002-6457-7381}\IsCorresp}
\addressSameAs{1}{Universit\'{e} Paris Cit\'{e}, CNRS, Laboratoire de
Chimie et de Biochimie Pharmacologiques et Toxicologiques, F-75006
Paris, France}
\email[E. Benedetti]{erica.benedetti@u-paris.fr}

\keywords{\kwd{[2.2]Paracyclophanes}\kwd{Planar chirality}\kwd{3D
luminophores}\kwd{Organic photocatalysts}\kwd{RNA ligands}}

\altkeywords{\kwd{[2.2]Paracyclophanes}\kwd{Chiralit\'{e}
planaire}\kwd{Luminophores 3D}\kwd{Photocatalyseurs
organiques}\kwd{Ligands d'ARN}}

\editornote{Article submitted by invitation}
\alteditornote{Article soumis sur invitation}

\thanks{CNRS, Paris Cit\'{e} University (IdEx Dynamique Recherche
pCp-Photocat - ANR-18-IDEX-0001), Agence Nationale de la Recherche
(ANR JCJC PhotoChiraPhane - ANR-19-CE07-0001-01)}

\begin{abstract}
Over the past few years, [2.2]paracyclophanes (pCps) have attracted
considerable attention due to their unique three-dimensional structure
and distinctive electronic properties. In this account, we explore
various strategies for selective modification of these molecules, with
a particular focus on controlling their planar chirality and tuning
their photophysical behavior. The versatility of pCps is further
illustrated through their broad scope of applications, spanning the
development of organic and organometallic luminophores, advances in
photocatalysis, and contributions to biochemical research. These
diverse applications underscore the strong potential of pCps as key
platforms for the design of innovative molecular systems.
\end{abstract}

\begin{altabstract}
Ces derni\`{e}res ann\'{e}es, les [2.2]paracyclophanes (pCps) ont
suscit\'{e} un vif int\'{e}r\^{e}t en raison de leur architecture
tridimensionnelle unique et de leurs propri\'{e}t\'{e}s
\'{e}lectroniques hors du commun. Dans ce compte rendu, nous exposons
diverses strat\'{e}gies permettant la modification s\'{e}lective de ces
mol\'{e}cules, en mettant tout particuli\`{e}rement l'accent sur le
contr\^{o}le de leur chiralit\'{e} planaire et la modulation de leurs
propri\'{e}t\'{e}s photophysiques. La polyvalence des pCps est
illustr\'{e}e par la diversit\'{e} de leurs applications, allant du
d\'{e}veloppement de luminophores organiques et organom\'{e}talliques
\`{a} des avanc\'{e}es en photocatalyse et en biochimie. Ces travaux
mettent en \'{e}vidence le fort potentiel des pCps en tant que
plateformes de choix pour la conception de syst\`{e}mes
mol\'{e}culaires innovants.
\end{altabstract}

\maketitle
{\vspace*{1pc}}

\twocolumngrid

\end{noXML}

\section{Introduction}

[2.2]Paracyclophane (pCp) is the smallest known member of the
[n.n]cyclophane family. This molecule was serendipitously discovered
and first isolated in 1949 by Brown and Farthing as an unexpected
byproduct of the gas-phase pyrolysis of \textit{para}-xylene~\cite{1}.\ 
X-ray diffraction analysis revealed that pCp consists of two benzene
rings, commonly referred to as decks, arranged in a cofacial
orientation and connected at the \textit{para} positions by two
ethylene bridges~\cite{2}.\ This molecular architecture forces the decks
into an unusual boat-like conformation (\mbox{Figure}~\ref{fig1}), in
which the bridgehead carbon atoms are displaced out of the plane
defined by the remaining trigonal carbon atoms. Consequently, the
distance between the carbon atoms bearing the ethylene bridges is
shorter than the overall inter-ring separation (2.78~{\AA} versus
3.09~{\AA}, respectively, Figure~\ref{fig1}).

\begin{figure}
\includegraphics{fig01}
{\vspace*{-.2pc}}
\caption{\label{fig1}Structure of [2.2]paracyclophane (pCp).}
{\vspace*{-.3pc}}
\end{figure}

These structural characteristics have a significant impact on the
electronic distribution and chemical reactivity of the molecule,
positioning pCp as a valuable scaffold for the design of novel aromatic
compounds with a distinctive three-dimensional framework. Accordingly,
significant research efforts have been dedicated to the synthesis and
functionalization of pCp, as well as the modulation of its
physicochemical properties and the exploration of its potential across
various scientific domains~\cite{3}.

In this account, we report our contributions to the chemistry of pCps,
at first by placing our research in its broader context and outlining
the strategies that we have developed to selectively functionalize the
aromatic rings of commercially available pCp. Our methods for
controlling the planar chirality inherent to these unique systems are
then discussed. Finally, the synthesis of novel families of
three-dimensional luminophores derived from pCp is described, and their
applications across different research areas are discussed, including
photocatalysis, coordination chemistry, and chemical biology.

\section{Tailoring the aromatic decks of{\hfill\break}
[2.2]paracyclophane} \label{sec2}

Since its discovery, numerous synthetic strategies have been developed
to try and access pCp in an efficient manner. In addition to the
industrial synthesis, which relies on the Hofmann elimination of
\textit{p}-methylbenzyl trimethylammonium hydroxide~\cite{4}, the
method reported by Brink in 1975 remains the most widely adopted and
highest-yielding approach at the laboratory scale~\cite{5}. This
approach involves the coupling of
1,4-bis(bromomethyl)benzene~\textbf{1} with
1,4-bis(mercaptomethyl)-benzene~\textbf{2} to produce
dithia[3.3]paracyclophane~\textbf{3}, followed by photochemical
desulfurization to yield pCp in 51\% overall yield (Scheme~\ref{sch1}).
This robust and reliable method has since enabled the synthesis of a
broad range of pCp derivatives~\cite{6,7,8}.

\begin{scheme*}
{\vspace*{-.2pc}}
\includegraphics{sc01}
{\vspace*{.4pc}}
\caption{\label{sch1}Synthesis and polymerization of
[2.2]paracyclophane.}
\end{scheme*}

[2.2]Paracyclophanes are remarkably stable toward acids, bases,
oxidants, or light, and retain their structural integrity up to
200~{\textdegree}C. Above this temperature, homolytic cleavage of the
ethylene bridges occurs, leading to ring opening of the pCp core. This
thermal behavior has been widely exploited in materials science,
particularly for polymer production via chemical vapor deposition (CVD)
processes~\cite{9,10,11,12}. For example, unsubstituted pCp is a key
precursor in the synthesis of parylene (Scheme~\ref{sch1})~\cite{13},
an aromatic polymer extensively used as a protective coating in
electronics, optics, and biomedical devices. 

Owing to its widespread industrial applications, pCp is now
commercially available at low cost. As a result, functionalized pCp
derivatives are nowadays most easily prepared via direct
functionalization of the parent compound, rather than through de novo
synthesis of substituted analogues. 

Each aromatic ring of the pCp scaffold offers four accessible
positions, allowing up to eight possible sites for derivatization.\ 
Monofunctionalization is typically achieved through electrophilic
aromatic substitution, enabling the introduction of diverse functions
such as bromine atoms, formyl, nitro, or ester motifs. Alternatively,
halogen--lithium exchange from brominated precursors followed by
trapping with suitable electrophiles allows the incorporation of a
broader array of functional groups, including amines, hydroxyls,
azides, thiols, carboxylic acids, and phosphines~\cite{14}.\ More
recently, direct \mbox{C--H} activation strategies have also emerged as
effective tools for regioselective modification of the pCp
core~\cite{15}.

From monosubstituted intermediates, various disubstituted pCps can be
easily prepared (Figure~\ref{fig2}). These are typically classified
according to their substitution pattern: \textit{ortho}, \textit{meta},
or \textit{para} when both substituents are on the same aromatic ring;
and \textit{pseudo-gem}, \textit{pseudo-ortho}, \textit{pseudo-meta},
or \textit{pseudo-para} when the substituents are located on both
decks.

\begin{figure*}
{\vspace*{-.3pc}}
\includegraphics{fig02}
{\vspace*{-.4pc}}
\caption{\label{fig2}Substitution patterns and nomenclature of pCps.}
{\vspace*{-.3pc}}
\end{figure*}

Higher substituted derivatives (tri- and tetrafunctionalized pCps) are
generally synthesized via sequential electrophilic substitutions on
di-substituted precursors~\cite{16}. However, systems bearing more than
four substituents are highly strained and remain uncommon in the
literature~\cite{17}.

In certain cases, the reactivity of the aromatic units in pCps can pose
notable synthetic challenges due to through-space electronic
delocalization between the closely positioned ${\uppi}$ systems.
Interestingly, reactivity patterns resembling those of isolated double
bonds have been observed in some cases~\cite{18,19}. Moreover, the
introduction of substituents on one deck can significantly influence
the electronic distribution across the molecule, thereby activating or
deactivating specific positions on the{\break} opposite ring.\ 
For~example, the introduction of electron-withdrawing groups can direct
selective functionalization to the \textit{pseudo-geminal} position, an
effect well known and extensively exploited in [2.2]paracyclophane
chemistry~\cite{20,21}.

Despite significant progress, the selective introduction of multiple
substituents onto a single aromatic ring of pCp remains a synthetic
challenge.\ In our studies, we have developed an efficient and
regioselective approach for synthesizing \textit{para}-disubstituted
pCps in a limited number of steps and with good overall yields. This
strategy relies on a Vilsmeier--Haack formylation of various
4-amino[2.2]paracyclophane derivatives (\textbf{4}, Table~\ref{tab1}),
enabling the installation of a formyl group opposite to the existing
electron-donating substituent.

\begin{table*}[t!]%tab1
\caption{\label{tab1}Para-formylation of 4-amino[2.2]paracyclophanes
\tpar{\protect\inlinefig{fx01}}\vspace*{-12pt}}
\tabcolsep12pt
\begin{tabular}{ccccc}
\thead
Entry & Product & R$^1$ & R$^2$ & Yield (\%)\\
\endthead
1 & \textbf{5a} & Me & Me & 90\\
2 & \textbf{5b} & Bn & Bn & 77\\
3 & \textbf{5c} & H & Bn & 72\\
4 & \textbf{5d} & Allyl & Allyl & 50\\
5 & \textbf{5e} & H & Fmoc & 42
\botline
\end{tabular}
{\vspace*{-.6pc}}
\end{table*}

The transformation is performed using POCl$_{3}$ (1~equiv.) in the
presence of DMF, with the \mbox{reaction} mixture gradually heated from
0 to 100~{\textdegree}C over 3~h.{\break} These conditions exhibit
broad substrate tolerance, accommodating tertiary and secondary amines
bearing alkyl, allyl, or benzyl substituents on the nitrogen atom, as
well as derivatives featuring mildly electron-withdrawing groups, such
as a 9-fluorenylmethyloxycarbonyl (Fmoc) motif (Table~\ref{tab1}). This
method provides access to a range of functionalized aldehydes in a
practical and scalable manner, generating versatile intermediates for
the construction of more elaborate molecular architectures based on the
pCp core~\cite{22}, as detailed in the following sections of this
account.

\section{Controlling planar chirality in{\hfill\break}
[2.2]paracyclophanes} \label{sec3}

Extensive efforts have been devoted to the investigation and
rationalization of the geometry of pCps. For~many years, it was
believed that the unsubstituted pCp adopted a fully eclipsed
conformation with D$_{2\mathrm{h}}$ symmetry. However, subsequent
experimental and theoretical studies have shown that, at very low
temperatures, the molecule favors a staggered conformation with D$_{2}$
symmetry, characterized by a torsional angle between 6 and
9{\textdegree}.\ As a result, the D$_{2\mathrm{h}}$ structure is now
considered as a transition state between two enantiomeric D$_{2}$
conformers (Figure~\ref{fig3}). Despite this, the unsubstituted pCp
remains achiral at room temperature due to the rapid interconversion
between its enantiomeric \mbox{conformations}~\cite{23,24,25}.

\begin{figure*}
{\vspace*{.4pc}}
\includegraphics{fig03}
{\vspace*{.4pc}}
\caption{\label{fig3}Achiral and planar chiral pCps.}
{\vspace*{.4pc}}
\end{figure*}

Substituted pCps can exhibit planar chirality due to their rigid,
strained structure, which prevents rotation of the aryl groups around
their axes. Monosubstituted pCps are inherently nonsymmetrical, but
disubstituted derivatives may or may not be chiral, depending on the
nature and position of their substituents (Figure~\ref{fig3}). Indeed,
\textit{ortho}, \textit{meta}, \textit{pseudo-gem}, and
\textit{pseudo-para} derivatives are achiral when both substituents are
identical.

On the contrary, \textit{para}, \textit{pseudo-ortho}, and
\textit{pseudo-meta} pCps display planar chirality even when bearing
the same substituents. A similar trend is observed for
\textit{tetra}-substituted derivatives (Figure~\ref{fig3})~\cite{14}.

To assign the absolute configuration of pCps, specific
Cahn--Ingold--Prelog rules (CIP conventions)~\cite{26} must be
followed. The less substituted aromatic ring of the pCp core is
positioned toward the front of the molecule, and the priority atom is
identified as the carbon of the ethylene bridge bonded to the aromatic
ring at the position nearest the highest-priority substituent. The
configuration is assigned by numbering the ring carbons beginning at
the priority atom, moving sequentially toward the highest priority
substituent, and including the aromatic quaternary carbon attached to
the ethylene bridge. The direction of numbering (clockwise or
counterclockwise) determines the R$_{\mathrm{p}}$ or S$_{\mathrm{p}}$
configuration, respectively (Figure~\ref{fig3}). 

Planar chirality in pCps was first identified by Gram and Allinger in
1955~\cite{27}. Early research in this domain focused on synthesizing
monosubstituted pCps and determining their absolute configuration.
Since the 1990s, chiral pCps have become valuable ligands in asymmetric
catalysis~\cite{28} and, more recently, key components in the
development of circularly polarized light-emitting
materials~\cite{29,30}. However, large-scale synthesis of
polysubstituted pCps with controlled chirality remains a significant
challenge, which still considerably limits their broader applications.

The synthesis of structurally complex enantiopure pCps typically
involves the functionalization of simpler optically active
intermediates.\ Over the years, various strategies have been developed
to obtain such compounds in an efficient manner. Techniques like
high-performance liquid chromatography (HPLC) on chiral stationary
phases are commonly used for enantiomer separation, although they
require costly equipment and large volumes of solvents. Classical
resolution methods, which rely on forming diastereoisomeric products
using stoichiometric amounts of chiral resolving agents, are also
frequently employed to generate \mbox{enantioenriched}~pCps. However,
these approaches often involve multi-step syntheses (i.e., formation of
the diastereomers, separation, and regeneration of the initial pCps),
which are time-consuming~\cite{31}.

\looseness=-1
In our studies, we have investigated kinetic resolution and
desymmetrization strategies as effective alternatives to traditional
methods for accessing optically active pCps. Kinetic resolution (KR)
constitutes a powerful approach wherein racemates undergo asymmetric
transformations in the presence of a chiral catalyst, with the two
enantiomers reacting at different rates. Ideally, at 50\% conversion,
one enantiomer is recovered as unreacted starting material, while the
other one is obtained as the product. In contrast, desymmetrization of
\textit{meso} derivatives enables the generation of enantiopure
compounds under similar catalytic conditions in yields up to 100\%, by
differentiating prochiral sites within an achiral molecule.

Starting from racemic aldehydes or centrosymmetric \textit{meso}
dialdehydes derived from pCp, we \mbox{employed} asymmetric transfer
hydrogenations (ATH) as key transformations to control planar
chirality~\mbox{\cite{16,32,33}}. After optimizing the reaction
conditions, enantioselective reductions were successfully carried out
using the commercially available Noyori's {catalyst}
RuCl($p$-cymene)[($R$,$R$)-TsDPEN] (($R$,$R$)-\textbf{Cat}, 1~mol\%) in a
1:1 iPrOH/DMF mixture at 0~{\textdegree}C, with $t$-BuOK (5~mol\%) as
the base. These reactions, which are operationally simple and easy to
implement, \mbox{delivered} a wide range of optically active products
in short times (Scheme~\ref{sch2}).

\begin{scheme*}
{\vspace*{-.1pc}}
\includegraphics{sc02}
{\vspace*{.5pc}}
\caption{\label{sch2}Kinetic resolution and desymmetrization of
aldehydes derived from [2.2]paracyclophanes.}
{\vspace*{-.4pc}}
\end{scheme*}

The resulting molecules possess diverse substituents, including
carbonyl or hydroxyl groups, and halogen atoms, on each aromatic ring
of the pCp core, thereby enabling further functionalization through a
variety of orthogonal transformations such as condensations,
nucleophilic substitutions, Grignard additions,
transition-metal-catalyzed couplings, and olefination reactions.
Enantiopure pCp-based aldehydes are thus now routinely prepared in our
laboratory on multigram scales, serving as valuable key intermediates. 

Notably, following our work, there has been a renewed interest in
controlling the planar chirality of [2.2]paracyclophanes through
catalytic chemical methods, resulting in a number of compelling
contributions to the field~\cite{35,36,37,38,39}. Among the various
strategies developed in this area, our approach has proven both viable
and competitive, and it has been successfully employed by other
research teams worldwide~\cite{40}.

\section{Modulating the photophysical properties of
[2.2]paracyclophanes} \label{sec4}

[2.2]Paracyclophanes are known to exhibit unique photophysical
properties arising from electronic conjugation between their two
aromatic rings, aided by both through-bond and through-space
\mbox{interactions}.\ Indeed, unsubstituted pCp displays a distinctive
UV--visible absorption spectrum, characterized by maxima at 225, 244,
286, and 302~nm \cite{41,42}. The absorption band at the longest
wavelength, commonly referred to as the cyclophane band, emerges in a
spectral region that is atypical for standard benzene derivatives, such
as xylenes. Furthermore, the molecule exhibits a broad fluorescence
emission band centered around 356~nm. These characteristics have led to
the widespread use of pCp as a core structure in the design of
three-dimensional organic luminophores.

Pioneering studies have focused on the development of various systems
that mimic excimers, transient dimers typically observed via
fluorescence spectroscopy. In contrast to true excimers, which exist
solely in the excited state, pCp-based analogues are stable in the
ground state, making them particularly well-suited as model compounds
for photophysical investigations. Notably, a variety of stilbene dimers
incorporating the pCp scaffold have been isolated and thoroughly
characterized~\cite{43,44,45}. Furthermore, di- and tetrasubstituted
pCp derivatives bearing both electron-donating and electron-withdrawing
groups have been designed to probe through-space charge-transfer
delocalization~\cite{47}. All these systems offer valuable insight into
electronic communication between stacked aromatic units within the
distinctive three-dimensional architecture of the pCp framework.

More recently, numerous studies have demonstrated that the synergistic
interplay between \mbox{planar} chirality and the distinctive
spectroscopic behavior of pCps can be effectively exploited for the
development of advanced circularly polarized luminescence (CPL)
emitters. Research on CPL active compounds has gained momentum, driven
by their promising applications in advanced optoelectronic
technologies, such as 3D displays, optical data storage, and
bioimaging~\cite{48}. Nevertheless, the rational design of organic
luminophores that combine high emission efficiency with strong
chiroptical activity remains a major challenge, spurring ongoing
innovation in molecular engineering.

\begin{scheme*}
{\vspace*{-.3pc}}
\includegraphics{sc03}
{\vspace*{.3pc}}
\caption{\label{sch3}Synthesis of pCp-based 3D coumarins.}
{\vspace*{-.6pc}}
\end{scheme*}

In this context, helicene-like structures featuring a pCp core have
been synthesized and extensively investigated for their CPL
properties~\cite{49}. Additionally, a variety of second-order molecular
architectures, such as V-, N-, M-, triangle-, propeller-, and X-shaped
frameworks, have been constructed from pCp
units~\cite{50,51,52,53,54,55,56,57}. These structurally complex
compounds exhibit remarkable optical properties, including high molar
extinction coefficients ($\varepsilon$), strong fluorescence with
significant quantum yields ($\Phi$), and impressive dissymmetry
factors~\cite{58} in both \mbox{absorption} ($g_{\mathrm{abs}}$) and emission
($g_{\mathrm{lum}}$). Such attributes render them promising candidates
for the development of advanced functional materials in the field of
chiral photonics.

\looseness=-1
As a complementary strategy to {modulate} the (chir)optical properties
of pCps we explored the {possibility} of {expanding} the pCp aromatic
framework to access functionalized polycyclic 
(hetero)aro\-matic~derivatives---three-dimensional analogues~of
classical aromatic dyes such as naphthalenes, coumarins, and
cyanines~\cite{59}. This approach has led to the development of chiral
luminophores with more compact molecular structures and enhanced
solubility, offering key advantages for solution-phase applications,
including asymmetric catalysis, supramolecular recognition, and chiral
sensing in complex \mbox{environments}.

All the new families of 3D luminescent compounds that we
developed~\cite{59} were synthesized in just a few steps, starting from
aldehyde intermediates, the chirality of which can be easily controlled
using the methods described earlier in this article. For example,
three-dimensional coumarin dyes were synthesized in three steps,
beginning with Dakin oxidation, conducted using H$_{2}$O$_{2}$ and
catalytic amount of H$_{2}$SO$_{4}$ in a CH$_{2}$Cl$_{2}$/MeOH mixture,
to form \mbox{4-hydroxy[2.2]paracyclophanes} \textbf{7} in up to 90\% yield.
These molecules were then esterified with various propiolic acid
derivatives under classical conditions (DCC and DMAP cat.\ in
CH$_2$Cl$_2$). The resulting esters \textbf{8} were subjected to
cyclization promoted by gold- and silver-based catalysts in
1,2-dichloroethane under microwave irradiation at 80~{\textdegree}C,
yielding the desired coumarin core \textbf{9} (Scheme~\ref{sch3}). In a
final diversification step, starting from brominated compounds,
Buchwald--Hartwig couplings were employed to introduce
electron-donating amino groups on the pCp scaffold~\cite{60}.

\begin{table*}[t!]%tab2
\tabcolsep10.5pt
\caption{\label{tab2}Spectroscopic properties of pCp-based coumarins
and flat analogues
\vspace*{4pt}\tpar{\protect\inlinefig{fx02}}\vspace*{-9pt}}
\begin{tabular}{ccccc}
\thead
Entry & Compound & $X$, $Y$ & ${\lambda}_{\mathrm{max}}^{\mathrm{abs}}$ (nm)
& $\lambda_{\mathrm{max}}^{\mathrm{em}}$ (nm)$^{\mathrm{d}}$\\
\endthead
{\mn}1$^{\mathrm{a}}$ & \textbf{9a} & H, Ph & 265, 300, 330 & 460\\
{\mn}2$^{\mathrm{a}}$ & \textbf{9b} & H, Me & 301, 319 & 435\\
{\mn}3$^{\mathrm{a}}$ & \textbf{9c} & H, $i$Pr & 300, 320 & 432\\
{\mn}4$^{\mathrm{a}}$ & \textbf{9d} & H, H & 304, 320 & 445\\
{\mn}5$^{\mathrm{a}}$ & \textbf{9e} & Br, Ph & 307, 325 & 450\\
{\mn}6$^{\mathrm{a}}$ & \textbf{9f} & Br, Me & 306, 320 & 425\\
{\mn}7$^{\mathrm{a}}$ & \textbf{9g} & H, $p$-MePh & 315 & 455\\
{\mn}8$^{\mathrm{a}}$ & \textbf{9h} & H, $p$-OMePh & 300, 330 & 455\\
{\mn}9$^{\mathrm{a}}$ & \textbf{9i} & H, $p$-ClPh, & 288, 310, 335 & 465\\
10$^{\mathrm{a}}$ & \textbf{9j} & H, $p$-OTfPh, & 280, 330 & 470\\
11$^{\mathrm{a}}$ & \textbf{9k} & H, $p$-CF$_3$Ph & 270, 335 & 475\\
12$^{\mathrm{a}}$ & \textbf{9l} & NHBoc, Ph & 317 & 450\\
13$^{\mathrm{a}}$ & \textbf{9m} & NH$_2$, Ph & 300, 330 & 560\\
14$^{\mathrm{a}}$ & \textbf{9n} & H, $p$-NHBocPh & 317 & 450\\
15$^{\mathrm{a}}$ & \textbf{9o} & H, $p$-NH$_2$Ph & 330 & 470\\
16$^{\mathrm{b}}$ & \textbf{10a} & -, Ph & 294 & 418\\
17$^{\mathrm{b}}$ & \textbf{10b} & -, Me & 286 & 413\\
18$^{\mathrm{c}}$ & \textbf{Coumarin~6} & -,- & 455 & 498
\botline
\end{tabular}
\tabnote{$^{\mathrm{a}}$10$^{-4}$~M solution in 1,2-dichloroethane.\ 
$^{\mathrm{b}}$10$^{-5}$~M solution in 1,2-dichloroethane.
$^{\mathrm{c}}$10$^{-5}$~M solution in CH$_2$Cl$_2$.
$^{\mathrm{d}}$No significant effects were observed on the emission
spectra while changing the excitation wavelength or the concentration
of the samples.}
\end{table*}

The impact of the pCp motif and its characteristic ``phane''
interactions on the spectroscopic properties of the synthesized
coumarins was investigated using unpolarized UV--visible absorption and
fluorescence spectroscopy. Overall, the three-dimensional dyes
exhibited bathochromic shifts in both absorption and emission spectra
compared to analogous planar structures (Table~\ref{tab2}).
Interestingly, the absorption maxima of the pCp-based coumarins remain
hypsochromically shifted relative to those of planar commercial dyes
such as \textbf{coumarin~6}, which possess a strong
{intramolecular} charge-transfer {character}
(Table~\ref{tab2}). The luminescence properties of the 3D coumarins,
which spanned the blue-to-green region of the electromagnetic spectrum,
were significantly influenced by the substitution pattern on the
out-of-plane aromatic ring of the pCp core. In particular, the
introduction of halogen atoms induced hypsochromic shifts in the
emission profiles compared to their unsubstituted counterparts
(Table~\ref{tab2}, entries~5 and~6 versus entries~1 and~2). Conversely,
amino-substituted derivatives bearing electron-donating groups
exhibited pronounced bathochromic shifts in their emission maxima
(Table~\ref{tab2}, entry~13 versus entry~1), highlighting the effective
modulation of luminescent properties through electronic effects. These
findings clearly demonstrate that precise control over the
photophysical behavior of these compounds can be achieved by modulating
both the nature and spatial arrangement of substituents around the
three-dimensional pCp\break framework.

All pCp-based coumarins demonstrated notable photostability, along with
exceptionally larger Stokes shifts (reaching up to 43~478~cm$^{-1}$) in
comparison with their flat analogues. However, these dyes generally
exhibited modest fluorescence quantum yields ($0.1\% < \Phi < 5\%$). 

\begin{figure*}
\vspace*{-1pt}
\includegraphics{fig04}
\vspace*{-2pt}
\caption{\label{fig4}Chiroptical properties of pCp-based coumarins
S$_{\mathrm{p}}$-\textbf{9b} and R$_{\mathrm{p}}$-\textbf{9b}. ECD and
CPL spectra were recorded in CH$_{2}$Cl$_2$ ($10^{-5}$~M,
$\lambda_{\mathrm{ex}} = 320$~nm).}
\vspace*{-1.5pt}
\end{figure*}

In collaboration with Dr.~J.~Crassous's group, we carried out the
chiroptical characterization of enantiopure planar chiral coumarins
obtained from optically active aldehyde precursors~\cite{60}. As
expected, electronic circular dichroism (ECD) spectra recorded in
CH$_{2}$Cl$_{2}$ (10$^{-5}$~M) displayed \mbox{well-defined} 
\mbox{mirror-image}
signatures for the two enantiomers of compound \textbf{9b}
(Figure~\ref{fig4}), with the S$_{\mathrm{p}}$ enantiomer exhibiting a strong
positive Cotton effect at 240~nm ($\Delta\varepsilon =
+64~\mathrm{M}^{-1}{\cdot}\mathrm{cm}^{-1}$) and a weaker negative one at
320~nm ($\Delta\varepsilon=-23~\mathrm{M}^{-1}{\cdot}\mathrm{cm}^{-1}$).
Complementary CPL measurements under identical conditions
($\lambda_{\mathrm{ex}} = 330$~nm) further revealed mirror-image
emission profiles, consistent with their enantiomeric nature
(Figure~\ref{fig4}). Overall, the pCp-based coumarin derivatives showed
promising chiroptical responses, with dissymmetry factors of
$g_{\mathrm{abs}} \approx 6.2 \times 10^{-3}$ at 360~nm and
$g_{\mathrm{lum}} \approx 4.0 \times 10^{-3}$ at 440~nm. These values
are especially noteworthy given the compact and rigid nature of the
molecular framework in contrast to the previously reported systems
based on extended \mbox{${\uppi}$-conjugation}.\ Additionally, the
$g_{\mathrm{lum}}/g_{\mathrm{abs}}$ ratio of ${\sim}$0.7 suggests minimal
structural \mbox{reorganization} upon excitation, an advantageous
feature for preserving chiroptical integrity in emissive applications.

Three-dimensional cyanine-type dyes based on the pCp scaffold were also
readily prepared from aldehyde intermediates, particularly those
obtained via the regioselective formylation strategy outlined in
Table~\ref{tab1}. In this case, key aldehyde \textbf{5a}, bearing a
dimethylamino group, underwent a Wittig-type reaction with compound
\textbf{11}, followed by \textit{N}-methylation of its benzothiazole
moiety. This sequence efficiently led to the formation of novel
luminescent compound \textbf{12}, which exhibited emission in the red
region of the electromagnetic spectrum (Scheme~\ref{sch4}). Once again,
both racemic and enantiopure products could be synthesized using the
strategies developed in our \mbox{laboratory}~\cite{61}.\looseness=-1

\begin{scheme*}
{\vspace*{.1pc}}
\includegraphics{sc04}
{\vspace*{.6pc}}
\caption{\label{sch4}Synthesis of a pCp-based 3D cyanine.}
\end{scheme*}

The photophysical properties of three-dimen\-sional cyanine dye
\textbf{12} were investigated in both dichloromethane and an aqueous
Tris-EDTA (TE) buffer, the latter containing 1\% DMSO to ensure full
solubilization of the organic compound. When comparing the two
environments, a modest hypsochromic shift in both absorption and
emission maxima was observed upon transitioning from the organic to the
aqueous medium ({Table}~\ref{tab3}).\ {Additionally}, both
the molar extinction coefficient and fluorescence quantum yield were
reduced in the TE buffer, indicating diminished brightness in the
aqueous phase.\looseness=-1

\begin{table*}[t!]%tab3
\tabcolsep10.3pt
\caption{\label{tab3}Spectroscopic properties of cyanine dyes in
different media
\vspace*{2pt}\tpar{\protect\inlinefig{fx03}}\vspace*{-9pt}}
\begin{tabular}{cccccc}
\thead
Dye$^{\mathrm{a}}$ & Solvent & $\lambda_{\mathrm{abs}}^{\mathrm{max}}$
(nm) & $\varepsilon_{\mathrm{max}}$ (M$^{-1}{\cdot}\mathrm{cm}^{-1}$) &
$\lambda_{\mathrm{em}}^{\mathrm{max}}$ (nm) & $\Phi_{f}$
(\%)$^{\mathrm{b}}$\\
\endthead
\morerows{1}{\textbf{12}} & CH$_2$Cl$_2$ & 597 & 46 ${\times}$ 10$^{3}$
& 645 & 2.0\\
& TE$^{\mathrm{c}}$ & 565 & 39 ${\times}$ 10$^{3}$ & 635 &
1.5{\vspace*{4pt}}\\
\morerows{1}{\textbf{13}} & CH$_2$Cl$_2$ & 553 & 44 ${\times}$ 10$^{3}$
& 607 & 6.2\\
& TE$^{\mathrm{c}}$ & 510 & 36 ${\times}$ 10$^{3}$ & 600 & 1.3
\botline
\end{tabular}
\tabnote{$^{\mathrm{a}}$10$^{-5}$~M solution. $^{\mathrm{b}}$Absolute
quantum yields. $^{\mathrm{c}}$1\% DMSO was added to fully solubilize
the dyes.}
{\vspace*{-2pt}}
\end{table*}

Compared to its flat analogue \textbf{13}~\cite{62}, pCp-based cyanine
\textbf{12} exhibited significantly red-shifted \mbox{absorption} and
emission spectra in both organic and aqueous media (Table~\ref{tab3}).\ 
This pronounced bathochromic shift aligns with observations made for
other pCp-derived fluorophores, including the coumarin chromophores
discussed earlier.\ This effect is attributed to the presence of the
second \mbox{aromatic} ring in the pCp scaffold, which serves as a mild
electron-donating group, thereby modulating the global electronic
properties of\break the dyes.

Overall, these results underscore the remarkable versatility of
pCp-based three-dimensional luminophores.\ By tailoring the
functionalization of the pCp core, we can precisely tune absorption and
emission profiles to cover the entire visible spectrum and develop
differently colored CPL emitters from enantiopure molecules~\cite{59}.
The diverse families of compounds we have isolated hold promise for a
wide range of applications in different domains, including coordination
chemistry, photocatalysis, and the chemistry--biology interface. Their
potential in these areas will be explored in greater detail in the
following sections.

\section{Lanthanide luminescence sensitization{\hfill\break} using
[2.2]paracyclophanes} \label{sec5}

In recent decades, the distinctive photophysical characteristics of
lanthanide ions (Ln) have garnered considerable interest, owing to
their sharp emission bands and prolonged luminescence
lifetimes~\cite{63}, which make them particularly attractive for
imaging and photonic applications~\cite{64,65,66}. In addition,
lanthanide-based organometallic complexes exhibit exceptional
photostability, effectively addressing a major limitation of
conventional organic fluorophores, namely, photobleaching under
prolonged or intense light exposure. A key limitation, however, arises
from the intrinsically low molar absorption coefficients of lanthanide
cations ($\varepsilon < 1~\mathrm{M}^{-1}{\cdot}\mathrm{cm}^{-1}$), which
severely restricts their direct excitation. To circumvent this issue,
the use of antenna ligands, chromophores capable of efficiently
absorbing light and transferring the harvested energy to the lanthanide
center, has become a widely adopted strategy for efficiently
sensitizing lanthanide emission~\cite{67,68}.

In this context, our group has investigated the potential of
luminophores derived from pCp as antenna or ligands for lanthanide
sensitization. While pCps have demonstrated significant utility in
transition metal coordination chemistry~\cite{69}, their application in
lanthanide systems, either as antennas or as coordinating ligands,
remains largely unexplored to date~\cite{70}. We thus identified a
promising opportunity to expand the functional utility of pCp-based
scaffolds by designing new Ln--pCp complexes with enhanced
photophysical performance.

\begin{scheme*}
\vspace*{-2pt}
\includegraphics{sc05}
{\vspace*{.5pc}}
\caption{\label{sch5}Synthesis of Ln complexes incorporating pCp-based
coumarins as antennas.}
{\vspace*{-.5pc}}
\end{scheme*}

\begin{table*}[t!]%tab4
\tabcolsep7.5pt
\caption{\label{tab4}Photophysical properties of Ln complexes
\textbf{17a} and \textbf{17b}
\vspace*{4pt}\tpar{\protect\inlinefig{fx04}}\vspace*{-10pt}}
\begin{tabular}{ccccccc}
\thead
Ln & $\lambda_{\mathrm{abs}}$ (nm)$^{\mathrm{a}}$ & $\varepsilon$
(L${\cdot}$mol$^{-1}{\cdot}\mathrm{cm}^{-1}$) & $\lambda_{\mathrm{em}}$
(nm)$^{\mathrm{a}}$ & $\tau_{\mathrm{obs}}$ ($\upmu$s)$^{\mathrm{a}}$ &
$\Phi^{\mathrm{b}}$ & ${\Phi_{\Delta}}^{\mathrm{c}}$\\
\endthead
\textbf{17a} & 332 & 48.5 ${\times}$ 10$^3$ & 980 & 9.48 & ${<}$0.01 & 0.00\\
\textbf{17b} & 332 & \061 ${\times}$ 10$^3$ & 422 & - & ${<}$0.01 & 0.45
\botline
\end{tabular}
\tabnote{$^{\mathrm{a}}$Solution in CH$_2$Cl$_2$ (10$^{-5}$~M);
$^{\mathrm{b}}$fluorescence quantum yield; $^{\mathrm{c}}$quantum
yield for singlet oxygen generation.}
{\vspace*{-.3pc}}
\end{table*}

As part of this study, in collaboration with Dr.~O.~Maury's group (ENS
Lyon), we successfully prepared a series of picolinate-based lanthanide
complexes bearing pCp-derived coumarin antennas
(Scheme~\ref{sch5})~\cite{71}. The synthesis of these molecular objects
began with compound \textbf{15}, obtained from a 3D coumarin bearing a
triple bond at its \mbox{\textit{pseudo-para}} position, via a Sonogashira
cross-coupling with iodo-picolinic ester \textbf{14}. Following
mesylation, the intermediate was coupled to 1,4,7-triazacyclononane
(TACN), yielding target ligand \textbf{16} in 15\% overall yield after
purification by column chromatography. Complexation with lanthanide
ions was then carried out via in-situ saponification, followed by the
addition of the hydrated lanthanide chloride at pH~6{\break}
(Scheme~\ref{sch5}).

Spectroscopic characterization revealed that the pCp--coumarin unit
undergoes rapid intersystem crossing from the singlet to the triplet
excited state [$E(T_{1}) = 19~500$~cm$^{-1}$]. The triplet-state
energy is well-matched for efficient energy transfer to Yb$^{3+}$ and
Gd$^{3+}$ ions. This was confirmed by excitation of the antenna at
332~nm, which resulted in the characteristic near-infrared (NIR)
luminescence of Yb$^{3+}$ in complex \textbf{17a}
($\lambda_{\mathrm{em}} = 980$~nm, Table~\ref{tab4}, entry~1).

\begin{figure*}
\vspace*{2pt}
\includegraphics{fig05}
\vspace*{1pt}
\caption{\label{fig5}Luminescence and magnetic properties of a Dy(III)
complex incorporating a pCp-based ligand.}
\vspace*{1pt}
\end{figure*}

Notably, under the same excitation conditions, Gd$^{3+}$-containing
complex \textbf{17b} was found capable of generating a singlet oxygen,
with a quantum yield of $\Phi_{\Delta} = 0.45$ (Table~\ref{tab4},
entry~2)~\cite{71}. These findings highlight the potential of pCp-based
architectures for the development of lanthanide complexes with tunable
and multifunctional properties~\cite{72}.

Lanthanide ions are currently the focus of extensive research in the
field of molecular magnetism~\cite{73}, as they are prime candidates
for the design of single-molecule magnets (SMMs).\ Unlike traditional
magnets, which consist of large assemblies of atoms, SMMs are composed
of discrete mono-, di-, or polynuclear complexes capable of retaining
magnetic information at low temperatures~\cite{74}. To fully harness
the potential of SMMs for practical use, it is crucial to investigate
their magnetic properties in relation to other physical
characteristics, such as luminescence and chirality. This could pave
the way for multifunctional materials in emerging technologies, such
as: quantum computing, where the integration of stable magnetic states
and optical properties could lead to more reliable qubits; molecular
electronics, where combining magnetic and luminescent properties may
improve device performance and enable further miniaturization; and
high-density data storage, where the ability to manipulate and store
information at the molecular level could transform data retention
capabilities. In this context, luminescent SMMs based on lanthanide
complexes, incorporating ligands with central, axial, or helical
chirality, have been developed~\cite{75}. Embedding rare-earth ions
within chiral organic frameworks facilitates chirality transfer from
the ligand to the metal center, generating circular anisotropies at the
lanthanide ion level. This can give rise to phenomena such as CPL and
magnetochiral dichroism (MChD)~\cite{76}. 
\mbox{Surprisingly,} \mbox{planar} chiral
ligands have yet to be utilized to modulate these intriguing properties
in lanthanide complexes.\looseness=1

Recently, in collaboration with Dr.~O.~Maury (ENS Lyon) and
Dr.~F.~Pointillart (Univ.\ Rennes~1), we employed racemic pCp-derived
phosphine oxides as ligands to finely tune the crystal field and
electronic environment surrounding Yb$^{3+}$ and Dy$^{3+}$ ions,
thereby enabling the manifestation of slow magnetic relaxation
(Figure~\ref{fig5}).\ The synthesized \mbox{complexes} also exhibited
distinct luminescence in the visible or NIR regions of the
electromagnetic spectrum. A magneto-structural correlation between the
emission and magnetic properties was established for these new
complexes, thereby contributing to a deeper understanding of the
interplay between these phenomena~\cite{77}.

Our laboratory is currently exploring the use of enantiopure pCps as
antennas or ligands for lanthanide ions, with the objective of
developing novel multifunctional molecular systems that integrate
luminescence, magnetism, and planar chirality.

\section{[2.2]Paracyclophanes as building blocks for the design of
organic photocatalysts} \label{sec6}

At the beginning of the last century, Ciamician recognized that visible
light could serve as a renewable and cost-effective energy source for
driving chemical reactions under mild and environmentally friendly
conditions~\cite{78}. Since then, the fields of photochemistry and
photocatalysis have unveiled numerous opportunities for reimagining
established reactions and pioneering pathways to previously
inaccessible products~\cite{79}. Over the years, a variety of highly
performant photocatalytic systems have been developed, ranging from
metal-based compounds such as ruthenium and iridium polypyridyl
\mbox{complexes} to fully organic molecules like eosin Y or acridinium
salts.\ Despite these inspiring advances, the quest continues for
novel, more versatile molecules capable of promoting a broader range of
catalytic photoreactions.\ Regardless of their intriguing photophysical
properties and considerable potential, pCps had remained largely
unexplored as catalysts in photochemical transformations until very
recently~\cite{40}.

As a proof of concept, and inspired by previous
reports~\cite{80,81,82}, our group demonstrated that pCp-based
coumarins can serve as organic photocatalysts, effectively promoting
desulfonylation reactions under light irradiation~\cite{83}.

Starting from a readily accessible model substrate (\textbf{19a},
Table~\ref{tab5}), prepared according to a reported
procedure~\cite{80}, coumarin derivative \textbf{9b} demonstrated
effective photocatalytic activity for the reductive cleavage of the
tosyl protecting group. Using a Hantzsch ester as the sacrificial
electron donor, irradiation at 300~nm led to 65\% conversion within 2~h
(Table~\ref{tab5}, entry~1). Prolonging the reaction time did not
improve this outcome (Table~\ref{tab5}, entry~2); however, catalyst
loading could be reduced from 20 to 5~mol\% without any loss in
efficiency (Table~\ref{tab5}, entries~3 and~4). A series of
structurally related pCp-based coumarins was evaluated to probe
structure--activity relationships. Interestingly, catalyst \textbf{9a}
bearing aryl substituents proved significantly less effective
(Table~\ref{tab5}, entry~7), indicating that an alkyl group on the
coumarin framework may be \mbox{crucial} for efficient photocatalysis
in this case. Control experiments further confirmed the key roles of
each component: no conversion was observed in the dark or in the
absence of the Hantzsch ester (Table~\ref{tab5}, entries~8 and~9),
while reactions conducted without the pCp-coumarin---or with
pCp-deprived analogue \textbf{10b}---resulted in only traces of
conversion (Table~\ref{tab5}, entries~10 and~11). These findings
underscore the unique contribution of the pCp moiety to the activity of
the photocatalyst. The presence of oxygen significantly suppressed the
deprotection (Table~\ref{tab5}, entry~12), and no conversion was
observed when TEMPO, a well-established radical scavenger, was added to
the reaction mixture (Table~\ref{tab5}, entry~13). Alternative reducing
agents were evaluated as well but did not exhibit performances
comparable to the Hantzsch ester (Table~\ref{tab5}, entries~14--16).

\begin{table*}[t!]%tab5
\tabcolsep15pt
\caption{\label{tab5}Optimization of the photodeprotection reaction
\vspace*{4pt}\tpar{\protect\inlinefig{fx05}}\vspace*{-12pt}}
\begin{tabular}{ccccc}
\thead
Entry & Photocat.\ (mol\%) & [H] & $t$ (h) & Conv. (\%)$^{\mathrm{e}}$\\
\endthead
\mn1\0 & \textbf{9b} (20) & \textbf{21} & \02 & 66\\
\mn2\0 & \textbf{9b} (20) & \textbf{21} & 16 & 71\\
\mn3\0 & \textbf{9b} (15) & \textbf{21} & \02 & 63\\
\mn4\0 & \textbf{9b} (5) & \textbf{21} & \02 & 65\\
\05$^{\mathrm{a}}$ & \textbf{9b} (5) & \textbf{21} & \02 & 64\\
\mn6\0 & \textbf{9c} (5) & \textbf{21} & \02 & 56\\
\mn7\0 & \textbf{9a} (5) & \textbf{21} & \02 & 26\\
\08$^{\mathrm{b}}$ & \textbf{9b} (5) & \textbf{21} & \02 & -\\
\mn9\0 & \textbf{9b} (5) & - & \02 & -\\
10\0 & - & \textbf{21} & \02 & \09\\
11\0 & \textbf{10b} (5) & \textbf{21} & \02 & 14\\
12$^{\mathrm{c}}$ & \textbf{9b} (5) & \textbf{21} & \02 & 19\\
13$^{\mathrm{d}}$ & \textbf{9b} (5) & \textbf{21} & \02 & -\\
14\0 & \textbf{9b} (5) & \textbf{22} & \02 & -\\
15\0 & \textbf{9b} (5) & \textbf{23} & \02 & -\\
16\0 & \textbf{9b} (5) & \textit{n}-Bu$_4$NBH$_4$ & \02 & -
\botline
\end{tabular}
\tabnote{Reactions were performed in a Rayonet photochemical reactor
equipped with eight 300~nm lamps ($T=\text{29~\textdegree}$C, $c =
0.05$~M). $^{\mathrm{a}}$Reaction performed under more diluted
conditions ($c=0.025$~M); $^{\mathrm{b}}$reaction performed in dark
($T=\text{25~\textdegree}$C, $c=0.05$~M); $^{\mathrm{c}}$reaction
performed under an oxygen atmosphere; $^{\mathrm{d}}$reaction performed
in the presence of TEMPO (1~equiv.); $^{\mathrm{e}}$determined by
$^{1}$H NMR analysis.{\vspace*{-.4pc}}}
\end{table*}

The scope of the reaction was subsequently examined using the
conditions optimized on substrate \textbf{19a}, as illustrated in
Scheme~\ref{sch6}. The deprotection of a range of sulfonyl groups,
including tosyl (Ts), phenylsulfonyl (SO$_{2}$Ph), and mesitylsulfonyl
(SO$_{2}$Mes), was tested using 5~mol\% of catalyst \textbf{9b}. In
line with the reactivity observed for the Ts group, efficient removal
of the phenylsulfonyl moiety afforded compound
\textbf{20a}$^{\mathbf{3}}$ in 59\% yield. Conversely, sulfonamides
bearing mesityl or mesyl groups proved unreactive under identical
conditions, yielding only trace amounts of the desired product.

\begin{scheme*}
{\vspace*{.3pc}}
\includegraphics{sc06}
{\vspace*{.6pc}}
\caption{\label{sch6}Scope of the photodeprotection reaction.}
\end{scheme*}

Substrates containing tosyl groups with a variety of functional motifs,
such as substituted (hetero)arenes, alkyl chains, and a Boc-protected
amine, were well tolerated, affording the corresponding products in
good yields.\ The method also \mbox{extended} to sulfonamides
incorporating alternative aroyl groups, although substrates bearing
electron-donating substituents showed reduced efficiency
(Scheme~\ref{sch6}).

Notably, the protocol was compatible with stereochemically sensitive
compounds. When enantiomerically enriched substrates were subjected to
the reaction conditions, the corresponding products were obtained with
full retention of enantiopurity. This indicates that the transformation
proceeds without racemization, even in the presence of base-sensitive
stereogenic centers (Scheme~\ref{sch6}).

It is worth highlighting that the presence of an aroyl group on the
sulfonamide was critical for successful cleavage. Substrates featuring
alternative groups such as acetyl, Boc, or methyl failed to undergo
transformation under the optimized conditions (Scheme~\ref{sch6}).

To gain deeper insight into the mechanism of the photodesulfonylation
promoted by pCp-based coumarins, we conducted a series of mechanistic
studies. Computational analysis realized in collaboration with
A.~Maruani (LCBPT UPCit\'{e}) revealed that energy transfer (EnT) from
the excited state of catalyst \textbf{9b} to the lowest excited state
of substrate \textbf{19a} is thermodynamically uphill ($\Delta
G_{\mathrm{EnT}} = +1.13$~eV), rendering this pathway unlikely. Based
on prior studies involving an iridium-based photocatalyst combined with
a Hantzsch ester~\cite{80}, we hypothesized that the sulfonamide
cleavage could proceed via a photoinduced electron transfer (ET)
mechanism.

Electrochemical measurements of the redox potentials of \textbf{9b},
\textbf{19a}, and \textbf{21}, combined with the determination of the
excited-state energy (E$^*$) of \textbf{9b} via absorption and
fluorescence spectroscopy, \mbox{enabled} the evaluation of the Gibbs
free energy for potential photoinduced electron-transfer processes.\ 
According to this analysis, ET from the \mbox{excited} \mbox{catalyst}
to the Hantzsch ester is thermodynamically favorable ($\Delta
G_{\mathrm{ET}} = -0.63$~eV). Conversely, direct ET from the excited
state of \textbf{9b} to substrate \textbf{19a} is
\mbox{thermodynamically} disfavored ($\Delta G_{\mathrm{ET}} =
+0.13$~eV). Furthermore, UV--Vis absorption studies excluded the
formation of electron donor--acceptor (EDA) complexes, as no
appreciable spectral changes were detected upon gradual addition of
either \textbf{19a} or \textbf{21} to a solution of \textbf{9b}.
Finally, the reaction was shown to halt immediately upon interruption
of light irradiation, thereby excluding the involvement of a
self-propagating radical chain process in the photocleavage mechanism.

Based on the collected experimental data, the photodesulfonylation was
proposed to proceed via the mechanism illustrated in Scheme~\ref{sch7}.

\begin{scheme*}
\includegraphics{sc07}
{\vspace*{.5pc}}
\caption{\label{sch7}Mechanistic proposal for the photodeprotection
mediated by pCp-based coumarins.}
\end{scheme*}

Upon irradiation at 300~nm, pCp-based catalyst \textbf{9b} is promoted
to its excited state (\textbf{A}), which then undergoes a
single-electron transfer (SET) with the Hantzsch ester. This step
generates dihydropyridine radical cation \textbf{C} and
coumarin-centered radical anion \textbf{B}. The radical anion
subsequently interacts with the reaction substrate, forming radical
intermediate \textbf{D} and regenerating the ground-state
photocatalyst. Note that the formation of intermediate \textbf{D}
aligns with analogous species previously identified in related
electrochemical processes~\cite{84}. Radical \textbf{D} then undergoes
homolytic cleavage of its \mbox{N--S} bond, yielding carboxamide anion
\textbf{E} and aryl sulfonyl radical $\mathrm{ArSO}_{2}^{\bullet}$. The final
desulfonylated product is formed through quenching reactions between
these species and dihydropyridine radical cation~\textbf{C}. The
proposed mechanistic pathway was further corroborated by theoretical
calculations carried out in collaboration with A.~Maruani (LCBPT
UPCit\'{e}).

Attaining precise control over chirality in photoinduced organic
transformations remains one of the foremost challenges in the field of
photocatalysis. While numerous reports have demonstrated satisfactory
enantioselectivities using costly transition-metal-based
catalysts~\cite{85}, there is growing interest in metal-free
strategies. These approaches often employ chiral organocatalysts that
function dually as stereocontrolling agents and
photosensitizers~\mbox{\cite{86,87,88}}.\ Despite these advances,
examples of asymmetric photocatalytic reactions driven by such
organocatalysts remain scarce~\cite{89}. Building on this background,
our current research is focused on investigating enantiopure planar
chiral pCp derivatives as photocatalysts to promote asymmetric
transformations, aiming to broaden the scope of light-driven
enantioselective photocatalytic processes.

\section{Developing RNA binders using{\hfill\break} [2.2]paracyclophane
scaffolds} \label{sec7}

Ribonucleic acids (RNAs) are fundamental biomolecules involved in the
regulation of a variety of different cellular processes, including,
for~\mbox{instance}, gene expression and protein synthesis~\cite{90}.
Beyond their canonical roles, RNAs have increasingly been recognized as
key actors in the onset and progression of various diseases, such as
certain cancers, as well as genetic or neurodegenerative
disorders~\cite{91,92}. Today, RNA is broadly recognized as a valuable
therapeutic target. However, despite this acknowledged potential,
developing small molecules that selectively bind to RNA and modulate
its function remains a significant challenge in medicinal chemistry. 

Most RNA-binding ligands identified to date are planar or rod-like
molecules that may show strong binding affinity but often lack
selectivity~\cite{93,94,95,96,97}. Their limited ability to distinguish
between closely related RNA structures, or even between RNA and DNA,
significantly restricts their therapeutic usefulness. Consequently,
there is an increasing need to discover and develop novel molecular
scaffolds that combine high specificity with strong binding to
well-defined RNA targets.

Small molecules interact with nucleic acids through diverse binding
modes. Cationic ligands primarily participate in electrostatic
interactions with the negatively charged phosphodiester backbone,
whereas flat aromatic compounds typically participate in
${\uppi}$--${\uppi}$ stacking interactions with nucleobases. These
interactions can occur via intercalation between base pairs or by
occupying the major and minor grooves of helical structures. However,
these binding modes are intrinsically limited in selectivity and often
fail to distinguish between RNA and DNA duplexes, owing to their
similar base-pairing architectures. 

To circumvent these limitations, recent studies have focused on
incorporating non-planar aromatic motifs that exploit the inherent
structural plasticity of RNA. Indeed, unlike DNA, RNA is predominantly
found in cell as single-stranded sequences and capable of folding upon
itself to generate complex secondary and tertiary architectures,
including bulges, internal loops, pseudoknots, and three-way junctions.
These unique structural features offer distinct molecular recognition
sites for small molecules. For instance, spirocyclic compounds have
demonstrated remarkable selectivity for bulged, non-canonical RNA
regions (Scheme~\ref{sch8}a)~\cite{98,99}.

\begin{scheme*}
{\vspace*{-.2pc}}
\includegraphics{sc08}
{\vspace*{.4pc}}
\caption{\label{sch8}Examples of three-dimensional ligands
preferentially targeting non-paired RNA structures.}
{\vspace*{-.4pc}}
\end{scheme*}

Similarly, triptycene-based ligands have been reported to specifically
target three-way junctions (Scheme~\ref{sch8}b)~\cite{100,101,102}.
Notably, these last compounds exhibited potential as modulators of the
heat shock response in \textit{E.~coli}, highlighting their functional
relevance as RNA-targeting agents. The non-planar architecture of these
molecules, which arranges aromatic groups across orthogonal planes,
appears to mitigate non-specific intercalation into double-helical
regions. This spatial configuration enhances selectivity for non-duplex
RNA motifs while minimizing off-target interactions with
double-stranded DNA, thus overcoming a common limitation of planar
aromatic RNA-binding compounds. 

Inspired by these precedents, we hypothesized that pCps could
preferentially drive recognition of non-helical RNA structural
motifs.\ Indeed, their rigid and sterically demanding architecture,
characterized by a 3.1~{\AA} distance between the benzene moieties
(Figure~\ref{fig1}), does not match the helical rise per base pair in
double-stranded RNA (2.6~{\AA}) or DNA (3.4~{\AA}), making
intercalation unlikely and effectively limiting interactions with RNA
or DNA duplexes (Figure~\ref{fig6}). 

\begin{figure*}
\includegraphics{fig06}
\caption{\label{fig6}Rationale for targeting non-paired RNA motifs
using pCp.}
{\vspace*{2pc}}
\end{figure*}

Guided by this rationale, we explored pCp as a central core for the
design of novel RNA-binding ligands. Simultaneously, we aimed to
exploit the intrinsic photophysical properties of pCps to monitor
ligand--RNA interactions via fluorescence spectroscopy, enabling
real-time observation of binding events.\looseness=-1

Cyanine dyes are well-established probes in chemical biology,
frequently used for nucleic acid staining~\cite{62,103,104}. These dyes
exhibit strong fluorescence turn-on behaviors upon target binding. We
therefore set out to compare the luminescence responses of pCp-based
cyanine dye \textbf{12} with those of analogous flat cyanine
\textbf{13} in the presence of nucleic acids.\looseness=-1

As described earlier in this article, both compounds exhibited low
emission in aqueous buffer (Table~\ref{tab3}). However, upon the
addition of increasing amounts of tRNA, a significant fluorescence
enhancement was observed for both cyanines, demonstrating that
incorporation of the pCp moiety into the luminophore does not
negatively impact the turn-on behavior of the cyanine
(Figure~\ref{fig7})~\cite{61}.

\begin{figure*}
\includegraphics{fig07}
\caption{\label{fig7}Turn-on fluorescence responses of cyanines
\textbf{12} (in blue) and \textbf{13} (in red) in the presence of
increasing amounts of tRNA.}
{\vspace*{2pc}}
\end{figure*}

Digestion studies with RNase A confirmed that the observed fluorescence
enhancement is attributable to the presence of RNA in
solution~\cite{35}. Since cyanines are known to form
aggregates~\cite{63}---a tendency also confirmed for pCp derivative
\textbf{12}---, the observed turn-on responses were attributed to
\mbox{disaggregation} processes triggered by the interaction of the
dyes with RNA.

We next compared the behavior of the flat and three-dimensional
cyanines in the presence of different types of nucleic acids.
Interestingly, flat compound \textbf{13} exhibited comparable
fluorescence turn-on responses with all tested nucleic acids
(Figure~\ref{fig8}, in red), indicating a non-selective interaction
profile. In contrast, three-dimensional pCp-based derivative
\textbf{12} displayed only modest fluorescence enhancements in the
presence of double-stranded DNA or RNA (Figure~\ref{fig8}, in blue),
while it showed markedly stronger turn-on behaviors with nucleic acids
containing multiple unpaired regions, with a clear preference for tRNA.

\begin{figure*}
\includegraphics{fig08}
\caption{\label{fig8}Turn-on fluorescence responses of cyanines
\textbf{12} and \textbf{13} (10$^{-6}$~M) in the presence of diverse
nucleic acid (0.4~mg/mL) in Tris-EDTA (TE) buffer at
20~{\textdegree}C.}
\end{figure*}

\begin{table*}[t!]%tab6
\tabcolsep23.5pt
\caption{\label{tab6}Dissociation constants ($\upmu$M) for RNA--cyanine
\textbf{12} interactions
\vspace*{4pt}\tpar{\protect\inlinefig{fx06}}\vspace*{-10pt}}
\begin{tabular}{ccccc}
\thead
I$^{\mathrm{a}}$ & II$^{\mathrm{a}}$ & III$^{\mathrm{a}}$ &
IV$^{\mathrm{b}}$ & V$^{\mathrm{b}}$\\
\endthead
{\phpm}14.22 & 24.53 & {\phpm}6.04 & {\phpm}0.54 & {\phpm}1.65\\
${\pm}$14.46 & ${\pm}$6.60 & ${\pm}$2.05 & ${\pm}$0.16 & ${\pm}$1.14
\botline
\end{tabular}
\tabnote{$^{\mathrm{a}}$10$^{-6}$~M solution of dye \textbf{12} in
Tris-EDTA (TE) buffer. $^{\mathrm{b}}$10$^{-7}$~M solution of dye
\textbf{12} in Tris-EDTA (TE) buffer. Data are presented as mean of the
three independent experiments ${\pm}$ standard deviation.}
{\vspace*{-.2pc}}
\end{table*}

Fluorescence titrations performed with custom-designed hairpin loops of
different sizes (\textbf{I}--\textbf{V}, Table~\ref{tab6}) further demonstrated
that pCp-based dye \textbf{12} interacts weakly with small loop
structures, while exhibiting higher binding affinity---reflected by
lower dissociation constants ($K_{\mathrm{d}}$)---for larger loops.
Remarkably, the dye showed a marked preference for a sequence
containing eight unpaired nucleotides ($K_{\mathrm{d}} \sim
0.54~\upmu$M, Table~\ref{tab6}). It is also worth noting that, at this
stage, both racemic and enantiopure compounds exhibited similar
behavior~\cite{35}.

In the future, the ability of enantiopure pCp-based luminophores to
emit circularly polarized luminescence may be harnessed to monitor
RNA--ligand interactions via CPL spectroscopy. This approach may offer
several advantages, including enhanced sensitivity and selectivity
stemming from the polarized nature of the emitted light, reduced
background interference relative to conventional fluorescence methods,
and the potential to provide detailed insights into the chiral
environment and binding-induced conformational changes of RNA
structures.

\section{Conclusions} \label{sec8}

Thanks to their unique three-dimensional geometry, distinctive
electronic properties, and atypical reactivity, [2.2]paracyclophanes
(pCps) have emerged as versatile molecular platforms attracting growing
interest across diverse areas of chemical research.

In this account, we have highlighted a variety of strategies that
enable the selective functionalization of their aromatic cores,
efficient control over planar chirality, and modulation of their
photophysical properties. The methods developed in our laboratory have
enabled access to structurally diverse pCp scaffolds with tunable
spectroscopic behaviors on synthetically useful scales. These rigid
$\uppi$-stacked systems exhibited significant potential in fields such
as organic and organometallic luminophore chemistry, photocatalysis,
and chemical biology. Nevertheless, important challenges remain to be
addressed. For example, the development of selective functionalization
protocols targeting the ethylene bridges and the \textit{meta} or
\textit{pseudo-meta} positions of these \mbox{scaffolds} could greatly broaden
their chemical diversity. Strategies to further modulate the \mbox{absorption}
and emission properties of functionalized pCps, such as attaining
higher brightness and enhanced CPL efficiency, also warrant continued
investigation. In lanthanide chemistry, pCp-based ligands with planar
chirality may lead to the development of next-generation luminescent
and multimodal metal complexes. The use of enantiopure chiral pCp
derivatives as photosensitizers in photoredox catalysis also remains
underexplored and could enable the design of novel light-activated
asymmetric transformations. Finally, our recent efforts to incorporate
the pCp motif into RNA-binding small molecules have opened promising
avenues for targeting non-paired structural motifs within nucleic
acids. However, further studies are required to better elucidate the
precise binding mode of pCp derivatives to RNA.

In summary, pCps represent a fascinating class of molecular
architectures that continue to captivate the chemistry community.
Despite the significant progress already achieved in their synthesis
and controlled functionalization, we are confident that ongoing
research on these original compounds will continue to drive innovation
across a range of disciplines, including organic synthesis, materials
science, and chemical biology.

\section*{Acknowledgments}
The authors extend their sincere thanks to all undergraduate, master's, and PhD students, as well as
postdoctoral researchers and collaborators, for their invaluable
contributions. Special thanks are due to J.~Crassous, L.~Favereaux, and
F.~Pointillart (Univ. Rennes~1); O.~Maury and L.~Abad-Galan (ENS Lyon);
A.~Maruani, S.~Lajnef, F.~Peyrot, C.~Sagn\'{e} and S.~Turcaud (Paris
Cit\'{e} University).

\section*{Declaration of interests}

The authors do not work for, advise, own shares in, or receive funds
from any organization that could benefit from this article, and have
declared no affiliations other than their research organizations.

\section*{Funding} 

The authors gratefully acknowledge the support of the CNRS and Paris
Cit\'{e} University (\textit{IdEx Dynamique Recherche
pCp-Photocat - ANR-18-IDEX-0001}), as well as funding from the
\textit{Agence Nationale de la Recherche} (\textit{ANR JCJC
PhotoChiraPhane - ANR-19-CE07-0001-01}). 

\CDRGrant[ANR]{ANR-18-IDEX-0001}
\CDRGrant[ANR]{ANR-19-CE07-0001-01}

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