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A Photoinduced Annulation Strategy Towards a Polycyclic
Heteroaromatic Chromophore: Scope, Mechanism,
Properties and Applications
Marine Labro,[a] Audrey Pollien,[a, b] Maëlle Mosser,[a] Delphine Pitrat,[a]
Jean-Christophe Mulatier,[a] Mathilde Seinfeld,[a] Tangui Le Bahers,*[a, d] Bruno Baguenard,[c]
Stéphan Guy,[c] Cyrille Monnereau,*[a] and Laure Guy*[a]
This article reports a detailed mechanistic and kinetic study of
an unusual photoreaction leading to the (diazonia)tetrabenzo-
naphthacene skeleton. The photo-triggered double intramolec-
ular nucleophilic aromatic substitution (SNAr*) has been inves-
tigated by varying the leaving groups. Photoreaction quantum
yields have been determined and mechanistic insights have
been supported by theoretical calculations using DFT and TD-
DFT methods. Additionally, we show that this light-triggered
formed diazonia constitutes a potent photosentitizer with a
singlet oxygen generation quantum yield of 0.55, both in
organic solvents and in water, which is an extremely relevant
value in view of PDT applications or use as an oxidation
photocatalyst in aqueous media. Once again, the experimental
observations were supported by TD-DFT calculations showing a
large density of triplet states below the S1excited state along
with large spin-orbit couplings. The reaction is not restricted to
solutions but can also occur in solid PDMS matrices thus
allowing for photochemical encoding of information that will
progressively vanish upon prolonged UV-exposure.
Introduction
Small polyaromatic and polycyclic heteroaromatic (PHA) mole-
cules combine unique and attractive optical and electronic
features of both fundamental relevance and practical
interest.[1–3] Effective electronic delocalization along their π-
conjugated backbone contributes to reducing the HOMO-
LUMO gap, which finds application in the design of chromo-
phores operating in the visible and near-infrared,[4,5] of photo-
redox active molecules for application in organophotocatalysis[6]
or as organic semiconductors, among many others.[7] Extended
π-conjugated scaffolds are also prone to supramolecular non-
covalent interactions,[8–10] and have been therefore used as
building blocks in functional self-assembled architectures,[11,12]
or else as probes for molecular recognition of a variety of
analytes, including biomolecules such as nucleobases.[13,14] In
that context, their intrinsic structural rigidity renders the vast
majority of PHA molecules highly fluorescent which facilitates
the detection of the aforementioned association processes.
Finally, the distortion of the molecular aromatic backbone from
planarity, induced by ring-strain, is at the origin of more exotic
properties of certain PHAs. These include the open-shell ground
state configuration (aka diradical), of great interest for the
construction of molecular magnets,[15,16] spintronic compounds,
and distortion induced increase of spin-orbit coupling (SOC),
giving access to room temperature phosphorescent materials or
singlet oxygen photosensitizers.[17,18]
Our group recently reported on a highly selective photo-
cyclization strategy presented Scheme 1. The easily accessible
organic precursor 2 a may be photocyclized by two nucleophilic
additions of the quinoleine moieties on the opposite triflate
substituted positions. After elimination of the triflate leaving
group, this photoinduced reaction leads to the formation of an
unprecedented (diazonia)tetrabenzo naphthacene derivative
3.[19] Back then, we showed that the conversion could be easily
monitored by UV-visible absorption or fluorescent spectro-
scopic methods. Furthermore, pure 3was isolated at 10 mg
scale as its chloride salt by simple extraction from the reaction
medium with a NaCl solution. By replacing triflate groups by
water-soluble pegylated groups in 2 b, the reaction could also
proceed in water and even in cellulo. In the latter case, 3
behaved as a selective binding molecule to G-quadruplex DNA
structures (G4), providing a stabilization that was comparable to
state-of-the-art compounds used in G4 targeted cancer therapy.
[a] M. Labro, A. Pollien, Dr. M. Mosser, D. Pitrat, J.-C. Mulatier, M. Seinfeld,
Prof. Dr. T. L. Bahers, Dr. C. Monnereau, Dr. L. Guy
ENS de Lyon, CNRS, Université Claude Bernard Lyon 1, LCH UMR 5182,
69342, Lyon cedex 07, France
E-mail: laure.guy@ens-lyon.fr
cyrille.monnereau@ens-lyon.fr
tangui.le_bahers@ens-lyon.fr
[b] A. Pollien
Université Paris-Saclay, ENS Paris-Saclay, DER Chimie, 91190, Gif-sur-Yvette,
France
[c] Dr. B. Baguenard, Prof. Dr. S. Guy
Univ. Lyon, CNRS, Institut Lumière Matière UMR 5306,
69622 Villeurbanne, France
[d] Prof. Dr. T. L. Bahers
Institut Universitaire de France, 5 rue Descartes,
75005 Paris, France
Supporting information for this article is available on the WWW under
https://doi.org/10.1002/cptc.202400199
© 2024 The Authors. ChemPhotoChem published by Wiley-VCH GmbH. This
is an open access article under the terms of the Creative Commons Attri-
bution License, which permits use, distribution and reproduction in any
medium, provided the original work is properly cited.
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In the present article, we further explore the potential of
this annulation reaction and the resulting diazonia compound,
investigating its potential for use in various optoelectronic
related applications. First, using a variety of precursors 2 n
(Scheme 2) that differ by the nature of the leaving group (X =F,
Cl, Br, I, OTf, OC(O)R, NR2, H), we evaluate the influence of the
latter on the photocyclization efficiency. Furthermore, based on
quantum chemical calculations, we propose a mechanism
accounting for the observed reactivity. We also study in detail
the photophysical features of compound 3: in particular, we
show that this molecule undergoes efficient distortion-induced
singlet-to-triplet excited state intersystem crossing (ISC),[20,21]
which we rationalize using TD-DFT. Finally, we highlight that
the photoinduced annulation reaction can operate not only in
solution, but also in the solid state, in doped PDMS matrices.
This feature highlights a possible use of the molecule for
temporary optical data-storage purposes, with possible applica-
tions in security and anti-counterfeiting[22,23] or UV-light expo-
sure tracing and dosimetry.[24]
Results and Discussion
Synthesis
Synthesis of all precursors 2 n could be achieved following
procedures that have been well established in previous works
from our group.[25,26] This synthetic pathway starts from the
commercially available 7-methoxy tetralone thus the final
skeleton always incorporates the 5,5’,6,6’-tetrahydro-[1,1’-
bibenzo[c]acridine]-2,2’-dialkoxy fragment and gives access to
oxygenated living group such as triflate (OTf 2 a) or poly-
ethylene glycol (OPEG5in 2 b). In this study, we choose to
extend the oxygenated series in order to optimize the photo-
cyclization quantum efficiency by comparing the leaving group
ability of the hydroxy 1, methoxy 2 c and the bis-esters 2 d–e.
The latter are obtained in one step from reaction of 1with the
corresponding acyl chloride. Halogen substituents were also
considered as leaving groups, leading us to develop an
approach for the introduction of all halogen atoms at the 2-2’
positions of this skeleton. As shown in Scheme 3, a Sandmeyer
reaction[27] at the last stage of the synthetic pathway afforded,
depending on the inorganic salt used in the quenching step of
the diazonium intermediate, either the unsubstituted com-
Scheme 1. Previous results: photoconversion to fluorescent diazonia 3from two precursors 2 a or 2 b.
Scheme 2. Series of photoreaction precursors 2 n covered in this study.
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pound 2 l or the chloro 2 f, bromo 2 g and iodo 2 h derivatives
from the 2,2’-diamino precursor 2 k. The synthesis of 2 k was
achieved in six steps from the commercial 7-nitro tetralone 4.
As already reported,[28,29] the nitro group of 4is first reduced by
iron in an acidic medium to give 5in 91 % yield. Then, the
selective bromination at the 8-position of 5is carried out using
N-bromo succunimide (NBS) to give compound 6in 75 % yield.
The Friedlander condensation between the tetralone 6and
the in situ generated 2-aminobenzaldehyde under microwave
irradiation at 70°C afforded compound 7in 70% yield. Bis
acetylation of the resulting 1-bromo-5,6-dihydro-
benzo[c]acridin-2-amine 7to give 8was necessary for the next
Ullmann coupling to proceed in good yield. Indeed, heating of
8at 160°C for about 36 hours with powdered copper yielded
the homo-coupling product 2 j almost quantitatively. Finally,
deacetylation under standard mild acidic condition gave the
expected bis-amine 2 k in 94 % yield.
2 l was synthesized by a Sandmeyer reaction following
commonly encountered protocols consisting in adding the
hypophosphorous acid solution onto a solution of the diazo-
nium. The reduced compound 2 l could only be isolated in poor
yield (14%) probably due to diazonium decomposition. For the
bis-halogenation reaction, we systematically used as the acid
source the hydrohalic acid matching the halogenating agent
(CuCl/HCl, CuBr/HBr, KI/HI) in order to avoid the formation of
mixtures of differently halogenated products. Finally 2 f–hwere
isolated in fair yields (~35 %). Unfortunately, all our attempts to
obtain the fluorinated derivative 2 i using fluorinating agents
(NEt3.3HF, NaBF4, BF3.Et2O) turned out unsuccessful. The alter-
native pathway described in Scheme 4 was then specifically
elaborated for 2 i. It takes advantage of the commercial
Scheme 3. Synthetic route for bis-halogenated 2 f–h, amino 2 j–kand hydrogenated compound 2 l with the exception of the fluorinated derivative 2 i.
Scheme 4. Specific synthetic route for the bis-fluorinated derivative 2 i.
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availability of 7-fluoro tetralone 11. However, direct bromina-
tion of 11 at the 8-position using the same conditions as
described for 5was not selective. Thus, using a strategy
reported in Refs. [30–32], the oxime 12 was synthesized in 98 %
yield and found to act efficiently as a directing group for the
Pd(OAc)2-catalyzed halogenation. After hydrolysis of the oxime
in acidic conditions, the expected 8-bromo-7-fluoro-1-tetralone
14 could finally be isolated in three steps with a satisfying 66 %
yield from the commercial source. As expected from the
electronic density in 14,[33,34] fair selectivity of the Ullmann
coupling at the CBr position was observed, and 15 was
isolated in a moderate yield (34%). As a final step, Friedlander
reaction on the two ketones gave the expected bis-fluoro 2 i
compound in 82% yield.
Photophysical Characterizations
With the series of compounds 2 n in hand, we then undertook a
systematic comparison of the efficiency of the light triggered
reactions among the series. First, we recorded the absorption
spectra of all compounds which, as anticipated, showed in all
cases similar transitions wavelengths as compared to the
previously reported compound 2 a (Figure 1), albeit with small
differences in their extinction coefficients values. Thus, the
excitation in the lowest-in-energy absorption bands was
possible for all the compounds at the same wavelength, namely
344 nm. Practically, we decided to perform the photoreactions
using either a 450 mW Xenon lamp equipped with a double
monochromator system within our spectrofluorimeter setup
(providing ~2 mW at l=344 nm) or a 340 nm LED (70 mA –
2.3 mW power) focused on the sample for larger scale reactions,
performed in standard glasswares.
No reaction occurred when starting from 2 c,2 j–l, demon-
strating that neither direct cleavage of the C-OMe and CH
bonds nor substitution of an amine or amide moiety was able
to initiate the photoactivated reaction.
In sharp contrast, as seen in Figure 2 and Figures S32–S46 in
the Supplementary Information, UV-vis monitoring of the
reactions of 2 a and 2 d–e,2 f–irespectively, as a function of the
irradiation time clearly revealed the concomitant decrease in
the absorbance of the precursor at 330 and 344 nm and the
increase of new bands at 400, 416 and 439 nm, with a similar
pattern for all photoconversions.
Moreover, in all cases, steady isosbestic points at 316 nm
and 351 nm were monitored throughout the whole photo-
conversion, which constitutes strong evidence of an exclusive
reactant-to-product conversion. Halides being the counterions
of some of the photoproducts, these reactions had to be
conducted in a mixture of acetonitrile and water to ensure the
solubility of the final dicationic product. Comparison of the
absorption spectra at long reaction times is presented in
Figure 3 and shows superimposable spectra for compounds 2a
and 2 d–iwhere almost complete conversion could be achieved
within less than 60 min for an exposure at 340 nm – 2.3 mW or
344 nm – 2 mW. This was expected as the photogenerated
product only differs by the nature of their counter-ions, which
are not expected to significantly affect the spectral signature in
dissociating solvents such as acetonitrile. The positions of the
isosbestic points resemble those observed in the previously
documented photoconversion of 2 a, and the final absorption
Figure 1. Comparison of the absorption spectra in ACN/Water 2/1 of 2 a,2 d,
2 e–i.
Figure 2. UV/Vis spectral evolution of a MeCN/H2O 2/1 solution of 2 a
(C=3.50 μM) at T=298 K under irradiation at 340 nm (LED).
Figure 3. Comparison of absorption spectra in MeCN/H2O 2/1 of recorded at
reactions time corresponding to the maximal conversion of 2 a and 2 d–ito
give 3.
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spectra confirm the anticipated formation of 3. For 2 f,2 g and
2 h, even at long reaction times (170, 185 and 120 min
respectively), photoconversions were still not complete as
proved by the residual absorption band at 345 nm. Moreover,
at long reaction times, the evolution of the absorbance at
typical wavelengths characteristic of the photoproduct (400,
416 and 439 nm) ended up diverging from the general trend,
and a deviation of the isosbestic point progressively occurred.
This is indicative of a photobleaching reaction competing with
the reaction of interest, and highlights the importance of
maximizing the efficiency of the latter by careful choice of the
leaving group, in order to promote exclusive formation of the
target photoproduct.
Theoretical Investigation of the Mechanism
The mechanism of this cyclization, which is only observed upon
light activation, was further investigated by quantum chemical
calculations. The energetic profile of two consecutive nucleo-
phile substitutions was computed at the TD-DFT level. Calcu-
lations were performed on the 2 a precursor, which exhibits one
of the highest photoconversion efficiencies. The reaction
profiles are provided in Figure 4. First, we can observe that the
reaction is overall exergonic meaning that both the first
nucleophilic substitution (leading to the molecule noted as the
intermediate I) and the second one (leading to the product)
stabilize the energy of the system with an overall stabilization
of about 200 kJ mol1. However, at the ground state (black
curve), the activation energy for the first nucleophilic substitu-
tion is notably large (around 190 kJmol1), supporting the fact
that the cyclization cannot thermally happen within a reason-
able temperature range, in agreement with experimental
observation. We then assumed that, after light absorption, the
molecule 2 a relaxes toward the lowest excited state, noted S1,
following Kasha’s rule. At this excited state, the computed
energy barriers are reduced by almost one order of magnitude.
This reduction originates from the population of an unoccupied
orbital having a bonding character between the N and C atoms
involved in the cyclization (see Figure 5). We also considered
the first triplet exited state since an intersystem crossing from
the S1state is a possibility. Although the reduction in the
energy barrier is not as significant as it is for the S1state, we still
computed a lower barrier in the triplet excited state, reduced
by a factor of 3, compared to the ground state. The character-
istic bond lengths associated to the transition states at the
different electronic states are provided in the Table 1.
Quantum Yields of Reaction
From the above photoconversions monitoring in the series, we
can qualitatively identify three behaviors depending on the
substituent located at the photoinduced SNAr sites. (i) Ether in
2 c, amide in 2 j, amine in 2 k or hydrogen in 2 l do not behave
as leaving groups and preclude the formation of photoinduced
products under the irradiation conditions tested. (ii) Chlorine,
Figure 4. Reaction path for the successive nucleophilic substitutions com-
puted at the S0, S1and T1states.
Figure 5. LUMO orbitals, singly occupied at the S1state showing the
bonding character between the N and C atoms involved in the bond
formation. (a) at the TS1 geometry of the S1excited state and (b) at the TS2
geometry of the S1excited state.
Table 1. Selected bond distance computed for the 2 a molecule and the
two consecutive transitions states at the S0, S1and T1electronic states.
dCN (Å) dCO (Å)
2 a/TS1/TS2 2 a/TS1/TS2
S03.020/1.956/1.686 1.416/1.806/1.513
S12.692/2.162/1.926 1.406/1.410/1.453
T13.023/2.127/1.926 1.410/1.411/1.441
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bromine and iodine in 2 f-g are intermediate leaving groups
that allow partial photochemical conversions accompanied by
other undesired pathways such as photobleaching or other
photodegradation processes. (iii) Triflate in 2 a, esters in 2 d and
2 e, fluorine in 2 i are good leaving groups. They result in a
clean and quantitative reageant-to-product conversion and
should be the preferred precursors for practical synthetic
purposes.
To assess the efficiency of the photochemical processes in a
more quantitative way, we then determined the quantum yields
Fof the reactions. In the chosen experimental conditions,
kinetics of the photoreaction relates to the photochemical
quantum yield Fof a given reaction according to Eq. (1).[35,36]
F¼kfit:C0
I0:ð110A0Þ(1)
where C0and A0are the concentration and the absorbance of
the solution at 340 nm, kfit is the reaction rate, I0, the photon
flux (molL1s1from the sources at 340 nm or 344 nm
determined by actinometry as previously described in detail[37]
and featured in Supplementary Information). The reaction rate
kfit can in turn be obtained from fitting the experimental kinetic
data using a mono-exponential kinetic model.
kfit and quantum yields measured for the herein synthesized
precursors are gathered in Table 2. Previously reported refer-
ence compound 2 a, featuring triflate substituents as leaving
groups, was first investigated in a 2/1 MeCN/H2O mixture using
the two different setups (LED or Xenon lamp). In both cases,
very similar photoreaction quantum yield values were obtained
using both setups, ie 7% (340 nm LED) and 6.2 % (344 nm Xe
lamp). A significant improvement of the reaction efficiency
could be achieved in the same solvent when replacing triflate
substituents by ester substituents as leaving groups : the
quantum yields for the esters 2 e and 2 d, were thus the highest
among the series with a value of 9.3 % for 2 e and 7.9 % for 2 d.
Among halogenated derivatives, fluorine in 2 i was by far the
most efficient leaving group albeit with a much lower quantum
yield (2.6%) as compared with the esters and triflate. The three
other halides, chlorine 2 f, bromine 2 g or iodine 2 h compara-
tively present lower quantum yield, all comprised, within
experimental errors between 1.4% and 1.2%. As reported for
SNAr*,[38] this reactivity order in the halide series, with F being
the most efficient leaving group as compared to other less
electronegative halides, follows a polarity reversal from reactant
to transition state commonly encountered for the regular
thermally activated SNAr of aryl halides.[39]
As discussed in the theoretical mechanical investigation
section, photocyclisation can occur from two distinct excited
states with different spin multiplicities: T1and S1. Although the
energy barrier is lower in the S1state, the considerably longer
lifetime[40] of triplet states raise questions about which state
might be involved in the mechanism. In order to address this
issue, photoconversion rate was studied on 2 b in a thoroughly
degassed, air-tight spectroscopic cuvette (see Figure S39 in
Supplementary Information for details). While the intrinsic short
lifetimes of singlet excited states are generally only marginally
affected by the presence of oxygen, diffusion-controlled
collisions between oxygen molecules and triplet excited state
molecules result in collision-induced energy transfers, signifi-
cantly reducing the excited state lifetime and their propensity
to react with other components in the medium. The observed
increase in reaction kinetics upon oxygen removal thus most
likely indicates that the intramolecular SNAr reaction initiating
the photocyclization of compound 2to 3occurs from the
molecule’s excited triplet state. As revealed by TD-DFT, an
energy barrier of 65 kJ/mol is associated with this process. For
such SNAr reactions, it is well established that this energy barrier
corresponds to the formation of the Meisenheimer activated
complex,[41] which is expected to be stabilized in polar solvents,
Table 2. Photoreaction quantum yields F½%measured with a LED at 340 nm or a Xe lamp at 344 nm(†).
CH3CN/H2O 2/1 CH3CN Chloroform Toluene Ethanol
1– 0 – – –
2 a 7:00:2 5:50:4 1:60:1 2:70:1 1:70 0:04
6:2y0:2
2 b 0:3y0:02 – – – –
2 c – 0 – – –
2 d 7:6y0:2 – – – –
2 e 9:3y0:1 – – – –
2 f 1:60:03 – – – –
2 g 1:40:03 – – – –
2 h 1:40:03 – – –
2 i 2:60:1 – – – –
2 j – 0 – – –
2 k – 0 – – –
2 l – 0 – – –
(–)=not determined.
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leading to an increase in the reaction kinetics. Thus, we have
also investigated the role of the solvent on the photocyclization
of the reference bis-triflated 2 a. Again, the UV-visible spectra of
the solutions before irradiation show the same absorption
bands with no solvatochromism in the reagent (see Figure S47
in the Supplementary Information). The conversions show
similar spectral evolution in all the solvents except in ethanol
(see Figures S32–S37 in the Supplementary Information) and
the quantum yields of the reaction have been determined at
340 nm using the LED as the irradiating source. This study
shows that reaction proceeds considerably faster in acetonitrile
or acetonitrile/water mixtures than in less polar dichloro-
methane or toluene in agreement with the stabilization of a
possible Meisenheimer intermediate in polar solvents. The
photoreaction in ethanol does not follow this general trend,
exhibiting even slower kinetics perhaps attesting for the
formation of a different photoproduct which was not further
characterized.
Singlet Oxygen Generation
A photoluminescence quantum yield Ff=14% was measured
for 3. This constitutes a relatively low emission efficiency
especially in comparison with other polycyclic aromatic and
heteroaromatic compounds, where nonradiative processes are
strongly restricted owing to the structural rigidity of the
molecules. Singlet-to-triplet intersystem crossing (ISC) might
thus be another possible mechanism accounting for the low-
fluorescence efficiency. Singlet oxygen generation was thus
monitored in deuterated chloroform, as an indirect method-
ology to probe and quantify triplet excited state formation
(quenching of triplet state through energy transfer to molecular
oxygen being a very efficient decay pathway in organic
molecules). We recorded the characteristic 1O2phosphores-
cence quantum yield and compared it with the signal obtained
with a known literature benchmark (perinaphtone, FD¼95 %
in chloroform). As anticipated, we found a high singlet oxygen
generation quantum yield FCDCl3
Dð3Þ ¼ 55 %. TD-DFT computa-
tions helped rationalizing the singlet oxygen generation proper-
ties of 3. The intersystem crossing (ISC) between the S1to the
triplet states that will eventually drive 1O2generation was
investigated by computing the energy of triplet states below S1
at the stable S1geometry along with the spin-orbit coupling
(SOC) between the S1and the triplet states. These calculations
(see Figure S49 in the Supplementary Information) revealed
that four triplet states are energetically lower than S1, two of
them within a 0.2 eV range to S1, and an average SOC values
ranging from 0.1 to 0.4 cm1, a standard value for organic
molecules.[42] The large density of triplet states close to S1, and
the relatively large SOC constant between these states are two
favorable features that account for large ISC efficiencies, which
can here occur by several possible paths from the S1to one of
the triplet states, and experimentally translates into high singlet
oxygen generation efficiency, which compares well with some
of the most classically used organic photosensitizers such as
methylene blue (FD¼52 %) rose bengal (FD¼76 %) or
tetraphenyl porphyrin (FD¼63 %).[43] In comparison with the
aforementioned molecules the reasonable water solubility of 3
in water, and the possibility to generate 3in physiological
media from the water soluble precursor 2 b makes it very
appealing in particular for bio-related applications, such as
photodynamic therapy (PDT) or else photoxidation catalysis in
aqueous environments. Thus, in a next step, we studied the
ability of compound 3to generate singlet oxygen upon
photoexcitation in water. Since singlet oxygen phosphores-
cence is not easily detectable in water, measurements were
performed with anthracene-9,10-dipropionic acid disodium salt
(ADPA) as a water soluble singlet oxygen scavenger. Using a
reported methodology[44] bleaching of anthracene lumines-
cence was monitored upon continuous irradiation of 3, and
linear regression to a first order kinetics model could be
obtained with good coefficient of determination (R2>0.995 see
Figure S48 in the Supplementary Information). Examination of
the slopes (detailed calculations are reported in references and
in the Supplementary Informations) enabled us to estimate a
singlet oxygen generation quantum yield which was very close
to that measured in organic solutions FH2O
Dð3Þ ¼ 55 %, and thus
constitutes an extremely relevant value in view of PDT
applications or photooxidation catalysis in water.
Application to Lithography in PDMS Matrix
Besides the possible applications of this new photoreaction in
solution, another interesting feature of this photocyclization is
its ability to efficiently generate a new species with radically
different spectroscopic properties upon irradiation in the UV-A,
which might be of potential interest for optical data storage or
anticounterfeiting applications. Bearing this in mind, we thus
investigated, in a last series of experiments, the possibility to
generate the photoinduced annulation reaction of 2 a into 3in
a solid matrix. Such practical application of chemical photo-
switches are often hampered by the impossibility to expand the
feasibility of reactions usually performed in solutions to
inherently constrained solid state environments. Thus, precursor
2 a which is easily accessible in gram scales and provides one of
the best photoconversion yield was thus loaded at 0.2 w % in
PDMS and shaped as 500 μm thick films. Upon irradiation of a
4 mm×5 mm× 0.5 mm solid sample at 340 nm, a photoreaction
similar to that observed in solution occurs according to a the
setup described Figure S50 in the Supplementary Information.
The conversion was easily followed by imaging the emission
(with a long path filter l>495 nm, the setup is shown in
Figure S51) from the sample fluorescence property upon
excitation at lexc =340 nm. The evolution of the luminescence
intensity (Figure 6 – top) reveals a marked increase of
luminescence with a maximum at about 7 min, which we
attribute to an efficient formation of the photocyclized product
3, as confirmed by the absorption spectra (Figure 6 – bottom)
of the doped PDMS sample recorded before and after the
conversion which corresponds perfectly to those measured in
solution. The irradiation, when extended to 10 min, results in a
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slight decrease (10%) of the fluorescence probably due to
photobleaching.
Having ascertained the possibility to induce photoconver-
sion at the solid state, we then imagined, as a proof of concept,
a rudimentary light exposure sensor using 340 nm as the
writing wavelength and 405 nm as the reading wavelength. The
luminescence of a control sample is maximised by a full
photoconversion upon exposure at 340 nm at a intensity about
6.2 mWcm2. The contrast between the control sample and a
non pre-irradiated sample, disposed side by side, is measured
as a function of exposure time at low-intensity UV light (340 nm
at 0.4 mW cm2for a detailed procedure see the Supplementary
Information). The emission, using a blue excitation lexc =
405 nm for an optimized intensity, is captured by a camera
(Figure 7 – left) and witnesses the increase of fluorescence of
the non pre-irradiated sample as a function of the exposure
time at low intensity at 340 nm. The intensity of the
fluorescence, extracted from the images, is plotted in Figure S51
in the Supplementary Information and allows us to draw the
evolution of the contrast (defined as ðI1I2Þ
ðI1þI2Þwhere I1and I2are the
intensities of the pre-irradiated zones and non pre-irradiated
zones respectively) between the two samples as a function of
the irradiation time (Figure 7 – right). Negatives values of the
contrast at long irradiation time are due to the slow photo-
bleaching of the control sample upon prolonged irradiation.
In a final experiment, we ascertained the possibility of a
controlled writing of an information (similar to a basic
“barcode”) by first irradiating the sample through a metallic
mask constituted of two slits (slit width 0.24 mm; separated
from 1.2 mm). We obtained after 10 minutes of exposure at the
highest power, two well defined fluorescence lines (see Fig-
ure 8) revealed under 405 nm excitation showing that the
pattern mask is well transferred to the sample. Then, we
repeated the contrast measurement between the pre-irradiated
written lines and the rest of the sample under low intensity UV
exposure. From images taken by the camera (Figure 8 – top),
the evolution of the contrast is now even much more visible.
Interestingly, to the naked eye, as soon as the contrast becomes
Figure 6. Photoconversion in PDMS at 340 nm. top: Monitoring of the
conversion of a 500 μm thick PDMS film doped at 0.2 w % with 2 a as a
function of the irradiation time; bottom: absorption spectra of a 500 μm thick
PDMS doped with 0.2 w % of 2 a before (red) and after (blue) 10 min of
irradiation.
Figure 7. Contrast monitoring. Left : images over time of a control sample
pre-irradiated (at 340 nm at the maximal intensity) compared to a non pre-
irradiated sample, both irradiated at low power at 340 nm; right : evolution
of the contrast as a function of the irradiation time.
Figure 8. Contrast monitoring of a unique sample after writing lines with a
mask. top: images over time of a sample pre-irradiated at 340 nm at the
maximal intensity through a mask (2 lines) then irradiated without the mask
at low power at 340 nm; bottom: evolution of the contrast as a function of
the irradiation time.
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negative, the line printed during pre-irradiation appears as
black while the intensity of its fluorescence does not change
thus making very clear the transition where the two areas have
the same intensity. In Figure 8 – bottom is plotted the contrast
as a function of the irradiation time determined from the
intensities extracted from the images (see Figure S53 in the
Supplementary Information). Even if scattering in the sample
can interfere with the measurement, the evolution of contrast
reproduces fairly well that measured on two independent
samples shown in Figure 7 making this imprinted PDMS
promising for the development of self-destructible molecular
barcode for example.[24]
Conclusions
In summary, we reported a synthetic and photophysical study
of a series of helicoidal molecules 2 n which upon irradiation at
340 nm can potentially photocyclize thus forming a diazonia
derivative 3reported for the first time only recently. The
determination of the photocyclization quantum yields within
the series reveals the prominent role of the nature of the
leaving group in the mechanism involving two nucleophilic
aromatic substitutions and showed that leaving groups such as
triflate or esters constitute the most efficient substituents in
order to facilitate the reaction. Theoretical calculations reveal
that the mechanism can only occur from the excited state.
Additionally, we have measured for this newly described
diazonia 3a fluorescence quantum yield (Ff) of 14 % when
excited at 405 nm and found an efficient photosentitizing
capability with a singlet oxygen generation quantum yield FD
of 55% making this new small molecule potentially relevant for
theranostic applications, a topic of interest which we are
currently exploring. Finally, to enlarge the scope of applicability
of this reaction, we succesfully implemented it in the solid state
in 500 μm thick PDMS films, at low loading of 2 a. We found out
that, in spite of the motional restriction imposed by the PDMS
matrix, conversion could still perform as cleanly as in the
solution. Moreover, a setup allowing for writing and reading at
different wavelengths was implemented. Monitoring the con-
trast between pre-irradiated zones and non-pre-irradiated zones
upon simultaneous exposure of both zones gave a good
indication of the dose or exposure time. Finally, the setup even
permitted to produce patterns (lines) with good resolution
thanks to the use of a mask, which constitutes a preliminary
proof-of-principle for a possible use of this material in
applications for high-security level information encoding such
self-destructible molecular barcodes.
Acknowledgements
We thank the French National Research Agency (ANR) for
financial support through grant ANR-20-CE07-0010. M. Labro
and M. Seinfeld are grateful for their Ph.D. scholarships funded
by the Ministère de l’Enseignement Supérieur et de la
Recherche and the ANR, respectively. We also thank the High-
Performance Computing resources of the Pôle Scientifique de
Modélisation Numérique (PSMN) at ENS-Lyon for computational
support.
Conflict of Interests
The authors declare no conflict of interest.
Data Availability Statement
The data that support the findings of this study are available in
the supplementary material of this article.
Keywords: photocyclyzation ·Diazonia ·Photosensitizer ·solid-
state photoconversion
[1] R. Dabestani, I. N. Ivanov, Photochem. Photobiol. 1999,70, 10.
[2] R. Rieger, K. Müllen, J. Phys. Org. Chem. 2010,23, 315.
[3] M. Stępień, E. Gońka, M. Żyła, N. Sprutta, Chem. Rev. 2017,117, 3479,
pMID: 27258218.
[4] C. Rdengiz, Turk. J. Chem. 2021,45, 1375.
[5] G. D. Sinenko, D. A. Farkhutdinova, I. N. Myasnyanko, N. S. Baleeva, M. S.
Baranov, A. V. Bochenkova, Int. J. Mol. Sci. 2021,22.
[6] N. A. Romero, D. A. Nicewicz, Chem. Rev. 2016,116, 10075, pMID:
27285582.
[7] J. E. Anthony, Chem. Rev. 2006,106, 5028, pMID: 17165682.
[8] P. Zygouri, G. Potsi, E. Mouzourakis, K. Spyrou, D. P. Gournis, P. Rudolf,
Curr. Org. Chem. 2015,19, 1791.
[9] J. Calbo, J. C. Sancho-García, E. Ortí, J. Aragó, Molecules 2018,23.
[10] H. Lee, D. Lee, Commun. Chem. 2022,5, 180.
[11] D. Lu, Q. Huang, S. Wang, J. Wang, P. Huang, P. Du, Front. Chem. 2019,
7.
[12] M. Mahl, M. A. Niyas, K. Shoyama, F. Würthner, Nat. Chem. 2022,14, 457.
[13] G. N. Roviello, D. Musumeci, V. Roviello, M. Pirtskhalava, A. Egoyan, M.
Mirtskhulava, Beilstein J. Nanotechnol. 2015,6, 1338.
[14] T. Malcomson, Photochem. Photobiol. Sci. 2022,21, 529.
[15] T. Y. Baum, S. Fernández, D. Peña, H. S. J. van der Zant, Nano Lett. 2022,
22, 8086, pMID: 36206381.
[16] A. Valentim, G. A. Bocan, J. D. Fuhr, D. J. García, G. Giri, M. Kumar, S.
Ramasesha, Phys. Chem. Chem. Phys. 2020,22, 5882.
[17] A. Escudero, C. Carrillo-Carrión, M. C. Castillejos, E. Romero-Ben, C.
Rosales-Barrios, N. Khiar, Mater. Chem. Front. 2021,5, 3788.
[18] X. Zhao, J. Liu, J. Fan, H. Chao, X. Peng, Chem. Soc. Rev. 2021,50, 4185.
[19] M. Deiana, M. Mosser, T. Le Bahers, E. Dumont, M. Dudek, S. Denis-
Quanquin, N. Sabouri, C. Andraud, K. Matczyszyn, C. Monnereau, L. Guy,
Nanoscale 2021,13, 13795.
[20] D. Sasikumar, A. T. John, J. Sunny, M. Hariharan, Chem. Soc. Rev. 2020,
49, 6122.
[21] D. Puchán Sánchez, P. Josse, N. Plassais, G. Park, Y. Khan, Y. Park, M.
Seinfeld, A. Guyard, M. Allain, F. Gohier, L. Khrouz, D. Lungerich, H. S.
Ahn, B. Walker, C. Monnereau, C. Cabanetos, T. Le Bahers, Chem. Eur. J.
2024,30, e202400191.
[22] S. Tang, Y. Zhang, P. Dhakal, L. Ravelo, C. L. Anderson, K. M. Collins, F. M.
Raymo, J. Am. Chem. Soc. 2018,140, 4485, pMID: 29561604.
[23] W. Ren, G. Lin, C. Clarke, J. Zhou, D. Jin, Adv. Mater. 2020,32, 1901430.
[24] X. Liu, Y. Zhang, J. D. Baker, F. M. Raymo, J. Mater. Chem. C 2017,5,
12714.
[25] L. Jierry, S. Harthong, C. Aronica, J.-C. Mulatier, L. Guy, S. Guy, Org. Lett.
2012,14, 288, pMID: 22176157.
[26] L. Guy, M. Mosser, D. Pitrat, J.-C. Mulatier, M. Kukułka, M. Srebro-Hooper,
E. Jeanneau, A. Bensalah-Ledoux, B. Baguenard, S. Guy, J. Org. Chem.
2019,84, 10870.
[27] H. H. Hodgson, Chem. Rev. 1947,40, 251.
[28] D. Bingchcu, L. Hejun, F. Hongbo, C. Yiqian, W. Hua, Bicyclo-substituted
pyrazolone azo derivative, preparation method thereof and application
thereof in medicaments 2010, CN101928281A.
Wiley VCH Mittwoch, 04.12.2024
2412 / 374628 [S. 216/217] 1
ChemPhotoChem 2024,8, e202400199 (9 of 10) © 2024 The Authors. ChemPhotoChem published by Wiley-VCH GmbH
ChemPhotoChem
Research Article
doi.org/10.1002/cptc.202400199
[29] N. Dharmarajan, B. Zhifeng, A. H. Tsou, R. K. Shah, J. R. Hagadorn,
Elastomeric formulations comprising branched EPDM polymers 2022,
US Patent 11,390,733.
[30] D. Kalyani, A. R. Dick, W. Q. Anani, M. S. Sanford, Org. Lett. 2006,8, 2523,
pMID: 16737304.
[31] D. Kalyani, A. R. Dick, W. Q. Anani, M. S. Sanford, Tetrahedron 2006,62,
11483.
[32] T. Ohwada, N. Tani, Y. Sakamaki, Y. Kabasawa, Y. Otani, M. Kawahata, K.
Yamaguchi, Proc. Natl. Acad. Sci. USA 2013,110, 4206.
[33] T. D. Nelson, R. D. Crouch, Cu, Ni, and Pd Mediated Homocoupling
Reactions in Biaryl Syntheses: The Ullmann Reaction, chapter 3, pa-
ges 265–555, John Wiley & Sons, Ltd 2004.
[34] P. E. Fanta, Chem. Rev. 1946,38, 139, pMID: 21016995.
[35] E. Stadler, A. Eibel, D. Fast, H. Freißmuth, C. Holly, M. Wiech, N. Moszner,
G. Gescheidt, Photochem. Photobiol. Sci. 2018,17, 660.
[36] M. Maafi, R. G. Brown, J. Photochem. Photobiol. A 2007,187, 319.
[37] J. Rouillon, C. Arnoux, C. Monnereau, Anal. Chem. 2021,93, 2926, pMID:
33476133.
[38] J. T. Bowler, F. M. Wong, S. Gronert, J. R. Keeffe, W. Wu, Org. Biomol.
Chem. 2014,12, 6175.
[39] N. A. Senger, B. Bo, Q. Cheng, J. R. Keeffe, S. Gronert, W. Wu, J. Org.
Chem. 2012,77, 9535, pMID: 23057717.
[40] D. S. McClure, J. Chem. Phys. 1949,17, 905.
[41] N. E. S. Tay, W. Chen, A. Levens, V. A. Pistritto, Z. Huang, Z. Wu, Z. Li,
D. A. Nicewicz, Nature Catalysis 2020,3, 734.
[42] J. Gibson, A. P. Monkman, T. J. Penfold, ChemPhysChem 2016,17, 2956.
[43] M. C. DeRosa, R. J. Crutchley, Coord. Chem. Rev. 2002,233–234, 351.
[44] M. Galland, T. Le Bahers, A. Banyasz, N. Lascoux, A. Duperray, A.
Grichine, R. Tripier, Y. Guyot, M. Maynadier, C. Nguyen, M. Gary-Bobo, C.
Andraud, C. Monnereau, O. Maury, Chem. Eur. J. 2019,25, 9026.
Manuscript received: May 30, 2024
Revised manuscript received: July 7, 2024
Accepted manuscript online: July 25, 2024
Version of record online: November 8, 2024
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