Tetrahedron Letters
Strong enhancement of two-photon absorption properties
in synergic ‘semi-disconnected’ multiporphyrin assemblies designed
for combined imaging and photodynamic therapy
Olivier Mongin a,b, Muniappan Sankar a, Marina Charlot a, Youssef Mir a, Mireille Blanchard-Desce a,c,
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a Chimie et Photonique Moléculaires (CNRS UMR 6510), Université de Rennes 1, Campus de Beaulieu, F-35042 Rennes Cedex, France
b Institut des Sciences Chimiques de Rennes (CNRS UMR 6226), Université de Rennes 1, Campus de Beaulieu, F-35042 Rennes Cedex, France
c Univ. Bordeaux, Institut des Sciences Moléculaires (CNRS UMR 5255), 351 Cours de la Libération, F-33405 Talence Cedex, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 19 July 2013
Revised 13 September 2013
Accepted 17 September 2013
Available online 25 September 2013
The synthesis and photophysical properties of new multiporphyrin assemblies are described. Their
design, based on a smooth electronic disconnection between two-photon absorbing (2PA) octupolar or
quadrupolar cores and the peripheral porphyrins, leads to a major increase in (non-resonant) 2PA
responses in the NIR, while fully retaining the fluorescence and photosensitization properties of isolated
porphyrins. This approach, which involves electronic coupling of semi-disconnected moieties in the
higher excited states of the synergic systems, is of interest to fully benefit from the advantages of
selective 2PA for application in combined two-photon high resolution imaging and photodynamic
therapy.
Keywords:
Sonogashira coupling
Porphyrin
Photosensitizer
Singlet oxygen
Ó 2013 Elsevier Ltd. All rights reserved.
Fluorescence
Two-photon absorption (2PA)
Photodynamic therapy (PDT) is a medical technique used in
oncology for the treatment of several tumours as well as in oph-
thalmology especially in the treatment of age-related macular
degeneration (ARMD).1,2 The use of a two-photon (2P) excitation
offers new perspectives for PDT, especially for the treatment of
small areas, such as small solid tumours. Indeed two-photon
absorption (2PA) offers several advantages, which include the abil-
ity for highly selective excitation in biological media and intrinsic
three-dimensional resolution as well as increased penetration
depth in tissues.3 This however calls for the use of optimized 2P
photosensitizers that should combine large 2PA cross-sections in
the biological spectral window (700–1100 nm) and high singlet
oxygen quantum yields (or ROS production). Most of the photosen-
sitizers currently used clinically or in clinical trials are porphyrin
derivatives, such as porfimer sodium (Photofrin) and verteporfin
(Visudyne). These compounds exhibit high singlet oxygen quan-
tum yields but low 2PA cross sections (10 and 50 GM, respectively)
in the NIR,4 as model tetraphenylporphine (TPP, 12 GM).5 Dramatic
enhancement of the 2PA cross-sections can be achieved in
porphyrinoids,6 or expanded porphyrins,7 in conjugated porphyrin
dimers, trimers and oligomers,8 planarized fused or bridged por-
phyrins,9 or supramolecular assemblies.8a,10 The extension of the
p-conjugated system involves the porphyrin or porphyrinoid mac-
rocycles thus leading to major modification of their photophysical
properties: a marked broadening and red-shift of the Q-bands is
observed resulting in residual one-photon absorption (1PA) over-
lapping with the 2PA band located in the NIR region. This promotes
resonance enhancement of the 2PA band leading to giant 2PA
cross-sections. Other consequences are however possible loss of
3D resolution (due to concomitant 1PA) and weakening of fluores-
cence and photosensitizing properties. Nevertheless biphotonic
photosensitizers that maintain significant fluorescence are highly
desirable to allow in vivo monitoring and subsequent localized
irradiation.
Here we describe our efforts toward the design of porphyrin-
based 2P photosensitizers exhibiting large 2PA in the NIR—with
no 1PA—and retaining the fluorescence as well as the excellent
photosensitization properties of the porphyrin moiety. Dendritic
antenna systems based on resonant energy transfer (FRET) from
peripheral 2P absorbers toward a single porphyrin core have been
previously designed.11 In contrast, our strategy is based on multi-
porphyrin assemblies with a weak conjugation between a central
2PA unit and peripheral porphyrins.
disconnection between the porphyrin moieties and the conjugated
-system is ensured by deviation from planarity (Fig. 1), so as to
A smooth electronic
p
retain some of the photochemical features of native porphyrins
(in particular singlet oxygen production and fluorescence).
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Corresponding author. Tel.: +33 5 40 00 67 32; fax: +33 5 40 00 69 94.
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.