Threading a Linear Molecule Through a Macrocycle Thanks to Boron: Optical Properties of the Threaded Species and Synthesis of a Rotaxane.

Two BODIPYs and two boron ß-diketonates were threaded through a macrocycle bearing a 2,2'-biphenol unit, showing thus the ability of boron to act as a gathering atom. The new threaded species were characterized by 1D and 2D NMR spectroscopy as well as by X-ray crystallography for one of them and their properties rationalized with quantum chemistry to unravel the vibronic contributions. The BODIPYs exhibited interesting fluorescence features with quantum yields up to 91 % and enhanced photostability compared to their non-threaded homologues. A rotaxane was synthesized using this threading strategy after stoppering and removing the boron with potassium hydroxide.

Giant Star-shaped meso-substituted Fluorescent Porphyrins with Fluorenyl-containing Arms Designed for Two-photon Oxygen Photosensitization.

In the continuation of previous studies on carbon-rich meso-tetraarylporphyrins featuring 2,7-fluorene units at their periphery, the effect of changing the peripheral dendritic arms for linear arms on their oxygen-photosensitizing ability, their fluorescence and their two-photon absorption (2PA) properties is now analyzed. Thus, starburst porphyrins possessing up to twenty conjugated fluorenyl units were isolated and studied. More precisely, a series of five new free-base porphyrins featuring fully conjugated arms incorporating an increasing number of fluorenyl groups connected via 1,2-alkenyl spacers were synthesized, along with their Zn(II) complexes. Upon excitation in the arm-centred π-π* absorption band, an efficient energy transfer takes place from the peripheral fluorenyl units to the central porphyrin core, leading to intense red-light emission and oxygen photosensitization by the latter. More interestingly, while the linear optical properties of these porphyrins were only slightly improved compared to those of their dendrimer analogues for photodynamic therapy (PDT) or fluorescence imaging, their 2PA cross-sections were much more significantly boosted, evidencing the key role played by different structures on nonlinear optical properties. Finally, by comparison with other porphyrin-based two-photon photosensitizers reported in the literature, we show that these new "semi-disconnected" starburst systems exhibit a remarkable trade-off between intrinsic 2PA, fluorescence and oxygen photosensitization.

Encapsulation of Hydrophobic Porphyrins into Biocompatible Nanoparticles: An Easy Way to Benefit of Their Two-Photon Phototherapeutic Effect without Hydrophilic Functionalization.

Star-shaped hydrophobic porphyrins, acting as powerful fluorescent two-photon photosensitizers for oxygen in organic solvents, can easily be loaded into PMLABe polymeric nanoparticles at various concentrations. In this contribution, the performance of these porphyrin-containing nanoparticles in terms of photodynamic therapy (PDT) is compared to those of the corresponding water-soluble porphyrin analogues when irradiated in MCF-7 cancer cells. While quite promising results are obtained for performing PDT with these nanoparticles, validating this approach as a mean for using more easily accessible and less expensive photosensitizers, from a synthetic perspective, we also show that their luminescence can still be used for bioimaging purposes in spite of their confinement in the nanoparticles, validating also the use of these nano-objects for theranostic purposes.

Synthesis and Photophysical Properties of 1,1,4,4-Tetracyanobutadienes Derived from Ynamides Bearing Fluorophores.

1,1,4,4-Tetracyanobutadienes (TCBDs) bearing a large diversity of fluorophores were prepared following a multi-step synthesis. In a crucial last step, all compounds were obtained from the corresponding ynamides, which were particularly suitable for the formation of the TCBDs in the presence of tetracyanoethylene via a [2+2] cycloaddition/retroelectrocyclization step (CA-RE). Several fluorenyl derivatives in addition to phenanthrenyl and terphenyl ones provided ynamide-based TCBDs affording remarkable emission properties covering a large range of wavelengths. Those compounds emit both in solid state and in solution from the visible region to the NIR range, depending on the molecular structures. Quantum yields in cyclohexane reached unforeseen values for such derivatives, up to 7.8 %. A huge sensitivity to the environment of the TCBDs has also been unraveled for most of the compounds since we observed a dramatic fall of the quantum yields when changing the solvent from cyclohexane to toluene, while they are almost non-emissive in dichloromethane.

Two-photon absorption properties of multipolar triarylamino/tosylamido 1,1,4,4-tetracyanobutadienes.

The synthesis and characterization of four new tetracyanobutadiene (TCBD) derivatives (1, 3c and 4b-c) incorporating tosylamido and 4-triphenylamino moieties are reported. Along with those of five closely related or differently branched TCBDs derivatives (2, 3a-b, 4c and 5), their linear and (third-order) nonlinear optical properties were investigated by electronic absorption spectroscopy and Z-scan measurements. Among these compounds, the tri-branched compounds 3c and 5 are the most active two-photon absorbers, with effective cross-sections of 275 and 350 GM at 900 nm, respectively. These properties are briefly discussed with the help of DFT calculations, focussing on structural and electronic factors, and contextualized with results obtained previously for related compounds.

Molecular engineering for optical properties of 5-substituted-1,10-phenanthroline-based Ru(II) complexes.

A series of homo- and heteroleptic Ru(ii) complexes [Ru(phen)3-n(phen-X)n](PF6)2 (n = 0-3, X = CN, epoxy, H, NH2) were prepared and characterized. The influence of electron-withdrawing or electron-releasing substituents of the 1,10-phenanthroline ligands on the photo-physical properties was evaluated. It reveals fundamental interests in the fine tuning of redox potentials and photo-physical characteristics, depending both on the nature of the substitution of the ligand, and on the symmetry of the related homo- or heteroleptic complex. These complexes exhibit linear absorption and two-photon absorption (2PA) cross-sections over a broad range of wavelength (700-900 nm) due to absorption in the intra-ligand charge transfer (ILCT) and the metal-to-ligand charge transfer (MLCT) bands. These 2PA properties were more particularly investigated in the 700-1000 spectral range for a family of complexes bearing electro-donating ligands (phen-NH2).

1,1,4,4-Tetracyanobutadiene-Functionalized Anthracenes: Regioselectivity of Cycloadditions in the Synthesis of Small Near-IR Dyes.

Two small 1,1,4,4-tetracyanobutadiene-functionalized chromophores were obtained by careful leverage of the regioselectivity of the cycloaddition reaction of tetracyanoethylene with anthracene-ynamide derivatives, inducing either a [2 + 2] or a [4 + 2] Diels-Alder process. DFT calculations unraveled the mechanism of the [2 + 2] cycloaddition-retroelectrocyclization reaction sequence with ynamides and elucidated the differing mechanisms in the two substrates. The synthesized dyes presented panchromatic absorption extending into the near-IR and far-red/near-IR photoluminescence in the solid state up to 1550 nm.

1,3,5-Triaryl-1,3,5-Triazinane-2,4,6-Trithiones: Synthesis, Electronic Structure and Linear Optical Properties.

The synthesis of four new 1,3,5-triaryl-1,3,5-triazinane-2,4,6-trithione derivatives (thioisocyanurates) and two new partially thionated analogues from the corresponding 1,3,5-triaryl-1,3,5-triazinane-2,4,6-triones (isocyanurates) is reported, together with their spectroscopic properties. DFT calculations and comparison with the corresponding isocyanurates evidence the impact of the oxygen-for-sulfur replacement on the electronic structure and linear optical properties of these heterocycles. A bathochromic shift of the absorption bands and more efficient quenching of the fluorescence was observed.

The Ouzo effect: A tool to elaborate high-payload nanocapsules.

We investigate the encapsulation in hybridosomes®, a type of capsules unique regarding their structure and method of elaboration. Hybridosomes® are made of a single shell of inorganic nanoparticles (~5 nm) crosslinked with a polymer and are easily obtained via spontaneous emulsification in a ternary mixture THF/water/butylated hydroxytoluene (BHT). Our main finding is that an exceptionally high concentration of a hydrophobic model dye can be loaded in the hybridosomes®, up to 0.35 mol.L-1 or equivalently 170 g.L-1 or 450,000 molecules/capsule. The detailed investigation of the encapsulation mechanism shows that the dye concentrates in the droplets during the emulsification step simultaneously with capsule formation. Then it precipitates inside the capsules during the course of solvent evaporation. In vitro fluorescence measurements show that the nano-precipitated cargo can be transferred from the core of the hybridosomes® to the membrane of liposomes. In vivo studies suggest that the dye diffuses through the body during several days. The released dye tends to accumulate in body-fat, while the inorganic nanoparticles remain trapped into the liver and the spleen macrophages.

Triarylisocyanurate-Based Fluorescent Two-Photon Absorbers.

The synthesis and characterization of six triarylisocyanurates, featuring 2,7-fluorenyl or 9,10-anthracenyl groups incorporated in their peripheral arms are reported. Photophysical studies reveal that these new octupolar derivatives are more fluorescent (ΦF ≥0.60 for all new compounds except for 1,3,5-tri(9H-fluoren-2-yl)-1,3,5-triazinane-2,4,6-trione 3) and present a red-shifted lowest absorption and emission compared to their known phenyl analogues of comparable size. Depending on the nature of the terminal substituent, fast intramolecular energy transfer among the three arms or localization of the excitation on a single branch occurs after population of their first singlet excited state. The latter effect was only observed in the presence of strongly electron-releasing substituents in polar media. These new chromophores are also better two-photon absorbers than the 1,4-phenylene-based isocyanurates reported so far, with cross sections σ2 ≥500 GM at 770 nm for 4-NPh2 the fluorenyl group containing (13) and the anthracenyl group containing (14) chromophores. All these spectroscopic features, analyzed with the help of quantum chemical calculations, are crucial for the design of new biphotonic fluorescent dyes.

Synthesis, characterization and unusual near-infrared luminescence of 1,1,4,4-tetracyanobutadiene derivatives.

Two 1,1,4,4-tetracyanobutadiene (TCBD) derivatives were prepared by [2+2]cycloaddition-retroelectrocyclization from ynamides bearing either a pyrene (1) or a perylene unit (2). In addition to panchromatic absorptions in 2, in the solid state, both compounds unexpectedly display NIR photoluminescence that could be detected up to about 1350 nm.

Phthalocyanine-Cored Fluorophores with Fluorene-Containing Peripheral Two-Photon Antennae as Photosensitizers for Singlet Oxygen Generation.

: A series of free base and Zn(II) phthalocyanines featuring fluorenyl antennae linked by methoxy or oxo bridges to the phthalocyanine core (Pc) were synthesized and characterized. Selected linear and nonlinear (two-photon absorption) optical properties of these new compounds were subsequently studied. As previously observed for related porphyrin dendrimers bearing 2-fluorenyl peripheral dendrons, an efficient energy transfer occurs from the peripheral antennae to the central phthalocyanine core following excitation in the fluorenyl-based π-π* absorption band of these chromophores. Once excited, these compounds relax to the ground state, mostly by emitting intense red light or by undergoing intersystem crossing. As a result, the tetrafunctionalized Zn(II) phthalocyanines are fluorescent, but can also efficiently photosensitize molecular oxygen in tetrahydrofurane (THF), forming singlet oxygen with nearly comparable yields to bare Zn(II) phthalocyanine (ZnPc). In comparison with the latter complex, the positive role of the fluorenyl-containing antennae on one- and two-photon brightness (2PA) is presently demonstrated when appended in peripheral (ß) position to the phthalocyanine core. Furthermore, when compared to known porphyrin analogues, the interest in replacing the porphyrin by a phthalocyanine as the central core to obtain more fluorescent two-photon oxygen photosensitizers is clearly established. As such, this contribution paves the way for the future development of innovative biphotonic photosensitizers usable in theranostics.

Functionalization of 9-thioxanthone at the 1-position: From arylamino derivatives to [1]benzo(thio)pyrano[4,3,2-de]benzothieno[2,3-b]quinolines of biological interest.

Original 1-amino substituted thioxanthone derivatives were easily prepared from the bare heterocycle by a deprotometalation-iodolysis-copper-catalyzed CN bond formation sequence. This last reaction delivered mono- or/and diarylated products depending on the aniline involved. 1-Amino-9-thioxanthone was also prepared and reacted with 2-iodoheterocycles. Interestingly, while 1-(arylamino)-9-thioxanthones could be isolated, their subsequent cyclization was found to deliver original hexacyclic derivatives of helicoidal nature. Evaluation of their photophysical properties revealed high fluorescence in polar media, indicating potential applications for biological imaging. These compounds being able to inhibit PIM1 kinase, their putative binding mode was examined through molecular modeling experiments. Altogether, these results tend to suggest the discovery of a new family of fluorescent PIM inhibitors and pave the way for their future rational optimization.

Fluorescent phosphorus dendrimers excited by two photons: synthesis, two-photon absorption properties and biological uses.

Different types of two-photon absorbing (TPA) fluorophores have been synthesized and specifically functionalized to be incorporated in the structure of phosphorus dendrimers (highly branched macromolecules). The TPA fluorophores were included in the periphery as terminal functions, in the core, or in the branches of the dendrimer structures, respectively. Also the functionalization in two compartments (core and surface, or branches and surface) was achieved. The consequences of the location of the fluorophores on the fluorescence and TPA properties have been studied. Several of these TPA fluorescent dendrimers have water-solubilizing functions as terminal groups, and fluorophores at the core or in the branches. They have been used as fluorescent tools in biology for different purposes, such as tracers for imaging blood vessels of living animals, for determining the phenotype of cells, for deciphering the mechanism of action of anticancer compounds, and for safer photodynamic therapy.

Biocompatible conjugated fluorenylporphyrins for two-photon photodynamic therapy and fluorescence imaging.

The photophysical properties of a new series of fluorenyl porphyrins bearing water-solubilising oligoethyleneglycol chains are described. These biocompatible compounds present very good two-photon absorption and singlet oxygen generation properties, while retaining some fluorescence in water. After testing in vitro on breast cancer cells, some of them were shown to be efficient non-toxic two-photon photosensitisers allowing for fluorescence imaging, thus demonstrating their theranostic potential.

Addressing Charge-Transfer and Locally-Excited States in a Twisted Biphenyl Push-Pull Chromophore.

We present the synthesis and spectroscopic characterization of a twisted push-pull biphenyl molecule undergoing photoinduced electron transfer. Steady-state and transient absorption spectra suggest, in this rigid molecular structure, a subtle interplay between locally-excited and charge-transfer states, whose equilibrium and dynamics is only driven by solvation. A theoretical model is presented for the solvation dynamics and, with the support of quantum chemical calculations, we demonstrate the existence of two sets of states, having either local or charge-transfer character, that only "communicate" thanks to solvation, which is the sole driving force for the charge-separation process.

Fluorenylporphyrins functionalized by electrochromic ruthenium units as redox-triggered fluorescence switches.

Two dyads containing tris- and tetrakis-meso-fluorenyl-substituted porphyrin and ethynylruthenium units, 1 and 2, were investigated by emission spectro-electrochemical (SEC) methods for their potential use as fluorescence switches. The ruthenium group as a potential electron donor and the porphyrin as a potential electron acceptor are connected by a phenylene bridge in 1 and by a fluorenylene bridge in 2. The new fluorenyl-linked dyad 2 was probed by UV-visible, near-infrared (NIR) and infrared (IR) absorption SEC methods, and the properties interpreted with the aid of hybrid-DFT computations, for comparison with reported data for 1. The porphyrin-based fluorescence of 1 decreased in intensity upon oxidation to 1+ and decreased further on oxidising 1+ to 12+. A much weaker change in the fluorescence intensity of 2 was observed upon oxidation to 2+ but the intensity decreased upon subsequent oxidation of 2+ to 22+. These findings contrast with data reported for some other porphyrins appended with redox-active ruthenium or iron units, where fluorescence intensities increase upon oxidation of the peripheral metal centers, but they match data reported more recently for closely related arrays. A rationale for these apparently contrasting observations is proposed.

Dendrimeric Nanoparticles for Two-Photon Photodynamic Therapy and Imaging: Synthesis, Photophysical Properties, Innocuousness in Daylight and Cytotoxicity under Two-Photon Irradiation in the NIR.

The synthesis and the photophysical properties of a new class of fully organic monodisperse nanoparticles for combined two-photon imaging and photodynamic therapy are described. The design of such nanoparticles is based on the covalent immobilization of a dedicated quadrupolar dye that combines excellent two-photon absorbing (2PA) properties, fluorescence and singlet oxygen generation ability, in a phosphorous-based dendrimeric architecture. First, a bifunctional quadrupolar dye bearing two different grafting moieties, a phenol function and an aldehyde function, was synthesized. It was then covalently grafted through its phenol function to a phosphorus-based dendrimer scaffold of generation 1. The remaining aldehyde functions were then used to continue the dendrimer synthesis up to generation 2, introducing finally 24 water-solubilizing triethyleneglycol chains at its periphery. A dendrimer confining 12 photoactive quadrupolar units in its inner scaffold and showing water solubility was thus obtained. Interestingly, the G1 and G2 dendrimers retain some fluorescence as well as significant singlet oxygen production efficiencies while they were found to show very high 2PA cross-sections in a broad range of the NIR biological spectral window. Hydrophilic dendrimer G2 was tested in vitro on breast cancer cells, first in one- and two-photon microscopy, which allowed for visualization of their cell internalization, then in two-photon photodynamic therapy. While being nontoxic in the dark and, more importantly, under exposure to daylight, dendrimer G2 proved to be a very efficient cell-death inducer only under two-photon irradiation in the NIR.

Linear and Third-Order Nonlinear Optical Properties of Triazobenzene-1,3,5-triazinane-2,4,6-trione (Isocyanurate) Derivatives.

The synthesis of three new isocyanurate derivatives 2-X (X=NO2 , H, NMe2 ) with azobenzene arms terminated by various X substituents is reported, and their linear and nonlinear absorption properties are studied. It is shown that mixtures that contain increased contents of cis-azo isomers can be reversibly generated upon photoirradiation at specific wavelengths from the most stable all-trans isomers with X=NO2 and H. In addition, we show that 2-X derivatives are two-photon absorbers with cross-section maxima around 120 GM for 2-NO2 , thus indicating that trans-to-cis isomerization might be achievable by two-photon excitation, whereas the photoinduced structural changes should have only a modest influence on these nonlinear absorption properties.

New Conjugated meso-Tetrafluorenylporphyrin-Cored Derivatives as Fluorescent Two-Photon Photosensitizers for Singlet Oxygen Generation.

A series of three conjugated meso-porphyrin dendrimers containing conjugated dendrons featuring 2,7-fluorenyl groups, incorporating overall 8, 12, or 28 fluorenyl units have been synthesized and characterized. The photophysical properties of these new compounds were studied in the context of photodynamic therapy. The relevant linear and nonlinear optical properties were measured in organic media and useful structure-properties relationships were derived.