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Fluorescent tetracyanobutadienes: new AIEgens for biophysical applications – Fluotet

The tetracyanobutadienes: new fluorescent molecules

Super electron acceptors to tune the optical properties of emissive compounds.

The unexpected fluorescence of tetracyanobutadienes derived from ynamides

Ynamides are molecules bearing a CC triple bond directly linked to a nitrogen, which bears an electron-withdrawing group. They readily react with tetracyanoethylene to afford molecules named tetracyanobutadienes (TCBDs) after a cascade reaction. Thanks to their four nitriles groups, these compounds are excellent electron acceptors, which gives them unique optical and electronic properties. They are able to absorb a huge number of photons over large wavelength range. However, it had been shown that they were unable to emit any photons (which is called fluorescence). Our laboratory was surprised to observed that some of of the TCBDs synthesized from ynamides were fluorescent, contrary to other TCBDs. In this project, we studied this unanticipated fluorescence in order to understand why these TCBD were an exception. Afterwards, we wanted to take profit of this original character to visualize a cellular membrane and to measure its internal pressure.

We synthesized a large series of TCBDs derived from ynamides. First, ynamide precursors had to be synthesized according to methodologies reported in the literature and previously tested in our laboratory. They were subsequently reacted with tetracyanoethylene to afford the corresponding TCBDs in high yields. The fluorescence of these TCBDs was then studied in solution and in the solid state with the help of spectrofluorimeters. Several solvents were used in order to study the impact of the medium on the emission properties. Artificial models of cellular membranes, named « micelles » and « liposomes », were used to investigate the behavior of our TCBDs in such an environment.

Numerous TCBDs bearing fluorophores were synthesized, especially in the fluorene series but not only. In particular, anthracenes, perylene and pyrene derivatives were isolated.
The fluorescence of all these compounds was investigated both in solution and in the solid state. All of them emit light but in very different wavelength ranges and with very different intensity. Noteworthy is the solid-state emission in the near infrared region of anthracene, perylene and pyrene derivatives up to 1550 nm, which could be very interesting in the frame of biomedical applications. In solution, the situation depends on the nature of the solvent. We supposed a strong solvatochromism. This property was deeply investigated with the dibutylfluorene TCBD by recording the emission in different solvents. In fact, we evidenced a strong dependence of the emission maximum as well as the emission intensity on the polarity of the solvent. In very apolar solvent like cyclohexane, the emission intensity is maximum but dramatically drop when shifting to toluene. When dichloromethane is used, almost no emission could be measured. In order to get more insights into the reason below this strong solvatochromism, a new collaboration with the group of Nathan McClenaghan in Bordeaux was established. Transient absorption spectroscopy will be used to decipher the deactivation pathways that are at stake.
Following this observation, the emission of most of the synthesized TCBDs was recorded in 3 solvents: cyclohexane, toluene and dichloromethane. In the great majority of TCBDs, the emission is maximum in cyclohexane, drops dramatically in toluene and is almost absent in dichloromethane, confirming thus the trend previously observed with dibutylfluorene TCBD.
All of these TCBDs are fluorescent in the solid state. Noteworthy is the near infrared emission of the perylene, pyrene and anthracene derivatives, up to 1550 nm.

In most cases, these TCBDs have shown remarkable emission properties. Interestingly, some TCBDs are able to emit photons in the near-infrared range. Invisible to naked eyes, these photons are very popular in the field biomedical imaging since they go through cellular tissues without being absorbed, contrary to photons in the visible range. Therefore, this property offers interesting and unexpected perspectives towards potential applications in bioimaging. Furthermore, we also demonstrated these TCBDs became fluorescent inside micelles and liposomes, which opens new possibilities, combined with the emission of near-infrared photons.

These results were reported in three articles in international peer-reviewed journals. The first paper describes the synthesis and characterization of the pyrene and perylene TCBDs, which are able to emit near-infrared light in the solid-state (Chem. Commun. 2020). The second paper describes the synthesis of anthracene derivatives and their emission in the near-infrared range in the solid state (Org. Lett. 2021). The third one deals with non-linear absorption of some TCBDs (Phys. Chem. Chem. Phys. 2021). When this report was written, two other manuscripts were submitted.

The aim of the project is to synthesize new 1,1,4,4-tetracyanobutadienes (TCBDs) from ynamides possessing the "aggregation induced emission" (AIE) property. The synthetic pathway towards this kind of compounds, which has recently been developed by the team of the scientific coordinator, consists in a sequence of [2+2]cycloaddition followed by a [2+2]retroelectrocyclization between tetracyanoethylene and ynamides. This method is tolerant to many functional groups and generally leads to TCBDs in high yields.
Compounds that have the AIE property exhibit fluorescence in the solid state (potentially as nano-aggregates dispersed in a liquid) but not in solution. This property comes from the restriction of the internal molecular movements (rotation, vibration) that allows for the radiative deactivation of the excited state, which is impossible when the molecule possesses "too many" degrees of freedom (non-radiative deactivation in this case). TCBDs that do not come from ynamides are generally not fluorescent at room temperature, neither in the solid state nor in solution. Consequently, this project would raise a new family of compounds having this remarkable property. Moreover, the emission maximum of the AIEgen TCBDs recently synthesized in our laboratory is located beyond 600 nm, which allow for biological applications since it does not compete with the natural autofluorescence that is encountered in living organisms.
Once the best emitters identified and characterized, two potential applications will be studied in order to take advantage of the restoration of the fluorescence of the TCBDs in strained medium. First, they will be made water-soluble in order to incorporate them into artificial membranes formed with a Langmuir trough, which would thus allow for their visualization by fluorescence. Given that the emission maximum of our TCBDs is very sensitive to the surrounding medium, one can imagine that this maximum could also be sensitive to the pressure applied to the membrane. In this case, it would constitute one of the first pressure sensors at the molecular level.
Finally, these TCBDs will be linked to substrates specific of some proteins such as sugar derivatives, which could allow for their specific visualization in vitro. Whether it be for working on membranes or be it on proteins, TCBDs could be linked to water-soluble groups by "click" chemistry from a common propargylic synthon for the these two applications.

Project coordination

Yann TROLEZ (Institut des Sciences Chimiques de Rennes)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.


ISCR Institut des Sciences Chimiques de Rennes

Help of the ANR 209,239 euros
Beginning and duration of the scientific project: January 2018 - 48 Months

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