Dataset Information

Smart photopharmacological agents: LaVO₄:Eu³⁺@vinyl phosphonate combining luminescence imaging and photoswitchable butyrylcholinesterase inhibition.

ABSTRACT: The combination of photoswitchability and bioactivity in one compound provides interesting opportunities for photopharmacology. Here, we report a hybrid compound that in addition allows for its visual localization. It is the first demonstration of its kind and it even shows high photoswitchability. The multifunctional nanomaterial hybrid, which we present, is composed of luminescent LaVO₄:Eu³⁺ nanoparticles and vinyl phosphonate, the latter of which inhibits butyrylcholinesterase (BChE). This inhibition increases 7 times when irradiated with a 266 nm laser. We found that it is increased even further when vinyl phosphonate molecules are conjugated with LaVO₄:Eu³⁺ nanoparticles, leading in total to a 20-fold increase in BChE inhibition upon laser irradiation. The specific luminescence spectrum of LaVO₄:Eu³⁺ allows its spatial localization in various biological samples (chicken breast, Daphnia and Paramecium). Furthermore, laser irradiation of the LaVO₄:Eu³⁺@vinyl phosphonate hybrid leads to a drop in luminescence intensity and in lifetime of the Eu³⁺ ion that can implicitly indicate photoswitching of vinyl phosphonate in the bioactive state. Thus, combining enhanced photoswitchability, bioactivity and luminescence induced localizability in a unique way, hybrid LaVO₄:Eu³⁺@vinyl phosphonate can be considered as a promising tool for photopharmacology.

SUBMITTER: Bikbaeva G

PROVIDER: S-EPMC11334978 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Smart photopharmacological agents: LaVO4:Eu3+@vinyl phosphonate combining luminescence imaging and photoswitchable butyrylcholinesterase inhibition.

Bikbaeva Gulia G Pilip Anna A Egorova Anastasiya A Medvedev Vasiliy V Mamonova Daria D Pankin Dmitrii D Kalinichev Alexey A Mayachkina Natalya N Bakina Lyudmila L Kolesnikov Ilya I Leuchs Gerd G Manshina Alina A

Nanoscale advances 20240624 17

The combination of photoswitchability and bioactivity in one compound provides interesting opportunities for photopharmacology. Here, we report a hybrid compound that in addition allows for its visual localization. It is the first demonstration of its kind and it even shows high photoswitchability. The multifunctional nanomaterial hybrid, which we present, is composed of luminescent LaVO4:Eu3+ nanoparticles and vinyl phosphonate, the latter of which inhibits butyrylcholines ...[more]

PMID: 39170980

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Project description:We have developed photochromic probes for the nicotinic acetylcholine receptor that exploit the unique chemical properties of the tetrafluoroazobenzene (4FAB) scaffold. Ultraviolet light switching and rapid thermal relaxation of the metastable cis configuration are the main drawbacks associated with standard AB-based switches. We designed our photoprobes to take advantage of the excellent thermodynamic stability of the cis-4FAB configuration (thermal half-life > 12 days at 37 °C in physiological buffer) and cis-trans photostationary states above 84%. Furthermore, the well-separated n-π* absorption bands of trans- and cis-4FAB allow facile photoswitching with visible light in two optical channels. A convergent 11-step synthetic approach allowed the installation of a trimethylammonium (TA) head onto the 4FAB scaffold, by means of an alkyl spacer, to afford a free diffusible 4FABTA probe. TAs are known to agonize nicotinic receptors, so 4FABTA was tested on mouse brain slices and enabled reversible receptor activation with cycles of violet and green light. Due to the very long-lived metastable cis configuration, 4FAB in vivo use could be of great promise for long term biological studies. Further chemical functionalization of this 4FAB probe with a maleimide functionality allowed clean cross-linking with glutathione. However, attempts to conjugate with a cysteine on a genetically modified nicotinic acetylcholine receptor did not afford the expected light-responsive channel. Our data indicate that the 4FAB photoswitch can be derivatized bifunctionally for genetically-targeted photopharmacology whilst preserving all the favorable photophysical properties of the parent 4FAB scaffold, however, the tetrafluoro motif can significantly perturb pharmacophore-protein interactions. In contrast, we found that the freely diffusible 4FABTA probe could be pre-set with green light into an OFF state that was biologically inert, irradiation with violet light effectively "uncaged" agonist activity, but in a photoreversible manner. Since the neurotransmitter acetylcholine has fully saturated heteroatom valences, our photoswitchable 4FABTA probe could be useful for physiological studies of this neurotransmitter.

Dataset Information

Smart photopharmacological agents: LaVO₄:Eu³⁺@vinyl phosphonate combining luminescence imaging and photoswitchable butyrylcholinesterase inhibition.

Publications

Smart photopharmacological agents: LaVO<sub>4</sub>:Eu<sup>3+</sup>@vinyl phosphonate combining luminescence imaging and photoswitchable butyrylcholinesterase inhibition.

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