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. 2022 Jun 16;27(12):3856.
doi: 10.3390/molecules27123856.

Imidazo[1,5- a]pyridine-Based Fluorescent Probes: A Photophysical Investigation in Liposome Models

Giacomo Renno  1   2 , Francesca Cardano  1 , Giorgio Volpi  1 , Claudia Barolo  1   2 , Guido Viscardi  1 , Andrea Fin  3
Affiliations

Imidazo[1,5- a]pyridine-Based Fluorescent Probes: A Photophysical Investigation in Liposome Models

Giacomo Renno et al. Molecules. .

Abstract

Imidazo[1,5-a]pyridine is a stable scaffold, widely used for the development of emissive compounds in many application fields (e.g., optoelectronics, coordination chemistry, sensors, chemical biology). Their compact shape along with remarkable photophysical properties make them suitable candidates as cell membrane probes. The study of the membrane dynamics, hydration, and fluidity is of importance to monitor the cellular health and to explore crucial biochemical pathways. In this context, five imidazo[1,5-a]pyridine-based fluorophores were synthesized according to a one-pot cyclization between an aromatic ketone and benzaldehyde in the presence of ammonium acetate and acetic acid. The photophysical features of prepared compounds were investigated in several organic solvents and probes 2-4 exhibited the greatest solvatochromic behavior, resulting in a higher suitability as membrane probes. Their interaction with liposomes as artificial membrane model was tested showing a successful intercalation of the probes in the lipid bilayer. Kinetic experiments were carried out and the lipidic phase influence on the photophysical features was evaluated through temperature-dependent experiments. The results herein reported encourage further investigations on the use of imidazo[1,5-a]pyridine scaffold as fluorescent membrane probes.

Keywords: fluorescence; imidazo[1,5-a]pyridine; large Stokes shift; liposome; membrane probes.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Structures of the synthesized compounds (1–5).
Figure 2
Figure 2
Synthetic approach toward the prepared compounds. (a) ammonium acetate, acetic acid, 110 °C, 5 h (1: 78%, 5: 80%); (b) ammonium acetate, acetic acid, 118 °C, 12 h (2: 96%, 4: 96%); (c) 1. ammonium acetate, acetic acid, 118 °C, 6 h; 2. (phenyl(pyridin-2-yl)methanone, 118 °C, 12 h (78%).
Figure 3
Figure 3
Photophysical properties of the reported probes 1–5. (a) Absorption (dashed) and emission (solid) spectra of compounds 1–5 in toluene. (b–f) Absorption (dashed) and emission (solid) spectra in different solvents for compounds 1 (b), 5 (c), 2 (d), 3 (e), 4 (f). The emission spectra were normalized to 0.1 intensity at the excitation wavelengths.
Figure 4
Figure 4
Kinetic experiments in DOPC (a–c) and DPPC (d–f) for compounds 2 (a,d), 3 (b,e), 4 (c,f). Probes concentration during the measurement: 7.28 × 10−7 M for 2, 3.7 × 10−6 M for 3 and 3.4 × 10−6 M for 4.
Figure 5
Figure 5
(a–c) Normalized emission profile in DOPC (solid line) and DPPC (dashed line) for compounds 2 (a), 3 (b), 4 (c). (d) Emission intensity vs. time in DOPC for 2 (red), 3 (magenta), 4 (purple). (d,e) Emission intensity vs. time DPPC for 2 (red), 3 (magenta), 4 (purple).
Figure 6
Figure 6
Normalized emission spectra of compounds 2 (a,d), 3 (b,e), 4 (c,f) in DOPC (a–c) and DPPC (d–f) over the heating cycles.
Figure 7
Figure 7
Normalized excitation spectra of compounds 2 (a,d), 3 (b,e), 4 (c,f) in DOPC (a–c), and DPPC (d–f) over the heating cycles.
See this image and copyright information in PMC

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