Water-soluble optical sensors: keys to detect aluminium in biological environment

Abstract

Metal ion plays a critical role from enzyme catalysis to cellular health and functions. The concentration of metal ions in a living system is highly regulated. Among the biologically relevant metal ions, the role and toxicity of aluminium in specific biological functions have been getting significant attention in recent years. The interaction of aluminium and the living system is unavoidable due to its high earth crust abundance, and the long-term exposure to aluminium can be fatal for life. The adverse Al³⁺ toxicity effects in humans result in various diseases ranging from cancers to neurogenetic disorders. Several Al³⁺ ions sensors have been developed over the past decades using the optical responses of synthesized molecules. However, only limited numbers of water-soluble optical sensors have been reported so far. In this review, we have confined our discussion to water-soluble Al³⁺ ions detection using optical methods and their utility for live-cell imaging and real-life application.

Fig. 1. Toxic effects of Al³⁺ in the biotic community.

Fig. 2. Different classes of water-soluble aluminium sensors.

Scheme 1. Structures of naphthyl-based Al³⁺ chemosensors (1, 2, 3, 4, and 5) and sensing mechanisms.

Fig. 3. (a and b) represent the absorption and emission spectra for compound 1 with Al³⁺, R = [Al³⁺]/[1] in the range R = 0 to 20 at pH = 3.9 ± 0.2, λ_ex = 360 nm. (c) Absorption spectra of 2 with Al³⁺; the inset displays the visible color change from yellow to reddish-yellow, (d) emission spectra of 2 (12.5 μM) with different concentrations of Al³⁺ in HEPES buffer (DMSO/water: 1/100) of pH = 7.4 at 25 °C; the inset exhibits the blue color of the complex under UV-light illumination (a and b) were reprinted with permission from ref. copyright 2004. Springer Nature, and (c and d) were reprinted with permission from ref. copyright 2012. Royal Society of Chemistry.

Fig. 4. (a) Fluorescence spectra of 3 (20 μM) with 2 equiv. of Al³⁺, λ_ex = 450 nm, λ_em = 490 nm, (b) variation in emission intensity of 4 (10 μM) upon Al³⁺ addition in 50 mM bis–tris buffer [Al³⁺] = 0–0.6 mM, λ_ex = 450 nm, (c) emission response of 4 (10 μM) toward Al³⁺ ion (34 μM) addition in the absence and presence of other metal ions (34 μM), (d) fluorescent images of HeLa cells; the above three images were obtained by only incubating with 4, the bottom images were obtained by incubating with 1 mM Al(NO₃)₃ and 10 μM of 4. Left panel shows fluorescent images (λ_ex = 480 nm, λ_em = 520 nm), middle panel DIC images and right panel merge images (a) was reprinted with permission from ref. copyright 2013. Elsevier, and (b–d) were reprinted with permission from ref. copyright 2014. Royal Society of Chemistry.

Fig. 5. (a) Absorption spectra of 5 with 0–2 equiv. of Al³⁺ in HEPES buffer, (b) the selectivity assay for 5 with other metal ions (Na⁺, K⁺, Ca²⁺, Cu²⁺, Zn²⁺, Cr³⁺, Cd²⁺, Co²⁺, Hg²⁺, Ni²⁺, Al³⁺) in HEPES buffer (pH = 7.0), λ_ex = 320 nm. Reprinted with permission from ref. copyright 2014. Elsevier.

Fig. 6. (a) The structure of chemosensor 6 and the Al³⁺ sensing mechanism, (b) and (c) demonstrate the changes in absorption and emission spectra of 6 (100 μM) with Al³⁺, respectively, (d) Selectivity assay for 6 in the presence of other metal ions, (e) Job's plot showing the 2 : 1 complex of 6 : Al³⁺. Reprinted with permission from ref. copyright 2017. Springer Nature.

Fig. 7. (a) Sensing mechanism of the julolidine-based probes; (b) fluorescence response of probe 8 to Al³⁺ in bis–tris buffer solution; inset: intensity at 487 nm vs. concentration of Al³⁺; (c) Fluorescence spectra representing the selectivity of probe 8 for Al³⁺ over other metal ions in bis–tris buffer solution; (d) observation of changes in the fluorescence intensity in HeLa cells incubated with 0 μM and 100 μM of Al³⁺ respectively for 5 h using probe 7 (d) was reprinted with permission from ref. copyright 2013. Elsevier, and (b and c) were reprinted with permission from ref. copyright 2016. Elsevier.

Fig. 8. (a) Fluorescence spectra and (b) absorption spectra of compound 9 upon the addition Al³⁺. Conditions: 99% water/DMSO (v/v) buffered by 50 mmol L⁻¹ NaAc-HAc at pH 5.0, the concentrations of 9 and EDTA were 50 μM, and the concentration of Al³⁺ was 25 μM, λ_ex = 403 nm, (c) luminescence and visible color change before and after Al³⁺ addition, (d) images of test papers based on 9 for the detection of Al³⁺, (e) proposed mechanism for the interaction between 9 and Al³⁺ and, (f) photos of 9 with 1 equivalent of different metal ions. Reprinted with permission from ref. copyright 2017. Wiley-VCH.

Fig. 9. (a) The proposed mechanism for emission changes of 10 with Al³⁺, and in the presence of Cu²⁺. (b) Fluorescence spectra (10.0 mM, λ_ex = 334 nm) with the addition of various metal ions (10.0 equiv.) in aqueous solution (Tris–HCl, 0.1 mM, pH 7.2). (c) Fluorescence intensity of 10 and its complexation with Al³⁺ in the presence of various metal ions. Black bar: 10 (10.0 mM) and 10 with 10.0 equiv. of other ions stated. Red bar: 10.0 mM of 10 and 10.0 equiv. of Al³⁺ with 10.0 equiv. of metal ions stated (λ_ex = 334 nm). Reprinted with permission from ref. copyright 2015. Royal Society of Chemistry.

Fig. 10. (a) The plausible binding mode of 11 with Al³⁺ and fluorescence mechanism of the PET processes. (b) Fluorescence spectra (10.0 μM, λ_ex = 335 nm) with the addition of various metal ions (10.0 equiv.) in aqueous solution (Tris–HCl, 10 mM, pH 7.2). (c) Fluorescence spectra (10.0 μM, λ_ex = 335 nm) upon the titration of Al³⁺ (0–2.5 equiv.) in aqueous solution (Tris–HCl, 10.0 mM, pH 7.2). (d) Fluorescence responses (10.0 μM, λ_ex = 335 nm) to various metal ions (10.0 μM) (black column) (10 equiv.) and upon the subsequent addition of Al³⁺ (red column) in aqueous solution (Tris–HCl, 10 mM, pH 7.2). Reprinted with permission from ref. copyright 2015. Japan Society for Analytical Chemistry.

Fig. 11. Fluorescence response of compounds 12 and 13 on addition of the selected cations. Reprinted with permission from ref. copyright 2017. Taylor & Francis Academic Journals.

Fig. 12. (a) The proposed binding mode of 14 with Al³⁺. (b) Fluorescence emission spectra of 14 (10 μM) in the presence of 5 equiv. of various metal ions in aqueous buffered solution (10 mM hexamine, pH 5.5) (λ_ex = 380 nm, slit = 12/8 nm, 430 nm cut off). (c) Fluorescence emission spectra and visible emission color change (inset) of 14 (10 μM) in aqueous buffered solution (10 mM hexamine, pH 5.5) with increasing concentration of Al³⁺ (λ_ex = 380 nm, slit = 12/8 nm, 430 nm cut off). Reprinted with permission from ref. copyright 2016. Elsevier.

Fig. 13. Structures and proposed binding modes of 15 (a) and 16 (b). Fluorescence responses of 10 μM of 15 (c) and 16 (d) to metal ions in the presence of 5 equiv. of various metal ions by an excitation wavelength at 315 nm in 10 mM hexamine buffer at pH 5.5. Fluorescence emission spectra of 10 μM of 15 (e) and 16 (f) in 10 mM hexamine buffer with increasing concentrations of Al³⁺. Reprinted with permission from ref. copyright 2021. Springer Nature.

Fig. 14. Structures and proposed binding modes of 17 (a), 18 (b), and 19 (c). Fluorescence spectra of 10 μM 17 (d), 18 (e), and 19 (f) in the presence of various metal ions (2 equiv.) in aqueous solution. Inset: The photograph of 17, 18, and 19 with various metal ions (2 equiv.) in aqueous solution under a 365 nm UV lamp. Competition analysis of 10 μM 17 (g), 18 (h), and 19 (i) to various metal ions in aqueous solutions. The black bars represent the intensity when mixed with 2 equiv. of other metal ions; the red bars represent the intensity when mixed with 2 equiv. of Al³⁺ and 2 equiv. of other metal ions. (j) Fluorescent detection of Al³⁺ using 17 by test paper under a 365 nm UV lamp after being immersed in different aqueous solutions (10⁻⁴ M) (from left to right, up: blank, Al³⁺, Co²⁺, Cr³⁺, Cu²⁺, and Fe³⁺; down: Hg²⁺, Mn²⁺, Na⁺, Ni²⁺, Pb²⁺, and Zn²⁺). (k) The monomolecular circuit for the INHIBIT logic gate. (l) Photographs of 19 test strips under a 365 nm UV lamp after being dipped into aqueous solutions of different metal ions (100 μM) (from left to right, up: Ba²⁺, Ce³⁺, Cd²⁺, Co²⁺, Al³⁺, Cr³⁺, Cu²⁺, and Fe³⁺; down: Hg²⁺, In³⁺, K⁺, Mn²⁺, Na⁺, Ni²⁺, Pb²⁺, and Zn²⁺). Reprinted with permission from ref. and copyright 2019. Elsevier.

Fig. 15. Silver-nanoparticle (Ag-NPs)-mediated sensing platform (20) for Al³⁺ ions in water. (a) Schematic representation of the sensing principle, (b) UV-Vis titration of Ag-NPs with increasing concentration of Al³⁺ ions; insets show linear and ratiometric response of optical absorption and color change of the solution before and after the addition of Al³⁺ ions, (c) shows the selectivity for Al³⁺ ions and the inset shows ratiometric response upon the addition of Al³⁺, Fe³⁺, and Cr³⁺ ions, (d) bar diagram representing the selectivity from the ratiometric optical response for different metal ions. Reprinted with permission from ref. copyright 2013. Springer Nature.

Fig. 16. Water-soluble Al³⁺ sensing platform using fluorescent organic nanoparticle 21. (a) Structure of 1,8-napthalimide ligand used for the synthesis of ONPs, (b) fluorescence properties of 1,8-napthalimide ligand and self-assembled ONPs, (c) TEM image of ONPs, (d) fluorescence response of ONPs using different metals ions, (e) titration of ONPs with increasing concentration of Al³⁺ ions, and (f) kinetic response of fluorescence intensity ratio with different concentration of Al³⁺ ions. Reprinted with permission from ref. copyright 2014. Royal Society of Chemistry.

Fig. 17. (a) Schematic illustration of GSH-Au NCs (22) synthesis and the fluorescence enhancement of GSH-Au NCs upon the addition of Al³⁺ ion due to the Al³⁺-triggered aggregation of the GSH-Au NCs. (b) Selectivity study of GSH-Au NCs toward Al³⁺ against other metal ions, (c) PL emission spectra of GSH-Au NCs solution after adding different concentrations of Al³⁺. Inset: digital photos of different concentrations of Al³⁺ processed GSH-Au NCs under UV light. (d and e) Confocal fluorescence images of AT-II cells co-incubated with the as-prepared Au NCs solution without (A) and with (B) 400 μM Al³⁺. Reprinted with permission from ref. copyright 2019. Elsevier.

Fig. 18. AIE-based sensing of Al³⁺. (a) Schematically showing the AIE process and Al³⁺ sensing. Cuvette picture show fluorescence color change upon AIE and Al³⁺ binding. (b) Effect of water addition in DMF solution of the probe causes emission enhancement due to AIE, (c) effect of metal ions on the emission property to show the selectivity toward Al³⁺ ions. (d–f) Fluorescence images of A549 cells (d) brightfield, in the presence (f), and absence of Al³⁺ (e). Reprinted with permission from ref. copyright 2019. Wiley-VCH.

Fig. 19. (a) Structure of PSSA, 24 (b) AIE effect upon the addition of ethanol content; the inset shows the increase in the emission quantum yield with an increasing percentage of ethanol. (c) Schematic representation of the sensing principle. (d) Effect of Al³⁺ addition on the emission intensity and the inset shows a plot of intensity variation with increasing concentration of Al³⁺ ions. (e) Bar diagram shows the selectivity of detection toward Al³⁺ over other metals. Reprinted with permission from ref. copyright 2019. Royal Society of Chemistry.

Ajmal Roshan Unniram Parambil