Polyoxa- and Polyazamacrocycles Incorporating 6,7-Diaminoquinoxaline Moiety: Synthesis and Application as Tunable Optical pH-Indicators in Aqueous Solution

Abstract

Synthetic approach to fluorescent polyaza- and polyoxadiazamacrocycles comprising a structural fragment of 6,7-diamino-2,3-diphenylquinoxaline has been elaborated using Pd-catalyzed amination providing target compounds in yields up to 77%. A series of nine novel N- and N,O-containing macrocyclic ligands differing by the number of donor sites and cavity size has been obtained. These compounds possess well-pronounced fluorescent properties with emission maxima in a blue region in aprotic solvents and high quantum yields of fluorescence, while in proton media, fluorescence shifts towards the green region of the spectrum. Using macrocycles 5c and 5e as examples, we have shown that such compounds can serve as dual-channel (colorimetric and fluorimetric) pH indicators in water media, with pH transition point and response being dependent on the macrocycle structure due to different sequences of protonation steps.

Keywords: Pd-catalysis; amination; colorimetry; fluorescence; macrocycles; pH indicator; quinoxaline.

Figure 1

Previously reported macrocyclic chemosensors based on quinoxaline signaling units.

Scheme 1

Synthesis of diamine 3 via Pd-catalyzed diamination of dibromoquinoxaline 1 with amine 2.

Scheme 2

Pd-catalyzed synthesis of oxaazamacrocycles 5a–d.

Scheme 3

Pd-catalyzed synthesis of polyazamacrocycles 5e–h.

Figure 2

Normalized fluorescence spectra of 3 and 5a–h (λ_ex = 405 nm) in MeCN.

Figure 3

(a) Normalized fluorescence spectra of 5e (λ_ex = 400 nm) in toluene (blue), dioxane (green), CH₂Cl₂ (violet), MeCN (yellow), MeOH (red), water (1 vol% MeOH, pH = 6, black); (b). Color evolution of solutions of ligand 5e observed in various solvents under UV light (λ = 365 nm).

Figure 4

(a) Evolution of the UV-vis absorption spectrum of 5c in acetonitrile ([5c] = 24.4 μM) upon addition of Cu(ClO₄)₂ (0–3.3 equiv.). Inset: changes of the absorbance as a function of the [Cu²⁺]_tot/[5c]_tot ratio at λ = 481 nm. (b) Evolution of the emission spectrum of 5c in acetonitrile ([5c]_tot = 4.2 μM, λ_ex = 409 nm) upon addition of Cu(ClO₄)₂ (0–3.3 equiv.). Inset: changes of the emission intensity as a function of the [Cu²⁺]_tot/[5c]_tot ratio at λ_em = 486 nm. The arrows show the change of the spectra.

Figure 5

(a) Spectrophotometric titration of 5c as a function of pH ([5c]_tot = 8.4 μM, 1 vol% MeOH,I = 0.1 M NaClO₄, pH = 0.7–7.2); (b) Fluorimetric titration of 5c as a function of pH ([5c]_tot = 4.2 μM, 0.5 vol% MeOH, I = 0.1 M NaClO₄, λ_ex = 420 nm, pH = 0.7–7.2). The arrows show the change of the spectra.

Figure 6

(a) Evolution of color of aqueous solution of ligand 5c with pH increase observed under visible light; (b) Absorbance changes with pH at λ = 480 nm for 5c; (c) Evolution of color of aqueous solution of ligand 5c with pH increase observed under UV light (λ = 365 nm), and (d) Emission intensity changes with pH at λ = 480 nm for 5c (λ_ex = 420 nm).

Figure 7

(a) Spectrophotometric titration of 5e ([5e]_tot = 31.1 μM, I = 0.1 M NaClO₄, pH = 1.0–6.0); (b) Fluorimetric titration of 5e as a function of pH ([5e]_tot = 8.04 μM, I = 0.1 M NaClO₄, λ_ex = 420 nm, pH = 1.0–6.0). The arrows show the change of the spectra.

Figure 8

Color evolution of aqueous solution of ligand 5e with pH increase observed under visible (a) and UV (λ = 365 nm) (b) light; (c) Emission intensity changes with pH at λ = 480 nm for 5e (λ_ex = 420 nm).

Figure 9

Labeling scheme for nitrogen atoms in chemosensors 5a and 5e and relevant compounds 7–9 reported in the literature.

Scheme 4

Proposed protonation sequences for quinoxalines 7 [36], 5c and 5e.