Glucose-derived receptors for photo-controlled binding of amino acid esters in water

Abstract

Selective receptors of amino acids in aqueous media are highly sought after as they may enable the creation of novel diagnostic and sensing tools. Photoswitchable receptors are particularly attractive for such purposes as their response and selectivity towards bioanalytes can be modulated using light. Herein we report glucose-based photoswitchable receptors of amino-acid methyl esters and biogenic amines in water. The tetra-ortho-fluoroazobenzene unit in the receptors structure allows to control the distance between their binding sites using light. The Z-isomers of both receptors, having these sites in closer proximity, bind lysine, ornithine and arginine esters significantly stronger compared to E-isomers, where the binding sites are further apart.

Fig. 1. Synthetic ion receptors.

a Glucose-based aryl crown ethers for enantio- and chemoselective binding of amino acid esters in water (refs. ^,); (b) photoswitchable receptor of inorganic anions (ref. ); (c) photoswitchable receptor of organic dianions (ref. ).

Fig. 2. Design of the photoswitchable receptors.

a Structures of glucose-derived photoswitchable receptors of amino acid esters 1 and 2; (b) schematic representation of the light-controlled binding of dicationic guests by the receptors.

Scheme 1

Synthesis of receptors 1 and 2. Reagents and conditions: (a) DMP, p-TsOH, acetone, r.t., 24 h, 85%; (b) BnBr, NaH, DMF, r.t., 6 h, 90%; (c) AcOH/H₂O = 3:2, 50 °C, 2 h, 95%; (d) AllBr (1 eqv.), NaH, DMF, r.t., 8 h, 40%; (e) Bis-chloro-diethylether, TBAI, 50%aq KOH, THF, 50 °C, 12 h, 90%; (f) KOH, diethylene glycol, 80 °C, 8 h, 85%; (g) FeCl₃, NH₄PF₆, CH₃CN, 40 °C, 48 h, 65%; (h) Pd/C, p-TsOH, MeOH/H₂O = 4:1, reflux, 5 h, 90%; (i) 7 (0.75 eqv.), NEt₃, CH₂Cl₂, r.t., 24 h; (j) NaBrO₃, Na₂S₂O₄, ethyl acetate/H₂O, r.t., 72 h, 1–30%; 2–40% over two steps.

Fig. 3. Photochromic characterization of receptors.

(a) UV-VIS spectra of 2 in H₂O (c = 100 µM); (b) fragments of ¹H NMR spectra of 2 in D₂O showing the signals of aromatic protons: directly after the synthesis of the receptor (top), after 15 s irradiation with 410 nm light (middle), after 160 min irradiation with 623 nm light (bottom).

Fig. 4. Computational modelling of receptor 1.

Lowest energy conformers of Z- and E-isomers of receptor 1 at the r²SCAN-3c(CPCM(water))+GFN2-xTB(ALPB(water)) level.

Fig. 5. Binding mode analysis.

(a) Stacked plot of ¹H NMR spectra (D₂O, 400 MHz, c = 2 mM, only selected regions are shown)—from the top: H-l-Lys-OCH₃, H-l-Lys-OCH₃ + E-1 (1 equiv.), H-l-Lys-OCH₃ + Z-1 (1 equiv.), Z-1; (b) proposed binding mode of H-l-Lys-OCH₃ by Z-1; (c) proposed binding mode of spermidine by E-1.