A straightforward synthesis of phenyl boronic acid (PBA) containing BODIPY dyes: new functional and modular fluorescent tools for the tethering of the glycan domain of antibodies

Abstract

We report here on the efficient and straightforward synthesis of a series of modular and functional PBA-BODIPY dyes 1-4. They are an outstanding example of the efficient merge of the versatility of the 3,5-dichloro-BODIPY derivatives and the receptor-like ability of the PBA moiety. The potential bioanalytical applicability of these tools was assessed by measuring the binding to glycan chains of antibodies by a Quartz Crystal Microbalance (QCM).

Fig. 1. (A) Structure of PBA-BODIPY derivatives 1–4. (B) Solution (1.0 mg mL⁻¹ in MeOH) of PBA-BODIPY derivatives (from the left to the right PDA-BODIPY 1, 4, 2, 3) (a) under white light and (b) under UV-light (λ_ex = 364 nm).

Scheme 1. Synthesis of the PBA-BODIPY 1–4. (a) CF₃COOH, 0 °C → r.t., 15 minutes, 74%; (b) NCS, THF, −78 °C → −20 °C, 18 h; (c) DDQ, CH₂Cl₂, r.t., 16 h, 75% over two steps; (d) BF₃Et₂O, CH₂Cl₂, r.t., 2 h, 75%; (e) aniline, CH₂Cl₂, 60 °C, 48 h, 58%; (f) aniline, 140 °C, 0.5 h; (g) ethylendiamine, r.t., 45 minutes, 44%.

Fig. 2. Normalized absorbance and fluorescence spectra of PBA-BODIPY 1–4 in MeOH (black line) physiological PBS buffer pH = 7.4 (green line), H₂O (blue line) and CH₂Cl₂ (red line). (A and B) PBA-BODIPY 1; (C and D) PBA-BODIPY 2; (E and F) PBA-BODIPY 3; (G and H) PBA-BODIPY 4.

Fig. 3. QCM experimental set up, where crystal 1 (A) was functionalized with 4, while crystal 2 (B) was kept as the negative control. The on-line QCM sensorgrams shows the resonance frequency shift occurred after antibody deposition on crystal 1 black solid line, (A) and crystal 2 (black dotted line, (B)).