Scope and Limitations of Boron Fluorescent Complexes from Stable Nitrile Oxides in ABPP Assays

Abstract

Anthracenenitrile oxide undergoes 1,3-dipolar cycloaddition reactions with 1-substituted-4-(prop-2-yn-1-yloxy)benzene affording the expected isoxazoles in good yields and as single regioisomers. N–O Bond cleavage and boron complexation afforded the corresponding boron complexes, derivatized with either a triple bond for click-chemistry applications or an oxime group for nitrile oxide 1,3-dipolar cycloaddition. The optical properties of these compounds show potential for employment as fluorescent tags in imaging techniques. The activity-based protein profiling assays showed good reactivity for the synthesized probes even with short peptide chains (epoxomicin). Scope and limitations are discussed in the light of the obtained results.

Fluorescent Probes from Aromatic Polycyclic Nitrile Oxides: Isoxazoles versus Dihydro‐1λ3,3,2λ4‐Oxazaborinines

“…We performed some UV‐Vis and fluorescence studies on both the isoxazole derivatives 14 a – h and the corresponding boron complexes 17 a – h , comparing the results with those previously obtained for compounds 5 and 6 (see Scheme ) . These studies will be propaedeutic to evaluate the potential use of the new compounds as chemical probes in ABPP investigations.…”

“…The oxime derivative 6 showed an absorption band at 384 nm (ϵ=5.00 ⋅ 10 3 mol −1 ) with a shoulder at 238 nm and vibrational peaks. Analogously, the BF 2 complex 5 shows an absorption band at 387 nm (ϵ=8.20 ⋅ 10 3 mol −1 ) along with several vibrational peaks . Table resumes the main photophysical characteristics of compounds 14 a – h and 17 a – h .…”

“…Hence, the electron attracting groups ( 14 b and 14 f and electron poor heteroaromatics 14 h ) give better results if compared with electron rich rings ( 14 d and 14 g ). In compounds 5 and 6 , the change in viscosity and polarity of the solvent mixture – hence moving from DCM, to MeOH and DMSO−H 2 O 1 : 1 – is accompanied with a decrease in the Φ F . Such an effect is not pronounced in the series of the isoxazoles.…”

“…We cannot state if these probes maintained their fluorescence during the interaction with the proteasome; it was also possible that the fluorophores maintained their optical properties but the excitation was not efficient. Alternatively, we cannot exclude a potential quenching or degradation (instability of the boron complex) during the interaction with the proteasome …”

9-Anthraldehyde oxime: a synthetic tool for variable applications

“…We wish to report some examples of 1,3-dipolar cycloadditions with alkynes such as the 1-iodo-4-(prop-2-yn-1yloxy)benzene (9a), 4-(prop-2-ynyloxy)benzaldehyde oxime (9b), and propargyl bromide (9c) that lead to obtain the 3-(anthracen-9-yl)-5-[(4-iodophenoxy)methyl]isoxazole (10a) in 55% yield, the 4-[[3-(anthracen-9-yl)isoxazol-5-yl]methoxy]benzaldehyde oxime (10b) in 66% yield and the 3-(anthracen-9-yl)-5-(bromomethyl)isoxazole (10c) in 75% yield, as single regioisomers (Scheme 6). The synthetic utility of these isoxazoles relies in themselves and upon the ease transformation into enamino ketones as the ligand for the preparation of boron complexes; in fact, after the N-O bond cleavage treatment with BF 3 •Et 2 O afforded the corresponding boron complexes, suitable for application as fluorescent tags [18][19][20].…”