Thermodynamic and structural study of complexation of phenylboronic acid with salicylhydroxamic acid and related ligands

Abstract

Stability constants of boronate complexes with a highly efficient bioconjugation ligand salicylhydroxamic acid, its derivatives and some structurally related compounds were determined by potentiometric and spectroscopic titrations at variable pH allowing one to obtain detailed stability – pH profiles and to identify the optimum pH for complexation with each ligand. The N,O‐binding of salicylhydroxamic acid via condensation of boronic acid with phenolic OH and hydroxamic NH groups was established by crystal structure determination of isolated complexes with phenylboronic and 4‐nitrophenylboronic acids. Although this type of binding is impossible for N‐methylated salicylhydroxamic acid it still forms stable boronate complexes supposedly involving unusual 7‐membered –O‐B‐O‐ cycle supported by 1H NMR studies. Hydroxamic acids lacking ortho‐OH group and salicyloyl hydrazide form less stable boronate complexes, which nevertheless possess stabilities similar to those of catechole complexes and may be useful for conjugation applications. In contrast to other ligands, which form tetrahedral anionic complexes, salicylamidoxime forms tetrahedral, but neutral boronate complex with high stability in weakly acid solutions. The highest affinity in neutral and acid solutions surpassing that of salicylhydroxamic acid is observed with 2,6‐dihydroxybenzhydroxamic acid (Kobs = 5.2 × 104 at pH 7.4). Fairly stable mono‐ and bisboronate complexes are formed with 2,5‐dihydroxy‐1,4‐benzdihydroxamic acid, which also possesses intense fluorescence and may serve as a boronic acid sensor with detection limit 4 μM. Results presented in this study provide quantitative basis for rational applications of hydroxamic acid derivatives in bioconjugation and sensing.

Improving Rare-Earth Mineral Separation with Insights from Molecular Recognition: Functionalized Hydroxamic Acid Adsorption onto Bastnäsite and Calcite

“…The hydroxamic acids L 1 –L 3 were prepared according to the literature − procedures (as detailed in the Supporting Information). The attempts to prepare di-hydroxamic acid L 4 were unsuccessful.…”

Boronate Ester Hydrogels for Biomedical Applications: Challenges and Opportunities

“…A more recent study reported the binding constants of several PBA/SHA derivative pairs. 113 Among the different SHA derivatives tested (i.e., SHA, N-methyl-SHA, ortho-hydroxyl-SHA, and 2,5-dihydroxy-1,4-benzdihydroxamic acid), SHA and ortho-hydroxyl-SHA had the highest K eq values at physiological pH (1.6 × 10 4 and 3.6 × 10 4 M −1 , respectively), making them interesting candidates for BE cross-linking. To date, a single hydrogel system based on PBA/SHA cross-linking has been reported.…”

Boronic acid based dynamic click chemistry: recent advances and emergent applications

“…Perhaps, the reaction of BA with salicylhydroxamic acids (SHA) has garnered the most attention besides that of boronate ester formation with diols. Discovered by Stolowitz and co-workers 63 in 2001, it has been applied extensively, and a detailed thermodynamic study was reported by Martínez-Aguirre et al 64 in 2018. With an association constant of 10 4 M −1 at pH 7.4 for the complex of phenylboronic acid (PBA) and SHA, the complex is stable at physiological pH, undergoing possible hydrolysis at pH < 5 ( Fig.…”