Despite their desirable attributes, boronic acids have had a minimal impact in biological contexts. A significant problem has been their oxidative instability. At physiological pH, phenylboronic acid and its boronate esters are oxidized by reactive oxygen species at rates comparable to those of thiols. After considering the mechanism and kinetics of the oxidation reaction, we reasoned that diminishing electron density on boron could enhance oxidative stability. We found that a boralactone, in which a carboxyl group serves as an intramolecular ligand for the boron, increases stability by 10⁴-fold. Computational analyses revealed that the resistance to oxidation arises from diminished stabilization of the p orbital of boron that develops in the rate-limiting transition state of the oxidation reaction. Like simple boronic acids and boronate esters, a boralactone binds covalently and reversibly to 1,2-diols such as those in saccharides. The kinetic stability of its complexes is, however, at least 20-fold greater. A boralactone also binds covalently to a serine side chain in a protein. These attributes confer unprecedented utility upon boralactones in the realms of chemical biology and medicinal chemistry.

尽管它们具有理想的属性，但硼酸在生物环境中的影响很小。一个重要的问题是它们的氧化不稳定性。在生理 pH 值下，苯硼酸及其硼酸酯被活性氧以与硫醇相当的速率氧化。在考虑氧化反应的机理和动力学后，我们推断硼上电子密度的降低可以提高氧化稳定性。我们发现硼内酯，其中羧基作为硼的分子内配体，稳定性增加了 10 ⁴-折叠。计算分析表明，抗氧化性是由于硼在氧化反应的限速过渡态中形成的 p 轨道的稳定性减弱而引起的。与简单的硼酸和硼酸酯一样，硼酸内酯与 1,2-二醇（如糖类中的那些）共价且可逆地结合。然而，其复合物的动力学稳定性至少高出 20 倍。硼酸内酯还与蛋白质中的丝氨酸侧链共价结合。这些属性赋予硼内酯在化学生物学和药物化学领域前所未有的效用。