Despite its seemingly simple nature, phenylboronic acid (PBA) plays an indispensable role in modern chemistry and biomedicine due to its unique molecular recognition capabilities and reactivity. From Nobel Prize-winning coupling reactions to revolutionary smart insulin delivery systems, this white crystalline powder is quietly changing our lives.
When discussing phenylboronic acid, the Suzuki coupling reaction—one of the achievements of the 2010 Nobel Prize in Chemistry—must be mentioned. In this reaction, phenylboronic acid, as a key boric acid component, undergoes cross-coupling with haloaromatic hydrocarbons under palladium catalysis, forming carbon-carbon bonds.
Derivatives such as 4-formylphenylboronic acid and 4-hydroxyphenylboronic acid are also common building blocks in the Suzuki reaction and are widely used in the synthesis of drug molecules, pesticide molecules, and bioactive molecules.
The core characteristic of phenylboronic acid lies in its reversible binding ability to cis-diols. Under physiological pH conditions, phenylboronic acid reacts with sugars such as glucose to form cyclic borate esters. This process involves a molecular configuration shift from planar trigonal (sp²) to tetrahedral (sp³), resulting in a detectable signal change.
Mechanism Summary: The cis-dihydroxy group of glucose combines with phenylboronic acid to form a stable borate ester anion, leading to a change in molecular charge state and conformation. This property forms the physical basis for many sensors.
Contact Lens-Based Continuous Glucose Monitoring: Researchers have integrated phenylboronic acid-functionalized hydrogels into contact lenses, using optical diffraction principles to monitor tear glucose concentration in real time. When blood glucose levels rise, the hydrogel expands, causing a change in the wavelength of diffracted light, which can be read via a smartphone. This sensor has a sensitivity of 0.1-30 mM and a response time within minutes, providing a non-invasive and convenient monitoring solution for diabetic patients.
Photonic Crystal Sensor: Utilizing photonic bandgap (PBG) materials combined with phenylboronic acid hydrogels, the volume change in the hydrogel caused by glucose binding leads to a structural color change—a visible change from red to blue—enabling naked-eye detection.
Intelligent Insulin Delivery System
This is one of the most promising clinical translational applications of phenylboronic acid. The working principle of the glucose-responsive insulin delivery system is ingenious: Hyperglycemic state: Glucose binds to phenylboronic acid → hydrogel network hydrophilicity increases → volume expansion → insulin release. Normal glycemic state: Boronic acid ester bonds break → hydrogel shrinks → drug release decreases. This "on-demand release" system effectively avoids the risk of hypoglycemia in traditional insulin therapy. Recent research in 2024 developed an injectable peptide hydrogel functionalized with phenylboronic acid, which not only exhibits glucose sensitivity but also responds to multiple stimuli such as GSH, H₂O₂, and pH, achieving precise controlled drug release.
Targeted Tumor Therapy
The specific binding of phenylboronic acid to sialic acid residues (containing cis-dihydroxy groups) on the surface of tumor cells makes it an ideal tool for targeted tumor therapy. By combining drugs with phenylboronic acid-modified carriers, the following can be achieved: Active targeting: Utilizing the overexpression of sialic acid in tumor tissues; Stimulus-responsive release: Binding to photosensitive groups (such as o-nitrobenzyl) to trigger drug release through light exposure. Phenylboronic acid, a "small molecule" with a molecular weight of only 122, carries the "big dreams" of modern chemistry. From Suzuki coupling in the laboratory to intelligent drug delivery in the clinic, from macroscopic crystal structures to microscopic molecular recognition, it spans the boundaries of multiple disciplines, including synthetic chemistry, materials science, and biomedicine.
Post time: Feb-09-2026
