Fabricating Water-Resistant and Stimuli Responsive Smart Hydrogels via Iminoboronate Chemistry

The construction and application of smart hydrogels often involve balancing the conflicting relationship between the stability and dynamics. Imine bond, as a type of dynamic chemical bonding, is commonly used in the construction of diverse smart hydrogels since it can effectively achieve the response to some external stimuli. However, its poor thermodynamic stability often leads to the limited crosslinking density and easy degradation of hydrogels in water and biofluids. To address this critical issue, a series of model smart hydrogels is prepared with highly water stability and stimuli responsiveness via the iminoboronate gelation of aminoglycosides and 8-arm PEG terminated with 2-acetylphenylboronic acid pinacol ester [(pin)-APBA]. Note that the presence of pinacol esters, as electron-donating agents and hydrophobic couplers with large steric hindrance, can keep the five-membered ring of iminoboronate intact and protect the nitrogen-boron (N─B) coordination bond from water molecules, offering the water resistance feature of the hydrogels. And the rapid responsiveness of the gels to stimuli (e.g., acid, H₂O₂ and unhindered amines) further confirmed that their dynamic nature, allowing the on-demand release of aminoglycosides with satisfactory antibacterial effect. This iminoboronate chemistry-based strategy can offer new opportunities toward stable and smart hydrogels with various applications in many fields.