One-step synthesis of well-defined molecularly imprinted nanospheres for the class-selective recognition and separation of β-blockers in human serum.

β-blockers are a class of medications that are used to treat abnormal heart rhythms and hypertension. Molecularly imprinted polymers (MIPs) capable of selective recognizing and extracting β-blockers from complex biological samples hold great promise in bioanalytical and biomedical applications, but developing such artificial receptor materials is still challenging. Herein, we introduce a simple one-step method for the synthesis of well-defined molecularly imprinted nanospheres in high yield (83.6-94.4%) via reversible addition-fragmentation chain transfer (RAFT) precipitation polymerization for the selective recognition and extraction of the β-blockers from human serum. The prepared MIPs are characterized in terms of morphology, pore properties, binding kinetics, capacity, selectivity, and recognition mechanisms. The uniform nanoscale-imprinted layer favored the rapid mass transfer of β-blockers. The binding studies showed the high adsorption capacity (126.8 μmol/g) and selectivity of the developed nanomaterial. The investigation on the recognition mechanism reveals that multiple driving forces participate in the binding between MIP and β-blockers, where hydrogen bonding plays as the dominating role for the specific recognition. The MIP was successfully applied for the direct enrichment of five β-blockers from human serum with HPLC recoveries ranging from 82.9 to 100.3% and RSD of 0.5-6.9% (n = 3).