Amidinium salt bridges for real-world applications of molecularly imprinted polymers

Günter Wulff and Klaus Mosbach pioneered the molecular imprinting technique in the 70s and 80s, respectively, using complementary approaches. An important development in noncovalent molecular imprinting was the use by Wulff of strong salt bridge interactions displayed by amidinium-phosphate and amidinium-phosphonate complexes in catalytically-active enzyme mimicking molecularly imprinted polymers (MIPs). Inspired by their work, others used amidine monomers and their strong pairing with carboxylate groups in the aim of generating molecular imprints in polar organic solvents and in aqueous solutions. The strong directional salt bridge association between amidine and carboxylate template yields MIPs with high affinity and specificity for their target, allowing applications even in challenging complex environments such as human sweat, urine, and cellular and tissue extracts. Herein, we review the use of amidine monomers as well as related guanidine monomers in molecular imprinting, from the time of Wulff to nowadays, highlighting recent advances and applications from the literature, and discuss future directions in this area. • Amidinium-carboxylate salt bridges exhibit high K a > 10 3 M -1 in polar protic solvents • Amidinium-carboxylate salt bridge finetunes the selectivity of MIP binding in water • Amidinium-carboxylate salt bridge allows selective recognition in complex matrices