A novel copolymer based on supramolecular motif 2,6-diaminopyridine and water-soluble acrylamide, poly[N-(6-acetamidopyridin-2-yl) acrylamide-co-acrylamide], was synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization with various monomer compositions. The thermoresponsive behavior of the copolymers was studied by turbidimetry and dynamic light scattering (DLS). The obtained copolymers showed an upper critical solution temperature (UCST)-type phase transition behavior in water and electrolyte solution. The phase transition temperature was found to increase with decreasing amount of acrylamide in the copolymer and increasing concentration of the solution. Furthermore, the phase transition temperature varied in aqueous solutions of electrolytes according to the nature and concentration of the electrolyte in accordance with the Hoffmeister series. A dramatic solvent isotope effect on the transition temperature was observed in this study, as the transition temperature was almost 10-12 degrees C higher in D2O than in H2O at the same concentration and acrylamide composition. The size of the aggregates below the transition temperature was larger in D2O compared to that in H2O that can be explained by deuterium isotope effect. The thermoresponsive behavior of the copolymers was also investigated in different cell medium and found to be exhibited UCST-type phase transition behavior in different cell medium. Such behavior of the copolymers can be useful in many applications including biomedical, microfluidics, optical materials, and in drug delivery. (c) 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019