pH‐Sensitive Polymethacrylates as Potential Contrast Agents in 19F MRI

19F MRI is a promising method of diagnosis that can complement the commonly used 1H MRI with gadolinium contrast agents. Copolymers containing fluoroorganic groups demonstrate many advantages as potential 19F MRI contrast agents. In this work, a series of copolymers based on 2,2,2‐trifluoroethyl methacrylate (TFEMA), 1,1,1,3,3,3‐hexafluoroisopropyl methacrylate (HFiPMA), 2‐(dimethylamino)ethyl methacrylate (DMAEMA), or 2‐hydroxyethyl methacrylate (HEMA) units are prepared using atom transfer radical polymerization. The highest S/N values in a 19F NMR spectra is achieved with a copolymer containing 15–25 wt% TFEMA or 18–22 wt% HFiPMA. Copolymers of HFiPMA show a strong effect of pH on T1 and T2 relaxation times while only T2 is significantly affected for the TFEMA copolymers. DFT calculations reveal that the phenomenon is most likely caused by the pH‐induced changes in the distance of fluoroorganic groups within a polymer chain. It is demonstrated that 2,2,2‐trifluoroethyl methacrylate, 2‐hydroxyethyl methacrylate, 2‐(dimethylamino)ethyl methacrylate, and 1,1,1,3,3,3‐hexafluoroisopropyl methacrylate (HFiPMA) based copolymers show strong pH‐dependent 19F NMR relaxation and aqueous solubility. The strongest pH–property relationship in the pH 4–9 range is observed in the case of HFiPMA copolymers. This provides a potential for 19F MR pH gradient imaging. The conformational changes due to protonation/deprotonation explain the observed behavior.