Exploring EPR Parameters of Re-187 Complexes for Designing New MRI Probes: From the Gas Phase to Solution and a Model Protein Environment

Breast cancer is one of the major types of cancer around the world, and early diagnosis is essential for successful treatment. New contrast agents (CAs), with reduced toxicology, are needed to improve diagnosis. One of the most promising Magnetic Resonance Imaging (MRI) CA is based on rhenium conjugated with a benzothiazole derivate (ReABT). In this sense, DFT has been used to evaluate the best methodology for calculating the hyperfine coupling constant (A(iso)) of ReABT. Then, a thermodynamic analysis was performed to confirm the stability of the complex. Furthermore, a docking study of ReABT at the enzyme PI3K active site and A(iso) calculations of ReABT in the enzyme environment were carried out. The best methodology for the A(iso) calculation of ReABT was using the M06L functional, SARC-ZORA-TZVP (for Re) and TZVP (for all other atoms) basis set, relativistic Hamiltonian, and the CPCM solvation model with water as the solvent which confirm that the relativistic effects are important for calculating the A(iso) values. In addition, thermodynamic analysis indicates that ReABT presents a higher stability and a lower toxicity than Gd-based CAs. The docking studies point out that ReABT interacts with amino acids residues of alanine, aspartate, and lysine from the PI3K active site. Considering the enzyme environment, A(iso) values decrease significantly. These findings indicate that the CA candidate ReABT could be a good candidate for a new contrast agent.