Exploring EPR parameters of 187 Re complexes for designing newMRI probes: from the gas phase to solution and a modelprotein environment

Abstract

Breast cancer is one of the major types of cancer around the world, and early diagnosis is essential for successful treatment. Newcontrast agents (CAs), with reduced toxicology, are needed to improve diagnosis. One of the most promising Magnetic ResonanceImaging (MRI) CA is based on rhenium conjugated with a benzothiazole derivate (ReABT). In this sense, DFT has been used toevaluate the best methodology for calculating the hyperfne coupling constant (Aiso ) of ReABT. Ten, a thermodynamic analysiswas performed to confrm the stability of the complex. Furthermore, a docking study of ReABT at the enzyme PI3K active site andAiso calculations of ReABT in the enzyme environment were carried out. Te best methodology for the Aiso calculation of ReABTwas 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 confrm that the relativistic efects are important for calculatingthe Aiso values. In addition, thermodynamic analysis indicates that ReABT presents a higher stability and a lower toxicity than Gd-based CAs. Te docking studies point out that ReABT interacts with amino acids residues of alanine, aspartate, and lysine from thePI3K active site. Considering the enzyme environment, Aiso values decrease signifcantly. Tese fndings indicate that the CAcandidate ReABT could be a good candidate for a new contrast agent.