Thermodynamics of Decorporol Complexes with Sr and Ca IonsA Combined Isothermal Titration Calorimetry and DFT Study.

Nuclear incidents release hazardous Sr, posing risks to health. Seeking chelating agents capable of removing Sr is critical for nuclear safety and development. In our work, the main goal was to develop a substantial yet straightforward method to support the design of viable, in vivo stable chelating agents for radiostrontium. To investigate, we implemented the highly accurate density functional theory (DFT)-based rSCAN-3c composite method and isothermal titration calorimetry (ITC). Our methods were validated through the characterization of calcium (Ca) and strontium (Sr) chelation by ethylenediaminetetraacetic acid (EDTA). The chosen DFT model was able to approximate the literature value (ΔΔ of 15.4 kJ/mol for the ion exchange reaction from Ca-EDTA to Sr-EDTA, compared to the literature value of 11.0 kJ/mol), while the thermodynamic parameters obtained from the ITC study of calcium EDTA chelation were almost identical to those found in the literature. With the validated methods, strontium chelation by (7,16-bis-malonate)-1,4,10,13-tetraoxa-7,16-diazacyclooctadecane-bis-malonic acid (Decorporol) was first synthesized and then examined. Our DFT calculations revealed that the exchange reaction from Ca to Sr with Decorporol has an exergonic (-14.1 kJ/mol) Gibbs free energy profile, which is also approved by the experimental Gibbs free energy change of -34.5 ± 1.1 kJ/mol obtained from the ITC measurements. Measurements at elevated temperatures and physiological conditions did not impact chelation significantly; therefore, in vivo application of the chelating agent is feasible.