Estimating stability constant and entropy for metal-ligand complexation reactions in blood plasma and microbial growth media

Linear free energy relationships (LFERs) derived from existing experimental data were employed to estimate stability constants for over 1000 metal–ligand complexes, encompassing approximately 90 metal ions and 50 biologically relevant ligands. Parallel correlations for the entropy of metal–ligand association were also established, enabling the calculation of stability constants across a temperature range of 0 to 125 °C for more than 1500 complexes. The ligand catalogue spans both low molecular weight compounds—such as amino acids, dicarboxylic acids, and vitamins—and high molecular weight species, including peptides and proteins. Additionally, novel methods were developed to estimate stability constants and complexation entropies using only the third-law entropy of the metal ion. The slopes and intercepts of the LFERs reflect underlying chemical principles, including ligand denticity, metal and ligand charge, metal ionic radius, and inductive and steric effects, thereby offering a mechanistic basis for these predictive approaches.