Metal speciation in blood plasma

Metal speciation in blood plasma is heavily influenced by proteins and peptides including transferrin, albumin, and glutathione. Despite this, few studies have incorporated these large molecules in speciation calculations, probably due to a lack of experimental measurements. Additionally, there is increasing evidence that metal complexes of small molecules are bioavailable. Due to the limitations posed by analytical techniques, thermodynamic models can serve as an excellent alternative to experimental measurements of metal speciation. In this work, we predict metal speciation for several biologically relevant metals incorporating complexes with proteins, peptides and small molecules. We supplemented experimental measurements from the literature with linear free energy estimates to fulfill the inventory of stability constants required to perform these calculations. In addition to evaluating the speciation of naturally present metals, we also predict the speciation of metals used for therapeutic applications like anticancer drugs, antidiabetics and antacids. Our results indicate that metal speciation is heavily dependent on pH and chelator concentration and can change drastically as metals move from blood plasma to inside cells. Additionally, metal speciation can be dominated by proteins like transferrin and is subject to change as metals cross the blood-brain barrier. Our results corroborate many experimental measurements and can help design future experiments investigating the biological impact of metal-based drugs and metal-toxicity.