Quantitative Structure-in Vivo Half-Life Relationships of Perfluorochemicals for Use as Oxygen Transporters

Quantitative structure-activity relationships of a series of perfluorochemicals (PFCs) for use as oxygen transporters were investigated in terms of their in vivo half-lives (t1/2). The logt1/2 values can be correlated by a linear combination of lipophilic (e.g., critical solution temperature (CST)), physicochemical (e.g., molecular weight and vapor pressure (Pv)) and topological (e.g., number of fluorines (NOF)) parameters on regression analyses. The most important excretion-rate-determining factor was the CST. The Pv alone of PFCs did not correlate well with logt1/2. However, a combination of CST and Pv produced the most meaningful and important correlation, indicating that Pv plays a pivotal role in the excretion and can be considered a kind of correction factor to the CST. The t1/2 can thus be predicted from the combination of CST and Pv. It can also be predicted from structural information : the smaller the NOF, the shorter the t1/2. The incorporation of hetero atom (s) such as nitrogen and oxygen in the PFC molecule, which has been considered to produce better emulsion stability but results in persistence in the body, had relatively little effect in terms of t1/2. These results suggested that, taking the emulsifiability of hetero atom-containing PFCs into consideration, a cyclic F-ether and F-tertiary amine with fused ring (s), containing fewer fluorines than acyclic analogues, might be a good candidate compound as an oxygen transporter.