The species- and site-specific acid–base properties of penicillamine and its homodisulfide

Penicillamine, penicillamine disulfide and 4 related compounds were studied by 1H NMR-pH titrations and case-tailored evaluation methods. The resulting acid–base properties are quantified in terms of 14 macroscopic and 28 microscopic protonation constants and the concomitant 7 interactivity parameters. The species- and site-specific basicities are interpreted by means of inductive and shielding effects through various intra- and intermolecular comparisons. The thiolate basicities determined this way are key parameters and exclusive means for the prediction of thiolate oxidizabilities and chelate forming properties in order to understand and influence chelation therapy and oxidative stress at the molecular level.