Abstract
Sodium stibogluconate is an effective but toxic Sb-containing antileishmanial drug. Despite having been in clinical use for over half a century, the chemical structure of this small-molecule drug remains unknown. Historically, the drug has been thought to comprise an intractable mixture of interconverting species. We report here nuclear magnetic resonance (NMR) spectroscopic experiments that provide the first evidence that the reaction between gluconate and [Sb(OH)(6)](-) produces primarily one molecular species. Multidimensional experiments allow the NMR resonances of this species to be fully assigned. Further experiments on authentic samples and clinical preparations of sodium stibogluconate confirm that the primary product of the reaction of gluconate and [Sb(OH)(6)](-) is the predominant antimony-containing component of the drug. The thermodynamic stability of this predominant species was assessed using a combination of (1)H and (121)Sb NMR spectroscopic measurements, which afforded a value of K = 1006 M(-1) for its formation from gluconate and [Sb(OH)(6)](-).