Arsphenamine (The nasty organometallic parade continues)
9th May 2006
Here is another distinctly unfriendly-looking molecule, arsphenamine. For 30-40 brutish years, this was our single best treatment for syphilis. We owe this distinct pleasure to Paul Ehrlich, father of chemotherapy (coined the term, along with “Magic Bullet.”) In the early 20th century, he was working on histology, or staining cells. He reasoned that if we had compounds that stained only certain types of cells, maybe we could find one that would kill certain cells. Like syphilis spirochetes.
While this was a primitive theory of selectivity, Elrich used it to good effect, and six hundred five dead ends later, he released arsphenamine upon the world:
While lavishly toxic, it wasn’t quite as bad as what we used before - compounds of mercury, which were even worse. The early 20th century ushered in chemotherapeutics as we know them today; penicillin followed shortly thereafter. By WWII, it had essentially supplanted arsphenamine as the drug of choice for syphilis.
It’s easy to forget that these nasty arsenic compounds were once cutting-edge. For a time, arsphenamine was the single most widely prescribed drug in the world.
Interest in the structure continued well after the drug’s useful clinical lifetime had long since passed. In this Chemical and Engineering News Article, it’s noted that a paper on the structure of arsphenamine was published in Angewandte Chemie International Edition just last year. This is one of the single best journals in chemistry.
The “historical” structure of arsphenamine is listed at top. For a long time, it was suggested that this was the structure. The paper from Brian Nicholson’s group proved that the compound existed as a oligoarsenocyclic trimer and pentamer. The continuing interest in arsphenamine today (also termed Salvarsan and Ehrlich 606, since it was the earlier-mentioned six hundred sixth compound tested - proof that abundant dead-ends and uncreative names are not a new development in pharma!) is a testament to how singular a discovery it was.
See you tomorrow!