Arsenic in Sponges
The Promise of Naturally Occurring Compounds in Medicine
Arsenicin A, As4O3(CH2)3 is a complex molecule containing four arsenic atoms in a cage-like structure. It’s found in tiny quantities in the New Caledonian marine sponge Echinochalina bargibanti and is the first poly-arsenic compound to have been isolated from nature. Its role in the marine sponge remains unknown, partly because of a lack of detailed knowledge about its chemical structure. The difficulty in determining its structure is that the quantity of Arsenicin A that can be extracted from living sponges is miniscule so the only diagnostic techniques chemists have been able to apply are those only requiring very small quantities, such as nuclear magnetic resonance and mass spectrometry.
However, to really get to grips with the detailed structure of the Arsenicin A molecule and its biochemical properties, requires much larger samples that can be studied by techniques like X-ray crystallography and analytical chemistry. Given the low natural concentrations of Arsenicin A, the most effective way to obtain a large quantity is to develop a method of synthesising it in the lab. Di Lu, is a graduate student in the Ligand Design and Synthesis Group at the Research School of Chemistry doing just that. Her honours project was to develop a synthetic process to construct Arsenicin A from other simpler arsenic compounds.
“Designing a synthesis process was particularly difficult when the exact structure of the desired compound wasn’t well known.” Di explains, “Computational chemists had calculated that there were six possible configurations of Arsenicin A based on the NMR data, but until we had enough to do a complete analysis it was very difficult to know which form the actual molecule took.”
After almost a years work, Di succeeded in developing a viable synthetic route to Arsenicin A. Spectral data for the product are consistent with those reported for the tetraarsenic compound isolated form the New Caledonian marine sponge and the structure has been confirmed by X-ray crystallography.
Following on the success of her Honours year, Di is now expanding her Arsenicin A work as part of her PhD studies. “Quite apart from providing substantial quantities of Arsenicin A for analysis, having a known method for its synthesis means that if it has useful properties we already have a way to create lots of it.” Di says. And there’s every reason to suspect it will have useful properties because Arsenicin A is a very similar compound to arsenic trioxide, except that it contains four rather than three arsenic atoms. Arsenic trioxide is well known as a highly effective treatment for a type of leukaemia known as Acute Promyelocytic Leukaemia.
“Arsenic compounds have quite a long history of medicinal use, although because Arsenic is a well known poison, patients are often apprehensive about its use.” Di says, “But you eat arsenic compounds every single day in many foods. And providing it’s the right compound and you don’t eat huge amounts, it’s fine because our bodies have quite a high tolerance to it.”
In fact in the days before antibiotics, arsenic compounds like Arsphenamine (also known as Salvarsan) were the only effective treatments for diseases like syphilis and sleeping sickness. Even today, arsenic compounds provide an effective treatment pathway for certain types of fungal and bacterial infections that cannot be treated with antibiotics. As work progresses on the understanding of the biological role of Arsenicin A, scientists like Di are hopeful that they may provide new and powerful tools in the treatment of disease.