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The Medical Periodic Table

Here’s the latest “medical periodic table”, courtesy of this useful review in Chemical Communications. Element symbols in white are known to be essential in man. The ones with a blue background are found in the structures of known drugs, the orange ones are used in diagnostics, and the green ones are medically useful radioisotopes. (The paper notes that titanium and tantalum are colored blue due to their use in implants).
Medical periodic table
I’m trying to figure out a couple of these. Xenon I’ve heard of as a diagnostic (hyperpolarized and used in MRI of lung capacity), but argon? (The supplementary material for the paper says that argon plasms has been used locally to control bleeding in the GI tract). And aren’t there marketed drugs with a bromine atom in them somewhere? At any rate, the greyed-out elements end up that way through four routes, I think. Some of them (francium, and other high-atomic-number examples) are just too unstable (and thus impossible to obtain) for anything useful to be done with them. Others (uranium) are radioactive, but have not found a use that other radioisotopes haven’t filled already. Then you have the “radioactive but toxic) category, the poster child of which is plutonium. (That said, I’m pretty sure that popular reports of its toxicity are exaggerated, but it still ain’t vanilla pudding). Then you have the nonradioactive but toxic crowd – cadmium, mercury, beryllium and so on. (There’s another question – aren’t topical mercury-based antiseptics still used in some parts of the world? And if tantalum gets on the list for metal implants, what about mercury amalgam tooth fillings?) Finally, you have elements that are neither hot not poisonous, but that no one has been able to find any medical use for (scandium, niobium, hafnium). Scandium and beryllium, in fact, are my nominees for “lowest atomic-numbered elements that many people have never heard of”, and because of nonsparking beryllium wrenches and the like, I think scandium might win out. I’ve never found a use for it myself, either. I have used a beryllium-copper wrench (they’re not cheap) in a hydrogenation room.
The review goes on to detail the various classes of metal-containing drugs, most prominent of them being, naturally, the platinum anticancer agents. There are ruthenium complexes in the clinic in oncology, and some work has been done with osmium and iridium compounds. Ferrocenyl compounds have been tried several times over the years, often put in place of a phenyl ring, but none of them (as far as I know) have made it into the general pharmacopeia. What I didn’t know what that titanocene dichloride has been into the clinic (but with disappointing results). And arsenic compounds have a long (though narrow) history in medicinal chemistry, but have recently made something of a comeback. The thioredoxin pathway seems to be a good fit for exotic elements – there’s a gadolinium compound in development, and probably a dozen other metals have shown activity of one kind or another, both in oncology and against things like malaria parasites.
Many of these targets, though, are in sort of a “weirdo metal” category in the minds of most medicinal chemists, and that might not reflect reality very well. There’s no reason why metal complexes wouldn’t be able to inhibit more traditional drug targets as well, but that brings up another concern. For example, there have been several reports of rhodium, iridium, ruthenium, and osmium compounds as kinase inhibitors, but I’ve never quite been able to see the point of them, since you can generally get some sort of kinase inhibitor profile without getting that exotic. But what about the targets where we don’t have a lot of chemical matter – protein/protein interactions, for example? Who’s to say that metal-containing compounds wouldn’t work there? But I doubt if that’s been investigated to any extent at all – not many companies have such things in their compound collections, and it still might turn out to be a wild metallic goose chase to even look. No one knows, and I wonder how long it might be before anyone finds out.
In general, I don’t think anyone has a feel for how such compounds behave in PK and tox. Actually “in general” might not even be an applicable term, since the number and types of metal complexes are so numerous. Generalization would probably be dangerous, even if our base of knowledge weren’t so sparse, which sends you right back into the case-by-case wilderness. That’s why a metal-containing compound, at almost any biopharma company, would be met with the sort of raised eyebrow that Mr. Spock used to give Captain Kirk. What shots these things have at becoming drugs will be in nothing-else-works areas (like oncology, or perhaps gram-negative antibiotics), or against exotic mechanisms in other diseases. And that second category, as mentioned above, will be hard to get off the ground, since almost no one tests such compounds, and you don’t find what you don’t test.

58 comments on “The Medical Periodic Table”

  1. jasdou says:

    What about Hg in Thimerosal? Considering it is widely found in various vaccines, surely it should have earned a blue background!

  2. Philip says:

    Scandium is used in bicycle frames. Could that be a medical use?

  3. exGlaxoid says:

    An interesting article. But as you say, there are some elements left out.
    I would also classify Iodine as a drug component, due to the thyoid hormones and Synthroid, plus the use of iodine/iodide disinfectants.
    Several bromide salts as well as organobromides have been used as pharmaceuticals. I think there is also an eye medicine containing bromine in some form. See below for more.
    http://en.wikipedia.org/wiki/Bromide
    “Bromide compounds, especially potassium bromide, were frequently used as sedatives in the 19th and early 20th century. Their use in over-the-counter sedatives and headache remedies (such as Bromo-Seltzer) in the United States extended to 1975, when bromides were withdrawn as ingredients, due to chronic toxicity.[3]
    This use gave the word “bromide” its colloquial connotation of a boring cliché, a bit of conventional wisdom overused as a calming phrase, or verbal sedative.”
    http://en.wikipedia.org/wiki/Organobromine_compound
    Pharmaceuticals
    “Commercially available organobromine pharmaceuticals include the vasodilator nicergoline, the sedative brotizolam, the anticancer agent pipobroman, and the antiseptic merbromin. Otherwise, organobromine compounds are rarely pharmaceutically useful, in contrast to the situation for organofluorine compounds. Several drugs are produced as the bromide (or equivalents, hydrobromide) salts, but in such cases bromide serves as an innocuous counterion of no biological significance.[3]”

  4. Gearoid says:

    Bromine was in some medicines in the past (particularly sedatives) and is a classic cause of an extremely negative anion gap (due to interference with the analyzer for chloride). It is no longer really used for this indication although it is in pyridostigmine and so technically should have a blue background.

  5. Karel Capek says:

    I’m not sure about bromine in approved pharmaceuticals. But Pepsi has included brominated oils in their beverages. Does Gatorade count as a drug? Its curative powers are surely not attributable to the presence of bromine. Why the FDA considers brominated compounds to be safe as a food additive is … puzzling.

  6. Mike says:

    Brompheniramine.

  7. Anon says:

    As I read this article, all I could think of was Tom Lehrer’s song.

  8. newnickname says:

    They list boron for boron neutron capture therapy (BNC) but do not mention bortezomib (Velcade) for myeloma.

  9. Flatland says:

    @4 The use of brominated vegetable oils been severely limited/phased out since the 70’s (GRAS revoked, concentration limited to

  10. processchemist says:

    Nicergoline contains a bromonicotinic acid ester on the ergolide scaffold

  11. Virgil says:

    Although to date shown mostly in animal models, Xenon and other noble gases can protect against neuronal and cardiac ischemic injury (e.g., PMID 19467886)

  12. Algirdas says:

    I am intrigued by the fact that tin is shown in white typeface – an essential element. I just did a pubmed search to close this apparent gap in my biochemistry knowledge – did not find anything definitive.
    One of the references found, “Ecotoxicol Environ Saf. 2003 Sep;56(1):180-9. Case study: bioavailability of tin and tin compounds. Rüdel H.” PMID: 12915151,
    has the following in the full text:
    Some studies suggest that tin is an essential trace element for humans (possibly as an ionic constituent of gastrine, a stomach-stimulating peptide hormone). Natural foods contain trace amounts of tin. It is assumed that the average daily intake is in the range 0.2–1 mg (Bulten and Meinema, 1991). In feeding experiments levels of 0.5–2 ppm of tin in the diet improved growth of rats by 25–60%.
    Bulten and Meinema reference is a book chapter on tin, from “Metals and Their Compounds in the Environment pg 1243-1259”.
    Further pubmed search for “gastrin tin” results in 7 hits, none seem relevant.
    While 60% improvement in the growth rate sounds quite significant, the article does not cite any known mechanism or other biochemical rationale. And it does imply non-zero growth rate and survival in the absence of tin, which excludes it from the list of essentials.
    Does anybody know more?

  13. Chemist with a cold says:

    http://en.wikipedia.org/wiki/Bromhexine
    I’ve used this one several times.
    And I agree that Iodine and Mercury should be on there.

  14. John Schilling says:

    Xenon is also used as a general anesthetic, primarily in Europe. I don’t believe the mechanism of action is well understood, but the narcotic effects of inert gasses under pressure are well known to e.g. technical divers. Xenon, unlike the rest, has anesthetic effect at less than one bar of pressure and so is medically useful.
    Also rather expensive, on the order of $15/l, but it apparently is safer and/or more effective than the traditional inhalants. Semi-closed-cycle systems have been developed to recover exhaled Xenon, which reduces the cost to the point where some people are willing to pay for it.
    Well, some large organizations, at least.

  15. great unknown says:

    Polonium has been used, allegedly, in assassinations. Surely that qualifies as medicinal. At least prophylactic.

  16. bob organometallic says:

    I think organic/medicinal chemists are used to making big, flatish, rigid structures that will bind tightly because they can’t wriggle around. The advantage of metal complexes, surely, is that you can make rigid, 3-dimensional structures with basically whatever you like decorating the outside. Surely this is a big advantage in making a strong-binding compound?
    the comparative lack of such compounds has to be down to a lack of experience/imagination of most organic chemists in such areas.

  17. Cerium? says:

    Anyone know what drug gets cerium colored blue?

  18. Andre says:

    As a transition metal chemist, I’m bugged by the greyness of tungsten and nickel. Both are such well-explored and (more or less) well-behaved metals that it’s surprising to me they aren’t more useful. Then again I know nothing about medicine, so maybe there’s some good reason why both exist as islands in a sea of utility.

  19. CHM says:

    @17
    I’m not a medicinal chemist, but I would think that metabolizing a metal complex poses a problem. How do you make sure the ligands stay on the metal? How do you make sure the metal won’t be reduced and precipitate in the liver?
    On the other side, the body already uses metal complexes to accomplish certain functions (e.g. hemes and B12).
    So either the medicinal chemists lack imagination, or they acknowledge the higher difficulty in developing organometallic drugs. Chances are the answer is somewhere in between.

  20. Myma says:

    Since they included some medical devices, they could have also included
    NiTi – stents
    CoCr – stents
    W – used as a radio-opacifier on some catheters
    Au, Bi and Ba are also used as radio-opacifiers

  21. mp says:

    ??? Structure of boromycin. J. D. Dunitz, D. M. Hawley, D. Miklos, D. N. J. White, Yu. Berlin, R. Marusic, V. Prelog, Helv. Chim. Acta. 54 (6): 1709–1713. doi:10.1002/hlca.19710540624

  22. mp says:

    ??? Structure of boromycin. J. D. Dunitz, D. M. Hawley, D. Miklos, D. N. J. White, Yu. Berlin, R. Marusic, V. Prelog, Helv. Chim. Acta. 54 (6): 1709-1713. doi:10.1002/hlca.19710540624

  23. newnickname says:

    @22 mp: boromycin: It’s a boron compound with biological activity but is not yet an FDA approved medicinal agent. There are several other organoborons in the pipeline but not yet successfully expurgated from the pipeline.
    When you submit your posts, please WAIT for the server to process it to avoid duplicate postings.
    People consume neutriceutical grade silica (silica gel; SiO2) for medical purposes (bone health, cancer, you name it) even tho’ the suppliers aren’t allowed to make unsupported claims about medical efficacy. Other silicon drugs have been investigated but, once again, are not FDA approved.

  24. Anonymous says:

    Tin is a drug ingredient in toothpaste- Stannous Fluoride

  25. Christophe Verlinde says:

    Gallium should also have a green color.
    According to DrugBank:
    “Gallium nitrate is a drug that is used to treat hyper-calcemia, or too much calcium in the blood. This condition may occur when individuals develop various types of cancer. Gallium nitrate is also known by the common brand name Ganite.”

  26. Here’s a Br drug.
    According to Wikipedia:”Bromocriptine (INN; trade names Parlodel, Cycloset), an ergoline derivative, is a dopamine agonist that is used in the treatment of pituitary tumors, Parkinson’s disease (PD), hyperprolactinaemia, neuroleptic malignant syndrome, and type 2 diabetes.”
    The Br is a substituent on the indole.

  27. Anonymous says:

    xenon is used for perfusion and ventilation imaging.
    inhaled 239Pu is massively toxic, due to high bioavailability, ingested 239Pu is much less toxic. 226Ra is worse…

  28. Anon says:

    Is anything known about the membrane permeability of metal complexes? Or would it be a completely case-by-case basis, depending on ligand properties and such?

  29. Paul Ivsin says:

    Interesting article, and GREAT comments thread that helps restore my faith in humans’ ability to comment productively on the internet. (Though I wish someone more qualified than me will take a shot at answering the questions about Sn in #12!)

  30. NUchemist says:

    I’m surprised bromazepam hasn’t been mentioned yet. Also, sila-haloperidol.

  31. Samuel71 says:

    Many psychedelic drugs contain bromine.

  32. Filip Kielar says:

    I’d recommend the “Bioinorganic Medicinal Chemistry” from Enzo Alessio to anyone from the “proper” medicinal chemistry side of things interested in where the thoughts of inorganic/bioinorganic chemists are going.

  33. Poul-Henning Kamp says:

    The toxicity of Plutonium has been deliberately overstated in propaganda, vastly overstated even, in an attempt to discourage people from even contemplating working with it.
    It seems plausible that this was aimed at anti-proliferation efforts, but the misinformation has caused no end of trouble for the atomic energy business, both because of the obvious “against” argument, but certainly also because their own employees subscribe to this misinformation.
    According to one of Los Alamos’ own internal publications, workers who were exposed to plutonium, as part of nuclear bomb manufacturing, are doing quite well, apart from the lack of information and follow-up studies:
    http://www.atomictraveler.com/PlutoniumHistory.pdf

  34. Tim Worstall says:

    “I think scandium might win out. I’ve never found a use for it myself, either.”
    No medical use that I know of. Bike frames, as above (about 0.1% Sc in Al), baseball bats, various other Al alloys. Fuel cells (SOFCs) and light bulbs (dopant in the mercury vapour) make up the usual list of uses.
    Global annual usage is about 10 tonnes a year at present.
    From you friendly neighborhood scandium dealer.

  35. gippgig says:

    I believe scandium triflate is used in organic synthesis so, while scandium isn’t used in drugs, it may be used to make drugs.

  36. A Nonny Mouse says:

    Ferroquine, a ferrocene containing anti-malarial is being developed by Sanofi- has no cross resistance with drugs of a similar structure. Iron seems to cause cell disruption in the parasite. Made a few hundred grams myself!

  37. Cymantrene says:

    Radon is found in several mineral waters, usually nicknamed as radium emanation (that was the first name for this gas). Some of these mineral waters were believed to have an invigorating effect even before recognising their radon-content. One such water is that of the Juventus-spring (a telling name) at the Rudas Bath at Budapest.

  38. Nick K says:

    Welcome Tim Worstall! I used to enjoy your posts on the Guardian CiF.
    A brominated antimalarial drug from Janssen has recently been approved.

  39. Morten G says:

    The paper by Wilcken et al 2013 that Derek did a whole post on has a section on drugs containing bromide and iodide. http://pubs.acs.org/doi/abs/10.1021/jm3012068
    What drugs contain helium?

  40. PJ Hansen says:

    @9 #5 was correct. Brominated oils are still in use for beverages. They were certainly in Fresca and Gatorade the last time I sought refreshment. The drinks possibly prevented me from passing out and hitting my head, so it still counts as a prophylactic.

  41. Matt S says:

    #40
    Hyperpolarized Helium-3 is used in lung MRI’s

  42. AML says:

    Ambroxol-A mucoactive drug used in respiratory diseases (not approved by US FDA)contains Bromine in the structure. http://en.wikipedia.org/wiki/Ambroxol

  43. AML says:

    Ambroxol-A mucoactive drug used in respiratory diseases (not approved by US FDA)contains Bromine in the structure. http://en.wikipedia.org/wiki/Ambroxol

  44. lelldar says:

    Liquid argon has been used in cryosurgery. There are some studies about its use as anaesthetic as well (at increased pressure) but I guess it’s not really (yet) used in practice.
    Argon lasers are important too (e.g. cancer treatments) but I guess those dont count.

  45. lelldar says:

    Also quite a few light elements which are not colored as half-orange can be used for diagnostics.
    E.g. for positron emission tomography (PET) carbon-11, nitrogen-13, oxygen-15 are used in addition to fluorine-18 (which is colored orange for that, I guess).
    Lead is gray in the table but
    Lead-213 is in Phase I trials (cancer drug). http://arevamed.areva.com/
    Many other green elements are only in trials (if I understood corrently) as well so I think that should be included, too. Then again it says in the paper that image is not comprehensive.
    The list goes on (for radioactive stuff)…
    Phosphorus-32 is used both for imaging and cancer treatments.

  46. Anonymous says:

    Argon beams are indeed widely used in surgery as coagulation devices.

  47. Luke Weston says:

    Arguably, Tc should be coloured green.
    I didn’t know Si, Sn, V, Mo, Ni and Mn were essential for human life – although some marine creatures use V as an active enzyme center.

    1. David Edwards says:

      Actually, Tc is used as a diagnostic tool, but I’m currently unaware of treatment usages, so perhaps it should stay orange in Derek”s table, until someone posts a properly verified therapeutic use for it. I’ve been through cardiac testing using TC-99 followed by some time in interesting imaging hardware.

  48. anon says:

    There’s two experimental beryllium drugs, both using the functional group -OBeF3:
    http://www.drugbank.ca/search?utf8=%E2%9C%93&query=formula%3A*Be*&commit=Search
    @18: Maybe cerium oxalate?

  49. anon says:

    Chlormerodrin, a diuretic, contained mercury:
    http://www.drugbank.ca/drugs/DB00534

  50. Canageek says:

    Helium? I thought that had yet to be reacted with anything? What are we using helium gas for? Unless we are counting its use in countering bends when deep sea diving?

  51. ecooke says:

    Halothane contains bromine. AFAIK it is still on the WHO essential drugs list.

  52. JohnKeel says:

    In answer to 51, Helium is used as a mixture with oxygen as part of treatment of severe asthma and other airway obstructions as it reduces the work of breathing by having more laminar flow.

  53. Canageek says:

    Thanks JohnKeel. SO it is the physical properties we are using, not the chemical properties.

  54. Cheminf says:

    GSK’s newly approved Mekinist (trametinib) certainly has an iodine.

  55. FormerChemist says:

    For another specific use of scandium-aluminium alloys, some handgun frames (specifically revolvers made by Smith & Wesson in their Airweight line) have utilized scandium …

  56. Mfernflower says:

    Bromocriptine

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