Metallome

Collaborative Computational Technologies for Biomedical Research

2011-12-06T19:00:00.001Z

It’s been a while since I read a science/technology book from back to back. And was it worth it? Definitely.

The book is about collaboration and is a collaboration. Ironically, the best-written chapters almost invariably are those by single authors. Which confirms my own theory that writing (including scientific writing) is not exactly collaborative activity. The contributions by Robert Porter Lynch [1], Robin W. Spencer [2], Victor J. Hruby [3], Edward D. Zanders [4], Brian Pratt [5] and Keith T. Taylor [6] are especially worth noting — I wish the whole book was written at the level of these chapters. Then again, collaboration is always a compromise. The material presented here is diverse and heterogeneous — what did you expect?

I am sure there are people who do all sorts of stuff using their smartphones, including scientific database browsing and chemical structure drawing [7]. This latter activity does not strike me as especially productive or convenient. (Also, makes me glad that the use of mobile phones while driving is outlawed in most of Europe.) In my view, for the purposes of computer graphics bigger is better: if I had a choice, I’d go for HIPerWall (25,600 × 8000 pixels) or, better still, HIPerSpace (35,840 × 8000 pixels) display walls [8]. Then I could draw some really large (in many senses) molecules.

As much as I enjoy reading the real (hardcopy) book, it could be nice to see it online, preferably in open access. For instance, Chapter 25 [9] has 196 references, all of them are URLs, and some of them are rather long ones. I’d love to be able to click on them rather than type!

Will the wikis, virtual communities and cloud computing replace the behemoth pharma companies and NCBI? A man can dream. Ekins et al. write [10]:

As a result of the recent recession there is a lot of drug discovery and development talent available now due to company lay-offs. If the software or other tools to enable this workforce to be productive and collaborate were available and they participated in the existing scientific collaboration networks, then there may be potential for enormous breakthroughs.

I wish I could share the authors’ optimism. Yes there is potential, but it is highly unlikely that unemployed researchers are in the mood to collaborate. In case you wonder why: being unemployed is a full-time occupation, which leaves preciously little spare time. I rather inclined to agree with Robin W. Spencer [2]:

Especially for cutting-edge scientific challenges, the participants you need are probably well paid and not particularly enthused by another tee shirt, coffee cup, or $100 voucher.

More quotes from this book can be found here.

I use this opportunity to lament the decline of old-fashioned copy editing [11]. I get used to the lack of any such luxury in open access publications: if the paper is accepted, the publisher tends to keep all your typos intact. But when you buy a book from John Wiley & Sons for a hundred something bucks, you’d expect some editorial intervention. (To be honest, I did not buy it. I can’t afford buying books at such prices anyway.) The major and minor irritations include:

Typos: “chpater” instead of “chapter” (p. 281) — I thought by now the text editing software should take care of these.
Tautologies: ‘The institutes of the national Institutes of Health’ (p. 496); ‘... we need to consider standards specifically for chemistry and biology. In chemistry specifically...’ (p. 202).
Impenetrable sentences, e.g. ‘Many aspects should be considered, such as a regulatory path for filing, potential market size, differentiability of the therapeutic and experience with and difficulty to carry out clinical trials in the disease of interest’ (p. 252) or ‘This will only be done by drawing from the mental resources of an extended scientific community in an innovative and complex, yet “daily practice”, manner that promises a profound impact on our ability to use existing data to generate new knowledge with the maximum conceivable serendipity’ (p. 454). You what?
Overabundance of acronyms (have a look at p. 497 and you’ll see what I mean).
Overabundance of buzz-words of yesteryear: crowdsourcing (see below), integration, leveraging, paradigm, stakeholder and so on. The worst offenders, however, are clear and clearly. Clearly, when these words is used too often, it is clear that something is not quite clear.

Now for “crowdsourcing”: I find the term not only ugly but offensive. As a scientist (once a scientist, always a scientist), I am open to collaboration. Also, as a scientist, I detest being part of a crowd. Period.

Don’t get me wrong: it is a good book. I wouldn’t hesitate to recommend it to any decent scientific library. But it could have been a great book.

Lynch, R.P. Collaborative innovation: essential foundation of scientific discovery. In: Ekins, S., Hupcey, M.A.Z. and Williams, A.J. (eds.) Collaborative Computational Technologies for Biomedical Research. John Wiley & Sons, Hoboken, 2011, pp. 19—37.
Spencer, R.W. Consistent patterns in large-scale collaboration. Ibid., pp. 99—111.
Hruby, V.J. Collaborations between chemists and biologists. Ibid., pp. 113—120.
Zanders, E.D. Scientific networking and collaborations. Ibid., pp. 149—160.
Pratt, B. Collaborative systems biology: open source, open data, and cloud computing. Ibid., pp. 209—220.
Taylor, K.T. Evolution of electronic laboratory notebooks. Ibid., pp. 303—320.
Williams, A.J., Arnold, R.J.G., Neylon, C., Spencer, R.W., Schürer, S. and Ekins, S. Current and future challenges for collaborative computational technologies for the life sciences. Ibid., pp. 491—517.
He, Z., Ponto, K. and Kuester, F. Collaborative visual analytics environment for imaging genetics. Ibid., pp. 467—490.
Bradley, J.-C., Lang, A.S.I.D., Koch, S. and Neylon, C. Collaboration using open notebook science in academia. Ibid., pp. 425—452.
Ekins, S., Williams, A.J. and Hupcey, M.A.Z. Standards for collaborative computational technologies for biomedical research. Ibid., pp. 201—208.
Clark, A. The lost art of editing. Guardian, 11 February 2011.

Kilogram, pterin, selenium

2011-11-23T18:00:00.003Z

I really enjoyed the latest issue of Chemistry International. Did you know that pterin is called “pterin” because it was first isolated from butterfly wings, and folic acid is “folic” because it was first found in leafy vegetables (from Latin folium)? I just learned that from Edward Taylor’s illuminating article on Alimta [1].

Next, two papers on kilogram in the “New SI”. Currently, kilogram is defined as a unit of mass equal to mass of the international prototype kilogram (IPK), which is a cylinder made of 90% platinum—10% iridium alloy kept at the International Bureau of Weights and Measures in France. The problem is, IPK is losing mass! But even if it did not, it is still not good that one of SI base units is linked to an artifact rather than to something more fundamental. The chemist in me prefers the definition of kilo based on carbon-12 mass [2] to the one based on Planck constant [3].

Finally, essay by Jan Trofast on discovery of selenium [4]. I didn’t know that Swedes discovered so many elements!

Taylor, E.C. (2011) From the wings of butterflies: The discovery and synthesis of Alimta. Chemistry International 33, 4—8.
Censullo, A.C., Hill, T.P. and Miller, J. (2011) Part I — From the current “kilogram problem” to a proposed definition. Chemistry International 33, 9—12.
Mills, I. (2011) Part II — Explicit-constant definitions for the kilogram and for the mole. Chemistry International 33, 12—15.
Trofast, J. (2011) Berzelius’ discovery of selenium. Chemistry International 33, 16—19.

Icosahedrite

2011-10-07T01:17:00.001+01:00

In 1982, Dan Shechtman observed unusual diffraction pattern in aluminium—manganese alloy [1, 2]. Almost 30 years later, he was awarded The Nobel Prize in Chemistry 2011 “for the discovery of quasicrystals”.

Earlier this year, the first naturally occurring quasicrystal was described. Icosahedrite Al₆₃Cu₂₄Fe₁₃ is a new mineral found in southeastern Chukhotka, Russia. It is named “for the icosahedral symmetry of its internal atomic structure, as observed in its diffraction pattern” [3].

Shechtman, D., Blech, I., Gratias, D. and Cahn, J. (1984) Metallic phase with long-range orientational order and no translational symmetry. Physical Review Letters 53, 1951—1953.
Fernholm, A. (2011) Crystals of golden proportions. Nobelprize.org.
Bindi, L., Steinhardt, P.J., Yao, N. and Lu, P.J. (2011) Icosahedrite, Al₆₃Cu₂₄Fe₁₃, the first natural quasicrystal. American Mineralogist 96, 928—931.

Do we need the terminal e?

2011-09-25T22:22:00.000+01:00

Chemical English, after all, is just a subset of English. As such, it suffers the same problem as English in general: the pronunciation of the words is far from obvious. What makes it worse for chemistry is absence of any authoritative pronunciation guide. (Since the last year’s post on this topic, the audio guide “Pronunciation of Chemical Terms”, originally hosted by Hong Kong Cyber Campus, has disappeared from the web.)

You’d think that the chemical terminology was developed after the Great Vowel Shift and therefore there must be less of gap between the spoken and written word. You’d be wrong. The gap is there, a-gaping.

For instance, the effect of silent terminal e on pronunciation of English words, including chemical terms, is simply unpredictable. Sometimes the terminal e makes no difference: both thiamine and thiamin are pronounced and mean the same. (Cf. “win” and “wine”.) In some other cases, it makes a lot of difference: chlorine (chemical element number 17) and chlorin (tetrapyrrole), or silicon (chemical element number 14) and silicone (a class of silicon-containing polymers).

Protein vs cysteine; cisplatin vs astatine; krypton vs ketone; phenol vs pyrrole — what is the point of terminal es? Wouldn’t we all be better off without them? That will spare us a few rules about elision of terminal vowels, for example.

Sometimes metal just plain rusts

2011-08-13T22:00:00.000+01:00

Our stainless steel forks and knives, which in England were literally stainless, even spotless, for years, here on Fuerteventura developed rust stains in a matter of days. What’s the matter?

I found this lovely quote from Brion Toss’s book [1]:

Sometimes metal just plain rusts. Stainless steel rusts more slowly, but tropical climates will get to it in just a few years. Galvanized steel left untended can dissolve in a matter of months.

Well said, but what exactly is wrong with “tropical climates”? High humidity and high temperature, that’s what.

But wait. Humidity in Fuerteventura is not higher than in England, right? We hardly have any rain on this island. But the temperature is definitely higher. As is the case with most chemical reactions, the corrosion rate increases with increasing temperature. Add to this salt air. (Salt acts as a catalyst of rusting.) No wonder cars rust quickly here.

Ah well, we always can use the chopsticks.

Toss, B. (1998) The Complete Rigger's Apprentice: Tools and Techniques for Modern and Traditional Rigging. International Marine/Ragged Mountain Press, Camden, Maine.

CYP7A1—cholest-4-en-3-one complex

2011-07-29T17:23:00.001+01:00

The crystal structure of human CYP7A1 (cholesterol 7α-monooxygenase) in complex with cholest-4-en-3-one has been solved [1].

PDB:3SN5

Phe—Val crosslink in symerythrin

2011-07-28T22:36:00.002+01:00

The crystal structure of diiron protein symerythrin from Cyanophora paradoxa reveals a novel C—C cross-link between valine and phenylalanine residues [1].

Cooley, R.B., Rhoads, T.W., Arp, D.J. and Karplus, P.A. (2011) A diiron protein autogenerates a valine-phenylalanine cross-link. Science 332, 929.

Open and closed P450 2B4

2011-06-18T18:25:00.002+01:00

The crystal structures of rabbit P450 2B4 covalently bound to the mechanism-based inactivator 4-tert-butylphenylacetylene in closed (a) and open (b) conformations have been solved [1].

(a)

(b)

Gay, S.C., Zhang, H., Wilderman, P.R., Roberts, A.G., Liu, T., Li, S., Lin, H.-l., Zhang, Q., Woods, V.L., Jr., Stout, C.D., Hollenberg, P.F. and Halpert, J.R. (2011) Structural analysis of mammalian cytochrome P450 2B4 covalently bound to the mechanism-based inactivator tert-butylphenylacetylene: insight into partial enzymatic activity. Biochemistry 50, 4903—4911.

Importance of being obsessive-compulsive

2011-04-26T21:47:00.001+01:00

Never underestimate the importance of naming. For instance, I would probably never read the excellent paper by Kuhn and Wahl-Jensen [1] if not for its title. (Seriously, read it. Although the note appears in Binomina, it is relevant to scientific nomenclature and terminology in general, not just biological taxonomy.) They write:

When terms get renamed just for the sake of renaming them then outrage at nomenclature experts is justified. But it is a two-way street. Nomenclature without discourse with the scientific community working in laboratories is useless — but science without nomenclature cannot be performed, either.

Conversely, Roderic Page argues that “quite a lot” of biology can be performed without “proper” taxonomic names [2], even though his

definition of “proper” name is a little loose: anything that had two words, second one starting with a lower case letter, was treated as a proper name.

Just imagine the fury of those who are “obsessive-compulsive about terminology” on reading that! Surely not any binomial name is “proper”? However, that is beyond the point. Linnaean names are just the labels. They may be preferable to NCBI tax_id codes because of aesthetic considerations but ultimately they are dispensable. We only cling to them because we believe that these labels have, as Robert M. Pirsig put it, “an intrinsic sacredness” of their own [3]:

One finds that in the Judeo-Christian culture in which the Old Testament ‘Word’ had an intrinsic sacredness of its own, men are willing to sacrifice and live by and die for words.

But what about chemistry? On the one hand, chemistry appears to be in a better position because of superiority of chemical nomenclature over, well, any other known nomenclature. The name constructed according to the rules of systematic chemical nomenclature holds the key to the structure of the entity in question. It does not mean that there could or should be only one “proper” name for one structure. For example, “tetrafluoridolead” (additive nomenclature) and “tetrafluoroplumbane” (substitutive nomenclature) correspond to the same entity, PbF₄. You don’t have to know it, because you can figure it out. Compare this with the situation in biology: there is no way to deduce that, say, Prunus dulcis and Amygdalus communis are synonyms.

On the other hand, we chemists often fall into the same trap as anyone else: we tend to believe that “proper” naming of a compound (of known structure) automatically improves our knowledge of it. But why? The terms can change. The nomenclature rules are changing. For a structure of certain complexity, the application of the same rules by different chemists (or different naming software) may result in different systematic names. Some structures as yet cannot be named by any software. So what? It is highly unlikely that a name which takes more than 100 characters will be used in any discourse. I distinctly remember thinking about it a few years ago while reading the draft of IUPAC Recommendations for rotaxane nomenclature [4]. Why not to use the (equally unpronounceable but more useful) InChI string instead?

Still, I wouldn’t dismiss the aesthetics that easily. For me, concise, clear, elegant is good; long, ambiguous, ugly is bad. And coming back to the title of [1]: “being obsessive-compulsive about terminology and nomenclature” is neither a vice nor a virtue. It is a mental condition that some people (myself included) have, for the better or the worse.

Kuhn, J.H. and Wahl-Jensen, V. (2010) Being obsessive-compulsive about terminology and nomenclature is not a vice, but a virtue. Bionomina 1: 11—14.
Page, R. (2011) Dark taxa: GenBank in a post-taxonomic world.
Pirsig, R.M. (1974) Zen and the Art of Motorcycle Maintenance.
Yerin, A., Wilks, E.S., Moss, G.P. and Harada, A. (2008) Nomenclature for rotaxanes and pseudorotaxanes (IUPAC Recommendations 2008). Pure Appl. Chem. 80, 2041—2068.

Amethyst

2011-04-08T23:13:00.001+01:00

Last Summer, we bought this crystal-growing kit in Oxfam. It contains ingredients and instructions to grow several types of crystals. Those nicknamed “quartz” and “emerald” in fact are monoammonium phosphate, NH₄H₂PO₄, while “amethyst” and “fluorite” are grown from a solution of potassium aluminium sulphate, KAl(SO₄)₂. Our latest experiment was to grow an “amethyst” crystal cluster. Timur and I prepared the solution, poured it over two stones from our garden and left to grow for a week. Here’s the result.

Chlorite dismutase

2011-03-22T22:00:00.002Z

Photosynthesis is not the only dioxygen-evolving biological process. For instance, chlorite dismutase (Cld; EC 1.13.11.49) catalyses the production of O₂ from chlorite (1):

ClO₂⁻ → Cl⁻ + O₂

(1)

The reaction (1) is not really disproportionation, and NC-IUBMB made a valid point that the term “chlorite dismutase” is “misleading”. Even so, the NC-IUBMB-approved, sorry, “accepted” name “chlorite O₂-lyase” for an oxidoreductase is equally absurd; I am going to ignore it.

Chlorite dismutase from Azospira oryzae exists as a homohexamer [1] while Cld from Dechloromonas aromatica [2] and enzyme from Candidatus Nitrospira defluvii [3] are homopentamers.

The active site contains a single haem group [Fe(ppIX)] coordinated by a proximal histidine residue. Goblirsch et al. [2] propose the mechanism where the reaction of chlorite within the distal pocket of Cld generates hypochlorite (ClO⁻) and a compound I intermediate [Fe(ppIX)O] (1a). Then ClO⁻ rebounds with compound I forming the chloride and dioxygen (1b):

ClO₂⁻ + [Fe(ppIX)] → ClO⁻ + [Fe(ppIX)O]	(1a)
ClO⁻ + [Fe(ppIX)O] → Cl⁻ + O₂ + [Fe(ppIX)]	(1b)

de Geus, D.C., Thomassen, E.A.J., Hagedoorn, P.-L., Pannu, N.S., van Duijn, E. and Abrahams, J.P. (2009) Crystal structure of chlorite dismutase, a detoxifying enzyme producing molecular oxygen. J. Mol. Biol. 387, 192—206.
Goblirsch, B.R., Streit, B.R., DuBois, J.L. and Wilmot, C.W. (2010) Structural features promoting dioxygen production by Dechloromonas aromatica chlorite dismutase. J. Biol. Inorg. Chem. 15, 879—888.
Kostan, J., Sjöblom, B., Maixner, F., Mlynek, G., Furtmüller, P.G., Obinger, C., Wagner, M., Daims, H. and Djinović-Carugo, K. (2010) Structural and functional characterisation of the chlorite dismutase from the nitrite-oxidizing bacterium “Candidatus Nitrospira defluvii”: Identification of a catalytically important amino acid residue. J. Struct. Biol. 172, 331—342.

Femtosecond X-ray nanocrystallography of PSI

2011-03-21T19:07:00.002Z

It is a well known fact (to those who know it well) that in order to obtain a decent diffraction pattern one has to grow a decent-size crystal first. Well, that is about to change. The PDB entry enigmatically named “femtosecond X-ray protein nanocrystallography” [1] in fact contains the structure of the photosystem I (PSI) from Thermosynechococcus elongatus solved by this new method [2]. In this work, more that 3 million diffraction patterns were collected from really small PSI crystals (from ~200 nm to 2 μm in size) illuminated by the new femtosecond X-ray laser, the Linac Coherent Light Source in Stanford. According to the authors,

We mitigate the problem of radiation damage in crystallography by using pulses briefer than the timescale of most damage processes.

PDB:3PCQ
Chapman, H.N., Fromme, P., Barty, A. et al. (2011) Femtosecond X-ray protein nanocrystallography. Nature 470, 73—77.

P450 from Actinoplanes teichomyceticus

2011-03-20T21:11:00.006Z

The crystal structure of the P450 monooxygenase from Actinoplanes teichomyceticus (CYP165D3) involved in biosynthesis of antibiotic teicoplanin has been solved [1].

Li, Z., Rupasinghe, S., Schuler, M. and Nair, S.K. (2011) Crystal structure of a phenol-coupling P450 monooxygenase involved in teicoplanin biosynthesis. Proteins: Structure, Function, and Bioinformatics 79, 1728—1738.

P450 monooxygenase AurH from S. thioluteus

2011-03-17T17:45:00.006Z

The first crystal structures of the unique P450 monooxygenase AurH from Streptomyces thioluteus have been solved [1].

Zocher, G., Richter, M.E.A., Mueller, U. and Hertweck, C. (2011) Structural fine-tuning of a multifunctional cytochrome P450 monooxygenase. J. Am. Chem. Soc. 133, 2292—2302.

Natural products

2011-01-27T22:00:00.001Z

Do a Google search and you’ll find all sorts of stuff claimed to be “natural products” — amazingly, some of them even are “chemical-free”! Now seriously. To quote IUPAC’s 1999 recommendations [1],

The nomenclature of natural products has suffered from much confusion.

That does not surprise me. What is surprising, however, that neither these nor the previous recommendations [2] tell us what the “natural products” are. Ditto the Gold Book. It may define terpenoids as “natural products and related compounds formally derived from isoprene units” but the natural products go without explanation. (Nor is it clear what “related compounds” are.) The very same Gold Book says that natural graphite is “a mineral found in nature”. Therefore, “natural” means “found in nature”. Right? Right. Is natural graphite a natural product? I am not sure.

Let us look in Webster then:

A chemical substance produced by a living organism; — a term used commonly in reference to chemical substances found in nature that have distinctive pharmacological effects. Such a substance is considered a natural product even if it can be prepared by total synthesis.

Is that any better? Both dioxygen and nitric oxide are produced by living organisms and have rather distinctive pharmacological effects, yet most chemists would hesitate to call them natural products. In The Concise Oxford Dictionary, the first definition of “natural” is

existing in or caused by nature; not artificial.

Of course human beings are parts of nature, but maybe this negative definition, “not artificial”, is indeed most useful?

In ChEBI, natural product (no definition so far) is an organic molecular entity (so no O₂ or NO here) and includes the following classes:

On the first glance, nothing looks particularly disturbing here. But I see a bit of a problem with ontology. First, all is a children of natural product have to be natural products. What if we have, say, (artificially) fluorinated carbohydrates? Are they still carbohydrates? If no, then the True path rule is broken. If yes, then some “unnatural” compounds will be considered natural products. I don’t mind that — perhaps that will cover “related compounds” (whatever they are) nicely.

Second, CHEBI:33243 belongs to chemical entity ontology, which is (or at least it should be) purely structure-based. The origin does not enter here. There is no such thing as intrinsic “naturalness” in a natural product molecule: natural product remains a natural product even if (artificially) prepared by total synthesis.

Natural products often are equated with secondary metabolites. This does not seem right. In ChEBI, secondary metabolite (“A metabolite that is not directly involved in the normal growth, development or reproduction of an organism” — another negative definition?) belongs to role ontology. (The role ontology sounded such a good idea at the time... no, don’t get me started.) At best, one can say some natural products have role “secondary metabolite”. Yuck.

To summarise: “natural product” appears to be a rather useless top-level term. Let us look at the sources of natural products: plants, fungi, bacteria, animals. What if, instead of saying “fungal natural product”, we say “fungi-specific compound”? In this case, we discard primary metabolites, other simple compounds found just about everywhere in the universe and are left with exactly what we want: molecules isolated from and specific for fungi.

Or are we? Antibiotics, naturally synthesised by fungi, are not naturally found in humans. But when we take them, they are naturally metabolised in our liver and eventually excreted with urine. Are these metabolites the natural products? If yes, are they fungal or animal or neither?

Revised Section F: Natural products and related compounds (IUPAC Recommendations 1999). Pure Appl. Chem. 71, 587—643 (1999).
Nomenclature of Organic Chemistry. Section F: Natural Products and Related Compounds. Recommendations 1976. Eur. J. Biochem. 86, 1—8 (1978).

It’s elementary

2010-11-14T00:00:00.000Z

According to IUPAC’s Principles of Chemical Nomenclature [1],

An element (or an elementary substance) is matter, the atoms of which are alike in having the same positive charge on the nucleus (or atomic number).

In certain languages, a clear distinction is made between the terms ‘element’ and ‘elementary substance’. In English, it is not customary to make such nice distinctions, and the word ‘atom’ is sometimes also used interchangeably with element or elementary substance. Particular care should be exercised in the use and comprehension of these terms.

An atom is the smallest unit quantity of an element that is capable of existence, whether alone or in chemical combination with other atoms of the same or other elements.

You can’t help noticing the circular nature of these definitions: An element is matter, the atoms of which have the same atomic number; while an atom is the smallest unit quantity of an element. And what are “atoms of the same or other elements” if not just “any atoms”?

Of course it is not helpful that ‘element’ is used for either ‘elementary substance’ or ‘atom’. The ChEBI solution was to get away from ‘element’. Instead, there are either atoms or elemental molecular entities. These belong to different branches of ontology, so they should not really be confused. Or at least, that was the idea.

In ChEBI, ‘elemental’ applies to any class of molecular entities which consist of only one type of atom, be they mono- or polyatomic. For instance, elemental oxygen can be mono-, di- or triatomic. On the other hand, the oxygen atom can be part of a non-elemental molecular entity.

If there is a scope for confusion, people will get confused. Here’s a question I heard on more than one occasion: what is the difference between monoatomic oxygen and oxygen atom? After all, any form of monoatomic oxygen, viz. oxide(•1−), oxide(2−), or neutral monooxygen, can also be referred to as an ‘oxygen atom’. Ditto any of the monooxygen groups: oxido (—O⁻), oxo (=O) and oxy (‒O‒). The thing is, they belong to different universes (which, properly, should be made disjoint):

monoatomic oxygen is a monoatomic entity is a molecular entity
monooxygen group is a group
oxygen atom is a atom

A group does not exist on its own: it is always a part of polyatomic entity and consists of at least one atom plus at least one bond. Monoatomic entity consists of one (and only one) atom and does exist on its own. Since we need ‘atom’ to define both groups and molecular entities, it is a good idea to keep atoms in an independent, disjoint branch.

Leigh, G.J., Favre, H.A. and Metanomski, W.V. Principles of Chemical Nomenclature: A Guide to IUPAC Recommendations, Blackwell Science, 1998, p. 3.

Ontology and reality

2010-09-13T21:21:00.002+01:00

One of these days, I keep promising myself, I am going to publish something incredibly clever about chemistry, ontology and/or chemical ontology. Then again, I need some incentive to do so, and there’s none in my view. In the meantime, I am happy that somebody else has bothered to write a paper dealing with so-called “realist” approach to ontology [1].

Personally, I never cared much about the “reality” as used in context of OBO Foundry Principles [2]:

Terms in an ontology should correspond to instances in reality.

Worse still is its “corollary”:

Ontologies consist of representations of types in reality — therefore, their preferred terms should consist entirely of singular nouns.

(Why? Does “reality” really consist of singular English nouns?)

Now Lord and Stevens confirm my gut feeling that “realism” (the authors take care to clarify that “realism” in [1] stands for “realism as practiced by BFO”) applied to ontology building often results in unnecessary complexity. Everybody who ever studied physics (or English) in school would agree that expression |dr/dt| is much better definition of speed than the one provided by PATO: “A physical quality inhering in a bearer by virtue of the bearer’s rate of change of position”. To quote [1],

It makes little sense to replicate the models of physics using English instead of a more precise mathematical notation.

Alas, this is exactly what BFO (and most of OBOs) are trying to do. By going “where science has gone before” without learning the language of the science, BFO & Co. keep reinventing the square wheel.

OK, what about chemistry? Chemistry has developed its own language which makes the plain-text definitions for molecular entities redundant. The 2-D diagram (connectivity) defines the molecule of interest better than a paragraph in English. In theory, the systematic name should provide the exactly same information (and thus to be usable as a definition). However, the systematic names for even relatively small molecules often are too complicated to be widely (or ever) used.

Take the systematic name (a) for beauvericin. You are extremely unlikely to either hear it (because it is more or less unpronounceable) or see it (it takes more than one line of text, which is annoying). More importantly, there is a certain limit of molecular complexity above which the systematic names (according the existing nomenclature rules, that is) simply cannot be generated. On the other hand, the diagram (b) is both beautiful and useful.

(a)	(3S,6R,9S,12R,15S,18R)-3,9,15-tribenzyl-4,10,16-trimethyl-6,12,18-tri(propan-2-yl)-1,7,13-trioxa-4,10,16-triazacyclooctadecane-2,5,8,11,14,17-hexone
(b)

Not only are the 2-D diagrams self-defining, they provide all the information needed to build the consistent ontology for molecular entities. With a few simple rules, the ontology will build itself from scratch, I promise. But this is a topic for another post.

Lord, P. and Stevens, R. (2010) Adding a little reality to building ontologies for biology. PLoS ONE 5, e12258.
OBO Foundry Principles.

Terminology vs nomenclature

2010-09-08T17:40:00.002+01:00

First published 8 September 2010 @ just some words

According to The Concise Oxford Dictionary,

nomenclature n. 1 a person’s or community’s system of names for things. 2 the terminology of a science etc. 3 systematic naming. 4 a catalogue or register.

terminology n. (pl. -ies) 1 the system of terms used in a particular subject. 2 the science of the proper use of terms.

I must say that these definitions do not add much clarity. Do you see any difference between “system of names for things” and “system of terms”? Moreover, the nomenclature (2) appears to be equated with the terminology. As for terminology (2), it is akin to terminology as defined by Wikipedia: “the study of terms and their use”, although I have my doubts whether there is such thing as “the science of the proper use of terms”. As was mentioned before, “logy” does not always mean “a subject of study or interest”. And what is “proper”?

On the other hand, Merriam-Webster defines terminology as

1 the technical or special terms used in a business, art, science, or special subject
2 nomenclature as a field of study

No, this does not help at all. Let us agree on the following: terminology is not nomenclature, and nomenclature is not terminology. I suggest these working definitions:

terminology:

nomenclature:

Completely different things. Terminology is a subset of vocabulary and, therefore, is part of the language. Nomenclature is a set of external rules. A good nomenclature system has few rules all of which should be understood and applied, preferably with reproducible results, by more than one person.

That is not to say that terminology does not depend on nomenclature or vice versa. Terms can be formed by systematic application of nomenclature rules — that’s what the nomenclature is devised for. But they also can arise by different mechanisms, just like any new words do. Often, terms are recruited from the existing lexicon and conferred new meanings. For instance, the word “residue” acquired specific meanings in fields of math, chemistry or law.

The Russian word for nomenclature, номенклатура, has an additional meaning: the bureaucratic class of Soviet Union and its descendants (as in “post-Soviet nomenklatura”).

Spoken chemistry

2010-07-27T22:00:00.006+01:00

As I was going, for the nth time, through the draft of the “new Blue Book”, it did strike me how much attention is paid to the appearance of a printed word. It is discussed in length what type of dash or bracket to use, which part of term has to be italicised and so on, whereas we often do not even know how to pronounce it. Which is a shame really, because I think IUPAC should take care of pronunciation (and comprehension of a spoken word) when coming with nomenclature recommendations. These are meant to improve the quality of chemical language, right? But the language where words cannot be pronounced is dead. (Think ancient Egyptian.)

Imagine we are given a task of recording an audio book on chemical nomenclature. Suddenly the names that look neat on paper become next to useless. Why? We do not pronounce parentheses (brackets, braces). We can’t pronounce sub- or superscripts. Ditto dashes, full stops and colons, which all can be parts of systematical names. Not to mention white space.

No, in olden days the pronunciation of your chemicals was taken seriously. Back in 1949, Dr. W. Bryce Orme wrote in a letter to British Medical Journal [1]:

Doctors and chemists are aware that difficulties occur in reaching consistency in the pronunciation of certain chemical terms, such as benzene and benzine, but generally it is conceded that the former should be rendered as ben'zēn and the latter ben'zin. It was, however, a shock to hear several highly qualified and distinguished chemists at a well-known pharmaceutical laboratory all referring to the radical CH₃ as mēthyl. I had the temerity to correct them and pointed out that the term was derived from the Greek μεθυ = wine + ύλη = wood. . . . Neither Dorland’s Medical Dictionary nor our old school friend, Liddell and Scott’s Lexicon, refers to any latitude in the pronunciation of methyl.

Well I never. American Chemical Society had a Nomenclature, Spelling and Pronunciation Committee, which even came up in 1934 with a list of recommended pronunciation for 437 terms [2]. Apparently, one even could order the complete report by writing to the chairman of the committee:

A charge of five cents per reprint (postage acceptable) to cover costs is made.

Sounds like a bargain, but that was quite a while ago. So far I was unable to get hold of the report. However, I found the next best thing: a list of about 400 common chemical terms that originally appeared on an audio tape prepared by Dr. M.P. Sammes and the Hong Kong Association for Science and Mathematics Education in 1988 [3]. Now, at long last, I know how to say “2-ethanoyloxybenzenecarboxylic acid”.

Orme, W.B. (1949) Points from letters: Pronunciation of chemical terms. Br. Med. J. 2 (4638), 1236.
Crane, E.J. (1934) The pronunciation of chemical words. J. Chem. Educ. 11, 454.
Sammes, M.P. Pronunciation of Chemical Terms.

Don’t trust your eyes

2010-05-11T14:44:00.002+01:00

Ultramarine differs from other inorganic pigments in that it does not contain any transition metals. It is the sulfur species that confer the colour: S₃^•− (blue ultramarine), S₂^•− (yellow ultramarine) or S₄ (red ultramarine). Green ultramarine contains both S₂^•− and S₃^•− [1].

You’d think that by now they should know what the structure of ultramarine is. But no. In the Inorganic Crystal Structure Database I’ve found only two structures called “ultramarine” (ICSD 27523 and 27524), both associated with a paper from 1936 [2]. The composition of ICSD 27523 is given as Na₈Al₆Si₆O₂₄S_2.5·(H₂O)_0.6. The structure (see figure below) is an aluminosilicate cage containing sodium cations and beautiful octahedral sulfur clusters. Wait a minute. S₇ clusters? Never heard about those before.

A more recent structure of deuterated lazurite, Na_7.5Al₆Si₆O₂₄S_4.5·(D₂O)_0.5 (ICSD 63022), also featuring S₇ octahedra, provided me with an explanation. The authors [3] wrote that

to accommodate the indications emerging from the difference maps, the octahedral model of sulfur occupancy was modified to reproduce a more even density inside cage by adding a further sulfur to the hollow octahedral shell, with sulfur occupancies rescaled accordingly to maintain S₃ overall.

I feel relieved if slightly disappointed.

Landman, A.A. (2003) Aspects of solid-state chemistry of fly ash and ultramarine pigments. Doctoral Thesis, University of Pretoria.
Podschus, E., Hofmann, U. & Leschewski, K. (1936) Röntgenographische Strukturuntersuchung von Ultramarinblau und seinen Reaktionsprodukten. Zeitschrift für anorganische und allgemeine Chemie 228, 305—333.
Tarling, S.E., Barnes, P. and Klinowski, J. (1988) The structure and Si,Al distribution of the ultramarines. Acta Crystallogr. B 44, 128—135.

Rhodothermus marinus HiPIP at 1.0 Å

2010-04-06T12:00:00.006+01:00

Meike Stelter and colleagues have solved the crystal structure of the reduced form of a high-potential iron–sulfur protein (HiPIP) from the thermophilic eubacterium Rhodothermus marinus.

This is the first structure of a HiPIP isolated from a nonphotosynthetic bacterium involved in an aerobic respiratory chain. The structure shows a similar environment around the cluster as the other HiPIPs from phototrophic bacteria, but reveals several features distinct from those of the other HiPIPs of phototrophic bacteria, such as a different fold of the N-terminal region of the polypeptide due to a disulfide bridge and a ten-residue-long insertion.

Popular health supplements

2010-03-20T14:00:00.006Z

David McCandless and Andy Perkins have created a generative data-visualisation of scientific evidence for popular health supplements. The more Google hits, the bigger the bubble. The greater the evidence for its effectiveness (according to PubChem abstracts and The Cochrane Collaboration), the higher a bubble. The evidence ranges from “none” to “strong” (through “slight”, “conflicting”, “promising” and “good”). This visualisation generates itself from this spreadsheet. As you can see, these supplements are quite a mixed bag, e.g.

L-lysine
(unspecified) arginine
selenium (in which form?)
fish oil
probiotics

Interestingly, of all the metals used as “health supplements”, only calcium (effective only for the specific condition of colorectal cancer) is above “worth it” line.

Hydrogen

2010-03-18T21:00:00.003Z

I say, Hydrogen is a bit unusual name for a boat. But here she is, the Thames sailing barge Hydrogen (1906) in Maldon, Essex.

She circumnavigated Great Britain for Bells Whisky and became charter barge based Maldon.

This page contains some historic photographs of Hydrogen.

Aluminium ion clock

2010-02-25T17:39:00.004Z

The scientists at the National Institute of Standards and Technology (NIST) created a new optical clock of unprecedented precision.

The clock, which is based on a single aluminium ion, could remain accurate to within one second over 3.7 billion years. The previous record was held by a clock with one mercury ion, which was good to one second in 1.7 billion years.

My, these are some mind-boggling figures.

I thought that one ²⁷Al⁺ ion should not take much space. But then, they needed another “logic ion”, ²⁵Mg⁺. And a vacuum chamber. And two lasers. (Not three lasers, as in earlier model which used Al⁺/Be⁺ pair, so I presume the new clock is more compact.) I couldn’t find in the preprint what are the dimensions of the whole contraption. However, the NIST press release features the photo of one of the authors, Chin-wen Chou, together with the famous clock. The caption says that

The ion is trapped inside the metal cylinder (center right).

Not exactly wristwatch size but easily fits in Big Ben.

Selenite

2010-02-11T22:30:00.011Z

In chemistry, selenite, [SeO₃]²⁻, is a diconjugate base of selenous acid, H₂SeO₃.
In mineralogy, selenite is a variety of gypsum, CaSO₄·2H₂O.
In science fiction, e.g. in The First Men in the Moon by H. G. Wells, the native inhabitants of the Moon are referred to as “Selenites”.

All three words are derived from Σελήνη, Greek for the Moon. Ironically, only fictitious Selenites have a “real” lunar connection.

(1)

(2)

Selenite (1) — not to be confused with selenate or selenide — is named similarly to other oxoanions of “ous” acids, such as sulfite or nitrite. The systematic name recommended by the Red Book is trioxidoselenate(2−). Now, Berzelius gave the element selenium its name by analogy with tellurium, which, in its turn, was named after Tellus, Latin for Earth. (Do you follow the logic?) The Mineral Information Institute gives an alternative explanation:

This is a reference to the silvery-gray color of metallic, non-crystalline selenium.

A similar line of thinking is responsible for naming of selenite (2):

From the Greek σελήυη, for “moon”, in allusion to the moon-like white reflections of the mineral or to the quality of the light transmitted by semi-pellucid gypsum slabs of cleavages used as windows.

Fine, but not as touching as this childhood belief:

When we were studying chemistry and the teacher talked about selenium, I thought that selenium was named after a Mexican pop star Selena who died during my childhood.

Speaking of Mexico: the world’s largest natural crystals, some as long as 11 meters, consist of selenite (2) and are found in Cueva de los Cristales in Chihuahua, Mexico.

The rise and fall of the Zinc World

2010-02-04T19:48:00.005Z

I like the way the journals such as Biology Direct now publish reviewers’ comments and authors’ responses together with a final version of the paper. The fact that reviewers’ names are made public ensure that reviewers are properly acknowledged as well as share some responsibility for releasing another pointless paper into the wild. The discussion is often more interesting than a paper. Take the couple of recent highly speculative articles on Zinc world and origin of life [1, 2]. Even though I myself would not recommend any of these manuscripts for publication (luckily nobody asked me), I am glad that these were eventually published, because I really enjoyed reading the reviews — and, occasionally, the authors’ responses.

Reviewer 4: Last but not least I find the last sentence of the paper rather revealing: what could the aesthetics of minerals to do with a scientific argument on the origin of life?

Author’s response: Aesthetic criteria are of great importance in scientific research <...> For example, my initial opposition to the idea of abiogenesis at the floor of the Hadean ocean, when I first heard about it, was purely aesthetic. I simply did not like the idea of the origin of life being in complete darkness.

Similarly, it could have been stated “I simply liked the idea of using a single type of metal cation to fulfill all life’s metal needs”. The authors acknowledge the need for transition metal ions for origin of life but argue that the zinc is preferred to other transition metals because it is not redox-active. (According to modern view, zinc is not a transition element at all — why to bring transition metals in the first place?) For example, both papers contain the statement that “iron, unlike zinc, is redox-active”. Wait a minute. Is it bad? Since zinc is not redox-active, it cannot be used as a redox cofactor, therefore there won’t be any oxidoreductases utilising zinc. But fear not; apparently, the authors think that NAD(P)H, FAD and FMN evolved before primitive life forms learned how to use Fe²⁺ ions safely.

Incidentally, the only danger of redox-active iron mentioned in these papers seems to be the “harmful hydroxyl radicals”. I would not worry much about them though because I don’t think they were the main hazard in largely anoxygenic environment. In general, conditions on Earth at the time were rather harsh. You would’t go outside without an oxygen mask and a very thick (a few inches?) layer of sunscreen. Now add, on top of that, ZnS-catalysed photosynthetic production of formaldehyde [2, equation 1]... yep, sounds a plausible enough way to kick off that life thing.

Mulkidjanian, A.Y. (2009) On the origin of life in the Zinc world: 1. Photosynthesizing, porous edifices built of hydrothermally precipitated zinc sulfide as cradles of life on Earth. Biology Direct 4, 26.
Mulkidjanian, A.Y. and Galperin, M.Y. (2009) On the origin of life in the Zinc world. 2. Validation of the hypothesis on the photosynthesizing zinc sulfide edifices as cradles of life on Earth. Biology Direct 4, 27.

BioMetals 2010

2010-01-24T20:00:00.005Z

Online registration for 7th International Biometals Symposium (BioMetals 2010) is now open. The meeting will take place in Tucson, Arizona, USA, July 25—30, 2010.

Sessions are planned on Arsenic: Toxicity and Transformation; Siderophores and Iron Transport; Interplay of Metals; Metals and Gene Regulation; Metals in Disease and Metal Transport. See the current list of invited speakers.

The conference is limited to 200 participants, so early registration is recommended.

Metals in ancient Egypt

2010-01-18T19:00:00.006Z

The al of “alchemy” is an Arabic article, but what about the rest of the word? Wikipedia mentions theories favouring Egyptian, Greek or Persian origin of the root. Whatever the etymology, it looks like ancient Egyptians knew quite a lot of chemistry.

This table of Egyptian symbols for the metals (don’t think any of them is in Unicode) misses two or three metals known to ancient Egyptians. According to Hamed A. Ead,

tin was used in the manufacture of bronze, and cobalt has been detected as a coloring agent in certain specimens of glass and glaze. Neither metal occurs naturally in Egypt, and it seems probable that supplies of ore were imported from Persia.

Mercury <...> is stated to have been found in Egyptian tombs of from 1500—1600 B.C.

Perhaps not surprisingly, the terminology used in ancient Egyptian chemical literature sometimes was deliberately misleading:

The use of the trade names for the purpose of concealing the character of the substance used where secrecy seemed desirable was not unknown at that period.

The secret names as the later alchemists used extensively: “blood of the serpent”, “blood of Hephaistos”, “blood of Vesta”, “seed of the lion”, “seed of Hercules”, “bone of the phyasimian”, etc.

The term “blood of the dove” used in the papyrus, von Lippmann has identified from other sources as meaning red lead or sometimes cinnabar.

Below minus forty

2010-01-09T17:00:00.005Z

Cold snap, you say? I do remember one New Year’s Day when the temperature in the Moscow region dropped below −40°. (Celsius or Fahrenheit? In this particular case, it’s the same: −40 °C = −40 °F = 233.15 K.) On 1 January 1979, we woke up in the (late) morning only to discover that we are stuck without any tea or hot food. We couldn’t switch on the gas cooker, which was running on propane/butane mixture. Why? As explained in this useful guide,

When the temperature of the liquids falls below its current boiling point the pressure inside the canister will no longer drive vapour out.

The boiling point of butane is −0.5 °C and that of propane is −42 °C; the temperature outside was below −42 °C, and the gas canisters were outside!

My mum called for a friendly neighbour who was better equipped than us. We kids did not worry too much about a guy warming up a gas canister with a blow torch. Anyway, everything went just fine and we had a wonderful day.

Seizure

2009-12-20T14:14:00.004Z

With all these holidays, it seems that I missed another great exhibition: “Seizure” by Roger Hiorns (open until 3 January 2010). According to Guardian,

Hiorns filled a bedsit with 75,000 litres of copper sulphate solution, which hardened over several weeks into crystals. The installation secured him a nomination for the Turner Prize.

What you see on the walls (floor, ceiling etc.) is copper sulfate pentahydrate (CuSO₄·5H₂O). A stylish way to refurbish an apartment.

Cobalt chlorium G and water fluoridation

2009-12-12T16:30:00.006Z

Two chemistry-related quotes from Dr. Strangelove:

You’ve obviously never heard of cobalt chlorium G. It has a radioactive half-life of 93 years.

Have you ever heard of a thing called fluoridation of water?

In contrast to fictitious “cobalt chlorium G”, water fluoridation is real. So is opposition to it. To quote the recent Australian study, “water fluoridation appears to be a low-risk, high-outrage controversy”. Luckily, the communist threat is no longer mentioned — or so I thought until I came across a recent publication quoting a Californian mum who wondered whether the dentist was “one of those socialists trying to poison us with fluoride”. From The Fluoride Wars: How a Modest Public Health Measure Became America’s Longest Running Political Melodrama:

It seemed such simple act at the time <in 1945>. A tap was turned, and water that had been chlorinated for many years without much fuss now carried a second chemical supplement to help keep us healthy. Soon, the taps would be turned in city after city across the nation. For most, it was another blessing bestowed on us by modern medical science. But for some, it was one chemical too many.

The Gold Book

2009-11-23T21:30:00.010Z

The Gold Book and the Silver Book (currently under revision) are two of the so-called colour books. Which kind of implies that gold and silver are colours. Not that IUPAC ran out of ‘real’ colours — e.g. they still could have chosen pink or yellow or black. For long time I thought that the reason behind naming the Gold Book ‘Gold Book’ was its (intended) role as a gold standard for chemical terminology. I was wrong. It was named in honour of Victor Gold (1922—1985), the British chemist who was the first author and compiler of the book. No such story with the Silver Book, I am afraid.

One of problems with the Gold Book (as opposed to other colour books) is that it deals with ‘general’ chemical nomenclature. Therefore, when it comes to terms which are different meanings in different fields of chemistry, the Gold Book gives more than one definition. Which one should be used? Take ligands. The definition 1 (coordination chemistry) is short and nice, while the definition 2 (biochemistry) is long and horrible. At least it mentions that in bioinorganic chemistry, one should be careful which definition to use.

In case of sulfides, there are three different meaning. Sulfides 1 (organic chemistry) is the replacement term for obsolete but less ambiguous ‘thioethers’, while sulfides 2 (inorganic chemistry) are “salts or other derivatives of hydrogen sulfide”. I am happy with salts but not with the “other derivatives”. Is sulfenic acid (IUPAC name ‘sulfanol’) a sulfide? As for sulfides 3, the definition goes “a term used in additive nomenclature”. Excellent.

Similarly, there is a consistency problem with related terms that are derived from different IUPAC recommendations. The entry for dipolar bond (1994) says:

The term is preferred to the obsolescent synonyms ‘coordinate link’, ‘coordinate covalence’, ‘dative bond’, ‘semipolar bond’.

And yet the more recent entry for dative bond (1999) does not mention that the term is obsolete. It is even states that

In spite of the analogy of dative bonds with covalent bonds, in that both types imply sharing a common electron pair between two vicinal atoms, the former are distinguished by their significant polarity, lesser strength, and greater length.

A textbook example of dative bond is the one in ammonium. Of course, all the N—H bonds are exactly the same, even if you choose to represent one of them with an arrow.

Visual maths

2009-11-19T21:31:00.005Z

Many old jokes are based on the stereotype of mathematicians as impractical freaks (as opposed to, say, chemists). Here’s one from my university days (as told by the lecturer in physical chemistry):

How to calculate the area of this figure? (Draws a squiggly figure on a blackboard.) A mathematician spends three days establishing the nature of the function and two days taking the integral. By the end of the week, the problem is solved. A chemist draws the figure on graph paper, cuts it out and weighs it on an analytical balance. The problem is solved in 10 minutes.

Note that the chemist, apart from being ‘simply’ practical, also provides more direct answer to the question.

I prefer graphics to formulae. If I can’t draw a graph, I won’t grasp a concept. Luckily, there are some great resources on the web. For instance, MatematicasVisuales contains a nice collection of Java applets which elegantly visualise a number of mathematical concepts. Examples range from geometry to probability.

This applet illustrates some aspects of the braid theory. Click on ‘draw’, enter a braid word, e.g. BcbACb, and see your braid! The applet also can ‘reduce’, or simplify, the braid diagram, as well as to solve the braid isotopy problem (‘compare’).

Chromium

2009-11-07T22:22:00.009Z

The name of chromium is derived from the Greek χρωμα (colour), because many of chromium compounds have bright colours. Chromium is also the name of the open-source browser project behind Google Chrome. Chrome is a hacker slang for the graphical user interface. The Chrome logo (a) features Google colours while the Chromium logo (b) is almost monochrome.

I liked the idea of Chrome for Linux without Google’s branding. I have followed this instruction to the letter to install Chromium on my Acer Aspire One netbook and it worked beautifully. Chromium certainly lacks lot of Firefox’s functionality but it does most things I need. Plus, it is very fast and you can change the appearance of browser using themes.

Some ChEBI news

2009-11-04T16:59:00.007Z

Wow. Today’s ChEBI news inform that

ChEBI release 62 is now available, containing 455,788 total entities, of which 19,236 are annotated entities and 607 were submitted via the ChEBI submission tool.

Looking back, I must say that ChEBI news lack consistency and therefore the users are bound to be confused. Before, we never said how many entities ChEBI contained in total. For the previous release, only “annotated” entities were counted:

ChEBI release 61 is now available, containing 18933 annotated entities, with 413 of those submitted via the ChEBI submission tool.

And a few releases back, “annotated” was not mentioned at all:

ChEBI release 58 contains 18186 entities with 175 of those submitted via the ChEBI submission tool.

Does “annotated” matter? Most ChEBI entries are annotated is some way. That includes all these thousands of compounds which just came from ChEMBL. What is meant here really is “annotated and approved by ChEBI curators”. But wait:

With this release, we’ve incorporated the compound records from the ChEMBL dataset and introduced a starring system to identify core (3-star) annotated ChEBI entries from entries annotated by the ChEMBL project and ChEBI submitters.

This is unfortunate that ChEBI introduced stars to signify entry quality. I think I am not the only one who firmly associates stars with user’s (external reviewer’s) rating. “Thou shalt not award no stars to thyself.” In addition, the star rating system usually implies that stars can be lost as well as gained, which is not the case in ChEBI: once the three-star status is reached, the entry stays as it is.

Oh well. Sure ChEBI is not perfect, but what is? Perhaps in a couple of releases we’ll see another change, stars replaced by other celestial bodies or flowers or traffic signs. Good night.

Metalloproteomics

2009-10-20T19:50:00.006+01:00

“Metalloproteomics” is a relatively new and not that widely known term. Today (20 October 2009), PubMed search produces only 13 hits. (The search for “metallomics” gives only twice as many hits.) The earliest use of the term is by Alfredo Sanz-Medel and by Scott et al. — incidentally, both papers were published online 23 December 2004.

Metalloproteomics by Eugene Permyakov (Wiley-Interscience, 2009) gives us a definition of the term:

Metalloproteomics is a proteomics of metal-binding proteins.

That’s easy, right? But wait. Check out the table of contents. It looks to me like another bioinorganic chemistry book, and a rather pricey one. It mostly deals with metalloproteins, but there are also Chapter 15, Interactions of metal cations with nucleic acids, and Chapter 16, “Nonphysiologic” metals. Nothing here is specifically proteomic or metallomic. I suppose that Chapter 3, Experimental methods used for studies of the binding of metal cations could be of some relevance to metalloproteomics. Then again, maybe not: how come that mass spectrometry, the most obvious proteomics technique, is not mentioned at all? And why metal cations only? Some metalloproteins contain vanadate. Maybe I am jumping to conclusions here (without even reading the book!), but this title is simply misleading.

Metal instruments

2009-10-11T20:00:00.007+01:00

This post was prompted by my recent exercises with trombone. Like many (but not all) brass instruments, trombone is actually made of brass, i.e. alloy of copper and zinc. Thus the English term “brass” is more pertinent than French cuivre or Russian медные (both mean “copper”). Still, it is misleading: saxophones (which are woodwind instruments) are also commonly made of brass. But then, I also heard of all-aluminium double bass which was patented in 1934 under the inconspicuous name “Musical instrument of the viol and violin type”.

Can one distinguish the sound of a silver flute from the sound of a gold flute? This study attempted to answer this question with a scientific experiment. Here’s the experimental setup:

A silver coated, full silver, 9 carat gold, 14 carat gold, 24 carat gold, platinum coated and all-platinum flute was played by 7 professional flutists (members of Viennese orchestras including the Vienna Philharmonic orchestra) in an anechoic chamber.

And the result?

As expected, the most significant assigned expressions for all instruments were the “contradictionary <contradictory?> expressions”: for example, the sound color of each instrument was evaluated as “bright” and simultaneously as “dark” or “full/round” and “thin/sharp”.

Tests with experienced professional flutists and listeners and one model of a flute made by Muramatsu from 7 different materials showed no evidence that the wall material has any appreciable effect on the sound color or dynamic range of the instrument. The common stereotypes used by flutists and flute makers are exposed as “stereotypes”.

So there. It’s a shame that Muramatsu does not make aluminium flutes.

Uranyl-binding protein

2009-09-30T23:15:00.009+01:00

“Uranyl ion” is the traditional name of dioxidouranium(2+), [UO₂]²⁺. According to Wikipedia, [UO₂]²⁺ is “the most common species encountered in the aqueous chemistry of uranium”. Wegner et al. designed a uranyl-selective DNA-binding protein using the template of NikR, a nickel-dependent transcriptional repressor from E. coli. The binding site of wild-type NikR was modified by a series of mutations (Val72Ser, His76Asp and Cys95Asp) to introduce extra hard equatorial ligands to favour binding of [UO₂]²⁺.

Wild-type NikR binds to its promoter DNA in the presence of Ni²⁺ ions, and a number of other divalent metal ions such as Cu²⁺, Zn²⁺, Co²⁺, Mn²⁺, and Cd²⁺ can also induce protein-DNA complex formation. However, NikR does not bind to DNA in the presence of 50 μM UO₂²⁺. The <triple> mutant NikR′ binds to DNA neither in the absence of metal ions nor in the presence of Ni²⁺ ions, but it forms a protein-DNA complex in the presence of UO₂²⁺. In comparison to NikR, the metal selectivity of NikR′ has been altered. Experiments with other metal ions show that the mutant protein only forms the protein-DNA complex in the presence of the uranyl cation while Ni²⁺, Zn²⁺, Co²⁺, Cu²⁺, Cd²⁺, Mn²⁺, and Fe²⁺ ions do not result in any observable complex formation. Attempts to load NikR with uranyl or NikR′ with Ni²⁺ did not yield any observable metal binding. Thus, this mutant NikR′ shows a uranyl-specific DNA-binding ability.

Coloured coins

2009-09-27T21:51:00.013+01:00

In contrast to gold-, silver- and copper-coloured coins (whatever metal they are made of), simply “coloured coins” sport the colours not usually associated with coinage metals. Or so I think, because so far I could not find any definitive guide to coloured coins. Wikipedia mentions them in an article on commemorative coins. I got interested in the subject since I discovered that the Sherlock Holmes Silver Coins produced by the New Zealand Mint (apparently, the legal tender of the Cook Islands) are graced by the images of Sherlock Holmes and Doctor Watson from Soviet-era films, such as The Hound of the Baskervilles.

The Tony Clayton’s website contains a very useful list of metals used in coins and medals. In particular, I have learned that niobium is used as coinage metal. In 2003, Münze Österreich pioneered the use of niobium for coin manufacturing, issuing a bimetallic €25 coin. According to this review,

The colouring <of the niobium insert> is made by a so called anodic oxidation of the material. With this treatment, by electrochemical processing a very thin niobium oxide layer is formed under controlled conditions. By refraction of light in the oxide layer so called interference colours are created which gives the colouring of the niobium. Depending on the processing parameters, the thickness of the oxide layer can be very well controlled, and gives the niobium its noble appearance. Depending on the thickness of the layer different colours are producible.

For instance, Latvian bimetallic Coin of Time (struck by Münze Österreich) consists of beautiful blue niobium centre enclosed in an outer silver ring. The obverse of the coin features the heraldic rose and the tiny Gothic script letters ℌ and ℜ standing for Heinrich Rose (1795—1864), discoverer of niobium.

Magnetic monopoles in spin ice

2009-09-23T14:00:00.009+01:00

Although the magnetic monopoles were postulated by Paul Dirac in 1931, the existence of these particles remains an open problem. This article surveys the recent breakthrough discoveries concerning magnetic monopoles within spin ice materials, dysprosium titanate (Dy₂Ti₂O₇) and holmium titanate (Ho₂Ti₂O₇).

Sulfimide bond in collagen IV

2009-09-21T18:00:00.008+01:00

The recent paper in Science describes the sulfilimine (sulfimide, in IUPACese) bond, “not previously found in biomolecules”, identified in collagen. The bond (>S=N–) cross-links methionine and hydroxylysine residues of adjoining protomers.

Stereochemistry of digitonin

2009-09-16T17:15:00.007+01:00

Following the call to the community from Antony Williams, I indulged in some chemical drawing. I did redraw structure 1 from this paper from scratch to get (a). This is very much like structure of digitonin in ChEBI (b), except for methyl group at C-20 which goes up in (a).

(a)

(b)

Muhr et al. wrote:

With our investigations, it was possible for the first time to confirm beyond all doubt the structure suggested by Tschesche and Wulff for digitonin by means of modern NMR techniques, and to assign all proton and carbon resonances.

Now I was not able to get to the full text of Tschesche and Wulff, but at least their abstract contains the German name “3[β-D-Glucopyranosyl(I)(1→3_Galakt.II)-β-D-galaktopyranosyl(II)(1→2_Gluc.III)-β-D-xylopyranosyl(1→3_Gluc.III)-β-D-glucopyranosyl(III) (1→4_Galakt.IV)-β-D-galaktopyranosyl(IV)(1→3-Digitog.)]5α,20β_F,25α Spirostantriol(2α,3β,15β)”, which kind of confirms 20β configuration. (The default configuration of spirostan is 20α.)

I guess this still does not answer what the “correct” structure of digitonin is. All we can say that Muhr et al. reported the structure (a).

Charge-shift bonding

2009-09-11T17:00:00.006+01:00

Here’s something one doesn’t see in a chemistry textbook. The recent perspective paper in Nature Chemistry deals with a distinct class of electron-pair bonding called “charge-shift” (CS) bonding, which exists alongside classical covalent and ionic bonding. And in not-so exotic molecules.

<A> striking example is the difference between H₂ and F₂; two homonuclear bonds that by all criteria should be classified as covalent bonds, but exhibit fundamental differences. Consider the energy curves (Fig. 1) of the two bonds calculated recently. Figure 1a shows that the H—H bond is indeed covalent; its covalent structure accounts for most of the bonding energy (relative to the ‘exact’ curve). By contrast, for the F—F bond in Fig. 1b, the covalent structure is entirely repulsive, and what determines the bonding energy and the equilibrium distance is the covalent–ionic mixing. This mixing leads to a resonance energy stabilization, which we have termed the ‘charge-shift resonance energy’ (RE_CS). Thus, despite their apparent similarity, the two bonds are very different; whereas the H—H bond is a true covalent bond, the F—F bond is a CS bond that is completely determined by the RE_CS quantity.

No less striking example is so-called inverted C—C bond in [1.1.1]propellane (described in a paper from the same group of authors), which “closely resembles the single bond of difluorine”.

Antarcticite

2009-09-01T11:30:00.007+01:00

Antarcticite is a mineral form of calcium dichloride hexahydrate. It was first discovered in Don Juan Pond in Antarctica, which is probably the saltiest (47% w/v) body of water on earth. Looking at crystal structure of antarcticite (below), one can see that both name “calcium dichloride hexahydrate” and formula CaCl₂·6H₂O are misleading, for there are two kinds of water in it. The structure comprises the alternating layers of (i) trigonal planar triaquacalcium(2+) ions and (ii) water and chloride ions. I suppose it should be named “triaquacalcium dichloride—water (1/3)” or “triaquacalcium dichloride trihydrate”, with formula [Ca(OH₂)₃]Cl₂·3H₂O.

Deferrochelatase

2009-08-18T22:45:00.007+01:00

I always thought that ferrochelatase (EC 4.99.1.1) has an absurd systematic name: “protoheme ferro-lyase (protoporphyrin-forming)”. Why? According to Enzyme Nomenclature,

Lyases are enzymes cleaving C—C, C—O, C—N and other bonds <in other words, any bond> by other means than by hydrolysis or oxidation.

“Protoheme ferro-lyase” implies that the reaction goes in the direction:

protoheme + 2 H⁺ → protoporphyrin + Fe²⁺

(a)

while ferrochelatase, in fact, catalyses the reverse reaction:

protoporphyrin + Fe²⁺ → protoheme + 2 H⁺

(b)

Usually, to release iron from protoheme, you have to break it. Heme oxygenase (EC 1.14.99.3) does it by sequential oxidation of heme into the linear tetrapyrrole, biliverdin.

However, this paper demonstrates that there could be another way to do it.

Until today, all known enzymes performing iron extraction from heme did so through the rupture of the tetrapyrrol skeleton. Here, we identified 2 Escherichia coli paralogs, YfeX and EfeB, without any previously known physiological functions. YfeX and EfeB promote iron extraction from heme preserving the tetrapyrrol ring intact. This novel enzymatic reaction corresponds to the deferrochelation of the heme. YfeX and EfeB are the sole proteins able to provide iron from exogenous heme sources to E. coli.

Thus, deferrochelatase catalyses the reaction (a) and, indeed, can be named “protoheme ferro-lyase (protoporphyrin-forming)”.

What is a correct InChI for chromate?

2009-08-13T17:15:00.013+01:00

During the IUPAC International Chemical Identifier (InChI) Subcommittee meeting in Glasgow last month, we touched upon the issue of normalisation of metal complexes. I did not realise before that even simple entity such as chromate(2−), drawn in different ways (a)—(c), will give different InChIs. (And different standard InChIs as well; and InChIKeys too.) This is, I am told, because the current InChI algorithm involves “disconnection” of metals before “normalisation”, while it really should do normalisation first. Bother.

(a)
InChI=1/Cr.4O/q;;;2*-1

(b)
InChI=1/Cr.4O/q-2;;;;

(c)
InChI=1/Cr.4O/q+2;4*-1

Ununbium gets a proper name

2009-07-17T15:20:00.005+01:00

With IUPAC officially recognising discovery of element 112, a lot of news articles (such as this one) appeared hailing the “new element”. Of course, only the name copernicium (in honour of Nicolaus Copernicus) is new; the element was discovered in 1996 and was known as ununbium (Uub). The proposed symbol for this metal is Cp, probably not the best choice considering that Cp is widely used as a shorthand for cyclopentadienyl group — imagine we have enough copernicium to synthesise bis(cyclopentadienyl)copernicium, Cp₂Cp! Fear not — according to WebElements,

as only a few atoms of element 112 have ever been made (through a nuclear reaction involving fusing a zinc atom with a lead atom) isolation of an observable quantity has never been achieved, and may well never be.

Iron trafficking as an antimicrobial target

2009-07-13T22:00:00.006+01:00

The August issue of BioMetals contains proceedings of Symposium on Siderophores held at the ACS Meeting in Philadelphia, 2008. This mini-review caught my attention.

Readers of Biometals are aware of the special challenges posed by the need to acquire iron: an absolutely essential but highly insoluble metal in most biota, and a jealously protected one inside the human body. Microbial systems for Fe uptake and trafficking are consequently highly developed and fundamentally interesting. Limiting Fe under laboratory conditions can be detrimental or lethal, offering a means for limiting microbial growth. The potential for medicinally impeding Fe metabolism is a commonly, if sometimes uncritically, cited justification for in-depth biological studies of Fe acquisition. In fact, derailing the Fe supply train, while plausible as an antimicrobial strategy, is still largely untested in practice.

Since the iron acquisition mechanisms in microbes and higher eukaryotes are fundamentally different, it is possible to deprive the pathogen from iron without harming the host — for instance, by inhibiting the siderophore biosynthesis.

Metal carbonyls

2009-06-28T14:30:00.011+01:00

Remember the nitro group? Let us consider even ‘simpler’ case of carbon monoxide. Almost invariably, the chemical databases represent CO as a charge-separated molecule (a) even though it would be as correct to draw it with triple bond and two lone pairs (b). I guess the reason to chose the representation (a) is that the software used for drawing/validating concerns itself with electron accountancy of separate atoms rather than whole molecule.

(a)

(b)

What about metal carbonyls? For instance, hexacarbonylvanadium, drawn with charge separation (c), looks really ugly. On the other hand, the software (e.g. ChemSketch) objects to the representation (d) (which, apparently, is preferred; cf. tetracarbonylnickel on p. 408 of IUPAC Recommendations) because it ‘wants’ the positive charge on triple-bonded oxygen.

(c)

(d)

The first viral P450

2009-06-19T22:03:00.006+01:00

It’s true: the genome of Mimivirus is bigger than some bacterial genomes, but it is still a virus. Or is it?

When and where I was doing my master’s degree (and that was more than 20 years ago, at the Department of Biochemistry of Medico-Biological Faculty), we were jokingly defining life as “the mode of existence of cytochrome P450”. I’ve always thought that viruses are not alive; therefore, they don’t need P450s. Now, this paper describes the expression of a P450 gene from Mimivirus in E. coli. The CO complex of the expressed protein shows the characteristic absorption spectrum of ‘functional’ P450, but its biological function remains unknown.

Calcium

2009-06-14T21:21:00.006+01:00

‘Calcium’ is the name given by Sir Humphry Davy to the metal that he first isolated by electrolysis in 1808. It is derived from Latin calx (lime) which most likely came from Greek χάλιξ (pebble, limestone). The English word ‘chalk’ is also derived from calx. My inner folk etymologist has successfully linked chalk with ‘calculation’ (via the blackboard, of course), but it seems that the connection is a bit older than blackboard: Latin calculus is simply a ‘little pebble’ used in calculations on an abacus. (Latin for chalk is not calx but creta, thus Cretaceous period.)

Not everything that starts with ‘calcium’ is a calcium compound. For instance, this chapter of Invitrogen’s Guide to Fluorescent Probes and Labeling Technologies contains a section on Calcium Green, Calcium Yellow, Calcium Orange and Calcium Crimson indicators. These compounds, upon binding Ca²⁺, exhibit a strong increase in fluorescence emission intensity. I suppose the corresponding fluorescent complexes then should be named something like ‘calcium Calcium Crimson’ and so on.

Wine metallomics

2009-06-03T12:00:00.004+01:00

I suppose everybody who follows this blog is acquainted with the theory linking the lead posoning and decline of Roman Empire. But sure that was a long time ago? Bad news, everybody: the wine we drink now still has the metals we really needn’t. According to this paper,

The THQ <target hazard quotient> values were determined as ranges from previously reported ranges of metal ion concentrations and were frequently concerningly high. Apart from the wines selected from Italy, Brazil and Argentina, all other wines exhibited THQ values significantly greater than one indicating levels of risk. The levels of vanadium, copper and manganese had the highest impact on THQ measures. Typical potential maximum THQ values ranged from 50 to 200 with Hungarian and Slovakian wines reaching 300. THQ values for a sample of red and white wines were high for both having values ranging from 30 to 80 for females based on a 250 mL glass per day.

Well, I’ll stick to Italian (post-Roman) wine then.

Bioinorganic and Biomedical Chemistry of Gold

2009-05-19T15:30:00.003+01:00

To please your inner aurophile, check out the special issue of Coordination Chemistry Reviews dedicated to Bioinorganic and Biomedical Chemistry of Gold. The (relatively) low toxicity and strong antiproliferative activity make gold complexes the promising anticancer drugs.

Aurophile, argentophile...

2009-05-14T16:16:00.007+01:00

One can expect that these terms have something to do with alchemistry. Wrong. Apparently, aurophilic bond is just a weak Au—Au bond, and argentophilic bond is a Ag—Ag bond. On the other hand, Merriam-Webster’s Medical Dictionary defines argentophilic (argyrophilic) as

having an affinity for silver — used of certain cells, structures, or tissues that selectively reduce silver salts to metallic silver.

“Cuprophilic” has been used in both senses, viz. Cu—Cu bond (as, for example, here) and “having an affinity for copper” (as in here). Similarly, “metallophilic” has been used to describe both “generic” metal—metal bond and for “metallophilic cells”. I find the use of this terminology in its former (more restrictive) sense both confusing and unnecessary. For example, this paper describes “Hg(II)···Pd(II) metallophilic interactions”. It could as well be named simply “Hg(II)—Pd(II) interactions”.

Colour-changing mechanophores

2009-05-09T12:19:00.006+01:00

The recent Nature publication shows that one can literally see a mechanically-induced ring-opening reaction.

Previously, we have shown with dissolved polymer strands incorporating mechanically sensitive chemical groups — so-called mechanophores — that the directional nature of mechanical forces can selectively break and re-form covalent bonds. We now demonstrate that such force-induced covalent-bond activation can also be realized with mechanophore-linked elastomeric and glassy polymers, by using a mechanophore that changes colour as it undergoes a reversible electrocyclic ring-opening reaction under tensile stress and thus allows us to directly and locally visualize the mechanochemical reaction. We find that pronounced changes in colour and fluorescence emerge with the accumulation of plastic deformation, indicating that in these polymeric materials the transduction of mechanical force into the ring-opening reaction is an activated process.

I guess we have to introduce a new ChEBI role: mechanophore.

Iron stars

2009-05-05T17:54:00.005+01:00

According to Freeman Dyson, in rather unimaginable 10¹⁵⁰⁰ years from now, and in case proton decay does not happen, most of nuclei will either fuse or decay into iron. This will leave the universe inhabited by “cold spheres of pure iron”. I think it is cool, even if I won’t live that long to see it. However, I came across a report of recent (2006) observation of ‘iron star’ with NASA's Spitzer Space Telescope. I don’t think these objects are the same as Dyson’s iron stars though, just the next best thing.

Copper butterfly

2009-05-04T16:30:00.008+01:00

In a recent paper, I came across this rather poetic description:

Each of the Cu(I) centers is trigonally coordinated by three S atoms, and each of the six dithiophosphate ligands is connected to a Cu₄ butterfly, where the hinge positions are occupied by two copper atoms situated at the vertex of the central tetrahedron and the wingtips are two capping Cu atoms.

However, to understand what they are talking about, one really should see one of these beautiful structures in 3D. I used this CIF file and Mercury program to create the image below.

How to draw a nitro group

2009-04-29T13:06:00.008+01:00

In our IUPAC Recommendations, section GR-8, “the nitro problem” is discussed in detail. To quote:

“The nitro problem” is one of the most familiar issues in chemical informatics: How should a nitro group be best represented? Experimentally, the two oxygen atoms are equivalent, so it would make sense to depict them symmetrically. However, any way to depict them symmetrically will either violate the popular “octet rule” or force a double positive charge on the nitrogen atom. Conversely, any attempt to honor the octet rule results in oxygen atoms that appear to be non-equivalent. Similar problems arise for molecules based on sulfur, phosphorus, and related elements. Furthermore, all of these are fairly common functional groups, and cannot readily be pushed aside as “unusual” cases.

The recommended representation of nitrobenzene is either (a) or (c) while (b) is not acceptable. Needless to say, (b) is exactly the way this compound is drawn in Beilstein database, while the search with charge-separated nitro query will not work.

(a)

(b)

(c)

But what is wrong with representation using “pentavalent” nitrogen? In my view, nothing. How else one should draw nitrogen dioxide (d)? One can think of nitro group as of nitrogen dioxide with a single bond instead of the unpaired electron.

(d)

For purely aesthetic reasons, the multiple charge-separated nitro groups are not good: too many charges without good reason. For example, hexanitroplatinate(2–) looks much nicer when the sketch shows only one charge, 2– (e), rather than 13 assorted charges as in (f).

(e)

(f)

Chinese element symbols in Unicode

2009-04-26T20:40:00.007+01:00

According to Chinese philosophy, there are only five elements:

Wood 木 (Mù)
Fire 火 (Huǒ)
Earth 土 (Tǔ)
Metal 金 (Jīn)
Water 水 (Shuǐ)

The union of five elements is known as 五行 (Wǔ xíng). In Chinese Periodic Table, 金 (Jīn) on its own means ‘gold’ while all other solid metals consist of two symbols, Jīn + something else, for instance 金 + 白 = 鉑 (platinum). The only liquid metal at room temperature, mercury (汞), does not include 金 but has 水 (Shuǐ) instead. There are many versions of Chinese Periodic Table on the web but personally I like this interactive one. Bizarrely, Unicode has three flavours for each of Chinese elements: ‘parenthesized’, ‘circled’ and ‘simple’. Again, I am sure that many people will not see these characters correctly.

Character	Name	Unicode	Decimal	Hexadecimal	Meaning
㈫	PARENTHESIZED IDEOGRAPH FIRE	U+322B	㈫	㈫	Fire (traditional element) or Tuesday
㊋	CIRCLED IDEOGRAPH FIRE	U+328B	㊋	㊋
火	CJK UNIFIED IDEOGRAPH-706B	U+706B	火	火
㈬	PARENTHESIZED IDEOGRAPH WATER	U+322C	㈬	㈬	Water (traditional element) or Wednesday
㊌	CIRCLED IDEOGRAPH WATER	U+328C	㊌	㊌
水	CJK UNIFIED IDEOGRAPH-6C34	U+6C34	水	水
㈭	PARENTHESIZED IDEOGRAPH WOOD	U+322D	㈭	㈭	Wood (traditional element) or Thursday
㊍	CIRCLED IDEOGRAPH WOOD	U+328D	㊍	㊍
木	CJK UNIFIED IDEOGRAPH-6728	U+6728	木	木
㈮	PARENTHESIZED IDEOGRAPH METAL	U+322E	㈮	㈮	Metal (traditional element) or gold (element) or Friday
㊎	CIRCLED IDEOGRAPH METAL	U+328E	㊎	㊎
金	CJK UNIFIED IDEOGRAPH-91D1	U+91D1	金	&#91d1;
㈯	PARENTHESIZED IDEOGRAPH EARTH	U+322F	㈯	㈯	Earth (traditional element) or Saturday
㊏	CIRCLED IDEOGRAPH EARTH	U+328F	㊏	㊏
土	CJK UNIFIED IDEOGRAPH-571F	U+571F	土	&#571f;

Another mystery solved

2009-04-23T00:00:00.006+01:00

Here’s a short fragment of Accident by Agatha Christie.

Evans paid no attention, but went on. ‘You interrupted me just now. After Marsh’s test, Merrowdene heated a substance in a test tube, the metallic residue he dissolved in water and then precipitated it by adding silver nitrate. That was a test for chlorates. A neat, unassuming little test. But I chanced to read these words in a book that stood open on the table. “H₂SO₄ decomposes chlorates with evolution of Cl₂O₄. If heated, violent explosions occur, the mixture ought therefore to be kept cool and only very small quantities used.”’

What book was that? Googling gave me The Elements of Chemical Arithmetic with a Short System of Elementary Qualitative Analysis by J. Milnor Coit, Ph.D., published in 1886. On page 80, section 103, I’ve found the original description (shortened in Agatha Christie’s version):

H₂SO₄ decomposes chlorates with evolution of Cl₂O₄, a greenish-yellow gas having a powerful odor. If heated, violent explosions occur; the mixture ought therefore to be kept cold, and only very small quantities should be used.

The full text of this, apparently, still very useful book is copyright-free.

Chemical symbols in Unicode

2009-04-21T17:59:00.022+01:00

I was told that the Unicode atom symbol ⚛ (which appeared in my previous post) is not represented correctly in other browsers, or, indeed, other PCs. This is because not all PCs have the fonts installed that can show these characters; or even when the font is there, one has to tell the browser to use it, e.g. <font>⚛</font>. That’s annoying.

Given a number of various symbols present in Unicode, I am surprised how little of them are genuinely related to chemistry, without having any other meaning. In fact, just three. Two of them, ⌬ and ⏣, mean the same and are quite useless — I’d prefer them rotated 90° so one could attach them by “bonds” to something else inline. The third, ⚗, means “chemical term” (in dictionary etc.); the scales, ⚖, even though may appear related to chemistry, really mean “legal term”. See the little table below for these and a few others which may be of some chemical relevance.

Character	Name	Unicode	Decimal	Hexadecimal	Meaning
☉	SUN	U+2609	☉	☉	Sun (astrology) or gold (alchemy)
☽	FIRST QUARTER MOON	U+263D	☽	☽	Moon (astrology) or silver (alchemy)
☿	MERCURY	U+263F	☿	☿	Mercury (astrology) or mercury (alchemy)
♀	FEMALE SIGN	U+2640	♀	♀	Venus (astrology) or copper (alchemy)
♁	EARTH	U+2641	♁	♁	Earth (astrology) or antimony (alchemy)
♂	MALE SIGN	U+2642	♂	♂	Mars (astrology) or iron (alchemy)
♃	JUPITER	U+2643	♃	♃	Jupiter (astrology) or tin (alchemy)
♄	SATURN	U+2644	♄	♄	Saturn (astrology) or lead (alchemy)
⌬	BENZENE RING	U+232C	⌬	⌬	Benzene ring (Kekulé structure)
⏣	BENZENE RING WITH CIRCLE	U+23E3	⏣	⏣	Benzene ring (delocalised)
☠	SKULL AND CROSSBONES	U+2620	☠	☠	Poison (chemistry etc.)
☢	RADIOACTIVE SIGN	U+2622	☢	☢	Radioactivity
☣	BIOHAZARD SIGN	U+2623	☣	☣	Biohazard
⚖	SCALES	U+2696	⚖	⚖	Legal term
⚗	ALEMBIC	U+2697	⚗	⚗	Chemical term
⚛	ATOM SYMBOL	U+269B	⚛	⚛	Nuclear installation

Metals and toponymy

2009-04-17T12:30:00.014+01:00

Some years ago, I’ve circulated this list among my colleagues at the EBI. I think it may be of interest to the readers of this blog as well. Here goes:

Copper was named after Cyprus, francium and gallium after France, germanium after Germany, polonium after Poland, ruthenium after Russia, and americium after (the United States of) America. Magnesium was named after Magnesia region in Greece, hassium after the land of Hesse (Hessen) in Germany, and californium after California. In addition, europium got his name after (continent of) Europe while the names of both scandium and thulium have something to do with Scandinavia. However, indium was named not after India but because of blue (indigo) line in its atomic spectrum. As for cities and villages, lutetium was named after Paris, hafnium after Copenhagen, holmium after Stockholm, strontium after Strontian in Scotland, berkelium after Berkeley in California, dubnium after Dubna in Russia^*, and rather unpronounceable darmstadtium after Darmstadt in Germany. Four elements (yttrium, erbium, terbium, ytterbium) took their names after otherwise little known Ytterby in Sweden. Rhenium was named after the (river) Rhine. All the place-name elements, except for germanium, are metals.

Apart from Argentina, I cannot think of any other country named after a metal or any other element (unless you count Cyprus again, which well could have been named after copper; the history is not very clear here). According to the Wikipedia, the smallest of Canary Islands, El Hierro (Spanish for ‘iron’) originally had a name ‘Hero’, later mutated into ‘Hierro’ and further latinised as ‘Ferro’ while having nothing to do with iron. Lead, South Dakota also has nothing to do with lead (metal). I am sure there are plenty of placenames featuring coinage metals (gold, silver, copper) in a variety of languages, but I better stop for now.

^* Dubna is the only town I know that has both flag and coat of arms featuring a ‘popular culture’ atom symbol ⚛

On biological role of titanium

2009-04-05T00:00:00.009+01:00

According to WebElements, “titanium has no biological role”. Having recently acquired a titanium (or rather, Ti₆AlV₄ alloy) dental implant, I am not convinced. To be a dental implant sounds like a perfectly valid biological role to me. Apparently, osteoblasts like to attach to titanium surface (more precisely, to titanium dioxide, TiO₂). However, it is not just the material that matters, it is the shape of the material as well. In the recent paper, in vivo bone binding to TiO₂ nanotubes and TiO₂ gritblasted surfaces was investigated. The authors have found that

after four weeks of implantation in rabbit tibias, pull-out testing indicated that TiO₂ nanotubes significantly improved bone bonding strength by as much as nine-fold compared with TiO₂ gritblasted surfaces.

Earlier this year, another study has demonstrated that the fate of human mesenchymal stem cells can be affected solely by the geometry of TiO₂ nanotubes:

Small (≈30-nm diameter) nanotubes promoted adhesion without noticeable differentiation, whereas larger (≈70- to 100-nm diameter) nanotubes elicited a dramatic stem cell elongation (≈10-fold increased), which induced cytoskeletal stress and selective differentiation into osteoblast-like cells...

Growing microtubes from polyoxometallate crystals

2009-03-31T13:30:00.008+01:00

The long-awaited first issue of Nature Chemistry is out. It has a number of excellent reviews and research articles; best of all, it is all in free access. The cover shows the artist's impression of "a growing microtube with a single polyoxometalate ion visible at the open end of the tube" [see Ritchie et al. (2009) Nature Chemistry 1, 47–52, and comment, Constable, E. (2009) Nature Chemistry 1, 22–23].

Stories of chronomes and metallomes

2009-03-27T23:45:00.008Z

I do not understand what principle is used by PubMed to indicate which papers are “related” to the one you are looking at. Take, for instance, the recent paper “Epigenetics: an important challenge for ICP-MS in metallomics studies” — among “Related Articles”, the top one is entitled “Chronoastrobiology: proposal, nine conferences, heliogeomagnetics, transyears, near-weeks, near-decades, phylogenetic and ontogenetic memories”. (Is that a real title? Yes it is.) True, the abstract, though truncated, makes an intriguing reading, but has it anything to do with metallomics (or epigenetics, for that matter)? The only passage related to any ome or omics is the following:

Structures in time are called chronomes; their mapping in us and around us is called chronomics. The scientific study of chronomes is chronobiology.

Well, I don’t know, Webster’s definition of chronobiology makes more sense to me and it does not use the dodgy concept of “chronome”. As for today, 27 March 2009, PubMed citations for chronome (61) and chronomics (39) visibly outnumber metallome (8) and metallomics (20), while there is none that combines any of the first pair of terms with any of the second pair of terms.

The enigmatic Metallosia

2009-03-23T22:01:00.008Z

True, there is a lot of stuff on the web, but this is not remotely enough. Take, for example, Metallosia. The very short Wikipedia entry says:

Metallosia is a genus of moth in the family Arctiidae.

According to this taxonomy page,

There are approximately 3 species in this genus: M. chrysotis · M. nidens · M. nitens

(I wonder what “approximately 3 species” could possibly mean. Could it be that M. nidens and M. nitens is actually one species plus one typo? Can one say that 2 is approximately 3?) I also can find Metallosia mentioned in the Natural History Museum catalogue but not much factual information either. On the other hand, it is not listed in the NCBI taxonomy database, which indicates that no sequence data from these moths are available (and which makes it non-existent for bioinformatics). Internet, I am disappointed. Where can I see Metallosia? How can I recognise it if I see it? And most importantly, does it have anything to do with metals?

Rhea has hatched

2009-03-21T20:30:00.007Z

I am pleased to announce that after years of hard work, the Rhea database finally went online. Rhea is a freely available, manually annotated database of chemical reactions created as a collaboration between the EBI and SIB. From the Rhea website:

In classical Greek mythology, Rhea (Greek

) was the daughter of Uranus and Gaia, and was known as the mother of gods. Her name is often linked to the Greek word

("flow") but has no relation to the word "reaction". Rhea is the name of a genus of flightless birds, also known as ñandú. Rhea is also the name of the second-largest moon of Saturn, which contains up to 75% water and may have a tenuous ring system. The image of Rhea (moon) is used in Rhea (database) logo.

Drawing ferrocene

2009-03-14T16:57:00.013Z

Ferrocene was discovered in 1951 and we still do not know the proper way to draw it. CrossFire example recommends to connect every carbon atom of the ring to the central metal atom. Which is fair enough and will be a valid query for CrossFire Gmelin database. Similarly, both ChEBI and NIST Webbook use decacoordinate iron in ferrocene structure (a). In this representation, all carbon—carbon bonds are single. But, according to IUPAC Recommendations, section GR-1.7.2,

coordination bonds to contiguous atoms (most commonly representing a form of π-bonding) should be drawn to indicate most clearly that special bonding pattern. Depictions that imply a regular covalent bond — and especially, depictions that show a regular covalent bond to each member of a delocalized system — are not acceptable.

In other words, the preferred representation is the one with bicoordinate iron and delocalised bond system (b). The problem with that is there is no agreed (as far as chemoinformaticans are concerned) way to do that, even though solutions for different applications (e.g. for Marvin Sketch) do exist. In MolBase, the coordination number of iron in ferrocene is 6 (and I do remember Mark Winter confirming that this is true). On yet another hand, Beilstein and ChemIDplus databases represent ferrocene as a standalone Fe²⁺ and two standalone cyclopenta-2,4-dienide anions (c), thus avoiding the question of coordination number altogether. Naturally, the decacoordinate-iron query will not work in Beilstein. (For InChI implications, see this discussion.)

(a)

(b)

(c)

Metallostar

2009-03-13T22:20:00.006Z

"Metallostar" is a relatively recent term: the oldest publication mentioning metallostars that I was able to find is dated 2000. It defines them as "complexes in which a single branching site bears a number of metallated arms". Something that looks too beautiful to be of any practical use, in fact metallostars appear to be promising MRI contrast agents. The metallostar of today's post, coming from the recent paper in Dalton Transactions, contains a central ruthenium atom and six lanthanoid(III) atoms (Y, Gd or Eu).

Teaball

2009-03-07T17:30:00.006Z

I was given this wonderful Teaball as a present from my colleagues. Except from the wooden handle (the wood is not specified), the rest is 18/10 stainless steel. In case you are not familiar with this nomenclature (as I was until the arrival of the Teaball), "18/10" stands for 18% chromium and 10% nickel. It is a far cry from the other kind of stainless steel teapots you can find in this country — no need to use paper napkin etc.

Novel haem-degrading protein

2009-03-06T19:28:00.007Z

This paper presents a beautiful octameric structure of HbpS, “a novel protein of previously unknown function from Streptomyces reticuli” complexed with iron. The authors “propose that the iron atom originates from the haem group and report subsequent biochemical experiments that demonstrate that HbpS possesses haem-degrading activity in vitro”. In the diagram taken from PDB:3FPW, the iron atoms are represented as grey spheres and phosphate ions are purple/red tetrahedra.

PubChem takes liberties with hydrogens

2009-03-01T20:38:00.008Z

The submitted structure (a) is C₃H₅O₅P, the PubChem shows C₃H₄O₅P⁺ (b). How did that happen? Why the deposited molecule lost hydride (H^–)?

(a)

(b)

In the case of structure C₁₆H₃₆MoN₆O₄P₂ (c), presumably submitted by NIST, it has acquired two hydrons in PubChem to become [C₁₆H₃₈MoN₆O₄P₂]²⁺ (d).

(c)

(d)

The Force is strong here

2009-02-28T11:03:00.004Z

If there is a gizmo I really crave to take control of, this is the one. As The NeoCube (Strong Force Inc.) website puts it,

The NeoCube is an entertainment device like no other in the world. Composed of 216 individual high-energy

rare-earth magnets, the NeoCube allows you to create and recreate an outrageous number of shapes and patterns... The NeoCube Alpha is perfect for gaming, expression, stress relief, dual hemispherical brain stimulation and much more

The rare earth metal in question is neodymium, which, according to Wikipedia, is not that rare at all. Which is a good news for all of us needing affordable dual-hemisphere brain stimulation.

Copper, zinc and haem in superoxide dismutase

2009-02-22T20:25:00.006Z

Why bacterioferritin needs a haem anyway? It's a very good question, and so far it does not have any good answer. The shortest one is, we don't really know. There are ferritins (in Escherichia coli as well) having exactly the same architecture which do not bind any haem. Bacterioferritin is not alone: Cu,Zn superoxide dismutase from Haemophilus ducreyi contains not only, as one may guess, copper and zinc (all Cu,Zn-SODs do), but also, for no reason, a haem. Once again, it is bound at the dimer interface, although this time it is asymmetrically bound with two different histidine residues provided by the two subunits. The authors show that the introduction of only three mutations at the dimer interface of the Cu,Zn-SOD from a related species, Haemophilus parainfluenzae, is sufficient to induce haem-binding ability. However, it does not change anything: we still don't know why the haem is there.

Zinc, haem and water in bacterioferritin

2009-02-20T09:14:00.007Z

This structure is a beauty: Willies et al. solved the structure of bacterioferritin from Escherichia coli to 1.9 Å. The hollow shell of bacterioferritin is made up of 24 identical subunits organised as 12 dimers. The two metals that the ferroxidase centre binds have previously been assigned as manganese or as a mixture of iron and zinc; now it has been shown that both are zinc. The haem is coordinated by two Met-52 residues from two subunits forming a dimer. Interestingly,

At the resolution of the structure presented, the electron density clearly shows the binding of haem in both conformations, each at half occupancy with no preference for either conformation

(the authors consistently use “conformation” throughout the paper but they really should say “orientation”, as they do in the figure legend). For the first time, a link is described between the internal and the external environment of the bacterioferritin via the cluster of water molecules and the haem; the authors suggest that this could be an electron-transport pathway.

Impossible figures

2009-02-14T17:41:00.010Z

I am sure everybody can see that the drawing (a) is an impossible figure. So I expect nobody will draw cubane like this; the correct drawing is (b).

(a)

(b)

In fact, if you pay attention, you will notice that the chemical databases are full of impossible figures. I just have corrected the drawing in ChEBI entry for codeinone (c). Next release, it will look like (d).

(c)

(d)

Corrine, Corrina

2009-02-13T19:38:00.028Z

The cover of Compendio de terminología química (the Spanish translation of IUPAC Gold Book) features the structure of corrin. So, I simply had to add the French (corrine) and Spanish (corrina) names to corrin entry. Undoubtedly, this will ensure that everyone who is googling for Corrine, Corrina will get to ChEBI. (Or maybe not: today there are about 315,000 results on Google, the top ones being the Wikipedia article and a Corrine, Corrina Home Page with a discography of over 160 different versions of this song.)

The Darwin coin

2009-02-12T13:30:00.005Z

Finally, something that has something to do with both Darwin and metals and that you can have in your pocket (quite unlike this bronze sculpture of young Darwin unveiled by Prince Philip today in Cambridge). To celebrate Charles Darwin's 200th birthday (today) and the 150th anniversary of the publication of On the Origin of Species, The Royal Mint issued a special Charles Darwin £2 Coin, although I am yet to see it in my change. (I am not talking here about £2 Silver Proof Coin or £2 Gold Proof Coin, which probably never will be in circulation.)

Heavy snow

2009-02-06T12:23:00.007Z

Yesterday, the BBC weather people promised some “heavy snow” which had never materialised. But what exactly is “heavy snow”? I think the snow made of heavy water should be heavy. In that case, it is either a water enriched with dideuterium oxide (D₂O) or heavy-oxygen water, H₂¹⁸O. Now, D₂O has melting point 3.82 °C (0 °C “normal” water) and temperature of maximum density 11 °C (4 °C “normal” water). I got these data from our office copy of CRC Handbook of Chemistry and Physics (83rd Edition), p. 6-4. Unfortunately there are not that much data on physical proterties of D₂O ice in this book, let alone snow. In fact, it does not contain the word “snow” in its index at all. It has SMOW though, literally on the next page. The table on p. 6-5

gives the density ρ of standard mean ocean water (SMOW), free from dissolved salts and gases, at a pressure of 101325 Pa.

(I wonder how much SMOW differs from any other water after all these purifications.) As for H₂¹⁸O, Handbook has nothing. Search in Gmelin database gives range of temperatures: from –0.01 to +0.3 °C. Hmm. Let’s just think that heavy water is D₂O and heavy snow is D₂O snow. According to this 3-year old thread (which has started with somebody asking this very important question: “Would it feel different to ski in snow made with heavy water?”), it may be pricey but at least it won’t melt at +3 °C. In the meantime, this BBC report tells us that

Some councils in England say they are running out of road salt.

I need to do some research on road salt next.

Irish patent IE48356

2009-02-04T23:40:00.009Z

I'd say, this is a very short patent.

Metal snow, anyone?

2009-02-03T16:30:00.006Z

It was snowing heavily yesterday, at least by English standards. Can I find something related to both snow and metal on the web? The googling for “metal snow” does not bring that many interesting results, mostly it’s all about metal tools related to snowy weather. All moderately interesting finds are rather old news. There are couple of papers from 1978 entitled “Plasma cooling by metal snow” (this and this). There, “metal snow” refers to the metal dust “liberated” from the walls of Tokamaks as a result of surface cracking. Another old news item concerns the heavy metal snow discovered on Venusian mountain tops back in 1995. According to Laura Schaefer and Bruce Fegley from Washington University in St. Louis (2004), this “snow” consists of compounds such as galena (lead sulfide), bismuthite (bismuth sulfide), and/or lead-bismuth sulfosalts. The most recent find (2008) is a photo promisingly titled Metal Snow Girl which does not show any snow either, but a snowman-like figure made of metal balls.

Boron boride

2009-01-31T12:42:00.007Z

All known structures of elemental boron contain icosahedral B₁₂ clusters. Recently, a new form of elemental boron called γ-B₂₈ has been characterised. Its structure resembles that of a sodium chloride, with the B₁₂ icosahedra and B₂ pairs playing the roles of ‘anions’ and ‘cations’, respectively.

“The example of γ-B₂₈ shows that significant ionicity can occur in elemental solids”, the authors wrote. “Because of the charge transfer between these two components, the new phase can be regarded as a boron boride (B₂)^δ+(B₂₈)^δ–.”

Molecules That Changed the World

2009-01-29T08:50:00.010Z

We’ve got this wonderful, profusely illustrated book bought for the office, called Molecules That Changed the World, by K. C. Nicolaou and T. Montagnon. I’d say some of the molecules mentioned there (like LSD) change not so much the world per se but our perception of the world. Still, I’d recommend every chemistry or chemistry-related department/lab to have this book.

On p. 42, it quotes Sir Robert Robinson’s wise words on the value of basic research (from his Nobel Lecture):

The synthesis of brazilin would have no industrial value; its biological importance is problematical, but it is worth while to attempt it for the sufficient reason that we have no idea how to accomplish the task. There is a close analogy between organic chemistry in its relation to biochemistry and pure mathematics in its relation to physics. In both disciplines it is in the course of attack of the most difficult problems, without consideration of eventual applications, that new fundamental knowledge is most certainly garnered.

Royal Society of Chemistry New

2009-01-24T19:51:00.017Z

By some amazing coincidence, the same day as I have resuscitated this blog, the Royal Society of Chemistry has published the first issue of Metallomics, “a new journal covering the research fields related to biometals”. Good news is that the first issue is free. Check the “enhanced HTML articles” (for instance, this one) which provide “chemical ontology terms” which are nothing else but ChEBI ontology terms, with links to ChEBI.

On a lighter, but still metal-related note, the article on RSC blog entitled Gold saved! lists a winner and four more solutions to “The Italian Job problem”. Cool.

Cucurbituril

2009-01-20T20:51:00.019Z

“Cucurbituril” may sound as a name of a natural product derived from some plant of Cucurbita genus. Wrong. There is a connection, though. According to this review,

In 1981, the macrocyclic methylene-bridged glycoluril hexamer (CB[6]) was dubbed cucurbituril by Mock and co-workers because of its resemblance to the most prominent member of the cucurbitaceae family of plants — the pumpkin.

My best 2-D representation for cucurbit[5]uril (a) does not look particularly pumpkiney. It is more like a sea urchin skeleton. Granted, its 3-D model (b) may look a bit like cleaned pumpkin devoid of top and bottom, but it still looks like a sea urchin skeleton (c) to me.

(a) cucurbit[5]uril in 2-D

(b) cucurbit[5]uril in 3-D

(c) sea urchin skeleton

Cucurbiturils, pumpkin-like or not, can be as useful as hunny pot that Pooh the Bear presented Eeyore: you can put things in them. For example, the platinum-containing anticancer drug oxaliplatin (d) can be put inside of cucurbit[7]uril to form a stable 1:1 complex (e). Jeon et al. suggest that this can increase the stability of the drug as well as to reduce unwanted side effects of oxaliplatin.

(d) oxaliplatin

(e) cucurbit[7]uril-oxaliplatin

Circumnames

2009-01-17T13:35:00.020Z

I came across these “circumnames” quite by chance: several compounds were mentioned in this paper and some other can be found in this astrochemistry database. Is there any elegant way to name them systematically?

(a) circumpyrene

(b) ovalene

(c) pyrene

For instance, ACD/Name gives the molecule (a) a systematic name dinaphtho[2,1,8,7-hijk:2',1',8',7'-stuv]ovalene, i.e. two naphtho groups are fused to the top and bottom of the ovalene (b) molecule, while the non-systematic name “circumpyrene” means that pyrene (c) core is completely encircled by fused benzene rings. Unfortunately, I was unable to generate ACD/Names for bigger molecules, such as circumcoronene (d) [i.e. coronene (e) encircled by fused benzene rings] and circumovalene (f). Apparently, ACD/Name cannot name compounds with more than 15 fused rings.

(d) circumcoronene

(e) coronene

(f) circumovalene

If the “core” structure is surrounded by two rows of fused benzene rings, the doubly “circum” names like circumcircumpyrene (g) and circumcircumcoronene (h) appear.

(g) circumcircumpyrene

(h) circumcircumcoronene

Deep Purple

2009-01-15T13:54:00.007Z

Continuing with hard rock theme: the December 2008 ChEBI Entity of the Month was a natural fluorochrome epicocconone, also known as “Deep Purple” and “Lightning Fast”. I think that will increase our traffic a bit as more and more Deep Purple fans discover wonders of ChEBI.

Definitions of heavy metal

2009-01-14T16:25:00.002Z

Anyone who wants to use the term “heavy metal” for any biological or chemical purpose, should consult this publication in Pure and Applied Chemistry first. It has great collection of useless definitions of this term and a conclusion:

The term “heavy metal” has never been defined by any authoritative body such as IUPAC. Over the 60 years or so in which it has been used in chemistry, it has been given such a wide range of meanings by different authors that it is effectively meaningless.

According to yet another definition (not included in the above paper),

Heavy metal is the 666th element in the periodic table of mixology. Heavy metal is the heaviest of the metals, even heavier than rocks.

A medication from the past

2009-01-13T14:23:00.002Z

Today somebody sent this to the ChEBI help desk:

I find a capsule in my medicine chest that I don’t recognize and wonder if it’s a medication of some kind from the past that I should still be taking. It’s yellow and brown, more or less, and labeled #26666. Thank you!

Keep taking it, maybe you’ll remember what it was.

The definition of metallome

2009-01-12T11:11:00.002Z

Just in case anyone wonders what the title of this blog means, here’s definition of metallome from Wikipedia.

The Metallome blog is created

2005-03-23T12:27:00.000Z

... and that's it.