Bioinorganic and Biomedical Chemistry of Gold

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...

One can expect that these terms have something to do with alchemy. 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

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

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

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

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

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

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

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.

Symbol	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

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

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

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

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

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

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 Ρέα; /ˈriːə/) was the daughter of Uranus and Gaia, and was known as the mother of gods. Her name is often linked to the Greek word ρείν (“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

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

“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

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

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

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)