Thursday, January 14, 2016

Dr. Bandwagon or How I Learned to Stop Worrying and Love the Cyclotron

Two weeks ago IUPAC announced the Discovery and Assignment of Elements with Atomic Numbers 113, 115, 117 and 118. The term "discovery" is a little misleading with respect to the superheavy elements. It's not like these elements were unexpectedly found at the bottom of a nuclear reactor or by painstakingly searching for new primary constituents of exotic metallic ores. Instead the researchers carefully designed experiments and bombarded nuclei with the hypothesis that certain combinations of lighter elements would fuse into superheavy atoms. So, the discovery is really only whether their synthetic hypothesis was correct or not. This does not diminish the significance of the outcome, but it feels like the connotation of "discovery" downplays the intellectual role of the researchers who did the experiments. Nevertheless, the nature of words and what we call things engenders a lot of strong opinions, especially the names of new elements. IUPAC, as arbiter of element names (and names of things in chemistry in general), is well aware of this especially after the Cold War era Battle Royale between research groups in the United States and Russia over the right to name elements 101 through 106.

The press release by IUPAC produced an immediate fervor in both the scientific community and the popular press. This is certainly a chance for chemistry (and physics) to take center stage in the public eye, so no one should blame anyone for taking full advantage of the opportunity. That goes double for publishers like Chemistry World and Nature, who have the chance to engage an audience that might ignore any number of other science and chemistry stories. In the excitement though, some people are overestimating their role in the process of naming elements.

First, the ridiculous suggestions. There are currently petitions that have received attention in the popular media to call 2 of the new elements 'lemmium' to honor heavy metal musician Ian 'Lemmy' Kilmister of Motörhead, and 'octarine' to honor Terry Prachett's Discworld series. At least the creators of the octarine petition are seeking an audience with the right people (JINR and LLNL) who actually get to suggest a name. The lemmium petition is directed directly toward IUPAC who only sanction/approve names suggested by the discoverers (although there is a clause stating the IUPAC can select a name if an appropriate suggestion is not made, which seems highly unlikely). Neither of these proposals meet IUPAC's guidelines for new element names. The rules state: "Elements can be named after a mythological concept, a mineral, a place or country, a property or a scientist". Unfortunately, "rocking hard" isn't exactly what IUPAC meant by a "property", so 'lemmium' is out. One could try to argue that 'octarine' is a mythological concept, but it's hardly the equivalent of 'promethium' named after the Greek god Prometheus. Check back in a few hundred years. Octarine gets traction now because the Discworld books are very popular, and Pratchett died recently. The periodic table is timeless. We don't know yet how timeless Discworld will be (sorry, folks). 

These suggestions are also counter to any suggestions the researchers might even brainstorm on a whiteboard. The initial reports on these elements starting appearing in the mid-aughts, so they've been waiting nearly, or more than, a decade for the independent confirmations of their experiments and approval by IUPAC needed to suggest an element name. Researchers also had to overcome serious obstacles to even try their experiments such as making and purifying radioactive, fairly shorted lived super heavy starting materials. With all the years, people and resources involved in this effort, does naming an element after a mid-tier musician with a well-documented substance abuse problem and a collection of Nazi paraphernalia even sound reasonable?** Can you even imagine that in the 10 years or so that they've been waiting to suggest an element name that the researchers haven't kicked the tires on a few ideas?

This gets to the central point. The researchers making new elements are doing difficult research. Coming up with a name is easy. They're really smart and creative people who don't need help with names. It's presumptuous to think any one us should have a say in what they chose. When I (Shawn) was interviewed for the ACS Reactions video, I was asked if I had a suggestion for a new element name. I answered no. Never in my wildest dreams did I think anyone would interview me about how elements were named, let alone be in a situation to name an element. I've had a longstanding interest in nuclear chemistry, but since I chose to study a different area, I abdicated any minute chance I had to name an element some time ago. In fairness, we had quite a lot to say about the structure of element names, and the new IUPAC naming guidelines. We specifically suggested modifying the naming conventions for group 17 and group 18 elementsthe halogens and noble elements; however, we never suggested any element names. Okay, we did suggest that 218Rn could beknown as astaton in jest, but no one seems to have listened.

In addition to ludicrous pop culture-inspired names, there have been calls to correct historic gender bias by naming new elements after women and a denouncement of names based on nationalism. We certainly would champion the choice if any of the research groups chose to honor one of the many women who have contributed to the expansion of the periodic table; however, it is unfair for anyone to graft their cause onto researchers who may be equally passionate about other worthy options. There's almost an implication that if researchers don't adopt some "altruistic" name that they will have done a disservice to science and the world. No where is that more apparent than the discussion of nationalistic names. Philip Ball has suggested 'levium' after Primo Levi, a Jewish Italian chemist and Holocaust survivor to send the message that the "periodic table is for all humanity". On the surface, these kinds of ideas sound inclusive, but given the pre-condemnation of a nationalistic Japanese element name from many quarters, even suggestions made in good faith can come off as sanctimonious.

Actually, the periodic table should not be a billboard to promote any cause; though it has unfortunately been exploited in the past. The most nationalistic names are from the late 19th century—germanium (Germany), gallium (France, from the Latin), and polonium (Poland), all named by a scientist from the respective countries. Francium followed this trend in 1939. These four elements stand out today as very nationalistic names.

There are other elements with regional names—scandium reflecting the pan-Scandinavianism enthusiasm of the 1870s. Europium and americium can be taken as referring to the continents rather than any one nation. Any nationalism behind 1828’s naming of ruthenium (Russia) seems weak since it reflected the location of discovery, not the discoverer. There is a bit of vanity in the city and local region element names. Invariably these reflect the location where the element was discovered: lutetium (Paris), holmium (Stockholm), hafnium (Copenhagen), berkelium (Berkeley), dubnium (Dubna), darmstadtium (Darmstadt), rhenium (Rhine River), hassium (Hesse), californium (California), livermorium (Livermore). These don't strike us as nationalistic. In addition, there are yttrium, ytterbium, terbium, and erbium, all named for Ytterby. In defense of this, a lot of elements were discovered in ores found there and ytterbium was named by a Swiss chemist. If the Swedes wanted to be nationalistic, it seems unlikely they'd chose the name of a village on a small island where quartz and feldspar were mined to make porcelain. Hardly the stuff of legend. Besides, how many people realize that hafnium references Copenhagen, Denmark?

There have been rumors that the Riken research group now credited with element 113 might choose the name 'japonium', and some have criticized this as nationalistic. While it's true that japonium would stick out like germanium, gallium, polonium, and francium, what is the deep rationale for criticizing japonium, other than "fairness" to those who had nothing to do with the work behind creating element 113? Japonium is still a rumor remember. In fact, "nationalistic" may not the right way to see any of these elements named for nations, regions, or cities. At worst, they are vanity names, but they celebrate where the work was done, where the element was first found or created. They tell part of the story behind the tablein a way that lemmium or octarine would not.

At the risk of sounding hypocritical, if the Riken group chooses to honor their homeland with an element name, we hope japonum is not the only one being considered. 'Nipponium'*** or 'nihonium' would reflect what the Japanese call their nation not an anglicized exonym; however, IUPAC credited element 113 to Riken, and they don't need our help either.
**Motörhead fans can direct all their hate tweets about this statement to @scburdet as @geochembrett has nothing to do with it.

***Nipponium was once suggested for element 75 (rhenium), but the discovery was later disproved. IUPAC has a restriction on reusing a name that has been "used" before, so 'nipponium' might be rejected. However, this clause has never been invoked. If the name only appears in a paper, but was not adopted or widely utilized, we believe it would still be acceptable.

Tuesday, January 12, 2016

Doomed to repeat history

I still "owe" the world and the EIC of Applied Materials and Interfaces a whistleblower-style disclosure of all the correspondence related to the Fe3+ sensor paper discussed in my previous posts (1, 2, 3). The problem is that I need to carve a few days out of my schedule to document everything properly. In the interim, I came across a couple of related papers recently that bear examination in more than 140 character tweets.

In reverse chronological order, today I saw the ASAP notification of this paper by Magri in RSC Advances. RSC Advances has been a significant contributor to potentially bogus Fe3+ sensor papers in the past, but seems to be aware of the problem now as evidence by this paper that has been in ASAP limbo for >7 months (tangent - there are ASAP papers there from 2013). Magri's paper follows a similar path to my groups study on another popular Fe3+ sensor. Magri's results demonstrate that the earlier study (cited 59 times according to Google Scholar) makes incorrect conclusions about the mechanism of fluorescence signal transduction. In short, the fluorescence quenching is not due to metal ion binding to the sensor's receptor, but rather inner filter effects stemming from Fe3+ inherent incompatibility with water at pH >4. I'd encourage people to read both papers because it will give great insight to the types of problems plaguing the fluorescent sensor field. The original Tetrahedron Letters paper lacks any absorption spectra, which would provide direct evidence of the expected inner filter effects however. Magri does the fluorescent sensor community a great service in publishing a thorough investigation like this.

This leads me to an ASAP Applied Materials and Interfaces paper that ruffles my feathers. The paper claims a signal transduction mechanism that involves forming a 5-coordinate Fe3+ complex with monodentate phenolic ligands in water (unbuffered, deionized). There is a component of the project that involves nanoparticle upconversion of light to excite the Nile Red fluorophore; however, at its core this system is essentially on a small molecule sensor. The fluorphore-ligand dyad (Nile Red-phenol) is reported to bind Fe3+, which quenches the fluorophore emission. Whether the excitation of the fluorophore is direct or from upconversion is not particularly relevant to the sensing mechanism. There are several red flags that suggest this cannot be the actual mechanism:
1. In addition to Fe3+ being incompatible with non-acidic water, monodentate phenols are unlikely to have strong interactions with Fe3+ in the presence of excess water ligands (unlike catechols, which take advantage of the chelate effect). It's even less likely that FeL2, FeL3 and higher order species will form in high concentrations. You will not find many (any) inorganic chemists who will buy into the author's coordination chemistry. Furthermore, evidence for these complexes being reasonable is demonstrated in non-aqueous solution (in DCM, SI Figure S8). Changing the solvent completely changes the  coordination chemistry and hydrolytic stability of the Fe3+ ion.
2. The absorption spectrum (Figure 3) has the hallmarks of particulate formation/light scattering. The individual spectra increasingly deviate from the baseline as Fe3+ is added
3. The procedures for working with Fe3+ in cells do not match the recommended protocols. Adding Fe3+ to the extracellular fluid does not result in an increase in free intracellular Fe3+. I do not believe anyone has studied this in enough detail to know what happens when you do this. I suspect a broad stress response (which could lead to all kinds of intracellular changes) and/or uptake of iron nanoparticles by endocytosis; however, this is speculation.

Clearly, the authors see a change when adding Fe3+, but their mechanism is wrong. There are many possibilities - inner filter effects, formation of iron nanoparticles, pH-induced changes from Fe3+ hydrolyisis. Every published study that fails to account for inorganic and photochemisty just perpetuates the myth that these protocols for handling Fe3+ in aqueous solution and cells provide valid results. This facilitates the publication of the next dubious study. I would alert the journal to this problem before publishing this blog; however, they've made it abundantly clear through our previous correspondence that they do not care whether or not papers published in the journal contain conclusions that are consistent with well-establish chemical concepts.