Friday, March 27, 2015

Tilting at Ferric Windmills

As documented last week, I contacted a journal about very questionable methods used to conclude ferric iron could be detected by fluorescence methods in water. I was already aware that this was not the only occurrence of a research group failing to properly account for the aqueous solution chemistry of Fe3+ in their studies. With a reignited hyperawareness about this problem in the fluorescence sensing field, I noticed another study making similar mistakes while catching up on recent literature this week. I alerted the EIC of this journal to the problem as well, and got a completely different response with respect to both the scientific and peer review concerns. Since this is an ongoing dialogue, I will not comment any further until the issue is resolved. This second incident prompted me to conduct a more thorough investigation of the underlying prevalence of these protocols in Fe3+ sensing.

Counts of papers containing questionable ferric sensing methodologies.
*indexed in webofknowledge as of 3/26/205.
Using webofknowledge, I searched the combination of (ferric OR Fe(III) OR Fe3+) AND (sensor OR probe) AND (water OR aqueous OR buffer) AND fluorescence. To decrease the volume of references to analyze, I limited the results to those from journals published by the ACS, the RSC and Wiley since they have a reputation for publishing reliable sensor papers (reducing the number of results from ~500 to ~150). I then went through the search results looking for evidence that the experiments would be at risk for giving spurious results. I am not sure about the exact speciation/stability of Fe3+ in mixed organic/aqueous solvents; however, my experience suggests that any significant amount of water will be problematic. I excluded several studies using 1% aqueous content in solvents like THF and methanol, as that seemed to be a relatively safe protocol. Anything with 20% or more water made the "suspicious list". The overwhelming majority claimed to work in pure water, aqueous pH ~ 7 buffer or with 50% or less organic solvent added to water/buffer. There are many fewer (not counted) that describe protocols for working and handling Fe3+ in acidified aqueous solution, and many others using pure organic solvent (also excluded from consideration). Of the 150 results, 51 contained possible problems. The results broken down by publication year and journal name are shown in the figure above.

The results are quite informative. Before the Rurack paper in 2005, there were no Fe3+ sensing papers in ACS/RSC/Wiley family of journals using water (his paper has been cited >250 times). My paper showing the errors in Rurack's aqueous results was published in 2010. The yearly trends however, suggest that the acceptance of questionable (invalid) Fe3+ titration protocols are increasing rather than decreasing. Presumably, every published paper using similar methods provides unwarranted precedence for adoption in future studies. Whether there is a connection or not is unclear, but Inorg. Chem. where my paper was published, has not published a problematic paper in the Fe3+ sensing field that I can find.

Full disclosure, there are a few papers in this collection that are difficult to analyze, particularly those from the polymer/materials literature. A more thorough investigation would be required to fully evaluate the results in detail. Furthermore, some of the studies have ambiguous or nonexistent experimental protocols in the paper and/or the supporting information, which makes evaluation difficult or impossible. If procedures for measuring/adjusting the pH are not listed, I assume that this was not a consideration. A few papers don't even list the counter ion for the Fe3+. Also, I excluded papers that may have had questionable handling of Fe3+ solutions (selectivity studies), but the Fe3+ response was not a significant component of the paper's discussion/conclusions. The 51 papers all attempt to conclude something specific about Fe3+ detection in aqueous solution. No papers from Elsevier or Springer were examined.

There are some common issues in many of the 51 papers. For example, making stock solutions of FeCl3 in water by just mixing (i.e. without adjusting the pH to <4), and titrating Fe3+ into neutral aqueous solution. Some use phosphate buffer, which would generate Fe(PO4), a water insoluble salt (assuming all the Fe3+ wasn't already precipitated as insoluble Fe(OH)3). A cringe-worthy method used in more than one paper to confirm Fe3+ binds to the sensor in aqueous solution, is mass spectroscopic detection of the ferric complex prepared in methanol. I have no doubt that they detected the complex, but Fe3+ in methanol is completely different than in water. The MS data in methanol does not confirm anything about the species that are (not) present in aqueous solution. 

What does one do in such a situation? Even if I was somehow asked to referee every paper on Fe3+ sensing, there were more papers on the topic published last year than I could possibly handle, even if they were the only kind of requests I received/accepted. A broad search suggests an upper limit of 190 Fe3+ sensor papers were published in 2014. I have no desire to comb the literature and complain to editors/authors every time I find a problematic paper. I've already published a paper in a good journal that includes a cautionary tale about these issues, but it does not seem to have permeated the sensing field zeitgeist. As I mentioned in the previous post, it's discouraging to find out that some individuals need a reminder about the relevant/underlying undergraduate inorganic chemistry. I have no doubt that researchers in other fields can point to similar problems in the literature on other topics. How does one effectively get through to journals, peer reviewers and researchers without wasting time that should be spent on other aspects of academic science? It seems antiquated in the information age that such mistakes should persist and be perpetuated, but the traditional practice of publishing an opposing research study is the only clear recourse.

No comments:

Post a Comment