Oct 30, 2018
research image
The preprint, which describes the application of a groundbreaking method to study organic compounds, was downloaded 19,000 times in a 24-hour period. 
 
The previous download record for any preprint on ChemRxiv was 15,000 downloads over a six-month-period.
 
“We have developed a way to look at small molecules with electron microscopes which will often allow us to unambiguously figure out the identity of molecules in minutes” said UCLA Chemistry & Biochemistry professor Hosea Nelson about the research discoveries leading to the preprint that he and co-authors posted on ChemRxiv over a week ago. “Using this technique, the speed at which we can formulate potentially life-saving drugs will be greatly accelerated; it will be like going from riding a tricycle to driving a Ferrari.”
 
Members of the UCLA Team behind the record-breaking preprint: Hosea Nelson, Tamir Gonen, Michael Martynowycz, Christopher Jones, Jose Rodriguez.  Not pictured is Johan Hattne.
 
As evidenced by the reaction across the scientific community, Nelson and his team have a right to be this excited.
 
The soon to be published paper titled, “The CryoEM method MicroED as a powerful tool for small molecule structure determination”, describes the team’s development of a new technique which will allow researchers to easily and quickly determine the structures of organic molecules using very small samples.
 
MicroED involves crushing powders between glass slides and depositing them on a copper grid with 1μm diameter holes, cooling them to liquid nitrogen temperatures and placing them in a Cryo-EM instrument. C. JONES ET AL., CHEMRXIV (2018).
 
When asked why he thought so much enthusiasm has been expressed for his team’s work, Nelson explained, “The paper is for organic chemists by organic chemists, with broad implications for curing diseases and saving lives through drug development.”  “We are excited about the potential applications of this new technique,” he added. “We hope to collaborate with the broader community to bring structural chemistry to the people.”
 
In Chemistry World, co-senior author Professor Brian M. Stoltz of Caltech is quoted as saying that the response to the team’s ChemRxiv preprint paper from the research community has been ‘truly overwhelming and exciting’. ‘So many new ideas are flying around, it will be exhilarating to see where this will lead,’ he said.
 
“While developing this technique I was amazed at how rapidly we could obtain high resolution, unambiguous chemical structures of organic molecules" said first author UCLA Chemistry & Biochemistry graduate student Christopher G. Jones, who is part of the Nelson group. "As chemists we typically devote so much time to interpreting and deconvoluting complex spectral data to identify our compounds. There is no doubt the widespread adaptation of this technique would greatly accelerate research efforts in both academia and industry.”
 
Below is a sampling of the huge wave of excitement which hit the web almost immediately:
 
"Astounded," "blown away," "astonished." Has there been another recent example in #chemistry of people going so nuts about a new advance? (Lila Guterman, Deputy News Editor, Science Magazine, on Twitter)
 
“Very few papers in recent times have made me sit up and do a double take, but this one did.  At one point the authors say they were “astounded” by the ease of the technique, and I don’t think that word is out of place at all.” (The Curious Wavefunction)
 
“I am blown away by this,” says Carolyn Bertozzi, a chemist at Stanford University in Palo Alto, California. “The fact that you can get these structures from [a sample] a million times smaller than a speck of dust, that’s beautiful.  It’s a new day in chemistry.” (Science Magazine)
 
 “The one-hour photo booth has met its molecular match” (Science News)
 
“Stefan Raunser, a cryo-EM expert at the Max Planck Institute of Molecular Physiology, Dortmund, Germany calls the study ‘outstanding’. He notes that some of his co-workers attended a workshop on MicroED that Gonen ran and ‘were impressed by the power of the technique and its ease of use’” (Chemistry World)
 
“There’s a phrase that leads off a paragraph in the UCLA/Caltech manuscript: “Astounded by the ease with which such high quality data was obtained. . .” and I think “astounded” will go for everyone who reads it. Another line, not many sentences later, is “Based on our findings, we anticipate that MicroED will be enthusiastically received by many types of small molecule chemists“, and buddy, they’ve got that right.” (Science Magazine)
 
“To see an over-the-counter cold and flu medicine capsule being cracked open and the heterogeneous powder inside analyzed at atomic-level resolution is awesome,” says Tom Maimone, an organic chemist at the University of California, Berkeley. “Even if this technique only works for a subset of organic small molecules, what is shown in these papers is stunning.” (Chemical & Engineering News)
 
"Another absolutely incredible advance in #cryo-EM promises to speed our ability to determine the atomic structure of small molecules that are key to biological discovery and #drug development." (NIH Director Francis S. Collins, on Twitter)
 
The process of applying MicroED to small molecule structural analysis. Here commercial progesterone (1) was analyzed and an atomic resolution structure determined at 1Å resolution. Grid holes are 1μm in diameter. C. JONES ET AL., CHEMRXIV (2018).
 
UCLA faculty senior authors are Professor Tamir Gonen of the Howard Hughes Medical Institute (HHMI) and professor in UCLA’s departments of Biological Chemistry and Physiology; Nelson; and Professor Jose A. Rodriguez, holder of the Howard Reiss Career Development Chair in the UCLA Department of Chemistry & Biochemistry
 
Stoltz is the fourth senior author. A graduate student in his group, Tyler Fulton, is another co-author, along with second author Michael W. Martynowycz and Johan Hattne, a postdoc and a research specialist, respectively, with Gonen’s group. 
 
Update: On November 2, 2018, the paper was published in ACS Central Science. 
 
Photo by Penny Jennings, UCLA Department of Chemistry & Biochemistry.