www.asiachem.news December 2021 | 101 once a new technology became widely available, like the case of the CRISPR gene-editing, it became so common that many people joined, including practitioners of theoretical, basic, and applied science. Nevertheless, the dynamic EM may remain a scientific niche. You are the obvious pioneer and most active player in the field, but you don’t want to remain lonely there. This situation raises several questions. First, what are the most significant achievements of your EM technology? EN: What have I achieved? I am still wondering. Perhaps, I am opening up a new era of “cinematic chemistry” for studying and teaching chemistry by using motion pictures at atomic resolution. In this broad sense, we are among microscopists working on such instruments as environmental TEM and super-resolution optical microscopy–technologies, however yet to be suitable for molecular-level studies. We started our research in 2004 and reported the first result in 2007 in Science Magazine. We received a wonderful reviewcomment, “The ability to image conformations of individual small molecules is “holy grail” of microscopy, and the authors present a convincing case that they have managed to do so.” Our discovery is an ultimate form of a long-lasting endeavor in seeing minute matters by our eye since Hooke’s Micrographia. EK: How do you encourage others to join the field? EN: This is a rather tricky question. Overall, our work initially createdmore skepticismthan enthusiasm among chemists and electron microscopists. In addition, chemists at the beginning of the 21st century were still happy with cartoons and sculptures of molecules, not interested in “molecular cinemas”. Instead, enthusiastic support came from school kids, laypeople, and scientists in other disciplines. Our most recent videos showing the time-course of “molecular shuttling”, “flat molecule converting to fullerene”, and “emergence of aNaCl crystal” have become a popular subject on Twitter and YouTube. The NaCl paper in JACS was viewed over 20,000 times within a few weeks after publication and has recorded the highest Altmetric score of >900 among all JACS publications. Do you know the fifty-second film showing a steam train coming at some distance? “The Arrival of a Train at La Ciotat Station” by the Lumiere Brothers in 1895. This historic cinematograph opened up “the era of cinema”. When this film was first shown to the public, the legend says the audience was so excited that they jumped out of their seats. After a hundred years, the era of the cinema is just coming to the world of chemistry. EK: And how can you expand, popularize, and democratize your science? Your technology depends on prohibitively expensive infrastructure, which is not affordable to most people. EN: Let’s think about the cost. Take cryo-EM as precedence to our case. Thirty years ago, when cryo-EM was first introduced, EM was a complex instrument to operate, and it was costly. Now it is everywhere. Nowadays, the electron microscopes that we use are available in every major institution, andeven an undergraduate can use them after a week of training. We still see some problematic relationships between chemistry and electron microscopy. Chemists are not yet interested in using EM, and electron microscopists believe organic molecules are too unstable. Microscopists are afraid of contamination by the vapor of organic molecules, which is not at all a problem in our 15-year experience. My group has essentially opened the door of EM-imaging to organic chemistry, particularly dynamic imaging of molecular motions and reactions. We demonstrated since 2007 that the observation of the dynamic behavior of single organic molecules in a carbon nanotube and studying it without decomposition is a norm rather than the exception. I say “without decomposition”, meaning that any organic molecules would be stably observed for one to tens of minutes until a carbon nanotube container decomposes. Here, pi-electron-rich molecules may be slowly converted to something else. This phenomenon may seem like “decomposition” for physicists, but it is not. It is a perfectly rational behavior of such molecules reacting via excited state or radical cation. EM-imaging provides a new opportunity for a single molecule study of such species. You can draw a perfect analogy to a laser spectroscopic study of reactive species, except that we can see the reacting molecules one by one in real space and in real-time. Like any microscopic research, the choice of the substrate that holds the specimen in place is crucial. In scanning probe microscopy, you need to literally immobilize the molecule on a substrate. We have discovered the use of a carbon nanotube as a “test-tube” and a “fishing rod”. We used the tube as a test tube and put the specimen loosely in the interior. Or we installed a “chemical fishhook” on the pointed tip of the fishing rod to capture the specimen. In both cases, the molecules are half fixed, half free to move or to react. You can also use a thin graphene sheet as a “fishing net”. EK: It looks like comparing themotion of a free dog with that of a chained dog. EN: This is a goodmetaphor. Ideally, wewould like to watch the free dog, but that is impossible as the molecules will fly away into the vacuum. Therefore, we chain the dog andwatch itsmovement. There is an additional essential function of our nanotube “fishing rod”. This conductive rod connects the specimen molecule to the TEM instrument, which is grounded. The EM-imaging ionizes the organic specimens to form radical cations like in mass spectrometry experiments. The conductive nanotube supplies an electron to bring the radical cation back to the neutral molecules. The tube, therefore, protects the molecule from uncontrollable reactions, that is, decomposition. We have been working on this mechanism for six years and just finished the study’s first phase under variable temperature/ variable voltage conditions. EK: It is precisely like the grounding technology in electrical engineering. ©MONTAGE INC. 2021 ©MONTAGE INC. 2021
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