A new toolset for studying chirality at the single molecule level
The absolute configuration of individual bulky tetramantane molecules can be assigned by visual inspection using low temperature atomic force microscopy.
Our paper published in Nature Communications 9, 2420 (2018) can be read from https://www.nature.com/articles/s41467-018-04843-z
It was Louis Pasteur, one of the founders of microbiology, who coined the aphorism “The role of the infinitely small in nature is infinitely great”. Apparently, this sentence also applies to Pasteur’s ground-breaking research on molecular chirality. Today we know that molecular chirality plays an important role in our everyday life, because enantiomers (i.e., mirror images) of the same molecules can interact with living organisms in completely different ways. This is reflected, for example, by our olfactory perception of chiral odorants: while the D-isomer of limonene has an orange-like odour the L-isomer smells piney-like. In biology, many compounds appear almost exclusively in either of the two forms. This so-called homochirality is, for example, observed for natural D-glucose, which is the most important energy source for cellular respiration while synthesized L-glucose is useless for living organisms.
Many (homo-)chirality related phenomena, in particular, the underlying molecular recognition mechanisms, are still not well understood. This is because it is difficult to study chirality at the level of individual molecules. Even though the analytical techniques have been tremendously improved since the time of Pasteur – who firstly separated different forms of tartaric acid crystals by hand under an optical microscope and subsequently analysed their optical rotation properties – it is still impossible to assign the absolute configuration (i.e., the absolute sense of handedness) of arbitrary individual molecules directly by visual inspection. Hence, this ability would constitute a major advance in chemistry and pave the way for unravelling persisting questions regarding the nature of molecular recognition.
In our study we are using low temperature atomic force microscopy (AFM) to image individual tetramantane molecules on a copper surface. By functionalizing the AFM tip with a single CO molecule we are able to obtain submolecular resolution, which is needed for precisely identifying the chemical structure and orientation of the molecules. This so-called “bond imaging” technique has been introduced several years ago by Leo Gross et al. (Science 325, 1110, 2009) and has become an indispensable tool for studying molecules on surfaces. To date the method has been mostly applied for studying flat aromatic molecules that adsorb planar on the surface. Apparently, since the method relies on constant height imaging without tip-sample feedback, the analysis of 3D compounds is not straightforward.
We picked out a nanodiamond molecule as our test object in order to demonstrate the possibility of assigning the absolute configuration even for arbitrary bulky compounds. Tetramantane (C22H28) represents the smallest chiral diamondoid built-up from only four adamantane units. For these aliphatic compounds neither their chirality nor the orientation can be determined using conventional scanning tunnelling microscopy. However, application of the bond imaging technique based on scans along customized height profiles allows to circumvent the lack of an active tip-sample feedback and finally enabled successful assignment of the absolute configuration by visual inspection.
Our approach represents a new toolset for studying molecular recognition that can enhance our understanding about the role of chirality in nature. Moreover, and more generally speaking, we believe that further refinements of the bond imaging methodology will enable researchers worldwide to address and answer very fundamental questions regarding molecular chemistry that have not been accessible before. Hence, I am very eager to follow the exciting results and advancements of the field that will emerge in the next years.
Original article: Daniel Ebeling, Marina Šekutor, Marvin Stiefermann, Jalmar Tschakert, Jeremy E. P. Dahl, Robert M. K. Carlson, André Schirmeisen, and Peter R. Schreiner, "Assigning the absolute configuration of single aliphatic molecules by visual inspection". Nature Communications 9, 2420 (2018)