Abstract
Deciphering absolute configuration of a single molecule by direct visual inspection is the next step in compound identification, with far-reaching implications for medicinal chemistry, pharmacology, and natural product synthesis. We demonstrate the feasibility of this approach utilizing low temperature atomic force microscopy (AFM) with a CO-functionalized tip to determine the absolute configuration and orientation of a single, adsorbed [123]tetramantane molecule, the smallest chiral diamondoid. We differentiate between single enantiomers on Cu(111) by direct visual inspection, and furthermore identify molecular dimers and molecular clusters. The experimental results are confirmed by a computational study that allowed quantification of the corresponding intermolecular interactions. The unique toolset of absolute configuration determination combined with AFM tip manipulation opens a route for studying molecular nucleation, including chirality-driven assembly or reaction mechanisms.
Highlights
Deciphering absolute configuration of a single molecule by direct visual inspection is the step in compound identification, with far-reaching implications for medicinal chemistry, pharmacology, and natural product synthesis
Since the time of Pasteur’s experiment, various analytical techniques have been perfected to help determine the absolute configurations of compounds, e.g., measurement of optical rotation, circular dichroism, X-ray analysis, NMR spectroscopic methods, etc.8, 9, but to assign absolute configuration of individual molecules directly by visual inspection remains a highly attractive goal10
Isolation and structure elucidation of natural products has progressed dramatically14, their identification by direct observation of single molecules would eliminate some persistent problems connected with natural product isolation and/or total synthesis, e.g., limited compound availability and a necessity for further functionalization requiring additional synthetic steps
Summary
Deciphering absolute configuration of a single molecule by direct visual inspection is the step in compound identification, with far-reaching implications for medicinal chemistry, pharmacology, and natural product synthesis. For small bulky molecules it is difficult and unreliable to assign their configuration by using standard STM measurements (i.e., without tip functionalization) and only a rough estimation of their orientation is feasible, as demonstrated for single tetramantane molecules on a Au(111) surface23, 24.
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