Molecular Coupling, Assembly, and Imaging

A central challenge to creating technologically useful molecular nanostructures is the question of how to induce molecules to covalently couple and self-assemble in pre-determined ways on surfaces. The creation of large, functional molecular structures that can be imaged and controlled on surfaces requires the development of techniques that result in precise covalent bonding between molecular building blocks. Fig. 1 1 shows three representative strategies for accomplishing this (many others exist). These techniques allow molecules to be attached to one another at exact locations so that subsequent molecular properties (which are intrinsically quantum mechanical) can be controlled and engineered.

Fig. 1: Sketches of three different molecular coupling strategies. Controlled covalent bonding of molecules using strategies like these is critical for performing atomically-precise bottom-up synthesis of functional molecular nanostructures, including nanomachines.

Characterizing the results of molecular assembly is another great challenge. The rearrangement of even a single chemical bond in a molecular nanostructure can dramatically change its electronic and magnetic properties, and so understanding structure at the single-bond level is necessary to fully characterize molecular properties. Conventional scanning tunneling microscopy (STM) measures the electronic wavefunction of molecular structures (i.e., the local density of states (LDOS)) but does not directly image chemical bonds.1 Transmission electron microscopy (TEM) is also not able to provide this information since organic molecules decompose too quickly in the TEM electron-beam. The best technique for performing single-bond-resolved mapping of molecular nanostructures on surfaces is CO-tip non-contact atomic force microscopy (nc-AFM) using a qPlus resonator.2 This technique was developed in collaborations between L. Gross, G. Meyer, F. Giessibl, and others.3,4 The qPlus AFM technique utilizes a quartz tuning fork oscillator with a short metal tip glued to one end5 Figs. 2a, b). Changes in the oscillator resonant frequency are measured as the tip is scanned across a surface and provide atomic-scale contrast. Functionalization of a qPlus nc-AFM tip with a single CO molecule provides the highest spatial resolution and makes it possible to obtain single-chemical-bond-resolved images of molecules on surfaces (Figs. 2c).4 Such images can even resolve bond order (i.e., distinguish single bonds from double bonds).6

Fig. 2: (a) Sketch of non-contact AFM configuration shows how surface interaction leads to a frequency shift of the cantilever resonator. (b) The qPlus tuning fork oscillator is the heart of highly versatile modern combined STM/AFM scanned probe instrumentation. (c) Functionalization of the tip of a qPlus nc-AFM with a single CO molecule allows single-chemical-bond-resolved imaging of molecular structures on surfaces.

The Crommie group has shown that it is possible to use CO-tip nc-AFM to image the products of surface chemical reactions with single-bond resolution (Fig. 3).7-9 This ability is critical for determining the products of chemical reactions used to stitch together molecules (i.e., self-assembly) as well as to characterize the effects of molecular structural changes. Figs. 3b-d, for example, show conventional STM images of three different products of the reactant molecule shown in Fig. 3a (synthesis of the reactant precursor was performed by F. Fischer’s group). The chemical structures of the product molecules are impossible to determine from STM images. Figs. 3c-h, , on the other hand, show the CO-tip nc-AFM images of these same molecular structures acquired by the Crommie group.7 The chemical bond structure is now clearly seen, allowing 6-membered rings to be distinguished from 4- and 5-membered rings, and yielding images that look nearly identical to the wireframe structural sketches below. These are the first single-bond-resolved images of a chemical reaction.7

Fig. 3: (a) STM image of enediyne molecular fragment before chemical reaction. (b)-(c) STM images of reaction products after annealing enediyne molecules on Ag(100). The chemical structure cannot be resolved by STM. (e)-(h) CO-tip functionalized qPlus nc-AFM images of precursor and reaction products allows their chemical structure to be imaged with single-bond resolution. These are the first bond-resolved, single-molecule images of a chemical reaction. (STM/AFM images: Crommie group; enediyne precursor synthesis: Fischer group).

The Crommie group has used CO-tip nc-AFM to image the results of Bergman-assisted coupling and alkyne coupling of precursor molecules on clean metal surfaces. Fig. 4 shows the self-assembly of enediyne precursor molecules (Figs. 4a, d) on Au(111) (synthesis of the reactant precursor by F. Fischer’s group). Upon annealing the surface, the enediyne molecules undergo Bergman cyclization to yield radical monomers (Figs. 4b, e).8 These radicals, which exhibit reactive unpaired electrons, polymerize to form oligomer chains as shown in Figs. 4c, f. Fig. 4g shows close-ups of the oligomer chain structure, revealing a dimerization of the bond lengths (i.e., a Peierls transition in this 1D chain).8

Fig. 4: (a) Sketch of enediyne precursor molecule. (b) After Bergman cyclization the enediyne molecule has unpaired electrons at its edges and is a radical. (c) The radicals are reactive and polymerize as they meet on the surface and self-assemble. (d)-(f) Chemical-bond-resolved CO-tip nc-AFM imaging of the polymerization process described above in (a)-(c) on Au(111) surface. (g) Close-up nc-AFM imaging reveals Peierls-like dimerization of the polymer bond-lengths. (nc-AFM images: Crommie group; enediyne precursor synthesis: Fischer group).

The Crommie group has shown that when the same enediyne precursor molecules are deposited onto Ag(100) they couple via a completely different mechanism (Fig. 5).9 Single-bond-resolved nc-AFM measurements show that the ends of the molecules connect before cyclization (i.e., ring formation) takes place (Figs. 5c-e). A sketch of this alkyne coupling mechanism is shown in Fig. 5a. Analysis of the intermediate steps of this reaction (characterized by direct imaging) reveal the influence of dissipation and entropy on the coupling process. These are the first single-bond-resolved images of the intermediate states that occur during a chemical reaction (Fig. 5c, d).9

Fig. 5:(a) Sketch of enediyne molecular precursors undergoing alkyne coupling and then subsequent cyclization. (b)-(e) CO-tip nc-AFM images of enediyne molecules following the reaction pathway sketched in (a). (c) and (d) show intermediate steps on the path from (b) to (e). These are the first bond-resolved, single-molecule images of an intermediate step in a chemical reaction. (nc-AFM imaging: Crommie group; enediyne precursor synthesis: Fischer group).


1 J. Tersoff & D. R. Hamann, "Theory of the scanning tunneling microscope", Physical Review B 31, 805 (1985).

2 F. J. Giessibl, "The qPlus sensor, a powerful core for the atomic force microscope", Review of Scientific Instruments 90, 011101 (2019).

3 L. Gross, F. Mohn, N. Moll, G. Meyer, R. Ebel, W. M. Abdel-Mageed & M. Jaspars, "Organic structure determination using atomic-resolution scanning probe microscopy", Nature Chemistry 2, 821 (2010).

4 L. Gross, F. Mohn, N. Moll, P. Liljeroth & G. Meyer, "The Chemical Structure of a Molecule Resolved by Atomic Force Microscopy", Science 325, 1110 (2009).

5 F. J. Giessibl, "High-speed force sensor for force microscopy and profilometry utilizing a quartz tuning fork", Applied Physics Letters 73, 3956 (1998).

6 L. Gross, F. Mohn, N. Moll, B. Schuler, A. Criado, E. Guitián, D. Peña, A. Gourdon & G. Meyer, "Bond-Order Discrimination by Atomic Force Microscopy", Science 337, 1326 (2012).

7 D. G. de Oteyza, P. Gorman, Y.-C. Chen, S. Wickenburg, A. Riss, D. J. Mowbray, G. Etkin, Z. Pedramrazi, H.-Z. Tsai, A. Rubio, M. F. Crommie & F. R. Fischer, "Direct Imaging of Covalent Bond Structure in Single-Molecule Chemical Reactions", Science 340, 1434 (2013).

8 A. Riss, S. Wickenburg, P. Gorman, L. Z. Tan, H.-Z. Tsai, D. G. de Oteyza, Y.-C. Chen, A. J. Bradley, M. M. Ugeda, G. Etkin, S. G. Louie, F. R. Fischer & M. F. Crommie, "Local Electronic and Chemical Structure of Oligo-acetylene Derivatives Formed Through Radical Cyclizations at a Surface", Nano Letters 14, 2251 (2014).

9 A. Riss, A. P. Paz, S. Wickenburg, H.-Z. Tsai, D. G. De Oteyza, A. J. Bradley, M. M. Ugeda, P. Gorman, H. S. Jung, M. F. Crommie, A. Rubio & F. R. Fischer, "Imaging single-molecule reaction intermediates stabilized by surface dissipation and entropy", Nature Chemistry 8, 678 (2016).