W.-H Soe

C Durand

O Guillermet

S Gauthier

H.-P Jacquot De Rouville

S Srivastava

C Kammerer

G Rapenne

C Joachim

Surface manipulation of a curved polycyclic aromatic hydrocarbon-based nanovehicle molecule equipped with triptycene wheels

With a central curved chassis, a four wheels molecule-vehicle was deposited on an Au(111) surface and imaged at low temperature using a scanning tunneling microscope. The curved conformation of the chassis and the consequent moderate interactions of the four wheels with the surface were observed. The dI/dV constant current maps of the tunneling electronic resonances close to the Au(111) Fermi level were recorded to identify the potential energy entry port on the molecular skeleton to trigger and control a driving of the molecule. A lateral pushing mode of molecular manipulation and the consequent recording of the manipulation signals confirm how the wheels can step by step rotate while passing over the Au(111) surface native herringbone reconstructions. Switching a phenyl holding a wheel to the chassis was not observed for triggering a lateral molecular motion inelastically and without any mechanic push by the tip apex. This points out the necessity to encode the sequence of the required wheel s action on the profile of potential energy surface of the excited states to be able to drive a molecule-vehicle.

1) Introduction

Single molecule nano-vehicles are a new class of organic molecules generally equipped with molecular legs, paddles or wheels chemical groups and able to be controllably driven on a surface with an atomic scale precision [1]. After their first complete design and synthesis with 2 legs & 2 wheels [2,3] and 4 wheels [4] at the beginning of the century, a large variety of molecule nano-vehicles have been proposed, synthesized and tested for example with two Binaphthyl paddles [5], or with a variety of molecular wheels like the four triptycene molecular group used bellow [6,7,8] or with four switchable legs [9].

Molecule nano-vehicles are expected to cargo an atomic scale load from one to another a specific location on a surface [10]. Their molecular skeleton is generally made of a central (rigid) planar molecular structure (called the chassis) where the molecular legs, paddle or wheels are chemically bound [1,2,4]. This chassis is supposed to be maintained at van der Waals distances away from the surface to minimize the lateral diffusion potential energy barrier of the molecule nano-vehicle on its supporting surface (or at least to make this barrier only dependent on its holders (legs, paddles, wheels)). Those holders must also ensure at least a reproducible step by step displacement of the nano-vehicle on this surface. For this displacement to be controllable, the nano-vehicle motive power can be delivered by a molecular motor chemical group directly embedded in the chemical structure of the chassis (apparent [11] or quantum [5,12]) or by the holder themselves when they are well synchronized together to achieve a controllable lateral motion on the surface [9].

We report here the surface deposition, LT-UHV-STM images recording, dI/dV mapping and single molecule manipulations of a four wheels molecule nano-vehicle equipped with a curved chassis. By its peculiar intramolecular mechanics, the concept of curved chassis was introduced by some of us [13] to moderate the interactions between the wheels and the supporting surface.

Certain molecular wheels like C 60 [6] or carborane [14] are known to lead to a very small lateral diffusion potential energy barrier for example on the Au(111) surface. In this case, the nanovehicle lateral motion is very difficult to control unless a more reactive supporting surface is selected to compensate for this small lateral diffusion barrier [15]. This can be a problem for nano-vehicles carrying a load because the load itself can be in this case also chemisorbed. In another context, the "pacman" molecule is a good example of a loadable molecule whose lateral diffusion barrier becomes so large that the molecule and its atoms cargo were not moving at all after loading more than 5 atoms [16]. On the contrary, other wheels like triptycenes present a large lateral diffusion barrier (mounted on a flat chassis [17]). Only STM molecular mechanical manipulation in a strong repulsive regime of mechanical interactions with the STM tip can succeed in putting it in motion laterally on the supporting surface, unless a well-adapted chassis is used to minimize the individual triptycene interactions with this metal surface [18].

The polycyclic aromatic hydrocarbon-based chassis equipped with four triptycene wheels (PAH-4W) shown in Fig. 1 was synthesized [13] with the goal to test how the curvature of this molecule favors or not the triptycene wheels rotation when physisorbed on an Au(111) surface.

We present in this paper our experimental conclusions on this chassis curvature effect. In section 2, the flash sublimation, the LT-UHV-STM images and the corresponding dI/dV mapping of the PAH-4W molecule are presented. In section 3, the LT-UHV-STM molecular mechanical manipulations are discussed together with our attempt, when one wheel appears to be up on the Au(111) surface, to drive the PAH-4W by tunneling inelastic effect just at the threshold of dismounting a wheel from the chassis. In section 4, the LT-UHV-STM manipulation results are discussed in terms of intramolecular mechanics taking into account the different molecular conformations observed on the Au(111) surface. The PAH-4W molecule was engaged by the Toulouse team in the first international 2017 nanocar race [1,19].

2) Sublimation and imaging of the PAH-4W nano-vehicle on Au(111)

An atomically clean Au(111) surface was UHV prepared following a standard sample preparation method using several cycles of Ar+ ion sputtering and annealing up to 450°C [20].

PAH-4W molecules were available in the form of a green powder material. Since the molecule is quite heavy with a molar mass of 2325 g.mol -1 (C 184 H 116 ), standard thermal sublimation using a Joule heated crucible only leads to molecular debris on the Au(111) surface (up to 500°C).

We have therefore built a specific flash evaporator using a small in section tungsten filament.

A solution of the PAH-4W molecules was first prepared selecting with care a low molecular weight solvent, here dichloromethane. Then, this filament was coated with the solution using a simple drop casting technique waiting for the droplet to dry before introducing this filament in the UHV chamber of the STM. While passing a few amperes of current intensity through this filament during a fraction of seconds, the filament is heated-up instantly. Many of the adsorbed molecules are destroyed like when using a thermal crucible evaporator but a few of them survive and are released from the hot filament to the surface [21]. Including the dI/dV mapping, all STM experiments were performed using one of the four scanning tunneling microscope heads of our ScientaOmicron low-temperature ultrahigh-vacuum STM instrument (LT-UHV 4-STM) operating at a base pressure of 10-10 mbar range at 5 K [20]. STM tips for scanning, molecular manipulations and spectroscopic measurements were prepared by electrochemical etching of a 250 micro-m tungsten wire. The tip apex was re-prepared in-situ on the Au(111) surface away from the PAH-4W molecules.

A typical constant current LT-UHV-STM image of the Au(111) reconstructed surface just after the molecules deposition is presented in Fig. 2. Many of the imaged adsorbates on this Au(111) surface are molecular fragments coming from PAH-4W molecules. However, a few intact PAH-4W molecules can be found at step edges and rarely on terraces when stabilized by the molecular fragments. Interestingly, they were found perpendicular and always atop the step with only one of their ends, with two tert-butyl groups positioned at the border of the step edge. We have evaluated the molecule density on the Au(111) surface to be of about one PAH-4W molecule per 50.000 nm 2 , enough to perform single molecule STS spectroscopy and single molecule manipulations. Notice that according to Fig. 2, we have succeeded to tune the filament heating time and the concentration of the initial dichloromethane solution of PAH-4W in such a way that the Au(111) herringbone reconstruction is largely intact on large terrace, a very important point for long distance lateral manipulation. In Fig. 2, some of STM imaged debris are clearly parts of PAH-4W molecules. A detail image of one PAH-4W molecule is presented in Fig. 3a with its corresponding elastic scattering quantum chemistry (ESQC) calculated dI/dV constant current image [22]. The four wheels, the chassis and the four tert-butyl chemical groups can be identified. The triptycene wheels have normally a larger tunnel conductance than the tert-butyl groups. But as presented in Fig. 3 insert, this is depending on the bias voltage and a relative contrast reversal between the wheels and the tert-butyls can also be observed while the central chassis is always showing a lower conductance. The surface conformation of a PAH-4W molecule adsorbed on Au(111) will be discussed below after detail dI/dV mappings and a few STM molecular manipulation sequences.

After this flash evaporation, the few PAH-4W molecules observed on the surface were systematically located on 500 nm x 500 nm portions of the Au(111) surface using the monoatomic steps configuration to record the position of each molecule on its surface portion. Here, we have taken advantage of the stability of our LT-UHV 4-STM to record their location with a sub-nanometer precision in the x and y directions on the Au(111) surface [20]. We have accumulated a stock of PAH-4W molecules coordinates sufficient to perform single molecule manipulation and STS tunnelling spectroscopy measurements. Fig. 2 is presenting a simple STM lateral manipulation of a single PAH-4W molecule out of its native step edge location to demonstrate that this PAH-4W molecule is intact and can be pushed away from this native physisorption site.

To identify the location of tunnelling conductance maxima along the PAH-4W molecular skeleton, STM dI/dV spectroscopic measurements were performed. At low bias voltage, this procedure is now a standard to identify the energy position of the molecular electronic states of the molecule close to the Fermi level when adsorbed for example on a metal surface. This procedure is also compulsory to identify the energy entry port for manipulating the molecule without any mechanical interaction between the STM tip apex and the molecule itself [5,12,23]. Fig. 3(a) is presenting a typical dI/dV spectrum where two tunnelling resonances at -1.65 V and -2.15 V and a third one at +2.10 V above the bulk gold Fermi level (E f , i.e., V = 0 ) can be observed. They were recorded at slightly different locations on the same PAH-4W molecule depending on the maxima and minima of differential conductance along this molecule. Very detailed dI/dV STM maps were also recorded at these tunnelling resonance energies to visualize the spatial variation of the electron probability density distribution along a PAH-4W molecule via the tunnelling differential conductance variations along the STM scans.

According to the interpretation of previously recorded dI/dV maps, for example on polyacene molecules like pentacene [24], the main molecular orbitals (MO) of the PAH-4W molecule contributing to the first electronic tunnel resonances at -1.65 V and +2.10 V are the HOMO and the LUMO respectively. Indeed, the central conjugated board of this molecule is not long enough to find for example molecular radical states contaminating the PAH-4W electronic ground state [30].

For comparison, the HOMO and LUMO electronic probability density of a free (not adsorbed) PAH-4W molecule in its Fig. 1 minimum energy conformation (Fig. 1, structure i) were calculated using a semi-empirical method (MOPAC [25]) and are presented in Fig. 3c. Because of the molecular design with its four wheels and also its tert-butyl groups bound to the central curved chassis via sigma-bonds, the electronic states near the HOMO-LUMO gap are well separated in energy between the wheels and the tert-butyl mono-electronic states. The HOMO and LUMO of a free PAH-4W molecule are mainly the chassis MO characterized by extended central  molecular orbitals on the chassis. According also to those calculations, the next set of PAH-4W MO and after the chassis ones, can be attributed to the wheels  MOs.

Following the experimental recorded dI/dV maps, the reverse is observed on the surface for the ground state tunnelling resonance (and below) i.e. the Fig. 3b dI/dV maps recorded at the -1.65 V and -2.15 V electronic resonances are showing a large four wheels MO contribution to the tunnel differential conductance as compared to the chassis. As expected, the first tunnelling resonance above E f (LUMO) is still located on the chassis. For the ground state resonance (HOMO), this reversal between the dI/dV resonances (identified using the dI/dV maps) and the Fig. 3c MO electron probability density maps is coming from the PAH-4W molecule conformation on the Au(111) surface with its chassis to surface distance certainly much larger than the triptycene wheel low phenyls distance to the surface. As a consequence, the wheels electronic states contributing to the PAH-4W electronic states move up in energy towards the ,chassis electronic state energy position because of their electronic interaction with the Au(111) surface. This was already observed on a molecule with a central axle terminated by a triptycene wheel at each extremity [18]. As a result, the first resonance recorded at -1.65 V can be attributed to electronic contributions coming both from the chassis and wheels electronic states lying after molecular adsorption in the same energy window. Furthermore, since the height of the chassis relative to the surface is certainly much larger than the triptycene wheel down phenyls distance to this surface (See Fig. 7), the wheels electronic states are contributing more than the chassis ones to the dI/dV map recorded at -1.65 V. The resonance observed at V = -2.15 V also originates from the wheels, as confirmed by ESQC calculated constant current STM image. This dI/dV interpretation indicates that the stable conformation of a PAH-4W molecule on Au(111) brings the four wheels down and the four tert-butyl chemical groups up relative to the surface because of the same STM contrast of those tert-butyl groups (See the Fig. 3a ESQC calculated image for the surface conformation with the wheels down and the tert-butyl groups up as in Fig. 7a). This will be discussed further below. More important is also the fact that the resonances at -1.65 V and -2.15 V are mainly located on the wheels. On the PAH-4W molecular skeleton, it indicates the locations where to pulse the bias voltage to bring some inelastic energy inside the molecule for a possible step by step STM manipulation along the surface without any mechanical contact of the PAH-4W molecule with the tip apex.

3) Single molecule manipulations

Two modes of STM single molecule manipulation were explored, first by pulsing the STM bias voltage for a few seconds at a specific location on the PAH-4W molecule and second by pushing this molecule using the tip apex.

3.1) Voltage pulsing mode

For the pulsing mode, the tip apex was positioned on a wheel and the bias voltage pulsed down to -2.0 V and up to +3.2 V. A -2.0 V pulse was high enough to access the first oxidation state of a wheel (See Fig. 3). In contrast, with a +3.2 V, the wheels first virtual reduced states are very difficult to reach since pulsing with a bias voltage just above +3.2 V led the targeted wheel to break and detach from the chassis.

Incidentally and among the different conformations of the PAH-4W molecule identified in Fig. 1, conformer (ii) was also observed from time to time on the surface. Figure 4 is presenting an example of such a conformer where the bottom-left tert-butyl is up according to Fig. 1(ii). But on the surface this bottom-left wheel will remain almost at the same height as compared to the three others due to the interaction with the surface. This PAH-4W conformation can be considered at first as a good candidate for monitoring the response of a wheel to the voltage pulse. When the bias voltage is applied with the tip apex positioned on the edge of this upwheel, it starts to fluctuate randomly in orientation relative to its rotation axle as observed in the current intensity time dependent signal presented in Figure 4(b). The current intensity is switching between 10 pA and 85 pA, corresponding alternatively and randomly to two molecular conformations of the triptycene wheel: respectively one phenyl pointing down towards the surface and one phenyl pointing up towards the tip apex. This indicates that a curved chassis can lead to an up-wheel conformation according to Fig. 1(ii). Furthermore, the switching from a down (Fig. 1 i) to an up-wheel (Fig. 1 ii) conformation requires to pass over a large energy barrier in the PAH-4W electronic ground state. Unfortunately, it cannot be performed on the wheels sitting down corresponding to the main PAH-4W conformation on the surface (Figure 7a). This comes from the fact that the consequent vibrational energy increase will mainly remain on the chassis. Here, the corresponding Fig. 3b dI/dV maps are indicating four very local conductance maxima at the centre of the chassis with no extension towards the wheels. This indicates that contrary to what was observed in the case of a chassis equipped with four switchable legs [9] and even with a curved chassis, the four wheels cannot be switched at the same time away from the surface and this will be incompatible with the possible accessible conformation of the chassis (Fig. 1(iii)) even on the surface. Furthermore, we do not have identified yet the tip apex position on the chassis (or on a given wheel) to trigger the corresponding two up-wheel chassis conformation change in the PAH-4W excited states accessible by a bias voltage pulse.

3.2) Mechanical manipulation mode

For the pushing mode and in a now standard mechanical molecular manipulation procedure [26], a PAH-4W molecule can be step by step manipulated on the Au(111) surface. A typical constant current manipulation signal is presented in Fig. 5 together with the tip trajectory. It was recorded during the manipulation sequence indicated also on the STM images before and after the manipulation. To record this Fig. 5 molecular manipulation signal, the molecule was initially found in its native as deposited step edge conformation and the tip apex was initially positioned on the centre of its chassis. The first 2 nm of the manipulation sequence corresponds to the detaching of the PAH-4W molecule from its step edge (Fig. 5(i)). It is generally a quite erratic sequence because the molecular mechanics of this detachment is dependent on the tip apex end atomic structure and because a step edge is not a very regular support for the molecule itself especially for a four wheels molecule. Then, from 2.0 nm to 3.4 nm and from 3.7 nm to 5.2 nm (Fig. 5, (ii) and (iv)), the constant current manipulation signal in this pushing mode is quite regular. In the Fig. 5 reported manipulation sequence, it is coming from the bottom-left wheel with respect to the direction of movement. Such types of constant current manipulation signals are resulting from the through molecule tunnel current intensity variation as a function of the detail of the mechanical deformation of the molecule during its manipulation. It had already been used to determine detailed intramolecular conformation changes in particular with a molecule equipped with four legs [27] and with a molecule equipped with two triptycene wheels [18].

The manipulation signal reported in Fig. 5 between 2.0 nm and 3.4 nm and between 3.7 nm and 5.2 nm is very similar to the one recorded in this last case when the wheels were not rotating [18]. This also indicates that after the first manipulation sequence (where the molecule had been detached from its step edge) the tip apex slides along the chassis to reach in this case the bottomleft wheel. The interruption of the regularity of the pushing mode manipulation signal between 3.4 nm and 3.7 nm is coming from the herringbone ridge. In this case, wheel after wheel, the molecule had to pass over this Au(111) surface reconstruction which is known to be quite difficult to pass over with a moderate mechanical push [28]. The oscillation period of the manipulation signal during the regular parts is about 0.28 nm i.e. close to the 0.288 nearest neighbour interatomic distance on the Au(111) surface. Notice that at the end of this Fig. 5 manipulation sequence, one of the four wheels attached to its triple bond axle was always found under the final tip position. This confirms that the largest mechanical interaction between the tip and the molecule is located in this part of the molecule and that the lateral motion of the tip during a constant current manipulation sequence leads the tip apex to reach this specific intramolecular location. Fig. 6 is presenting another example of a PAH-4W molecule manipulation sequence performed in five steps continuously and without any STM imaging during this sequence. Characteristic behaviours appear along this sequence at 3 nm and at 8 nm tip apex positions starting from the presented initial tip apex position on the chassis. At these tip locations, the manipulation signal suddenly jumps up, remains up for about 2 nm with a typical manipulation signature (see Fig. 6 inserts) and then drops down to its previous relative z tip height value. We interpret this manipulation signature as a rotation of the wheels while passing over the herringbone reconstruction as it was observed recently by pushing on a "dimer of triptycene wheels" molecule [18]. It also indicates that before the start of Fig. 6 manipulation sequence, two phenyl rings out of the three on each triptycene wheel were in interaction with the Au(111) surface. It was the minimum energy conformation of the PAH-4W molecule before the Fig. 6 sequence (see the discussion section below). The wheel axle height variation during a wheel rotation is about 220 pm (Fig. 6) and the recorded manipulation signal jump up at 3 nm and 8 nm is about 120 pm. A third jump in the manipulation signal seems to have occurred at 13 nm but has been obscured. This can be due to either a tip apex condition change or a wrong tip positioning for such a wheel rotation sequence, because of a wrong orientation of the PAH-4W molecule relative to the underneath herringbone reconstruction orientation. This results in a fast drop of the manipulation signal at the beginning of fourth manipulation step.

The PAH-4W can also be manipulated over very long distances in a pushing mode with the tip apex remaining in between the four wheels. We have succeeded in runs of about 25 nm. The difficulty in such long pushing manipulation sequences is the successive passage over a large number of herringbone reconstructions since already passing a succession of three reconstructions is delicate as presented in Fig. 6. Notice that without success, we have also tried to observe in the manipulation signal the rotation of the wheels during a passage over an Au(111) mono-atomic step in the constant current manipulation. Here, it was found difficult with a clear signature in the variation of the tunnel current to record a regular and classical mechanical motion of the PAH-4W molecule passing wheel after wheel over an Au(111) step edge 0.22 nm in height. The PAH-4W molecule is not a rigid object with rigid rotating wheels and its classical mechanical motion is difficult to define [29]. All the deformed parts of the molecule during its collision with the step edge are contributing to the tunneling current variations.

4) Discussions

On a surface, a long range single molecule nanocar run is dependent on the accessible conformations of the molecule while adsorbed on its supporting surface. Those conformations are determined by the multi-dimensional electronic ground state potential energy surface (PES) of this molecule completed for a controlled drive on this surface by the manifold topology of the low lying electronic excited states PES. The surface ground state conformations of molecule nano-vehicles equipped with lateral holders are also very dependent on the competition between the chassis and the holder's interactions with the supporting surface. The curved chassis of the PAH-4W molecule studied here was designed to master this competition as compared to a planar chassis [8]. On the supporting Au(111) surface, the PAH-4W chassis is constrained to curve up at its extremities letting the four triptycene wheels to be less interacting with the surface than in the case of a planar chassis. Experimental constant current STM images and molecular mechanics optimization on surface are confirming how the chassis effectively curves up at its two ends in its minimal energy conformation as presented in Fig 7a . As a consequence, the STM contrast delivered by the four tert-butyl end groups is smaller than the STM contrast given by the four triptycene wheels (See Fig. 3). This curved conformation is still preserving enough the interactions between the wheels and the surface for them to be able to turn while passing over the Au(111) herringbone reconstructions as observed experimentally in Fig. 6. In the other possible and stable conformation calculated for the PAH-4W molecule on the Au(111) surface, the four tert-butyl groups are down to the surface and the centre of the chassis is curved up (see Fig. 7b). In this conformation, the four triptycenes are too far away from the surface to be stabilized and will rotate freely with no interaction with this surface. The formal Fig. 7a conformation is confirmed by ESQC STM constant current image calculations performed exactly with this conformation. The latter Fig. 7b conformation was not observed on the Au(111) surface.

In the Fig. 7a minimal energy surface conformation, the activation of a lateral motion of the PAH-4W molecule using a bias voltage pulse was not observed. This activation would require to switch up the conformation of each phenyl holding the triptycene wheel axle in such a way to make free the rotation of each wheel relative to the surface, but with the wheels (and not the four tert-butyls) still holding the chassis on the surface. Such switching event was not observed.

With a positive voltage pulse larger than + 3.2 V, it was possible to break one wheel out of the chassis. The switching up of one (or more) phenyl holding a wheel imposes too much a constraint to the chassis. Furthermore, and as observed, such a conformation is not accessible energetically on the low lying excited states PES of the PAH-4W molecule adsorbed on the Au(111) surface. A bias voltage pulse applied at the center of the chassis may have been an answer to activate this switching because of the peculiar localization on the chassis of the + 2.1 V dI/dV resonance. Unfortunately, the provided energy is not large enough to trigger the simultaneous switching of the four phenyl groups holding the wheels. Even if the reactive path on the corresponding excited states PES was existing, the sequence of switching events in time for the PAH-4W molecule to move classically in one direction would have to be encoded in those potential energy surface.

5) Conclusions

A four wheels molecule nano-vehicle with a curve central molecular chassis was deposited on an Au(111) surface and imaged at low temperature using a scanning tunneling microscope. The consequent moderate interactions of those four wheels with the Au(111) surface was confirmed.

Along the molecular chassis, constant current dI/dV maps were recorded to locate the possible energy entry port for a controlled manipulation of the molecule. The switching of the phenyl holding a wheel to the chassis was not observed to trigger a lateral molecular motion by inelastic tunneling effect through the molecule when the STM tip apex is located on this phenyl. A standard STM tip mechanical manipulation of the molecule was used to confirm how the wheels can step by step rotate while passing over an Au(111) surface native herringbone reconstruction. This rotation was time-dependent recorded by following in real time the variation of the tunneling current intensity during such a manipulation. New molecules must now be designed in such a way that the sequence of wheel rotations be defined on the profile of potential energy surface of the excited states to be able to drive a molecule-vehicle by an inelastic tunneling effects starting from the ground electronic states of the molecule nano-vehicle. [27]. The central molecular chassis is in blue and the 4 triptycene molecular wheels in red (the chemical group marked with a "2"). Optimized structure i is showing how the 4 triptycene wheels are pushed down the chassis through a steric saddle shape chassis structure, with 4 wheels down and 4 tert-butyls groups up, due to deformation induced by the presence of two five-membered rings on the central part of the chassis. In the case of other optimized structure ii (or iii, not found experimentally), the deformation occurs in 3 wheels and 1 tert-butyl group (2 wheels and 2 tert-butyls groups respectively) up and 1 wheel and 3 tert-butyls groups (2 wheels and 2 tert-butyls groups) down. The experimental differential conductance (dI/dV) maps recorded at the bias voltage identified in (a) (they realize a projection of the PAH-4W electronic probability density of these molecular electronic states on a two dimensional plane). In order to determine which mono-electronic molecular states are composing the experimentally observed electronic probability density maps, molecular orbitals of the free PAH-4W are represented at the bottom row (c) and were calculated using the semi-empirical PM7-MOPAC package [27]. Notice that the electron density of not only HOMO and LUMO but also up to HOMO-7 crowds into the chassis. The first mono-electronic state located on a wheel is arising at HOMO-8. The 4 wheel states are electronically separated from each other and can be found between HOMO-8 to HOMO-11. Only one was represented in (c). Images sizes are 4 nm x 4 nm for topographic image and 5 nm x 5 nm for dI/dV maps. 3). In this conformation, the four triptycene wheels are gently deformed from 120° in the gas phase to 134° as exemplified in (a2). The curved up chassis conformation (b) detailed in (b2) was never observed experimentally. Here the 4 wheels are maintained far away from the surface by the chassis (b3). According to ASED+, the energy difference between (a) and (b) is 0.138 eV.

Figure 1 :

 1 Figure 1:The chemical skeleton (left) and three possible optimized conformations of the free PAH-4W molecule using the MOPAC package[27]. The central molecular chassis is in blue and the 4 triptycene molecular wheels in red (the chemical group marked with a "2"). Optimized structure i is showing how the 4 triptycene wheels are pushed down the chassis through a steric saddle shape chassis structure, with 4 wheels down and 4 tert-butyls groups up, due to deformation induced by the presence of two five-membered rings on the central part of the chassis. In the case of other optimized structure ii (or iii, not found experimentally), the deformation occurs in 3 wheels and 1 tert-butyl group (2 wheels and 2 tert-butyls groups respectively) up and 1 wheel and 3 tert-butyls groups (2 wheels and 2 tert-butyls groups) down.

Figure 2 :

 2 Figure 2: Typical STM images just after the molecule sublimation process. Since intact PAH-4W molecules are mainly stabilized at the step edges, the probability of finding molecules decreases inversely to the terrace width. Only one intact molecule was found in top STM image area (1 molecule per 5000 nm 2 ) by comparison with two intact molecules in bottom left image (1 molecule per 1800 nm 2 ). Bottom right image series shows a sequence of 3 lateral manipulations to detach the molecule from its initial step edge. First image of the series is corresponding to the dotted area of the large bottom left STM image. All images were taken with tunnel current I = 10 pA and bias voltage V = 200 mV. Lateral mechanical manipulation condition for the right series: I = 10-20 nA with V = 50 mV.

Figure 3 :

 3 Figure 3: (a) Typical scanning tunneling dI/dV spectra recorded at slightly different tip locations on the molecule chassis but near the wheel. The corresponding low voltage experimental image is presented also in (a) with the location of the tip during spectroscopic measurements indicated as blue and red spots (corresponding to the blue and red curves, respectively). The corresponding dI/dV ESQC calculated image is presented in (a). Three distinct peaks, one at positive as first virtual reduced state and two at negative bias voltage as first and second virtual oxidation states, are observed and identified by vertical dotted lines. (b)The experimental differential conductance (dI/dV) maps recorded at the bias voltage identified in (a) (they realize a projection of the PAH-4W electronic probability density of these molecular electronic states on a two dimensional plane). In order to determine which mono-electronic molecular states are composing the experimentally observed electronic probability density maps, molecular orbitals of the free PAH-4W are represented at the bottom row (c) and were calculated using the semi-empirical PM7-MOPAC package[27]. Notice that the electron density of not only HOMO and LUMO but also up to HOMO-7 crowds into the chassis. The first mono-electronic state located on a wheel is arising at HOMO-8. The 4 wheel states are electronically separated from each other and can be found between HOMO-8 to HOMO-11. Only one was represented in (c). Images sizes are 4 nm x 4 nm for topographic image and 5 nm x 5 nm for dI/dV maps.

Figure 4 :

 4 Figure 4: (a) An STM image of the PAH-4W having the conformation presented in Fig. 1(ii). Here the bottom-left tert-butyl group shows a relatively smaller lobe than the other three tertbutyls because it is down sideways and is related to the lift up of the neighboring bottom-left wheel. No significant difference in contrast between this wheel and the other three in the constant current image. (b) A real time recording of the tunneling current at V = 3.2 V measured for the tip located on the lifted up wheel edge indicated by the red dot in (a). The current is fluctuating between 10 pA and 85 pA because of the random oscillations of this wheel. (Constant current image (a): I = 10 pA and bias voltage V = 200 mV).

Figure 5 :

 5 Figure 5: Typical tip height variations during an STM constant current lateral mechanical molecule manipulation with tip trajectory indicated on the images before (left) and after (right) manipulation. The manipulation signal can be separated in four sequences; (sequence i, blue background) 0.0 → 2.0 nm, the molecule was pulled apart from step edge leading to the highest mechanical interaction location of the tip apex with the molecule. This is the location of the corresponding wheel shaft, on the bottom-left wheel in this case. (Sequence ii, green) 2.0 → 3.4 nm, the molecule was manipulated by normal mechanical pushing mode characterized by a 0.28 nm period signal, which coincides approximately with the nearest neighbour interatomic distance on the Au(111) surface. (Sequence iii, pink) 3.4 → 3.7 nm, the wheel is interacting with the herringbone ridge and is responsible for the main manipulation signal jump. (Sequence iv, green) 3.7 → 5.2 nm, the molecule was manipulated the same way as compared to sequence ii (Constant current images: I = 10 pA and bias voltage V = 200 mV).

Figure 6 :

 6 Figure 6: Another example of a PAH-4W mechanical molecule manipulation.Here the manipulations were performed five times in a row without any STM imaging during this manipulation sequence. The first 2 nm of the manipulation signal are essentially identical to the first example, that is, a complete PAH-4W molecule was detached from a stable adsorption site created with a broken molecule. From 2.0 nm to 24.5 nm, the molecule was pushed by the tip apex in a normal manipulation mode except five discontinuous points at 3, 5, 8, 10, and 13 nm. The first and third jumps up of the manipulation signal (at 3 and 8 nm, respectively) are the same event and are corresponding to a wheel rotation as illustrated in the left-half of the bottomleft diagram, here the wheel axis height changes during rotation. The second and fourth jumps up of this manipulation signal (at 5 and 10 nm, respectively) are also similar events as the first (third) one. In this case, the wheel rotates like with a decrease of the wheel axis height as illustrated in the second half of the diagram. The last one is obscured by either a tip apex condition change or a wrong tip positioning (Constant current images: I = 10 pA and bias voltage V = 200 mV).

Figure 7 :

 7 Figure 7: The two different PAH-4W surface main minimum energy molecular conformations (a) and (b) calculated using the ASED+ [32] semi-empirical molecular mechanics approach on the fcc Au(111) surface. The central curved down chassis conformation (a) with its characteristics up ter-butyls (a2) is the minimum energy conformation. It was used for the dI/dV constant current ESQC STM image calculation (see Fig.3). In this conformation, the four triptycene wheels are gently deformed from 120° in the gas phase to 134° as exemplified in (a2). The curved up chassis conformation (b) detailed in (b2) was never observed experimentally. Here the 4 wheels are maintained far away from the surface by the chassis (b3). According to ASED+, the energy difference between (a) and (b) is 0.138 eV.

Acknowledgements: This work was supported by the University Paul Sabatier (Toulouse, France), the Centre National de la Recherche Scientifique (CNRS), the Agence Nationale de la Recherche (ANR) (ACTION project ANR-15-CE29-0005). This work has received funding from the European Union's Horizon 2020 research and innovation program under the project MEMO, grant agreement No 766864. We also would like to thank Peugeot, Actia and Air Liquide for their kind and financial supports during this work and J. Bonvoisin for discussion about the free conformation of the PAH-4W molecule.


Claire Kammerer

Guillaume Erbland

Yohan Gisbert

Toshio Nishino

Kazuma Yasuhara

Gwénaël Rapenne
email: gwenael-rapenne@ms.naist.jp

Biomimetic and Technomimetic Single Molecular Machines

ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

Introduction

A machine (latin machina, which itself comes from the ancient Greek mekkanê, meaning: ingenious invention, device, trick) is a complex manufactured object capable of using a source of energy to perform on its own or under the guidance an operator, one or more specific tasks. Molecular machines have not been invented by mankind, they have existed for a very long time in Nature. Biological molecular machines are of formidable efficiency and are at the origin of various complex biological processes necessary for the functioning and survival of living organisms. A molecular-level machine can be defined as a molecule or an assembly of molecular components designed to perform a precise function in response to a controlled stimulus. This active field of research has been recently highlighted with the 2016 Nobel Prize of Chemistry awarded to J.-P. Sauvage, Sir J. F. Stoddart and B. L. Feringa for their seminal contributions to "the design and synthesis of molecular machines" 1 which revolutionized the way chemists think about molecular systems and their motions. Their remarkable achievements opened the door to a new dimension of chemistry with the control of motions at the molecular level, the molecular world moved from a static library to a dynamic dimension, like when cinema has been discovered after the reign of photography. Animated molecules took the place of immobile structures. Their work over the past three decades is at the origin of an incredible variety of molecular machines with a few of them described in this highlight review.

Our strategy for designing new molecular machines uses both a biomimetic 2 and a technomimetic 3 approach. Biomimetic molecules are designed by taking inspiration from Nature, where a considerable number of biochemical machineries like rotative ATP synthase 4 are used in all the living systems, to imitate (mimic) natural functions or materials. Motors and gears have been designed by using simplified structures to give access to artificial molecular motors and gears. A technomimetic molecule is a compound designed to resemble macroscopic machinery at the molecular level, also transposing the motions that these objects are able to undergo. According to this definition, technomimetic molecules can be also biomimetic but in that case, we usually define the molecule as a biomimetic entity. For instance, in the last decade, we synthesized rolling prototypes like nanowheels, 5 wheelbarrows 6 and nanocars. 7 Operating on a single molecule in charge of the machinery is the physical limit of miniaturization. On a surface, the mechanical properties of a single molecule are essentially classical so its manipulation with a scanning tunneling microscope (STM) tip is a convenient way adapted to the classical motions we are willing to control. When a statistical amount of molecular machines is studied in solution or in a crystal, it is possible to obtain a lot of information through spectroscopic or crystallographic techniques but these are the result of the average behavior of a very large assembly of molecules. To reach the reality of only one molecule, we need to address and measure the mechanical properties on a single molecule. 8 Also, the ultimate miniaturization of mechanical machines is reached when the targeted function is realized with the minimum amount of matter, i.e. a single molecule. This is what we achieved by working with a STM. The molecules described here have been designed to be adsorbed on a surface and then studied individually.

Biomimetic Machines: Molecular Motors and Gears

Synthetic molecular motors

Among the world of machines, a motor is a machine which consumes energy to produce work repetitively and progressively in a system via a unidirectional and controlled movement of one of its parts. 9 The inspiration of such motors comes both from the macroscopic world where motors are very common and from Nature with the fascinating machinery of muscles 10 for translational motors or ATP synthase 4 for rotating motors. Some very elegant examples of molecular rotary motors have already been described but they have been studied collectively and have in general many degrees of freedom. 11 There are basically three families of motors depending what kind of energy is provided to the system. As energy source, most of the motors are using a chemical energy i.e. energy coming from chemical's transformations or light and only a few are using electrons. Biomimetic or technomimetic strategies are not linked to a specific source of energy. In our research, we use the tip of the Scanning Tunneling Microscope (STM) to very locally provide electrons to the molecule we want to rotate. The molecules developed in our group have been designed with the intention to be studied individually with a STM to avoid to have only access to the average behaviour of an assembly of molecules. This implies our target molecules to be as rigid as possible in the chemical world and have minimal degrees of freedom in order to be manipulated on a surface with a maximum control on their motion.

Inspiration from Nature: ATP Synthase

Each human being consumes an average of 40 kg of adenosine triphosphate (ATP) per day, as a source of energy released by the exergonic hydrolysis of ATP mediated by various ATPase enzymes to give adenosine diphosphate (ADP) and phosphate (Pi). Synthesis of ATP and thus storage of energy takes place according to the reverse reaction, i.e. phosphorylation of ADP. The biological machinery where this process occurs is ATP synthase, 4 an enzyme present in the cell membrane (Figure 1). The source of energy is the trans-membrane proton concentration gradient, that is transformed into chemical energy in the additional phosphate bond.

As shown on Figure 1, ATP synthase is constituted of two parts: the first one, called F1, is in the extracellular medium whereas the second, called F0, is incorporated in the membrane. F0 is composed of a stator (a and b units) and of a mobile part, the rotor, constituted of 10 to 12 proteic subunits (c) depending on the cells. In the presence of a trans-membrane proton concentration gradient, a flow of protons occurs at the interface between a and c domains through the successive protonation -rotationdeprotonation of c subunits. Indeed, when a proton is fixed on a negatively charged amino acid of subunit c, this subunit is neutralized and moves away from the positively charged subunit a towards the membrane due to its less polar environment. Repetition of this process with all the c subunits leads away the whole rotor, and deprotonation of c subunits occurs after a complete turn, with the liberation of protons in the other compartment. The rotor which is a proton-fueled turbine, extends into an axle () in the F1 part, and the movement of this axle induces a conformational change of the three  subunits, thereby triggering the synthesis of ATP.

It is important to note that the structure of ATP synthase, and in particular of the a and c units, imposes a unidirectional motion of the rotor. Interestingly, the reverse reaction, i.e. the hydrolysis of ATP to ADP, can also be mediated by the same enzyme with a rotation in the opposite direction, leading to pumping of protons against the electrochemical gradient. Inspired by this high-performance natural device, chemists challenged themselves to reach the same result on a smaller scale. Indeed, this biomachine is constituted of different biological macromolecules with a total size of 10 nm in diameter and about 25 nm in length (> 500 000 Daltons) which is much larger than the usual molecular size. In our group, we designed 12 a molecular motor about one order of magnitude smaller in each dimension and 300 times lighter with a molar mass of 1882 g.mol -1 .

As exemplified by ATP synthase, a key parameter for the possible recovery of useful work is the organization of the assembly of motors. The efficiency of this enzyme is for instance directly related to its trans-membrane location, since compartmentalization is a prerequisite for the creation of an electrochemical gradient. In this context, our goal was to study surface-mounted artificial motors, so as to obtain an identical orientation within the assembly of motors as opposed to machines studied in solution. All the artificial rotary molecular motors designed and synthesized in our group are thus composed of an azimuthal rotor, parallel to the surface, and of a stator specifically functionalized to provide tight anchoring on surface. Both rotor and stator, featuring rigid scaffolds, are coordinated to a central metal atom which acts as a rotation axle. After synthesis and deposition on surface, such ruthenium-and europium-based motors were submitted to a suitably oriented electrical field with the STM to induce rotary motion.

An organometallic piano-stool molecular motor

The first family of motors reported by our group was directly inspired by the motion of the rotor subunit in ATP synthase, triggered by coulombic interactions with its environment. Indeed, the motor was designed to be tightly anchored on a surface via its stator subunit, and to be located between two nanoelectrodes (i.e. in a nanojunction). 13 The top C5-symmetrical rotating subunit comprised a central core surrounded by five rigid arms, each terminated by an electroactive ferrocene group (Fc) selected for its stability at the +II and +III oxidation states and the full reversibility of the related redox processes. As depicted in Figure 2, oxidation of the ferrocene unit located near the anode would release a positively charged ferrocenium, which would subsequently be repelled by coulombic interaction and driven away towards the cathode. This motion would bring the next ferrocene group close to the anode for an oxidative process, while the ferrocenium group would approach the cathode and be reduced to regenerate a neutral ferrocene. As a result, the successive oxidation-reduction cycles would drive the rotation, and electrical energy would be converted into a rotary motion. However, it is important to note that unidirectional motion can only be achieved in this system provided the two possible paths from anode to cathode are different, i.e. if this horizontal setup is dissymmetric. This condition would for instance be reached by placing the motor dissymmetrically between the two electrodes.

Figure 2. Electrochemical actuation of the motor between two electrodes.

From a structural point of view, motors belonging to this family are all based on organometallic pianostool ruthenium(II) complexes. 13 The C5-symmetrical rotor subunit is a penta(aryl)cyclopentadienyl ligand, carrying rigid arms terminated by ferrocene groups. As stator, a rigid hydrotris(indazolyl)borate ligand was selected for its ability to lift up the ruthenium center (and thus the rotor) from the surface via the location of nitrogen coordinating sites. 14 On the opposite side, this tripodal ligand was equipped with three functional groups allowing strong adsorption on surface, thereby preventing translation, rotation and rocking motions of the stator during scanning probe microscopy studies.

A family of molecular motors was synthesized according to this design, with esters as anchoring groups 15 compatible with the insulating oxide surfaces used as a support for nanoelectrodes (Figure 3). 16 Keeping the ferrocene terminal groups, the internal structure of the arms was in particular varied, with the introduction of organic 16b and organometallic 16a insulating spacers to prevent undesired intramolecular electron transfers. Unfortunately, in spite of the impressive technological advances in the field of surface physics, addressing such a single-molecule motor within a nanojunction composed of nanoelectrodes is still impossible nowadays, due to the size difference between the smallest nanoelectrodes and the molecular motor. The distance between the two electrodes could be as small as 45 nm, but the height of such nanojunction would be one order of magnitude higher than the molecule possibly leading to direct electron transfers between electrodes without crossing the molecular motor.

+ + _

In the meantime, it was envisioned as an alternative strategy to place the molecular motor in a vertical setup, with the tip of the STM acting as a localized atomic-scale electrode and the metallic conductive surface being considered as an infinite electrode. In such setup, the STM tip is used as a source of electrical energy but also to monitor the rotary motion of the motor. Since the scanning tunneling microscopy is not a time-resolved technique, a possible movement can only be evidenced by comparison of the images obtained before and after triggering the rotation. It thus appeared necessary to lower the symmetry of the upper rotating part, not only as a probe for rotation on STM images but also to achieve unidirectional rotation. 17 Theoretical studies were undertaken to compare the ground-state potential energy profile of similar ruthenium-based motors carrying symmetric and dissymmetric rotors and assess their ability to undergo unidirectional rotation. 18 As depicted on Figure 4, in the dissymmetric structure, one ferrocene group was substituted with a methyl group, to afford one sterically and electronically different arm. Since a conductive surface is necessary for STM studies, the ester anchoring groups located on the stator were replaced with thioether groups, particularly suitable for coinage metals.

The ground-state potential energy profile of each prototype adsorbed on Au(111) was calculated (semiempirical ASED+ and DFT) methods as a function of the rotation angle of the rotor subunit. For the symmetric motor (Figure 4, bottom), the potential energy profile features 15 wells, in good agreement with the combined C5 and C3 respective symmetries of the rotor and stator. The saw-tooth shape of the curve is related to interactions between the phenylene groups in the rotor's arms and the indazole rings of the stator. However, this feature is not sufficient to achieve unidirectional motion as the height of the activation barrier remains constant (0.25 eV). In the case of the dissymmetric motor (Figure 4, top), 15 local minima are present and an additional periodicity of 120° is now observed as a result of the introduction of one truncated arm. The saw-tooth profile is in this case characterized by variable rotation barriers in the 0.22-0.35 eV range, implying that one direction of rotation is favored at each local minimum. According to these theoretical studies in the ground state, dissymmetrization of the structure of the rotor may lead to unidirectional rotation and this interesting candidate was thus synthesized 12,[START_REF] Erbland | For an optimized synthesis of the tripodal ligand[END_REF] and deposited on a Au(111) surface. STM imaging of single molecules at 77 K indicated that this motor (Figure 4, top) exhibit non-directional free rotation at that temperature due to Brownian motion. When the temperature is lowered to 5 K, rotation stops as can be seen by the dissymmetric shape of the rotor on the STM image. 18 At that temperature, it was shown that a voltage pulse applied with the STM tip on one of the arms of the motionless rotor triggers its rotation, and successive excitations on the same arm lead to stepwise unidirectional rotary motion. More interestingly, we demonstrated that the clockwise or counter-clockwise direction of rotation is directly controlled by the nature of the arm excited by the STM tip and can be inverted at will (Figure 5).

We thus developed the first reversible electron-fueled molecular motor, based on an organometallic piano-stool ruthenium complex. It is important to mention here that, contrary to the initial concept, electron transfers in this vertical setup are too fast for any redox process to occur in the electroactive groups. Rotation of the molecular motor is triggered by inelastic electron energy transfer through lowlying excited states, with a directionality imposed by the shape of the potential energy profile in these excited states. Studies are currently underway to estimate the motive power of this molecular motor.

A double-decker europium molecular motor

Another type of azimuthal molecular motor was next targeted, with the aim of obtaining a controllable self-assembled monolayer to be studied as a collective assembly on surface.

An heteroleptic europium(III) double-decker complex was designed, incorporating a naphthalocyanine stator and a porphyrin rotor (Figure 6, left). The naphthalocyanine stator was functionalized with eight thioether anchoring groups, bearing long alkyl chains to tune the distance between motors within the self-assembly. The porphyrin stator was functionalized on opposite meso positions with donor butoxyphenyl and acceptor cyanophenyl groups, respectively. The upper rotating subunit was thus dissymmetric, with a donor-acceptor character highlighted by a permanent electric dipole moment of 8 D. The target compound was synthesized 20 and deposited by sublimation on Au(111). At 5 K, it was observed by STM that the individual rotors undergo free random rotation, which can be accounted for by very low rotation barriers in such double-decker complexes. Alternatively, deposition on Cu(111) afforded highly ordered self-assembled two-dimensional domains exhibiting hexagonal symmetry (Figure 7). 21 Strikingly, at 80 K, the motors within this network are motionless at low bias voltage, also revealing a parallel alignment of the electric dipoles thereby suggesting the existence of intermolecular interactions (Figure 6, center). At higher voltage, all the motors are rotating (Figure 6, right) and a deeper analysis revealed that there exists a voltage for which a synchronized switch of a large domain of rotors can occurs around a bias voltage of 1.2 V. This simultaneous collective switching when applying an electric field from the tip of a STM is triggered by dipolar interactions within the hexagonal ferroelectric network of molecular rotors, thereby highlighting intermolecular communication between single molecules of the network. We thus achieved the controlled and synchronized rotation of single dipolar molecular motors within a self-assembled monolayer, which opens the ways to the operation of assemblies of molecular machines packed on surface using an electrical stimulus.

Following our work in the field of molecular motors, for which an electrical stimulus induced the controlled rotation of single molecules, we next aimed at exploiting the work provided by such motors, in particular via a transfer of the rotary motion to neighbouring molecules. This implies first to get a deeper understanding of the mechanical transmission of motion at the molecular scale which we envisioned to study on surface trains of molecular gears mechanically actuated by the tip of a STM.

Synthetic molecular gears

Gears have long been considered as a human invention, with the oldest known machine involving gearing mechanisms being the Antikythera machine which dates back to the Hellenistic period. However, gearing patterns are found in the animal kingdom and functional micrometric gears were unexpectedly discovered recently in the insect's world. 22

Natural micrometric gears in the insect's world

Burrows and Sutton studied the nymphs of the planthopper Issus coleoptratus, belonging to a class of insects known for their impressive jumps induced by fast and powerful movements of their hind legs. These authors disclosed in 2013 that a curved strip of 10-12 gear teeth is incorporated in the exoskeleton of these insects' legs, each tooth being 9 µm thick and 15-30 µm wide as observed by Scanning Electron Microscopy (Figure 8). 22 By means of high-speed video, the study revealed that both cogwheels are engaged to each other during the preparation of the jump and the propulsion, which allows a synchronous movement of the legs on a µs scale. Indeed, both legs are mechanically coupled via this gearing mechanism, which leads to higher synchronization of their movement as compared to simple neural excitation. Interestingly, the teeth are dissymmetric, thereby having only one direction of powered rotation.

Figure 8. The nymph of the planthopper Issus coleoptratus (left) and a Scanning Electron Microscopy image of the intricated micrometric gears located on the hind legs (right). From Ref 22. Adapted with permission from AAAS.

Design of nanometric gears to be studied on-surface as single molecules

As early as in 1980, Mislow [START_REF] Hounshell | Proc. Natl. Acad. Sci[END_REF] and Iwamura [START_REF] Kawada | [END_REF] independently reported the first examples of molecular bevel gears studied in solution and featuring intricated triptycene moieties. In 2012 Siegel et al. synthesized the first molecular spur gears after careful molecular design and DFT studies to optimize the inter-axle distance, highlighting the importance of this parameter in molecular gearing mechanisms. 25 Very recently, Shionoya et al. reported a Pt(II)-centered molecular gear, wherein the two azaphosphatriptycene cogwheels are very elegantly disengaged or engaged via photo-or thermallyinduced cis-trans isomerization, respectively. 26 In contrast with molecular gears studied in solution, solely allowing intramolecular processes, intermolecular gearing becomes possible on a supporting surface, used to maintain the relative orientation of rotation axles and the distance between the cogwheels. To the best of our knowledge, intermolecular gearing on surface was demonstrated for the first time in 2007 by Moresco et al. in a rack and pinion device. 27 Indeed, when a single star-shaped molecule of penta(p-tert-butylphenyl)-(p-tertbutylpyrimido)benzene was moved laterally via STM manipulation along the edge of an island of the same molecules on Cu(111), rotation of the single molecule was evidenced on successive STM images by following the relative position of the N-tagged arm. Further studies at the single molecule scale on Au(111) revealed that it is possible to achieve a stepwise rotation of such star-shaped molecule when mounted on an atomic scale axis. 28 Unfortunately all attempts to transfer the rotary motion to a neighbouring molecule proved unsuccessful, since diffusion of the molecules precluded the desired motion. This seminal work thus underlines the importance of identifying appropriate rotation axles for intermolecular gearing to take place on surface. In this context, one of the strategies relies on a metalloorganic rotation axle, in which the ligand provides tight anchoring on the surface through specific functional groups, and the metal ion acts as a ball bearing. It thus appeared that the architecture of the previously-reported ruthenium-based motor would be particularly suitable, especially as it was observed during STM experiments that lateral manipulation of such single ruthenium complexes is possible at 77 K when molecular diffusion is frozen at 5 K. This would thus allow the construction of trains of gears of various lengths at 77 K, with finely tuned inter-axle distances, and subsequent cooling to 5 K would maintain the spatial arrangement of molecules during gearing experiments.

In these experiments, the STM tip is used as a source of mechanical energy to induce the rotary motion of the first cogwheel by pushing on one of the teeth (Figure 9). If the gearing mechanism occurs, the propagation of the rotary motion through the alignment of molecules will then be evidenced by comparing the STM images of the initial and final states, meaning that in our initial design one of the teeth has to be chemically or sterically tagged.

Molecular gears with 1D and 2D paddles

Some of the specifications for an intermolecular transfer of rotary motion at the molecular scale are still open questions. Indeed, it is obvious that the presence of a rotation axle, the inter-axle distance and the teeth interlocking are major parameters, but the influence of the nature and structure of the teeth is still difficult to anticipate.

A first star-shaped ruthenium complex involving four biphenyl teeth and one chemically-tagged phenylpyridine tooth was thus designed (Figure 10, left). Unfortunately, theoretical studies carried out on two such interacting molecular gears showed that a vertical deformation of the teeth due to their relative flexibility can lead to gear slippage, thus preventing any gearing mechanism.

In order to disfavor gear slippage, it is now envisioned to increase the size of the teeth, moving from 1D-biphenyl teeth to larger 2D teeth, such as pyrene-derived units. Due to steric hindrance, these flat paddles would lie perpendicular to the central cyclopentadienyl ring and even if vertical deformation occurs, the contact surface between two contiguous paddles should be sufficient to propagate the rotary motion. The synthesis of this new generation of molecular gears carrying 2D-paddles is currently underway.

Technomimetic Machines: Wheels, Wheelbarrows and Nanocars

Controlled rotational motions are very important not only for molecular motors but also more generally for technomimetic-like molecule such as weels or more complex nanovehicles like a two-wheels nanowheelbarrow or four-wheels nanocars. Nanovehicles are molecular machines basically composed of a chassis and wheels, 29 typically one or two for a barrow, 30 four for a nanocar 31 or more for nanotrucks and nanotrains. 32 In order to build such nanovehicles, the choice of the wheel is a very important parameter. It must allow the entire functionalized molecule to move easily on the surface by its rolling motion. As pioneers in the field, we proposed triptycenes 33 to act as rolling elements and synthesized the first nanovehicle 30 while two years later Tour's group reported a family of nanovehicles 34 using [60]fullerenes wheels. Let us start with an axle terminated with two wheels.

A dimer of triptycenyl wheel

Triptycene [START_REF]Iptycenes chemistry from synthesis to applications[END_REF] is a very attractive building block since its symmetry and rigidity allow it to be exploited on surfaces. Several examples of molecular devices have been reported where the key fragment is based on triptycene, such as molecular gears, 36,25 motors, 11a gyroscopes 37 and brakes. 38 Our prototype of a wheel dimer is the bisethynyltriptycene presented Figure 11. Its deposition on a Cu(110) surface has been achieved very cleanly by sublimation under high vacuum. On the image obtained, each bright lobe corresponds to one triptycene and therefore, a pair of lobes constitutes the image of a dimer as confirmed by calculations. 39 No fragmentation or decomposition has been observed confirming their interest as STM-compatible fragments. Molecules were deposited and studied at 5K under ultra-high vacuum. Unidirectional rotation of the wheel by inducing the translation of the molecule with a step-by-step rotation of the wheels upon pushing with the STM tip was demonstrated for the first time. The tip was moved across the molecular axle at constant height, while the tunneling current was recorded at the same time. The motion has been understood thanks to the study of the tunneling current recorded at constant tip height during the motion. In the case of rolling motion, a "hat-shaped" signal appears while sliding of the molecule on the surface induced a periodic electric current directly linked with the periodicity of the surface. Typically, one wheel is left in its initial position while the other one rotates and in a few cases the rolling of both wheels has been observed. This behavior seems to very be highly dependent of the precise shape of the tip.

Even though rotation is the preferential motion in the macroscopic world, rolling of a wheel at the nanoscale has been more difficult to obtain. Behind the molecule selected to act as a wheel, the choice of the surface is very important. For instance Cu(100) is too flat. A more corrugated surface such as Cu( 110) is essential to allow the rolling of a wheel because according to DFT calculations, the angle of two phenyl rings of the triptycene is not 120° anymore like calculated for the molecule without Cu surface, but 140° to maximize their interactions with the metallic surface. The characteristic mechanisms of hopping and rolling motions are reflected in different molecular displacements.

This was the first direct proof of the rolling motion of a wheel which encouraged us to develop more complex nanovehicles with two or four wheels. Extension of this work on silicon-based surfaces has also shown some very interesting motions with a good mobility and the control of the directionality 40 at the nanoscale at room temperature which is very important for practical applications of molecular machines. 41

A molecular wheelbarrow

When we started in the field, recent advances in the imaging and manipulation of single molecules with LT-STM stimulated us to synthesize technomimetic nanoscale molecular objects exhibiting unique mechanical properties like this molecular wheelbarrow. 6 In the case of a macroscopic wheelbarrow, pushing the wheelbarrow results in the translation of the molecule with simultaneous rotation of the wheel. Our molecular analog has been design to achieve such motion at the molecular scale. Its skeleton is made of a Polycyclic Aromatic Hydrocarbons (PAHs) which, due to its rigidity, can be easily manipulated by the STM tip. In addition they can provide us with a potential cargo zone able to transport atoms or small molecules on surfaces. They are also relatively resistant to the deposition techniques which are basically based on sublimation of the molecule upon heating.

The wheelbarrow is constituted of two legs and two wheels connected to a polycyclic aromatic hydrocarbon platform (Figure 12). The two legs (in green) are 3,5-di-tert-butylphenyl groups which have been been shown to have the phenyl groups nearly perpendicular to the main aromatic board.

Moreover, the tert-butyl groups connected to the PAHs are used to increase organic solubility and are easily observed by STM techniques, inducing a good contrast in the image. The two 4-tert-butylphenyl groups were selected to play the role of handles (in blue) for subsequent manipulation with the tip of the microscope. The second axle is equipped with two 9-triptycenyl groups acting as wheels (in red). Figure 12 shows one of the possible conformations of the molecule obtained by semi-empirical calculation and the two three-cogged wheels which can freely rotate along the axle due to the acetylenic spacers. Standard sublimation techniques usually used to depose molecules in the STM did not give any positive results due to the large weight of the molecule (1802 g.mol -1 ). In particular, the presence of the triple bonds tends to induce decomposition at the required high temperature, yielding some rearrangement reactions on the surface. 43 Using some fast heating techniques, we successfully imaged a few intact molecular wheelbarrows on a Cu(100) surface as shown in Figure 13 and identified by comparison with calculated images. 44 Manipulation at 5K resulted in a change of conformation of the molecule which confirmed the molecularity of the observed object but unfortunately, lateral motion of the wheelbarrow was not achieved. This was explained by a very strong interaction between the molecule and the metallic surface of copper mainly due to the large aromatic planar structure which can interact with the surface.

To obtain more mobile molecules, we decided to extend our studies to four-wheel molecules, which we named nanocars.

A planar four-wheel nanovehicle

The polyaromatic fragment used as chassis in the molecular wheelbarrow was too short to sterically accommodate four wheels. Therefore, we have developed the synthesis of a larger chassis based on a perylene unit (in blue). 7 As shown on Figure 14, the extended perylene polyaromatic contain eight tert-butyl groups to enhance the solubility of this system and again the four triptycenyl wheels (in red) were connected along the two axles thanks to the ethynyl spacers which ensure a very low rotation barrier. 42 This nanovehicle has been deposited on Au(111), however, due to its planarity and the resulting high interaction of the polyaromatic chassis with the surface, it has been very difficult to move it. 45 Only a few non-reproducible movements have been obtained by pushing with the tip of the STM (5K, under UHV conditions).

To increase the mobility of such large molecule, we designed a similar nanocar build around a curved chassis which would have a lower interaction with the surface.

A curved four-wheel nanovehicle

To decrease the interaction of the molecule with the surface, our strategy has been to use a highly curved polyaromatic chassis. During the synthesis of the planar nanocar, it appeared that if we decreased the number of tert-butyl groups on the precursor from two at the meta positions to one at the para position, dimerization of the half-chassis following the Scholl-type oxidative coupling gave an overcyclized perylene platform bearing a fragment of hexa-peri-hexabenzocoronene (in blue) on each extremity of the molecule. This was due to a smaller steric allowing different phenyl rings to be co-planar during the reaction, which was not the case with the former precursor having eight tert-butyl groups. 7 As shown on Figure 15 (center), the overcyclized chassis has a curved shape according to a geometric optimization of this second generation nanocar. Like in fullerene derivatives, this geometry can be explained by the presence of alternating five and six-membered rings in the polycyclic aromatic hydrocarbon platform. As expected, the curved nanocar bearing only four tert-butyl groups is much less soluble than the planar one which explains the lower yield and difficulties to achieve the two last steps with satisfying yields. Also, the spectroscopic properties are very different, the planar nanocar is pink while the curved one is dark green.

STM study of this molecule gave a very clear image compared to the planar one with a very high contrast for the four triptycene wheels. 46 This is due to a smaller interaction of the curved polyaromatic chassis and this molecule has indeed shown a much higher mobility on the Au(111) surface under the pushing or pulling, leading to its selection for the first nanocar race. 47

Participation to the first nanocar race

Due to its green colour, we named our curved nanocar "the green buggy". The last week-end of April 2017, six teams from three continents competed in Toulouse with their racers. Three nanocars from Austria, France and the USA were technomimetic, incorporating wheels, and the three other models from Germany, Japan and Switzerland were not, since they did not use wheels. 48 It must be noted that there is no need at the nanoscale to have technomimetic-based nanocars with wheels as a prerequisite for mobility. For instance, the very elegant japanese nanocar similar to a butterfly 49 or the winner of the race, the swiss dragster, 50 both lacked wheels fragments. According to the published rules, the common surface used was Au(111) with a track of 100 nm long including two turns.

The french nanocar has the advantage of being very robust. After deposition by sublimation, it has been identified on the surface. As shown in Figure 16, the triptycene wheels appear as very bright spots compared to the central polyaromatic core.

To move it directionally we explored two strategies. First, we tried to find a way for an electronic excitation to induce the movement but we failed. Since direct pushing with the STM tip was forbidden by rule, an alternative strategy has been to pull the molecule which allowed us to cover an impressive distance of 25 nm in a few seconds. Unfortunately, the jury refused to homologate our pulling strategy and we were disqualified from the race, remembering the moto from Pierre de Coubertin, the creator of the modern Olympic games, which emphasizes that "the importance is to participate". Anyway, we have been very satisfied to receive the "prize of elegance" thanks to the very smart STM images obtained for our nanocar. In Spring 2021, a second Nanocar race will take place with thirteen competitors already registered beyond them a franco-japanese team composed of the authors of this highlight review. We designed a new dipolar nanocar and its synthesis is underway in NAIST (Japan) before to have its mobility and driving ability tested on a Au(111) surface in CEMES (France).

Conclusion and perspectives

Biomimetic and technomimetic strategies are complementary and they both gave rise to various nanomachines with controlled molecular motions. Unfortunately the extremely low operating temperature, typically 5 K, prevents any kind of practical applications and our strategy is now to operate at higher temperature. In the case of molecular motors, from our ruthenium complex to the europium double decker we already moved from 5 to 80 K with some interesting synchronized and collective motions.

Although some progress has been made, it is still a long way to practical applications but there is already a lot to learn from the behaviour of single molecules. For instance, transporting in a controlled way atoms or molecules on a surface is a challenging topic for matter transport at the nanoscale. For that last purpose our nanovehicles are of great interest since they provide an appropriate shape to act as an efficient cargo zone.

Figure 1 .

 1 Figure 1. ATP synthase incorporated in a membrane, with a trans-membrane proton concentration gradient leading to the synthesis of ATP.

Figure 3 .

 3 Figure 3. Molecular motors bearing five ferrocene terminal groups. Molecules in the center and in the right include bicyclooctane and platinum spacers (in grey) to insulate the extremity of the arms to minimize intramolecular electron transfers.

Figure 4 .

 4 Figure 4. Effect of desymmetrization on the shape of the ground state potential energy curve during the rotation along the Ru-Cp axle.

Figure 5 .

 5 Figure 5. CPK representation of the motor undergoing unidirectional rotation, depending on the position of the STM tip. a) tip above a ferrocene group inducing a counterclockwise rotation. b) tip above the tolyl group inducing a clockwise rotation.

Figure 6 .

 6 Figure 6. Double-decker molecular motor based on a europium(III) complex with its schematic representation used in Fig. 7 (left) and STM images at low voltage (center, -0.55 V, 0.2 nA, the molecules are not rotating and appear as rod) and high voltage (right, 1.6 V, 0.2 nA, the molecule are all rotating).

Figure 7 .

 7 Figure 7. Synchronized switch at a bias voltage of 1.2 V. Images and respective schematic representations before (a) and after (b) the application of an electric field induced by the STM tip (position of the tip shown by a yellow circle).

Figure 9 .

 9 Figure 9. Principle of the motion transmission through a molecular gear train actuated by a STM tip.

Figure 10 .

 10 Figure 10. Evolution of ruthenium-based molecular gears: from 1D arms (1 st generation) to 2D paddles (2 nd generation).

39

 39

Figure 11 .

 11 Figure 11. Chemical structure of a dimer of wheels and its motion under the pushing of a STM tip. (1) the tip approaches the molecule, (2) the tip induces the 120° rotation of one triptycene wheel and (3) the tip continues its motion.

42

 42

Figure 12 .

 12 Figure 12. CPK model showing the minimum energy conformation of the molecular wheelbarrow (left), chemical structure (center) and its macroscopic analog (right).

Figure 13 .

 13 Figure 13. The molecular conformation obtained by interacting the molecule on the surface (left), the corresponding calculated image using ESQC (center) and the experimental STM image of the molecular wheelbarrow on Cu(100) (right) at 5K under UHV conditions.

Figure 14 .

 14 Figure 14. Chemical structure of the nanocar (left), its CPK model showing its planar conformation (center) and two STM image showing the pushing of the molecule on a Au(111) surface.

Figure 15 .

 15 Figure 15. Chemical structure of the nanocar (left), CPK model of the chassis before the connection of the four wheels showing its highly curved conformation (center) and two STM image showing the pushing of the molecule on a Au(111) surface.

Figure 16 .

 16 Figure 16. The french team (G. Rapenne, C. Kammerer and C. Durand) with their official dark green t-shirt received the "prize of elegance" from the jury. In the flask the powder of the '"green buggy" and its STM image superimposed with the chemical structure. The four luminous spots fit perfectly with the position of the four wheels.

Acknowledgements

This work was supported by the University Paul Sabatier (Toulouse, France) and the Centre National de la Recherche Scientifique (CNRS). It has received funding from the Agence Nationale de la Recherche (ANR) (ACTION project ANR-15-CE29-0005) and from the European Union's Horizon 2020 research and innovation programme under the project MEMO, grant agreement No 766864. This research was also partly supported by the JSPS KAKENHI Grant in aid for Scientific Research on Innovative Areas "Molecular Engine (No.8006)" 18H05419. We are also grateful to the researchers who participated in all the work discussed here and whose names appear in the references, and in particular the talented PhD and Post-doctoral students who achieved the synthesis of these systems: Alexandre Carella, Guillaume Vives, Henri-Pierre Jacquot de Rouville, Roman Stefak, Romain Garbage, Agnès Sirven and Dr. Gorka Jimenez-Bueno, as well as Dr. Francesca Moresco, Dr. Leonhard Grill, Dr Sébastien Gauthier, Dr Corentin Durand and Prof. Saw-Waï Hla for STM studies, and Dr. Christian Joachim, Jorge Echeveria-Lopez and Dr. Xavier Bouju for theoretical calculations. Dr Colin Martin is also warmly acknowledged for his careful reading and improving of our manuscript.


Yohan Gisbert

Seifallah Abid

Gaëlle Bertrand

Nathalie Saffon-Merceron

Claire Kammerer

Gwénaël Rapenne
email: rapenne@cemes.fr

Modular synthesis of pentaarylcyclopentadienyl Ru-based molecular machines via sequential Pd-catalysed cross couplings

A dissymmetric piano-stool ruthenium(II) complex bearing different halogens on the rotor part was efficiently prepared and subsequently used as key building block in the modular synthesis of rotative molecular machines via palladium-catalysed "Sonogashira/Suzuki-Miyaura" sequences. Applying this novel synthetic route to various cross-coupling partners, prototypes of molecular winches and gears specifically designed for studies at the single-molecule scale were efficiently obtained.

Technomimetic molecules 1 are compounds designed to resemble macroscopic machinery at the molecular level, also transposing the motions that these objects are able to undergo. Among them, rotative molecular machines including motors have attracted a lot of attention 2 but only a few have efficiently been used to produce a work 3 or have been studied at the single molecular scale level. 4 In this context, we designed and synthesised a family of molecular motors based on ruthenium(II) halfsandwich complexes, bearing a pentaarylcyclopentadienyl ligand as rotor and a hydrotris(indazolyl)borate ligand as stator. 5 On-surface studies by Scanning Tunneling Microscopy (STM) highlighted the prime importance of structural dissymmetry in the rotating subunit, as a source of directionality 6 and as a tag to monitor the induced motion. 7 Indeed, the ruthenium complex incorporating four identical p-ferrocenylphenyl substituents and one different tolyl group on the cyclopentadienyl ligand was shown to undergo unidirectional and reversible motion when fuelled with electrons. 6 Following this result, our current work aims at the determination and exploitation of the motive power of such a motor. A structurally analogous molecular winch was thus designed by extending the truncated arm with an amide-based linker and a long polyethylene glycol (PEG-24) chain in view of single-molecule atomic force microscopy (AFM)-based force spectroscopy measurements (Fig. 1, right). 8 Additionally, a preliminary synthetic study towards molecular gears was recently performed, yielding ruthenium complexes with five identical 1D or 2D fragments surrounding the pentaphenylcyclopentadienyl core via five-fold Suzuki-Miyaura or Sonogashira cross-couplings. 9 The resulting prototypes all involve C5-symmetric cogwheels, which will presumably preclude direct evidence of a possible transfer of motion within a train of such gears. To ease on-surface studies and gain deeper understanding of mechanics at the molecular scale, it appears crucial to provide molecular gears bearing a dissymmetrised cogwheel (Fig. 1, left).

Fig. 1 Targeted new rotative molecular machines for on-surface mechanical studies: a dissymmetric gear and a winch.

In this communication, we thus report the synthesis of two new prototypes of Ru-based rotative molecular machines, such as a gear and a winch, via a highly modular synthetic strategy.

With a view to accessing a family of ruthenium complexes incorporating one discriminated arm on the cyclopentadienyl ligand, we opted for a modular strategy involving late-stage functionalisation of a 1,2,3,4,5-penta(p-halogenophenyl)cyclopentadienyl hydrotris(indazolyl)borate ruthenium(II) precursor. Such key intermediates may be engaged in various transition metal-catalysed cross-coupling reactions to yield target molecules with high structural diversity, as reported for the synthesis of diverse molecular motors and gears. 10 However, in contrast to previous work leading to symmetrical cyclopentadienyl platforms through five-fold cross-couplings, discrimination of one position out of five is now required.

A Suzuki-Miyaura cross-coupling was first investigated to functionalise one single position under statistical conditions starting from the pentabrominated key precursor. 11 Poor efficiency was observed, even after optimisation, and low yields of the desired mono-biphenylene product, mixed with products of polysubstitution, were obtained due to the equivalence of the five independent brominated positions. It was thus envisioned to discriminate one halogen position in the 1,2,3,4,5-penta(phalogenophenyl)cyclopentadienyl ruthenium(II) precursor, taking advantage of the enhanced reactivity of aryl iodides compared to aryl bromides in palladium-catalysed cross-couplings, and more particularly under Sonogashira conditions. 12 Dissymmetric key precursor 1 (Scheme 1) incorporating one preactivated p-iodophenyl group was thus designed, to allow for chemoselective monofunctionalisation and subsequent preparation of dissymmetric rotary molecular machines bearing high structural diversity via sequential cross-coupling reactions.

Scheme 1 Synthesis of 1-(p-iodophenyl)-2,3,4,5-tetra(p-bromophenyl)cyclopentadienyl hydrotris (indazolyl)borate ruthenium(II) (1).

1-(p-Iodophenyl)-2,3,4,5-tetra(p-bromophenyl)cyclopenta-dienyl hydrotris(indazolyl)borate ruthenium(II) complex 1 was synthesised in four steps starting from 2,3,4,5-tetra(pbromophenyl)cyclopenta-2,4-dienone 2 (Scheme 1). 1,2-Addition of 4-iodophenyllithium at -78 °C afforded the corresponding cyclopentadienol 3 in 94% yield. Subsequent bromination under acidic conditions, using a mixture of hydrobromic and acetic acids, led to the corresponding bromocyclopentadiene 4, obtained as a 1:2:2 mixture of regioisomers in 96% yield. Oxidative addition onto Ru3(CO)12 was then performed in toluene at 100 °C to provide bromidodicarbonylruthenium(II) complex 5, carrying a dissymmetrised penta(p-halogenophenyl)cyclopentadienyl ligand. It is important to note that no competitive insertion of ruthenium into the CAr-I bond was observed, in spite of the high reactivity of such position towards oxidative addition. The yield of 72% in this chemoselective step is similar to that obtained with the analogous symmetrical hexabrominated precursor, thus demonstrating that the presence of the p-iodophenyl substituent has no negative effect on this reaction. Finally, ligand exchange on complex 5 in the presence of thioether-functionalised thallium hydrotris(indazolyl)borate TlTp 4Bo,6-CH2SEt in acetonitrile under microwave irradiation gave the desired 1-(p-iodophenyl)-2,3,4,5tetra(p-bromophenyl)cyclopentadienyl hydrotris (indazolyl)borate ruthenium(II) complex 1 in 59% yield. As expected, lowering the symmetry of the Cp ligand renders NMR spectra more complex compared to the symmetrical counterparts. 9,13 However, combination of mass spectrometry giving the expected mass and isotopic distribution (see ESI) and 2D NMR unambiguously confirmed the presence of a single p-iodophenylene and four p-bromophenylene units surrounding the central cyclopentadienyl ring. Free rotation within the complex was evidenced at room temperature by the chemical equivalence of the three indazole groups.

I I

Single crystals were also obtained by slow evaporation of a solution of complex 1 in a 1:1 mixture of dichloromethane and methanol, allowing us to resolve the structure by X-ray diffraction (Figure 2). [START_REF]Selected data for 1: C65H54BBr4IN6RuS[END_REF] In the structure, only one brominated position is distinct, the four others corresponding to a combination of bromine and iodine densities, due to different orientations of the molecule in the crystal. Complex 1, carrying one pre-activated p-halogenophenyl moiety, was next exploited as key building block for the modular and selective synthesis of rotary molecular machines. In our work dedicated to the synthesis of molecular gears prototypes involving porphyrins as bidimensional paddles, the cogwheel diameter was modulated as a function of the nature of the spacer between the cyclopentadienyl platform and the porphyrin. Starting from symmetrical penta(p-halogenophenyl) cyclopentadienyl ruthenium(II) precursors, molecular gears prototypes with shorter 4,4'-biphenyl and longer phenylethynylphenyl linkers were obtained via five-fold Suzuki-Miyaura or Sonogashira crosscouplings, respectively, in the presence of the appropriate porphyrinic partner. 8 It is now envisioned to exploit the length of the linker as a strategy to differentiate one paddle, while keeping the same structure for all of them. Indeed, this structural modification leading to dissymmetrised cogwheels including one longer arm will facilitate STM studies on surface, with a direct monitoring of the molecular motion.

In our efforts towards the synthesis of symmetrical cogwheels, five-fold Sonogashira cross-coupling reactions on the symmetric penta(p-iodophenyl)cyclopentadienyl ruthenium(II) precursor were performed using PdCl2(PPh3)2 and CuI as the catalytic system in triethylamine at 45 °C. 9 Further investigations revealed that the pentabrominated analog is also prone to Sonogashira couplings with similar yield under much harsher conditions involving Pd(OAc)2/SPhos and CuI as catalytic system in a DMF/diisopropylamine mixture at 95 °C. The striking difference in reaction conditions for the conversion of p-iodophenyl and p-bromophenyl precursors opened the way for the chemoselective functionalisation of 1 via successive cross-coupling reactions.

Scheme 2 Synthetic route to the molecular winch (11) and dissymmetric gear (7). Porphyrin A is Nickel(II) 5-(4-ethynylphenyl)-10,15,20-tris(3,5-di-tert-butylphenyl)porphyrin and Porphyrin B is Nickel(II) 5,10,15-tris(3,5-di-tert-butylphenyl)-20-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) phenyl)]porphyrin. Ar = 3,5 di-tert-butylphenyl.

Reaction of key precursor 1 with 1.5 eq. of A3B-type porphyrin A bearing a terminal alkyne (Scheme 2) was thus carried out under mild conditions in the presence of PdCl2(PPh3)2 (1 mol-%) and CuI (0.6 mol-%) as catalysts in a mixture of tetrahydrofuran and triethylamine (4:1). After 24h at 45 °C, product 6 resulting from a single Sonogashira coupling was isolated as a red solid in 51% yield. Interestingly, it was observed during optimisation that an increase of temperature up to 80 °C leads to the formation of a mixture of bis-porphyrin functionalised side-products resulting from an additional Sonogashira coupling on a bromophenylene position. In the next step, a four-fold Suzuki-Miyaura cross-coupling was achieved on 6, in order to functionalise the remaining p-bromophenylene groups and introduce the four shorter 4,4'-biphenyl linkers. Complex 6 was thus reacted with 8 eq. of an A3B-type porphyrin B bearing a boronic ester (Scheme 2) as coupling partner, in the presence of PdCl2(dppf) (10 mol-%/Br) as catalyst and a large excess of cesium carbonate as base in a DMF/water (99:1) system. 9 After 48 h at 100 °C, complex 7 incorporating five identical porphyrin fragments but different spacers was isolated in 36% yield (i.e. 77% per single coupling). The structure of this molecular gear prototype carrying a dissymmetric cogwheel was unambiguously confirmed by mass spectrometry and NMR spectroscopy, revealing the presence of one longer phenylethynylphenyl and four short 4,4'-biphenyl linkers around the central cyclopentadienyl moiety. The UV-visible spectrum of compound 7 resembles that of 6, with a Soret band at 418 nm and a Q band at 529 nm. No shift of these bands was observed but an additive effect was noticed, with an increase of the molar extinction coefficients (e.g. from 254 000 in 6 to 1 396 000 mol -1 dm 3 cm -1 in 7 for the Soret band, see ESI) in line with the number of porphyrin units present in such molecules.

This first example of dissymmetric ruthenium-based molecular gear was thus obtained in two steps, via successful sequential chemoselective Sonogashira / four-fold Suzuki-Miyaura cross-couplings from key intermediate 1, bearing one pre-activated position.

The same synthetic strategy relying on building block 1 was considered for the preparation of a molecular winch prototype. The latter was designed in view of single molecule force spectroscopy experiments to investigate the motive power of the ruthenium-based molecular motor previously reported by our group. 5 To this aim, derivatisation of the motor's structure through a functionalisation of the shorter p-methylphenylene arm with a long polyethylene glycol (PEG-24) chain was envisioned, using a propargylamide moiety as linker.

In this synthetic sequence, monofunctionalisation of key precursor 1 with tert-butyloxycarbonylprotected (BOC-protected) propargylamine was successfully achieved via a chemoselective Sonogashira cross-coupling under mild conditions. The resulting tetra(p-bromophenyl) cyclopentadienyl ruthenium complex 8, obtained in 75% yield, was further engaged in a four-fold Suzuki-Miyaura coupling with ferrocene boronic acid pinacol ester to give the corresponding tetraferrocenyl derivative 9 in a 16% yield. Deprotection of the propargylamine moiety was next conducted under mild conditions using trimethylsilyl triflate in the presence of lutidine. 15 Indeed, standard BOC cleavage procedures involving trifluoroacetic acid led to decomposition of the Ru(II) complex, which appeared unstable under acidic conditions. Finally, the long PEG chain required for force spectroscopy experiments was covalently linked to the motor scaffold through a condensation between free propargylamine 10 and a monodisperse methoxy-PEG24-propionic acid partner, activated as an N-hydroxysuccinimidyl ester. After 24h at room temperature in the presence of triethylamine, the desired molecular winch prototype 11 was isolated in 69% yield (from 9) and its structure was unambiguously confirmed by mass spectrometry and NMR spectroscopy.

In conclusion, the dissymmetric 1-(p-iodophenyl)-2,3,4,5-tetra(p-bromophenyl)cyclopentadienyl hydrotris(indazolyl)borate ruthenium(II) complex was efficiently prepared and subsequently used as a key building block in the modular synthesis of ruthenium-based molecular machines incorporating a dissymmetrised rotating platform. Indeed, selective functionalisation of the pre-activated precursor was achieved via palladium-catalysed "Sonogashira/Suzuki-Miyaura" cross-coupling sequences to afford new prototype of molecular winches and molecular gears. The mechanical studies on surface and at the single molecule scale are currently underway.

Fig. 2

 2 Fig.2 Side view (a) and top view(b) of the molecular structure of ruthenium complex 1. Thermal ellipsoids drawn at 50% probability, hydrogen atoms, solvent molecules and disordered atoms are omitted for clarity. The cp ligand is distant of the ruthenium atom by 1.79 Å and the average distance between the three coordinated nitrogens and the ruthenium centre is 2.26 Å.

Acknowledgements

This work was supported by the University Paul Sabatier (Toulouse) and CNRS. It has received funding from the ANR (ACTION project ANR-15-CE29-0005), the European Union's Horizon 2020 research and innovation programme under the project MEMO, grant agreement No 766864, the JSPS KAKENHI grant in aid for Scientific Research on Innovative Areas "Molecular Engine (No.8006)" 18H05419. Y.G. thanks the MESR for a PhD Fellowship. Dr Colin Martin is warmly acknowledged for his careful reading and improving of our manuscript.