Dr Toshio Nishino

Dr Colin J Martin

Hiroki Takeuchi

Dr Florence Lim

Prof. Dr Kazuma Yasuhara

Dr Yohan Gisbert

Dr Seifallah Abid

Dr Nathalie Saffon-Merceron

Prof. Dr Claire Kammerer

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

G Rapenne Cemes

Jean-Marie Lehn

Dipolar Nanocars Based on a Porphyrin Backbone

The design and synthesis of a new family of nanocars is reported. To control their motion, we integrated a dipole which can be tuned thanks to strategic donor and acceptor substituents at the 5-and 15-positions of the porphyrin backbone. The two other meso positions are substituted with ethynyltriptycene moieties which are known to act as wheels. Full characterization of nine nanocars is presented as well as the electrochemistry of these push-pull molecules. DFT calculations allowed us to evaluate the magnitude of the dipoles and to understand the electrochemical behavior and how it is affected by the electron donating and accepting groups present. An X-ray crystal structure of one nanocar has also been obtained.

INTRODUCTION

Molecular vehicles or nanocars are molecular machines able to be moved in a controlled manner at the nanoscale on a surface. The first prototypes were technomimetic [1] containing both chassis and four wheels. [2][3][4] In this technomimetic family, Feringa et al. proposed a very impressive nanovehicle with four motors as wheels. [5] Nevertheless, such nanocars were often designed to mimic the function of vehicles without keeping the structural design of macroscopic cars. For instance, recent developments (see below) have shown that the function of vehicles can be maintained at the nanoscale with less and even no wheels. In 2013, in a perspective article named "Molecule concept nanocars: Chassis, wheels and motors?" [6] , a competition was proposed whereby all nanocar designers could meet to test and compare their prototypes. This challenge stimulated the design and the synthesis of many kinds of nanocars following, or not, technomimetic designs, some of which participated in the first nanocar race four years later. This nanocar race was held on a metallic surface inside of a 4-tip STM with an independent control for each tip and allowed for the deposition by sublimation of four molecules with different mass, composition and sublimation temperature. Six competitors from Austria, Germany, Japan, Switzerland, USA and France participated with their own design and strategies to speed up and control the motion of their nanocars on a metallic surface. [7] The variety of the molecules was very wide with structures containing from 42 atoms (C22H17N3) for the Swiss team [8] to 642 atoms (C244H222N120O56) for the US team. [9] Three nanocars, those from the USA, Austria and France, were technomimetic containing general shapes similar to a macroscopic car with a planar chassis and two to four wheels. [9][10][11] The other groups from Japan, Germany and Switzerland did not use wheels since mobility at the nanoscale does not require them [12][13][14] as nanovehicle designs do not follow the same rules as macroscopic vehicles. For instance, to deal with the gravity forces at the macroscopic level, wheel rotation is very efficient, but at the nanoscale gravity is negligible compared to van der Waals interactions between molecules and the surface. To have an efficient nanocar two criteria are essential: first molecules must be able to diffuse on the surface, so the molecule-surface interaction must be minimized. Second, to be able to control the direction of the motion a good understanding of the mechanism of this motion is needed. For example, the very smart butterfly-shaped nanocar developed by the Japanese team used binaphthyl fragments to separate the molecule from the metallic substrate, but also as a source of motion provided by the inelastic excitation of the molecule without any mechanical contact of the STM tip. [12] In our case, the molecule we proposed as a nanocar was based on a large polyaromatic hydrocarbon chassis [15] functionalized with four triptycene wheels (Figure 1). [START_REF]Iptycenes chemistry from synthesis to applications[END_REF] Despite the advantage of being very robust, our molecule was not mobile without mechanical contact and only direct pushing or pulling with the STM tip was able to induce a motion. [START_REF] Soe | [END_REF] In our research on molecular motors, [18][19] we synthesized a double-decker motor with a dipolar rotor and have been able to rotate it clockwise or counter-clockwise synchronously as a self-assembled monolayer without any mechanical contact by using the electric field generated by the tip apex of the STM. [20] James Tour, one of the pioneers in the field of nanocars, was the first to explore the ability of dipoles as effective handles under the effect of an electric field. [21] This non-contact strategy to control the motion of dipolar molecules at the nanoscale was confirmed during the first nanocar race, where the fastest nanocars were found to also have a strong permanent dipole. [8,10] In 2021, a second nanocar race will be organized. [22] For this new challenge, we decided to exploit movable dipolar molecules. In this article we describe the design and synthesis of a nanocar family with a tunable permanent dipole to explore the influence of the magnitude of the dipole on the properties of the nanocar in term of speed, movability and directionality. For instance, intuitively, we could think that increasing the value of the dipole would increase the speed of the molecule. But is it correct at the nanoscale where intuition often does not follow the quantum laws? Is it still possible to keep control of the molecule?

Herein we report the design and synthesis of a new family of nanocars built on a central porphyrin backbone, a very stable organic architecture which offers the possibility to be functionalized dissymmetrically using many types of substituent groups. DFT calculations and electrochemical analysis have been performed to systematically understand the behavior of such molecules.

RESULTS AND DISCUSSION

Molecular design

Our general design is shown in Figure 2, porphyrins were selected as the central platform because of their planar structure and high stability. They are also rigid molecular structures which is desirable to allow for a minimum number of degrees of freedom and to maximize the direct conversion of electric field-dipole interactions into translational motion. Since preparation of porphyrins is very versatile and can give rise to many types of substitution at the meso position, [23][24] it is possible to fine tune the amplitude of the dipole moment with minimal change in the synthetic strategy. A combination of pertinent electron-donating and electron-withdrawing substituents can give us access to a family of varying dipoles. This will allow us to manipulate molecules without direct contact with the electric field induced by the STM tip. Another parameter to be minimized by design is the diffusion energy of the molecule.

Figure 2. General structure of the nanocars described in this paper. A represents an acceptor (electronwithdrawing functionalized phenyl group) and D is a donor (electron-donating functionalized phenyl group).

Large and rigid polyaromatic -molecules tend to interact strongly with the metallic surface, limiting the movability of the molecule. [25] To enhance this, the aromatic planar structure of the porphyrin has to be lifted up from the surface. For that purpose, donor and acceptor substituents have been introduced on the phenyl ring at the 5-and 15-positions. These phenyl groups can't be coplanar with the porphyrin backbone which contribute to the lift up of the porphyrin as well as the presence of triptycenes introduced at the two other meso positions (10 and 20). These fragments are also known to diffuse easily on the surface and have sometimes been shown to have the capacity to rotate. [26] A lower diffusion energy will result in a better movability by decreasing the physical and/or chemical adsorption of the molecule onto the surface. The porphyrin has to be metallated to avoid partial metalation on the metallic surfaces used. In addition, it is well-known that porphyrins can form supramolecular architectures via axial coordination to a metal center as in the case of zinc, [27] or by - interactions, implying that our designed nanocars have potential applications in loading and carrying cargo molecules.

Determination of the dipole moment by DFT calculation

DFT calculations of metal-free and zinc containing porphyrin-based nanocars were carried out to systematically investigate the influence of substituents introduced onto the porphyrin ring on the molecules' dipole moment. All calculations were performed with the Gaussian09 suite of programs [START_REF] Frisch | Gaussian 09 Revision A.02[END_REF] in vaccuo, using the WB97XD functional, taking into account long range interactions and dispersion corrections with the 6-31G* basis set, a larger basis set than the 6-21G* reported for previous similar compounds [START_REF] Verykios | [END_REF] . We selected three kinds of electron-donating groups, namely 3,5-bis-tert-butylphenyl, 3,5-dibutoxyphenyl and 4-N,N-dihexylaminophenyl, and three kinds of electron-withdrawing units, namely 3,5-bis-trifluoromethylphenyl, 4-cyanophenyl and 4-nitrophenyl. The results of DFT dipole calculations are summarized in table 1.

Table 1. DFT calculations of the dipole moment of the free-base porphyrins and their zinc containing analogues.

The dipole moments range from 5.0 D to 9.9 D. As expected, the presence of the zinc metal center has negligible influence on the dipole, with a calculated slightly lower value of about 0.1 D in each case. The smallest dipole moment (5.0 D) was estimated for the nanocar having 3,5-bis-tert-butylphenyl and 3,5-bis-trifluoromethylphenyl as electron-donating and electron-withdrawing groups, respectively (2d).

On the other hand, the largest dipole moment (9.9 D) was observed for the nanocar having 3,5dibutoxyphenyl and 4-nitrophenyl groups (6d). This result implied that our methodology, namely introduction of electron-donating and -withdrawing group as a perturbation module unit, enables us to control the total dipole moment precisely with a wide variety of amplitude.

Synthesis

The general synthetic scheme for porphyrin-based nanocars 1d to 9d is detailed in Scheme 1. Porphyrins having different substituents at the 5-and 15-positions, which are key structures of our nanocars were synthesized by conventional methods, namely condensation of two different aldehydes and dipyrromethane followed by oxidation of the intermediate porphyrinogen. [30] The symmetric porphyrins and polymeric species were removed by silica gel column chromatography and reprecipitation to afford the desired dissymmetric porphyrins 1a to 9a in moderate yields. Porphyrins having 3,5-di-tertbutylphenyl or 3,5-dibutoxyphenyl units as electron-donating groups were converted into their zinc complexes. The meso positions of these zinc porphyrins were then brominated using Nbromosuccinimide to obtain the nanocar precursors 1c to 6c.

Scheme 1. General synthetic scheme of dipolar porphyrin-based nanocars 1d to 9d.

In the case of porphyrins having 4-N,N-dihexylaminophenyl groups, bromination via the same scheme did not work well due to the occurrence of further brominations on the 4-di-hexylaminophenyl moiety. This over-bromination is certainly due to the strong electron donating character of the dialkylamino moiety on the phenyl ring. Instead we carried out bromination of the free-base porphyrins 7a to 9a at -40°C followed by zinc complexation to give 7c to 9c in satisfying yield. 9-Ethynyltriptycene [31] was introduced on the brominated meso positions of the porphyrin scaffold using Sonogashira coupling conditions to afford the porphyrin-based nanocars 1d to 9d as their zinc complexes.

The nine porphyrin-based nanocars (Table 1) have been synthesized following this general strategy. These have been fully characterized by 1 H-NMR, 13 C-NMR, 2D NMR, UV-Visible spectroscopy, MALDI-TOF MS, electrochemistry, and one of them by single crystal X-ray analysis. All the data are given in the experimental part and supporting information.

As a representative example we will discuss in more detail the characterization of the nanocar with 3,5di-tert-butylphenyl as the donor and 4-cyanophenyl as the acceptor group (1d). UV-visible spectroscopy showed the expected characteristic porphyrin absorptions, with an intense Soret band at 438 nm and a pair of Q bands at 580 and 629 nm. MALDI-TOF MS gave the molecular ion peak [M] + corresponding to the nanocar at m/z = 1213.5 which is in agreement with the calculated isotopic pattern (Figure S19a of the supporting information). All the nanocars synthesized showed similar behaviors (Table 2 and Figure S22 of the supporting information). We can notice that nanocars containing the 4-N,Ndihexylaminophenyl donating group (7d, 8d and 9d) show a relative decrease in their molar extinction coefficient but the bands are strongly enlarged, maybe because of some H-bonds between the amino group and the solvent. After excitation in the Soret band, the nanocars emit light in the red color from 632 to 635 nm for 1d to 6d and at lower energies (646 to 652 nm) for nanocars 7d to 9d. Additionally, apolar symmetric analogues carrying two donors such as 3,5-bis-tert-butylphenyl (10d), 3,5dibutoxyphenyl (11d) and 4-N,N-dihexylaminophenyl groups (12d) were studied in comparison with their polar counterparts. The aromatic region of the 1 H-NMR spectrum (Figure 3) fits very well with the expected structure of 1d and indicates that this nanocar has Cs symmetry in solution. Four sets of doublets corresponding to the protons at the -pyrrolic positions of the porphyrin are observed (solid circle, Figure 3), confirming the 5,15-dissymmetrically-substituted structure. Moreover, observation of four sets of triptycene signals (solid triangle, Figure 3) implied that structural oscillation of the two triptycenes around the ethynyl spacer is fast enough on NMR timescales.

X-ray structure

Single crystals of the nanocar 1d with 3,5-di-tert-butylphenyl as donor group and 4-cyanophenyl as acceptor group (Figure 3) that were suitable for X-ray structural analysis were obtained by diffusion of methanol vapor into a benzene solution containing the nanocar. As shown in Figure 4, neighboring porphyrins arranged in an antiparallel fashion to annihilate the total dipole moment of the crystal. Compared to the DFT calculated structure, the molecule in the crystal is slightly bent due to some intermolecular CH- interactions not present in the calculations. Furthermore, a methanol molecule, used as non-solvent to crystallize the molecule, coordinates at the axial position of the zinc ion in a classical manner. [32] As a result the zinc ion shows a square pyramidal coordination geometry and is located slightly out of the plane defined by the four pyrrolic nitrogens of the porphyrin (d=0.270(2) Å). This shows the ability of this porphyrin-based nanocar to load cargo molecules through axial coordination to the zinc center.

Electrochemical properties of the nanocars

The effect of the electron-donating and electron-withdrawing substituents introduced into the porphyrin backbone on the redox properties was examined using cyclic voltammetry in dichloromethane. Figure 5 shows the voltammograms of the porphyrin-based nanocar series containing 3,5-di-tert-butylphenyls as electron donating units (1d to 3d) along with their symmetrically substituted analogue 10d. Upon oxidation all four compounds gave rise to two reversible redox waves (Figure 5) which can be attributed to the one electron oxidation of the porphyrin ring (E0' = 0.51 V and 0.84 V for 2d, 0.49 V and 0.82 V for 1d, 0.49 V and 0.82 V for 3d vs. Fc/Fc + ). Comparing with the symmetrically substituted porphyrin with two 3,5-di-tert-butylphenyl groups 10d (E0' = 0.42 V and 0.77 V vs. Fc/Fc + ), a positive shift in oxidation potentials (approximately 50 to 90 mV) was observed resulting from the increasing electron density in the HOMO, related to the donating groups present. This behavior appears reasonable taking into account the results of the DFT calculations as the electron density of the HOMO orbital is localized onto the central porphyrin ring rather than peripheral phenyl ring (see SI figures S31 and S32). Similar patterns are observed (See Supporting information) for the nanocars having 3,5-dibutoxyphenyl moieties as the electron donating groups (4d to 6d), with oxidations seen between E0' = 0.49-0.50 V and 0.82-0.84 V, in each case (Figure S25 in the Supporting Information). Here again the oxidation potentials are at slightly higher compared to their symmetrically substituted analogue 11d which occur at E0' = 0.46 V and 0.78 V. Interestingly all of the porphyrins containing the 4-N,N-dihexylaminophenyl donating group (7d to 9d) show a relative decrease in oxidation potential at 0.33 V and between 0.51-0.52 V, while the symmetrically substituted 4-N,N-dihexylaminophenyl analogue porphyrin 12d shows a further decrease to as low as 0.24 V and 0.36 V. This can be rationalized from the DFT calculations of the porphyrins in which contribution to the HOMO from the electron donating groups is only observed for the 4-N,N-dihexylaminophenyl compounds (see SI). As such it would be predicted that these are the only cases in which the substituent affects the HOMO stability and the resulting electrochemical oxidation potential.

Looking at the electrochemical reductions, a number of trends can also be observed. In most cases application of a negative potential results in low current irreversible reductions starting below -1.45 V. This is observed for all systems except one, indicating these irreversible reductions occur on the peripheral groups rather than the porphyrin core; as the symmetric analogue of the 3,5-di-tertbutylphenyl porphyrins 10d is the only case where such reductions cannot occur it is the only system where they are not observed (Figure 6). This is followed by a single electron quasi-reversible reduction (of similar current response to the one electron oxidations) between -1.58 V and -1.81 V (Figure 6 and Table 3, mentioned as Red2). As with the oxidations these reductions vary with the electronic nature of the substituents present; however it is the electron-withdrawing group that affects the reduction potential rather than the electron-donating group as in the oxidation cases. With the 4-nitrophenyl withdrawing group having the largest effect, either positive or negative, on the reduction potential. That the electrondonating part of the molecule affects the oxidation potential (and HOMO level) while the electronwithdrawing part affects the reduction potential (and LUMO level) offers an excellent method for the tuning of future targets both in terms of electronic properties and dipole moments Using these reversible electrochemical oxidations and quasi-reversible reductions, an estimation of the frontier orbital levels for each zinc porphyrin complex can be calculated from the onset potential of each redox response [33] . This gives values of the band gap for each complex that can be compared to both those calculated from the onset of the Soret band in the absorption spectra and for the calculated orbitals of the zinc porphyrins by DFT. It is important to note that due to the presence of solvent and electrolyte, it is not reasonable to compare the band gap values obtained directly with those calculated using DFT or absorption. However a systematic comparison of the trends resulting from changes in donors and acceptors will give information on their effect and how they are seen from different methods. Such a comparison shows clear trends in the band gaps with the smallest values always observed in the presence of 4-N,N-dihexylaminophenyl electron donating groups and those systems containing 4-nitrophenyl electron withdrawing groups deviating the most from the others.

Table 3. Electrochemical redox potentials (in V vs Fc/Fc + ), and band gaps (in eV) from electrochemical data, UV-Vis spectra and DFT calculations for all zinc nanocars 1d to 9d with the corresponding aromatic groups Ar1 and Ar2 and their apolar symmetric analogues 10d to 12d.

CONCLUSIONS

In this work, a series of nine prototypes of dipolar nanocars with different amplitude of dipole moments from 5.0 to 9.9 D were prepared and fully characterized. One of these nanocars (1d) is also already registered to participate in the second nanocar race which will be organized in 2021. [22] Work is now underway to investigate by STM the correlation between the amplitude of the dipole moment of the nanocar with their movability on metallic surfaces. We would like to establish the laws describing the motion of such molecules at the nanoscale under the influence of an STM tip-induced electric field. The more efficient nanocar will be the one with the best compromise between the speed and the controllability.

Such donor-acceptor porphyrins may also find applications in thin film devices and materials including light emitting devices, photovoltaic cells and field effect transistors. [34][35][36] Ar 1 Ar 2 N°- -

[(3,5-di t Bu)Ph] -[(4-CN)Ph] -[(3,5-di t Bu)Ph] -[(3,5-diCF 3 )Ph] -[(3,5-di t Bu)Ph] -[(4-NO 2 )Ph] -[(3,5-di t Bu)Ph] -[(3,5-di t Bu)Ph] -[(3,5-diOBu)Ph] -[(4-CN)Ph] -[(3,5-diOBu)Ph] -[( 3

EXPERIMENTAL SECTION

A typical synthetic procedure is described below for the nanocar with a 3,5-di-tert-butylphenyl as donor group and 4-cyanophenyl as accepting group (1d). All the other nanocars presented in Table 1 (2d to 9d) are described in the supporting information document. The apolar nanocars with trans-A2B2 porphyrins, used as reference in the electrochemistry section, have been synthesized following the same synthetic strategy from the following porphyrins. 5,15-(3,5-Di-tert-butylphenyl) porphyrin 10d and 5,15-(3,5-dibutoxyphenyl)porphyrin 11d were synthesized directly via condensation of the corresponding aldehydes and dipyrromethane. 5,15-(4-N,N-dihexylaminophenyl) porphyrin 12d was afforded as a byproduct of dissymmetric porphyrin synthesis.

General methods:

Synthetic procedures were carried out under dry nitrogen atmosphere, unless otherwise specified. All reagents and solvents were purchased at the highest commercial quality available and used without further purification, unless otherwise stated. Trifluoroacetic acid, chloroform, 4-nitrobenzaldehyde, copper iodide, methanol, anhydrous N,N-dimethylformamide, N-bromosuccinimide, and zinc acetate dihydrate were purchased from FUJIFILM Wako Pure Chemical Corporation. 3,5-Bis(tertbutyl)benzaldehyde was purchased from Aldrich. Dichloromethane, 2,3-dichloro-5,6-dicyano-1,4benzoquinone (DDQ), anhydrous tetrahydrofuran and triethylamine were purchased from Nacalaitesque. Pyrrole, 4-cyano-benzaldehyde and bis(triphenylphosphine) palladium(II)dichloride were purchased from TCI. 9-Ethynyltriptycene, [31] dipyrromethane, [37] 4-(N,Ndihexylamino)benzaldehyde [38] and 3,5-dibutoxybenzalde-hyde [39] were prepared according to the literature procedures. The complexation reaction of a porphyrin with zinc ion under microwave irradiation was carried out by utilizing CEM Discover SP in a glass pressure tube equipped with PTFEcoated magnetic stirring bar. Silica gel column chromatography and thin-layer (TLC) chromatography were performed using Wakosil ® 60 and Merck silica gel 60 (F254) TLC plates, respectively. 1 H and 13 C NMR spectra were recorded on a JEOL JNM-ECA600 (600 MHz for 1 H; 150 MHz for 13 C) spectrometer or a JEOL JNM-ECX400P (400 MHz for 1 H; 100 MHz for 13 C) spectrometer at a constant temperature of 298 K. Tetramethylsilane (TMS) was used as an internal reference for 1 H and 13 C NMR measurements in CDCl3 and DMSO-d6. Chemical shifts (δ) are reported in ppm. Coupling constants (J) are given in Hz and the following abbreviations have been used to describe the signals: singlet (s); broad singlet (br. s); doublet (d); triplet (t); quadruplet (q); quintuplet (quint); multiplet (m). Full assignments of 1 H and 13 C NMR spectra were made with the assistance of COSY, HMBC, and HSQC spectra when necessary. The MALDI-TOF mass spectrometry was performed using Bruker Daltonics Autoflex II spectrometer and JEOL JMS-S300 spectrometer. DCI mass spectrometry was performed with a Waters GCT Premier spectrometer for desorption chemical ionization (CH4). The fluorescence spectra were recorded with a Hitachi F-7000 spectrometer in chloroform solution at 20 ± 0.1 °C in 1.0 cm quartz cells. The absorption spectra were obtained using Hitachi U-3310 spectrometer in CHCl3 solution at 20 ± 0.1 °C in 1.0 cm quartz cells. Absorption Gap values Egap were calculated from the low energy onset frequency of the absorption Soret band (λon) such that Egap = hc/λon giving Egap (in eV) = 1240/λon (in nm). Cyclic voltammetry measurements were performed with ALS electrochemical analyzer Model 630DA at room temperature in HPLC grade dichloromethane containing 0.1 M TBAPF6 as supporting electrolyte at concentrations of 500 µmol in a standard one-component cell, working under an Ar atmosphere and equipped with a  3 mm glassy carbon working electrode, a Pt wire counter electrode and Ag/Ag + reference electrode at a scan rate of 100 mV.s -1 at 20 °C. All solutions were deoxygenated by Ar bubbling for at least 20 min; the obtained E 0 ' vs. Ag/Ag + values were converted into those of Fc/Fc + based on the measured redox potential of ferrocene. TBAPF6 used as electrolyte was recrystallized from ethanol and dried under reduced pressure for 12 hr at 100 °C. Ferrocene was sublimated under reduced pressure at 80 °C.

5-(3,5-di-tert-butylphenyl)-15-(4-cyanophenyl)porphyrin (1a)

This reaction was performed under a nitrogen atmosphere and all reaction vessels were dried up. 3,5-Di-tert-butylbenzaldehyde (326 mg, 1.5 mmol), 4-cyanobenzaldehyde (197 mg, 1.5 mmol) and dipyrromethane (440 mg, 3.0 mmol) were dissolved in dichloromethane (300 mL) and the solution was deoxygenated by bubbling nitrogen for 20 min. Trifluoroacetic acid (413 µL, 5.4 mmol) was added and the resulting solution was stirred at room temperature for 30 min under dark. Then, DDQ (1.0 g, 4.6 mmol) and triethylamine (730 µL, 6.0 mmol) were added. The reaction mixture was stirred at room temperature for further 2 h, and then silica gel (40 mL) was added. The resulting mixture was evaporated and the crude compound was preadsorbed on the silica gel. The crude material was purified by silica gel column chromatography (5 x 12 cm, hexane : dichloromethane = 3 : 7) to afford crude purple solid. Washing with acetone gave the free-base porphyrin 1a as a purple solid (292 mg, 32%). 1

5-(3,5-di-tert-butylphenyl)-15-(4-cyanophenyl)porphyrinato zinc (1b)

A mixture of chloroform (7.5 mL) and methanol (7.5 mL) containing 5-(3,5-di-tert-butylphenyl)-15-(4cyanophenyl)porphyrin (1a, 241 mg, 402 µmol) and Zn(OAc)2•2H2O (179 mg, 817 µmol) was added to the pressure tube. The resulting mixture was heated under microwave irradiation at 100 °C for 20 min, then 120 °C for 3 x 10 min. The reaction mixture was evaporated and the residue was washed with methanol to afford a mixture of the desired compound and the starting free-base porphyrin. The crude material and Zn(OAc)2•2H2O (177 mg, 805 µmol) were heated under microwave irradiation in a mixture of chloroform (10 mL) and methanol (10 mL) at 120 °C for 10 min. After completion of the reaction, the volatiles were evaporated and the residue was washed with methanol and water to afford the zinc porphyrin 1b as a purple solid (253 mg, 95%). 1

10,20-dibromo-5-(3,5-di-tert-butylphenyl)-15-(4-cyanophenyl) porphyrinato zinc (1c)

5-(3,5-di-tert-butylphenyl)-15-(4-cyanophenyl)porphyrinato zinc (1b, 199 mg, 200 µmol) was dissolved in a mixture of dichloromethane (55.8 mL) and pyridine (1.2 mL). The solution was stirred in an ice bath. N-bromosuccinimide (112 mg, 628 µmol) was then added to the mixture and the resulting solution was allowed to warm to room temperature. After 20 h of stirring, acetone (20 mL) was added to quench the reaction. The volatiles were evaporated and the residue was washed with methanol to afford the dibrominated porphyrin 1c as a purple solid (172 mg, 70%). 1

Nanocar 10,20-di(triptycen-9-ylethynyl)-5-(3,5-di-tert-butylphe-nyl)-15-(4-cyanophenyl) porphyrinato zinc (1d)

10,20-Dibromo-5-(3,5-di-tert-butylphenyl)-15-(4-cyanophenyl)porphyrinato zinc (1c, 84 mg, 150 µmol), 9-ethynyltriptycene (169 mg, 607 mol), Pd(PPh3)2Cl2 (11 mg, 16 µmol) and CuI (3.0 mg, 16 µmol) were suspended in a mixture of tetrahydrofuran and triethylamine (4 : 1 (v/v), 7.5 mL). The resulting mixture was deoxygenated by freeze-pump-thaw method (three times) and then refluxed for 12 h. The reaction mixture was filtered through celite and the filtrate evaporated. The crude compound was preadsorbed onto silica gel (5 mL) and purified by silica gel column chromatography (4 x 14 cm, hexane : dichloromethane = 4 : 6) to afford a crude green solid. This solid was further purified by reprecipitation from dichloromethane and methanol to give the nanocar 1d as a green solid (123 mg, 67%). 1 [M] + : 1213.4062, found 1213.4053; UV/Vis (CHCl3): λmax (ε / mol -1 dm 3 cm -1 ) = 438 (489100), 580 (17200), 629 nm (40300).

Crystal data of nanocar with a 3,5-di-tert-butylphenyl as donor group and 4-cyanophenyl as accepting group (1d):

Single crystals grown in a mixture of benzene/methanol were selected in mother liquor from a flask and covered with perfluorated polyether oil on a microscope slide. An appropriate crystal was selected using a polarizing microscope, fixed on the tip of a MiTeGen© MicroMount, transferred to a goniometer head, and shock cooled by the crystalcooling device. Crystallographic data for the nanocar were collected at 193(2) K on a Bruker-AXS Kappa APEX II Quazar diffractometer equipped with a 30W air-cooled microfocus source using Mo Kα radiation (λ=0.71073 Å). Phi-and omega-scans were used. Space group was determined on the basis of systematic absences and intensity statistics. Semi-empirical absorption correction was employed. [40] The structure was solved using an intrinsic phasing method (SHELXT), [41] and refined using the least-squares method on F 2 . [41] All non-H atoms were refined with anisotropic displacement parameters. Hydrogen atoms were refined isotropically at calculated positions using a riding model with their isotropic displacement parameters constrained to be equal to 1.5 times the equivalent isotropic displacement parameters of their pivot atoms for terminal sp 3 carbon and 1.2 times for all other carbon atoms. The selected crystal was very weakly diffracting and it was not possible to model the disorder of 1.5 molecules of solvent (C6H6). Therefore, the SQUEEZE [42] function of PLATON was employed to remove this residual electron density. CCDC-1997293 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via https://www.ccdc.cam.ac.uk/structures/. Selected data: C86H62N50Zn, C6H6, M=1324.88, monoclinic, space group C2/c a=46.699 (10) Å, b= 30.016(6) Å, c=11.760(2) Å, =90°, =99.082(5)°, =90° V=16278(6) Å 3 , Z=8, crystal size 0.300 x 0.030 x 0.020 mm 3 , 219187 reflections collected (14328 independent, Rint = 0.3675), 899 parameters, 0 restraints, R1[I>2(I)]=0.0909, wR2[all data]=0.2829, largest diff. peak and hole: 0.447 and -0.579 eÅ -3 . More details can be found in the Supporting Information.

Computational Methods:

All calculations were performed with the Gaussian09 package. [START_REF] Frisch | Gaussian 09 Revision A.02[END_REF] We used the hybrid dispersive functional WB97XD with the basis set 6-31-G* in vaccuo. Frequency calculation showed no negative frequencies confirming that resulting structures were in the minimum. For compounds 8d, 9d and 10d the 'nosymm' input command was used. Dipole moments were obtained from the output fchk file.

Figure 1 .

 1 Figure 1. Chemical structure and STM image on Au(111) of the nanocar used in the first nanocar race (U = 1.1 V, I = 5 pA). Scale bar: 1 nm.

Figure 4 .

 4 Figure 4. Side view (a) of the molecular structure of two neighboring nanocars 1d showing their antiparallel arrangement and the coordination geometry of porphyrin center (b, meso substituents were omitted in this view). The hydrogen atoms and crystal solvents were omitted for clarity. Color code: Zn, green; C, gray; N, blue; O, red.

Figure 5 .

 5 Figure 5. Cyclic voltammograms of oxidation region of Zn porphyrin derivatives 1d-3d and 10d having a 3,5-di-tert-butylphenyl substituent on the 5-position and a 4-cyanophenyl (a), 3,5bistrifluoromethylphenyl (b), 4-nitrophenyl (c) or 3,5-di-tert-butylphenyl (d) substituent on the 15position, in CH2Cl2 containing 0.1 M TBAPF6 at 20 °C at a scan rate of 100 mV.s -1 . [Substrate] = 500 µM.

Figure 6 .

 6 Figure 6. Cyclic voltammograms of reduction region of Zn porphyrin derivatives 1d-3d and 10d having a 3,5-di-tert-butylphenyl substituent on the 5-position and a 4-cyanophenyl (a), 3,5bistrifluoromethylphenyl (b), 4-nitrophenyl (c) or 3,5-di-tert-butylphenyl (d) substituent on the 15position, in CH2Cl2 containing 0.1 M TBAPF6 at 20 °C at a scan rate of 100 mV.s -1 . [Substrate] = 500 µM.

a

  Red 2 are all quasi-reversible b Determined from electrochemical values of the HOMO and LUMO (Ox on -Red on ) for the Zn porphyrins c Calculated from DFT values of the HOMO and LUMO for the Zn porphyrins in the gas phase d Determined from the onset potential of the Soret band in the UV-Vis. spectra for the Zn porphyrins i = irreversible reduction (ignored for onset).

Table 2 .

 2 UV-Visible data (full spectra given in SI) and luminescence properties of the nanocars 1d to

9d and their apolar symmetric analogues 10d to 12d. ([Substrate] = 2 M in CHCl3)

  Comparison of integrals of the triptycenyl signals with the porphyrin's protons confirms a ratio of two triptycenes per porphyrin.

	Figure 3. Aromatic region of the 1 H-NMR spectrum of the nanocar 1d with a 3,5-di-tert-butylphenyl as
	donor group and 4-cyanophenyl as accepting group (400 MHz, CDCl3). Protons corresponding to β-
	positions of porphyrin ring and to triptycenes were depicted as solid circle (•) and solid triangle (▲),
	respectively.
	nm (mol -1 dm 3 cm -1 ) l max (e) Soret N°4 l max (e) Q-bands	Exc. (nm) Em. (nm) Luminescence
	1d	38 (493600)	580 (17200) 629 (40300) 438	635
	2d	438 (522900)	581 (17300) 629 (40950) 438	634
	3d	439 (396850)	580 (18050) 630 (48800) 438	634
	10d	437 (495600)	580 (14800) 632 (41200) 438	637
	4d	439 (483300)	581 (17600) 628 (37000) 439	633
	5d	439 (526550)	579 (17400) 627 (37500) 439	632
	6d	439 (404900)	580 (18500) 627 (37250) 439	632
	11d	439 (538950)	580 (16350) 629 (38800) 439	634
	7d	435 (268250)	584 (13750) 635 (27800) 435	651
	8d	435 (275850)	584 (13850) 635 (27200) 435	652
	9d	436 (231250)	585 (14300) 635 (27550) 435	646
	12d	432 (165300)	587 (12050) 642 (28200) 435	661

From CV b From DFT c From UV-Vis d Red 2 a Red 1 Red on Ox 1 Ox 2 Ox on (in V vs Fc/Fc + )

									Band gap (eV)
	1d	1.77	-1.54 i	-1.58	0.49	0.82	0.41	1.99	5.28	2.66
	2d	-1.80	-1.52 i	-1.56	0.51	0.84	0.44	2.00	5.27	2.67
	3d	-1.60	-1.60 i	-1.45	0.49	0.82	0.42	1.87	5.28	2.60
	10d	-1.58	-	-1.50	0.42	0.77	0.35	1.85	5.25	2.66
	4d	-1.72	-1.54 i	-1.58	0.49	0.82	0.42	2.00	5.30	2.64
	5d	-1.70	-1.52 i	-1.55	0.50	0.84	0.43	1.98	5.30	2.66
	6d	-1.80	-1.61 i	-1.68	0.50	0.83	0.43	2.11	5.29	2.57
	11d	-1.81	-1.61 i	-1.62	0.46	0.78	0.39	2.01	5.29	2.67
	7d	-1.81	-1.54 i	-1.57	0.33	0.51	0.25	1.82	5.20	2.42
	8d	-1.78	-1.42 i	-1.59	0.33	0.52	0.25	1.84	5.18	2.42
	9d	-1.68	-1.56 i	-1.54	0.33	0.52	0.25	1.79	5.21	2.40
	12d	-1.77	-1.62 i	-1.60	0.24	0.36	0.17	1.77	5.16	2.40

  H NMR (600 MHz, CDCl3/TMS): δ = 10.35 (s, 2H), 9.44 (d, J = 4.8 Hz, 2H), 9.42 (d, J = 4.8 Hz, 2H), 9.16 (d, J = 4.2 Hz, 2H), 8.98 (d, J = 4.2 Hz, 2H), 8.42 (d, J = 8.4 Hz, 2H), 8.13-8.12 (m, 4H), 7.85 (t, J = 1.8 Hz, 1H), 1.57 (s, 18H), -3.09 (d, J = 10.8 Hz, 2H); 13 C NMR (100 MHz, CDCl3/TMS): δ = 149.2, 147.9, 146.4, 145.5, 145.3, 142.8, 139.7, 134.2, 132.6, 131.8, 131.4, 130.7, 130.5, 130.1, 126.3, 124.2, 122.5, 121.7, 121.5, 121.3, 114.2, 105.7, 35.1, 31.8. HR-MS (DCI/CH4) calcd. for C41H38N5 [MH] + : 600.3127, found 600.3131.

  H NMR (400 MHz, DMSO-d6/TMS): δ = 9.67-9.65 (m, 4H), 8.84 (d, J = 4.8 Hz, 2H), 8.78 (d, J = 4.8 Hz, 2H), 8.37 (d, J = 8.0 Hz, 2H), 8.30 (d, J = 8.0 Hz, 2H), 7.99 (d, J = 1.2 Hz, 2H), 7.88 (t, J = 1.6Hz, 1H), 1.54 (s, 18H); 13 C NMR (100 MHz, DMSO-d6/TMS): δ = 156.7, 148.6, 148.4, 148.2, 148.0, 145.3, 144.2, 133.3, 132.7, 132.1, 131.7, 130.8, 128.4, 128.6, 124.5, 122.7, 119.4, 114.6, 114.2, 106.4, 100.2, 67.4, 35.0, 31.7. HR-MS (ESI): calcd. for C41H33Br2N5Zn [M] + : 817.0394, found 817.0387.

  H NMR (400 MHz, CDCl3/TMS): δ = 10.16 (d, J = 4.8 Hz, 2H), 10.14 (d, J = 4.8 Hz, 2H), 9.16 (d, J = 5.2 Hz, 2H), 8.98 (d, J = 4.8 Hz, 2H), (m, 8H), 8.13-8.11 (m, 4H), 7.85 (t, J = 1.8 Hz, 1H), 7.57 (dd, J = 1.0, 7.5 Hz, 6H), 7.23 (td, J = 1.2, 7.5 Hz, 6H), 7.17 (td, J = 1.3, 7.4 Hz, 6H), 5.64 (s, 2H), 1.57 (s, 18H). 13 C NMR (150 MHz, CDCl3/TMS): δ = 152.7, 152.5, 151.0, 149.4, 148.9, 147.2, 145.1, 144.7, 140.8, 134.8, 134.2, 132.5, 132.0, 131.6, 130.6, 129.6, 126.0, 125.6, 123.8, 122.9, 121.4, 119.9, 111.9, 101.7, 94.7, 91.8, 54.9, 53.5, 35.1, 31.8; HR-MS (MALDI, DCTB): calcd. for C85H59N5Zn

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 European Union's Horizon 2020 research and innovation program under the project MEMO, grant agreement No 766864 and from the JSPS KAKENHI grant in aid for Scientific Research on Innovative Areas "Molecular Engine (No.8006)" 18H05419. C.J.M. thanks the JSPS KAKENHI Grant-in-Aid for Early-Career Scientists (19K15312) Y.G. thanks the French Ministry of National Education for a PhD Fellowship. We would like also to thank Dr. M. Miyake and Dr. T. Shikano (Institute for Research Initiatives, NAIST) for their constant support in the management of our International Collaborative Laboratory for Supraphotoactive Systems between CEMES and NAIST from 2014. The DFT calculations appearing in this article were performed using HPC resources from CALMIP (Grant 2020-p20041).

KEYWORDS: molecular machines • nanocar • porphyrinoids • donor-acceptor systems • triptycene


Dr Yohan Gisbert

Dr Seifallah Abid

Prof. Dr Claire Kammerer
email: kammerer@cemes.fr

Prof. Dr Gwénaël Rapenne
email: rapenne@cemes.fr

G Rapenne Cemes

Baldridge

Siegel

Molecular Gears from Solution to Surfaces

Keywords: cyclopentadienyl ligand, ruthenium, scanning tunneling microscopy, single molecule, triptycene

This review highlights the major efforts devoted to the development of molecular gears over the past forty years, from the pioneering covalent bis-triptycyl systems undergoing intramolecular correlated rotation in solution, to the most recent examples of gearing systems anchored on a surface, allowing for intermolecular transmission of mechanical power. Emphasis is laid on the different strategies devised progressively to control the architectures of molecular bevel and spur gears, as intramolecular systems in solution or intermolecular systems on surfaces, while aiming at increased efficiency, complexity and functionality.

Introduction

Molecular machines are ubiquitous in biological processes, where they perform specific tasks as a consequence of a stimulus, with a high level of control and efficiency. [START_REF] Balzani | Molecular Devices and Machines -A Journey into the Nano World[END_REF] Over the last decades, tremendous progress in synthetic and supramolecular chemistry has opened the way for the emergence of artificial molecular machines, carefully designed to master motions at the molecular level. This flourishing field was recently recognized by the Nobel committee with the 2016 prize awarded to J.-P. Sauvage, [START_REF] Sauvage | [END_REF] Sir J. F. Stoddart [3] and B. L. Feringa [4] for their pioneering investigations on mechanicallyinterlocked molecules and overcrowded alkenes, respectively. A broad variety of molecular architectures programmed to perform work have been reported to date and investigated in solution [5] or on surface. [6] Some of them have been designed in a technomimetic [7] way, i.e. taking macroscopic machines as an inspiration, such as molecular scissors, [8] pumps, [9] wheels, [10] wheelbarrows, [11] vehicles, [6b-e,12] winches, [13] elevators [14] and robotic arms. [15] Integration of several such machines into nanoscale machineries is highly desirable as it would allow the emergence of complex functional devices, but this remains a challenging task since it requires the interconnection of individual molecular units.

At the macroscopic scale, transmission of mechanical power between distinct machine elements is performed, among others, by gear systems, which in particular allow a modulation of speed and torque by an appropriate choice of the meshed cogwheels. Macroscopic gears are classified according to two criteria: i) the relative (external or internal) contact between cogwheels and ii) the relative orientations of rotation axes. External gears undergo synchronized disrotatory motion of the meshed cogwheels, and within this category, spur gears display parallel rotation axes while bevel gears are defined by the presence of intersecting rotation axes (Figure 1). Incidentally, micrometric gearing systems were recently found in nature, as part of the exoskeleton of the planthopper Issus coleoptratus, an insect recognized for its impressive jumps. [16] Studies revealed that the function of such meshed cogwheels located on the insect's hind legs are to provide mechanical coupling leading to highly synchronized movements. In contrast, man-made decimeter-scale gears dedicated to the transfer of mechanical power were already available during the Hellenistic period, giving rise to highly sophisticated machineries as evidenced by the Antikythera Mechanism (150-100 BC) that was discovered in a shipwreck in 1901. [17] Since ancient Greek times, numerous systems of increasing complexity have been engineered, exploiting gears as key elementary mechanical units. The size of cogwheels could be gradually reduced over the centuries as a consequence of technological progress and miniaturization could be pursued down to the nanometer scale using e-beam lithography to produce the smallest solid-state cogwheels reported to date, with a diameter of 70 nm. [18] However, this top-down strategy aiming at an ultimate miniaturization of cogwheels is now reaching its physical limits. As an alternative, technomimetic bottom-up approaches have been devised during the past 40 years to design and synthesize cogwheels at the molecular scale, and subsequently assemble them in a controlled manner into functional gearing systems.

This review aims at highlighting major progress in this field, from the pioneering work of Iwamura [19] and Mislow [20] on covalently linked triptycyl moieties undergoing intramolecular correlated rotation in solution, to the most recent examples of gearing systems anchored on a surface, allowing for the intermolecular transmission of mechanical power.

Intramolecular Gears in Solution

In the 70's, Oki investigated the rotation around single C(sp 3 )-C(sp 3 ) bonds in overcrowded systems, such as bonds located at the bridgehead positions of triptycene moieties. [21] In most cases, the energy barriers were high enough to isolate the different rotamers, thus revealing restricted rotary motion due to non-bonded interactions in these sterically-hindered structures. In contrast, unexpectedly low rotation barriers were also encountered in highly congested systems, where the correlated rotation of two submolecular units becomes the most energetically-favorable pathway, thus opening the way for the development of intramolecular gearing systems.

Bevel gears: from historical bis-triptycyl systems to switchable gears

The first systems involving meshed sub-molecular fragments and allowing for correlated motion were described by Iwamura in 1980. [19] These pioneering examples of intramolecular gears consisted of two triptycene units, acting as cogwheels, arranged in an angular way around an oxygen atom or a methylene CH2 group (Figure 2). In spite of the significant steric hindrance, as evidenced by the wide angles around the oxygen or carbon atoms, nearly unhindered rotation of both triptycene moieties down to -94°C was evidenced by Variable Temperature NMR spectroscopy. These results highlighted that the coupled rotation of two interlocked sub-molecular units in overcrowded systems may lead to conformational changes at very low energetic cost, by comparison with the independent rotation of a single subunit relative to the other. Correlated motion in such systems was further investigated by Mislow, who reported the same year an independent theoretical and experimental study on similar bis-triptycyl systems with CHOH or CH2 as central fragments (Figure 2). [20] Importantly, a single benzene ring in each triptycene moiety was substituted with methyl groups on the 2,3-positions, thus allowing for the discrimination of one tooth of each cogwheel. This labeling strategy was exploited to probe dynamic gearing in these early systems by use of stereochemical analysis, and such desymmetrization of cogwheels has been applied ever since to investigate correlated motion in a variety of intra-and intermolecular gear prototypes.

These pioneering works from Iwamura and Mislow unveiled the possibility of unhindered rotation in overcrowded molecular structures, thus opening the way for the development of numerous intermeshed systems undergoing intramolecular correlated motion in solution. In a technomimetic approach, various types of molecular gear-like architectures have been synthesized to mimic the different gearing arrangements used in macroscopic machinery, such as coaxial gearing systems [22] and more frequently spur-and bevel-gears. In the latter cases, triptycene moieties have been extensively exploited as prototypical molecular cogwheels with intrinsic-C3 symmetry.

In line with Iwamura and Mislow's preliminary reports, efforts have initially focused on molecular Trp2X bevel gears, composed of two triptycyl (Trp) cogwheels connected via their bridgehead position to a variety of central linkers (X), such as single-atoms (NH, [23] PH, [24] SiH2, [25] GeH2 [25] ) or molecular fragments (ethylene [26] or pyridine-2,6-dicarboxamide [27] ). The influence of the linker (affecting the angle between rotation axes and the Trp-Trp distance) and of the triptycene substitution pattern on the efficiency of the gearing process was investigated. [28] In the bevel gear systems involving a single atom as linker, a very low activation energy of 1-2 kcal.mol -1 is required for coupled disrotatory motion of the triptycenes, whereas conrotatory motion leading to gear slippage occurs with a high energy barrier of 32-45 kcal.mol -1 . [28] As a consequence, geared rotation in such bis-triptycenes is much more favorable than slippage, which can be quantified by gearing fidelity, defined as the average number of disrotatory geared rotations per conrotatory slipping rotations (Fgear = kgearing / kslippage). [29] The large difference in activation energies between gearing vs slippage pathways leads to gearing fidelities at 298 K above 10 23 for these systems. [30] These outstanding efficiencies can be explained by the difficulty required for the cogwheels to escape from their meshed configuration, which would require further enlargement of the wide angles between rotation axes. Following these fundamental studies, major improvements in the functionality of such bis-triptycyl gearing systems were brought by possible stimuli-responsive variations of the angle between the rotation axes, i.e. by introducing clutch-declutch mechanisms in a technomimetic mindset. The first example of a switchable gearing system was reported in 2008 by Setaka, Kira et al., [31] with two meshed triptycene units connected to a central silicon difluoride linker (Scheme 1). The authors showed that addition of potassium fluoride in combination with 18-crown-6 efficiently induced fluorination of the silane linker to afford the corresponding penta-substituted silicate anion. This resulted in a change from a tetrahedral to a trigonal bipyramid geometry, with the triptycyl moieties located on both apical positions. Accordingly, the angle between Si-C rotation axes was increased to 178°, thus preventing correlated rotation of the triptycenes. This process could be reversed by addition of excess water, showing that this silicon-based bevel gear system can be selectively clutched or declutched under the action of an external chemical stimulus.

Scheme 1.

Example of a chemical stimulus-responsive intramolecular bevel gear system, allowing for selective and reversible clutch-declutch mechanism via a geometry change at the central silicon atom. It must be noted both phase isomers (dl and meso) act as meshed molecular gears.

Other molecular systems featuring clutching mechanisms were developed later, taking advantage of different stimuli to achieve redox-, photo-or thermally-controlled gear coupling or uncoupling. [32] In particular, a notable metallo-organic bevel gear based on a square planar platinum(II) complex was shown to undergo engagement or disengagement of the triptycene-derived cogwheels as a consequence of heating or photoirradiation, respectively (Scheme 2). [33] In this very elegant example, Shionoya and collaborators present the design and synthesis of azaphosphatriptycene monodentate ligands with a methoxy group as a chemical tag on one benzene ring, allowing for coordination of transition metals through the phosphine moiety. Scheme 2. Bis(azaphosphatriptycene)platinum(II) dichloride complex as an example of metallo-organic bevel gear system, undergoing reversible disengagement and engagement as a consequence of photoand thermally-induced cis-trans isomerization. Adapted with permission from Ref. 33. Copyright 2017, Springer Nature. This ligand was employed to synthesize the corresponding cis-bis(azaphosphatriptycene)platinum(II) dichloride complex, as a prototype of meshed bevel gear system displaying correlated rotation of both ligands. Irradiation of this square planar complex efficiently promoted cis-trans isomerization, resulting in a configuration where the two coordinated cogwheels stand opposite to each other and are thus disengaged. This light-induced declutch mechanism could be reversed through thermal equilibration back to the favored cis-complex. Molecular bevel gears involving two triptycenes as cogwheels have been thoroughly investigated, with a striking evolution of their design to display very elegant switch function. In contrast, the development of intramolecular spur gears, with cogwheels meshed in a parallel arrangement, is still in its infancy.

Spur gears

The first example of a molecular structure displaying two triptycene units with parallel rotation axes was reported in 1999 by Bryan et al. [34] Both triptycenes were incorporated symmetrically in crown ethers via their bridgehead positions, to yield bis(9,10-triptycyl)-26-crown-6 and bis(9,10-triptycyl)-32crown-8 derivatives (Figure 3). Crystal structure analysis of both molecules demonstrated that the crown cavity is forced open by the bulky triptycene subunits, but to the best of our knowledge, correlated rotation was not confirmed due to the flexibility of the crown ether framework. Ten years later, in a perspective article, Siegel detailed the requirements for the development of bistriptycyl spur gears in a technomimetic way, i.e. using a rigid stator capable of maintaining two triptycene cogwheels in a parallel alignment by means of tailored shafts. [29] Importantly, in order for the cogwheels to be engaged, it is crucial that an entire benzene ring of one triptycene fits between two benzene rings of the neighboring triptycene, which is more challenging than in angular bis-triptycyl bevel gears. This highlights the utmost importance of the distance between parallel rotation axes in the design of intramolecular spur gears, as a compromise between attractive van der Waals interactions and excessive strain preventing rotation. While acetylene and bisacetylene fragments were constantly used as shafts, various designs of rigid stators were reported, with distances between the points of shaft attachment in the 5.0 -8.1 Å range (Figure 3). Prototypes of spur gears with the shortest distance were reported by Toyota et al., who exploited anthracene as stator, [35] whereas a bis(benzimidazole) scaffold with a distance of 8.1 Å was selected by Siegel et al. based on computational models. [30] In both cases, X-ray crystal structures reveal that the alkynyl shafts are bent, respectively outward and inward, due to interactions between triptycenes.

Very recently, Houk and Garcia-Garibay focused on norbornane-fused dibenzobarrelene as stator since this structure mimics the fusion of two triptycenes and may thus provide suitable inter-cogwheel distance. [36] However, none of these prototypes exhibited a strong preference for geared rotation over gear slippage, and in most cases, geared rotation could not be clearly evidenced by Variable Temperature NMR experiments.

2D metadynamics simulations were thus performed to establish the energy landscape for the rotational motion of both cogwheels, and energy barriers for gear slippage vs geared rotation were obtained by these potential mean force calculations. Interestingly, this theoretical study showed that gearing is favoured over slippage in the case of the bis(benzimidazole) spur gear reported by Siegel, since the activation barrier for slippage is higher (3.5 kcal.mol -1 ) than for gearing (2.4 kcal.mol -1 ). However, at room temperature, both gearing and slippage are expected to occur very rapidly, which strongly limits the functionality of such gear. Finally, for both prototypes with shorter inter-axes distances, barrier to slippage is lower than that to gearing, leading to a higher preference for slippage. To date, no example of a spur gear has been shown to exhibit high gearing fidelity, thus underlining the difficulties associated with the design of such systems, which appears much more challenging than for bevel gears.

A stimuli-responsive clutch-declutch mechanism was explored for spur gears with two triptycene cogwheels covalently linked to the second and fourth pyridine groups of a switchable quinquepyridine stator (Scheme 3). [37] In the absence of a metal ion, the foldamer adopts a linear conformation, due to electronic repulsion between adjacent pyridyl moieties, which results in the engagement of both triptycenes. Upon addition of silver cations, the formation of a mononuclear silver complex leads to a large-amplitude conformational change which brings the triptycyl units to lateral positions, in a disengaged state. Addition of chloride anions induces decomplexation, and the quinquepyridine stator recovers its linear conformation associated with meshed cogwheels, thus demonstrating the reversibility of the switch function.

Scheme 3.

Example of a chemical stimulus-responsive intramolecular spur gear system, allowing for a selective and reversible clutch-declutch mechanism via a conformational change resulting from silver complexation.

The intramolecular gear systems described in the first parts of this review all involve triptycene derivatives as cogwheels, owing to their bulkiness, rigidity, rather straightforward synthesis and highly symmetrical shape reminiscent of macroscopic paddlewheels. However, it is important to note that such prototypical scaffolds with three-fold symmetry are not ideal technomimetic candidates, since macroscopic three-toothed solid gears are not well-suited for correlated motion. Moving away from the seminal bis-triptycyl architectures, efforts have been devoted to the development of intramolecular gearing systems displaying increased complexity, with i) various cogwheel structures and higher teeth numbers, ii) higher numbers of meshed cogwheels, and iii) gearing ratios different from the 1:1 ratio obtained with two identical cogwheels.

N N N N N N N N N N Ag Ag Cl Engaged Disengaged

Increasing the complexity of gearing systems

Apart from triptycene derivatives, a few examples of scaffolds used as cogwheels in intramolecular functional gears have been reported in the literature, such as the four-toothed pentiptycenes, [38] tetraphenylcyclobutadienes, [39] and porphyrins. [40] To achieve a propagation of rotation over longer distances, an organized and robust arrangement of more than two cogwheels has to be set up, allowing for tight control over the relative distances and orientations between cogwheels. Diverse strategies have thus been explored to increase the number of cogwheels, based either on covalent or coordination frameworks.

Correlated motion in intermeshed covalent frameworks

An early example of linearly arranged triptycyl trimers, with oxygen atoms as linkers, was reported in 1986 by Iwamura. [41] This extended bevel gear system indeed underwent disrotatory correlated motion, but further increments of cogwheel number in such linear architecture were not attempted. Another strategy towards increased numbers of simultaneously meshed gears was the design of macrocyclic frameworks incorporating three to six triptycene units connected by both bridgehead positions. [42] Such macrocyclic structures were mostly synthesized through successive cross-coupling reactions with bis(ethynyl)triptycene as precursors, leading to a variety of shapes as a function of coupling partners.

An example of triangular macrocycle with six cogwheels operating as three independent pairs of bevel gears is depicted in Figure 4. Despite being very elegant, these systems display weak meshing because of their inherent flexibility. As an alternative, six mutually intermeshed triptycene moieties were circularly arranged around a central benzene core via ethynyl linkers (Figure 5). [43] This very hindered hexasubstituted benzene derivative was synthesized through a cobalt-catalyzed cyclotrimerization of triyne precursors, carrying two triptycenes at their extremities. X-ray diffraction analysis of the product revealed a strong structural engagement of the six triptycenes, involving pi-pi stacking between lateral benzene rings of neighboring cogwheels, and coupled rotation was evidenced by Variable Temperature 1 H NMR spectroscopy.

R R R R R R R = O(CH 2 ) 7 CH 3
Interestingly, in this study an unusual way to hinder the correlated motion of the six triptycene fragments was achieved by addition of a [RuCp*(NCMe)3]PF6 complex, leading to the coordination of RuCp* to one of the triptycenes' aromatic rings. As a result, the whole motion within the molecule was significantly restricted, and the RuCp* fragment can thus be considered as a chemical shim. The corresponding ruthenium complex appeared to be very stable and robust and could be isolated by chromatography before characterization. This shimming process is thus irreversible, not allowing for a stimuli-responsive reversible control of correlated motion. Beside covalent frameworks, another strategy towards intramolecular gears with increased complexity relies on coordination frameworks, with weaker bonds acting as shafts for the cogwheels composing the mechanical system. The combination of a wide variety of metallic centers and ligands allows for more synthetic modularity and leads to a broader range of accessible architectures, thanks to the variety of coordination modes.

Correlated motion in intermeshed coordination frameworks

A second notable example of circularly arranged multiple gear system was reported by Shionoya et al., consisting of a lantern-type dirhodium complex surrounded by four hexamethyltriptycene carboxylate ligands acting as meshed gears (Figure 6a). [44] In this complex, two additional ligands such as diethyl ether or pyridine derivatives, located on axial positions, were successfully exploited as control units to modulate the rate of correlated rotation, based on their steric hindrance. [45] The versatility of coordination chemistry was also exploited to access new cogwheel structures, thus opening the way for the implementation of gearing ratios, which is a key function in macroscopic gears.

In 1997, Stevens and Richards reported the design and synthesis of a cobalt-based metallocene complex, involving a tetraphenylcyclobutadienyl ligand meshed with a lateral triptycene unit (Figure 6b). [39] In Finally, Shinkai, Takeuchi et al. synthesized an impressive multi-porphyrinic architecture with different porphyrin sub-units used as suitable central cores for cogwheels, owing i) to their coordination ability to a wide variety of metal centers and ii) to multiple possibilities of functionalization on their outer rim. The central metal thus acts as a connector to the gear shaft, which is an apical ligand, while peripheral substituents, in particular located on meso positions, act as the teeth. This modular platform was exploited in different prototypes of structurally complex molecular bevel gears displaying correlated motion of four-toothed cogwheels. [40] One of these systems, which displays three intermeshed porphyrinic cogwheels, is depicted in Figure 7. [40a] The central bis(porphyrinate)lanthanum heteroleptic double decker incorporates one of the cogwheels, with the lanthanum atom acting as rotation axis, and the lower deck is further trans-functionalized with two lateral rhodium porphyrins via pyridyl units as shafts. Intrinsically, both rhodium porphyrins (in blue) have a higher rotation rate than the lanthanum double decker, but it has been shown that the rotation rate of the lateral rhodium cogwheels within this complex was decreased due to meshing interactions with the central porphyrin. In addition, the authors nicely showed that it is possible to disengage the cogwheels by basic treatment. Indeed, addition of triethylamine resulted in a dramatic increase in the rotation rate of lateral porphyrins, following a conformational change of the lanthanum double-decker triggered by the deprotonation of the uncoordinated pyrrole core. This disengagement is reversed through addition of trifluoroacetic acid, thus leading to a chemically controlled clutch-declutch system.

Multiple strategies to enhance complexity in molecular gearing systems, and in particular to increase the number of intermeshed cogwheels, have been envisioned but remain limited to intramolecular rigid structures, dictating the relative distance and orientation of cogwheels. Due to the continuous random motion of molecules in solution, it is indeed not conceivable to design intermolecular gears in such medium, which is a strong limitation for the development of multi-component nanomachineries. Moreover, the macroscopic picture of one cogwheel actuating the next one, i.e. of the transmission of mechanical power, is not relevant in solution as both cogwheels undergo thermally-induced random oscillations, which are harnessed in disrotatory coupled rotations due to mechanical engagement.

To propagate rotation over longer distances, new strategies were envisioned to control the orientation of molecules and their relative distances, including the preparation of 3D-frameworks such as amphidynamic crystals (Figure 8). Such very promising structures, which allow for a compromise between molecular order and molecular motion with liquid-like dynamics, have been reviewed recently. [46] As a complementary strategy towards long distance propagation of motion, the confinement of gearing systems in two dimensions has been envisioned, with the possibility to probe mechanical behaviors down to the single-molecule scale thanks to Scanning Probe Microscopy techniques.

Intermolecular Gears on Surfaces

Adsorption of molecular cogwheels on a surface offers a key asset to promote intermolecular gearing since the relative orientation of independent molecules can be controlled, which has prompted the development of spur gears. As in intramolecular systems, a crucial prerequisite for correlated motion is an appropriate and constant distance between the cogwheels, thus implying that molecular diffusion must be prevented. Preliminary studies on intermolecular gearing have been performed at low temperature (77 K or 5 K), taking advantage of Scanning Tunneling Microscopy (STM) under Ultra-High Vacuum (UHV) to monitor motion with sub-molecular resolution. Since STM is not timeresolved, rotation of single-molecule cogwheels is evidenced by comparison of successive images, which usually requires the presence of a steric or chemical tag in the molecular structure. In addition to imaging capabilities, the tip of a STM can also be used for the mechanical actuation of single molecules, leading to their translation or rotation. Therefore, starting from motionless cogwheels organized in a train of gears at low temperature (5 K), it can be envisioned to induce the rotation of the first cogwheel by mechanical actuation with the STM tip and observe the transmission of mechanical power from one molecule to the next through disrotatory correlated motion. However, before focusing on single molecules, the first studies of gearing systems on surfaces were achieved in self-assemblies of cogwheels.

Self-assembled gearing devices on surface

Already back in 1998, Gimzewski et al. investigated by STM the behavior of propeller-shaped hexa-tert-butyldecacyclene molecules on a Cu(111) surface under UHV. [47] At monolayer coverage, a self-assembled 2D network of immobile molecules was observed, whereas a coverage slightly below one complete monolayer allowed for the thermally-driven rotation of some single-molecule propellers within the bearing formed by the surrounding molecules. This pioneering work about (non-directional) molecular rotors on surfaces raised key questions about the mechanics of surface adsorbed molecular systems.

The very first example of intermolecular gearing was reported in 2007 in a molecular rack-and-pinion device exploiting penta(p-tert-butylphenyl)-(p-tert-butylpyrimido)benzene as six-pointed star-shaped molecule. [48] The self-assembled monolayer obtained on Cu(111) at low temperature acts here as the rack, displaying indentations on its border. The STM lateral manipulation of a single molecule along the edge of this molecular island, with the STM tip precisely located above the central benzene ring, results in a rotation of the molecule in addition to the STM-induced translation. This rotary motion was evidenced by comparison of successive STM images following the relative positions of the heteroaromatic pyrimidine tooth behaving as a chemical tag. The concept is illustrated in Figure 9. The rotation results from the interlocking between the tert-butyl groups of the self-assembled rack and those of the single molecule, thus acting as a pinion. It is important to note that in this experiment, diffusion of molecular species is prevented since i) the rack stands as a self-assembled monolayer and ii) the pinion is trapped under the STM tip, which provides a rotation axis.

Following this first example of an external gearing system built on a surface, further studies were performed at single-molecule scale to achieve the transfer of mechanical power from one molecule to the next one via synchronized disrotatory motion. As shown in this rack-and-pinion system, adsorption of custom-made molecules on a surface allows for a homogeneous orientation of rotation axes over the population of molecular gear prototypes. The critical point to build trains of molecular gears stands now in the anchoring of individual cogwheels. Indeed, all attempts using pairs of the abovementioned molecules in close contact failed to transfer rotation from one molecule to the next, due to the favored diffusion of the second molecule over its desired rotation.

Anchoring of single-molecule cogwheels on surface to build trains of gears

Single metal atoms as rotation axes

Following the seminal work on the rack-and-pinion device, the same hexa(aryl)benzene cogwheel prototype, incorporating a pyrimidyl chemical tag, was studied at the single-molecule scale on a Au(111)

surface. [49] Even at low-temperature (5 K), such molecules displayed high mobility on Au( 111), but it was demonstrated that an atomic scale impurity located at the elbow of the herringbone reconstruction can efficiently act as a stable pinning center. Indeed, once mounted and centered on top of this defect via STM lateral manipulation, the molecule underwent stepwise concentric rotations upon mechanical actuation by the STM tip. While the random distribution of atomic scale impurities hampers their use to build trains of anchored molecular cogwheels, this pioneering concept was recently extended to the use of single metal atoms as pinning centers. On a Pb(111) surface at 5 K, single Cu atoms were successfully exploited as fixed rotation axes for the same hexa(aryl)benzene cogwheel prototype. [50] First, the sixpointed molecule is translated towards a single Cu atom by STM lateral manipulation and centered on top of it, owing to privileged interactions between copper and the central benzene ring (Figure 10). Then, a second molecule is approached and entangled with the first one. Importantly, this second molecule is not mounted on a Cu single atom, as it acts as a handle to stabilize the cogwheel and drive its controlled and concentric rotation. Finally, another cogwheel centered on top a Cu single atom is approached by STM lateral manipulation to build a molecular gear system, involving two cogwheels with Cu shafts and one additional handle for the driver molecule. The distance between Cu rotation axes was carefully optimized as it should be i) small enough to allow meshing of the cogwheels, leading to transmission of rotation by repulsive interactions between the teeth, but ii) large enough to avoid attraction between cogwheels, which would generate a stable supramolecular dimer unable to undergo correlated motion.

With an optimal Cu-Cu distance of 1.9 nm, a functional gear system was built and the rotation of the driver molecule (induced by STM mechanical manipulation of the handle) was successfully transmitted to the second molecular cogwheel. In an attempt to increase the size of this gear system, the diameter of the cogwheels was extended by inserting an additional phenyl moiety in each tooth. [51] The same set-up involving two cogwheels mounted each on a Cu atom and an additional handle molecule was successfully implemented, but optimization of the inter-axis distance did not reveal any appropriate relative position of the cogwheels allowing for correlated motion. As mentioned above, attraction prevails at short distances and when the cogwheels are located further apart, the flexibility of the p-tert-butylbiphenyl teeth leads to gear slippage.

These pieces of work highlight the challenges encountered in the development of intermolecular singlemolecule gear systems on surfaces, requiring the identification of appropriate surfaces and atomic scale rotation axes, in direct relationship with the structure of the molecular cogwheels. For the latter, the design of the central core is intimately related to the nature of rotation axes, while the teeth structure has to prevent flexibility. Since this field is still in its infancy, such empirical approaches by trial and error allow progressive identification of appropriate strategies towards intermolecular functional systems.

Direct chemical anchoring

An alternative approach to restrict diffusion of molecular cogwheels on a metallic surface consists of using direct chemical bonding. In 2008, Gao et al. reported the anchoring of single zinc phthalocyanines on Au(111) via a strong chemical bond arising between a gold adatom and one of the outer nitrogen atoms of the phthalocyanine structure. [52] Such anchoring totally prevents molecular diffusion at 77 K while rotation of the molecular species is observed. However, the off-center position of this chemical rotation axis generated in situ leads to non concentric motion, which is a pre-requisite for geared rotation.

Inspired by coordination chemistry and the known ability of cyclopentadienyl ligands to bind to a wide variety of metal centers with  5 hapticity, Moresco et al focused on pentaarylcyclopentadienyl scaffolds as prototypes of star-shaped cogwheels. [53] Sublimation of bromocyclopentadiene precursors led to the homolytic cleavage of the C-Br bond and, as a result, pentaarylcyclopentadienyl radicals were thus deposited on the Au(111) surface. Structural characterization by STM along with DFT simulations confirmed the adsorption geometry of the cogwheel, with the central cyclopentadiene core lying parallel to the surface. In this system, the five carbon atoms contribute to the bonding with three gold atoms underneath, which leads to concentric rotations around this chemical axis. Efficiency of such an anchoring strategy in molecular gearing was demonstrated with a sterically tagged cogwheel, incorporating a single p-tert-butylphenyl tooth among four shorter phenyl teeth. A train of three coupled cogwheels was built and upon mechanical actuation of the driver molecule by STM manipulation of the tert-butyl group, disrotatory motion of the two followers was observed (Figure 11). This chemicallyanchored system, involving three meshed cogwheels, is the longest functional intermolecular train of gears reported to date. In the two previous strategies aimed at anchoring single molecule cogwheels on the surface, tailored cogwheels were synthesized as purely organic frameworks and assembly with the rotation axis was achieved in situ upon deposition on the surface. As an alternative, it was envisioned to take advantage of the concepts of coordination chemistry to pre-assemble prior to on-surface deposition the cogwheel and possible anchoring groups around a central metal atom which can act as rotation axis. In this way, the structure of the resulting functional metallo-organic species can be controlled and improved by modular synthetic routes, with the aim of reaching optimal mechanical properties.

Single-molecule cogwheels mounted on metallo-organic anchors

Molecular azimuthal rotors based on ruthenium complexes have been developed for two decades in our group with a variety of functions being targeted, such as motors, [6f,6h,54] turnstiles, [55] and winches. [13] Importantly, these technomimetic molecular machines have been studied by STM at the single-molecule scale on metallic surfaces at low temperature. As a result, beside the ligand acting as an azimuthal rotor, the design of such ruthenium complexes includes a second ligand meant to act as anchoring unit on the surface, to preclude any diffusion process during on-surface investigations. Hydrotris(indazolyl)borates exhibiting a facial  3 coordination mode have in particular been widely exploited as tripodal stator subunit, [54b,56] with specific functional groups appended to the 6-position of indazole cores. Ethylthioethers have been selected to provide tight adsorption on noble metals, and it has been shown that diffusion is indeed totally frozen at 5 K while translation of the ruthenium complexes by STM lateral manipulation is possible at 77 K. This property is particularly interesting to set up trains of molecular gears, since individual cogwheels pre-assembled with both their rotation axis and their anchoring unit could be moved at 77 K from their initial random location to build up linear arrangements of ruthenium complexes with controlled intermolecular distances. Lowering the temperature to 5 K would then lock this multi-molecular set-up, while mechanically-induced azimuthal rotation of the upper ligand would still be possible. In line with earlier reports about piano-stool ruthenium complexes acting as molecular machines, pentaarylcyclopentadienyl ligands were selected as prototypical star-shaped cogwheels to be pre-assembled using ruthenium as a rotation axis, lifted up from the surface by a scorpionate ligand as anchoring unit.

In the first series of prototypes, synthetic efforts were focused on the preparation of metallo-organic architectures incorporating C5-symmetric cogwheels with a variety of teeth and displaying increasing diameters. [56b] The modular synthetic approach relied on a single-step post-functionalization of a penta(p-bromophenyl)cyclopentadienyl ruthenium(II) complex as key precursor, [5758] via five-fold cross-coupling reactions. Teeth of increasing lengths and contact areas were thus incorporated, such as small methyl-and tert-butyl-substituted phenyl moieties, carbazoles, BODIPYs and finally flat bidimensional porphyrins, leading to cogwheel diameters over 5 nm.

In anticipation of on-surface investigations by STM, a second series of pentaporphyrinic prototypes were designed with a lower symmetry of the upper rotating subunit. [58] Steric labelling was successfully achieved by varying the length of the spacer between the cyclopentadienyl core and the porphyrinic macrocycle, using a longer phenylethynylphenyl fragment instead of 4,4'-biphenylenes (Figure 12, top).

Starting from penta(p-halogenophenyl)cyclopentadienyl ruthenium(II) as a key building block bearing a single pre-activated p-iodophenyl group, controlled insertion of the labelled tooth was achieved by a chemoselective Sonogashira cross-coupling followed by four-fold Suzuki-Miyaura reactions to append the shorter teeth. [13] The same approach involving sequential chemoselective couplings was next applied to the synthesis of chemically-tagged cogwheels, expected to exhibit improved intermolecular mechanical interactions due to the homogeneity of the teeth shapes. To induce sub-molecular contrast on STM images, the electronic properties of one single porphyrinic paddle were modulated as compared to the four others, either by changing the nature of the central metal atom or by appending electron-withdrawing substituents. In the example shown below (Figure 12, bottom), the organic skeletons of the cogwheels are perfectly symmetric but different metal ions (one zinc and four nickel) are coordinated in the porphyrins. The resulting desymmetrized prototypes of pentaporphyrinic cogwheels, pre-assembled to their ruthenium rotation axis and their scorpionate anchoring unit, are currently studied as single molecules on surface.

Summary and Outlook

Over the past forty years, tremendous efforts have been devoted to the development of functional gearing systems at the molecular scale. As pioneers in the field, Iwamura and Mislow unveiled correlated disrotatory motion as an energetically favorable pathway in highly constrained systems, and reported the first examples of intramolecular bevel gears based on covalently linked bis-triptycyl scaffolds. Ever since, progress in the field led to a variety of intramolecular bevel and spur gears, displaying increased levels of complexity and functionality, such as stimuli-responsive behaviors. We would like also to mention a very innovative approach to the transmission of molecular motion developed recently by the group of Harry Anderson. [59] They successfully achieved correlated rotary motion of two oligopyridyl wheels, not by a direct gearing mechanism in a disrotatory pathway but through the intermediate of a polyporphyrinic belt leading to a conrotatory process. Contrary to the molecular gears reviewed in this article, the two wheels thus rotate in the same direction and these supramolecular systems including both wheels and the surrounding belt can be considered as caterpillar tracks according to technomimetic principles.

In these systems designed for in-solution studies, gearing mechanisms are however inherently limited to intramolecular correlated motion of sub-molecular fragments, which strongly limits their use in the quest for multi-molecular nanomachineries. Strategies for intermolecular gearing have thus been explored, including the preparation of 3D-frameworks and the confinement of molecular cogwheels in two dimensions. In the latter case, Scanning Tunneling Microscopy offers the opportunity to probe mechanical behaviors down to the single-molecule scale. The key parameter for successful correlated disrotatory motion between independent molecular cogwheels is the absence of diffusion. Several strategies have been devised for the anchoring of individual molecules on a surface. Specificallydesigned cogwheels have been centered on top of a single metal atom acting as rotation axis, preassembled in solution to a metallo-organic anchor or directly chemically-bound to the metallic surface. This latter option has given rise to the longest functional intermolecular train of gears, involving three meshed cogwheels undergoing correlated disrotatory motion.

Following these milestones in the field, several challenges to increase the complexity and functionality of intermolecular gear systems remain to be tackled. First, rigid cogwheels with larger diameters and increasing numbers of teeth should be designed, possibly allowing for the implementation of gearing ratios on surfaces. In addition, the self-assembly of individual cogwheels into highly-ordered monodimensional networks with appropriate intermolecular distances would be highly desirable in order to generate trains of gears over long distances, without requiring STM manipulation to position each molecule. Finally, connection of gear trains to compatible molecular motors as sources of mechanical power should be investigated in anticipation of the development of multi-molecular machineries at the nanoscale.

Figure 1 .

 1 Figure 1. a) Structure of a macroscopic spur gear system with parallel rotation axes; b) Structure of a macroscopic bevel gear system with intersecting rotation axes.

Figure 2 .

 2 Figure 2. a) Molecular structure of the series of bis-triptycyl bevel gears initially reported by Iwamura and Mislow; b) X-ray crystal structure of bis(triptycyl)ether, with faded CPK model to highlight steric congestion and meshing of the triptycene cogwheels.

Figure 3 .

 3 Figure 3. Structure of a macroscopic spur gear system and molecular structures of reported bis-triptycyl spur gears, incorporating a variety of stators.

Figure 4 .

 4 Figure 4. Covalent macrocyclic framework incorporating three pairs of engaged triptycene units in a constraint triangular configuration.

Figure 5 .

 5 Figure 5. Synthesis of a circularly arranged sextuple triptycene gear molecule (top) and its rotation control by coordination of an organometallic shim (RuCp*) (bottom). Adapted with permission fromRef.43. Copyright 2017, American Chemical Society.

  CH 2 ) 11 CH 3 this organometallic gearing system, correlated motion thus occurs between four-and three-toothed wheels, as one of the rare examples of gearing ratio at the molecular scale.

Figure 6 .

 6 Figure 6. Examples of bevel gears incorporated in coordination frameworks. Adapted with permission from Ref. 44. Copyright 2016, American Chemical Society.

Figure 7 .

 7 Figure 7. Molecular structure (left) of a porphyrin-based bevel gear. Two porphyrinatorhodium(III)based cogwheels (blue) are connected to pyridyl groups at the meso position of the porphyrin in the La(III) double decker unit. The rotational motion of the La(III) double decker cogwheel (red) was decreased by adding a base, while the rotation rate of both rhodium(III) cogwheels was dramatically increased, thanks to the conformational change from the uncoordinated pyrrole NH group to a deprotonated N -group. Consequently, the bevel-gear-shaped rotor was converted from a meshing state to an independent state. Adapted with permission from Ref. 40b. Copyright 2011, Wiley-VCH.

Figure 8 .

 8 Figure 8. Structure of amphidynamic crystals composed of spacer (in blue: dicarboxylates such as terephthalate, biphenyl-4,4′-dicarboxylate, and triptycene-9,10-dicarboxylate), metal cluster (in grey) and rotor units featuring meshed triptycene cogwheels. Reproduced/Adapted with permission from Ref. 46. Copyright 2020, Royal Society of Chemistry.

Figure 9 .

 9 Figure 9. Different steps 1 to 4 of the geared rotation of a single molecular pinion along the edge of the rack of a self-assembled monolayer of the same molecules. A macroscopic rack-and-pinion (top right) and the chemical structure of the cogwheels (middle right). The pyrimidine chemical tag of the moved cogwheel is indicated in blue.

Figure 10 .

 10 Figure 10. Structure of the molecular cogwheel (top right) and STM images showing the disrotatory correlated motion of two cogwheels anchored on single Cu atoms, when actuated via a molecular handle. Adapted from Ref. 50 with permission from the ACS, Copyright 2019.

Figure 11 .

 11 Figure 11. Structure of the star-shaped molecular cogwheel in its radical state (right) and STM images showing the disrotatory correlated motion of three cogwheels directly anchored on a Au(111) surface upon mechanical actuation by the STM tip (the red arrow highlights the trajectory of the tip) (left). The cogwheel on the right is not meshed with the driver, hence no rotation is observed. Adapted from Ref. 53 with permission from the ACS, Copyright 2020.

Figure 12 .

 12 Figure12. Structure of two desymmetrized pentaporphyrinic cogwheels mounted on metallo-organic anchors. The upper one has a longer tooth (in green) with an additional ethynyl spacer while the bottom one only differs by the metal coordinated in the porphyrins, one zinc (in green) and four nickel (in blue).

N N N

Acknowledgements

This work was supported by the University Paul Sabatier (Toulouse) and CNRS. It has received funding from 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 and the KAKENHI Grant-in-Aid for Challenging Research (20K21131). Y.G. thanks the French Ministry of National Education for a PhD Fellowship. Dr. Colin Martin is warmly acknowledged for his careful reading and improving of our manuscript.