ARTICLES PUBLISHED ONLINE: 14 SEPTEMBER 2014 | DOI: 10.1038/NCHEM.2057
Dynamic covalent chemistry of bisimines at the solid/liquid interface monitored by scanning tunnelling microscopy Artur Ciesielski, Mohamed El Garah, Sébastien Haar, Petr Kovaříček, Jean-Marie Lehn* and Paolo Samorì* Dynamic covalent chemistry relies on the formation of reversible covalent bonds under thermodynamic control to generate dynamic combinatorial libraries. It provides access to numerous types of complex functional architectures, and thereby targets several technologically relevant applications, such as in drug discovery, (bio)sensing and dynamic materials. In liquid media it was proved that by taking advantage of the reversible nature of the bond formation it is possible to combine the error-correction capacity of supramolecular chemistry with the robustness of covalent bonding to generate adaptive systems. Here we show that double imine formation between 4-(hexadecyloxy)benzaldehyde and different α,ω-diamines as well as reversible bistransimination reactions can be achieved at the solid/liquid interface, as monitored on the submolecular scale by in situ scanning tunnelling microscopy imaging. Our modular approach enables the structurally controlled reversible incorporation of various molecular components to form sophisticated covalent architectures, which opens up perspectives towards responsive multicomponent two-dimensional materials and devices.
S
upramolecular chemistry1–3 relies on the use of non-covalent interactions to self-assemble chemical entities, with a level of precision on the subnanometre scale, to form materials that exhibit programmed chemical and physical properties. However, the labile nature of non-covalent interactions means the stability of the self-assembled structures is limited, especially in liquid media, and this thereby jeopardizes their technological exploitation. In this regard, the possibility of constructing molecular architectures based on chemical elements that interact through more robust, yet reversible, bonds, has evolved supramolecular chemistry towards dynamic covalent chemistry (DCC)4,5. Significantly, DCC shares numerous features with supramolecular chemistry—in particular, they both rely on reversible bonds that enable the formation of products under thermodynamic control. Both supramolecular chemistry and DCC are modular because they allow for the selection and exchange of (supra)molecular components4–8, and thus represent branches of constitutional dynamic chemistry9,10. However, there are two major differences between these two types of reversible chemistry approaches. The equilibration processes are much slower in DCC systems when compared to supramolecular ones, because in the former covalent bonds have to be broken and reformed. Moreover, supramolecular chemistry concerns the formation of non-covalently tethered aggregates (supermolecules and/or supramolecular architectures), which are by nature more fragile than the structures produced by DCC. For these reasons DCC has emerged as an efficient and versatile strategy for the design and synthesis of complex molecular structures. Although early examples of supramolecularly assisted covalent synthesis relied strongly on kinetically controlled reactions for post-assembly covalent modification11, the DCC method takes advantage of the reversible nature of bond formation, for example disulfide12, acetal13,14, ester15, imine16–21 and boroxine (B3O3)22,23 bonds, to allow the generation of new covalent structures under thermodynamic control.
Functional groups that involve a carbonyl or C=N unit, such as imines, esters or amides, are of special interest because they may undergo disconnection/reconnection cycles (for example, trans reactions like imination, esterification and amidation). In particular the reversible nature of imine bond formation makes it an attractive process for use in DCC5–11,24, because the (amine + carbonyl) condensation into imine-type compounds usually takes place under mild conditions. In general, imines can participate in three types of equilibrium-controlled reactions: (1) hydrolysis, in which the imine reverts back to the precursors, that is, amine and carbonylcontaining compound(s), on the addition of water; (2) transamination, in which, with the introduction of a second amine (or carbonyl-based molecule), the original imine may undergo an exchange of the amine residue to give a new imine; (3) imine– imine exchange, in which, on the introduction of a second imine, the two imines can undergo a reaction whereby the amine components are exchanged24. Dynamic exchanges that involve the C=N bonds in imines, hydrazones and oximes are the most widely used dynamic covalent reactions. They have been applied to the syntheses of complex two-dimensional (2D) and threedimensional (3D) molecular architectures, covalent organic frameworks and the construction of self-sorting systems, rotary switches and molecular walkers21,25 and to study motional covalent dynamics26. The dynamic behaviour of imines is of special interest in view of its central role in chemistry and biochemistry27 as well as in materials science28,29. Over the past decade, on-surface chemistry has attracted considerable attention in nanoscience and molecular electronics, because it represents a novel bottom-up approach for producing defined functional nanostructures through the rigorous covalent coupling of organic precursor molecules under kinetic control30–33. The need to explore ordered architectures at the molecular scale has made scanning tunnelling microscopy (STM)34 a widely employed extremely powerful tool to study supramolecular materials at their interfaces
ISIS & icFRC, Université de Strasbourg & CNRS, 8 allée Gaspard Monge, 67000 Strasbourg, France. * e-mail: [email protected]; [email protected] NATURE CHEMISTRY | ADVANCE ONLINE PUBLICATION | www.nature.com/naturechemistry
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DOI: 10.1038/NCHEM.2057
A 0.5 equiv. B12
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Figure 1 | Condensation of aldehyde A with α,ω-diamines. Schematic representation of condensation reactions of aldehyde A (4-(hexadecyloxy)benzaldehyde) with α,ω-diamines B2 (1,2-diaminoethane, red), B6 (1,6-diaminohexane, green) and B12 (1,12-diaminododecane, blue) that yield bisimines A2B2, A2B6 and A2B12, respectively. The constitutional covalent dynamic processes of bistransimination, that is, the reversible imine exchange reaction, takes place in the presence of a competing diamine, and thus the new bisimine A2B6 is formed when B6 is mixed with A2B2, which leads to a dynamic equilibrium of the products. Similarly, bisimine A2B12 is produced when B12 is mixed with either A2B2 or A2B6.
with submolecular resolution, and provides direct insights into the supramolecular world35–40. The subnanometre resolution that can be achieved by STM imaging makes it possible to gain detailed information on molecular interactions; thus, it is a crucial tool to assist in the design of molecular modules that undergo controlled self-assembly at surfaces under various experimental conditions (temperature, pressure and concentration) to form the chosen supramolecular structures. Beyond the mere visualization of the 2D ordering of physisorbed monolayers, recent studies have shown that STM has much potential application in a vast variety of topics, such as monitoring molecular dynamics41,42, molecule manipulation43–47, surface chirality48 and so on. Among the self-assembled structures investigated by STM, those that comprise boroxines49,50 and imines51,52 are particularly stimulating because they can be explored further in the context of surface-assisted DCC, for example on-surface formation and/or the breaking of B3O3 bonds53. Although condensation of an amino group with a carbonyl functionality to form an imine/Schiff base has been studied by STM both in an ultrahigh vacuum54,55 and at a water/gold interface56, the implementation of reversible covalent bonds, such as the C=N one, has not been explored. Herein we report a submolecularly resolved STM mapping of the surface-mediated reversible exchange processes of aliphatic bisimines that occur at the solid/liquid interface on a highly oriented pyrolitic graphite (HOPG) surface. We focused our attention on (1) the condensation of 4-(hexadecyloxy)benzaldehyde (A) with different α,ω-diamines, that is, 1,2-diaminoethane (B2), 1,6-diaminohexane (B6) and 1,12-diaminododecane (B12), as well as on (2) the constitutional covalent (reversible) dynamic processes of bistransimination, that is, diamine exchange on the bisimines, as illustrated on Fig. 1. Both the aldehyde and the α,ω-diamines are equipped with long aliphatic chains, which are known to exhibit a high affinity for the HOPG surface and therefore promote the molecular physisorption with respect to its solvation. However, the interactions between molecules and the HOPG surface are of a van der 2
Waals type, and therefore offer a dynamic scenario characterized by potential desorption and readsorption. The surface-mediated processes described here, together with their covalent, yet reversible, type of structures, make imines a class of compounds that presents a particularly rich and wide palette of structural features, as well as of constitutional dynamic behaviours.
Results and discussion Initially, we investigated the self-assembly of A by applying a drop of a 0.1 mM solution of A in 1-phenyloctane on the HOPG surface. The STM image of the obtained monolayer (Fig. 2a) showed a crystalline structure that consists of lamellar architectures. In this 2D crystal, molecules A are physisorbed flat on the surface. The supramolecular motif is stabilized by relatively strong molecule–graphite van der Waals interactions (for details, see the Supplementary Information) and molecule–molecule van der Waals and dipole– dipole interactions. The self-assembly of A molecules can be described by the formation of trimer-like subunits (indicated in red in Fig. 2b), which further expand into lamellar arrays characterized by an assembly that consists of an aldehyde-to-aldehyde motif within a given lamella and tail-to-tail packing between adjacent lamellae. None of the α,ω-diamine derivatives (B2, B6 or B12) was found to form ordered structures at the liquid/solid interface, which highlights their highly dynamic nature on the graphite surface on a timescale faster than that of STM imaging, as determined by their low affinity for HOPG. In situ generation of bisimines. STM was used to probe the in situ synthesis of bisimines by the addition of 0.5 equiv. α,ω-diamines (that is, B2, B6 or B12) on top of a pre-existing monolayer of A. To this end, a 2 µl drop of a 0.1 mM solution (pyridine: 1-phenyloctane, 1:99 vol:vol) of B2, B6 or B12 was deposited on top of a monolayer of A formed by applying a 4 µl drop of a 0.1 mM solution of A in 1-phenyloctane on the HOPG surface. A small amount of pyridine was added to ensure solubilization of all
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Figure 2 | STM images of self-assembled 2D nanopatterns. a,c,e,g, Monolayer of aldehyde A (a) and bisimines A2B2 (c), A2B6 (e) and A2B12 (g) at the liquid/graphite interface self-assembled from a solution in 1-phenyloctane. Tunnelling parameters: average tunnelling current (It ) = 10–15 pA, bias voltage (Vt ) = 400–600 mV. b,d,f,h, Molecular packing motifs of A, A2B2, A2B6 and A2B12 are shown in panels b, d, f and h, respectively. Crystalline patterns obtained from each molecule self-assembled on HOPG are described by the unit cell size (vectors a and b). Bright spots linearly aligned (easily visible on the STM images) can be attributed to the phenyl rings of the A units. The only difference between the A2B2, A2B6 and A2B12 structures is the value of the c parameter (that is, the distance between the phenyl rings (length of the B bridge)), whereas the value of parameter d (which corresponds to the length of two hexadecyloxy chains) remains constant. For clarity, bisimine cores (the spacers between C=N bonds) are highlighted using different colours (B2, red; B6, green; B12, blue).
three compounds, especially B12 (see Supplementary Information for details). In all three cases, the addition of α,ω-diamine resulted in the desorption of A followed by formation of new
types of 2D crystals (Fig. 2c,e,g). These changes can be attributed to the formation of A2B-type bisimines by condensation between the carbonyl group of A and the amino groups of B molecules, with the production of water as the side product (Fig. 1). Interestingly, regardless of the length of the diamine main chain (C2H4 for B2, C6H12 for B6 and C12H24 for B12), the observed monolayers of A2B2, A2B6 and A2B12 exhibit a similar lamellar assembly motif. For the crystalline pattern obtained from each molecule self-assembled on HOPG, the unit cell parameters, that is, the length of the vectors a and b, angle between the vectors, α unit cell area (A), number of molecules in the unit cell (Nmol ) and area occupied by a single molecule in the unit cell (Amol , with Amol = A/Nmol ) are given in Table 1. In the 2D crystals, the long hexadecyloxy side chains of the A units are clearly visible, and are physisorbed flat on the surface, whereas the different orientation of spacer chains (that is, the main chain of the B units) with respect to the underlying HOPG surface affects their electronic coupling, and therefore they do not appear as clearly as the hexadecyloxy chains. Furthermore, linearly aligned bright spots (noticeably visible on the STM images) can be attributed to the phenyl rings of the A units. Further comparison of the unit cell parameters of all the monolayers self-assembled at the HOPG/solution interface (Table 1) reveals that the only difference between these structures is the value of the c vector, that is, the distance between the phenyl rings (length of the B bridge). Importantly, STM measurements on ex situ synthesized (see Supplementary Information for the details) bisimines revealed the formation of monolayers that present identical unit cell parameters when compared with in situ synthesized bisimines, which provides unambiguous evidence of the successful condensation between aldehydes and diamines, and consequent formation of covalent C=N bonds at the phenyloctane/graphite interface. Condensation reactions that occur at the solid/liquid interface were found to be typically much faster when compared to the same reactions performed in solution, most probably for two main reasons: (1) at the solid/liquid interface the concentration is at least higher than a saturation regime, whereas in bulk solution the concentration is typically much lower, and (2) the confinement in quasi-2D may facilitate the reaction by lowering the activation barrier57. In the present case, the rates and rate constants of the condensation and exchange reactions determined by 1H NMR spectroscopy revealed that, at the concentration used for STM experiments (that is, 0.1 mM), the time needed to produce 3.5 × 1013 A2B molecules (which corresponds to the number of molecules in a tightly packed monolayer that covers a 1 × 1 cm2 graphite surface) is 104 times longer in solution than that at the solid/liquid interface (for details on rate-constant determination, see the Supplementary Information and Supplementary Excel macro). In the extreme case of a reaction that occurs ‘literally’ on the surface, the molecular concentration would be four orders of magnitude greater than that in solution. In the present case, because of (1) the different areas occupied by the precursor and product molecules, and (2) the steric hindrance requirements for rehybridization of nitrogen atoms from sp 2 to sp 3 that occurs in the first step of the reaction, the condensation between aldehyde A and α,ω-diamine derivatives takes place through a desorption/bisimination/readsorption process. Moreover, even in the region near to the surface, one can expect a much greater concentration than in solution, similarly to the well-known case of the Stern layer for electrolytes. However, no models have hitherto been developed that allow for a quantitative description of the concentration of an apolar molecule in an apolar liquid with increasing distance from a solid substrate. In situ bistransimination. To explore fully the reversible nature of C=N bonds, and to gain insight into the bistransimination processes
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Table 1 | Unit-cell parameters of A2B2, A2B6 and A2B12 monolayers. Structure A A2B2 A2B6 A2B12
a (nm) 3.98 ± 0.31 4.73 ± 0.42 5.88 ± 0.54 6.51 ± 0.62
b (nm) 1.71 ± 0.11 0.60 ± 0.06 0.60 ± 0.06 0.60 ± 0.06
α (°) 92 ± 2 90 ± 2 90 ± 2 90 ± 2
c (nm) NA 0.81 ± 0.01 1.94 ± 0.01 2.58 ± 0.01
d (nm) NA 3.92 ± 0.01 3.94 ± 0.01 3.93 ± 0.01
A (nm2) 6.80 ± 0.43 2.84 ± 0.28 3.53 ± 0.35 3.91 ± 0.39
N mol 6 1 1 1
A mol (nm2) 1.36 ± 0.43 2.84 ± 0.28 3.53 ± 0.35 3.91 ± 0.39
NA, not available.
of A2B molecules, successive in situ imination/bistransimination cycles were performed. On the in situ addition of 0.5 equiv. B2 on top of a pre-existing monolayer of A (Fig. 3a), the A2B2 motif was obtained (Fig. 3b). On the subsequent addition of B6 (0.5 equiv.) solution, the A2B2 monolayer was transformed into an A2B6 structure (Fig. 3c). Finally, the addition of a drop of B12 (0.5 equiv.) solution resulted in the formation of an A2B12 2D pattern (Fig. 3d). In view of the different areas occupied by single A, A2B2, A2B6 and A2B12 molecules (see Table 1) in the lamellar motif, we can conclude that the bistransimination reaction takes place in the region near to the surface, that is, in the supernatant solution, and thus requires the occurrence of partial or full molecular desorption followed by readsorption. Such desorption also facilitates the condensation reaction by allowing for the increase in steric volume caused by the sp 2 to sp 3 rehybridization that occurs in the first step. Once transimination is taking place
on a single molecule embedded in a molecular lamella (typically positioned at the domain boundaries (see the Supplementary Information)), a structural defect in the supramolecular 2D structure is created. This structural defect can act as the seed for the disassembly of adjacent molecules, which ultimately leads to the transformation of the entire adlayer. Also, dynamic processes such as transformation in the molecular patterns at surfaces (for example, Oswald ripening) that occur in 2D58,59 are known to start at surface defect sites, either because of a defect in the substrate structure or of a domain boundary/structural mismatch in the adlayer assembly. Although in the case of aldehyde plus diamine condensations (A + B2, A + B6 and A + B12) the addition of diamine was always followed by a desorption/readsorption process (lasting about 15 minutes), bistransimination reactions (A2B2 to A2B6 and A2B6 to A2B12) were found to be much faster. Interestingly, the
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Figure 3 | STM representative images of in situ condensation/bistransimination processes. a,b, On the in situ addition of B2 on top of a pre-existing monolayer of A (a), the A2B2 motif can be obtained (b). c, On the subsequent addition of B6 solution, the A2B2 monolayer was transformed into an A2B6 structure (c). d, Finally, the addition of a drop of B12 solution resulted in the formation of an A2B12 2D pattern. e,f, Monolayers of A2B6 (e) and A2B12 (f) can be obtained by depositing a drop of B6 and B1 on top of pre-existing monolayers of A. g, Bistransimination of A2B2 with B12 resulted in the formation of A2B12 monolayers. Tunnelling parameters: It = 10–15 pA, Vt = 400–600 mV. The size of the STM images (a–g) is 18 nm × 18 nm. The bistransimination reactions—dynamic exchange of diamines on the bisimines—are labelled as constitutional dynamics. 4
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Figure 4 | STM representative images of the A2B12 transition into A2B6. a, Reverse in situ bistransimination processes were examined by the addition of B6 solution on top of the existing A2B12 monolayer. b, After about 280 minutes, the formation of bicomponent architectures was observed and showed the coexistence of A2B12 (blue arrows) and A2B6 (green arrows) lamellae. c, The reverse in situ bistransimination reaction was completed after about 430 minutes, as evidenced by the disappearance of A2B12 lamellae. The size of the STM images (a–c) is 28 nm × 28 nm.
rate of the bistransimination processes at the solid/liquid interface and the formation of the new monolayer structures depend on the length of the α,ω-diamine; for example, A2B2 monolayers transform into A2B6 after 3.0 ± 0.3 minutes of a desorption/readsorption process, whereas A2B12 monolayers are formed 1.0 ± 0.1 minute after the addition of the B12 solution on top of the A2B6 structure (for details, see Supplementary Section 4.2). Furthermore, it is important that, although the number of components in the supernatant solution during the consecutive bistransiminations increases, only one type of supramolecular pattern is formed at the solid/liquid interface, which corresponds to self-assembled structures composed of the bistransimination product that contains the variable B unit, which suggests the minor role of the desorption kinetics. Conversely, in processes governed by desorption kinetics, one can expect that the equilibrium state of the reactions must contain both species in the ratio k1/k2 = c2/c1 , which is not valid in the present case as only one species on the surface is found constantly through many experiments. This observation can be further explained by the different free energies of physisorption of bisimines with altered B units, which decrease significantly with the increasing length of B. This is in line with previous observations of the macromolecular fractionation that occurs in the physisorption at the solution/graphite interface in a polydisperse molecular system, and reveals a preferential adsorption of longer molecules in the case of an unaltered rigidity of the molecules, that is, for molecular lengths below the Kuhn length. The thermodynamics of physisorption at the solid/liquid interface is ruled by the minimization of the free energy. The physisorption is an exothermic reaction: minimization of the enthalpy is achieved by the maximum packing density at the surfaces, which can be obtained equally by the formation of tight 2D assemblies of either short (A2B2) or long (A2B12) molecules. Conversely, for translational entropy reasons, the adsorption of longer versus shorter molecules at the interface is favoured, because on immobilization at the interface the molecules lose translational entropy per particle. Thus, there is more entropy loss for the adsorption of smaller than of larger/longer molecules, because more small molecules are required to cover the same surface area. For longer chains, the entropic contribution per unit mass to the overall free energy increases because of the reduced configurational space of the molecule at the interface60. Thus, in the present study the
preferential physisorption at the solution/graphite interface of the molecules comprises the longer bridge, that is A2B12, with respect to the shorter A2B2 and A2B6 bridges, may be considered as entropy-driven selective adsorption. As discussed in the previous section, monolayers of A2B6 (Fig. 3e) and A2B12 (Fig. 3f ) can be obtained by depositing a drop of B6 and B12 on top of pre-existing monolayers of A. Finally, bistransimination of A2B2 with B12 resulted in the formation of A2B12 monolayers. Reverse in situ bistransimination. We then extended our studies to the reverse in situ bistransimination processes of the investigated bisimines. To this end, a drop of equimolar solution of B6 and/or B2 was applied on top of a pre-existing monolayer of A2B12. Not surprisingly, diamine exchange was not observed, confirming the significance of the free energy of physisorption in governing the monolayer stabilization. Equimolar bistransimination (1 equiv. added diamine) is expected to be a stepwise process. On the addition of the diamine B6, one of the C=N bonds of the bisimine A2B12 is cleaved, with the formation of two species; that is, two monoimines with different diamine moieties condensed with aldehyde groups, for example AB12 and AB6, in equal amounts. At the solid/liquid interface, the AB12:AB6 ratio and ultimately the number of A2B12 and/or A2B6 molecules that physisorb into ordered patterns at the surface depends on the difference in free energies of physisorption. In other words, in the case of equimolar bistransimination only the species with the lowest free energy will adsorb on the HOPG surface. However, by changing the bistransimination conditions, especially the concentration of the diamine deposited on top of the A2B12 monolayer, the equilibrium of the diamine exchange process can be shifted towards the species that incorporates a shorter B unit. To this end, 100 equiv. B6 (2 µl of a 20 mM solution in pyridine:1-phenyloctane, 1:99 vol:vol) was applied on top of the A2B12 monolayer (Fig. 4a). After about 280 minutes, the formation of a bicomponent architecture was observed, as indicated in Fig. 4b, which shows the coexistence of A2B12 (blue arrows) and A2B6 (green arrows) lamellae. Although the A2B6 + B12 bistransimination process is very rapid (one minute), the A2B12 + B6 reaction was completed only after about 430 minutes, as evidenced by the disappearance of A2B12 lamellae (over 1 µm2 area, accessible with STM).
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Neither A2B12 + B2 nor A2B6 + B2 bistransimination could be accomplished at the solid/liquid interface. Despite exploring very high molar ratios (up to 1,000 equiv. diamine B2), as well as long reaction times (up to two days) by means of STM, neither the coexistence of different species nor the diamine exchange could be observed. Adsorption-driven reaction and selection from a dynamic library of bisimines. Dynamic covalent libraries present the ability to undergo constituent amplification in a mixture through component selection in response to a physical stimulus or a chemical effector4–8,61,62. In view of the results above, it was of interest to check the effect of surface-adsorption forces on the set of bisimines investigated. Experiments were conducted to investigate the occurrence of such features on a surface. Thus, on deposition of a drop of a mixture of A2B2, A2B6 and A2B12 (equimolar concentration), only A2B12 patterns were observed, which indicates a surface-induced selection of the library constituent that presents the thermodynamically moststable physisorption. HPLC analysis of a toluene solution of a mixture of 2 equiv. A and three α,ω-diamines (B2 + B6 + B12 (1 equiv. each)) showed, as expected, a statistical distribution of the three monoimines, together with small amounts (1–5%) of the three bisimines (see the Supplementary Information). A 1H NMR investigation of a more concentrated solution of the same compounds in d8-toluene revealed a statistical distribution of the corresponding bisimines (see the Supplementary Information). In marked contrast, deposition of a dilute solution (as used for the HPLC analysis) of the same compounds in phenyloctane on the HOPG surface revealed the formation of patterns of the bisimines A2B12 exclusively, which indicates that adsorption (1) drives the reaction completion, as the deposited solution contains mainly monoimines whereas the surface is covered by bisimine molecules, and (2) leads to an exclusive constituent selection of a specific bisimine (for example A2B12) from the dynamic library of imines present in the solution, as seen in the selective nature of the adsorptioninduced pattern formation on the surface (see the Supplementary Information for details). The overall process is free-energy driven through the interplay of gain in enthalpy on molecular physisorption and loss of translational entropy63. In the present experiments, the free energy of physisorption acts as an effector and/or driving force that amplifies a given constituent of a dynamic covalent library. The process is reminiscent of the selective formation of a single entity on crystallization from a mixture of three equilibrating constituents64. The results above taken together stress the crucial role of interactions with the surface as the selection force that drives the outcome of covalent chemical reactions, allowing or inhibiting given transformations and thus leads to a surface-controlled product formation and reaction selectivity that is essentially different from the product distribution observed in solution.
Conclusions In summary, we provide here evidence for DCC at the solid/liquid interface by monitoring, with subnanometre resolution, the occurrence of chemical reactions under thermodynamic control. In particular, the bisimine formation of 4-(hexadecyloxy)benzaldehyde with different α,ω-diamines and reversible bistransimination reactions can be monitored in situ by STM. The aldehyde molecules (A) were first transformed into bisimine on condensation with different aliphatic α,ω-diamines (B) and the latter interconverted between different A2B structures. The surface-mediated bistransimination reactions and their visualization at the solid/liquid interface open new avenues for understanding the parameters, such as packing and adsorption, that affect thermodynamic and kinetic features of covalent dynamic processes at a 6
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surface, and lead, in particular, to constituent selection and selective pattern formation. Of particular significance is the ability of adsorption free energy to act as a physical agent that drives completion of a reaction and selection of a given constituent of a dynamic covalent library. The data described allow the presentation of a full picture of constitutional dynamic processes at a solid/liquid interface by providing the covalent dynamic counterpart to the extensively studied formation of supramolecular assemblies through non-covalent interactions35–40. The ability to incorporate specific functionalities at predefined positions also paves the way towards the bottom-up construction of robust, sophisticated multicomponent molecular nanostructures as a key element in novel responsive 2D molecular materials and devices.
Methods For the synthesis and analysis of A, A2B2, A2B6 and A2B12, STM experimental details as well as additional STM, NMR and HPLC experiments and calculation of adsorption energies, see the Supplementary Information.
Received 16 December 2013; accepted 5 August 2014; published online 14 September 2014
References 1. Whitesides, G. M., Mathias, J. P. & Seto, C. T. Molecular self-assembly and nanochemistry—a chemical strategy for the synthesis of nanostructures. Science 254, 1312–1319 (1991). 2. Lehn, J-M. Supramolecular Chemistry: Concepts and Perspectives (Wiley, 1995). 3. Hoeben, F. J. M., Jonkheijm, P., Meijer, E. W. & Schenning, A. P. H. J. About supramolecular assemblies of pi-conjugated systems. Chem. Rev. 105, 1491–1546 (2005). 4. Rowan, S. J., Cantrill, S. J., Cousins, G. R. L., Sanders, J. K. M. & Stoddart, J. F. Dynamic covalent chemistry. Angew. Chem. Int. Ed. 41, 898–952 (2002). 5. Jin, Y., Yu, C., Denman, R. J. & Zhang, W. Recent advances in dynamic covalent chemistry. Chem. Soc. Rev. 42, 6634–6654 (2013). 6. Lehn, J-M. Dynamic combinatorial chemistry and virtual combinatorial libraries. Chem. Eur. J. 5, 2455–2463 (1999). 7. Corbett, P. T. et al. Dynamic combinatorial chemistry. Chem. Rev. 106, 3652–3711 (2006). 8. Miller, B. L. Dynamic Combinatorial Chemistry in Drug Discovery, Bioorganic Chemistry, and Materials Science (Wiley, 2009). 9. Lehn, J-M. From supramolecular chemistry towards constitutional dynamic chemistry and adaptive chemistry. Chem. Soc. Rev. 36, 151–160 (2007). 10. Lehn, J-M. in Constitutional Dynamic Chemistry (ed. Barboiu, M.) 1–32 (Topics in Current Chemistry 332, Springer, 2012). 11. Fyfe, M. C. T. & Stoddart, J. F. Synthetic supramolecular chemistry. Acc. Chem. Res. 30, 393–401 (1997). 12. Black, S. P., Sanders, J. K. M. & Stefankiewicz, A. R. Disulfide exchange: exposing supramolecular reactivity through dynamic covalent chemistry. Chem. Soc. Rev. 43, 1861–1872 (2014). 13. Fuchs, B., Nelson, A., Star, A., Stoddart, J. F. & Vidal, S. B. Amplification of dynamic chiral crown ether complexes during cyclic acetal formation. Angew. Chem. Int. Ed. 42, 4220–4224 (2003). 14. Cacciapaglia, R., Di Stefano, S. & Mandolini, L. Metathesis reaction of formaldehyde acetals: an easy entry into the dynamic covalent chemistry of cyclophane formation. J. Am. Chem. Soc. 127, 13666–13671 (2005). 15. Kaiser, G. & Sanders, J. K. M. Synthesis under reversible conditions of cyclic porphyrin dimers using palladium-catalysed allyl transesterification. Chem. Commun. 1763–1764 (2000). 16. Cordes, E. H. & Jencks, W. P. On the mechanism of Schiff base formation and hydrolysis. J. Am. Chem. Soc. 84, 832–837 (1962). 17. Layer, R. W. The chemistry of imines. Chem. Rev. 63, 489–510 (1963). 18. Dayagi, S. & Degani, Y. Methods of Formation of the Carbon–Nitrogen Double Bond 64–83 (Interscience, 1970). 19. Tauk, L., Schroder, A. P., Decher, G. & Giuseppone, N. Hierarchical functional gradients of pH-responsive self-assembled monolayers using dynamic covalent chemistry on surfaces. Nature Chem. 1, 649–656 (2009). 20. Bonnett, R. in Carbon–Nitrogen Double Bonds (1970) (ed. Patai, S.) 597–662 (Wiley, 2010). 21. Belowich, M. E. & Stoddart, J. F. Dynamic imine chemistry. Chem. Soc. Rev. 41, 2003–2024 (2012). 22. Cote, A. P. et al. Porous, crystalline, covalent organic frameworks. Science 310, 1166–1170 (2005). 23. Korich, A. L. & Iovine, P. M. Boroxine chemistry and applications: a perspective. Dalton Trans. 39, 1423–1431 (2010).
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24. Ciaccia, M., Cacciapaglia, R., Mencarelli, P., Mandolini, L. & Di Stefano, S. Fast transimination in organic solvents in the absence of proton and metal catalysts. A key to imine metathesis catalyzed by primary amines under mild conditions. Chem. Sci. 4, 2253–2261 (2013). 25. Rue, N. M., Sun, J. L. & Warmuth, R. Polyimine container molecules and nanocapsules. Isr. J. Chem. 51, 743–768 (2011). 26. Kovaříček, P. & Lehn, J-M. Merging constitutional and motional covalent dynamics in reversible imine formation and exchange processes. J. Am. Chem. Soc. 134, 9446–9455 (2012). 27. Ramström, O. & Lehn J-M. Drug discovery by dynamic combinatorial libraries. Nature Rev. Drug. Discov. 1, 26–36 (2002). 28. Zhao, D. H. & Moore, J. S. Reversible polymerization driven by folding. J. Am. Chem. Soc. 124, 9996–9997 (2002). 29. Giuseppone, N. Toward self-constructing materials: a systems chemistry approach. Acc. Chem. Res. 45, 2178–2188 (2012). 30. Gourdon, A. On-surface covalent coupling in ultrahigh vacuum. Angew. Chem. Int. Ed. 47, 6950–6953 (2008). 31. Hossain, M. Z. et al. Chemically homogeneous and thermally reversible oxidation of epitaxial graphene. Nature Chem. 4, 305–309 (2012). 32. Saywell, A., Schwarz, J., Hecht, S. & Grill, L. Polymerization on stepped surfaces: alignment of polymers and identification of catalytic sites. Angew. Chem. Int. Ed. 51, 5096–5100 (2012). 33. Di Giovannantonio, M. et al. Insight into organometallic intermediate and its evolution to covalent bonding in surface-confined Ullmann polymerization. ACS Nano 7, 8190–8198 (2013). 34. Binnig, G., Rohrer, H., Gerber, C. & Weibel, E. Surface studies by scanning tunneling microscopy. Phys. Rev. Lett. 49, 57–61 (1982). 35. Rabe, J. P. & Buchholz, S. Commensurability and mobility in 2-dimensional molecular-patterns on graphite. Science 253, 424–427 (1991). 36. De Feyter, S. & De Schryver, F. C. Two-dimensional supramolecular selfassembly probed by scanning tunneling microscopy. Chem. Soc. Rev. 32, 139–150 (2003). 37. Jackson, A. M., Myerson & J. W., Stellacci, F. Spontaneous assembly of subnanometre-ordered domains in the ligand shell of monolayer-protected nanoparticles. Nature Mater. 3, 330–336 (2004). 38. MacLeod, J. M., Ivasenko, O., Perepichka, D. F. & Rosei, F. Stabilization of exotic minority phases in a multicomponent self-assembled molecular network. Nanotechnology 18, 424031–424040 (2007). 39. Ciesielski, A., Schaeffer, G., Petitjean, A., Lehn, J-M. & Samorì, P. STM insight into hydrogen-bonded bicomponent 1D supramolecular polymers with controlled geometries at the liquid–solid interface. Angew. Chem. Int. Ed. 48, 2039–2043 (2009). 40. Ciesielski, A., Palma, C-A., Bonini, M. & Samorì, P. Towards supramolecular engineering of functional nanomaterials: pre-programming multi-component 2D self-assembly at solid–liquid interfaces. Adv. Mater. 22, 3506–3520 (2010). 41. Ciesielski, A., Lena, S., Masiero, S., Spada, G. P. & Samorì, P. Dynamers at the solid–liquid interface: controlling the reversible assembly/reassembly process between two highly ordered supramolecular guanine motifs. Angew. Chem. Int. Ed. 49, 1963–1966 (2010). 42. Ciesielski, A. & Samorì, P. Supramolecular assembly/reassembly processes: molecular motors and dynamers operating at surfaces. Nanoscale 3, 1397–1410 (2011). 43. Grill, L. et al. Nano-architectures by covalent assembly of molecular building blocks. Nature Nanotech. 2, 687–691 (2007). 44. Hulsken, B. et al. Real-time single-molecule imaging of oxidation catalysis at a liquid–solid interface. Nature Nanotech. 2, 285–289 (2007). 45. Perepichka, D. F. & Rosei, F. Extending polymer conjugation into the second dimension. Science 323, 216–217 (2009). 46. Mielke, J. et al. Molecules with multiple switching units on a Au(111) surface: self-organization and single-molecule manipulation. J. Phys. Condens. Matter 24, 394013 (2012). 47. den Boer, D. et al. Detection of different oxidation states of individual manganese porphyrins during their reaction with oxygen at a solid/liquid interface. Nature Chem. 5, 621–627 (2013). 48. Ghijsens, E, et al. A tale of tails: alkyl chain directed formation of 2D porous networks reveals odd–even effects and unexpected bicomponent phase behavior. ACS Nano 7, 8031–8042 (2013). 49. Dienstmaier, J. F. et al. Synthesis of well-ordered COF monolayers: surface growth of nanocrystalline precursors versus direct on-surface polycondensation. ACS Nano 5, 9737–9745 (2011).
50. Dienstmaier, J. F. et al. Isoreticular two-dimensional covalent organic frameworks synthesized by on-surface condensation of diboronic acids. ACS Nano 6, 7234–7242 (2012). 51. Hu, F. Y. et al. In situ STM investigation of two-dimensional chiral assemblies through Schiff-base condensation at a liquid/solid interface. ACS Appl. Mater. Interfaces 5, 1583–1587 (2013). 52. Wang, X. Y. et al. Structural motif modulation in 2D supramolecular assemblies of molecular dipolar unit tethered by alkylene spacer. J. Phys. Chem. C 117, 16392–16396 (2013). 53. Guan, C. Z., Wang, D. & Wan, L. J. Construction and repair of highly ordered 2D covalent networks by chemical equilibrium regulation. Chem. Commun. 48, 2943–2945 (2012). 54. Weigelt, S. et al. Covalent interlinking of an aldehyde and an amine on a Au(111) surface in ultrahigh vacuum. Angew. Chem. Int. Ed. 46, 9227–9230 (2007). 55. Weigelt, S. et al. Surface synthesis of 2D branched polymer nanostructures. Angew. Chem. Int. Ed. 47, 4406–4410 (2008). 56. Tanoue, R. et al. Thermodynamically controlled self-assembly of covalent nanoarchitectures in aqueous solution. ACS Nano 5, 3923–3929 (2011). 57. Piot, L., Bonifazi, D. & Samorì, P. Organic reactivity in confined spaces under scanning tunneling microscopy control: tailoring the nanoscale world. Adv. Func. Mater. 17, 3689–3693 (2007). 58. Stabel, A., Heinz, R., De Schryver, F. C. & Rabe, J. P. Ostwald ripening of 2-dimensional crystals at the solid–liquid interface. J. Phys. Chem. 99, 505–507 (1995). 59. Samorí, P., Müllen, K. & Rabe, H. P. Molecular-scale tracking of the self-healing of polycrystalline monolayers at the solid–liquid interface. Adv. Mater. 16, 1761–1765 (2004). 60. Samorí, P., Severin, N., Müllen, K. & Rabe, J. P. Macromolecular fractionation of rod-like polymers at atomically flat solid–liquid interfaces. Adv. Mater. 12, 579–582 (2000). 61. Cheeseman, J. D., Corbett, A. D., Gleason, J. L. & Kazlauskas, R. J. Receptorassisted combinatorial chemistry: thermodynamics and kinetics in drug discovery. Chem. Eur. J. 11, 1708–1716 (2005). 62. Belenguer, A. M., Friscic, T., Day, G. M. & Sanders, J. K. M. Solid-state dynamic combinatorial chemistry: reversibility and thermodynamic product selection in covalent mechanosynthesis. Chem. Sci. 2, 696–700 (2011). 63. Bonini, M. et al. Competitive physisorption among alkyl-substituted pi-conjugated oligomers at the solid–liquid interface: towards prediction of self-assembly at surfaces from a multicomponent solution. Small 5, 1521–1526 (2009). 64. Baxter, P. N. W., Lehn, J-M. & Rissanen, K. Generation of an equilibrating collection of circular inorganic copper(I) architectures and solid-state stabilisation of the dicopperhelicate component. Chem. Commun. 1323–1324 (1997).
Acknowledgements We thank M. Cecchini for enlightening discussions. P.K. acknowledges the Université de Strasbourg for a doctoral fellowship. This work was supported by the European Community through the European Research Council projects SUPRAFUNCTION (GA257305) and SUPRADAPT (GA-290585), the Agence Nationale de la Recherche through the LabEx project Chemistry of Complex Systems (ANR-10-LABX-0026_CSC) and the International Center for Frontier Research in Chemistry.
Author contributions A.C., P.S. and J-M.L. conceived the experiments and designed the study. P.K. participated in the planning of the study and carried out the synthesis and characterization in solution (HPLC, and NMR and mass spectroscopy). M.E.G. and S.H. performed the STM experiments. M.E.G., A.C. and P.S. interpreted the STM data. J-M.L. and P.K. interpreted the chemical data. All authors discussed the results and contributed to the interpretation of data. A.C., P.S. and J-M.L. co-wrote the paper. All authors contributed to editing the manuscript.
Additional information Supplementary information and chemical compound information are available in the online version of the paper. Reprints and permissions information is available online at www.nature.com/reprints. Correspondence and requests for materials should be addressed to J-M.L. and P.S.
Competing financial interests
The authors declare no competing financial interests.
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Dynamic covalent chemistry of bisimines at the solid/liquid interface monitored by scanning tunnelling microscopy Artur Ciesielski, Mohamed El Garah, Sébastien Haar, Petr Kovaříček, Jean-Marie Lehn* and Paolo Samorì* Dynamic covalent chemistry relies on the formation of reversible covalent bonds under thermodynamic control to generate dynamic combinatorial libraries. It provides access to numerous types of complex functional architectures, and thereby targets several technologically relevant applications, such as in drug discovery, (bio)sensing and dynamic materials. In liquid media it was proved that by taking advantage of the reversible nature of the bond formation it is possible to combine the error-correction capacity of supramolecular chemistry with the robustness of covalent bonding to generate adaptive systems. Here we show that double imine formation between 4-(hexadecyloxy)benzaldehyde and different α,ω-diamines as well as reversible bistransimination reactions can be achieved at the solid/liquid interface, as monitored on the submolecular scale by in situ scanning tunnelling microscopy imaging. Our modular approach enables the structurally controlled reversible incorporation of various molecular components to form sophisticated covalent architectures, which opens up perspectives towards responsive multicomponent two-dimensional materials and devices.
S
upramolecular chemistry1–3 relies on the use of non-covalent interactions to self-assemble chemical entities, with a level of precision on the subnanometre scale, to form materials that exhibit programmed chemical and physical properties. However, the labile nature of non-covalent interactions means the stability of the self-assembled structures is limited, especially in liquid media, and this thereby jeopardizes their technological exploitation. In this regard, the possibility of constructing molecular architectures based on chemical elements that interact through more robust, yet reversible, bonds, has evolved supramolecular chemistry towards dynamic covalent chemistry (DCC)4,5. Significantly, DCC shares numerous features with supramolecular chemistry—in particular, they both rely on reversible bonds that enable the formation of products under thermodynamic control. Both supramolecular chemistry and DCC are modular because they allow for the selection and exchange of (supra)molecular components4–8, and thus represent branches of constitutional dynamic chemistry9,10. However, there are two major differences between these two types of reversible chemistry approaches. The equilibration processes are much slower in DCC systems when compared to supramolecular ones, because in the former covalent bonds have to be broken and reformed. Moreover, supramolecular chemistry concerns the formation of non-covalently tethered aggregates (supermolecules and/or supramolecular architectures), which are by nature more fragile than the structures produced by DCC. For these reasons DCC has emerged as an efficient and versatile strategy for the design and synthesis of complex molecular structures. Although early examples of supramolecularly assisted covalent synthesis relied strongly on kinetically controlled reactions for post-assembly covalent modification11, the DCC method takes advantage of the reversible nature of bond formation, for example disulfide12, acetal13,14, ester15, imine16–21 and boroxine (B3O3)22,23 bonds, to allow the generation of new covalent structures under thermodynamic control.
Functional groups that involve a carbonyl or C=N unit, such as imines, esters or amides, are of special interest because they may undergo disconnection/reconnection cycles (for example, trans reactions like imination, esterification and amidation). In particular the reversible nature of imine bond formation makes it an attractive process for use in DCC5–11,24, because the (amine + carbonyl) condensation into imine-type compounds usually takes place under mild conditions. In general, imines can participate in three types of equilibrium-controlled reactions: (1) hydrolysis, in which the imine reverts back to the precursors, that is, amine and carbonylcontaining compound(s), on the addition of water; (2) transamination, in which, with the introduction of a second amine (or carbonyl-based molecule), the original imine may undergo an exchange of the amine residue to give a new imine; (3) imine– imine exchange, in which, on the introduction of a second imine, the two imines can undergo a reaction whereby the amine components are exchanged24. Dynamic exchanges that involve the C=N bonds in imines, hydrazones and oximes are the most widely used dynamic covalent reactions. They have been applied to the syntheses of complex two-dimensional (2D) and threedimensional (3D) molecular architectures, covalent organic frameworks and the construction of self-sorting systems, rotary switches and molecular walkers21,25 and to study motional covalent dynamics26. The dynamic behaviour of imines is of special interest in view of its central role in chemistry and biochemistry27 as well as in materials science28,29. Over the past decade, on-surface chemistry has attracted considerable attention in nanoscience and molecular electronics, because it represents a novel bottom-up approach for producing defined functional nanostructures through the rigorous covalent coupling of organic precursor molecules under kinetic control30–33. The need to explore ordered architectures at the molecular scale has made scanning tunnelling microscopy (STM)34 a widely employed extremely powerful tool to study supramolecular materials at their interfaces
ISIS & icFRC, Université de Strasbourg & CNRS, 8 allée Gaspard Monge, 67000 Strasbourg, France. * e-mail: [email protected]; [email protected] NATURE CHEMISTRY | ADVANCE ONLINE PUBLICATION | www.nature.com/naturechemistry
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A 0.5 equiv. B12
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Figure 1 | Condensation of aldehyde A with α,ω-diamines. Schematic representation of condensation reactions of aldehyde A (4-(hexadecyloxy)benzaldehyde) with α,ω-diamines B2 (1,2-diaminoethane, red), B6 (1,6-diaminohexane, green) and B12 (1,12-diaminododecane, blue) that yield bisimines A2B2, A2B6 and A2B12, respectively. The constitutional covalent dynamic processes of bistransimination, that is, the reversible imine exchange reaction, takes place in the presence of a competing diamine, and thus the new bisimine A2B6 is formed when B6 is mixed with A2B2, which leads to a dynamic equilibrium of the products. Similarly, bisimine A2B12 is produced when B12 is mixed with either A2B2 or A2B6.
with submolecular resolution, and provides direct insights into the supramolecular world35–40. The subnanometre resolution that can be achieved by STM imaging makes it possible to gain detailed information on molecular interactions; thus, it is a crucial tool to assist in the design of molecular modules that undergo controlled self-assembly at surfaces under various experimental conditions (temperature, pressure and concentration) to form the chosen supramolecular structures. Beyond the mere visualization of the 2D ordering of physisorbed monolayers, recent studies have shown that STM has much potential application in a vast variety of topics, such as monitoring molecular dynamics41,42, molecule manipulation43–47, surface chirality48 and so on. Among the self-assembled structures investigated by STM, those that comprise boroxines49,50 and imines51,52 are particularly stimulating because they can be explored further in the context of surface-assisted DCC, for example on-surface formation and/or the breaking of B3O3 bonds53. Although condensation of an amino group with a carbonyl functionality to form an imine/Schiff base has been studied by STM both in an ultrahigh vacuum54,55 and at a water/gold interface56, the implementation of reversible covalent bonds, such as the C=N one, has not been explored. Herein we report a submolecularly resolved STM mapping of the surface-mediated reversible exchange processes of aliphatic bisimines that occur at the solid/liquid interface on a highly oriented pyrolitic graphite (HOPG) surface. We focused our attention on (1) the condensation of 4-(hexadecyloxy)benzaldehyde (A) with different α,ω-diamines, that is, 1,2-diaminoethane (B2), 1,6-diaminohexane (B6) and 1,12-diaminododecane (B12), as well as on (2) the constitutional covalent (reversible) dynamic processes of bistransimination, that is, diamine exchange on the bisimines, as illustrated on Fig. 1. Both the aldehyde and the α,ω-diamines are equipped with long aliphatic chains, which are known to exhibit a high affinity for the HOPG surface and therefore promote the molecular physisorption with respect to its solvation. However, the interactions between molecules and the HOPG surface are of a van der 2
Waals type, and therefore offer a dynamic scenario characterized by potential desorption and readsorption. The surface-mediated processes described here, together with their covalent, yet reversible, type of structures, make imines a class of compounds that presents a particularly rich and wide palette of structural features, as well as of constitutional dynamic behaviours.
Results and discussion Initially, we investigated the self-assembly of A by applying a drop of a 0.1 mM solution of A in 1-phenyloctane on the HOPG surface. The STM image of the obtained monolayer (Fig. 2a) showed a crystalline structure that consists of lamellar architectures. In this 2D crystal, molecules A are physisorbed flat on the surface. The supramolecular motif is stabilized by relatively strong molecule–graphite van der Waals interactions (for details, see the Supplementary Information) and molecule–molecule van der Waals and dipole– dipole interactions. The self-assembly of A molecules can be described by the formation of trimer-like subunits (indicated in red in Fig. 2b), which further expand into lamellar arrays characterized by an assembly that consists of an aldehyde-to-aldehyde motif within a given lamella and tail-to-tail packing between adjacent lamellae. None of the α,ω-diamine derivatives (B2, B6 or B12) was found to form ordered structures at the liquid/solid interface, which highlights their highly dynamic nature on the graphite surface on a timescale faster than that of STM imaging, as determined by their low affinity for HOPG. In situ generation of bisimines. STM was used to probe the in situ synthesis of bisimines by the addition of 0.5 equiv. α,ω-diamines (that is, B2, B6 or B12) on top of a pre-existing monolayer of A. To this end, a 2 µl drop of a 0.1 mM solution (pyridine: 1-phenyloctane, 1:99 vol:vol) of B2, B6 or B12 was deposited on top of a monolayer of A formed by applying a 4 µl drop of a 0.1 mM solution of A in 1-phenyloctane on the HOPG surface. A small amount of pyridine was added to ensure solubilization of all
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Figure 2 | STM images of self-assembled 2D nanopatterns. a,c,e,g, Monolayer of aldehyde A (a) and bisimines A2B2 (c), A2B6 (e) and A2B12 (g) at the liquid/graphite interface self-assembled from a solution in 1-phenyloctane. Tunnelling parameters: average tunnelling current (It ) = 10–15 pA, bias voltage (Vt ) = 400–600 mV. b,d,f,h, Molecular packing motifs of A, A2B2, A2B6 and A2B12 are shown in panels b, d, f and h, respectively. Crystalline patterns obtained from each molecule self-assembled on HOPG are described by the unit cell size (vectors a and b). Bright spots linearly aligned (easily visible on the STM images) can be attributed to the phenyl rings of the A units. The only difference between the A2B2, A2B6 and A2B12 structures is the value of the c parameter (that is, the distance between the phenyl rings (length of the B bridge)), whereas the value of parameter d (which corresponds to the length of two hexadecyloxy chains) remains constant. For clarity, bisimine cores (the spacers between C=N bonds) are highlighted using different colours (B2, red; B6, green; B12, blue).
three compounds, especially B12 (see Supplementary Information for details). In all three cases, the addition of α,ω-diamine resulted in the desorption of A followed by formation of new
types of 2D crystals (Fig. 2c,e,g). These changes can be attributed to the formation of A2B-type bisimines by condensation between the carbonyl group of A and the amino groups of B molecules, with the production of water as the side product (Fig. 1). Interestingly, regardless of the length of the diamine main chain (C2H4 for B2, C6H12 for B6 and C12H24 for B12), the observed monolayers of A2B2, A2B6 and A2B12 exhibit a similar lamellar assembly motif. For the crystalline pattern obtained from each molecule self-assembled on HOPG, the unit cell parameters, that is, the length of the vectors a and b, angle between the vectors, α unit cell area (A), number of molecules in the unit cell (Nmol ) and area occupied by a single molecule in the unit cell (Amol , with Amol = A/Nmol ) are given in Table 1. In the 2D crystals, the long hexadecyloxy side chains of the A units are clearly visible, and are physisorbed flat on the surface, whereas the different orientation of spacer chains (that is, the main chain of the B units) with respect to the underlying HOPG surface affects their electronic coupling, and therefore they do not appear as clearly as the hexadecyloxy chains. Furthermore, linearly aligned bright spots (noticeably visible on the STM images) can be attributed to the phenyl rings of the A units. Further comparison of the unit cell parameters of all the monolayers self-assembled at the HOPG/solution interface (Table 1) reveals that the only difference between these structures is the value of the c vector, that is, the distance between the phenyl rings (length of the B bridge). Importantly, STM measurements on ex situ synthesized (see Supplementary Information for the details) bisimines revealed the formation of monolayers that present identical unit cell parameters when compared with in situ synthesized bisimines, which provides unambiguous evidence of the successful condensation between aldehydes and diamines, and consequent formation of covalent C=N bonds at the phenyloctane/graphite interface. Condensation reactions that occur at the solid/liquid interface were found to be typically much faster when compared to the same reactions performed in solution, most probably for two main reasons: (1) at the solid/liquid interface the concentration is at least higher than a saturation regime, whereas in bulk solution the concentration is typically much lower, and (2) the confinement in quasi-2D may facilitate the reaction by lowering the activation barrier57. In the present case, the rates and rate constants of the condensation and exchange reactions determined by 1H NMR spectroscopy revealed that, at the concentration used for STM experiments (that is, 0.1 mM), the time needed to produce 3.5 × 1013 A2B molecules (which corresponds to the number of molecules in a tightly packed monolayer that covers a 1 × 1 cm2 graphite surface) is 104 times longer in solution than that at the solid/liquid interface (for details on rate-constant determination, see the Supplementary Information and Supplementary Excel macro). In the extreme case of a reaction that occurs ‘literally’ on the surface, the molecular concentration would be four orders of magnitude greater than that in solution. In the present case, because of (1) the different areas occupied by the precursor and product molecules, and (2) the steric hindrance requirements for rehybridization of nitrogen atoms from sp 2 to sp 3 that occurs in the first step of the reaction, the condensation between aldehyde A and α,ω-diamine derivatives takes place through a desorption/bisimination/readsorption process. Moreover, even in the region near to the surface, one can expect a much greater concentration than in solution, similarly to the well-known case of the Stern layer for electrolytes. However, no models have hitherto been developed that allow for a quantitative description of the concentration of an apolar molecule in an apolar liquid with increasing distance from a solid substrate. In situ bistransimination. To explore fully the reversible nature of C=N bonds, and to gain insight into the bistransimination processes
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Table 1 | Unit-cell parameters of A2B2, A2B6 and A2B12 monolayers. Structure A A2B2 A2B6 A2B12
a (nm) 3.98 ± 0.31 4.73 ± 0.42 5.88 ± 0.54 6.51 ± 0.62
b (nm) 1.71 ± 0.11 0.60 ± 0.06 0.60 ± 0.06 0.60 ± 0.06
α (°) 92 ± 2 90 ± 2 90 ± 2 90 ± 2
c (nm) NA 0.81 ± 0.01 1.94 ± 0.01 2.58 ± 0.01
d (nm) NA 3.92 ± 0.01 3.94 ± 0.01 3.93 ± 0.01
A (nm2) 6.80 ± 0.43 2.84 ± 0.28 3.53 ± 0.35 3.91 ± 0.39
N mol 6 1 1 1
A mol (nm2) 1.36 ± 0.43 2.84 ± 0.28 3.53 ± 0.35 3.91 ± 0.39
NA, not available.
of A2B molecules, successive in situ imination/bistransimination cycles were performed. On the in situ addition of 0.5 equiv. B2 on top of a pre-existing monolayer of A (Fig. 3a), the A2B2 motif was obtained (Fig. 3b). On the subsequent addition of B6 (0.5 equiv.) solution, the A2B2 monolayer was transformed into an A2B6 structure (Fig. 3c). Finally, the addition of a drop of B12 (0.5 equiv.) solution resulted in the formation of an A2B12 2D pattern (Fig. 3d). In view of the different areas occupied by single A, A2B2, A2B6 and A2B12 molecules (see Table 1) in the lamellar motif, we can conclude that the bistransimination reaction takes place in the region near to the surface, that is, in the supernatant solution, and thus requires the occurrence of partial or full molecular desorption followed by readsorption. Such desorption also facilitates the condensation reaction by allowing for the increase in steric volume caused by the sp 2 to sp 3 rehybridization that occurs in the first step. Once transimination is taking place
on a single molecule embedded in a molecular lamella (typically positioned at the domain boundaries (see the Supplementary Information)), a structural defect in the supramolecular 2D structure is created. This structural defect can act as the seed for the disassembly of adjacent molecules, which ultimately leads to the transformation of the entire adlayer. Also, dynamic processes such as transformation in the molecular patterns at surfaces (for example, Oswald ripening) that occur in 2D58,59 are known to start at surface defect sites, either because of a defect in the substrate structure or of a domain boundary/structural mismatch in the adlayer assembly. Although in the case of aldehyde plus diamine condensations (A + B2, A + B6 and A + B12) the addition of diamine was always followed by a desorption/readsorption process (lasting about 15 minutes), bistransimination reactions (A2B2 to A2B6 and A2B6 to A2B12) were found to be much faster. Interestingly, the
A2B2
A
A2B6
A2B12
d NH2–(CH2)12–NH2
c
NH2–(CH2)2–NH2
a
NH2–(CH2)6–NH2
g
b
NH2–(CH2)12–NH2
e f NH2–(CH2)6–NH2
NH2–(CH2)12–NH2
Constitutional dynamics
Figure 3 | STM representative images of in situ condensation/bistransimination processes. a,b, On the in situ addition of B2 on top of a pre-existing monolayer of A (a), the A2B2 motif can be obtained (b). c, On the subsequent addition of B6 solution, the A2B2 monolayer was transformed into an A2B6 structure (c). d, Finally, the addition of a drop of B12 solution resulted in the formation of an A2B12 2D pattern. e,f, Monolayers of A2B6 (e) and A2B12 (f) can be obtained by depositing a drop of B6 and B1 on top of pre-existing monolayers of A. g, Bistransimination of A2B2 with B12 resulted in the formation of A2B12 monolayers. Tunnelling parameters: It = 10–15 pA, Vt = 400–600 mV. The size of the STM images (a–g) is 18 nm × 18 nm. The bistransimination reactions—dynamic exchange of diamines on the bisimines—are labelled as constitutional dynamics. 4
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a
c
b A2B12
A2B12/A2B6
A2B6
281–430 min
431–700 min
+ 100 equiv. NH2–(CH2)6–NH2 0 s to 280 min
Time
Figure 4 | STM representative images of the A2B12 transition into A2B6. a, Reverse in situ bistransimination processes were examined by the addition of B6 solution on top of the existing A2B12 monolayer. b, After about 280 minutes, the formation of bicomponent architectures was observed and showed the coexistence of A2B12 (blue arrows) and A2B6 (green arrows) lamellae. c, The reverse in situ bistransimination reaction was completed after about 430 minutes, as evidenced by the disappearance of A2B12 lamellae. The size of the STM images (a–c) is 28 nm × 28 nm.
rate of the bistransimination processes at the solid/liquid interface and the formation of the new monolayer structures depend on the length of the α,ω-diamine; for example, A2B2 monolayers transform into A2B6 after 3.0 ± 0.3 minutes of a desorption/readsorption process, whereas A2B12 monolayers are formed 1.0 ± 0.1 minute after the addition of the B12 solution on top of the A2B6 structure (for details, see Supplementary Section 4.2). Furthermore, it is important that, although the number of components in the supernatant solution during the consecutive bistransiminations increases, only one type of supramolecular pattern is formed at the solid/liquid interface, which corresponds to self-assembled structures composed of the bistransimination product that contains the variable B unit, which suggests the minor role of the desorption kinetics. Conversely, in processes governed by desorption kinetics, one can expect that the equilibrium state of the reactions must contain both species in the ratio k1/k2 = c2/c1 , which is not valid in the present case as only one species on the surface is found constantly through many experiments. This observation can be further explained by the different free energies of physisorption of bisimines with altered B units, which decrease significantly with the increasing length of B. This is in line with previous observations of the macromolecular fractionation that occurs in the physisorption at the solution/graphite interface in a polydisperse molecular system, and reveals a preferential adsorption of longer molecules in the case of an unaltered rigidity of the molecules, that is, for molecular lengths below the Kuhn length. The thermodynamics of physisorption at the solid/liquid interface is ruled by the minimization of the free energy. The physisorption is an exothermic reaction: minimization of the enthalpy is achieved by the maximum packing density at the surfaces, which can be obtained equally by the formation of tight 2D assemblies of either short (A2B2) or long (A2B12) molecules. Conversely, for translational entropy reasons, the adsorption of longer versus shorter molecules at the interface is favoured, because on immobilization at the interface the molecules lose translational entropy per particle. Thus, there is more entropy loss for the adsorption of smaller than of larger/longer molecules, because more small molecules are required to cover the same surface area. For longer chains, the entropic contribution per unit mass to the overall free energy increases because of the reduced configurational space of the molecule at the interface60. Thus, in the present study the
preferential physisorption at the solution/graphite interface of the molecules comprises the longer bridge, that is A2B12, with respect to the shorter A2B2 and A2B6 bridges, may be considered as entropy-driven selective adsorption. As discussed in the previous section, monolayers of A2B6 (Fig. 3e) and A2B12 (Fig. 3f ) can be obtained by depositing a drop of B6 and B12 on top of pre-existing monolayers of A. Finally, bistransimination of A2B2 with B12 resulted in the formation of A2B12 monolayers. Reverse in situ bistransimination. We then extended our studies to the reverse in situ bistransimination processes of the investigated bisimines. To this end, a drop of equimolar solution of B6 and/or B2 was applied on top of a pre-existing monolayer of A2B12. Not surprisingly, diamine exchange was not observed, confirming the significance of the free energy of physisorption in governing the monolayer stabilization. Equimolar bistransimination (1 equiv. added diamine) is expected to be a stepwise process. On the addition of the diamine B6, one of the C=N bonds of the bisimine A2B12 is cleaved, with the formation of two species; that is, two monoimines with different diamine moieties condensed with aldehyde groups, for example AB12 and AB6, in equal amounts. At the solid/liquid interface, the AB12:AB6 ratio and ultimately the number of A2B12 and/or A2B6 molecules that physisorb into ordered patterns at the surface depends on the difference in free energies of physisorption. In other words, in the case of equimolar bistransimination only the species with the lowest free energy will adsorb on the HOPG surface. However, by changing the bistransimination conditions, especially the concentration of the diamine deposited on top of the A2B12 monolayer, the equilibrium of the diamine exchange process can be shifted towards the species that incorporates a shorter B unit. To this end, 100 equiv. B6 (2 µl of a 20 mM solution in pyridine:1-phenyloctane, 1:99 vol:vol) was applied on top of the A2B12 monolayer (Fig. 4a). After about 280 minutes, the formation of a bicomponent architecture was observed, as indicated in Fig. 4b, which shows the coexistence of A2B12 (blue arrows) and A2B6 (green arrows) lamellae. Although the A2B6 + B12 bistransimination process is very rapid (one minute), the A2B12 + B6 reaction was completed only after about 430 minutes, as evidenced by the disappearance of A2B12 lamellae (over 1 µm2 area, accessible with STM).
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Neither A2B12 + B2 nor A2B6 + B2 bistransimination could be accomplished at the solid/liquid interface. Despite exploring very high molar ratios (up to 1,000 equiv. diamine B2), as well as long reaction times (up to two days) by means of STM, neither the coexistence of different species nor the diamine exchange could be observed. Adsorption-driven reaction and selection from a dynamic library of bisimines. Dynamic covalent libraries present the ability to undergo constituent amplification in a mixture through component selection in response to a physical stimulus or a chemical effector4–8,61,62. In view of the results above, it was of interest to check the effect of surface-adsorption forces on the set of bisimines investigated. Experiments were conducted to investigate the occurrence of such features on a surface. Thus, on deposition of a drop of a mixture of A2B2, A2B6 and A2B12 (equimolar concentration), only A2B12 patterns were observed, which indicates a surface-induced selection of the library constituent that presents the thermodynamically moststable physisorption. HPLC analysis of a toluene solution of a mixture of 2 equiv. A and three α,ω-diamines (B2 + B6 + B12 (1 equiv. each)) showed, as expected, a statistical distribution of the three monoimines, together with small amounts (1–5%) of the three bisimines (see the Supplementary Information). A 1H NMR investigation of a more concentrated solution of the same compounds in d8-toluene revealed a statistical distribution of the corresponding bisimines (see the Supplementary Information). In marked contrast, deposition of a dilute solution (as used for the HPLC analysis) of the same compounds in phenyloctane on the HOPG surface revealed the formation of patterns of the bisimines A2B12 exclusively, which indicates that adsorption (1) drives the reaction completion, as the deposited solution contains mainly monoimines whereas the surface is covered by bisimine molecules, and (2) leads to an exclusive constituent selection of a specific bisimine (for example A2B12) from the dynamic library of imines present in the solution, as seen in the selective nature of the adsorptioninduced pattern formation on the surface (see the Supplementary Information for details). The overall process is free-energy driven through the interplay of gain in enthalpy on molecular physisorption and loss of translational entropy63. In the present experiments, the free energy of physisorption acts as an effector and/or driving force that amplifies a given constituent of a dynamic covalent library. The process is reminiscent of the selective formation of a single entity on crystallization from a mixture of three equilibrating constituents64. The results above taken together stress the crucial role of interactions with the surface as the selection force that drives the outcome of covalent chemical reactions, allowing or inhibiting given transformations and thus leads to a surface-controlled product formation and reaction selectivity that is essentially different from the product distribution observed in solution.
Conclusions In summary, we provide here evidence for DCC at the solid/liquid interface by monitoring, with subnanometre resolution, the occurrence of chemical reactions under thermodynamic control. In particular, the bisimine formation of 4-(hexadecyloxy)benzaldehyde with different α,ω-diamines and reversible bistransimination reactions can be monitored in situ by STM. The aldehyde molecules (A) were first transformed into bisimine on condensation with different aliphatic α,ω-diamines (B) and the latter interconverted between different A2B structures. The surface-mediated bistransimination reactions and their visualization at the solid/liquid interface open new avenues for understanding the parameters, such as packing and adsorption, that affect thermodynamic and kinetic features of covalent dynamic processes at a 6
DOI: 10.1038/NCHEM.2057
surface, and lead, in particular, to constituent selection and selective pattern formation. Of particular significance is the ability of adsorption free energy to act as a physical agent that drives completion of a reaction and selection of a given constituent of a dynamic covalent library. The data described allow the presentation of a full picture of constitutional dynamic processes at a solid/liquid interface by providing the covalent dynamic counterpart to the extensively studied formation of supramolecular assemblies through non-covalent interactions35–40. The ability to incorporate specific functionalities at predefined positions also paves the way towards the bottom-up construction of robust, sophisticated multicomponent molecular nanostructures as a key element in novel responsive 2D molecular materials and devices.
Methods For the synthesis and analysis of A, A2B2, A2B6 and A2B12, STM experimental details as well as additional STM, NMR and HPLC experiments and calculation of adsorption energies, see the Supplementary Information.
Received 16 December 2013; accepted 5 August 2014; published online 14 September 2014
References 1. Whitesides, G. M., Mathias, J. P. & Seto, C. T. Molecular self-assembly and nanochemistry—a chemical strategy for the synthesis of nanostructures. Science 254, 1312–1319 (1991). 2. Lehn, J-M. Supramolecular Chemistry: Concepts and Perspectives (Wiley, 1995). 3. Hoeben, F. J. M., Jonkheijm, P., Meijer, E. W. & Schenning, A. P. H. J. About supramolecular assemblies of pi-conjugated systems. Chem. Rev. 105, 1491–1546 (2005). 4. Rowan, S. J., Cantrill, S. J., Cousins, G. R. L., Sanders, J. K. M. & Stoddart, J. F. Dynamic covalent chemistry. Angew. Chem. Int. Ed. 41, 898–952 (2002). 5. Jin, Y., Yu, C., Denman, R. J. & Zhang, W. Recent advances in dynamic covalent chemistry. Chem. Soc. Rev. 42, 6634–6654 (2013). 6. Lehn, J-M. Dynamic combinatorial chemistry and virtual combinatorial libraries. Chem. Eur. J. 5, 2455–2463 (1999). 7. Corbett, P. T. et al. Dynamic combinatorial chemistry. Chem. Rev. 106, 3652–3711 (2006). 8. Miller, B. L. Dynamic Combinatorial Chemistry in Drug Discovery, Bioorganic Chemistry, and Materials Science (Wiley, 2009). 9. Lehn, J-M. From supramolecular chemistry towards constitutional dynamic chemistry and adaptive chemistry. Chem. Soc. Rev. 36, 151–160 (2007). 10. Lehn, J-M. in Constitutional Dynamic Chemistry (ed. Barboiu, M.) 1–32 (Topics in Current Chemistry 332, Springer, 2012). 11. Fyfe, M. C. T. & Stoddart, J. F. Synthetic supramolecular chemistry. Acc. Chem. Res. 30, 393–401 (1997). 12. Black, S. P., Sanders, J. K. M. & Stefankiewicz, A. R. Disulfide exchange: exposing supramolecular reactivity through dynamic covalent chemistry. Chem. Soc. Rev. 43, 1861–1872 (2014). 13. Fuchs, B., Nelson, A., Star, A., Stoddart, J. F. & Vidal, S. B. Amplification of dynamic chiral crown ether complexes during cyclic acetal formation. Angew. Chem. Int. Ed. 42, 4220–4224 (2003). 14. Cacciapaglia, R., Di Stefano, S. & Mandolini, L. Metathesis reaction of formaldehyde acetals: an easy entry into the dynamic covalent chemistry of cyclophane formation. J. Am. Chem. Soc. 127, 13666–13671 (2005). 15. Kaiser, G. & Sanders, J. K. M. Synthesis under reversible conditions of cyclic porphyrin dimers using palladium-catalysed allyl transesterification. Chem. Commun. 1763–1764 (2000). 16. Cordes, E. H. & Jencks, W. P. On the mechanism of Schiff base formation and hydrolysis. J. Am. Chem. Soc. 84, 832–837 (1962). 17. Layer, R. W. The chemistry of imines. Chem. Rev. 63, 489–510 (1963). 18. Dayagi, S. & Degani, Y. Methods of Formation of the Carbon–Nitrogen Double Bond 64–83 (Interscience, 1970). 19. Tauk, L., Schroder, A. P., Decher, G. & Giuseppone, N. Hierarchical functional gradients of pH-responsive self-assembled monolayers using dynamic covalent chemistry on surfaces. Nature Chem. 1, 649–656 (2009). 20. Bonnett, R. in Carbon–Nitrogen Double Bonds (1970) (ed. Patai, S.) 597–662 (Wiley, 2010). 21. Belowich, M. E. & Stoddart, J. F. Dynamic imine chemistry. Chem. Soc. Rev. 41, 2003–2024 (2012). 22. Cote, A. P. et al. Porous, crystalline, covalent organic frameworks. Science 310, 1166–1170 (2005). 23. Korich, A. L. & Iovine, P. M. Boroxine chemistry and applications: a perspective. Dalton Trans. 39, 1423–1431 (2010).
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© 2014 Macmillan Publishers Limited. All rights reserved.
NATURE CHEMISTRY
ARTICLES
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24. Ciaccia, M., Cacciapaglia, R., Mencarelli, P., Mandolini, L. & Di Stefano, S. Fast transimination in organic solvents in the absence of proton and metal catalysts. A key to imine metathesis catalyzed by primary amines under mild conditions. Chem. Sci. 4, 2253–2261 (2013). 25. Rue, N. M., Sun, J. L. & Warmuth, R. Polyimine container molecules and nanocapsules. Isr. J. Chem. 51, 743–768 (2011). 26. Kovaříček, P. & Lehn, J-M. Merging constitutional and motional covalent dynamics in reversible imine formation and exchange processes. J. Am. Chem. Soc. 134, 9446–9455 (2012). 27. Ramström, O. & Lehn J-M. Drug discovery by dynamic combinatorial libraries. Nature Rev. Drug. Discov. 1, 26–36 (2002). 28. Zhao, D. H. & Moore, J. S. Reversible polymerization driven by folding. J. Am. Chem. Soc. 124, 9996–9997 (2002). 29. Giuseppone, N. Toward self-constructing materials: a systems chemistry approach. Acc. Chem. Res. 45, 2178–2188 (2012). 30. Gourdon, A. On-surface covalent coupling in ultrahigh vacuum. Angew. Chem. Int. Ed. 47, 6950–6953 (2008). 31. Hossain, M. Z. et al. Chemically homogeneous and thermally reversible oxidation of epitaxial graphene. Nature Chem. 4, 305–309 (2012). 32. Saywell, A., Schwarz, J., Hecht, S. & Grill, L. Polymerization on stepped surfaces: alignment of polymers and identification of catalytic sites. Angew. Chem. Int. Ed. 51, 5096–5100 (2012). 33. Di Giovannantonio, M. et al. Insight into organometallic intermediate and its evolution to covalent bonding in surface-confined Ullmann polymerization. ACS Nano 7, 8190–8198 (2013). 34. Binnig, G., Rohrer, H., Gerber, C. & Weibel, E. Surface studies by scanning tunneling microscopy. Phys. Rev. Lett. 49, 57–61 (1982). 35. Rabe, J. P. & Buchholz, S. Commensurability and mobility in 2-dimensional molecular-patterns on graphite. Science 253, 424–427 (1991). 36. De Feyter, S. & De Schryver, F. C. Two-dimensional supramolecular selfassembly probed by scanning tunneling microscopy. Chem. Soc. Rev. 32, 139–150 (2003). 37. Jackson, A. M., Myerson & J. W., Stellacci, F. Spontaneous assembly of subnanometre-ordered domains in the ligand shell of monolayer-protected nanoparticles. Nature Mater. 3, 330–336 (2004). 38. MacLeod, J. M., Ivasenko, O., Perepichka, D. F. & Rosei, F. Stabilization of exotic minority phases in a multicomponent self-assembled molecular network. Nanotechnology 18, 424031–424040 (2007). 39. Ciesielski, A., Schaeffer, G., Petitjean, A., Lehn, J-M. & Samorì, P. STM insight into hydrogen-bonded bicomponent 1D supramolecular polymers with controlled geometries at the liquid–solid interface. Angew. Chem. Int. Ed. 48, 2039–2043 (2009). 40. Ciesielski, A., Palma, C-A., Bonini, M. & Samorì, P. Towards supramolecular engineering of functional nanomaterials: pre-programming multi-component 2D self-assembly at solid–liquid interfaces. Adv. Mater. 22, 3506–3520 (2010). 41. Ciesielski, A., Lena, S., Masiero, S., Spada, G. P. & Samorì, P. Dynamers at the solid–liquid interface: controlling the reversible assembly/reassembly process between two highly ordered supramolecular guanine motifs. Angew. Chem. Int. Ed. 49, 1963–1966 (2010). 42. Ciesielski, A. & Samorì, P. Supramolecular assembly/reassembly processes: molecular motors and dynamers operating at surfaces. Nanoscale 3, 1397–1410 (2011). 43. Grill, L. et al. Nano-architectures by covalent assembly of molecular building blocks. Nature Nanotech. 2, 687–691 (2007). 44. Hulsken, B. et al. Real-time single-molecule imaging of oxidation catalysis at a liquid–solid interface. Nature Nanotech. 2, 285–289 (2007). 45. Perepichka, D. F. & Rosei, F. Extending polymer conjugation into the second dimension. Science 323, 216–217 (2009). 46. Mielke, J. et al. Molecules with multiple switching units on a Au(111) surface: self-organization and single-molecule manipulation. J. Phys. Condens. Matter 24, 394013 (2012). 47. den Boer, D. et al. Detection of different oxidation states of individual manganese porphyrins during their reaction with oxygen at a solid/liquid interface. Nature Chem. 5, 621–627 (2013). 48. Ghijsens, E, et al. A tale of tails: alkyl chain directed formation of 2D porous networks reveals odd–even effects and unexpected bicomponent phase behavior. ACS Nano 7, 8031–8042 (2013). 49. Dienstmaier, J. F. et al. Synthesis of well-ordered COF monolayers: surface growth of nanocrystalline precursors versus direct on-surface polycondensation. ACS Nano 5, 9737–9745 (2011).
50. Dienstmaier, J. F. et al. Isoreticular two-dimensional covalent organic frameworks synthesized by on-surface condensation of diboronic acids. ACS Nano 6, 7234–7242 (2012). 51. Hu, F. Y. et al. In situ STM investigation of two-dimensional chiral assemblies through Schiff-base condensation at a liquid/solid interface. ACS Appl. Mater. Interfaces 5, 1583–1587 (2013). 52. Wang, X. Y. et al. Structural motif modulation in 2D supramolecular assemblies of molecular dipolar unit tethered by alkylene spacer. J. Phys. Chem. C 117, 16392–16396 (2013). 53. Guan, C. Z., Wang, D. & Wan, L. J. Construction and repair of highly ordered 2D covalent networks by chemical equilibrium regulation. Chem. Commun. 48, 2943–2945 (2012). 54. Weigelt, S. et al. Covalent interlinking of an aldehyde and an amine on a Au(111) surface in ultrahigh vacuum. Angew. Chem. Int. Ed. 46, 9227–9230 (2007). 55. Weigelt, S. et al. Surface synthesis of 2D branched polymer nanostructures. Angew. Chem. Int. Ed. 47, 4406–4410 (2008). 56. Tanoue, R. et al. Thermodynamically controlled self-assembly of covalent nanoarchitectures in aqueous solution. ACS Nano 5, 3923–3929 (2011). 57. Piot, L., Bonifazi, D. & Samorì, P. Organic reactivity in confined spaces under scanning tunneling microscopy control: tailoring the nanoscale world. Adv. Func. Mater. 17, 3689–3693 (2007). 58. Stabel, A., Heinz, R., De Schryver, F. C. & Rabe, J. P. Ostwald ripening of 2-dimensional crystals at the solid–liquid interface. J. Phys. Chem. 99, 505–507 (1995). 59. Samorí, P., Müllen, K. & Rabe, H. P. Molecular-scale tracking of the self-healing of polycrystalline monolayers at the solid–liquid interface. Adv. Mater. 16, 1761–1765 (2004). 60. Samorí, P., Severin, N., Müllen, K. & Rabe, J. P. Macromolecular fractionation of rod-like polymers at atomically flat solid–liquid interfaces. Adv. Mater. 12, 579–582 (2000). 61. Cheeseman, J. D., Corbett, A. D., Gleason, J. L. & Kazlauskas, R. J. Receptorassisted combinatorial chemistry: thermodynamics and kinetics in drug discovery. Chem. Eur. J. 11, 1708–1716 (2005). 62. Belenguer, A. M., Friscic, T., Day, G. M. & Sanders, J. K. M. Solid-state dynamic combinatorial chemistry: reversibility and thermodynamic product selection in covalent mechanosynthesis. Chem. Sci. 2, 696–700 (2011). 63. Bonini, M. et al. Competitive physisorption among alkyl-substituted pi-conjugated oligomers at the solid–liquid interface: towards prediction of self-assembly at surfaces from a multicomponent solution. Small 5, 1521–1526 (2009). 64. Baxter, P. N. W., Lehn, J-M. & Rissanen, K. Generation of an equilibrating collection of circular inorganic copper(I) architectures and solid-state stabilisation of the dicopperhelicate component. Chem. Commun. 1323–1324 (1997).
Acknowledgements We thank M. Cecchini for enlightening discussions. P.K. acknowledges the Université de Strasbourg for a doctoral fellowship. This work was supported by the European Community through the European Research Council projects SUPRAFUNCTION (GA257305) and SUPRADAPT (GA-290585), the Agence Nationale de la Recherche through the LabEx project Chemistry of Complex Systems (ANR-10-LABX-0026_CSC) and the International Center for Frontier Research in Chemistry.
Author contributions A.C., P.S. and J-M.L. conceived the experiments and designed the study. P.K. participated in the planning of the study and carried out the synthesis and characterization in solution (HPLC, and NMR and mass spectroscopy). M.E.G. and S.H. performed the STM experiments. M.E.G., A.C. and P.S. interpreted the STM data. J-M.L. and P.K. interpreted the chemical data. All authors discussed the results and contributed to the interpretation of data. A.C., P.S. and J-M.L. co-wrote the paper. All authors contributed to editing the manuscript.
Additional information Supplementary information and chemical compound information are available in the online version of the paper. Reprints and permissions information is available online at www.nature.com/reprints. Correspondence and requests for materials should be addressed to J-M.L. and P.S.
Competing financial interests
The authors declare no competing financial interests.
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