Olefin metathesis and quadruple hydrogen bonding: A powerful combination in multistep supramolecular synthesis

Abstract

We show that combining concepts generally used in covalent organic synthesis such as retrosynthetic analysis and the use of protecting groups, and applying them to the self-assembly of polymeric building blocks in multiple steps, results in a powerful strategy for the self-assembly of dynamic materials with a high level of architectural control. We present a highly efficient synthesis of bifunctional telechelic polymers by ring-opening metathesis polymerization (ROMP) with complementary quadruple hydrogen-bonding motifs. Because the degree of functionality for the polymers is 2.0, the formation of alternating, blocky copolymers was demonstrated in both solution and the bulk leading to stable, microphase-separated copolymer morphologies.

During the last few decades, the increased demand for miniaturization of functional materials has greatly stimulated the development of polymerization techniques enabling the preparation of well defined nanostructures. A widely studied class of self-organized materials with domain sizes and/or specified functionality on the nanometer scale is that of block copolymers (1). Phase segregation behavior in these materials depends on the number of blocks, their volume fraction, chain flexibility, architecture, and the extent of repulsion between the blocks, known as the Flory–Huggins interaction parameter, χ. Currently, most materials and polymer scientists focus their thinking of block copolymer preparation and self-assembly in a forward manner. However, a retrosynthetic analysis back to simple and accessible components, employing an intelligent interplay of covalent and noncovalent reaction steps, may be envisioned to benefit the preparation of complex materials, just like the organic chemist employs this type of analysis in the synthesis of complex natural products (2). Retrosynthetic analysis may open many new routes to materials through multistep syntheses including both supramolecular and chemical steps along the way: supramolecular multistep synthesis.

Recent developments in the field of supramolecular polymer chemistry have shown that small complementary as well as self-complementary building blocks can afford well defined products through self assembly (3, 4). However, to obtain materials with desired macroscopic properties, the supramolecular functionalities need to be separated by polymeric spacers. In this way, shorter macromonomers can be elongated or stitched together through reversible interactions.

Advantages of assembling multiblock copolymers through strong reversible, noncovalent interactions include a modular approach in synthesis, ease of processing, self-healing, facile and selective removal of sacrificial blocks, and an extra level of hierarchical control and self-organization of functional materials (5). Examples of such molecular recognition motifs leading to self-assembled functional materials of well defined architectures in a hierarchical manner have been reported recently (5, 6). Although the concept for the synthesis of telechelic polymers with complementary supramolecular binding motifs has been reported very recently (7), true copolymer properties were not substantiated either in solution or in the bulk. This finding can be attributed to the rather low association constants inherent to the complementary recognition motif used. The strength of the noncovalent interaction affixed to the polymers is expected to be essential in overcoming the driving force of phase segregation. Indeed, Binder et al. (8) showed that high association constants between complementary motifs are required to obtain reversible supramolecular block copolymer morphologies. In this respect, hydrogen-bonding (H-bonding) arrays are appealing because of their synthetic accessibility and their directionality and because they allow the tuning of binding constants between 10 and 10⁹ M⁻¹ in organic solvents. Much of the research into main-chain H-bonded materials has focused on the 2-ureido-pyrimidinone (UPy) moiety because of its ease of synthesis, high dimerization constant (K_dim ≥ 10⁷ M⁻¹), (9) and the low melt viscosity of the emerging materials (10).

Recently, Li and coworkers (11, 12) reported the strong and selective complexation of the 6[1H] tautomeric form of UPy, 1, with 2,7-diamido-1,8-naphthyridines (Napy), 2, by means of quadruple H-bonds as shown in Fig. 1. More recently, we showed that the dual complexation modes of the UPy result in concentration-dependent selectivity, favoring UPy–Napy heterocomplexation over UPy homodimerization by a factor of >20:1 above 0.1 M (K_a = 5 × 10⁶ M⁻¹ in CHCl₃) (13). Because of this high selectivity and strength, the UPy–Napy heterodimer seems eminently suitable for constructing supramolecular block copolymers with high degrees of polymerization (DP) both in solution and in the bulk.

Fig. 1.

The UPy group can form self-complementary dimers through an AADD quadruple H-bonding array. Upon addition of a Napy group, a UPy–Napy heterodimer is formed by UPy tautomerization to an ADDA H-bonding array to complement the DAAD array of Napy.

Retrosynthesis of a microphase-separated material based on a combination of covalent and noncovalent steps is illustrated in Fig. 2. Such a material requires immiscible polymeric components, in which macrophase separation is prevented by strong and complementary noncovalent bonds between the telechelic blocks. Telechelic polymers with multiple H-bonding endgroups have been prepared by means of postpolymerization modification routes (14–22). However, incomplete reaction leads to small, yet detrimental, amounts of monofunctionalized polymers, which act as chain stoppers. Even a small percentage of monofunctional material (<1%) can lead to a dramatic reduction in the molecular weight (23, 24) and hence material properties of the polymer. Thus, it was decided to first prepare small molecules with the desired H-bonding end groups and then grow the polymer chains in between these groups. This goal may be accomplished through the ring-opening metathesis polymerization (ROMP) of a cyclic olefin in the presence of a bifunctional UPy or Napy chain transfer agent (CTA). The use of complementary H-bonding motifs and truly telechelic components with high association constants, required for controlling microphase-separated morphologies, makes the combination of covalent and noncovalent reaction steps more demanding. Therefore, a supramolecular protecting group (SPG) strategy in each of the convergent pathways in the retrosynthetic scheme was undertaken to tackle the detrimental coordination of Napy with the ROMP catalyst, as well as premature polymerization of the UPy CTA.

Fig. 2.

A retrosynthetic analysis of a material with microphase separation stemming from a block copolymer prepared from supramolecular polymeric components.

Results and Discussion

Design of the Supramolecular System.

The preparation of supramolecular block copolymers was achieved with X–X and Y–Y bifunctional macromonomers, which are telechelic polymers bearing UPy (X) and Napy (Y) endgroups. Telechelic polymers with an endgroup functionality of precisely two (F_n = 2.0) were easily synthesized through ROMP (25, 26) in the presence of a CTA, thereby eliminating the need to perform any further reactions on the polymer. Conceptually, the ROMP of a cyclic olefin in the presence of a symmetric CTA bearing either UPy or Napy moieties essentially can be viewed as growing a polymer in between the two H-bonding motifs. Fig. 3 illustrates the ROMP of a cyclic olefin in the presence of a bisUPy or bisNapy CTA. Additionally, it was found that a SPG (27–29) (Z) was required during the polymerization, illustrated graphically as a monofunctional entity in the retrosynthesis (Fig. 2).

Fig. 3.

ROMP of a cyclic olefin with a CTA containing supramolecular functionalities, X or Y, in the presence of a SPG, Z.

Fig. 3 illustrates the ROMP of a cyclic olefin in the presence of a CTA with either UPy (X) or Napy (Y) functionalities, as well as the SPG (Z). During the polymerization process, the use of a UPy-based SPG, 18, is very important. When the CTA contains Napy moieties, the monofunctional UPy is necessary to prevent any ruthenium catalyst coordination to the naphthyridines; when the functionality of the CTA is a UPy, the protecting group serves to limit build-up of viscosity during the polymerization (24).

SPGs using metathesis polymerization have been reported before for the protection of triple H-bond arrays with thymine derivatives (27, 28). However, they could not be used here with UPy and Napy functionalities. Because of its dual binding modes, UPy derivatives are able to bind both UPy and Napy moieties. To facilitate its removal from an apolar polymer, UPy derivative 18 bearing a triethylene glycol tail was designed. The branched chain on the pyrimidinone ring aids its solubility in apolar solvents, whereas the triethylene glycol tail ensures solubility in a variety of polar solvents like THF and methanol.

Moreover, the use of ROMP and a CTA with supramolecular functionalities allows for a large variation of the main-chain polymer with UPy or Napy endgroups. Simple alteration of the cyclic olefin monomer used during the ROMP, followed by mixing of the A–A and B–B macromonomers, will result in the self-assembly of many new supramolecular block copolymers with tunable properties and pendent functionalities. Additionally, it will allow for the straightforward inclusion of synthetically orthogonal blocks, introduction of electroactive blocks, and the preparation of dynamic thermoplastic elastomers.

Synthesis of Supramolecular Macromonomers for Block Copolymers.

For synthetic ease, both cis- (3) and trans- (4) bisUPy CTAs with a C4 spacer as well as the trans-bisNapy CTA with a C6 spacer(5) were first used in an attempt to prepare the α,ω-telechelic polymers by ROMP (see Supporting Text and Fig. 7, which are published as supporting information on the PNAS web site). Unfortunately, the relative steric crowding of the supramolecular moieties around the internal olefin either completely prevented or severely limited the use of these CTAs in the ROMP of cyclooctene. Therefore, two new CTAs were prepared with a larger carbon spacer between the UPy and Napy groups (Fig. 4).

Fig. 4.

BisUPy and bisNapy CTAs with 20-carbon linkers.

The synthetic routes to CTAs with a C20 spacer are depicted in Scheme 1, which is published as supporting information on the PNAS web site. The C20 CTAs were prepared in four or five high-yielding steps from either undecyl-bromide or undecenoic-acid, and both routes employed homodimerization through olefin cross-metathesis. Because any monofunctional UPy or Napy CTA would be detrimental in the preparation of α,ω-telechelic polymers, removal of any nondimerized material was done carefully by successive recrystallization or column chromatography. Furthermore, bisUPy CTA (6) was purified by multiple precipitations from MeOH, and bisNapy CTA (7) was purified by column chromatography. Both 6 and 7 were analyzed for purity by MS, FTIR, and ¹H and ¹³C NMR.

With CTAs 6 and 7 and SPG 18 in hand, ROMP of cyclooctene was carried out. This monomer was chosen for a number of reasons, including the following: (i) its well known reactivity for ROMP, and (ii) the produced poly(octenamer) is a polymer of commercial interest and can be subsequently hydrogenated to linear polyethylene. All polymerizations were performed in dry 1,2-dichloroethane (DCE) for 48 h at 55°C under an argon atmosphere. Typically, monomer:catalyst ratios of 5,000–7,000:1 were used with concentrations varying from 1.5 to 3 M, allowing for endgroup functionality to be ≥99.98%. To investigate the influence of the SPG, a number of polymerizations were performed with the CTAs under varying conditions and led to an optimal ratio of 2.4 equivalents of 18 relative to CTA. Furthermore, ROMP of cyclooctene in the presence of trans-3-hexene as a CTA was carried out at varying monomer:CTA ratios to obtain reference polymers without any interacting chain ends.

Deprotection of the Supramolecular Macromonomers.

After solving the problems of catalyst coordination and high viscosity during the polymerization with a SPG, a method affording complete deprotection was sought. Luckily, the design of the SPG enabled facile and complete deprotection by precipitation of THF solutions of the crude polymerization mixtures into methanol. The UPy SPG was designed to be highly soluble both in apolar as well as polar organic solvents. The branched ethyl-pentyl tail on the pyrimidinone ring served to greatly increase solubility of UPy dimers in chloroform, toluene, and DCE, as well as to induce solubility of UPy–Napy heterodimers. This process proved necessary as Napy CTA 7 was sparingly soluble in DCE, the solvent of choice for subsequent ROMP polymerizations in this study. Additionally, incorporation of the triethylene glycol tail, which extends from the ureido group, imparts solubility of the SPG in both ethanol and methanol. Although the introduction of a SPG was accomplished by the self-assembly of a highly soluble monofunctional UPy, complete deprotection occurred by first disrupting the quadruple H-bonding arrays (dissolving the polymerization mixtures in THF) followed by selective solvation of 18 in MeOH and simultaneous precipitation of the telechelic ROMP polymers. The precipitated polymer mixtures in MeOH were subjected to centrifugation, isolated, redissolved in THF, and reprecipitated from MeOH. This cycle was carried out three times in total to ensure complete removal of any monofunctional UPy SPG.

Characterization of Telechelic Supramolecular Macromonomers.

After complete removal of SPG 18, both telechelic UPy (19) and telechelic Napy (20) ROMP polymers were characterized by several methods outlined below. For both UPy and Napy polymers, ¹H NMR was used to calculate the number of monomer repeat units between the supramolecular end groups and thus M_n values of 4,418 g/mol (19) and 3,963 g/mol (20), respectively. ¹H NMR was also helpful in confirming SPG removal (see Fig. 8a, which is published as supporting information on the PNAS web site). The bottom spectrum illustrates the H-bonding region of the ¹H NMR spectrum for polymer 20; after the first precipitation of the polymer from MeOH, peaks arising from the UPy–Napy heterodimer are clearly visible. Although the majority of the SPG was removed by precipitation, a small amount remained attached to the ROMP polymer. After several precipitation cycles described above, the monofunctional UPy SPG was completely removed from the polymer, and H-bonding peaks were absent in the NMR spectrum (top spectrum, Fig 8a).

MALDI-TOF MS also proved to be helpful in characterization of the telechelic ROMP polymers; a representative spectrum can be seen in Fig. 8b for a polymer with Napy endgroups. One set of polymer peaks can be observed with a mass difference of 110.1 atomic mass units (amu); the Inset clearly shows that the H⁺, Na⁺, and K⁺ adducts each fly quite readily, and the masses can be ascribed to a polymer chain with a precise number of cyclooctene units inserted into the original CTA. The m/z peak at 1,429.1 arises from exactly 5 cyclooctene monomers, the original mass of the CTA 7 (877.2 g/mol) plus 1 proton. Moreover, SPG 18 and CTA 7 were not observed in the MALDI spectrum.

In addition to MALDI-TOF MS and ¹H NMR, both FTIR and UV/vis spectrometry provided relevant information about the deprotection of UPy SPG from telechelic Napy polymer 20. When all of the SPG was removed, the FTIR spectrum revealed a pronounced NH absorption at 3,311 cm⁻¹, indicating that the NH groups of the Napy moieties were not H-bonded to any UPy SPG. Before complete deprotection, a broader peak ≈3,300 cm⁻¹ was observed. A UV/vis spectrum of free Napy shows an absorption starting at 300 and ending sharply at 350 nm, with a maximum at 346 nm and several vibronic subpeaks at lower wavelengths. Upon UPy heterocomplexation, however, a new shoulder appeared at 355 nm for the Napy chromophore (30). After three precipitations from MeOH, the UV/vis of the telechelic bisNapy polymer did not display the characteristic UPy-Napy shoulder at 355 nm, also indicating complete removal of the UPy SPG.

Because the UPy telechelic polymers were capable of forming elongated supramolecular polymers through self-assembly of the self-complementary H-bonding motifs, they could be further characterized with respect to their purity by Ubbelhode viscometry in chloroform. Until now, only small-molecule bisUPy materials have displayed a high dependence of specific viscosity on concentration above the overlap concentration (the specific viscosity increases with c^3.5–3.7) as predicted by Cates (31) (entry 3, Table 1). Previously, telechelic UPy polymers prepared by postpolymerization modification routes, such as UPy₂ (polydimethylsiloxane) (entry 4, Table 1; see ref. 32), have yielded exponents of ≤3. This result is likely due to the presence of monofunctional polymer chains that act as chain stoppers and severely limit the virtual DP and thus specific viscosity of the polymer solutions. After purification of UPy telechelic ROMP polymer 19 by removal of any UPy SPG, viscosity measurements revealed a specific viscosity vs. concentration dependence of 3.72 on a double-logarithmic plot (entry 1, Table 1). To conclusively show that the reduced slopes of previous systems arise from the presence of chain stoppers, and hence incomplete functionalization of polymer chains, the Ubbelohde viscometry experiment was repeated with a chloroform solution in which 2 mol % of monofunctional UPy SPG 18 was intentionally added to the pure UPy telechelic ROMP polymer. Entry 2 in Table 1 clearly shows that the slope (over the same concentration range) had decreased to 2.62. A polyoctenamer with the same molecular weight as 19 was prepared with CH₃ endgroups as a control, with a slope of 1.32 (entry 5, Table 1).

Table 1.

Slopes from double-logarithmic plots of specific viscosity (η_sp) vs. concentration from Ubbelohde viscometry (in CHCl₃) of several telechelic supramolecular polymers

Entry	Endgroups	Spacer	Slope
1	UPy	Polyoctenamer (19)	3.72*
2	UPy/18	Polyoctenamer (19) + 2% 18	2.62*
3	UPy	(CH2)6†	3.76‡
4	UPy	Polydimethylsiloxane§	1.51‡
5	CH3	Polyoctenamer	1.32*

*25°C.

^†Ref. 23.

^‡20°C.

^§Ref. 32.

Preparation and Characterization of Supramolecular Block Copolymers.

Finally, once both UPy and Napy telechelic polymers (macromonomers) were individually prepared and well characterized, preparation of AA plus BB supramolecular block copolymers was attempted. Again, Ubbelohde viscometry was used to illustrate supramolecular block copolymer formation in solution. As mentioned earlier, a major advantage of using the dual binding capability of UPy with Napy is that it enables the preparation of high-molecular-weight polymeric materials over a wide range of UPy:Napy ratios (13). To this end, we prepared a chloroform solution containing a Napy telechelic ROMP polymer 20 with UPy CTA 6 in a 1:5 (wt/wt) ratio (1:18 molar ratio of Napy:UPy groups). UPy CTA 6 was chosen for several reasons, allowing for better characterization of the same viscometry solution by both ¹H NMR as well as UV/vis spectroscopy. A double-logarithmic plot of the specific viscosity vs. concentration for the AA plus BB system yields a slope of 3.5 (see Fig. 9a, which is published as supporting information on the PNAS web site). A series of UV/vis spectra illustrate a titration of UPy CTA 6 into Napy telechelic ROMP polymer 20 in CHCl₃ ranging from 0 to 15 equivalents (Fig. 9b). When Napy endgroups undergo heterodimerization with the UPy moieties, a shoulder at 355 nm is visible in the UV/vis spectrum (see above) (30). In such a solution, the shorter C20 bisUPy CTA monomers undergo self-assembly to form a supramolecular polymer, and the Napy telechelic ROMP polymers are incorporated into the polymer chains by forming complementary H-bonding interactions with a fraction of the UPy groups. The result is a supramolecular AA/BB block copolymer with C20 units and large polyoctenamer units in the same chain! This result is clearly the case, as the UV/vis spectrum of the CHCl₃ solution used for solution viscometry (Fig. 9b, red curve) indicates that all Napy groups are bound by a UPy.

We also wanted to see whether the high association constant between the UPy and Napy motifs would allow the formation of block copolymers in bulk with stable microphase separation. This investigation ultimately would lead to the controlled formation of many block copolymer morphologies by the supramolecular assembly of the component blocks. Atomic force microscopy (AFM) was useful in characterizing the film morphologies arising from the self-assembly of UPy telechelic and Napy telechelic polymers. Therefore, films of telechelic bisNapy ROMP polymer 20 and a telechelic bisUPy poly(ethylene-butylene) (21; bisUPy-PEB) (M_n = 4,100 g/mol; see ref. 14) were studied by tapping-mode AFM. A bisUPy-PEB was used with bisNapy polyoctenamer 20 to provide contrast in the AFM images. Block copolymer films were prepared by solution-blending of the individual components in toluene followed by drop-casting onto glass slides.

In contrast to a film of pure 20 (Fig. 5b), mixtures of 20 with bisUPy-PEB 21 yielded (clear) macroscopically homogeneous films, which also showed microphase-separated domains upon inspection with AFM. To determine the distribution and size of the microdomains, additional information was obtained by varying the ratio of 20 to 21 in the films (30/70 and 70/30 mol %).^† The phase image (Fig. 5a) shows microphase separation demonstrating the formation of domains consisting of two chemically different blocks. The topographic (height) images (see Fig. 10, which is published as supporting information on the PNAS web site) show flat and homogeneous films (rms roughness of ±1 and ±3 nm, respectively). The pronounced phase contrast indicates that chemical inhomogeneities have developed through self-assembly bringing about microphase separation. It is noteworthy that when bisNapy telechelic polymer 20 was used in excess (see Supporting Text), the supramolecular polymer chains were on average triblocks.

Fig. 5.

Tapping-mode AFM images of Napy telechelic polyoctenamer 20 and bisUPy–PEB 21. (a) Phase image of a 70/30 mol % 20:21 film. (b) Height image of a Napy telechelic polyoctenamer 20 film.

Through varying the molar ratio of Napy:UPy telechelic polymers, the phase images allowed for assignment of the light features to the bisNapy telechelic polyoctenamer (hard) block. The polyoctenamer block also displayed a feature size of 15 nm and was extremely regular in appearance regardless of whether it was the majority or minority component block. Moreover, these hard domains existed in the films rather than laying on top of the films as indicated by the smooth height images. In contrast to the mixtures where both polymeric blocks contained supramolecular end groups, reference experiments carried out with bisNapy telechelic ROMP polymer 20 and PEB (22) (33) without UPy groups did not give rise to microphase-separated structures. Rather, these mixtures produced turbid films and macrophase-separated domains as can be clearly seen in the AFM images yielding the large z-ranges and rms values for the films (Fig. 5b and Supporting Text).

Differential scanning calorimetry (DSC) also was carried out on 20, 21, and mixtures correlating to the supramolecular copolymer films were imaged with AFM. When bisUPy-PEB 21 was added to bisNapy polyoctenamer 20, the melting peak arising from the semicrystalline polyoctenamer block shifted to lower temperatures accordingly (Table 2, entries 1–3). Moreover, the amount of crystallinity in the block copolymers decreased with increasing weight percentage of the amorphous PEB blocks. These data are all consistent with the AFM images, indicating that a supramolecular block copolymer is indeed formed. However, when DSC was carried out on a mixture of bisNapy polyoctenamer 20 with an excess of PEB 22 that did not bear any UPy groups at the chain ends (Table 2, entry 5), the crystallinity due to the polyoctenamer actually increased. This result can be rationalized by the macrophase separation of the blend (see Fig. 10 and also Fig. 11, which is published as supporting information on the PNAS web site). The much smaller weight fraction of 20 in a matrix of amorphous PEB 22 undergoes macrophase separation in the melt resulting in confinement and a more compact and ordered crystalline domain upon cooling.

Table 2.

DSC data for supramolecular block copolymers

Entry	Polymer*	Tm, °C	ΔH, J/g	Tg, °C
1	20	48.2	37.8	−10.7
2	21	—	—	−58.2
3	20:21 (64:36)	47.5	34.2	−59.6
4	20:21 (25:75)	46.7	32.2	−58.2
5	20:22 (24:76)	45.3	41.3	−61.9

*Values in parentheses are ratios of the polymers (wt/wt).

Conclusions

A retrosynthetic approach was outlined to obtain supramolecular block copolymers. Successful preparation of both UPy and Napy containing telechelic polymers with an endgroup functionality of precisely two was achieved by ROMP in the presence of a bifunctional CTA. CTAs with a C20 linker could be synthesized on large scale in excellent purity through homodimerization by means of olefin cross-metathesis. Problems arising from UPy self complementarity and Napy–ruthenium catalyst coordination were overcome by introduction of a UPy protection group, which could easily be removed from the crude reaction mixture by multiple precipitations of the polymer from methanol.^‡

Purity of the ROMP polymers (macromonomers) bearing supramolecular endgroups was vital for subsequent self-assembly and was substantiated by using ¹H NMR, MALDI-TOF MS, FTIR, and UV/vis spectroscopy. Self-assembly of the UPy and Napy telechelic polymers into supramolecular block copolymers was demonstrated in solution by a variety of techniques including Ubbelohde viscometry and UV/vis spectroscopy. Initial studies on the solid-state structures of these copolymers by tapping-mode AFM indicate that microphase-separated morphologies are adopted.

Additionally, the dual binding capabilities of UPy can be exploited to prepare block copolymers with a wide range of compositions. Contrary to most supramolecular polymers bearing complementary binding motifs whose DP and material properties are heavily dependent upon a stoichiometry of exactly 1:1 (Fig. 6a), a supramolecular copolymer formed from telechelic bisUPy and bisNapy polymers retains a high DP over a wide range of UPy/Napy ratios (Fig. 6b). This characteristic allows for both practical and synthetically diverse preparations of supramolecular block copolymers. More importantly, access to the entire composition range of block copolymers can be achieved through tuning the molecular weight of the majority component that exists between the two UPy moieties. Fig. 6c illustrates how the polymeric block between the Napy groups is fixed (in red), whereas the polymeric block length and weight fraction in blue (coming from the bisUPy telechelic materials) is tunable and depends on the ratio of UPy to Napy.

Fig. 6.

Theoretical graphs and molecular picture of DP vs. AA/BB monomer ratios. (a) Virtual DP of a supramolecular copolymer vs. the ratio of the component A and B blocks when A and B are only complementary. (b) Virtual DP of a supramolecular copolymer vs. the ratio of the component A and B blocks when A is both self-complementary and complementary to B. (c) Tuning a supramolecular block copolymer by the UPy to Napy ratio.

We believe that the outlined retrosynthetic strategy in combination with the supramolecular protection methodology will allow for the versatile design and preparation of complex, multicomponent systems by means of supramolecular multistep synthesis.

Materials and Methods

General Methods.

All synthetic procedures were performed under inert atmosphere of dry argon unless stated otherwise. Commercial solvents and reagents were used without purification unless stated otherwise. 1,4-Dioxane was distilled over LiAlH₄, and chloroform and pyridine were dried over 4-Å molecular sieves before use. Extra dry DCE (water < 50 ppm) for the polymerization reactions was obtained from Acros Organics and used as received. Deuterated chloroform was dried and deacidified over activated alumina (type I) and stored on 4-Å molsieves. ¹H and ¹³C NMR spectra were recorded on a Gemini 300, Mercury 400, or Inova 500 spectrometer (all from Varian). Chemical shifts are reported in ppm relative to tetramethylsilane and multiplicities as singlet (s), doublet (d), triplet (t), quartet (q), and multiplet (m). MALDI-TOF results were obtained by using a PerSeptive Biosystems Voyager-DE PRO spectrometer with an α-cyanohydroxycinnamic acid or a neutral 2-[(2E)-3-(4- tert-butylphenyl)-2-methylprop-2-enylidene] malononitrile matrix. IR spectra were recorded on a PerkinElmer Spectrum One FTIR spectrometer with a Universal ATR sampling accessory. Elemental analysis was performed on a PerkinElmer 2400 series II CHNS/O analyzer. Melting points were determined on a Büchi Melting Point B-540 apparatus. Analytical gel-permeation chromatography was carried out in THF on two PL Gel single pore size (100 Å) 30-cm columns, with a particle size of 3 μm (Polymer Labs) connected in series with a SPD-M10Avp photodiode array UV/vis detector (Shimadzu) measuring between 190 and 370 nm. Reported molecular weights were obtained against polystyrene standards.

Viscosity Measurements.

Solution viscosities were measured by using Schott-Geräte Ubbelohde microviscometers with suspended level bulb in automated setups with Schott-Geräte AVS/S measurement tripods and AVS 350 measurement devices. The microviscometers were thermostated in a water bath at 25.00 (±0.01)°C. Samples were filtered over 1-μm polytetrafluoroethylene filters before measurement. Specific viscosities were corrected by using the appropriate Hagenbach correction factors.

AFM Measurements.

AFM images were recorded under ambient conditions by using a Digital Instruments Multimode Nanoscope IV operating in the tapping-mode regime by using microfabricated silicon cantilever tips (PPP-NCH, 300–330 kHz, 42 N/m, tip radius 10 nm); scanner 5962EV was used with scan rates 0.5–1.25 Hz, scan angle 0°; feedback signals were optimized, and A_sp/A₀ was adjusted to 0.6. Images shown are subjected to a first-order plane-fitting procedure to compensate for sample tilt. The phase images were recorded simultaneously with the topographic images. The roughness data are rms values, which are derived as standard deviations of all height values in an image. Films were dropcasted onto glass slides from a 5 wt % toluene solution.

Thermal Analysis.

DSC measurements were performed on a PerkinElmer Differential Scanning Calorimeter Pyris 1 with Pyris DSC Autosampler and PerkinElmer CCA7 cooling element under a nitrogen atmosphere. Thermal parameters were determined from the second heating curve (10°C/min).

Synthesis.

UPy-imidazolide (8) was prepared as reported by Keizer et al. (34), 7-(2-ethyl-hexanoylamino)-2-chloro-1,8-naphthyridine (12) was synthesized as reported by Ligthart et al. (35); trans- and cis-1,4-diamino-2-butene·2HCl were prepared similar to a literature procedure (36); 2- n-butylureido-6-methyl-4[1H]pyrimidinone (1) was prepared as reported by Beijer et al. (37); and bisUPy-PEB (21) (14) and reference PEB (22) (34) were prepared as described.

General procedure of ROMP polymerizations with CTA (19 and 20):

A dried 50-ml RB flask was charged with CTA 6 or 7 (0.29 mmol) and UPy SPG 18 (0.65 mmol; see Scheme 2, which is published as supporting information on the PNAS web site). Dry DCE (0.7 ml) was added under argon together with a stirbar. After obtaining a clear solution, cyclooctene (0.37 ml) was added. Subsequently, a solution of second-generation Grubbs ruthenium catalyst (1.0 mg, 1.18 μmol) in DCE (0.5 ml) was injected. The reaction mixture immediately turned highly viscous and was stirred at 55°C for 48 h. The solution was cooled to room temperature, and 1.0 ml of chloroform was added. The viscous solution was added dropwise into 100 ml of methanol with added BHT to prevent cross-linking. The white precipitate was isolated by centrifugation. The white solid was dissolved in THF, and the precipitation process was repeated twice to afford the supramolecular polymers as white powders, which were free of the UPy protecting group.

2{2-[2-(2-Methoxyethoxy)ethoxy]ethyl}ureido-6-(3-heptyl)-4[1H] pyrimidinone (18):

To a solution of ethylpentyl isocytosine (5.16 g, 24.7 mmol) in 30 ml of dry chloroform in a 50-ml round-bottom flask, 1,1-carbonyl-diimidazole (5.20 g, 32.0 mmol) was added and stirred for 4 h at room temperature under inert atmosphere. To the mixture 30 ml of CHCl₃ was added, washed with water (3 × 10 ml), dried over MgSO₄, and evaporated to give the crude imidazolide, which was used immediately for the next step. The UPy–imidazolide was dissolved in 20 ml of chloroform, followed by the addition of 2-(2-(2-methoxyethoxy)ethoxy)ethylamine 23 (3.72 g, 22.8 mmol) and stirred overnight (16 h) at 50°C under inert atmosphere. The solution was cooled to room temperature, and chloroform (120 ml) was added. The solution was washed with 1 M HCl (3 × 40 ml), water (10 ml), and brine (10 ml), dried over MgSO₄, and evaporated to yield the title compound as a pale-yellowish oil (8.0 g, 90%). ¹H NMR (CDCl₃): δ = 13.11 (broad, 1H, N H), 11.92 (broad, 1H, N H), 10.24 (broad, 1H, N H), 5.74 (s, 1H, C HCO), 3.61 (m, 6H, C H₂O), 3.42 (m, 4H, NHCH₂CH₂), 3.30 (s, 3H, OC H₃), 2.25 (m, 1H, CC H), 1.62–1.45 (m, 4H, C H₂), 1.29–1.16 (m, 4H, C H₂) ppm; ¹³C NMR (CDCl₃): δ = 172.94, 156.90, 155.31, 154.72, 71.92, 70.50, 70.28, 69.38, 58.95, 50.12, 45.28, 39.50, 32.82, 29.26, 26.55, 22.42, 13.83, 11.64 ppm; MALDI-TOF MS: (m/z) calcd. 398.25; observed: 399.41 (M+H⁺), 421.39 (M+Na⁺), 437.37 (M+K⁺); FTIR (ATR): ν = 3224, 2959, 2929, 2873, 1697, 1656, 1609, 1584, 1556, 1528, 1453, 1394, 1351, 1316, 1253, 1200, 1106, 1029, 921, 842, 803 cm⁻¹.

The synthetic procedures and characterization for the other compounds presented in the work are available in Supporting Text.

Abbreviations

CTA

chain transfer agent

DCE

1,2-dichloroethane

DP

degrees of polymerization

DSC

differential scanning calorimetry

Napy

2,7-diamido-1,8-naphthyridines

PEB

poly(ethylene-butylene)

ROMP

ring-opening metathesis polymerization

SPG

supramolecular protecting group

UPy

2-ureido-pyrimidinone.