Olefin metathesis and quadruple hydrogen bonding:A powerful combination in multistepsupramolecular synthesisOren A. Scherman, G. B. W. L. Ligthart, Haruki Ohkawa, Rint P. Sijbesma*, and E. W. Meijer*
Laboratory of Macromolecular and Organic Chemistry, Eindhoven University of Technology, P.O. Box 513, 5600 MB Eindhoven, The Netherlands
Edited by Jack Halpern, University of Chicago, Chicago, IL, and approved June 13, 2006 (received for review March 28, 2006)
We show that combining concepts generally used in covalentorganic synthesis such as retrosynthetic analysis and the use ofprotecting groups, and applying them to the self-assembly ofpolymeric building blocks in multiple steps, results in a powerfulstrategy for the self-assembly of dynamic materials with a highlevel of architectural control. We present a highly efficient syn-thesis of bifunctional telechelic polymers by ring-opening met-athesis polymerization (ROMP) with complementary quadruplehydrogen-bonding motifs. Because the degree of functionality forthe polymers is 2.0, the formation of alternating, blocky copoly-mers was demonstrated in both solution and the bulk leading tostable, microphase-separated copolymer morphologies.
During the last few decades, the increased demand forminiaturization of functional materials has greatly stimu-
lated the development of polymerization techniques enablingthe preparation of well defined nanostructures. A widely studiedclass of self-organized materials with domain sizes and�orspecified functionality on the nanometer scale is that of blockcopolymers (1). Phase segregation behavior in these materialsdepends on the number of blocks, their volume fraction, chainflexibility, architecture, and the extent of repulsion between theblocks, known as the Flory–Huggins interaction parameter, �.Currently, most materials and polymer scientists focus theirthinking of block copolymer preparation and self-assembly in aforward manner. However, a retrosynthetic analysis back tosimple and accessible components, employing an intelligentinterplay of covalent and noncovalent reaction steps, may beenvisioned to benefit the preparation of complex materials, justlike the organic chemist employs this type of analysis in thesynthesis of complex natural products (2). Retrosynthetic anal-ysis may open many new routes to materials through multistepsyntheses including both supramolecular and chemical stepsalong the way: supramolecular multistep synthesis.
Recent developments in the field of supramolecular polymerchemistry have shown that small complementary as well as self-complementary building blocks can afford well defined productsthrough self assembly (3, 4). However, to obtain materials withdesired macroscopic properties, the supramolecular functionalitiesneed to be separated by polymeric spacers. In this way, shortermacromonomers can be elongated or stitched together throughreversible interactions.
Advantages of assembling multiblock copolymers through strongreversible, noncovalent interactions include a modular approach insynthesis, ease of processing, self-healing, facile and selective re-moval of sacrificial blocks, and an extra level of hierarchical controland self-organization of functional materials (5). Examples of suchmolecular recognition motifs leading to self-assembled functionalmaterials of well defined architectures in a hierarchical mannerhave been reported recently (5, 6). Although the concept for thesynthesis of telechelic polymers with complementary supramolecu-lar binding motifs has been reported very recently (7), true copol-
ymer properties were not substantiated either in solution or in thebulk. This finding can be attributed to the rather low associationconstants inherent to the complementary recognition motif used.The strength of the noncovalent interaction affixed to the polymersis expected to be essential in overcoming the driving force of phasesegregation. Indeed, Binder et al. (8) showed that high associationconstants between complementary motifs are required to obtainreversible supramolecular block copolymer morphologies. In thisrespect, hydrogen-bonding (H-bonding) arrays are appealing be-cause of their synthetic accessibility and their directionality andbecause they allow the tuning of binding constants between 10 and109 M�1 in organic solvents. Much of the research into main-chainH-bonded materials has focused on the 2-ureido-pyrimidinone(UPy) moiety because of its ease of synthesis, high dimerizationconstant (Kdim � 107 M�1), (9) and the low melt viscosity of theemerging materials (10).
Recently, Li and coworkers (11, 12) reported the strong andselective complexation of the 6[1H] tautomeric form of UPy, 1, with2,7-diamido-1,8-naphthyridines (Napy), 2, by means of quadrupleH-bonds as shown in Fig. 1. More recently, we showed that the dualcomplexation modes of the UPy result in concentration-dependentselectivity, favoring UPy–Napy heterocomplexation over UPy ho-modimerization by a factor of �20:1 above 0.1 M (Ka � 5 � 106 M�1
in CHCl3) (13). Because of this high selectivity and strength, theUPy–Napy heterodimer seems eminently suitable for constructingsupramolecular block copolymers with high degrees of polymer-ization (DP) both in solution and in the bulk.
Retrosynthesis of a microphase-separated material based on acombination of covalent and noncovalent steps is illustrated in Fig.2. Such a material requires immiscible polymeric components, inwhich macrophase separation is prevented by strong and comple-mentary noncovalent bonds between the telechelic blocks. Telech-elic polymers with multiple H-bonding endgroups have been pre-pared by means of postpolymerization modification routes (14–22).However, incomplete reaction leads to small, yet detrimental,amounts of monofunctionalized polymers, which act as chainstoppers. 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 wasdecided to first prepare small molecules with the desired H-bondingend groups and then grow the polymer chains in between thesegroups. This goal may be accomplished through the ring-openingmetathesis polymerization (ROMP) of a cyclic olefin in the pres-ence of a bifunctional UPy or Napy chain transfer agent (CTA). Theuse of complementary H-bonding motifs and truly telechelic com-
Conflict of interest statement: No conflicts declared.
This paper was submitted directly (Track II) to the PNAS office.
ponents with high association constants, required for controllingmicrophase-separated morphologies, makes the combination ofcovalent and noncovalent reaction steps more demanding. There-fore, a supramolecular protecting group (SPG) strategy in each ofthe convergent pathways in the retrosynthetic scheme was underta-ken to tackle the detrimental coordination of Napy with the ROMPcatalyst, as well as premature polymerization of the UPy CTA.
Results and DiscussionDesign of the Supramolecular System. The preparation of supramo-lecular block copolymers was achieved with X–X and Y–Y bifunc-tional macromonomers, which are telechelic polymers bearing UPy(X) and Napy (Y) endgroups. Telechelic polymers with anendgroup functionality of precisely two (Fn � 2.0) were easilysynthesized through ROMP (25, 26) in the presence of a CTA,thereby eliminating the need to perform any further reactions onthe polymer. Conceptually, the ROMP of a cyclic olefin in thepresence of a symmetric CTA bearing either UPy or Napy moietiesessentially can be viewed as growing a polymer in between the twoH-bonding motifs. Fig. 3 illustrates the ROMP of a cyclic olefin inthe presence of a bisUPy or bisNapy CTA. Additionally, it wasfound that a SPG (27–29) (Z) was required during the polymer-
ization, illustrated graphically as a monofunctional entity in theretrosynthesis (Fig. 2).
Fig. 3 illustrates the ROMP of a cyclic olefin in the presence ofa CTA with either UPy (X) or Napy (Y) functionalities, as well asthe SPG (Z). During the polymerization process, the use of aUPy-based SPG, 18, is very important. When the CTA containsNapy moieties, the monofunctional UPy is necessary to prevent anyruthenium catalyst coordination to the naphthyridines; when thefunctionality of the CTA is a UPy, the protecting group serves tolimit build-up of viscosity during the polymerization (24).
SPGs using metathesis polymerization have been reported be-fore for the protection of triple H-bond arrays with thyminederivatives (27, 28). However, they could not be used here with UPyand Napy functionalities. Because of its dual binding modes, UPyderivatives are able to bind both UPy and Napy moieties. Tofacilitate its removal from an apolar polymer, UPy derivative 18bearing a triethylene glycol tail was designed. The branched chainon the pyrimidinone ring aids its solubility in apolar solvents,whereas the triethylene glycol tail ensures solubility in a variety ofpolar solvents like THF and methanol.
Moreover, the use of ROMP and a CTA with supramolecularfunctionalities allows for a large variation of the main-chain poly-mer with UPy or Napy endgroups. Simple alteration of the cyclicolefin monomer used during the ROMP, followed by mixing of theA–A and B–B macromonomers, will result in the self-assembly ofmany new supramolecular block copolymers with tunable proper-ties and pendent functionalities. Additionally, it will allow for thestraightforward inclusion of synthetically orthogonal blocks, intro-duction of electroactive blocks, and the preparation of dynamicthermoplastic elastomers.
Synthesis of Supramolecular Macromonomers for Block Copolymers.For synthetic ease, both cis- (3) and trans- (4) bisUPy CTAs with aC4 spacer as well as the trans-bisNapy CTA with a C6 spacer(5)were first used in an attempt to prepare the �,�-telechelic polymersby ROMP (see Supporting Text and Fig. 7, which are published assupporting information on the PNAS web site). Unfortunately, the
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–Napyheterodimer is formed by UPy tautomerization to an ADDA H-bonding array to complement the DAAD array of Napy.
Fig. 2. A retrosynthetic analysis of a material with microphase separationstemming from a block copolymer prepared from supramolecular polymericcomponents.
Fig. 3. ROMP of a cyclic olefin with a CTA containing supramolecularfunctionalities, X or Y, in the presence of a SPG, Z.
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relative steric crowding of the supramolecular moieties around theinternal olefin either completely prevented or severely limited theuse of these CTAs in the ROMP of cyclooctene. Therefore, two newCTAs were prepared with a larger carbon spacer between the UPyand Napy groups (Fig. 4).
The synthetic routes to CTAs with a C20 spacer are depicted inScheme 1, which is published as supporting information on thePNAS web site. The C20 CTAs were prepared in four or fivehigh-yielding steps from either undecyl-bromide or undecenoic-acid, and both routes employed homodimerization through olefincross-metathesis. Because any monofunctional UPy or Napy CTAwould be detrimental in the preparation of �,�-telechelic polymers,removal of any nondimerized material was done carefully bysuccessive recrystallization or column chromatography. Further-more, bisUPy CTA (6) was purified by multiple precipitations fromMeOH, and bisNapy CTA (7) was purified by column chromatog-raphy. Both 6 and 7 were analyzed for purity by MS, FTIR, and 1Hand 13C NMR.
With CTAs 6 and 7 and SPG 18 in hand, ROMP of cyclooctenewas 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 commercialinterest and can be subsequently hydrogenated to linear polyeth-ylene. All polymerizations were performed in dry 1,2-dichloroeth-ane (DCE) for 48 h at 55°C under an argon atmosphere. Typically,monomer:catalyst ratios of 5,000–7,000:1 were used with concen-trations varying from 1.5 to 3 M, allowing for endgroup function-ality to be �99.98%. To investigate the influence of the SPG, anumber of polymerizations were performed with the CTAs undervarying conditions and led to an optimal ratio of 2.4 equivalents of18 relative to CTA. Furthermore, ROMP of cyclooctene in thepresence of trans-3-hexene as a CTA was carried out at varyingmonomer:CTA ratios to obtain reference polymers without anyinteracting chain ends.
Deprotection of the Supramolecular Macromonomers. After solvingthe problems of catalyst coordination and high viscosity during thepolymerization with a SPG, a method affording complete depro-tection was sought. Luckily, the design of the SPG enabled facileand complete deprotection by precipitation of THF solutions of thecrude polymerization mixtures into methanol. The UPy SPG wasdesigned to be highly soluble both in apolar as well as polar organicsolvents. The branched ethyl-pentyl tail on the pyrimidinone ringserved to greatly increase solubility of UPy dimers in chloroform,toluene, and DCE, as well as to induce solubility of UPy–Napyheterodimers. This process proved necessary as Napy CTA 7 wassparingly soluble in DCE, the solvent of choice for subsequentROMP polymerizations in this study. Additionally, incorporation ofthe 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 theself-assembly of a highly soluble monofunctional UPy, completedeprotection occurred by first disrupting the quadruple H-bondingarrays (dissolving the polymerization mixtures in THF) followed by
selective solvation of 18 in MeOH and simultaneous precipitationof the telechelic ROMP polymers. The precipitated polymer mix-tures in MeOH were subjected to centrifugation, isolated, redis-solved in THF, and reprecipitated from MeOH. This cycle wascarried out three times in total to ensure complete removal of anymonofunctional UPy SPG.
Characterization of Telechelic Supramolecular Macromonomers. Af-ter complete removal of SPG 18, both telechelic UPy (19) andtelechelic Napy (20) ROMP polymers were characterized byseveral methods outlined below. For both UPy and Napy poly-mers, 1H NMR was used to calculate the number of monomerrepeat units between the supramolecular end groups and thus Mnvalues of 4,418 g�mol (19) and 3,963 g�mol (20), respectively. 1HNMR was also helpful in confirming SPG removal (see Fig. 8a,which is published as supporting information on the PNAS website). The bottom spectrum illustrates the H-bonding region ofthe 1H NMR spectrum for polymer 20; after the first precipi-tation of the polymer from MeOH, peaks arising from theUPy–Napy heterodimer are clearly visible. Although the major-ity of the SPG was removed by precipitation, a small amountremained attached to the ROMP polymer. After several pre-cipitation cycles described above, the monofunctional UPy SPGwas completely removed from the polymer, and H-bondingpeaks were absent in the NMR spectrum (top spectrum, Fig 8a).
MALDI-TOF MS also proved to be helpful in characterizationof the telechelic ROMP polymers; a representative spectrum can beseen in Fig. 8b for a polymer with Napy endgroups. One set ofpolymer peaks can be observed with a mass difference of 110.1atomic mass units (amu); the Inset clearly shows that the H�, Na�,and K� adducts each fly quite readily, and the masses can beascribed to a polymer chain with a precise number of cycloocteneunits inserted into the original CTA. The m�z peak at 1,429.1 arisesfrom exactly 5 cyclooctene monomers, the original mass of the CTA7 (877.2 g�mol) plus 1 proton. Moreover, SPG 18 and CTA 7 werenot observed in the MALDI spectrum.
In addition to MALDI-TOF MS and 1H NMR, both FTIR andUV�vis spectrometry provided relevant information about thedeprotection of UPy SPG from telechelic Napy polymer 20. Whenall of the SPG was removed, the FTIR spectrum revealed apronounced NH absorption at 3,311 cm�1, indicating that the NHgroups of the Napy moieties were not H-bonded to any UPy SPG.Before complete deprotection, a broader peak �3,300 cm�1 wasobserved. A UV�vis spectrum of free Napy shows an absorptionstarting at 300 and ending sharply at 350 nm, with a maximum at346 nm and several vibronic subpeaks at lower wavelengths. UponUPy heterocomplexation, however, a new shoulder appeared at 355nm for the Napy chromophore (30). After three precipitations fromMeOH, the UV�vis of the telechelic bisNapy polymer did notdisplay the characteristic UPy-Napy shoulder at 355 nm, alsoindicating complete removal of the UPy SPG.
Because the UPy telechelic polymers were capable of formingelongated supramolecular polymers through self-assembly of theself-complementary H-bonding motifs, they could be further char-acterized with respect to their purity by Ubbelhode viscometry inchloroform. Until now, only small-molecule bisUPy materials havedisplayed a high dependence of specific viscosity on concentrationabove the overlap concentration (the specific viscosity increaseswith c3.5–3.7) as predicted by Cates (31) (entry 3, Table 1). Previ-ously, telechelic UPy polymers prepared by postpolymerizationmodification routes, such as UPy2 (polydimethylsiloxane) (entry 4,Table 1; see ref. 32), have yielded exponents of �3. This result islikely due to the presence of monofunctional polymer chains thatact as chain stoppers and severely limit the virtual DP and thusspecific viscosity of the polymer solutions. After purification of UPytelechelic ROMP polymer 19 by removal of any UPy SPG, viscositymeasurements revealed a specific viscosity vs. concentration de-pendence of 3.72 on a double-logarithmic plot (entry 1, Table 1). To
Fig. 4. BisUPy and bisNapy CTAs with 20-carbon linkers.
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conclusively show that the reduced slopes of previous systems arisefrom the presence of chain stoppers, and hence incomplete func-tionalization of polymer chains, the Ubbelohde viscometry exper-iment was repeated with a chloroform solution in which 2 mol %of monofunctional UPy SPG 18 was intentionally added to the pureUPy telechelic ROMP polymer. Entry 2 in Table 1 clearly showsthat the slope (over the same concentration range) had decreasedto 2.62. A polyoctenamer with the same molecular weight as 19 wasprepared with �CH3 endgroups as a control, with a slope of 1.32(entry 5, Table 1).
Preparation and Characterization of Supramolecular Block Copoly-mers. Finally, once both UPy and Napy telechelic polymers (mac-romonomers) were individually prepared and well characterized,preparation of AA plus BB supramolecular block copolymers wasattempted. Again, Ubbelohde viscometry was used to illustratesupramolecular block copolymer formation in solution. As men-tioned earlier, a major advantage of using the dual binding capa-bility of UPy with Napy is that it enables the preparation ofhigh-molecular-weight polymeric materials over a wide range ofUPy:Napy ratios (13). To this end, we prepared a chloroformsolution containing a Napy telechelic ROMP polymer 20 with UPyCTA 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 bettercharacterization of the same viscometry solution by both 1H NMRas well as UV�vis spectroscopy. A double-logarithmic plot of thespecific viscosity vs. concentration for the AA plus BB system yieldsa slope of 3.5 (see Fig. 9a, which is published as supportinginformation on the PNAS web site). A series of UV�vis spectraillustrate a titration of UPy CTA 6 into Napy telechelic ROMPpolymer 20 in CHCl3 ranging from 0 to 15 equivalents (Fig. 9b).When Napy endgroups undergo heterodimerization with the UPymoieties, a shoulder at 355 nm is visible in the UV�vis spectrum(see above) (30). In such a solution, the shorter C20 bisUPy CTAmonomers undergo self-assembly to form a supramolecular poly-mer, and the Napy telechelic ROMP polymers are incorporatedinto the polymer chains by forming complementary H-bondinginteractions with a fraction of the UPy groups. The result is asupramolecular AA�BB block copolymer with C20 units and largepolyoctenamer units in the same chain! This result is clearly thecase, as the UV�vis spectrum of the CHCl3 solution used forsolution viscometry (Fig. 9b, red curve) indicates that all Napygroups are bound by a UPy.
We also wanted to see whether the high association constantbetween the UPy and Napy motifs would allow the formation ofblock copolymers in bulk with stable microphase separation. Thisinvestigation ultimately would lead to the controlled formation ofmany block copolymer morphologies by the supramolecular assem-bly of the component blocks. Atomic force microscopy (AFM) wasuseful in characterizing the film morphologies arising from theself-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) (Mn �4,100 g�mol; see ref. 14) were studied by tapping-mode AFM. AbisUPy-PEB was used with bisNapy polyoctenamer 20 to providecontrast in the AFM images. Block copolymer films were preparedby solution-blending of the individual components in toluenefollowed by drop-casting onto glass slides.
In contrast to a film of pure 20 (Fig. 5b), mixtures of 20 withbisUPy-PEB 21 yielded (clear) macroscopically homogeneousfilms, which also showed microphase-separated domains uponinspection with AFM. To determine the distribution and size of themicrodomains, additional information was obtained by varying theratio of 20 to 21 in the films (30�70 and 70�30 mol %).† The phaseimage (Fig. 5a) shows microphase separation demonstrating theformation of domains consisting of two chemically different blocks.The topographic (height) images (see Fig. 10, which is published assupporting information on the PNAS web site) show flat andhomogeneous films (rms roughness of �1 and �3 nm, respectively).The pronounced phase contrast indicates that chemical inhomo-geneities have developed through self-assembly bringing aboutmicrophase separation. It is noteworthy that when bisNapy telech-elic polymer 20 was used in excess (see Supporting Text), thesupramolecular polymer chains were on average triblocks.
Through varying the molar ratio of Napy:UPy telechelic poly-mers, the phase images allowed for assignment of the light featuresto the bisNapy telechelic polyoctenamer (hard) block. Thepolyoctenamer block also displayed a feature size of 15 nm and wasextremely regular in appearance regardless of whether it was themajority or minority component block. Moreover, these harddomains existed in the films rather than laying on top of the filmsas indicated by the smooth height images. In contrast to themixtures where both polymeric blocks contained supramolecularend groups, reference experiments carried out with bisNapy telech-elic ROMP polymer 20 and PEB (22) (33) without UPy groups didnot give rise to microphase-separated structures. Rather, thesemixtures produced turbid films and macrophase-separated domainsas can be clearly seen in the AFM images yielding the large z-rangesand rms values for the films (Fig. 5b and Supporting Text).
Differential scanning calorimetry (DSC) also was carried out on20, 21, and mixtures correlating to the supramolecular copolymerfilms were imaged with AFM. When bisUPy-PEB 21 was added tobisNapy polyoctenamer 20, the melting peak arising from thesemicrystalline polyoctenamer block shifted to lower temperaturesaccordingly (Table 2, entries 1–3). Moreover, the amount ofcrystallinity in the block copolymers decreased with increasingweight percentage of the amorphous PEB blocks. These data are all
†Because the molecular weights of the two telechelic polymers are virtually the same, thepercent mole ratios also express the volume fractions.
Table 1. Slopes from double-logarithmic plots of specificviscosity (�sp) vs. concentration from Ubbelohde viscometry (inCHCl3) of several telechelic supramolecular polymers
Fig. 5. Tapping-mode AFM images of Napy telechelic polyoctenamer 20 andbisUPy–PEB 21. (a) Phase image of a 70�30 mol % 20:21 film. (b) Height imageof a Napy telechelic polyoctenamer 20 film.
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consistent with the AFM images, indicating that a supramolecularblock copolymer is indeed formed. However, when DSC wascarried out on a mixture of bisNapy polyoctenamer 20 with anexcess of PEB 22 that did not bear any UPy groups at the chain ends(Table 2, entry 5), the crystallinity due to the polyoctenameractually increased. This result can be rationalized by the mac-rophase separation of the blend (see Fig. 10 and also Fig. 11, whichis published as supporting information on the PNAS web site). Themuch smaller weight fraction of 20 in a matrix of amorphous PEB22 undergoes macrophase separation in the melt resulting inconfinement and a more compact and ordered crystalline domainupon cooling.
ConclusionsA retrosynthetic approach was outlined to obtain supramolecu-lar block copolymers. Successful preparation of both UPy andNapy containing telechelic polymers with an endgroup function-ality of precisely two was achieved by ROMP in the presence ofa bifunctional CTA. CTAs with a C20 linker could be synthesizedon large scale in excellent purity through homodimerization bymeans of olefin cross-metathesis. Problems arising from UPy selfcomplementarity and Napy–ruthenium catalyst coordinationwere overcome by introduction of a UPy protection group, whichcould easily be removed from the crude reaction mixture bymultiple precipitations of the polymer from methanol.‡
Purity of the ROMP polymers (macromonomers) bearing su-pramolecular endgroups was vital for subsequent self-assembly andwas substantiated by using 1H NMR, MALDI-TOF MS, FTIR, andUV�vis spectroscopy. Self-assembly of the UPy and Napy telechelicpolymers into supramolecular block copolymers was demonstratedin solution by a variety of techniques including Ubbelohde viscom-etry and UV�vis spectroscopy. Initial studies on the solid-statestructures of these copolymers by tapping-mode AFM indicate thatmicrophase-separated morphologies are adopted.
Additionally, the dual binding capabilities of UPy can be ex-ploited to prepare block copolymers with a wide range of compo-sitions. Contrary to most supramolecular polymers bearing com-plementary binding motifs whose DP and material properties areheavily dependent upon a stoichiometry of exactly 1:1 (Fig. 6a), asupramolecular copolymer formed from telechelic bisUPy andbisNapy polymers retains a high DP over a wide range of UPy�Napyratios (Fig. 6b). This characteristic allows for both practical andsynthetically diverse preparations of supramolecular block copoly-mers. More importantly, access to the entire composition range ofblock copolymers can be achieved through tuning the molecularweight of the majority component that exists between the two UPymoieties. Fig. 6c illustrates how the polymeric block between theNapy groups is fixed (in red), whereas the polymeric block lengthand weight fraction in blue (coming from the bisUPy telechelicmaterials) is tunable and depends on the ratio of UPy to Napy.
We believe that the outlined retrosynthetic strategy in combina-tion with the supramolecular protection methodology will allow forthe versatile design and preparation of complex, multicomponentsystems by means of supramolecular multistep synthesis.
Materials and MethodsGeneral Methods. All synthetic procedures were performed underinert atmosphere of dry argon unless stated otherwise. Commercialsolvents and reagents were used without purification unless statedotherwise. 1,4-Dioxane was distilled over LiAlH4, and chloroformand pyridine were dried over 4-Å molecular sieves before use. Extradry DCE (water � 50 ppm) for the polymerization reactions wasobtained from Acros Organics and used as received. Deuteratedchloroform was dried and deacidified over activated alumina (typeI) and stored on 4-Å molsieves. 1H and 13C NMR spectra wererecorded on a Gemini 300, Mercury 400, or Inova 500 spectrometer(all from Varian). Chemical shifts are reported in ppm relative totetramethylsilane and multiplicities as singlet (s), doublet (d), triplet(t), quartet (q), and multiplet (m). MALDI-TOF results wereobtained by using a PerSeptive Biosystems Voyager-DE PROspectrometer with an �-cyanohydroxycinnamic acid or a neutral2-[(2E)-3-(4- tert-butylphenyl)-2-methylprop-2-enylidene] malono-nitrile matrix. IR spectra were recorded on a PerkinElmer Spec-trum One FTIR spectrometer with a Universal ATR samplingaccessory. Elemental analysis was performed on a PerkinElmer2400 series II CHNS�O analyzer. Melting points were determinedon a Buchi Melting Point B-540 apparatus. Analytical gel-permeation chromatography was carried out in THF on two PL Gelsingle pore size (100 Å) 30-cm columns, with a particle size of 3 �m(Polymer Labs) connected in series with a SPD-M10Avp photo-diode array UV�vis detector (Shimadzu) measuring between 190and 370 nm. Reported molecular weights were obtained againstpolystyrene standards.
Viscosity Measurements. Solution viscosities were measured byusing Schott-Gerate Ubbelohde microviscometers with suspendedlevel bulb in automated setups with Schott-Gerate AVS�S mea-surement tripods and AVS 350 measurement devices. The micro-viscometers were thermostated in a water bath at 25.00 (�0.01)°C.Samples were filtered over 1-�m polytetrafluoroethylene filtersbefore measurement. Specific viscosities were corrected by usingthe appropriate Hagenbach correction factors.
‡It should be mentioned that the UPy protecting group displays a delicate balance betweenease of removal (i.e., polarity of the derivative) and affinity for self-association in combi-nation with association to Napy derivatives. UPy derivatives bearing ethylene glycolsubstituents longer than three repeat units display a lower Kdim value and are able tocoordinate to a transition metal.
Table 2. DSC data for supramolecular block copolymers
*Values in parentheses are ratios of the polymers (wt/wt).
Fig. 6. Theoretical graphs and molecular picture of DP vs. AA�BB monomerratios. (a) Virtual DP of a supramolecular copolymer vs. the ratio of thecomponent A and B blocks when A and B are only complementary. (b) VirtualDP of a supramolecular copolymer vs. the ratio of the component A and Bblocks when A is both self-complementary and complementary to B. (c) Tuninga supramolecular block copolymer by the UPy to Napy ratio.
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AFM Measurements. AFM images were recorded under ambientconditions by using a Digital Instruments Multimode NanoscopeIV operating in the tapping-mode regime by using microfabricatedsilicon cantilever tips (PPP-NCH, 300–330 kHz, 42 N�m, tip radius10 nm); scanner 5962EV was used with scan rates 0.5–1.25 Hz, scanangle 0°; feedback signals were optimized, and Asp�A0 was adjustedto 0.6. Images shown are subjected to a first-order plane-fittingprocedure to compensate for sample tilt. The phase images wererecorded simultaneously with the topographic images. The rough-ness data are rms values, which are derived as standard deviationsof all height values in an image. Films were dropcasted onto glassslides from a 5 wt % toluene solution.
Thermal Analysis. DSC measurements were performed on aPerkinElmer Differential Scanning Calorimeter Pyris 1 with PyrisDSC Autosampler and PerkinElmer CCA7 cooling element undera nitrogen atmosphere. Thermal parameters were determined fromthe second heating curve (10°C�min).
Synthesis. UPy-imidazolide (8) was prepared as reported by Keizeret al. (34), 7-(2-ethyl-hexanoylamino)-2-chloro-1,8-naphthyridine(12) was synthesized as reported by Ligthart et al. (35); trans- andcis-1,4-diamino-2-butene�2HCl were prepared similar to a literatureprocedure (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 dried50-ml RB flask was charged with CTA 6 or 7 (0.29 mmol) and UPySPG 18 (0.65 mmol; see Scheme 2, which is published as supportinginformation on the PNAS web site). Dry DCE (0.7 ml) was addedunder argon together with a stirbar. After obtaining a clear solution,cyclooctene (0.37 ml) was added. Subsequently, a solution ofsecond-generation Grubbs ruthenium catalyst (1.0 mg, 1.18 �mol)in DCE (0.5 ml) was injected. The reaction mixture immediatelyturned highly viscous and was stirred at 55°C for 48 h. The solutionwas cooled to room temperature, and 1.0 ml of chloroform wasadded. The viscous solution was added dropwise into 100 ml ofmethanol with added BHT to prevent cross-linking. The white
precipitate was isolated by centrifugation. The white solid wasdissolved in THF, and the precipitation process was repeated twiceto afford the supramolecular polymers as white powders, whichwere free of the UPy protecting group.2{2-[2-(2-Methoxyethoxy)ethoxy]ethyl}ureido-6-(3-heptyl)-4[1H] pyrimidi-none (18): To a solution of ethylpentyl isocytosine (5.16 g, 24.7mmol) 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 stirredfor 4 h at room temperature under inert atmosphere. To the mixture30 ml of CHCl3 was added, washed with water (3 � 10 ml), driedover MgSO4, and evaporated to give the crude imidazolide, whichwas used immediately for the next step. The UPy–imidazolide wasdissolved in 20 ml of chloroform, followed by the addition of2-(2-(2-methoxyethoxy)ethoxy)ethylamine 23 (3.72 g, 22.8 mmol)and stirred overnight (16 h) at 50°C under inert atmosphere. Thesolution 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 evaporatedto yield the title compound as a pale-yellowish oil (8.0 g, 90%). 1HNMR (CDCl3): � � 13.11 (broad, 1H, N H), 11.92 (broad, 1H, NH), 10.24 (broad, 1H, N H), 5.74 (s, 1H, C HCO), 3.61 (m, 6H, CH2O), 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; 13CNMR (CDCl3): � � 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):� � 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 othercompounds presented in the work are available in Supporting Text.
We thank Eveline van der Aa for help in synthesis and purification ofseveral compounds; Dr. Pascal Jonkheijm for AFM measurements; andHenk Keizer (Suprapolix BV, Eindhaven, The Netherlands) and HolgerKautz (Degussa AG, Hanau, Germany) for samples 21 and 22, respec-tively. This work was supported by National Science Foundation MPS-DRF Award CHE-0401407 and by the Nederlandse Organisatie voorWetenschapelijk Onderzoek.
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