Dynamic Sub-10-nm Nanostructured Ultrathin Films of Sugar

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Dynamic Sub-10 nm Nanostructured Ultrathin Films of SugarPolyolefin Conjugates Thermoresponsive at Physiological Temperatures Samantha R Nowak, Wonseok Hwang, and Lawrence R. Sita J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.6b13285 • Publication Date (Web): 03 Apr 2017 Downloaded from http://pubs.acs.org on April 4, 2017

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Dynamic Sub-10 nm Nanostructured Ultrathin Films of Sugar-Polyolefin Conjugates Thermoresponsive at Physiological Temperature s Samantha R. Nowak, Wonseok Hwang and Lawrence R. Sita* Laboratory of Applied Catalyst Science and Technology, Department of Chemistry and Biochemistry University of Maryland, College Park, Maryland 20742 Email: [email protected] Spin-casting of a cellobiose-atactic polypropene (CB-aPP) conjugate (1) from a 0.1% (w/w) n-butanol : hexane solution onto highly-oriented pyrolytic graphite (HOPG) and carbon-coated Si(100) spontaneously produced microphase-separated sub-10 nm nanostructured ultrathin films in the form of alternating CB and aPP lamellar domains (d = 6.60 ± 0.68 nm) that are oriented perpendicular to the substrate surface. Thermal annealing at modest temperatures (e.g., 50 – 100 °C), and as low as the physiologically-relevant temperature of 38 °C, serves to drive a structural transition that yields a parallel stacked bilayer assembly as the thermodynamically-favored nanostructure. These results establish the advantage of low molecular weight, narrow polydispersity and amorphous, low Tg, poly(α-olefinate)s (xPAOs) as a new class of hydrophobic building block for amphiphilic materials, and sugar-PAO conjugates in particular, for the development of stimuli-responsive, nanostructured materials for technological applications at physiological temperatures. ABSTRACT:

Investigations of stimuli-responsive (also known as ‘smart’) materials that undergo structural reorganization in response to changes in environmental conditions (e.g., temperature, light, humidity and pH) are of intense academic interest due to the wealth of new science and technologies that can emerge.1-3 However, the development of thermoresponsive nanostructured ultrathin films4 of a smart material that can be triggered to undergo a well-defined structural transition in the solid state on practical time scales (e.g. minutes, hours or days) and at physiologically-relevant temperatures (e.g., 36 – 39 °C) for potential use in biomedical or bioengineering applications has never before been achieved.5 This challenge becomes even more daunting if one sets the additional bar of establishing and maintaining sub-10 nm domain periodicity for each of the two ordered nanostructures of the smart ultrathin film. More to the point, according to the current best strategy for achieving sub-10 nm dimensions,6 a very low overall chain length, N, of a self-assembling amphiphile must work in synergy with a very large Flory-Huggins interaction parameter, χ, between immiscible domains since the spacing parameter, d, of the resulting nanostructure scales according to: d ≈ N2/3χ1/6. Thus, in the limit of small values of N, and in particular, those that fall below the minimum chain entanglement length, a fine balance between the enthalpic and entropic contributions to the free energy of the system must continually be struck as a function of temperature in order to avoid the emergence of a far simpler, and much less interesting, thermoresponsive behavior that originates with an order-to-disorder phase transition. Herein, we now present, to the best of our knowledge, the first candidate for a smart material that meets all of the above criteria. Further experimental and theoretical interrogations of this model system should now prove instrumental in the elucidation of a set of guiding principles that can be used for future de novo designs of other thermoresponsive sub-10 nm nanostructured smart materials that are optimized for functional applications at physiological temperatures.

Figure 1. (Top) structure of cellobiose-atactic polypropene (CB-aPP) conjugate (1). a) ps-tm AFM phase map of ‘as-cast’ ultrathin film (h = 30 nm) of 1 on a HOPG substrate. b) SAXS data for a bulk sample of 1 (unannealed). c) GISAXS data for an as-cast ultrathin film of 1 on HOPG. d) GISAXS data for same ultrathin film of 1 in c) after thermal annealing in vacuo at 100 °C for 3 h.

We have recently reported that sugar-polyolefin conjugates in which a saccharide-based polar ‘head’ group is attached to an end-group-functionalized poly(α-olefinate) (xPAO) hydrophobic ‘tail’ represent a new category of self-assembling amphiphile that, based on the occupied free volume of the polar domain, lies in size between those of small molecular surfactants and ‘giant’ surfactants (GSs) - and much smaller than that of amphiphilic block copolymers (BCPs).6-9 Further, by selecting different αolefin monomers (e.g. propene vs. 4-methyl-1-pentene) and different number-average degrees of polymerization, DPn, a variety of xPAOs of very narrow molecular weight distribution (polydispersity) [i.e., Đ (Mw/Mn) ≤ 1.15] and tunable occupied free volume for the polyolefin domain in the sugar-polyolefin conjugate, can be designed and easily synthesized on the kilogram scale through the process of living coordinative chain transfer polymerization (LCCTP).10-12 Finally, these xPAOs possess an atactic

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Figure 2. Time-dependent series of ps-tm AFM phase map images recorded at 25 °C of an ultrathin film (h = 30 nm) of 1 on HOPG that was thermally annealed (in vacuo) at 60 °C for different lengths of time. a) as-cast ultrathin film of 1, b) same film annealed for a total of 14 h, c) zoomed-in region within white square of b), d) same film annealed for a total of 24 h, e) zoomed-in region within white square of d), f) same film annealed for a total of 48 h.

stereochemical microstructure for the polyolefin backbone, and this structural feature, along with a low DPn value, contribute to an amorphous polyolefin domain that is associated with a low, sub-ambient glass transition temperature, Tg (vide infra). In a preliminary test of the self-assembling capabilities of sugar-polyolefin conjugates, a monosaccharide β-D-galactose (G) head group, with a calculated occupied free volume, V, of 472 Å3, was coupled to an atactic polypropene (aPP) tail (DPn = 20, Đ = 1.15) which is characterized by a single low Tg of -20 °C.8 Gratifyingly, this G-aPP conjugate was found to adopt a cylindrical morphology with d = 6.40 ± 0.19 nm for a nanostructured ultrathin film supported on the native SiO2 layer of Si(100). However, subsequent thermal annealing of these ultrathin films of GaPP at 60 °C for extended periods of time only resulted in the appearance of longer-range order for the cylindrical domains, and not the emergence of an alternative nanostructure, as assessed by phase-sensitive, tapping mode atomic force microscopy (ps-tm AFM).13 In the present work, a more refined design for a sugarpolyolefin conjugate that could manifest a richer phase diagram that is required for development of a smart material was pursued. Thus, as Figure 1 depicts, this new design incorporates a disaccharide cellobiose (CB) head group (V = 985 Å3) that is coupled to an aPP tail (DPn = 31, Đ = 1.09) through a triazole linkage formed through the ‘click’ chemistry used to synthesize CB-aPP (1) in high yield (see Supporting Information).14 Selection of the CB domain for 1 was guided by the desire to increase further, visà-vis G-aPP, the magnitude of χ while keeping N very low in order to achieve a sub-10 nm nanostructure. It was further anticipated that the disaccharide CB domain would also now make a larger contribution to the establishment of more complex temperature- dependent phase behavior. Indeed, as revealed by a differential scanning calorimetry (DSC) analysis of 1, a second Tg now appeared at 60 ° C for the CB domain in addition to the low Tg of

-20 °C associated with the aPP domain. Thus, as hoped for, 1 now exhibits bulk properties that are more in keeping with those expected of a microphase-segregated BCP.6 Ultrathin films of 1 with a film height, h, of < 50 nm were obtained on highly-oriented pyrolytic graphite (HOPG) substrates through spin-casting at 2000 rpm of a 0.1% (w/w) solution of this sugar-polyolefin conjugate in a 1:1 n-butanol : hexane mixture.14 Figure 1a presents a ps-tm AFM phase-map image for one of these ‘as-cast’ ultrathin films of 1 in which a ‘classic’ fingerprint nanostructured morphology with a d value of 6.60 ± 0.68 nm is observed. Small angle x-ray scattering (SAXS) of a thermally unannealed bulk sample of 1 (see Figure 1b), along with grazing incident SAXS (GISAXS) for an ultrathin film of 1 supported on a carbon-coated Si(100) (c-Si) substrate prepared under identical conditions (see Figure 1c), served to confirm a nanostructure morphology that consists of alternating CB and aPP lamellar domains that are oriented perpendicular to the HOPG surface.15 Quite surprisingly, however, after thermal annealing (in vacuo) at 100 °C for 3 h, GISAXS data for these ultrathin films of 1 on c-Si revealed that a distinct structural change had occurred to produce a new nanostructured morphology that can best be accounted for by assuming that the CB and aPP lamellar domains are now orientated parallel to the supporting substrate (see Figure 1d).16 Additional thermal annealing studies confirmed that a similar structural change could be achieved at lower temperatures after longer periods of time (e.g., 50 °C, 48 h).14 Finally, in contrast to G-aPP, use of the native SiO2 layer of Si(100) as a hydrophilic surface did not provide well-ordered nanostructured ultrathin films of 1. Figure 2 presents a time-dependent series of ps-tm AFM phase map images recorded at room temperature for a single ultrathin film of 1 on HOPG that was thermally annealed at 60 °C for different lengths of time. Thus, to begin, these data show that a pronounced change in the perpendicular lamellar morphology of the as-cast ultrathin film of 1 occurred even after the relatively short

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period of time of 14 h (cf. Figures 2a and 2b). More to the point, Figure 2c presents a zoomed-in region of the ps-tm AFM phase map for the 14 h time point in which it can be clearly seen that the initial perpendicular lamellar morphology has been replaced by one in which the CB and aPP are heterogeneously mixed with no apparent short- or long-range order for these domains. However, this new ultrathin film of Figure 2b now displays the emergence of a nascent underlying stacked layered assembly. Indeed, after an additional period of annealing of this ultrathin film of 1 at 60 °C for a total of 24 h, this new parallel multi-layer stacked structure is even more well-defined with a repeating stack step height of 6.29 ± 0.11 nm, as determined from a cross section profile of the corresponding height map (see SI) of the ps-tm AFM phase map shown in Figure 2d. Curiously, the zoomed-in region of this stacked layer structure that is presented in Figure 2e also shows what appears to be either spherical or perpendicularly-oriented cylindrical CB domains that are uniformly 1 nm in diameter and evenly dispersed as a disordered, but close-packed, assembly within an aPP matrix (cf. the small dark ‘spots’ appearing on the stacked layers). Finally, extended heating at 60 °C for a total of 48 h now yielded a uniform parallel-stacked ultrathin film of 1 that shows no evidence of CB and aPP phase segregation at the air-film surface (see Figure 2f). Additional data obtained from dynamic light scattering (DLS) of the 0.1% (w/w) n-butanol : hexane solution of 1 is supportive of the formation of micelles that are 6 nm in diameter (see SI). While an investigation of the solution assembly of 1 and related conjugates in solution is the topic of a separate study, it is plausible that the pre-association of CB and aPP domains prior to spincasting provides a mechanism for kinetic formation of the initially observed perpendicular lamellar morphology of the as-cast films. Furthermore, data previously obtained from angle-dependent Xray photoelectron spectroscopy (XPS) of stacked layers of a peracetylated derivative of G-aPP provided support for a bilayer structure for each of the layers.8 Accordingly, it is assumed in the present work that the thermodynamically-favored annealed nanostructure for 1 on HOPG (or c-Si) consists of a stacked tail head-head-tail (T-H-H-T) bilayer assembly in which the aPP tail is favored at both the substrate-film and air-film interfaces. GISAXS data obtained with a more powerful light source will be required to elucidate better structural models for the metastable nanostructures that were discovered in Figures 2b and 2d.5d Finally, the question arises as to whether a rich phase diagram for 1 exists for which other nanostructured morphologies can be accessed through simple manipulation of the occupied free volume of the polyolefin domain. To address this question, a second derivative CB-aPP (1’) was made with a slightly longer aPP tail (e.g., DPn = 57, Đ = 1.08). A SAXS analysis of a bulk sample of 1’, annealed at 80 °C for 10 h, now revealed the presence of a cylindrical morphology and GISAXS analysis of an annealed ultrathin film of 1’ also displayed a more complex phase morphology (see SI). Efforts are now underway to systematically investigate the phase map with a larger family of CB-aPP derivatives. Due to the large change in surface properties that is expected for the nanostructural phase transition documented in Figures 1 and 2, it became a primary interest to determine if these ultrathin films of 1 would also be thermoresponsive in identical fashion at physiologically-relevant temperatures for potential use in biomedical nanodevice applications. Gratifyingly, as the data in Figure 3 document, this objective could indeed be achieved through simple thermal annealing (in vacuo) of an initial as-cast ultrathin film of 1 at 38 °C for a total of 72 h to reach the final stacked bilayer nanostructure.14 As a final consideration, in recent years, there has been considerable interest in the design of new amphiphilic materials, and in

Figure 3.ps-tm AFM phase map images recorded at room temperature of a) an as-cast ultrathin film of 1 on HOPG and b) same ultrathin film of a) that was thermally annealed in vacuo at 38 °C for 72 h.

particular, BCPs and GSs, that can provide access to sub-10 nm feature sizes for ultrathin films for use in nanodevice fabrication and applications.6,7 As previously mentioned, a very low overall chain-length, N, coupled with an exceptionally high value of χ is an essential prerequisite for the design of new BCP and GS precursors to sub-10 nm microphase-separated nanostructures. In prior studies with BCPs and GSs conducted by others, establishing high values of χ for such low molecular weights has almost invariably involved choosing a hydrophobic polymer that is either amorphous with a high Tg, (e.g., polystyrene), or that is highly crystalline with a high melting temperature, Tm, even if it possesses a low Tg (e.g., polyethylene). As a result, temperatures above 100 °C have been required to thermally anneal BCP and GS based ultrathin films to reach the final thermodynamically-favored nanostructured morphology.5c,5d,6,7 To the best of our knowledge, however, the solid-state dynamic behavior of a sub-10 nm nanostructured ultrathin film of an amphiphilic BCP or GS that undergoes an order-to-order structural transition at low temperature has yet to be documented. In conclusion, the present results provide further support for the targeted use of xPAOs as a new class of hydrophobic building block and they serve to establish sugar-polyolefin conjugates as a new platform that can be used for the design and development of stimuli-responsive, nanostructured smart materials for applications at physiological temperatures. Acknowledgment. This work was supported, in part, by the National Science Foundation (CHE-1152294) and for the purchase of a SAXS/WAXS instrument (DMR-1228957). Supporting Information Available. Experimental details. This material is available free of charge via the Internet at http://pubs.acs.org.

References 1. For a review of stimuli-responsive polymers in solution, see: Ma, X.; Tian, H. Acc. Chem. Res. 2014, 47, 1971. 2. For reviews of stimuli-responsive polymers in the solid state, see: a) Cao, Z.-Q.; Wang, G.-J. Chem. Rec. 2016, 16, 1398; b) Zhai, L. Chem. Soc. Rev. 2013, 42, 7148. 3. For a review on emerging applications of responsive polymer materials, see: Cohen Stuart, M. A.; Huck, W. T. S.; Genzer, J.; Muller, M.; Ober, C.; Stamm, M.; Sukhorukov, G. B.; Szleifer, I.; Tsukrak, V. V.; Urban, M.; Winnik, F.; Zauscher, S.; Luzinov, I.; Minko, S. Nat. Mater. 2010, 9, 101. 4. Fasolka, M. J.; Mayes, A. M. Annu. Rev. Mater. Res. 2001, 31, 323. 5. a) Zhang, X.; Yager, K. G.; Fredin, N. J.; Wook Ro, H.; Jones, R. L.; Karim, A.; Douglas, J. F. ACS Nano 2010, 7, 3653.; b) Sun, Y.; Henderson, K. J.; Jiang, Z.; Strzalka, J. W.; Wang, J.; Shull, K. R. Macromolecules 2011, 44, 6525.; c) Majewski, P. W.; Yager, K. G. Soft Matter 2016, 12, 281. d) Majewski, P. W.; Yager, K. G. J. Phys. Condens. Matter 2016, 28, 403002. 6. For reviews of high χ, low N, block copolymers, see: a) Hawker, C. J.; Russell, T. P. MRS Bull. 2005, 30, 952. b) Sinturel, C.; Bates, F.

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S.; Hillmyer, M. A. ACS Macro Lett. 2015, 4, 1044. c) Durand, W. J.; Blachut, G.; Maher, M. J.; Sirard, S.; Tein, S.; Carlson, M. C.; Asano, Y.; Zhou, S. X.; Lane, A. P.; Bates, C. M.; Ellison, C. J.; Willson, C. G. J. Polym. Sci., A Polym. Chem. 2015, 53, 344. 7. For a recent review of giant surfactants (GS), see: Yu, X.; Yue, K.; Hsieh, I.-F.; Li, Y.; Dong, X.-H.; Liu, C.; Xin, Y.; Wang, H.-F.; Shi, A.-C.; Newkome, G. R.; Ho, R.-M.; Chen, E.-Q.; Zhang, W.-B.; Cheng, S. Z. D. Proc. Natl. Acad. Sci. USA 2013, 110, 10078. 8. Thomas, T. S.; Hwang, W.; Sita, L. R. Angew. Chem. Int. Ed. 2016, 55, 4683. 9. Based on space-filling models, the occupied free volume, V, of the C60 fragment of a recently reported C60-polystyrene GS7 is 5500 Å3. 10. a) Zhang, W.; Sita, L. R. J. Am. Chem. Soc. 2008, 130, 442. b) Zhang, W.; Wei, J.; Sita, L. R. Macromolecules 2008, 41, 7829. c) Wei, J.; Zhang, W.; Sita, L. R. Angew. Chem. Int. Ed. 2010, 49, 1768. d) Wei, J.; Wickham, R.; Sita, L. R. Angew. Chem. Int. Ed. 2010, 49, 9140. e) Wei, J.; Hwang, W.; Zhang, W.; Sita, L. R.; J. Am. Chem. Soc. 2013, 135, 2132.

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11. Sita, L. R. Angew. Chem. Int. Ed. 2009, 48, 2464. 12. For a preliminary description of the application of LCCTP for the synthesis of end-group-functionalized atactic polypropene, see: Wei, J.; Wickham, R.; Sita, L. R. Polym. Prepr. 2010, 51, 370. 13. a) van Dijk, M. A.; van den Berg, R. Macromolecules 1995, 28, 6778. b) Leclere, P.; Lazzaroni, R. Bredas, J. L. Yu, J. M.; Dubois, P.; Jerome, R. Langmuir 1996, 12, 4317. 14. Experimental details are provided in the Supporting Information. 15. a) Glatter, O.; Kratky, O. Small Angle X-Ray Scattering; Academic Press: New York, NY, 1982. b) Lee, B.; Park, I.; Yoon, J.; Park, S.; Kim, J.; Kim, K.; Chang, T.; Ree, M. Macromolecules 2005, 38, 4311. 16. a) Di, Z.; Posselt, D.; Smilgies, D.; Papadakis, C. M. Macromolecules 2010, 43, 418.. b) Yoon, J.; Jun, S.; Ahn, B.; Heo, K.; Jin, S.; Iyoda, T.; Yoshida, H.; Ree, M. J. Phys. Chem. B 2008, 112, 8486.

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