Subscriber access provided by Duquesne University - Gumberg Library

Article

Preparation and Characterization of a Polymer-Based “Molecular Accordion Abdalla H. Karoyo, and Lee D. Wilson Langmuir, Just Accepted Manuscript • Publication Date (Web): 02 Mar 2016 Downloaded from http://pubs.acs.org on March 2, 2016

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a free service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are accessible to all readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

Langmuir is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Preparation and Characterization of a Polymer-Based “Molecular Accordion” Abdalla H. Karoyo and Lee D. Wilson* Department of Chemistry, University of Saskatchewan, 110 Science Place, Saskatoon, SK S7N 5C9, Canada. KEYWORDS: Cyclodextrin; Polymer; Phase Transition; Cross-linked; Responsive ABSTRACT: A urethane-based polymer material, denoted HDI-1, was obtained from the addition reaction of βcyclodextrin (β-CD) with 1,6-hexamethylene diisocyanate (HDI) at the 1:1 mole ratio. In aqueous solution and ambient temperature conditions, HDI-1 adopts a compact (coiled) morphology where the cross-linker units become coiled and are partially self-included in the annular hydroxyl (interstitial) region of β-CD. As the temperature is raised or as pnitrophenol (PNP) was included within the β-CD cavity and the non-inclusion sites of the polymer, an extended (uncoiled) morphology was adopted. The equilibrium distribution between the extended and the compact forms of HDI-1 is thermally and chemically switchable, in accordance with the hydration properties and host-guest chemistry of this responsive polymer system. The molecular structure of this water-soluble urethane polymer and its host-guest complexes with PNP were investigated using spectroscopic (Raman, 1H NMR, induced circular dichroism), dynamic light scattering (DLS) and calorimetric (DSC) methods in aqueous solution at ambient pH, and compared with native β-CD. This study reports on the unique supramolecular properties of a polymer that resemble a thermally and chemically responsive “Molecular Accordion”.

INTRODUCTION The use of polymers, colloids, and supramolecular tectons as porogens in nanocasting strategies yield a wide 1-3 variety of novel imprinted porous materials. By analogy, the development of macromolecular porous materials with tunable morphology, textural parameters, and physicochemical properties is possible by embedding a macrocyclic porogen into a cross-linked polymer framework. Cyclodextrins (CDs) such as α-, β-, and γ-CDs are among the most widely studied macrocyclic host compounds, in part, due to their remarkable ability to form inclusion complexes with a diverse range of organic guest molecules in condensed phases and gaseous 4,5 states. Incorporation of a β-CD within a polymer framework represents a modular design approach with significant potential for the controlled tuning of the molecular recogni6-8 tion properties of functional macromolecular materials. Supramolecular self-assembly that is accompanied by structure and property changes in response to external stimuli is shown by an emerging class of “smart” or “functional” porous materials with improved solid phase extrac4,8,9-14 tion (SPE) and molecular recognition properties. The introduction of temperature sensitive compounds such as polyacrylamides (PAMs) and oligo(ethylene glycol)s (OEGs) into polymers and low molar mass scaffolds has been widely reviewed as the main strategy for preparing thermorespon15-20 sive smart materials. As well, azobenzenes have been widely used as macromolecular prepolymers for photosensitive materials due to their ability to undergo reversible isomerization from a linear and flat E-form to a more compact 21-23 and kinked Z-form upon UV and visible light irradiation. The use of CDs as porogenic components for smart polymer materials is important in various fields ranging from separation and adsorption science to advanced drug delivery sys-

tems. The sorption and host/guest recognition properties of 3,8,12,15 CD-based polymers are influenced by the surface area, pore structure, and the relative accessibility of the binding sites (i.e., inclusion and interstitial) of the polymer framework. Inclusion site accessibility for polymers containing βCD is essential for the formation of well-defined host/guest 24-26 inclusion complexes. CD-based polymers are known to display tunable physicochemical properties that extend the 3,13,27 range of conventional sorbent materials. The sorption properties of β-CD urethane polymers reveal that the adsorbent surface structure may provide multiple binding sites for adsorbates via the inclusion and non-inclusion (interstitial) sites with variable hydrophile-lipophile characteristics. Thus, rational adsorbent design accounts for the inclusion site accessibility of β-CD and the role of the interstitial framework domains via tuning the cross-link density of the polymer by selection of a cross-linker agent with suitable physicochemi12,26,27 cal properties. 28 Ma and Li reported that p-nitrophenol (PNP) 9 -1 forms remarkably stable (Keq ~10 M ) inclusion complexes with urethane polymers. By comparison, inclusion complexes between native β-CD and PNP have lower stability -1 29 (Keq ~197 M ). The binding constant for a CD-based polyurethane with a C8 perfluorocarbon guest was estimated at ca. 3 -1 30 1.0×10 mol.L . The anomalously large binding constant for the polymer/PNP system reported by Ma and Li is attributed to an artefact arising from secondary binding sites (interstitial domains) that were unaccounted for in the original 28 study. The measurement of the unbound equilibrium concentration of PNP does not account for binding sites with different modalities unless appropriate models are employed such as the dual mode adsorption model for CD-based poly31 mers. Silva et al. reported an amphiphile CD with two

ACS Paragon Plus Environment

Langmuir 32

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

33

recognition sites while Mohamed et al. and Ling et al. reported dual binding sites (i.e. inclusion and interstitial domains) in a thermodynamic sorption study of PNP with CDbased polymers. Dual mode adsorption was independently reported for the sorption properties of several types of poly34 mer adsorbents containing β-CD. As well, evidence of multi-modal sorption may be inferred from thermodynamic up35 take parameters for such CD polymers. However, there is a need to carry out further structural and physicochemical studies that characterize the nature of these sorption sites using complementary methods. In this study, we report a water soluble polymer (HDI-1) containing hexamethylene diisocyanate (HDI) and βCD with unique host/guest inclusion properties that are stimuli responsive (temperature and guest concentration). The structural characterization of the urethane-based HDI-1 polymer was carried out at various conditions using spectro1 scopic (Raman, H NMR, and ICD), DLS, and differential scanning calorimetry (DSC) methods. The studies were carried out in aqueous solution at 295 K and variable temperature (VT), in the presence and absence of PNP as a model guest species at pH 6. The results of this study are anticipated to provide a greater understanding of the molecular level details of the sorption process for urethane-based CD polymer and its host-guest chemistry with PNP in aqueous solution. This study will contribute to further development of “smart” SPE sorbent materials with multi-modal binding and 2,3,9,12 tunable molecular recognition properties.

MATERIALS AND METHODS Materials β-CD was purchased from VWR Canada Ltd. 1,6hexamethylene diisocyanate (HDI), dimethyl acetamide (DMA), p-nitrophenol (PNP), methanol, anhydrous ethyl ether, potassium bromide, and 4Å (8–12 mesh) molecular sieves were purchased from Sigma-Aldrich Canada Ltd. Deuterium oxide (D2O) was obtained from Cambridge Isotope Laboratories Inc. All materials were used as received unless specified otherwise. None of the materials in this study required any specialized safety precautions. Synthesis of CD-based polymer The synthesis of a cross-linked polymer containing 31 β-CD was adapted from a previous report, as outlined by the following procedure. DMA was dried with 4Å (8–12 1 mesh) molecular sieves. The H NMR spectrum of DMA was recorded before and after the addition of molecular sieves, and the water content was estimated to be ~0.5%. The 1:1 βCD/diisocyanate HDI polymer material (cf. Scheme 1) was prepared by adding 1 mmol of dried β-CD to a round bottom flask with stirring until dissolved in 10 mL of DMA followed by the addition of 1 mmol HDI in 30 mL of DMA to the reaction mixture. The solution was stirred with heating at 68±2 o C for 24 h under argon and cooled to room temperature after completion. The excess DMA was removed under vacuum (pressure ~1 mbar). The subsequent addition of cold methanol (~0°C) to the gelled product was followed by filtration through Whatman no. 2 filter paper. The crude product was washed with methanol in a Soxhlet extractor for 24 h to remove unreacted reagents and low molecular weight oligomers. The polymer product was dried in a pistol dryer for 24 h, ground into a powder, and passed through a size 40 mesh

Page 2 of 17

sieve to ensure a uniform particle size. A second cycle of washing in the Soxhlet extractor with anhydrous diethyl ether for 24 h was followed by drying, grinding, and sieving, as outlined above. The HDI-1 polymer material was characterized using FT-IR and NMR spectroscopy, thermoanalytical methods, 36 and elemental analyses, as described in detail elsewhere. The HDI-1 acronym and number designation indicates the stoichiometric 1:1 (β-CD:HDI cross-linker) ratio where the relative mole quantity of β-CD is taken to be unity. OCN OH

OH

+

n HO

OH

OH

n O

OH

H N

O

NCO O

O N H

n

Scheme 1. Addition reaction of β-CD and HDI at the 1:1 mole ratio to form HDI-1 polymer. The cross linker is hypothesized to react with the primary annular hydroxyl sites of β-CD. The degree of polymerization is denoted by n. EXPERIMENTAL SECTION Raman Spectroscopy Raman spectra were obtained using a Renishaw system 2000 with an instrumental resolution (λ/2) of 0.257 μm (laser spot size). Raman samples were prepared as evaporated liquid films on a glass microscope slide by evaporation of water at ambient temperature (295 K), followed by analysis of different regions to ensure sample homogeneity and reproducibil37 ity. The utility of this methodology was recently outlined. The argon ion laser excitation wavelength was 514 nm at the -1 following operating conditions: scan range (3500–500 cm ), 10 mW laser power with 100% load, magnification (50×), cosmic ray removal, 30 s detection time, and multiple (15) accumulative scans. 1

H NMR Spectroscopy 1 1 The H NMR experiments (1-D H NMR, COSY, TOCSY, 38,39 ROESY) were performed on a 3-channel Bruker Avance (DRX) spectrometer operating at a proton resonance frequency of 500.13 MHz with a variable temperature (VT) control unit. NMR samples were prepared in D2O at pD ~6 and HDI-1/PNP mole ratios of 1:1, 1:3 and 1:5; defined by theβ-CD 1 mole content of HDI-1 relative to PNP. All H NMR spectra were referenced externally to tetramethylsilane (TMS, δ = 0.0 ppm) with a recycle delay (2 s) and a 90° pulse length (10 μs). For all selective pulse 1-D total correlation spectroscopy 39 (TOCSY) experiments, the spin-lock power level (8.46 dB), spin-lock time (200 ms), number of acquisitions (8), spectral width (12 ppm), and spectral data were collected with 32k data points. For all 2-D rotating-frame Overhauser effect spectroscopy (ROESY) and enhanced gradient selective pulse 39 (1-D gROESY) experiments, the spin-lock times were varied from 100–400 ms. The spectra were acquired with a spectral width of 12 ppm in 2 k data points (2-D gROESY) and 32 k data points (1-D ROESY) with 16 scans. The spin-lock power levels for the 2-D ROESY and 1-D gROESY experiments were set to 21.33 dB. All the NMR spectra were acquired at 295 K except for VT studies (278 to 348 K). Dry nitrogen gas was

ACS Paragon Plus Environment

Page 3 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

used to regulate the temperature of the heating and cooling cycles, respectively. Differential Scanning Calorimetry Differential scanning calorimetry (DSC) of β-CD and HDI-1 in the presence and absence of PNP in aqueous solution were acquired using a TA Q20 thermal analyzer with hermetically sealed pans. The polymer or β-CD samples were prepared as 1% (w/w) aqueous solution in deionized water and scanned over a temperature range of 25 to 70 °C with a fixed scan rate (10 °C/min). Dry nitrogen gas was used to regulate the sample temperature and to purge atmospheric gases from the sample compartment. Induced Circular Dichroism Induced Circular dichroism (ICD) spectra of β-CD and HDI-1 in the presence and absence of PNP were recorded on a PiStar 180 spectrophotometer (Applied Photophysics) at a fixed scan rate (50 nm/min) and a 0.1 nm resolution. The quartz sample cell had a 10.0 mm path length and the 250–400 nm spectral region was analyzed. An average of 30 scans were recorded for ICD spectra and the wavelength calibration was performed with a camphor sulphonic acid solution (0.89 3 -1 -1 mg/mL) in water (Δε = 2.40 dm mol cm at 290.5 nm). Dynamic Light Scattering (DLS) The average hydrodynamic size of HDI-1 in solution and its complexes with PNP were measured using dynamic light scattering (DLS) on a Nano-ZS (Malvern Instrument Inc.) at a scattering angle of 90°. Aqueous solutions of HDI-1 (≤1% w/w) and their complexes with PNP (1:1, 1:2, 1:3, and 1:5 HDI1:PNP with respect to the β-CD content) were prepared and analyzed at pH ~6 and variable temperature (VT) from 298– 348 K (HDI-1 solution). The solution samples were filtered using an Acrodisc PTFE microfilter with a pore size of 0.2 µm to eliminate dust particles from the samples. Each experiment was performed at least 15 times in triplets to obtain statistical information to minimize standard errors. RESULTS AND DISCUSSION Physicochemical Characterization of the HDI-1 Polymer 1 1D H NMR 1 Figure 1 illustrates the H NMR spectra for HDI-1 and the precursors (HDI and β-CD) at pD ~6 in D2O at 295 1 K. The spectral assignment of the H signatures for β-CD 40 were made according to previous reports. An unequivocal 1 H NMR assignment of the hexamethylene (C6) cross-linker unit of HDI-1 was established using a combination of 1-D/2-D 1 TOCSY and H COSY NMR spectra (cf. Fig. S1-S3; SI) according to the assignment in Fig. 2. A comparison of the spectra 1 for HDI-1 and β-CD reveal similar H NMR signatures for the β-CD macrocycle. The resonance lines of the C6 (i.e., -CαH2, CβH2 and CγH2) groups of HDI-1 are broadened and shifted upfield relative to the HDI monomer unit (cf. Fig. 1 b-c, shown by arrows) due to cross-linking. The latter effect is anticipated to influence the hydration characteristics of the HDI-1 polymer as well as the conformational preference of part or the entire linker domain, resulting in the observed chemical shift (δ) and linewidth changes for the α- and βCH2 groups. Published results of HDI-based polymers do not generally show broadened NMR lines for the C6 linker unit, 1 especially for H NMR spectra in organic solvents such as DMSO-d6, where the degree of self-assembly is attenuat-

36,41,42

ed. The observed line broadening in D2O is attributed 37,43 to hydrophobic hydration and self-assembly which are known to affect the conformational preference and phase 44,45 behavior of such aliphatic substituents.

HOD

** Hα

*

* Hβ

(c)

Hγ (b)

H 5H 6

H1

H3

H2

H4 (a)

1

Figure 1. 1-D H NMR spectra (a) β-CD, (b) HDI, and (c) HDI-1. Asterisk (*) denotes residual solvent (DMA and ethyl ether). (OH)n H5

(a)

H3

(OH)n

(b)

(OH)n

α

γ (c)

β Figure 2. Molecular structures for (a,b) β-CD and (c) HDI linker (not drawn to scale). The CD intracavity (H3, H5) and extracavity (H1, H2, H4, H6) nuclei, and the C6 crosslinker unit are labeled. The conformation of the cross-linker unit of HDI-1 is expected to vary relative to the free (unbound) crosslinker. For example, partial self-inclusion of the C6 linker unit within the inclusion site or annular hydroxyl region of CD likely lowers the surface area and the Gibbs free energy of 18 hydration. The apolar environment of the CD cavity differs from bulk solution, as evidenced by upfield shifts of the C6 chain of HDI-1 in D2O. 1 A series of VT H NMR experiments were performed between 278 K and 348 K to further understand the nature of the broadening of the C6 signatures of HDI-1 (cf. Fig. 1). The NMR results for the VT studies are shown in Figure 3a-b. The chemical shift variation with temperature provides insight about the conformation of the linker units in solution due to 1 hydration effects and self-assembly. The H NMR signatures for β-CD and the C6 cross-linker display continuous downfield shifts as the temperature increases (cf. Fig. 3a). Moreover, the C6 resonances of HDI-1 show an observable line sharpening with increasing temperature. The chemical shift and line width varies during the heating cycle in Figure 3a for the polymer is thermally reversible upon cooling of the system, as shown in Fig. 3b. The resonance lines of the C6 linker unit of HDI-1 in solution show substantial broadening at 278 K.

ACS Paragon Plus Environment

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 4 of 17

348 K

*

328 K

*

328 K

*

308 K

*

348 K

*

298 K

*

(a)

298 K

*

278 K

*

308 K

*

*

278 K

(b) 1

Figure 3. H NMR spectra in D2O and variable temperature of HDI-1; (a) heating cycle, and (b) cooling cycle.

Thermally induced phase transitions for OEG-α-CD 18 in D2O reported by Yan et al. reveal sharp and well resolved 1 H NMR resonances at low temperature. At elevated temperature, the signals of OEG-α-CD became broader and less 1 intense. The broadening of the H nuclei at higher temperature results from the dehydration of the OEG units in the 1 modified CDs which lower the mobility of the H nuclei giving rise to broadened signals. The thermal behavior of the HDI-1 polymer herein is unique because hydrophobic hydration phenomena and conformational changes play a role in stabilizing its structure in solution. The observed line broadening and temperature effects indicate that the C6 linker undergoes substantial changes in hydration and conformation of the n-alkyl chain of HDI over the observed temperature range. It may be inferred from the results herein (vide infra) that the C6 chain of HDI is coiled near the annular hydroxyl region of β-CD and uncoils to an extended form upon heating. Such an equilibrium process is exothermic in nature as depicted in Scheme 2. The extended (uncoiled) form of HDI-1 is expected to display deshielding while the compact (coiled) form results in shielding effects due to more apolar contacts and reduced hydration of HDI-1, in agreement with results in Fig. 3.

+T

-T “Compact” form

“Extended” form

Scheme 2. Thermally induced switching between the compact and extended forms of HDI-1 in aqueous solution at ambient pH conditions.

Similar NMR line broadening effects were previously reported for noncovalent complexes between native β-CD and n-alkyl carboxylates in D2O, along with CD polymers 43, 44 with fluorescent dyes. As well, alkylated β-CD derivatives 45,46 alkyl substituents and atwere reported to self-include tenuate conformational motility. The structure of HDI-1 reported herein contains an average of two urethane bonds per macrocycle with the pri25 mary hydroxyl groups of β-CD (cf. Scheme 1). The apolar contribution of two proximal C6 chains attached to the narrow annulus of β-CD for HDI-1 may interact cooperatively, as compared with two isolated hexamethylene groups at opposite sides of the β-CD macrocycle. The resonance lines of the C6 chain of HDI-1 does not sharpen significantly over the temperature range and provide further support that hydrophobic hydration and interfacial binding plays an important role for the thermal switching shown in Scheme 2. Evidence of cooperative association (i.e., monomers→micelles→large aggregates) of oligoethylene grafted β-CD monomers was recently shown in a small-angle X-ray and light scattering 47 study. 1

2D H NMR The self-inclusion process of the HDI-1 polymer was further investigated using 2D ROESY NMR at variable tem1 perature (VT; 308 and 338 K). Fig. 4 shows the H 2D VT ROESY results for HDI-1 at 308 K (a) and 338 K (b). Cross peaks between Hα (A) and Hβ/Hγ (B; see expanded inset regions) of HDI-1 with the intracavity region of β-CD are evident. At lower temperature (308 K), the C6 units of HDI1show correlations with the intracavity nuclei (H3, H5) of βCD (cf. Fig. 4a). In particular, Hα displays strong correlations with the H3/H5 protons of the CD; whereas, the Hβ/Hγ reveal correlations with both the intracavity protons, as well as with H6. We conclude from the results of Fig. 4a that the HDI-1 polymer is partially self-included in the annular region of β1 CD in agreement with Scheme 2 and the H NMR VT results.

ACS Paragon Plus Environment

Page 5 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

Hα

Hβ Hγ

B

A B’ A’

(b)

(a) 1

Figure 4. 2D H ROESY NMR spectra for HDI-1 at 500 MHz and variable temperature; (a) 308 K and (b) 338 K. The insets show expanded dipolar interactions between β-CD and HDI-1. According to the results in Fig. 4a, the part in close proximity to the C6 group shows dipolar contacts with the β-CD cavity. The CH2 groups in the central region of the C6 linker lie closer to the extra-cavity region. At higher temperature (338 K; Fig. 4b), the dipolar interactions between Hα of HDI-1 and H3/H5 nuclei of β-CD are attenuated. Furthermore, the interactions of Hβ/Hγ with H6 are enhanced at the expense of similar interactions with the intracavity protons (H3/H5). Fig. 4 provides direct evidence of the equilibrium switching of the HDI-1 polymer between the compact and the extended conformations with temperature (Scheme 2). We conclude from Fig. 1 and 3 that the observed NMR chemical shift/line width variation and temperature effects for HDI-1 are consistent with the partial inclusion and/or association of several CH2 groups in the annular region of β-CD. This concurs with the 2D ROESY results herein (cf. Fig. 4) and the results of Nozaki et al. for β-CDpNIPAAm 48 gels. The volume of the host cavity of β-CD is sufficient to 43 accommodate ca. 8 CH2 groups. Fig. 3 shows pronounced downfield/upfield δ values at variable temperature, consistent with the temperature dependence of uncoiling and coiling of the C6 unit between compact and extended forms (cf. Scheme 2). The thermally induced switching between the compact and extended forms of the C6 cross-linker units par49,50 allels the exothermic nature of such processes governed 51 by hydrophobic effects.

Physicochemical Characterization of the HDI-1/PNP Complex 2-D ROESY NMR The inclusion properties of β-CD and the HDI-1 urethane polymer were studied with PNP as a model guest using 2-D NMR methods to evaluate the occurrence of dipolar interactions for a well-defined host/guest system in aqueous solu52,53 1 tion. Fig. 5a-b illustrate the H 2-D ROESY NMR spectra for HDI-1 and PNP at the 1:3 and 1:5 mixing ratios in aqueous

solution at ambient pH, where pH < pKa of PNP. The mixing ratios (1:3/1:5 HDI-1:PNP) are based on the ratio of the β-CD content of HDI-1 relative to PNP (cf. Experimental Section). The appearance of trace residual solvents (i.e., DMA δ ~2–3 ppm and diethyl ether δ ~1.1 ppm; ~2% w/w) was noted in the 1-D/2-D spectra (cf. Figures 1 and 5). These trace solvents 32 have been reported elsewhere and do not adversely affect the NMR results reported herein. In Fig. 5a, the 2-D ROESY results of the 1:3 HDI1/PNP complex reveal that the ortho (Ho) and meta (Hm) protons of PNP correlate with the intracavity protons (H3 and H5) of β-CD (cf. Scheme 3). The 2-D NMR results provide strong evidence of an inclusion complex between β-CD and PNP. The dipolar correlations in Fig. 5a agree with independ52-54 ent results and indicate that PNP adopts specific inclusion geometry. The phenol ring of PNP is directionally included within the β-CD cavity where the NO2 group is oriented toward the interstitial region of β-CD and the solvent, as shown in Scheme 3. The 2-D spectra of the 1:5 HDI-1/PNP complex are shown in Fig. 5b and reveal results comparable to those shown in Fig. 5a. However, the dipolar correlations corresponding to inclusion of PNP within the β-CD cavity (H3, H5) are clearly evident and become enhanced as the equilibrium fraction of bound guest species increases. 32 In a recent sorption study of CD-based urethane polymers, the linker domains and β-CD inclusion sites were involved in the sorption of PNP. The linker domains were reported to play a greater role as the degree of cross-linking increases for HDI-based polymer materials. An increase in the cross-linker content of such materials correlate with a decreased water solubility. The 2-D NMR results (cf. Figure 5) do not reveal 1 any significant dipolar correlations between the H nuclei of PNP (~7.0-8.0 ppm) and those of theC6 units of HDI-1 (~1.01.5 ppm) for these conditions (region not shown in the scale). Polymers with greater cross-linker content (2- and 3-fold higher values) are more likely to exhibit greater dipolar correlations with the interstitial (non-inclusion) sites. However, polymers with higher cross-linker content were excluded

ACS Paragon Plus Environment

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 6 of 17

1

Figure 5. 2-D H NMR ROESY spectra in D2O at 500 MHz and 298 K; (a) 1:3 HDI-1/PNP, (b) 1:5 HDI-1/PNP. β-CD/PNP correlations are shown by rectangles. The resonance region for HDI nuclei (1.5 – 1.0 ppm) is not shown in the scale.

D ROESY NMR experiment may have sensitivity limitations 47 due to line broadening effects of the C6 unit of HDI-1 resulting in attenuation of the dipolar correlations with PNP, as observed. As well, weak NOEs occur when the solubility of 38,39,55 the host-guest system is limited.

Scheme 3. Inclusion binding mode between β-CD inclusion site of HDI-1 with p-nitrophenol (PNP). One of the urethane bond linkages is denoted by the wavy line in the primary annular hydroxyl region. Note: The binding presentation is not drawn to scale.

from this study due to their limited water solubility. In the case of the dipolar interactions for β-CD and HDI-1 in Fig. 4, the presence of a guest molecule may attenuate such interactions as a result of conformational switching to an extended form of the HDI-1. However, the guest and the linker units may simultaneously be included within the CD cavity as long as the mole ratios of the guest and interaction with the C6 linker is favored. Fig. 6 shows the 2D ROESY NMR results for HDI-1/PNP mixture at the 2:1 mole ratio and 308 K. According to Fig. 6, both the C6 units of HDI-1 and the PNP guest are included within the β-CD cavity. By contrast, dispersion interactions for C6 nuclei of HDI-1 are evident which suggests a preferred pseudo-compact conformation of the HDI-1 polymer in the presence of a guest. The compact form of HDI-1 described above is likely to attenuate the dipolar interactions between the C6 units of HDI-1 and PNP at ambient temperature conditions. The formation of a self-included complex between β-CD and the C6 domains are favored at these conditions, according to Scheme 2. Furthermore, the 2-

1

Fig. 6. 2-D H NMR ROESY spectra for 1:2 HDI-1/PNP in D2O at 500 MHz, 308 K and spin-lock time 0f 400 ms. 1-D Selective ROESY NMR To enhance the sensitivity of the dipolar interactions between PNP and the interstitial domains of the HDI-1 polymer, 1-D enhanced gradient selective ROESY NMR (gROESY) spectra were obtained for the 1:5 HDI-1/PNP system. The greater PNP loading for the 1:5 host/guest system implies that the excess guest may interact with the intersti-

ACS Paragon Plus Environment

Page 7 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

tial domains of HDI-1 as a secondary binding site relative to the β-CD cavity of HDI-1. The optimal spin-lock pulse was determined to be ~350 ms at 295 K for β-CD and HDI-1, where 1-D gROESY has been reported to improve reliability 55 1 and sensitivity of NOEs. The H nuclei of β-CD and the C6 units of the HDI-1 were selectively irradiated while the corresponding dipolar correlations with PNP were observed as inverted resonance signals. The 1-D selective gROESY results for the 1:5 HDI1/PNP complex are shown in Fig. 7. The NMR lines of PNP in Fig. 7 are influenced by the irradiation collective nuclei of βCD (H3, H5, H2, H4, H6) at 3.8 – 3.4 ppm (b). As well, irradiation of the exterior (H1) nuclei of β-CD at 5.0 ppm revealed dipolar correlation with PNP (a), consistent with the 2D re56 sults in Fig. 5 and other related systems. Of much interest to the 1-D selective gROESY results is the irradiation of the C6 nuclei of HDI-1 at 1.5 – 1.0 ppm which revealed notable dipolar interactions between HDI-1 and PNP (c). We can conclude from the 1-D gROESY results that PNP binds near the C6 domain of HDI-1. In general, the 1:5 host/guest system showed enhanced dipolar contact between the ortho and meta protons of PNP with the cavity nuclei of β-CD along with the C6 cross-linker domains, relative to the 1:3 HDI1/PNP system (cf. Fig. S4; SI). As noted above, the host-guest interactions of HDI1 polymer is influenced by the relative guest content and the role of temperature-induced conformation of HDI-1 according to Figs. 3-6 and Schemes 2 and 4. The enhanced dipolar correlations for the 1:5 HDI-1/PNP system in Fig. 7 is understood according to the greater equilibrium fraction of bound guest at these conditions. Similar 1D/2D ROESY experiments at higher temperature were complicated by COSY-type peaks for 1-D gROESY and attenuated ROE effects in 2-D ROESY. COSY-type peaks in 1-D gROESY spectra were reported to arise due to non-dephased coherence from unwanted nu55 clei. Changes in relaxation rates and variable dynamics of the C6 chain at elevated temperature may cause further complications in such NOE experiments.

(c) HDI-1 (1.5-1.0 ppm) (b) CD (3.8-3.4 ppm) (a) H1 (5.0 ppm)

Figure 7. 1-D selective gROESY results for the 1:5 HDI-1/PNP system at 298 K, showing irradiation of (a) H1 ~5.0 ppm, (b) βCD nuclei ~3.8 – 3.4 ppm, and (c) HDI-1 copolymer nuclei ~1.5 – 1.0 ppm.

Raman Spectroscopy The presence of various types of functional groups (e.g., -OH, -NO2, C-H, C=C, C-O, etc.) afford an opportunity to investigate the spectroscopic signatures of the interactions 57-59 between HDI-1 and PNP. Fig. 8 shows the expanded Raman spectra for the HDI-1, guest (powder form of PNP), and the respective HDI-1/PNP mixtures at variable mixing ratios (1:1 to 1:5). Table 1 lists the main Raman bands observed in Fig. 8. The spectra for HDI-1 were recorded as air-dried films on glass slides while PNP was measured in its crystalline powder form. The Raman spectrum of pure PNP (Fig. 8f) is comparable to PNP in aqueous solution reported by Ni et 59 al. The spectral lines for pure PNP (cf. Fig. 8f) are relatively sharp in contrast to the Raman signatures for HDI-1 (a), which display relatively broad bands. In general, the Raman shifts for PNP in the presence of HDI-1 are relatively -1 small (∆ν ≤10 cm ; cf. Table 1) while the line broadening for certain Raman signatures (bands 1,2,4–7) of PNP in the complexes (Fig. 8b-e) are more pronounced relative to pure PNP in its crystalline form. The Raman frequency shifts and the appearance of broader spectral lines are attributed to differences in the molecular environment of PNP in its bound 60state (i.e. inclusion sites and interstitial domains) of HDI-1. 63 The molecular polarizability of bulk solution and the binding sites of HDI-1 differ and result in small Raman shifts with large intensity variations, in accordance with changes in hy64-67 dration and microenvironment of the guest. The use of Raman spectroscopy for the study of 68-75 noncovalent host-guest complexes is well established. 68 Choi et al. recently examined the Raman spectra of freeze dried complexes formed between α-CD, β-CD, and modified β-CD with o-, m-, and p-nitrophenol, respectively. Despite the limited quantitative analyses of the results, the authors -1 concluded that small Raman shifts (≤6 cm ) were observed for the phenyl C=C and C-H stretching bands of the nitro75 phenol guests. Sardo et al. reported ab initio calculations in a Raman study of α-, β-, and γ-CD with methylated phenols. The guest Raman bands were attributed to bound and unbound species (cf. Table 3 in ref. 75). DFT calculations of the Raman intensity and normal mode analysis of the βCD/permethrin system provided information on the struc74 ture of the host-guest complex, as reported by Li et al. Wit73 licki et al. demonstrated that a thorough quantitative analysis of the Raman intensity variations of the cyclobis(paraquat-p-phenylene)/tetrathiafulvalene system provided estimates of binding constants in good agreement with results obtained from UV-Vis-NIR titrations. The guest Raman signatures for the HDI-1/PNP systems reported herein show spectral features that vary over the range of the host-guest mole ratios investigated (1:1 to 1:5). In Fig. 8, a notable feature is the appearance of a new -1 Raman signature ca. 1610 cm (bands 6 & 7) where its intensity increases as the level of PNP increases. This band corresponds to enhancement of one of the skeletal bands (C=C) of 64 PNP in its polymer-bound form. At a lower 1:1 mixing ratio (b), the ring breathing (band 1), sym. NO2 (bands 2 and 5), CO (band 4), C-C (band 6), and C-H stretching (band 9) for PNP are slightly shifted and broadened significantly (cf. Table 1). In particular, bands 2, 4, 7, and 10 appear significantly broader for the complexes relative to pure crystalline PNP.

ACS Paragon Plus Environment

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 8 of 17

Table 1. Raman Shift Data for Host and Guest Raman Bands (1-9) for HDI-1/PNP Complexes at Various Mole Ratios (1:1 to 1:5) and Crystalline PNP at 295 K.* Bands

1

2

HDI-1/PNP

ν (C-C)

ν (-NO )

s

Ratios HDI

3

s

ν (-NO )

2

s

2

4

5

6,7

8

ν (C-O)

ν

ν(-C=C)

ν(-CH )

-C-(NO2)

δ(C-N)

-

-

2896

-

s

S

δ(-CH)

9 ν(=C-

2

H)

-

-

-

1:1

862

1112

-

1288

1334

1592, 1612

2901

3074

1:2

863

1112

-

1288

1334

1592, 1612

2901

3075

1:3

865

1112

-

1288

1334

1592, 1612

2901

3074

1:5

867

1108

-

1282,

1328

1591, 1606

2901

3072

1326

1585, 1612

-

3078

1297 PNP

871 (850)

1215

1113 1

(1167) (1117)

1

1282 (1284)

1

(1586)

2

(3084)

2

1

*(-) No Signal, 1Ref. 59, 2Ref. 68

5 1

2

3

4

6, 7

* *

8

9 (f)

*

(e) (d) (c) (b) (a)

Figure 8. Raman spectra of solution evaporated films at 295 K for (a) HDI linker, (b) 1:1, (c) 1:2, (d) 1:3, and (e) 1:5 HDI-1/PNP complexes, and (f) crystalline solid PNP. Notable line shape/intensity changes for the 1:5 HDI-1/PNP mixture are shown with asterisks.

ACS Paragon Plus Environment

Page 9 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

The broader vibrational bands of PNP as a polymer-bound form, along with intensity variations indicate that the guest exists in its bound and unbound states. The results of Wit73 licki et al. for the cyclobis(paraquat-p-phenylene)/ tetrathiafulvalene similarly illustrate that substantial intensity changes of specific Raman bands occur upon complex for68 mation. Complementary results were reported for PNP which further support that noncovalent complexes occur for β-CD and HDI-1. As the HDI-1/PNP mole ratio increases from 1:1 to 1:5, the resonance lines sharpen and closely resemble those of crystalline PNP. The effect arises from the greater contribution of unbound PNP at these conditions. HDI-1 adopts a linear and extended morphology with increasing temperature as illustrated in Fig. 4 and Scheme 2. A similar change in morphology of HDI-1 was induced at ambient temperature when the concentration of 76,77 PNP is increased (cf. Scheme 4). The linear form of HDI-1 relates to cross-linking of HDI at the primary hydroxyl groups of β-CD at the narrow side of the annulus (cf. Scheme 1). The C6 cross-linker is apolar in nature and the accessibility of the β-CD inclusion sites depend on the hydration environment and the equilibrium state for the compact and extended forms (cf. Scheme 2) of HDI-1. We suggest that the preparation of air-dried films for Raman analysis may bias the conformational preference of the linker unit for HDI-1 and its complexes toward a pseudo-compact form. In contrast, the topology of HDI-1 and its complexes with PNP in solution, as described by the coupled equilibria illustrated in Scheme 5 since the presence of solvent, guest, and temperature affect the position of equilibrium. The role of the interstitial regions in guest binding, as well as the temperatureand guest-dependent equilibrium switching between the compact and extended conformations of HDI-1 were further probed using ICD, DSC, and DLS experiments.

Scheme 5. Equilibrium switching between compact and extended forms of HDI-1, according to temperature and guest concentration effects.

Induced Circular Dichroism (ICD) Induced circular dichroism (ICD) has been widely 18,78-80 The used for the study of CD inclusion complexes. magnitude of the ICD effect is reflected by the amount of elliptical polarized light generated upon inclusion of an achiral guest within the β-CD cavity. Figs. 9a-b illustrate the ICD spectra in aqueous solution at pH 6 for the titration of β-CD and HDI-1 with PNP, respectively. The ICD spectra are plotted as ellipticity (θ; degrees) against wavelength (nm). In the case of β-CD with no added guest, no apparent ICD is observed in the 250–400 nm region (cf. Fig. 9). The addition of incremental amounts of PNP gives rise to an ICD band centered ca. 320 nm, where its intensity increases as the guest concentration increases up to the 1:5 β-CD/PNP mole ratio. The maximum ICD intensity corresponds to the greatest fraction of bound β-CD and provides unequivocal support that inclusion complexes are formed. Mendicuti and Gonzá79 lez-Álvarez have studied the ICD spectra for complex formation between naphthyl guests and β-CD, where binding constants were quantitatively estimated by analyzing the θ18 values vs. guest concentration. Similarly, Yan et al. used the intensity of ICD θ-values to deduce the degree of dye inclusion within OEG-α-CD. The ICD spectra for HD1-1 polymer in aqueous solution at variable concentration of PNP is shown in Figure 9b for similar conditions described in Fig. 9a. An ICD band centered ca. 320 nm is observed for increasing guest concentration as noted for the β-CD/PNP system. However, a lower θvalue occurs at the 1:5 HDI-1/PNP mole ratio relative to the β-CD/PNP system. The attenuation of the ICD band for the HDI-1/PNP system is attributed to competitive binding of dye at the interstitial domains of the C6 cross-linker region of HDI-1. These secondary binding sites of HDI-1 result in a reduction of the inclusion bound PNP. The ICD results in Fig. 9b provide strong support that inclusion complexes are formed for each system (β-CD/PNP and HDI-1/PNP). In particular, the ICD results provide support that secondary binding occurs between PNP and the C6 linker sites of HDI-1, in agreement with the 1D gROESY results described above. Moreover, competitive binding in the interstitial region by the C6 cross-linker of HDI-1 in accordance with Fig. 4 cannot be ruled out. The greater θ values for the 1:5 HDI-1/PNP mixture may provide additional support that the conformational changes of the HDI-1 polymer to an uncoiled form result in increased inclusion binding at higher θ-values. DSC measurements were used to further probe thermally induced transitions of the HDI-1 in order to support the results of Fig. 4. Differential Scanning Calorimetry (DSC) Figure 10 illustrates DSC results for β-CD, HDI-1, and HDI-1/PNP complexes at variable mole ratios in aqueous solution at pH 6 over the temperature range 20 to 70°C (293343 K). The occurrence of subtle endothermic peaks was noted for β-CD, and provides further support of the role of hydration processes of the host system over this temperature 51 range.

+PNP

-PNP Scheme 4. Guest-induced switching between compact and extended forms of the HDI-1 in aqueous solution at ambient pH conditions, where ovals represent the guest (PNP). The compact form may self-include of the permethylene linker unit.

Similar DSC results are observed for HDI-1 and HDI-1/PNP systems. However, a unique endotherm is evident for HDI-1 ca. 54 °C that is not observed for the HDI1/PNP systems. The HDI-1/PNP complexes (1:1 to 1:5) reveal the absence of the endotherm at ~54 °C. The latter endo-

ACS Paragon Plus Environment

Langmuir therm for HDI-1 relates to the guest induced equilibrium switching between the compact and extended forms of the 81,82 host system (cf. Scheme 2) as the temperature increases 83 consistent with the results of Fig. 4. Hu et al. observed a similar reversible temperature-induced swelling effect for a urethane polymer-based hydrogel using DSC, as compared with results for HDI-1 in Fig. 10.

12

onto PPG and PEG reveal glass transition temperatures (~42– 43 °C) where a reversible transition occurs from clear sol → gel → turbid sol over a similar temperature range (~22–55 84 °C). A related thermo-reversible expansion/contraction was observed between 20–40 °C for gold nanoparticles with an 85 elastin-like polymer coating. The thermodynamics of solvation for HDI-1 and the formation of a supramolecular complex with PNP result in substantive hydration changes of the polymer which shift the equilibrium conformation of the C6 cross-linker from a coiled to an extended form.

8 4

θ (degrees)

0 -4 -8

β−CD β−CD/PNP (2:1) β−CD/PNP (1:1) β−CD/PNP (1:2) β−CD/PNP (1:3) β−CD/PNP (1:5)

-12 -16 -20 -24

4

(a) 250

300

350

400

450

λ (nm) 2 0

Figure 10. DSC thermograms for β-CD, HDI-1, and HDI1/PNP mixtures in aqueous solution. The dashed line is provided as a guide.

-2

θ (degrees)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 10 of 17

-4 -6 -8

HDI-1 HDI/PNP (1:1) HDI/PNP (1:2) HDI/PNP (1:3) HDI/PNP (1:5)

-10 -12 -14

(b) 260

280

300

320

340

360

380

λ (nm)

Figure 9. ICD spectra of host-guest complexes in aqueous solution; (a) β-CD/PNP, and (b) HDI-1/PNP at variable host-guest mole ratios at 295 K

Similarly, hydrogel nanoparticles of hydrophobized pullulan were observed to undergo thermal transition with 81 refolding of carbonic anhydrase B in aqueous solution. Comparable phase transitions were observed over a wide temperature range (28 to 40 °C) by Xie and Hsieh for poly(Nisopropylacrylamide) composite hydrogels containing cellu82 lose. The absence of the thermally driven endotherm transition for the HDI-1/PNP complexes is circumvented when HDI-1 binds PNP at the C6 cross-linker to favor the extended form shown in Scheme 4. In the bound state, changes in hydration of the annular hydroxyl region of β-CD favor the extended form of the polymer upon inclusion of PNP due to host-guest interactions in the interstitial region. Thermogelling copolymers that contain methylated β-CD grafted

Dynamic Light Scattering (DLS) The DLS technique was used successfully to monitor protein folding and polymer-based nanoparticles through 86,87 DLS results of changes in the hydrodynamic radius (RH). HDI-1 in aqueous solution were obtained at variable temperature (Fig. 11a) and variable PNP mole fraction (Fig. 11b), respectively. The results indicate significant changes in hydrodynamic diameters (DH) of HDI-1 in response to temperature and guest concentration. In Fig. 11a, the VT-DLS results show variation of DH from ca. 105 nm at 298 K to ca. 170 nm at 348 K. Similarly, an increase in DH (ca. 100 to 200 nm) was noted as HDI-1 binds to increasing amounts of PNP (cf. Fig. 11b). 88 Galantini et al. reported a DLS study of branched supramolecular dimers/trimers based of β-CD that forms complexes with adamantane. The hydrodynamic radii (RH ≤10 nm) increased at higher concentration where the molecular weight of HDI-1 was estimated ca. 12,000 amu (cf. Fig. S4-S5), in accordance with the occurrence of elongated polymer structures. In the case of polymer inclusion complexes (PICs), DLS was shown to give columnar-type associates with large hy89,90 drodynamic radii of about 100–200 nm. The temperature dependence of DH for polymer and PIC systems are nontrivial to interpret since other phenomena such as dehydration, micellization and aggregation may prevail at certain 91-93 polymer concentrations. Herein, a relatively low concentration (< 1 % w/w) of HDI-1 was employed. The increasing value of DH for HDI-1 in Fig. 11 concurs with the unwinding of the polymer chain due to temperature effects and the inclu-

ACS Paragon Plus Environment

Page 11 of 17

Langmuir 93

180 170

Dh (nm)

160 150 140 130 120 110 100 290

300

310

320

330

340

350

Temp. (K) 240

200

Dh (nm)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

sion of PNP guest within the polymer chain network. Thus, PNP displaces the self-included C6 linker from the β-CD cavity to favour the elongated form of HDI-1, as supported by the VT NMR results (cf. Fig. 3). A noteworthy observation from the DLS-VT results is the polydispersity index (PDI) can be used to define the order-disorder phase transition of such 94 polymer materials. The lowest PDI value for the 1 % HDI-1 solution was observed at 55 °C (0.34), in agreement with the transition detected via DSC in solution where a transition occurs over the same temperature range for HDI-1, attributed to a rod-to-coil transition in such macromolecule sys18,95 tems.

160

absence of PNP. At ambient temperature, HDI-1 adopts a coiled conformation which undergoes transition to an uncoiled form at elevated temperature (50-55 °C). Similarly, HDI-1 undergoes a transition from a coiled to an uncoiled form at ambient temperature upon addition of a guest (pnitrophenol). The observed equilibrium switching of HDI-1 between states occurs due to changes in hydrophobic hydra18,47 tion and volumetric effects. HDI-1 is a unique cyclodextrin-based polymer due to its ability to undergo structural transition with temperature and complex formation with a suitable guest. By contrast, highly cross-linked forms of β-CD display properties that are typical of conventional CD-based polymers. Thus, the unique thermo- and chemo-reversible switching between the compact and extended forms of HDI-1 is likened 18, 96 to a “Molecular Accordion”, , as illustrated by Schemes 2 and 4. The structural transition between the compact vs extended forms of HDI-1 are accompanied by substantial variation in hydration and volumetric properties of the system that parallel the swelling phenomena of dextran-based hydrogels and cyclodextrin core polymers with a star-based mor17,97 phology. The textural and morphological properties of hydrogels in their hydrated and dry states are supported by the well-established equilibrium swelling theory of Flory98 Rehner. In turn, this provides a theoretical framework for further understanding of the “Molecular Accordion” behavior observed for the HDI-1 polymer to be examined in future studies. The supramolecular “Molecular Accordion” is tunable due to the ease with which the morphology and surface chemistry can be tailored according to a facile and modular synthetic design reported herein. The unique “catch and release” behavior of HDI-1 will lead to significant technological developments of “smart materials” and other supramolecular constructs to yield improved solid phase extraction (SPE), phase transfer catalysis, sensors and advanced drug delivery systems.

ASSOCIATED CONTENT

120

Supporting Information 80 0

1

2

3

4

5

HDI-1/PNP mole ratio

Figure 11. DLS results recorded as change in hydrodynamic diameter of HDI-1 copolymer with (a) temperature (298 to 348 K), and (b) relative PNP mole ratio (a zero value refers to the absence of PNP).

2-D COSY for HDI-1, 1-D TOCSY for HDI-1 (β-CD), 1-D TOCSY for HDI-1 (HDI), 1-D gROESY for 1:3 HDI-1/PNP, gel permeation chromatography for HDI-1, and MALDI-TOF for HDI-1.

AUTHOR INFORMATION Corresponding Author * [email protected] Tel. 13069662961, Fax: 13069664730

CONCLUSIONS A polymer with a linear morphology (HDI-1) was formed by the reaction of β-CD and hexamethylene diisocyanate (HDI) at the 1:1 mole ratio. The physicochemical and binding properties of HDI-1 were investigated using spec1 troscopy ( H NMR, Raman, and ICD), calorimetry, and light scattering in aqueous solution. Evidence of the formation of well-defined polymer inclusion complexes between HDI-1 and PNP were observed, in accordance with a unique structural transition of HDI-1 that depends on temperature in the

Author Contributions The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript. Authors have contributed equally.

ACKNOWLEDGMENTS The authors are grateful for the support provided by the Natural Sciences and Engineering Research Council (NSERC) and the University of Saskatchewan for support of

ACS Paragon Plus Environment

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

this research. M. H. Mohamed is gratefully acknowledged for provision of a research sample of HDI-1 for preliminary studies. AHK wishes to acknowledge Dr. Keith Brown and Jason Maley for experimental support with solution NMR spectroscopy and circular dicroism. LDW acknowledges Dr. Josiah Obiero for assistance with GPC analysis of HDI1.

ABBREVIATIONS CD: Cyclodextrin, HDI: Hexamethylene diisocyanate, PNP: p-nitrophenol, VT: Variable Temperature.

Page 12 of 17

(11) Kopeček, J. Hydrogel Biomaterials: A smart future? Biomaterials 2007, 28, 5185–5192. (12) Crini, G. Recent Developments in Polysaccharide-based Materials used as Adsorbents in Wastewater Treatment. Prog. Polym. Sci. 2005, 30, 38–70. (13) Folch-Cano, C.; Yazdani-Pedram, M.; Olea-Azar, C. Inclusion and Functionalization of Polymers with Cyclodextrins: Current Applications and Future Prospects. Molecules 2014, 19, 14066-14079, and refs. cited therein. (14) Crini, G. Review: A History of Cyclodextrins Chem. Rev. 2014,114 (21), 10940-10975,and refs. cited therein. (15) Ren, L.; Liu, T.; Guo, J.; Guo, S. A Smart pH Responsive Graphene/Polyacrylamide Complex via Noncovalent Interaction. Nanotechnol. 2010, 21, 335701-335707.

REFERENCES REFERENCES

(1) S. Polarz, S.; Antonietti, M. Porous Materials via Nanocasting Procedures: Innovative Materials and Learning about Soft-matter Organization Chem. Commun. 2002, 2593– 2604. (2) Karoyo, A. H.; Wilson, L. D. Nano-Sized CyclodextrinBased Molecularly Imprinted Polymer Adsorbents for Perfluorinated Compounds – A Mini-Review, Nanomaterials, 2015, 5, 981-1003. (3) Alsbaiee, A.; Smith, B. J.; Xiao, L.; Ling, Y., Helbling, D. E.; Dichtel, W. R. Rapid removal of organic micropollutants from water by a porous β-cyclodextrin polymer. Nature, 2016, 529, 190–194. (4) Dodziuk, H., Ed. Cyclodextrins and Their Complexes: Chemistry, Analytical Methods, Applications; Wiley-VCH: Weinheim, Germany, 2006. (5) Steed, J.W.; Atwood, J.L. In Supramolecular Chemistry, 2nd ed.; John Wiley & Sons, Ltd.: West Sussex, UK, 2009. (6) Mahmud, S. T.; Wilson, L. D. Synthesis and characterization of surface modified mesoporous silica materials with β-cyclodextrin. Cogent Chem. 2016, 2, 1132984-1133003. (7) Morin-Crini, N.; Crini, G. Environmental applications of water-insolubleβ-cyclodextrin–epichlorohydrin polymers. Prog. Polym. Sci. 2013, 38, 344–368. (8) Chen, G.; Jiang, M. Cyclodextrin-based inclusion complexation bridging supramolecular chemistry and macromolecular self-assembly. Chem. Soc. Rev. 2011, 40, 2254–2266. (9) Soldatov, D.V. Soft Supramolecular Materials. J. Inclusion Phenom. Macrocyclic Chem. 2004, 48, 3–9.

(16) Kim, J. I.; Kim da, Y.; Kwon, D. Y.; Kang, H. J.; Kim, J. H.; Min, B. H.; Kim, M. S. An Injectable Biodegradable Temperature-responsive Gel with an Adjustable Persistence Window. Biomaterials 2012, 33, 2823-2834. (17) Li, Y.; Guo, H.; Zheng, J.; Gan, J.; Wu, K.; Lu, M. Thermoresponsive and Self-assembly Behaviors of Polyoligo(ethylene glycol)-Methacrylate-based Cyclodextrin Cored Star Polymer and Pseudo-graft Polymer. Colloids and Surfaces A: Physicochem. Eng. Aspects 2015, 471, 178-189. (18) Yan, J.; Li, W.; Zhang, X.; Liu, K.; Wu, P.; Zhang, A. Thermoresponsive Cyclodextrins with Switchable Inclusion Abilities. J. Mater. Chem. 2012, 22, 17424-17428. (19) Hu, Z.; Cai, T.; Chi, C. Thermoresponsive Oligo(ethylene glycol)-Methacrylate-based Polymers and Microgels. Soft Matter 2010, 6, 2115-2123. (20) de las Heras Alarcόn, C.; Pennadam, S.; Alexander, C. Stimuli Responsive Polymers for Biomedical Applications. Chem. Soc. Rev. 2005, 34, 276-285. (21) Jiang, D. L.; Aida, T. Photoisomerization in Dendrimers by Harvesting of Low-energy Photons. Nature 1997, 388, 454456. (22) Junge, D. M.; McGrath, D. V. Photosensitive Anzobenzene-Containing Dendrimers with Multiple Discrete States. J. Am. Chem. Soc. 1999, 121, 4912-4913, and refs. cited therein. (23) Bleger, D.; Liebig, T.; Thiermann, R.; Maskos, M.; Rabe, J. P.; Hecht, S. Light-Orchestrated Macromolecular “Accordions”: Reversible Photoinduced Shrinking of Rigid-Rod Polymers. Angew. Chem. Int. Ed. 2011, 50, 12559-12563.

(10) Gao, J. H.; Gu, H. W.; Xu, B. Multifunctional Magnetic Nanoparticles: Design, Synthesis, and Biomedical Applications. Acc. Chem. Res. 2009, 42(8), 1097–1107.

ACS Paragon Plus Environment

Page 13 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

(24) Liu, C.; Zhang, W.; Yang, H.; Sun, W.; Gong, X.; Zhao, J.; Sun, Y.; Diao, G. A Water-Soluble Inclusion Complex of Pedunculoside with the Polymer β-Cyclodextrin: A Novel Anti-Inflammation Agent with Low Toxicity. PLoS One. 2014, 9(7), e101761-70. (25) Mohamed, M. H.; Wilson, L.D.; Headley, J. V. Estimation of the Surface Accessible Inclusion Sites of βcyclodextrin based Copolymer Materials. Carbohydr. Polym. 2010, 80, 186–196. (26) Wilson, L.D.; Mohamed, M.H.; Headley, J.V. Surface Area and Pore Structure Properties of Urethane-based Copolymers Containing β-cyclodextrin. J. Colloid Interface Sci. 2011, 357, 215–222. (27) van de Manakker, F.; Vermonden, T.; van Nostrum, C.F.; Hennink, W.E. Cyclodextrin-based Polymeric Materials: Synthesis, Properties, and Pharmaceutical/Biomedical Applications. BioMacromol. 2009, 10, 3157–3175. (28) Ma, M.; Li, D. New Organic Nanoporous Polymers and Their Inclusion Complexes. Chem. Mater. 1999, 11(4), 872– 874. (29) Eftink, M. R.; Harrison, J. C. Calorimetric Studies of pnitrophenol Binding to α- and β-cyclodextrin. Bioorg. Chem. 1981,10(4), 388-398. (30) Karoyo, A. H.; Wilson, L. D. Tunable Macromolecularbased Materials for the Adsorption of Perfluorooctanoic and Octanoic Acid Anions. J. Colloid. Interf. Chem. 2013, 402, 196203. (31) Silva, O. F.; Fernández, M. A.; Pennie, S. L.; Gil, R. R.; de Rossi, R. H. Synthesis and Characterization of an Amphiphilic Cyclodextrin, a Micelle with two Recognition Sites. Langmuir 2008, 24, 3718–3726. (32) Mohamed, M. H.; Wilson, L. D.; Headley, J. V.; Peru, K. M. Investigation of the Sorption Properties of β-cyclodextrinbased Polyurethanes with Phenolic Dyes and Naphthenates. J. Colloid Interface Sci. 2011, 356, 217–226. (33) Li, H.; Meng, B.; Chai, S-H.; Liu, H.; Dai, S. Hypercrosslinked β-cyclodextrin porous polymer: an adsorptionfacilitated molecular catalyst support for transformation of water-soluble aromatic molecules. Chem. Sci., 2016, 7, 905909, and refs. cited therein. (34) García-Zubiri, I. X.; González-Gaitano, G.; Isasi, J. R. Sorption Models in Cyclodextrin Polymers: Langmuir, Freundlich, and a Dual-mode Approach. J. Colloid Interface Sci. 2009, 337(1), 11–18. (35) Mohamed, M. H.; Wilson, L. D.; Headley, J. V.; Peru, K. M. Thermodynamic Properties of Inclusion Complexes Between β-Cyclodextrin and Naphthenic Acid Fraction Components. Energy and Fuels, 2015, 29 (6), 3591–3600, and refs. cited therein.

(36) Mohamed, M. H.; Wilson, L. D.; Headley, J. V. Design and characterization of novel β-cyclodextrin based copolymer materials. Carbohydr. Res. 2011, 364, 219–229. (37) Rabolt, J. F.; Schlotter, N. E.; Swalen, J. D. Spectroscopic studies of thin film polymer laminates using Raman spectroscopy and integrated optics J. Phys. Chem. 1981, 85, 4141-4144. (38) Berger, S.; Braun, S. In 200 and More NMR Experiments: A Practical Course, Wiley-VCH: Weinheim, 2004. (39) Kessler, H.; Oschkihat, H.; Griesinger, C.; Bermel, W. Transformation of Homonuclear Two-Dimensional NMR Techniques into One-Dimensional Techniques Using Gaussian Pulses. J. Mag. Res. Chem. 1986, 70, 106–133. (40) Webb, G. A. Annual Reports on NMR Spectroscopy. London, New York, Academic Press Inc.; 1993 (vol. 7); and references cited therein. (41) Gerbaud, G.; Hediger, S.; Gadella, A.; Bardet, M. Synthesis and solid-state NMR study of chromium complexes of per (3, 6-anhydro)-α-cyclodextrin based polymers. Carbohydr. Polym. 2008, 73, 64–73. (42) Yamaguchi, I.; Takenaka, Y.; Osakada, K.; Yamamoto, T. Preparation and characterization of polyurethanecyclodextrin pseudopolyrotaxanes. Macromolecules 1999, 32, 2051–2054. 1

(43) Wilson, L. D.; Verrall, R. E. A H NMR study of cyclodextrin - hydrocarbon surfactant inclusion complexes in aqueous solutions. Can. J. Chem. 1998, 76, 25–34. (44) Mao, Q.; Liu, K.; Li, W.; Yan, J.; Zhang, A. OEGylated cyclodextrin-based thermoresponsive polymers and their switchable inclusion complexation with fluorescent dyes. Polym. Chem. 2015, 6, 1300-1308. (45) Memişğoğlu-Bilensoy, E.; Hincal, A. A.; Bochot, A.; Trichard , L.; Duchene, D. In Microencapsulation - Methods and Industrial Applications, 2nd ed.; Benita, S., Ed.; Taylor & Francis Group: Boca Raton, Florida, 2006; Vol. 158, p 269– 295. (46) Han, Y.; Cheng, K.; Simon, K.A.; Lan, Y.; Sejwal, P.; Luk, Y. A biocompatible surfactant with folded hydrophilic head group: Enhancing the stability of self-inclusion complexes of ferrocenyl in a β-cyclodextrin unit by bond rigidity J. Am. Chem. Soc. 2006, 128, 13913–13920. (47) Lombardo, D.; Longo, A.; Darcy, R.; Mazzaglia, A. Structural Properties of Nonionic Cyclodextrin Colloids in Water. Langmuir 2004, 20, 1057–1064. (48) Nozaki, T.; Maeda, Y.; Kitano, H. Cyclodextrin Gels Which Have a Temperature Responsiveness. J. Polym. Sci., Part A: Polym. Chem. 1997, 35, 1535–1541. (49) Rekharsky, M. V.; Inoue, Y. Complexation Thermodynamics of Cyclodextrins. Chem. Rev. 1998, 98, 1875–1918.

ACS Paragon Plus Environment

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

(50) Yang, M.; Chu, L. -Y.; Xie, R.; Wang, C. Molecular-Recognition-Induced Phase Transitions of Two Thermo-Responsive Polymers with Pendent β-Cyclodextrin Groups. Macromol. Chem. Phys. 2008, 209, 204–211. (51) Blokzij, W.; Engberts, J. B. F. N. Hydrophobic Effects: Opinions and Facts. Chem. Int. Ed. 1993, 32, 1545–1579. (52) Wood, D. J.; Hruska, F. E.; Saenger, W. Proton NMR study of the inclusion of aromatic molecules in. alphacyclodextrin. J. Am. Chem. Soc. 1977, 99, 1735–1740. (53) Schneider, H. -J.; Hacket, F.; Rüdiger, V. NMR Studies of Cyclodextrins and Cyclodextrin Complexes. Chem. Rev. 1998, 98, 1755–1786. (54) Inoue, Y.; Kanda, Y.; Yamamoto, Y.; Kobayashi, S. Nmr study on the formation and geometry of inclusion complexes of 6-O-(α-maltosyl) cyclomalto-hexaose and-heptaose with p-nitrophenol in aqueous solution. Carbohydrate Res. 1992, 226 (2), 197–208, and refs. cited therein. (55) Furrer, J. One-dimensional ROESY experiments with full sensitivity and reliable cross-peak integration when applied to natural products. J. Nat. Prod. 2009, 72, 1437–1441. (56) Poorghorban, M.; Karoyo, A. H.; Grochulski, P.; Verrall, 1 R. E.; Wilson, L. D.; Badea, I. A H NMR Study of Host/Guest Supramolecular Complexes of a Curcumin Analogue with βCyclodextrin and a β-Cyclodextrin-Conjugated Gemini Surfactant. Mol. Pharmaceutics 2015, 12, 2993-3006. (57) Lamcharfi, E.; Kunesch, G.; Meyer, C.; Robert, B. Investigation of cyclodextrin inclusion compounds using FT-IR and Raman spectroscopy. Spectrochim. Acta, Part A. 1995, 51, 1861–1870.

Page 14 of 17

(62) Iliescu, T.; Baia, M.; Miclǎuş, V. A Raman spectroscopic study of the diclofenac sodium–β-cyclodextrin interaction Eur. J. Pharm. Sci. 2004, 22, 487–495. (63) Lamcharfia, E.; Kunescha, G.; Meyer, C.; Robert, B. Investigation of cyclodextrin inclusion compounds using FT-IR and Raman spectroscopy Spectrochim. Acta Part A 1995, 51, 1861–1870. (64) Schmid, E. D.; Moschallski, M.; Peticolas, W. L. Solvent effects on the absorption and Raman spectra of aromatic nitrocompounds. Part 1. Calculation of preresonance Raman intensities. J. Phys. Chem. 1986, 90, 2340–2346. (65) Kumar, K; Carey, P. R. Resonance Raman spectra and structure of some complex nitroaromatic molecules. J. Chem. Phys. 1975, 63, 3697–3707. (66) Kelley, A. M. Resonance Raman Intensity Analysis of Vibrational and Solvent Reorganization in Photoinduced Charge Transfer. J. Phys. Chem. 1999, 103, 6891–6903. (67) Šašić, S.; Kuzmanović, M. Raman spectroscopic study of acetone–phenol mixtures. J. Raman Spectrosc. 1998, 29, 593– 599. (68) Choi, S. -H.; Ryu, E-N.; Ryoo, J. J.; Lee, K-P. FT-Raman Spectra of o-, m-, and p-Nitrophenol Included in Cyclodextrins. J. Incl. Phenom. Macrocycl Chem. 2001, 40, 271-274. (69) Mangolim, C. S.; Moriwaki, C.; Nogueira, A. C.; Sato, F.; Baesso, M. L.; Neto, A. M.; Matioli, G. Curcumin–βcyclodextrin inclusion complex: Stability, solubility, characterisation by FT-IR, FT-Raman, X-ray diffraction and photoacoustic spectroscopy, and food application. Food Chem. 2014, 153 (15), 361–370.

(58) Maeda, Y.; Kitano, H. Inclusional complexation by cyclodextrins at the surface of silver as evidenced by surfaceenhanced resonance Raman spectroscopy. J. Phys. Chem. 1995, 99, 487–488.

(70) Vrielynck, L.; Lapouge, C.; Marquis, S.; Kister, J.; Dupuy, N. Theoretical and experimental vibrational study of phenylurea: structure, solvent effect and inclusion process with the β-cyclodextrin in the solid state. Spectrochim. Acta Part A 2004, 60, 2553–2559.

(59) Ni, F.; Thomas, L.; Cotton, T.M. Surface-enhanced resonance raman spectroscopy as an ancillary high-performance liquid chromatography detector for nitrophenol compounds. Anal. Chem. 1989, 61, 888–894.

(71) Rossi, B.; Verrocchio, P.; Viliani, G.; Scarduelli, G.; Mancini, I.; Guella, G.; Rossi, F. Vibrational dynamics of inclusion complexes by Raman scattering: an experimental and numerical study. Philos. Mag. 2007, 87, 559-567.

(60) Arrais, A.; Savarino, P. Raman spectroscopy is a convenient technique for the efficient evaluation of cyclodextrin molecular inclusion complexes of azo-dyes colorants and largely polarizable guest molecules. J. Incl. Phenom. Macrocycl Chem. 2009, 64, 73–81.

(72) Arrais, A.; Savarino, P. Raman spectroscopy is a convenient technique for the efficient evaluation of cyclodextrin inclusion molecular complexes of azo-dye colorants and largely polarisable guest molecules. J. Incl. Phenom. Macrocycl. Chem. 2009, 64, 73–81.

(61) Witlicki, E.H.; Hansen, S.W.; Christensen, M.; Hansen, T.S.; Nygaard, S.D.; Jeppesen, J.O.; Wong, E.W.; Jensen, L.; Flood, A.H. Determination of Binding Strengths of a HostGuest Complex Using Resonances Raman Scattering. J. Phys. Chem. A. 2009, 113, 9450–9457.

(73) Witlicki, E. H.; Hansen, S. W.; Christensen, M.; Hansen, T. S.; Nygaard, S. D.; Jeppesen, J. O.; Wong, E. W.; Jensen, L.; Flood, A. H. Determination of Binding Strengths of a Host− Guest Complex Using Resonance Raman Scattering. J. Phys. Chem. A 2009, 113, 9450–9457. (74) Li, W.; Lu, B.; Sheng, A.; Yang, F.; Wang, Z. Spectroscopic and theoretical study on inclusion complexation of beta-

ACS Paragon Plus Environment

Page 15 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

cyclodextrin with permethrin. J. Mol. Struct. 2010, 981, 194– 203. (75) Sardo, M.; Amado, A.M.; Riberio-Claro, P.J.A. Inclusion compounds of phenol derivatives with cyclodextrins: a combined spectroscopic and thermal analysis. J. Raman Spectrosc. 2009, 40, 1624–1633. (76) Li, K.; Guo, L.; Liang, Z.; Thiyagarajan, P.; Wang, Q. Oligo (p-phenyleneethynylene)-based coil–rod–coil triblock copolymer: Synthesis and controlled self-organization in solution. J. Polym. Sci., Part A: Polym. Chem. 2005, 43, 6007– 6019. (77) Yang, C.; Ni, X.; Li, J. New thermogelling copolymers composed of heptakis (2, 6-di-O-methyl)-β-cyclodextrin, poly (propylene glycol), and poly (ethylene glycol). J. Mater. Chem. 2009, 19, 3755–3763. (78) Park J. W.; Lee S. Y.; Song, H.J.; Park, K. K. Selfinclusion behavior and circular dichroism of aliphatic chainlinked beta-cyclodextrin-viologen compounds and their reduced forms depending on the side of modification. J. Org Chem. 2005, 11, 70(23), 9505-13. (79) Mendicuti, R. F.; González-Álvarez, M. J. Supramolecular Chemistry: Induced Circular Dichroism to Study Host− Guest Geometry. J. Chem. Educ. 2010, 87, 965–968. (80) Berbenni, V.; Marini, A.; Bruni, G. Thermogravimetric study of the dehydration process of α-cyclodextrin: comparison between conventional and high-resolution TGA. Thermochim. Acta 1998, 322, 137–151.

serum albumin by means of dynamic light scattering. Mat. Sci. Eng. C 2008, 28, 594–600. (87) Dolatkhah, A.; Wilson, L. D. Magnetite/Polymer Brush Nanocomposites with Switchable Uptake Behavior Toward Methylene Blue. ACS Appl. Mater. Interfaces, 2016, DOI: 10.1021/acsami.5b11599. (88) Galantini, L.; Jover, A.; Leggio, C.; Meijide, F.; Pavel, N. V.; Tellini, V. H. S.; Tato, J. V.; Tortolini, C. Early Stages of Formation of Branched Host− Guest Supramolecular Polymers. J. Phys. Chem. B, 2008, 112, 8536–8541. (89) Topchieva, I. N.; Panova, I. G.; Kurganov, B. I.; Spiridonov, V. V.; Matukhina, E. V.; Filippov, S. K.; Lezov, A. V. Noncovalent Columnar Structures Based on β-Cyclodextrin. Colloid J. 2008, 70(3), 356–365. (90) Liu, J.; Sondjaja, H. R.; Tam, K. C. α-Cyclodextrininduced self-assembly of a double-hydrophilic block copolymer in aqueous solution. Langmuir 2007, 23, 5106–5109.

(91) Uguzdogan E.; Camli, T.; Kabasakal, O. S.; Patir, S.; Ozturk, E.; Denkbas, E. B.; Tuncel, A. A new temperature sensitive polymer: Poly(ethoxypropylacrylamide). A new temperature-sensitive polymer: Poly (ethoxypropylacrylamide) Eur. Polym. J. 2005, 41, 2142–2149.

(92) Isojima, T.; Lattuada, M.; Vander Sande, J. B.; Hatton, T. A. Reversible clustering of pH- and temperature-responsive Janus magnetic nanoparticles. ACS Nano, 2008, 2 (9), 1799– 1806.

(81) Akiyoshi, K.; Sasaki, Y.; Sunamoto, J. Molecular chaperone-like activity of hydrogel nanoparticles of hydrophobized pullulan: thermal stabilization with refolding of carbonic anhydrase B. Bioconj. Chem. 1999, 10(3), 321–324.

(93) Liu, J.; Chen, G.; Guo, M.; Jiang, M. Dual StimuliResponsive Supramolecular Hydrogel Based on Hybrid Inclusion Complex (HIC). Macromolecules 2010, 43, 8086–8093.

(82) Xie, J.; Hsieh, Y. Thermosensitive poly (n-isopropylacrylamide) hydrogels bonded on cellulose supports. J. Appl. Polym. Sci. 2003, 89, 999–1006.

(94) Lynda, N. A.; Meuler, A. J.; Hillmyer, M. A. Polydispersity and block copolymer self-assembly. Prog. Polym. Sci. 2008, 33, 875–893.

(83) Hu, J.; Liu, B.; Liu, W. Temperature/pH Dual Sensitive N-isopropylacrylamide/ Polyurethane Copolymer Hydrogelgrafted Fabrics Text. Res. J. 2006, 76, 853-860.

(95) Shin, J.; Cherstvy, A. G.; Metzler, R. Kinetics of polymer looping with macromolecular crowding: effects of volume fraction and crowder size. Soft Matter, 2015, 11, 472-488.

(84) Yang, C.; Ni, X.; Li, J. New thermogelling copolymers composed of heptakis (2, 6-di-O-methyl)-β-cyclodextrin, poly (propylene glycol), and poly (ethylene glycol). J. Mater. Chem. 2009, 19, 3755–3763. (85) Alvarez-Rodríguez, R.; Arias, F. J.; Santos, M.; Testera, A. M.; Rodríguez –Cabello, J. C. Gold Tailored Photosensitive Elastin-like Polymer: Synthesis of Temperature, pH and UV-vis Sensitive Probe. Macromol. Rapid Commun. 2010, 31, 568–573. (86) Aschi, A.; Mbarek, N.; Othman, M.; Gharbi, A. Study of thermally and chemically unfolded conformations of bovine

(96) Ringsdorf, H.; Venzmer, J.; Winnik, F. M. Interaction of Hydrophobically-Modified Poly-N-isopropylacrylamides with Model Membranes – or Playing a Molecular Accordion. Angew. Chem. Int. Ed. Engl.1991, 30, 315−318, and refs. cited therein. (97) Ferreira, L.; Figueiredo, M.M.; Gil, M.H.; Ramos, M.A. Structural analysis of dextran-based hydrogels obtained chemoenzymatically. J. Biomed. Mater. Res. Part B, 2006, 77B, 55–64. (98) Flory, P. J.; Rehner, J. Statistical mechanics of crosslinked polymer networks. I. Rubberlike elasticity. J. Chem. Phys. 1943, 11, 521–527.

ACS Paragon Plus Environment

Langmuir

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Insert Table of Contents artwork here

ACS Paragon Plus Environment

Page 16 of 17

Page 17 of 17

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Langmuir

“Switchable” structural transition for a synthetic "smart" polymer material at variable temperature and guest concentration 254x190mm (96 x 96 DPI)

ACS Paragon Plus Environment