Controllable Self-Assembly of Amphiphilic Tadpole-Shaped Polymer

Subscriber access provided by Iowa State University | Library

Interface Components: Nanoparticles, Colloids, Emulsions, Surfactants, Proteins, Polymers

Controllable Self-Assembly of Amphiphilic Tadpole-Shaped Polymer SingleChain Nanoparticles Prepared through Intrachain Photo-Cross-Linking Srinivas Thanneeru, Weikun Li, and Jie He Langmuir, Just Accepted Manuscript • DOI: 10.1021/acs.langmuir.8b03095 • Publication Date (Web): 23 Jan 2019 Downloaded from http://pubs.acs.org on January 26, 2019

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 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 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.

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 24 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

Controllable Self-Assembly of Amphiphilic Tadpole-Shaped Polymer Single-Chain Nanoparticles Prepared through Intrachain Photo-Cross-Linking Srinivas Thanneeru,a Weikun Li,a Jie He*,a,b a

Department of Chemistry, bPolymer Program, Institute of Materials Science, University of Connecticut, Storrs, CT 06269, United States Email: [email protected] (JH)

Abstract

We report the use of intramolecular cross-linking chemistry as a tool to control the self-assembly of amphiphilic di-block copolymers (di-BCPs). Two amphiphilic di-BCPs of poly(N,N'-dimethyl acrylamide)-block-polystyrene (PDMA-b-PS) with photo-cross-linkable cinnamoyl groups in either hydrophobic or hydrophilic blocks were prepared using reversible addition fragmentation chain transfer polymerization. Intramolecular photo-cross-linking of cinnamoyl groups led to the formation of tadpole-shaped polymer single-chain nanoparticles (SCNPs) consisting of a self-collapsed block as the “head” and an uncross-linked block as the “tail”. When intramolecular photo-crosslinking was carried out in hydrophobic PS blocks, a clear morphological transition from branched cylindrical micelles (for the linear di-BCP) to completely spherical micelles at a dimerization degree of ~63% was observed. A pattern of morphological transitions from cylindrical micelles to spherical micelles is observed through stepwise downsizing the length of cylindrical micelles when increasing the self-collapse degree of PS blocks. Whereas, in case of photo-cross-linking carried out in hydrophilic PDMA blocks, the size of micelles showed a dramatic increase due to the shift of hydrophobic-to-hydrophilic balance. When the cross-linking degree of PDMA blocks reached > 60%, tadpole-shaped SCNPs assembled into nonconventional aggregates with non-smooth surface. Our results illustrate the impact of chain topologies on the self-assembly outcomes of amphiphilic di-BCPs which likely opens a door to control the micellar morphologies from just one parent linear di-BCP, rather than re-synthesizing BPCs with different volume fractions of the two blocks.

1

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 2 of 24

1. Introduction Self-assembly of amphiphilic block copolymers (BCPs) in aqueous solution is an inexpensive bottom-up strategy to create new polymeric nanostructures potentially useful in drug delivery, 1 nanomedicine,2 catalysis3 and other areas. Control of the self-assembly nanostructures of amphiphilic BCPs usually relies on the ratio or volume fraction of hydrophilic and hydrophobic blocks,.4 One classical illustration of this principle is the use of highly asymmetric amphiphilic BCPs with a short hydrophilic block length to prepare crew-cut micelles.5-6 On the other hand, chain topology and architecture of amphiphilic BCPs has a great impact on the self-assembly outcome in solution.7 The studies on self-assembly of non-linear amphiphilic BCPs, e.g., brush polymers,8-9 star-like polymers,10 dendritic polymers11 and cyclic polymers,12 showed nonconventional micellar nanostructures with precisely designing topological structures and functionalities. For example, cyclic polymer brushes can self-assemble into cylindrical tubes which are unusual in linear BCPs.13, Simulation results demonstrated the possibility to produce a new family of complex self-assembled nanostructures, not existing (or not been observed yet) in linear BCPs when they tethered to 1-D nanoparticles.14-16 Despite tremendous progress made in the synthesis of non-linear polymers in the past two decades, the precise design of non-linear polymers and a systematical study on their self-assembly behaviors are still technically challenging.

Among those non-linear BCPs, tadpole-shaped polymers consisting of a nanoparticle head attached with a flexible polymer tail have a close structural similarity to linear BCPs.17-23 Tadpole-shaped polymers can be prepared via intramolecular cross-linking of one block of a linear BCPs.22-23 Tadpole-shaped polymer single chain nanoparticles (SCNPs), as a close analogue to their parent linear BCPs, are ideal models to understand how the chain topology and chain conformation can influence the self-assembly outcomes. Self-collapse of polymer chains largely varies the chain flexibility that will impact self-assembly thermodynamics and kinetics. First of all, intramolecular crosslinking diminishes chain entanglement, since the relative viscosity of intramolecularly cross-linked polymers show almost no correlations with its concentration.24-25 For an amphiphilic BCP with a self-collapsed core-forming block, less chain entanglement will lead to the formation of loose micelles. One example reported by Chen and co-workers shows the self-assembly of monotailed tadpole-shaped SCNPs via intramolecular cross-linking of amphiphilic diBCP, poly(ethylene oxide)-b-poly(2-cinnamoyloxyethyl methacrylate) in water. It is interesting that micelles from tadpole-shaped SCNPs can dissociate into smaller aggregates upon sonication.26 In the absence of interchain entanglement within the micellar cores, chain escape becomes feasible.27 Additionally, intramolecular cross-linking alters other physicochemical properties of linear BCPs, e.g. hydrodynamic radius and polymer-solvent interaction parameter,28-32 which will have an impact on the self-assembly thermodynamics of polymers in solution.26, 33-41 The change in the relative mole fraction of the two blocks will shift the hydrophilic-to-hydrophobic balance of BCPs, known to be critical to tune the self-assembly morphologies. The self-collapse also promotes intrachain interaction and weakens the polymer-solvent interaction that will change the self-assembly tendency, i.e., critical micelle

2


Page 3 of 24 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

concentration (CMC) and critical water concentration. Zhao and his group reported the preparation and selfassembly of monotethered tadpole-shaped amphiphiles of poly(2-(dimethylamino)ethyl methacrylate)-bpolystyrene (PDMAEMA-b-PS) through the quaternization of PDMAEMA blocks.39-40 In a selective solvent, the tadpole-shaped amphiphiles could self-assemble into spherical micelles. When increasing the degree of quaternization (or the cross-linking density of PDMAEMA blocks), the micellar morphology changed from spherical micelles to cylindrical micelles and vesicles. Our group showed the preparation of tadpole-shaped SCNPs, based on the intramolecular collapse of amphiphilic di-BCPs of poly(ethylene oxide)-b-poly[methyl methacrylateco-3-(trimethoxysilyl)propyl

methacrylate)]

[PEO-b-P(MMA-co-TMSPMA)]

using

hydrolysis

and

polycondensation reaction of trimethoxysilane groups.42-43 The amphiphilic tadpole-like SCNPs with hydrophobic “hard” silica nanoparticle heads and hydrophilic PEO tethers were able to self-assemble into aggregates with different morphologies in a mixed solvent of THF/water.

In this contribution, we consider to use intramolecular cross-linking as a tool to control the self-assembly outcomes of linear BCPs and their SCNPs. For example, when simply varying the cross-linking density of the head-forming block, a library of tadpole-shaped SCNPs can be obtained at different collapse degrees of the head-forming block. In view of comparing the differences in self-assembly behaviors of amphiphilic linear di-BCPs with their tadpoleshaped SCNPs, the question we would like to address is whether the self-assembly morphologies are determined and eventually controllable by the cross-linking density of tadpole-shaped SCNPs. In this contribution, we use two di-BCPs with photo-cross-linkable cinnamoyl groups in either hydrophilic or hydrophobic blocks to prepare tadpole-shaped SCNPs (Scheme 1). Photo-cross-linking chemistry of cinnamoyl groups is chosen to carry out in the two blocks, since it is expected to have minimum impact on the chemical nature and the molecular weight of the parent linear di-BCPs; additionally, it is spatially and temporally controllable to produce tadpole-shaped SCNPs at any cross-linking density as desired.44-54 Cinnamoyl esters undergo photochemical [2+2] cycloaddition without additional chemical cross-linkers nor cleave leaving groups. This allows to preserve the similarity in chemical composition and thus to compare the self-assembly of linear di-BCPs and their tadpole-shaped SCNPs at different collapse degrees of head-forming blocks as a means to understand the effect of chain topology on the self-assembly of amphiphilic di-BCPs. Intramolecular cross-linking on either of the blocks does show significant impact on the self-assembly outcomes of polymers. In case of photo-cross-linking core-forming hydrophobic blocks in amphiphilic di-BCPs, a pattern of morphological transitions from cylindrical micelles to spherical micelles is observed through stepwise downsizing the length of cylindrical micelles. Our study illustrates an alternative approach to tune the micellar morphologies using just one parent linear di-BCP, other than re-synthesizing a library of di-BCPs with different volume fractions of the two blocks.

3


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 24

Scheme 1. (a) Chemical structures showing the synthesis of linear BCPs of PDMA35-b-P(St110-co-CEMA35) and P(DMA210-co-CEMA38)-b-PS190 (b) Schematic representation of preparation of tadpole shaped SCNPs by intramolecular photo cross-linking reaction of cinnamoyl groups.

2. Experimental 2.1 Materials Styrene (St, 99%), 2-(trimethylsilyloxy) ethyl methacrylate (HEMATMS, 96%), N,N'-dimethyl acrylamide (DMA, 99%) were passed through a short aluminum oxide column prior to use. 2,2'-Azobis(isobutyronitrile) (AIBN) was recrystallized twice from ethanol. Cinnamoyl chloride (98%), potassium fluoride (KF; 99%), tetrabutyl ammonium fluoride (TBAF; 97%), triethylamine (TEA; 98%) was purchased from J.T Baker and used as received. All other chemicals were purchased from Sigma-Aldrich and used as received unless otherwise noted. Deionized water (High-Q, Inc. 103S Stills) with resistivity of >10.0 MΩ was used for all self-assembly experiments.

2.2 Polymer Synthesis and Characterizations Synthesis of poly(N,N'-dimethyl acrylamide) (PDMA) macro-chain transfer agent (CTA) The PDMA macro-CTA was synthesized using reversible addition fragmentation chain transfer (RAFT) polymerization and it was further used to grow the di-BCPs with hydrophobic polystyrene (PS). In a typical synthesis, 2-(2-cyanopropyl) dithiobenzoate (CPDB, 223.2 mg, 1.01 mmol), DMA (6 g, 60.6 mmol) and AIBN (33.1 mg, 0.202 mmol) were dissolved in 3 mL of anisole (99%, anhydrous) in a 10 mL round-bottomed flask. The reaction mixture was degassed under vacuum and refilled with nitrogen for 15 min. Then, the flask was placed in a pre-heated oil bath at 70 oC for 10 h. After polymerization, the reaction mixture was cooled to room temperature;

4


Page 5 of 24 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 polymer was collected after three times of precipitation in diethyl ether and dried under vacuum at 40 oC for 24 h. The obtained polymer has a number-average molecular weight (Mn) of 3,400 g mol-1 and a molar mass dispersity (Ð=Mw/Mn) of 1.10 according to gel permeation chromatography (GPC) measurements using polystyrene (PS) standards. From proton nuclear magnetic resonance (1H NMR) spectrum in CDCl3, the number of repeat units was calculated to be 35 using the conversion for DMA.

Synthesis of PDMA35-b-P(St110-co-HEMATMS35) PDMA35 was subsequently used as a macro-chain transfer agent (PDMA35-CTA) to grow di-BCPs. PDMA35-CTA (150 mg, 0.042 mmol), styrene (3.78 g, 36.4 mmol), HEMATMS (834.6 mg, 6.4 mmol) and AIBN (1.2 mg, 7 mol) were dissolved in 2 mL of anisole in a 25 mL flask. The reaction mixture was then degassed under vacuum and refilled with nitrogen for 15 min. The flask was sealed and placed in a pre-heated oil bath at 85 oC. After the polymerization was done, the reaction mixture was cooled to room temperature. The polymer was collected after three times of precipitation in hexane and dried under vacuum overnight at 40 oC. The polymer has a Mn of 57,000 g mol-1 and Ð of 1.26 from GPC analysis. The number of repeat units of St and HEMATMS was calculated from 1

H NMR to be 110 and 35, respectively, using PDMA35-CTA as an internal standard.

Synthesis of P(DMA210-co-HEMATMS38) macro-RAFT agent For the synthesis of P(DMA-co-HEMATMS), CPDB (22.3 mg, 0.1 mmol), DMA (5 g, 50.5 mmol), HEMATMS (1.02 g, 5.1 mmol) and AIBN (3.3 mg, 0.02 mmol) were dissolved in 5 mL of anisole in a 25 mL flask. The reaction mixture was degassed under vacuum and refilled with nitrogen for 15 min. Then, the flask was placed in a preheated oil bath at 70 oC for 4 h. After polymerization, the reaction mixture was cooled to room temperature. The polymer was collected after three times of precipitation in hexane and dried under vacuum for 24 h. The obtained polymer has a Mn of 21,800 g mol-1 and Ð of 1.25. The number of repeat units of DMA and HEMATMS was calculated to be 210 and 38, respectively, using 1H NMR spectroscopy.

Synthesis of P(DMA210-co-HEMATMS38)-b-PS190 P(DMA210-co-HEMATMS38)-CTA (1.39 g, 0.05 mmol), St (5 g, 48.1 mmol) and AIBN (1.6 mg, 9 mmol) were dissolved in 6 mL of anisole in a 25 mL flask. The solution was degassed under vacuum and refilled with nitrogen for 15 min. Then the flask was placed in a pre-heated oil bath at 85 oC. After polymerization, the reaction mixture was cooled down to room temperature. The polymer was collected after three times of precipitation in hexane and dried under vacuum for 24 h. The obtained polymer has a Mn of 52,300 g mol-1 and Ð of 1.40 from GPC analysis. The number of repeat units of St was calculated to be 190 using 1H NMR spectroscopy.

Post-polymerization functionalization of di-BCPs

5


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 24

The conversion of trimethylsilyl (TMS) ether to photo-cross-linkable cinnamoyl ester was performed via hydrolysis of TMS ether followed by esterification of cinnamoyl chloride in one step reaction. Typically, 1.2 g of PDMA-bP(St-co-HEMATMS) (1.9 mmol with respect to the TMS groups), KF (221.4 mg, 3.82 mmol), TBAF (12.1 mg, 38 mol) were first dissolved in 75 mL of THF. The reaction mixture was first purged with nitrogen for 15 min. After one hour, 2.5 equivalents of cinnamoyl chloride (791.4 mg, 4.75 mmol) and triethylamine (0.53 mL, 3.82 mmol) were added to the polymer solution. The reaction was then conducted at 0 oC for 2 h and then at room temperature for another 24 h. After the reaction, the polymer solution was passed through a neutral alumina (Al2O3) column using THF as an eluent to remove triethylamine hydrochloride. The solution was then concentrated and precipitated twice in hexane, dried under vacuum for 24 h. The conversion of HEMATMS to photo-cross-linkable cinnamoyl moieties (CEMA) was confirmed by 1H NMR. The polymer, PDMA35-b-P(St110-co-CEMA35), has a Mn of 78.7 kg mol-1 and Ð of 1.48 from GPC. The conversion of TMS ethers in P(DMA210-co-HEMATMS38)-b-PS190 to P(DMA210-co-CEMA38)-b-PS190 was carried out using similar procedures described above. The characterization results of the two di-BCPs are given in Table 1.

Table 1. Molecular weight and dispersity of linear BCPs and their SCNPs Polymers a

Mn, NMR

Mn, GPC

(kg/mol) b (kg/mol) c

Ð of

Mn of

linear BCPs

c

Ð of

SCNPs (kg/mol)

RH of

SCNPs c

(nm)

c

RH of

BCPs SCNPs (nm)d

(nm)d

--

--

PDMA35-RAFT

3.5

3.4

1.11

--

--

PDMA35-b-P(St110-co-HEMATMS35)

22

57

1.26

--

--

PDMA35-b-P(St110-co-CEMA35)

24

78.7

1.48

34.1

1.52

4.2

2.8

P(DMA210-co-HEMATMS38)

35.6

21.8

1.25

--

--

--

--

P(DMA210-co-HEMATMS38)-b-PS190

48.2

52.3

1.40

--

--

--

--

P(DMA210-co-CEMA38)-b-PS190

50.4

72.3

1.36

23.6

1.59

7.0

3.3

--

a

The repeat unit numbers was calculated from 1H NMR; bThe number-average molecular weights were calculated

from 1H NMR; cThe number-average molecular weights and dispersity were determined by GPC.

2.3 Preparation of SCNPs 50 mg of di-BCPs PDMA35-b-P(St110-co-CEMA35) or P(DMA210-co-CEMA38)-b-PS190) was dissolved in 100 mL of chloroform (0.5 mg/mL). The solution was first stirred for 4 h at room temperature prior to photo-cross-linking reaction. The photodimerization was performed upon exposure to UV light (OmniCure Series S1500 UV lamp with 8 mm diameter light guide, and intensity of 100 mW cm-2 passed a filter of 320-390 nm,). The dimerization degree (DD) of cinnamoyl groups was monitored by UV-vis spectroscopy and calculated using the peak intensity at 280

6


Page 7 of 24 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

nm, respectively. The solution was further concentrated using rotary evaporator under vacuum. SCNPs were precipitated in hexane and dried under vacuum overnight.

2.4 Self-Assembly of Linear BCPs and SCNPs 2 mg of linear BCPs or SCNPs was first dissolved in 2 mL of DMF. 2 mL of 60 vol% of deionized (DI) water in DMF was then added slowly into the above solution under strong stirring. The addition rate was controlled using a syringe pump at a rate of 50 μL/min. The solution was further stirred for 8 h before 4 mL of DI water was added to quench the self-assembly. Afterward, the samples were dialyzed against water for 24 h to remove DMF. Distilled water was changed every 5-6 hours. For the TEM sample preparation, a drop of the sample solution was added on a carbon-coated copper grid for few minutes, and the excess solution was removed with a strip of filter paper.

2.5 Characterizations GPC measurements were performed on a Waters GPC-1 (1515 HPLC pump and Waters 717 Plus auto injector) equipped with a Varian 380-LC evaporative light scattering detector (ELSD), a Waters 2487 dual absorbance detector, and three Jordi Gel fluorinated DVB columns (1−100K, 2−10K, and 1−500 Å). THF (Fisher, HPLC grade) was used as an elution solvent at a flow rate of 1.25 mL/min, and PS standards were used for molecular weight and molecular weight distribution calibration. The data was processed using Empower GPC software (Waters, Inc.). Proton nuclear magnetic resonance (1H NMR) spectra were recorded on a Bruker Avance 400 MHz spectrometer. Transmission electron microscopy studies were carried out using 2006 Tecnai T12 TEM with an accelerating voltage of 120 kV. The TEM samples were prepared by casting the suspension of assemblies on a carbon coated copper grid (300 mesh). Scanning electron microscope (SEM) images of the micellar assemblies were recorded using a FEI Nova NanoSEM 450 with an accelerating voltage of 10 kV and a beam current of 10 mA. SEM samples were prepared by casting the suspension of the micellar assemblies on a silicon wafer and dried at room temperature. The hydrodynamic diameters of BCPs and SCNPs were measured using an ALV/CGS-3 MD goniometer system, consisting of a 22 mW He−Ne laser at a wavelength of 632.8 nm and avalanche photodiode (APD) detector located at an angle of 90o. All samples filtered using 0.45

m PTFE filters prior DLS measurements.

3. Results and Discussion 3.1 Synthesis and Characterizations of linear di-BCPs The synthetic route of amphiphilic di-BCP with a hydrophobic PS block and a hydrophilic PDMA block is given in Scheme 1a. We prepared two di-BCPs having photo-cross-linkable cinnamoyl moieties in either PS block or PDMA block using RAFT polymerization. For both di-BCPs, PDMA macro-RAFT agent was first synthesized using 2-(2-cyanopropyl) dithiobenzoate as a RAFT agent. HEMATMS was used as a monomer precursor to copolymerize in PS or PDMA blocks and then convert into cinnamoyl ester. Post-polymerization functionalization

7


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 24

was carried out in one step by combining the hydrolysis of HEMATMS with the esterification using excess cinnamoyl chloride.55 Hydrolysis of TMS groups was catalyzed by KF and 2 mol% of TBAF as a phase-transfer catalyst. Table 1 summarizes the molecular weights and dispersity indexes of di-BCPs.

Figure 1. (a) UV-vis spectra of PDMA35-b-P(St110-co-CEMA35) recorded in CHCl3 after UV irradiation (inset) showing photodimerization upon exposing to UV light at different times (b) 1H NMR spectra of polymer PDMA35b-P(St110-co-CEMA35) before (black) and after (red) photodimerization reaction measured in CDCl 3. The peaks marked with “*” are from residual THF. 1

H NMR spectra of PDMA35-CTA, PDMA35-b-P(St110-co-HEMATMS35) and PDMA35-b-P(St110-co-CEMA35) are

presented in Figure S1. The copolymerization of St and HEMATMS is evident from the resonance peak d at 0 ppm assigned to methyl groups on TMS. The ratio of St and HEMATMS was estimated by comparing the intergal of the peak d and the peak b (protons on the aromatic ring of PS). After deprotecting HEMATMS and grafting of cinnamoyl esters, the resonance peak d disappeared and the new peaks at 7.38 ppm and 7.50 ppm for cinnamoyl groups were seen. The conversion of HEMATMS to cinnamoyl esters is close to 100% since the number of CEMA matches with that of HEMATMS. PDMA35-b-P(St110-co-CEMA35) shows a small molecular weight increase from

8


Page 9 of 24 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

57 kg mol-1 to 78.7 kg mol-1, further confirming the functionalization of cinnamoyl groups. Another di-BCP of P(DMA210-co-CEMA38)-b-PS190 with photo-cross-linkable cinnamoyl groups in hydrophilic PDMA block was prepared using similar procedures (see Figure S2).

3.2 Preparation and Characterization of SCNPs It is well-known that cinnamoyl esters undergo photochemical [2+2] cycloaddition or photodimerization under λ > 300 nm.56-57 Photodimerization allows us to tune cross-linking density and collapse degree of polymer chains more rationally. It does not require additional chemical cross-linkers nor cleave leaving groups that potentially preserve close chemical similarity of linear di-BCPs and their SCNPs. When dissolving the di-BCP of PDMA35-b-P(St110co-CEMA35) in CHCl3 as a good solvent for both blocks at a concentration of 0.03 mg/mL, photodimerization of cinnamoyl esters was first studied using UV-vis spectroscopy. Figure 1a shows the absorption spectral change of the polymer solution upon exposure to UV light (320-390 nm, 100 mW cm-2). The continuous decrease of the absorbance at 280 nm over irradiation time indicates the dimerization of cinnamoyl groups. The dimerization degree defined as 1-At/A0 where At and A0 are the absorbance after an irradiation time of t and the initial absorbance at 280 nm, respectively, can be calculated.25 The result is given as an inset in Figure 1a. The kinetic plot of dimerization degree vs. irradiation time suggests that the dimerization of cinnamoyl groups took place efficiently at a low concentration and the dimerization degree reached up to 70% after 30 min. The dimerization can also be confirmed from NMR spectra before and after UV irradiation (Figure 1b). The decrease in intensity and broadening of peaks for protons on the C=C bond of cinnamoyl groups at 6.3 and 7.6 ppm clearly indicate the occurrence of dimerization. The peak f of PDMA methyl groups at 2.9 ppm and the aromatic protons of PS blocks also show a slight broadening, due to the loss of chain mobility. Photo-cross-linking induced by photodimerization of cinnamoyl groups in hydrophobic PS blocks can thus yield SCNPs with a hydrophobic PS head of tethered with a hydrophilic PDMA tail (see Scheme 1b).

Likewise, for polymer P(DMA210-co-CEMA38)-b-PS190, photodimerization of cinnamoyl groups in the hydrophilic PDMA blocks was carried out under similar conditions. The dimerization of cinnamoyl groups in P(DMA 210-coCEMA38)-b-PS190 shows a faster rate compared to that in PDMA35-b-P(St110-co-CEMA35). The dimerization degree can reach up to 79% when irradiated for 15 min (Figure S3). This is likely because P(DMA210-co-CEMA38)-b-PS190 has a slightly longer, more flexible cross-linkable block to allow further dimerization.

9


Langmuir

(c)

6

(b)

9

12

15

18

Intensity (a.u)

21

24

Elution Time (min)

27

3.0

2.5

70 60

2.0

50 1.5 40 30

1.0 10

20

30

40

50

12

30

80

0

Dimerization degree

15

18

21

24

27

30

Elution Time (min)

33

70 2.5 60 50

2.0

40 1.5 30 20

1.0 0

60

Dimerization Degree (%)

36

3.0

(d) Mw/Mn Number Average Mw (kg/mol)

Intensity (a.u)

Dimerization degree

Mw/Mn

(a)

Number Average Mw (kg/mol)

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 24

10 20 30 40 50 60 70

Dimerization Degree (%)

Figure 2. (a) GPC traces of the linear di-BCP PDMA35-b-P(St110-co-CEMA35) and its SCNPs at different dimerization degrees: 0%, 13.9%,32.7%, 38.2%, 59.0%, and 63.9 % (bottom to top). (b) Plotting the change of the apparent molecular weight and dispersity of PDMA35-b-P(St110-co-CEMA35) as a function of dimerization degree. (c) GPC traces of the linear di-BCP P(DMA210-co-CEMA38)-b-PS190 and its SCNPs at different dimerization degrees: 0%, 36.5%, 41.1%, 60.8%, 67.6%, and 69.6 % (bottom to top). (d) Plotting the change of the apparent molecular weight and dispersity of P(DMA210-co-CEMA38)-b-PS190 as a function of dimerization degree.

To confirm whether the cross-linking reaction occurred intramolecularly, GPC measurements were performed for di-BCPs and their SCNPs. The elution time of GPC is delicate to changes in the hydrodynamic volume of individual polymer chains. Intramolecular coil-to-particle transition would result in the collapse of polymer chains thus reducing in hydrodynamic volume and increasing the elution time. Figure 2a shows the GPC traces of PDMA 35-bP(St110-co-CEMA35) at different dimerization degrees during photo-dimerization of cinnamoyl esters. A continuous increase of elution time indicates the formation of SCNPs via intramolecular photo-cross-linking. The absence of

10


Page 11 of 24 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

peaks at shorter retention times is also evident that there is no intermolecular photo-cross-linking. At a higher crosslinking density, the shrinkage in hydrodynamic volume becomes higher. The changes in apparent molecular weight and dispersity of PDMA35-b-P(St110-co-CEMA35) were plotted as a function of dimerization degree in Figure 2b. The Mn decreased from 78.7 kg/mol of the linear di-BCP to 34.1 kg/mol of SCNPs at a cross-linking degree of 63.9%. The GPC traces for the di-BCP of P(DMA210-co-CEMA38)-b-PS190 and its SCNPs at different dimerization degrees are given in Figure 2c. Similarly, no elution peaks at a shorter retention time suggests the occurrence of intramolecular photo-cross-linking. The decrease in molecular weight becomes more pronounced at a higher crosslinking density. The corresponding changes in molecular weight and dispersity in regard to the dimerization degree for P(DMA210-co-CEMA38)-b-PS190 are plotted as shown in Figure 2d. For both di-BCPs, a similar trend was noticed for the molecular weight drop upon cross-linking the di-BCPs. But the decrease of molecular weight vs. dimerization degree is faster for PDMA35-b-P(St110-co-CEMA35) compared to P(DMA210-co-CEMA38)-b-PS190. This is ascribed to the less mole fraction of photo-cross-linkable cinnamoyl groups present in a long hydrophilic block (~15.5%) for P(DMA210-co-CEMA38)-b-PS190; while compared to that in PDMA35-b-P(St110-co-CEMA35) (~24%).

Figure 3. (a, b) Representative TEM images of SCNPs prepared from PDMA35-b-P(St110-co-CEMA35) at a dimerization degree of 63.9%. (c) The size distribution of the SCNPs measured from TEM images by averaging

11


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 12 of 24

more than 50 particles. (d) Hydrodynamic radius of PDMA35-b-P(St110-co-CEMA35) before (black) and after (red) intramolecular cross-linking, measured in CHCl3 by dynamic light scattering.

The change in hydrodynamic radius upon intramolecular cross-linking has been confirmed using DLS. The hydrodynamic radius (RH) of the linear di-BCP of PDMA35-b-P(St110-co-CEMA35) is 4.2 nm, slightly larger than that of its SCNP (2.8 nm) at a cross-linking degree of 63.9% (Figure 3d). This corresponds to the shrinkage in hydrodynamic volume of 67% upon intramolecular cross-linking. The coil radius of the linear di-BCP and SCNP can also be estimated from the scaling law, RHGPC = 1.44×10-2×Mn0.561, from GPC results in THF.58 The hydrodynamic radius for the linear di-BCP and SCNP of PDMA35-b-P(St110-co-CEMA35) was calculated to be ca. 8 and 5 nm, respectively. The hydrodynamic volume shrinkage after intramolecular collapse measured from GPC is calculated to be 76%, slightly higher than the result measured from DLS. Similar tendency was observed for P(DMA210-co-CEMA38)-b-PS190 (see Figure S4). The discrepancy in the correlation between the RH values measured from GPC and DLS is due to the fact that the tadpole-shape chains are not isotropic random coils as linear polymer chains described in the scaling law.

Electron microscopy was further used to evaluate the size of tadpole-shaped SCNPs. Figure 3 shows the representative TEM images of SCNPs prepared from PDMA35-b-P(St110-co-CEMA35). The resultant SCNPs are almost spherical with small contrast from collapsed PS blocks. The average diameter of SCNPs is 16.4 ± 3.1 nm measured from TEM images (Figure 3c). This is in agreement with the reported values for SCNPs.59

3.3 Self-Assembly of Tadpole-Shaped SCNPs from PDMA35-b-P(St110-co-CEMA35) The change in chain topology is expected to control the self-assembly nanostructures of tadpole-shaped SCNPs.43, 60-61

In view of different dimerization degrees of cinnamoyl groups in SCNPs, the collapse degree of individual

chains varies; that is, the hydrodynamic size of the “head” in tadpole-shaped amphiphiles, is controllable by crosslinking density. For example, in case of PDMA35-b-P(St110-co-CEMA35), photo-cross-linking in hydrophobic PS blocks thus leads to the formation of tadpole-shaped amphiphiles with a hydrophobic head tethered by a hydrophilic PDMA tail. The “lock-in” chain conformation of the hydrophobic block can influence the self-assembly thermodynamically by varying the interactions between polymer-solvent and polymer-polymer.62 On one hand, the collapse of the hydrophobic block can increase the polymer-solvent interaction parameter (χ). Intramolecular collapse of individual polymer chains would reduce the solvent quality since the chain segments interact intramolecularly in the collapsed state.63 When adding a selective solvent to the polymer solution, tadpole-shaped amphiphiles with a collapsed hydrophobic head would favor to assemble into micelles enthalpically. On the other hand, the collapsed hydrophobic blocks will have minimum entanglement within the core of micelles because of the intramolecularly locked topology. The entropic contribution from the hydrophobic hydration will be reduced

12


Page 13 of 24

for SCNPs. Self-collapsed polymer chains are expected to form less hydrated unimers compared to coiled linear diBCPs.64 This would decrease the entropic contribution slightly to the overall self-assembly process.

0% 30% 42% 58% 63%

Scattering Intensity (a.u.)

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

0.053 mg/mL 0.126 mg/mL -3

10

-2

-1

10 10 Polymer Concentration (mg/mL)

Figure 4. CMC measurements of the linear BCP of PDMA35-b-P(St110-co-CEMA35) and its SCNPs at different dimerization degrees. The scattering intensity is plotted as a function of polymer concentration in DMF/water (7/3, v/v).

The self-assembly of those amphiphiles can be triggered by adding water as a selective solvent to a solution of the linear di-BCP and SCNPs of PDMA35-b-P(St110-co-CEMA35) in dimethylformamide (DMF). To prepare each sample, photo-cross-linking of cinnamoyl groups was carried out at a predetermined exposure time in CHCl3. After irradiation, the dimerization degree was determined by UV-vis spectroscopy. We purified the SCNPs by precipitation in hexane for self-assembly studies. Critical micelle concentration (CMC) of linear di-BCP and SCNPs was first measured in a mixed solvent of DMF/water (7/3, v/v) in the concentration range of 0.001 to 0.5 mg/mL. The scattering intensity measured from DLS is plotted against the concentration of polymers in Figure 4. The CMC of each sample was determined by the intersection of the two tangential lines drawn through low and high scattering regions. The linear di-BCP of PDMA35-b-P(St110-co-CEMA35) has a CMC of 0.126 mg/mL. No obvious change in the CMC was seen at a dimerization degree below 30%. When further increasing the dimerization degree, the CMC of SCNPs starts to decrease. When the dimerization degree of cinnamoyl groups reaches > 40%, the CMC of SCNPs reduces to 0.053 mg/mL. The CMC also shows a minimum change even with a dimerization degree of 63%. The

13


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 14 of 24

decrease in CMC suggests that the SCNPs favor to form micelles compared to linear di-BCPs. Photo-cross-linking of cinnamoyl groups does not alter the mole fraction of the two blocks or the hydrophilic-to-hydrophobic balance of the polymer. Although self-collapsed hydrophobic PS blocks are more compacted compared to the random coil of the linear di-BCP, the segregated PS blocks in micellar aggregates are completely dehydrated and collapsed in the core of micelles. The decrease in the CMC is likely due to the change in polymer-solvent interaction where the self-collapsed PS blocks favor to segregate.63 This implies that the self-assembly of SCNPs is enthalpically driven by the hydrophobicity similar to that of surfactants.35

(a)

(b)

(c)

200 nm

(f)

(e)

(d)

200 nm

200 nm

200 nm

200 nm

200 nm

Figure 5. Representative TEM images of self-assembly morphologies for the linear di-BCP PDMA35-b-P(St110-coCEMA35) and its SCNPs at different dimerization degrees: (a) 0%, (b) 11.3%, (c) 32.3%, (d) 41.3%, (e) 57.7% and (f) 62.5%. The initial concentration of the di-BCP and its SCNPs is 1 mg mL-1 in DMF.

When fixing the molecular weight of the hydrophilic PDMA block and varying the dimerization degree of hydrophobic PS block, the morphological evolution of SCNPs was investigated in pure water. The linear BCP of PDMA35-b-P(St110-co-CEMA35) formed branched cylindrical micelles (see Figure 5a). The cylindrical micelles are uniform in diameter of 53 ± 4 nm measured from TEM images. At a dimerization degree of 11.3%, there is a minimal change in the assembled nanostructures of cylindrical micelles (Figure 5b). Y junctions and cylindrical

14


Page 15 of 24 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

loops are present.65 When the dimerization degree reaches 32%, a clear change in the micellar nanostructures is seen from TEM. Those branched cylindrical micelles are broken down to form much shorter cylindrical micelles capped with spherical micelles. When further increasing the dimerization degree to 41.3% and 57.7 %, the morphological change becomes more obvious. Cylindrical micelles are shortened, and spherical micelles become dominating at a higher dimerization degree (Figure 5d and e). When the dimerization degree reaches 62.5%, the micellar morphology changes exclusively into spherical micelles (Figure 5f).

It is interesting to point out that the average diameter of all aggregates is in the range of 50-55 nm in regardless of their nanostructures and the degree of self-collapsed (Figure S5). In other words, the dimension of assembled nanostructures is independent on the intramolecular cross-linking density of core-forming blocks. If further assuming that the segregated PS blocks are completely dehydrated in polymer micelles, the degree of self-collapse show a minimum impact on the packing state of PS blocks in micellar cores. For the linear BCP, the degree of hydrophobic PS stretching (S) can be estimated by S = R/Ro where R and Ro are the core radius of micellar aggregates and the root-mean-square end-to-end distance of PS blocks, respectively.66 Ro can be calculated based on the equation Ro = bN1/2 where b is the Kuhn length of the PS block (1.8 nm for PS) and N is the number of Kuhn monomers (N = n/6.92, n is the number of PS repeat units) in the polymer chain. 67 Ro for PDMA35-b-P(St110-coCEMA35) is calculated to be 8.2 nm. Since the diameter of cylinder micelles is close to that of spherical micelles, the stretching degree of the hydrophobic PS in all aggregates is around 3 which is in highly stretched state. Note that, the stretching degree of the self-collapsed PS blocks is slightly higher since the radius of the polymer coil would decrease after intramolecular cross-linking. This is somewhat different from the reported examples of amphiphilic BCPs where the core-formed block is usually less stretched in cylinder micelles with less curvature to increase the number of hydrophilic blocks per surface area.68 The result also suggests that self-collapsed PS blocks behave as “soft” nanospheres and can be deformed or highly stretched, like polymer random coils but unlike the “hard” tethered nanospheres reported previously.42

Then, what determines self-assembly outcomes of tadpole-shaped SCNPs when comparing to its parent linear BCP? As described in CMC results, we noted that, the CMC decreases when the dimerization degree reached > 30%. This is somewhat consistent with our observation in self-assembly where cylindrical micelles become shortened. If one considers that the hydrophobic effect of tadpole-shaped SCNPs is still identical to that of the linear di-BCP, the morphological transitions of SCNPs at various dimerization degrees is therefore driven by unfavorable interaction of collapsed hydrophobic polymer chains with solvent. The self-assembly of tadpole-shaped SCNPs occurred at a lower concentration to form spherical micelles. This morphological transition differs from earlier reports of linear BCPs where hydrophobic-to-hydrophilic ratios are fundamentally responsible for the assembled nanostructures.

15


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 16 of 24

3.4 Self-Assembly of Tadpole-Shaped SCNPs from P(DMA210-co-CEMA38)-b-PS190 The self-assembly of SCNPs can also be modulated by controlling the self-collapse degree of the hydrophilic blocks. For P(DMA210-co-CEMA38)-b-PS190, photo-cross-linking of hydrophilic PDMA blocks can result in the formation of tadpole-shaped SCNPs with a hydrophilic PDMA head tethered by a hydrophobic PS tail, resembling the molecular structure of surfactants. The “lock-in” chain conformation of the hydrophilic block will not change the thermodynamic driving force to self-assemble those amphiphiles because the hydrophobic PS tails are identical for the linear di-BCP and SCNPs if assuming the PS block does not interfere with intramolecular cross-linking of PDMA. Similarly, the CMC of P(DMA210-co-CEMA38)-b-PS190 di-BCP and SCNPs at various dimerization degrees are measured using light scattering. It is remarkable that the CMC of those tadpole-shaped SCNPs is nearly independent on the cross-linking degree of the hydrophilic head. The linear di-BCP and SCNPs show very close CMC values in the range of 0.09 to 0.1 mg/mL (Figure 6). This is indicative of the unaltered hydrophobicity of PS tails for the tendency of micellization, when carrying out the intramolecular photo-cross-linking of hydrophilic PDMA blocks.

Figure 6. CMC measurements of the linear di-BCP P(DMA210-co-CEMA38)-b-PS190 and its SCNPs at different dimerization degrees as indicated in the Figure legend. The scattering intensity is plotted as a function of polymer concentration in DMF/water (7/3, v/v).

Self-assembly nanostructures of P(DMA210-co-CEMA38)-b-PS190 at various dimerization degrees were investigated as summarized in Figure 7. Without photo-cross-linking, the linear di-BCP of P(DMA210-co-CEMA38)-b-PS190 having a long hydrophilic block favors to form spherical micelles (Figure 7a). The average size of spherical micelles is 38 ± 5 nm. Intramolecular cross-linking of the hydrophilic PDMA blocks results in the growth of micelles. At a dimerization degree of 28%, a bimodal distribution of micelles is clearly seen in Figure 7b. Small micelles are close to 40 nm similar to that of linear di-BCP micelles; while the size of larger micelles is in the range of 80-120 nm. Further increase in the cross-linking degree of hydrophilic PDMA blocks to 47%, large compound micelles are

16


Page 17 of 24 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

observed under TEM. Those large compound micelle are fairly spherical with a diameter of 309 ± 39 nm. The increase in the size of micellar aggregates is attributed to the decrease in the hydrodynamic volume of the hydrophilic PDMA blocks which causes hydrophilic/ hydrophobic imbalance. At a fixed hydrophobic block length, the reduction in the flexibility of PDMA blocks will be less hydrated as hydrophilic brushes to stabilize micelles compared to non-cross-linked ones. The shrinkage in the corona chain volume will also expose hydrophobic PS segments to water. To compensate the change in surface hydrophilicity, larger micelles with less surface curvatures are observed as seen in Figure 7b and c (also see Figure S6 for more SEM images).

Figure 7. Representative TEM images of self-assembly morphologies for the linear di-BCP P(DMA210-coCEMA38)-b-PS190 and its SCNPs at different dimerization degrees: (a) 0%, (b) 28%, (c) 47%, (d) 60.8%, and (e) 64.6%. (f) is a zoom-in image of (e) to show the irregular surface topologies of aggregates. The initial concentration of the di-BCP and SCNPs is 1 mg mL-1 in DMF.

It is interesting to note that unconventional micelles were observed at even higher dimerization degrees of PDMA blocks. For example, the formation of 1-D giant cylindrical micelles with a diameter of ~110 nm was observed at a dimerization degree of ~60% (Figure 7d and Figure S6b); while, largely irregular spherical aggregates were obtained at an even higher dimerization degree (Figure 7e). Both assemblies show non-smooth surface. 1-D giant cylindrical micelles are highly branched and capped with spherical micelles. The surface protrusions are more evident for the SCNPs at a dimerization degree of 64.6% (Figure 7f). Those irregular spherical aggregates are

17


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 18 of 24

uniform with a diameter of 408 nm (see Figure S6 for more SEM images). Their surfaces show some layered features with concaved topologies. It is currently unclear on the interior structures of those aggregates. Although we do not have good controls on the topological features of spherical micelles at current stage, intramolecular crosslinking of corona-forming blocks may open new possibility to design those micelles with defined surface topologies. We expect that these unconventional micelles with concaved surface topologies can be used in biological applications especially for cell adhesion/targeting during drug delivery. These polymer micelles with non-smooth surfaces might be potentially beneficial for improving permeability of drug delivery vehicles.69-70

4. Conclusions To summarize, we demonstrated the use of intramolecular photo cross-linking of linear di-BCPs to form tadpoleshaped SCNPs as a tool to control the outcomes of polymer self-assembly in solution. We designed two di-BCPs with photo-cross-linkable cinnamoyl groups in either hydrophilic or hydrophobic block. The intramolecular crosslinking induced by photodimerization of cinnamoyl groups resulted in the formation of tadpole-shaped SCNPs. Photodimerization of cinnamoyl groups is an efficient method to prepare SCNPs without significantly varying the chemical composition and molecular weight of di-BCPs. This allows us to compare the self-assembly of linear diBCPs and their tadpole-shaped SCNPs at different collapse degrees of head-forming blocks as a means to understand the effect of chain topology on the self-assembly nanostructures of amphiphilic di-BCPs. The linear diBCP of PDMA35-b-P(St110-co-CEMA35) self-assembled to branched cylinder micelles in water. The photo-crosslinking of the hydrophobic PS blocks led to the morphological transition to short cylinder micelles and eventually to spherical micelles at a dimerization degree above 60%. We showed that the “soft” hydrophobic head formed by the intramolecular collapse of PS blocks could be stretched as the linear PS block, since the core size of all micellar aggregates was comparable in regardless of the collapse degree of PS blocks. Self-assembly of the linear di-BCP of P(DMA210-co-CEMA38)-b-PS190 showed spherical micelles in water. We show that the self-assembly outcomes of polymers are controllable in a “stepwise” manner through intramolecular cross-linking degree of the hydrophobic head. The cross-linking of hydrophilic PDMA blocks caused hydrophilic/ hydrophobic imbalance resulting in the size increase of micelles. Unconventional micelles with non-smooth surface topologies were observed at higher dimerization degree of PDMA blocks. Those results offer insight into the rational design of assembled nanostructures of polymeric amphiphiles through a non-synthetic perspective. Tadpole-shaped amphiphiles potentially will be of interest to design non-conventional micelles with tunable surface topologies as well.

Acknowledgement J.H. is grateful for the financial support of start-up grants from the University of Connecticut and the American Chemical Society Petroleum Research Fund. The authors thank Professors Elena Dormidontova and Mu-Ping Neih for their insightful discussion on the self-assembly studies. The SEM/TEM studies were performed using the

18


Page 19 of 24 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

facilities in the UConn/FEI Center for Advanced Microscopy and Materials Analysis (CAMMA). This work was also partially supported by the Green Emulsions Micelles and Surfactants (GEMS) Center and FEI Company under an FEI-UConn partnership agreement.

References 1.

Elsabahy, M.; Wooley, K. L., Design of polymeric nanoparticles for biomedical delivery applications.

Chem. Soc. Rev. 2012, 41 (7), 2545-2561. 2.

Blanazs, A.; Armes, S. P.; Ryan, A. J., Self‐assembled block copolymer aggregates: from micelles to

vesicles and their biological applications. Macromol. Rapid Commun. 2009, 30 (4‐5), 267-277. 3.

Vriezema, D. M.; Comellas Aragonès, M.; Elemans, J. A. A. W.; Cornelissen, J. J. L. M.; Rowan, A. E.;

Nolte, R. J. M., Self-Assembled Nanoreactors. Chem. Rev. 2005, 105 (4), 1445-1490. 4.

Zhang, L.; Eisenberg, A., Formation of crew‐cut aggregates of various morphologies from amphiphilic

block copolymers in solution. Polym. Adv. Technol. 1998, 9 (10‐11), 677-699. 5.

Zhang, L.; Eisenberg, A., Multiple Morphologies of "Crew-Cut" Aggregates of Polystyrene-b-poly(acrylic

acid) Block Copolymers. Science 1995, 268 (5218), 1728-1731. 6.

Discher, D. E.; Eisenberg, A., Polymer Vesicles. Science 2002, 297 (5583), 967-973.

7.

Yue, K.; Liu, C.; Huang, M.; Huang, J.; Zhou, Z.; Wu, K.; Liu, H.; Lin, Z.; Shi, A.-C.; Zhang, W.-B.;

Cheng, S. Z. D., Self-Assembled Structures of Giant Surfactants Exhibit a Remarkable Sensitivity on Chemical Compositions and Topologies for Tailoring Sub-10 nm Nanostructures. Macromolecules 2017, 50 (1), 303-314. 8.

Miyake, G. M.; Weitekamp, R. A.; Piunova, V. A.; Grubbs, R. H., Synthesis of isocyanate-based brush

block copolymers and their rapid self-assembly to infrared-reflecting photonic crystals. J. Am. Chem. Soc. 2012, 134 (34), 14249-14254. 9.

Fenyves, R.; Schmutz, M.; Horner, I. J.; Bright, F. V.; Rzayev, J., Aqueous Self-Assembly of Giant

Bottlebrush Block Copolymer Surfactants as Shape-Tunable Building Blocks. J. Am. Chem. Soc. 2014, 136 (21), 7762-7770. 10.

Li, Z.; Kesselman, E.; Talmon, Y.; Hillmyer, M. A.; Lodge, T. P., Multicompartment Micelles from ABC

Miktoarm Stars in Water. Science 2004, 306 (5693), 98-101. 11.

Percec, V.; Wilson, D. A.; Leowanawat, P.; Wilson, C. J.; Hughes, A. D.; Kaucher, M. S.; Hammer, D. A.;

Levine, D. H.; Kim, A. J.; Bates, F. S., Self-assembly of Janus dendrimers into uniform dendrimersomes and other complex architectures. Science 2010, 328 (5981), 1009-1014. 12.

Williams, R. J.; Dove, A. P.; O'Reilly, R. K., Self-assembly of cyclic polymers. Polym. Chem. 2015, 6 (16),

2998-3008.

19


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

13.

Page 20 of 24

Schappacher, M.; Deffieux, A., Synthesis of macrocyclic copolymer brushes and their self-assembly into

supramolecular tubes. Science 2008, 319 (5869), 1512-1515. 14.

Horsch, M. A.; Zhang, Z.; Glotzer, S. C., Self-assembly of polymer-tethered nanorods. Phys. Rev. Lett.

2005, 95 (5), 056105. 15.

Zhang, Z.; Horsch, M. A.; Lamm, M. H.; Glotzer, S. C., Tethered nano building blocks: Toward a

conceptual framework for nanoparticle self-assembly. Nano Lett. 2003, 3 (10), 1341-1346. 16.

Ma, S.; Hu, Y.; Wang, R., Self-Assembly of Polymer Tethered Molecular Nanoparticle Shape Amphiphiles

in Selective Solvents. Macromolecules 2015, 48 (9), 3112-3120. 17.

Yu, X.; Zhang, W.-B.; Yue, K.; Li, X.; Liu, H.; Xin, Y.; Wang, C.-L.; Wesdemiotis, C.; Cheng, S. Z., Giant

molecular shape amphiphiles based on polystyrene–hydrophilic [60] fullerene conjugates: click synthesis, solution self-assembly, and phase behavior. J. Am. Chem. Soc. 2012, 134 (18), 7780-7787. 18.

Zhang, W.-B.; Yu, X.; Wang, C.-L.; Sun, H.-J.; Hsieh, I.-F.; Li, Y.; Dong, X.-H.; Yue, K.; Van Horn, R.;

Cheng, S. Z., Molecular nanoparticles are unique elements for macromolecular science: From “nanoatoms” to giant molecules. Macromolecules 2014, 47 (4), 1221-1239. 19.

Wang, Z.; Li, Y.; Dong, X.-H.; Yu, X.; Guo, K.; Su, H.; Yue, K.; Wesdemiotis, C.; Cheng, S. Z. D.; Zhang,

W.-B., Giant gemini surfactants based on polystyrene-hydrophilic polyhedral oligomeric silsesquioxane shape amphiphiles: sequential "click" chemistry and solution self-assembly. Chem. Sci. 2013, 4 (3), 1345-1352. 20.

Hanlon, A. M.; Lyon, C. K.; Berda, E. B., What is next in single-chain nanoparticles? Macromolecules

2015, 49 (1), 2-14. 21.

Harth, E.; Horn, B. V.; Lee, V. Y.; Germack, D. S.; Gonzales, C. P.; Miller, R. D.; Hawker, C. J., A facile

approach to architecturally defined nanoparticles via intramolecular chain collapse. J. Am. Chem. Soc. 2002, 124 (29), 8653-8660. 22.

Tao, J.; Liu, G., Polystyrene-block-poly (2-cinnamoylethyl methacrylate) tadpole molecules.

Macromolecules 1997, 30 (8), 2408-2411. 23.

Njikang, G.; Liu, G.; Curda, S. A., Tadpoles from the Intramolecular Photo-Cross-Linking of Diblock

Copolymers. Macromolecules 2008, 41 (15), 5697-5702. 24.

Seo, M.; Beck, B. J.; Paulusse, J. M. J.; Hawker, C. J.; Kim, S. Y., Polymeric Nanoparticles via Noncovalent

Cross-Linking of Linear Chains. Macromolecules 2008, 41 (17), 6413-6418. 25.

He, J.; Tremblay, L.; Lacelle, S.; Zhao, Y., Preparation of polymer single chain nanoparticles using

intramolecular photodimerization of coumarin. Soft Matter 2011, 7 (6), 2380. 26.

Zhou, F.; Xie, M.; Chen, D., Structure and Ultrasonic Sensitivity of the Superparticles Formed by Self-

Assembly of Single Chain Janus Nanoparticles. Macromolecules 2014, 47 (1), 365-372. 27.

Prhashanna, A.; Dormidontova, E. E., Tadpole and Mixed Linear/Tadpole Micelles of Diblock

Copolymers: Thermodynamics and Chain Exchange Kinetics. Macromolecules 2017, 50 (4), 1740-1748.

20


Page 21 of 24 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

28.

Langmuir

Hanlon, A. M.; Rodriguez, K. J.; Chen, R.; Bright, E.; Berda, E. B., Characterization of Single-Chain

Polymer Nanoparticles: Analytical Techniques. In Single-Chain Polymer Nanoparticles, Wiley-VCH Verlag GmbH & Co. KGaA: 2017; pp 91-138. 29.

Altintas, O.; Barner‐Kowollik, C., Single Chain Folding of Synthetic Polymers by Covalent and Non‐

Covalent Interactions: Current Status and Future Perspectives. Macromol. Rapid Commun. 2012, 33 (11), 958-971. 30.

Lyon, C. K.; Prasher, A.; Hanlon, A. M.; Tuten, B. T.; Tooley, C. A.; Frank, P. G.; Berda, E. B., A brief

user's guide to single-chain nanoparticles. Polym. Chem. 2015, 6 (2), 181-197. 31.

Mavila, S.; Eivgi, O.; Berkovich, I.; Lemcoff, N. G., Intramolecular Cross-Linking Methodologies for the

Synthesis of Polymer Nanoparticles. Chem. Rev. 2016, 116 (3), 878-961. 32.

Gonzalez-Burgos, M.; Latorre-Sanchez, A.; Pomposo, J. A., Advances in single chain technology. Chem.

Soc. Rev. 2015, 44 (17), 6122-6142. 33.

Liu, J.; Liu, G.; Zhang, M.; Sun, P.; Zhao, H., Synthesis and self-assembly of amphiphilic Janus laponite

disks. Macromolecules 2013, 46 (15), 5974-5984. 34.

Wang, X.; Yang, Y.; Gao, P.; Yang, F.; Shen, H.; Guo, H.; Wu, D., Synthesis, self-assembly, and

photoresponsive behavior of tadpole-shaped azobenzene polymers. ACS Macro Lett. 2015, 4 (12), 1321-1326. 35.

Yu, X.; Zhang, W.-B.; Yue, K.; Li, X.; Liu, H.; Xin, Y.; Wang, C.-L.; Wesdemiotis, C.; Cheng, S. Z. D.,

Giant Molecular Shape Amphiphiles Based on Polystyrene–Hydrophilic [60]Fullerene Conjugates: Click Synthesis, Solution Self-Assembly, and Phase Behavior. J. Am. Chem. Soc. 2012, 134 (18), 7780-7787. 36.

Zhang, J.; Tanaka, J.; Gurnani, P.; Wilson, P.; Hartlieb, M.; Perrier, S., Self-assembly and disassembly of

stimuli responsive tadpole-like single chain nanoparticles using a switchable hydrophilic/hydrophobic boronic acid cross-linker. Polym. Chem. 2017, 8 (28), 4079-4087. 37.

Fan, W.; Tong, X.; Farnia, F.; Yu, B.; Zhao, Y., CO2-Responsive Polymer Single-Chain Nanoparticles and

Self-Assembly for Gas-Tunable Nanoreactors. Chem. Mater. 2017, 29 (13), 5693-5701. 38.

Giacomelli, C.; Schmidt, V.; Aissou, K.; Borsali, R., Block copolymer systems: from single chain to self-

assembled nanostructures. Langmuir 2010, 26 (20), 15734-44. 39.

Wen, J.; Yuan, L.; Yang, Y.; Liu, L.; Zhao, H., Self-assembly of monotethered single-chain nanoparticle

shape amphiphiles. ACS Macro Lett. 2013, 2 (2), 100-106. 40.

Wen, J.; Zhang, J.; Zhang, Y.; Yang, Y.; Zhao, H., Controlled self-assembly of amphiphilic monotailed

single-chain nanoparticles. Polym. Chem. 2014, 5 (13), 4032-4038. 41.

Xu, F.; Fang, Z.; Yang, D.; Gao, Y.; Li, H.; Chen, D., Water in Oil Emulsion Stabilized by Tadpole-like

Single Chain Polymer Nanoparticles and Its Application in Biphase Reaction. ACS Appl. Mater. Interfaces 2014, 6 (9), 6717-6723. 42.

Li, W.; Kuo, C.-H.; Kanyo, I.; Thanneeru, S.; He, J., Synthesis and Self-Assembly of Amphiphilic Hybrid

Nano Building Blocks via Self-Collapse of Polymer Single Chains. Macromolecules 2014, 47 (17), 5932-5941.

21


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

43.

Page 22 of 24

Li, W.; Thanneeru, S.; Kanyo, I.; Liu, B.; He, J., Amphiphilic Hybrid Nano Building Blocks with

Surfactant-Mimicking Structures. ACS Macro Lett. 2015, 4 (7), 736-740. 44.

Altintas, O.; Willenbacher, J.; Wuest, K. N.; Oehlenschlaeger, K. K.; Krolla-Sidenstein, P.; Gliemann, H.;

Barner-Kowollik, C., A mild and efficient approach to functional single-chain polymeric nanoparticles via photoinduced Diels–Alder ligation. Macromolecules 2013, 46 (20), 8092-8101. 45.

Fan, W.; Tong, X.; Yan, Q.; Fu, S.; Zhao, Y., Photodegradable and size-tunable single-chain nanoparticles

prepared from a single main-chain coumarin-containing polymer precursor. Chem. Commun. 2014, 50 (88), 1349213494. 46.

Li, G.; Tao, F.; Wang, L.; Li, Y.; Bai, R., A facile strategy for preparation of single-chain polymeric

nanoparticles by intramolecular photo-crosslinking of azide polymers. Polymer 2014, 55 (16), 3696-3702. 47.

Frank, P. G.; Tuten, B. T.; Prasher, A.; Chao, D.; Berda, E. B., Intra‐Chain Photodimerization of Pendant

Anthracene Units as an Efficient Route to Single‐Chain Nanoparticle Fabrication. Macromol. Rapid Commun. 2014, 35 (2), 249-253. 48.

Hanlon, A. M.; Martin, I.; Bright, E. R.; Chouinard, J.; Rodriguez, K. J.; Patenotte, G. E.; Berda, E. B.,

Exploring structural effects in single-chain “folding” mediated by intramolecular thermal Diels–Alder chemistry. Polym. Chem. 2017, 8 (34), 5120-5128. 49.

Rodriguez, K. J.; Hanlon, A. M.; Lyon, C. K.; Cole, J. P.; Tuten, B. T.; Tooley, C. A.; Berda, E. B.; Pazicni,

S., Porphyrin-Cored Polymer Nanoparticles: Macromolecular Models for Heme Iron Coordination. Inorg. Chem. 2016, 55 (19), 9493-9496. 50.

Zhu, B.; Qian, G.; Xiao, Y.; Deng, S.; Wang, M.; Hu, A., A convergence of photo‐bergman cyclization and

intramolecular chain collapse towards polymeric nanoparticles. J. Polym. Sci., Part A: Polym. Chem. 2011, 49 (24), 5330-5338. 51.

Wang, P.; Pu, H.; Jin, M., Single‐chain nanoparticles with well‐defined structure via intramolecular

crosslinking of linear polymers with pendant benzoxazine groups. J. Polym. Sci., Part A: Polym. Chem. 2011, 49 (24), 5133-5141. 52.

Heiler, C.; Offenloch, J. T.; Blasco, E.; Barner-Kowollik, C., Photochemically Induced Folding of Single

Chain Polymer Nanoparticles in Water. ACS Macro Lett. 2017, 6 (1), 56-61. 53.

Harper, T.; Slegeris, R.; Pramudya, I.; Chung, H., Single-Phase Photo-Cross-Linkable Bioinspired

Adhesive for Precise Control of Adhesion Strength. ACS Appl. Mater. Interfaces 2017, 9 (2), 1830-1839. 54.

Fan, W.; Tong, X.; Li, G.; Zhao, Y., Photoresponsive liquid crystalline polymer single-chain nanoparticles.

Polym. Chem. 2017, 8 (22), 3523-3529. 55.

Qin, S.; Matyjaszewski, K.; Xu, H.; Sheiko, S. S., Synthesis and Visualization of Densely Grafted

Molecular Brushes with Crystallizable Poly(octadecyl methacrylate) Block Segments. Macromolecules 2003, 36 (3), 605-612.

22


Page 23 of 24 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

56.

Langmuir

Kato, M.; Ichijo, T.; Ishii, K.; Hasegawa, M., Novel synthesis of photocrosslinkable polymers. J. Polym.

Sci., Part A: Polym. Chem. 1971, 9 (8), 2109-2128. 57.

Henselwood, F.; Liu, G., Water-soluble nanospheres of poly (2-cinnamoylethyl methacrylate)-block-poly

(acrylic acid). Macromolecules 1997, 30 (3), 488-493. 58.

Pomposo, J. A.; Perez-Baena, I.; Lo Verso, F.; Moreno, A. J.; Arbe, A.; Colmenero, J., How Far Are Single-

Chain Polymer Nanoparticles in Solution from the Globular State? ACS Macro Lett. 2014, 3 (8), 767-772. 59.

Pomposo, J. A.; Rubio-Cervilla, J.; Moreno, A. J.; Lo Verso, F.; Bacova, P.; Arbe, A.; Colmenero, J.,

Folding Single Chains to Single-Chain Nanoparticles via Reversible Interactions: What Size Reduction Can One Expect? Macromolecules 2017, 50 (4), 1732-1739. 60.

Yamamoto, T.; Tezuka, Y., Cyclic polymers revealing topology effects upon self-assemblies, dynamics

and responses. Soft Matter 2015, 11 (38), 7458-7468. 61.

Chu, Y.; Zhang, W.; Lu, X.; Mu, G.; Zhang, B.; Li, Y.; Cheng, S. Z.; Liu, T., Rational controlled

morphological transitions in the self-assembled multi-headed giant surfactants in solution. Chem. Commun. 2016, 52 (56), 8687-8690. 62.

Zhang, L.; Eisenberg, A., Thermodynamic vs kinetic aspects in the formation and morphological transitions

of crew-cut aggregates produced by self-assembly of polystyrene-b-poly (acrylic acid) block copolymers in dilute solution. Macromolecules 1999, 32 (7), 2239-2249. 63.

Cheng, L.; Hou, G.; Miao, J.; Chen, D.; Jiang, M.; Zhu, L., Efficient Synthesis of Unimolecular Polymeric

Janus Nanoparticles and Their Unique Self-Assembly Behavior in a Common Solvent. Macromolecules 2008, 41 (21), 8159-8166. 64.

Shen, H.; Zhang, L.; Eisenberg, A., Thermodynamics of crew-cut micelle formation of polystyrene-b-poly

(acrylic acid) diblock copolymers in DMF/H2O mixtures. J. Phys. Chem. B 1997, 101 (24), 4697-4708. 65.

Jain, S.; Bates, F. S., On the origins of morphological complexity in block copolymer surfactants. Science

2003, 300 (5618), 460-464. 66.

Mai, Y.; Eisenberg, A., Self-assembly of block copolymers. Chem. Soc. Rev. 2012, 41 (18), 5969-85.

67.

Rubinstein, M.; Colby, R., Oxford University Press; New York: 2003. Polymer Physics.

68.

Zana, R.; Kaler, E. W., Giant micelles: properties and applications. CRC Press: 2007; Vol. 140.

69.

Massignani, M.; LoPresti, C.; Blanazs, A.; Madsen, J.; Armes, S. P.; Lewis, A. L.; Battaglia, G., Controlling

cellular uptake by surface chemistry, size, and surface topology at the nanoscale. Small 2009, 5 (21), 2424-2432. 70.

LoPresti, C.; Massignani, M.; Fernyhough, C.; Blanazs, A.; Ryan, A. J.; Madsen, J.; Warren, N. J.; Armes,

S. P.; Lewis, A. L.; Chirasatitsin, S., Controlling polymersome surface topology at the nanoscale by membrane confined polymer/polymer phase separation. ACS Nano 2011, 5 (3), 1775-1784.

23


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

Table of Contents

The use of intramolecular cross-linking chemistry as a tool to control the self-assembly of amphiphilic di-block copolymers is demonstrated.

24


Page 24 of 24

Controllable Self-Assembly of Amphiphilic Tadpole-Shaped Polymer

Recommend Documents