Synthesis of Polymers and Polymer Brushes Through Raft Polymerization Via Flow Chemistry

SYNTHESIS OF POLYMERS AND POLYMER BRUSHES THROUGH RAFT POLYMERIZATION VIA FLOW CHEMISTRY

PIAORAN YE

Submitted in partial fulfillment of the requirements for the degree of

Master of Science

Macromolecular Science & Engineering

CASE WESTERN RESERVE UNIVERSITY

May, 2017 CASE WESTERN RESERVE UNIVERSITY SCHOOL OF

GRADUATE STUDIES

We hereby approve the thesis/dissertation of

Piaoran Ye candidate for the degree of Master of Science*.

Committee Chair

Dr. Rigoberto C. Advincula

Committee Member

Dr. Lei Zhu

Committee Member

Dr. Jon Pokorski

Date of Defense

03/31/2017

*We also certify that written approval has been obtained for any

proprietary material contained therein.

ii List of Contents

List of Contents ...... iii

List of Tables ...... v

List of Figures ...... vi

Acknowledgement ...... x

Abstract ...... xi

Chapter One Introduction ...... 1

1.1 Controlled radical polymerization ...... 1

1.2 Synthesis of polymer brushes via CRP ...... 5

1.3 Polymerization in continuous system ...... 17

1.4 “graft from” or “graft onto” strategy in continuous system ...... 21

1.5 Objective ...... 26

References ...... 28

Chapter Two Highly-Efficient RAFT Polymerization in Ethanol/Water via Flow Chemistry

...... 42

iii 2.1 Experimental section ...... 42

2.2 Results and discussion ...... 46

References ...... 61

Chapter Three Continuous Fabrication of Polymer Brushes Grafted Silica Microparticles and Block Copolymers ...... 65

3.1 Experimental section ...... 65

3.2 Results and discussion ...... 73

References ...... 91

Chapter Four Conclusions and Future Work ...... 92

4.1 Conclusions ...... 92

4.2 Future work ...... 93

Bibliography ...... 95

iv List of Tables

Table 2.1. Comparative RAFT polymerization in flow reactor and batch reactor ...... 48

Table 2.2. k and half-life of ACVA in water at different temperatures ...... 53

Table 3.1. Molecular weight and molar mass dispersity of polymers cleaved from silica microparticles ...... 80

v List of Figures

Figure 1.1. General Mechanism for ATRP11 ...... 2

Figure 1.2. Mechanism of NMP16 ...... 3

Figure 1.3. General steps of the RAFT CTA processes occurring in dithioester-mediated radical polymerization22 ...... 5

Figure 1.4. Example of “graft onto” and “graft from”30 ...... 6

Figure 1.5. Surface initiated RAFT polymerization via (A) initiator attachment (B) CTA attachment ...... 12

Figure 1.6. Silica-supported RAFT CTAs. The X can be H, OMe, OEt, or OSi54 ...... 14

Figure 1.7. Comparison between (A) conventional ATRP from surface and (B) novel

“grafting-through” strategy56 ...... 16

Figure 1.8. Scheme of a separation column used for modification84 ...... 23

Figure 1.9. Scheme and mechanism of cerium catalyzed polymerization in the PDMS column. (A) Oxidation of the PDMS column. (B) Mechanism of free radical generation by cerium catalyst. (C) Polymerization of 2-acrylamido-2-methylpropanesulfonic acid

(AMPS)84 ...... 24

vi Figure 2.1. Scheme of the instruments and experiment process ...... 45

Figure 2.2. 1H NMR spectrum of 2-(((butylthio)carbonothioyl)thio)propanoic acid .. 47

Figure 2.3. FT-IR spectra of (A) PEGMEMA300, (B) raw product after polymerization (sample

5) and (C) purified product (sample 5) ...... 54

Figure 2.4. 1H NMR spectrum of (A) raw product before purification (sample 5), (B) all of the samples before purification ...... 55

Figure 2.5. 1H NMR spectrum of the polymers synthesized at 100 °C via flow reactor56

Figure 2.6. GPC trace of sample 10 ...... 60

Figure 3.1. Scheme of the closed circular flow system ...... 68

Figure 3.2. Scheme of the grafting poly(PEGMEMA)-b-PNIPAM from silica microparticles process ...... 70

Figure 3.4. FT-IR spectrum of CTA modified silica microparticles and pristine silica microparticles ...... 75

Figure 3.5. FT-IR spectrum of silica microparticles grafted by poly(PEGMEMA) within different flow time ...... 76

Figure 3.6. Silica microparticles grafted by poly(PEGMEMA) within different flow time77

vii Figure 3.7. TGA results of (A) samples prepared within different flow time and (B) different monomer concentration ...... 79

Figure 3.8. GPC traces for polymer brushes synthesized with (A) different flow time and

(B) monomer concentration ...... 80

Figure 3.9. SEM images of (A) pristine silica, (B) silica grafted by poly(PEGMEMA) within 3 h, (C) silica grafted by poly(PEGMEMA) with 0.5 h ...... 82

Figure 3.10. FT-IR spectrum for (A) poly(PEGMEMA) (grafted witn 2.5 h)and poly(PEGMEMA)-b-PNIPAM, (B) zoom-in spectrum of the range for wavenumber between

1300 to 1400 cm-1 ...... 83

Figure 3.11. TGA results for poly(PEGMEMA) (grafted within 1 h) and poly(PEGMEMA)-b-

PNIPAM ...... 84

Figure 3.12. NMR spectrum of (A) cleaved poly(PEGMEMA) (grafted within 2.5 h), (B) cleaved poly(PEGMEMA)-b-PNIPAM ...... 85

Figure 3.13. GPC traces for cleaved poly(PEGMEMA) (grafted within 1 h) and poly(PEGMEMA)-b-PNIPAM ...... 86

Figure 3.14. Static water contact angles of silica microparticles grafted by polymers under different conditions. (A) sample grafted by poly(PEGMEMA) with 0.24 M in 1.5 h. (B)

viii sample grafted by poly(PEGMEMA) with 0.8 M in 0.5 h. (C) sample grafted by poly(PEGMEMA) with 0.8 M in 3 h. (D) sample grafted by poly(PEGMEMA)-b-PNIPAM tested at room temperature. (E) sample grafted by poly(PEGMEMA)-b-PNIPAM tested at

60 °C ...... 88

Figure 3.15. Gelation happened in batch reactor ...... 90

Acknowledgement

First of all, I thank my advisor, Professor Rigoberto Advincula, for his guidance. During my master project, he has shared his experience and knowledge with me and also provided technical support. Also, I would like to thank my mentor, Dr. Pengfei Cao, who constantly instructed me in my research work and writing skills during his busy postdoctoral periods.

I also want to extend my thanks to Qiyi Chen, Al de leon, Joey Mangadlao, Katrina

Pangilinan, Brylee Tiu, Zhe Su, Yunhui Yan, Lihan Rong, Jin Ge and other group members for their selfless support and help. Last but not least, I would like to thank my family.

Thanks for their support all the way. Without it I would not go so far here.

x Synthesis of Polymers and Polymer Brushes through RAFT Polymerization via Flow Chemistry

Abstract

PIAORAN YE

Firstly, a commercial flow reactor was used to synthesize poly(PEGMEMA) via RAFT polymerization. The tunable pressure makes it possible to conduct polymerization at high temperature in aqueous solution. Compared with the same reaction in conventional batch reactor, this flow system can lead to higher polymerization efficiency. The flow rate and initiator concentration were also well studied to tune the monomer conversion and the molar mass dispersity (Ð) of the obtained polymers. Poly(PEGMEMA) and poly(PEGMEMA)-b-PNIPAM brushes were also grafted from the silica microparticles by such continuous system at high temperature with increased pressure. The flowing nature makes it possible to conduct multi-step reactions with simple purification process which saves time and cost. TGA, FT-IR, SEM were utilized to characterize the polymer modified microparticles. GPC and NMR were also used to measure the brushes cleaved from particles.

Chapter One Introduction

1.1 Controlled radical polymerization

Controlled radical polymerization (CRP) has been paid much attention and developed for many years. Different from the conventional free radical polymerization, CRP in typical cases owns unique properties, such as low molar mass dispersity and controlled molecular weight, which belong to living polymerization. As one kind of living polymerization, CRP usually needs an agent containing the functional group which can keep active during the polymerization and turned into hibernation once the reactions finish. Since the dormant species remain the ability to grow again, the CRP becomes a popular candidate, being used to synthesize homo and block copolymers with different architectures such as hyperbranched polymers, dendrimers, star-like polymers, etc.1-10 Comparing with ionic polymerization, another well-known branch of living polymerization, the CRP usually needs more mild conditions and thus becomes easier to work with. There are three major types of CRP, which are named atom transfer radical polymerization (ATRP), nitroxide- mediated polymerization (NMP) and reversible addition-fragmentation chain transfer

(RAFT) polymerization.

ATRP utilizes the alkyl halide (to be as initiator) and metal complex to complete the 1

atom transfer process which can lead to the well-defined molecular weight of polymers

(Figure 1.1).11 The metal complex, also known as the catalyst, can contain Cu, Fe, Ni, etc.

When in the presence of the initiator and the metal complex, the equilibrium which generates the free radicals can be formed. Matyjaszewski et al. reported the first ATRP in

1995.12 By utilizing l-phenylethyl chloride (1-PECl) as the initiator, CuCl as the catalyst, and

2,2'-Bipyridine (bpy) as the ligand, polymerization of styrene was completed at 130 °C with narrow molar mass dispersity lower than 1.5. The linear kinetic plot (number average molecular weight versus monomer conversion) shows the well-controlled living polymerization was achieved.

Figure 1.1. General Mechanism for ATRP11

Further studies focusing on different kinds of monomers, initiators (either chloride or bromide compounds), different reaction environment (either organic systems or aqueous 2

systems), and different species of ligand (like bpy, dNbpy, PMDETA, Me6TREN, etc.) have been studied in the recent years.13-15

Instead of using metal complex, NMP, as another kind of CRP, usually uses alkoxyamine to obtain the living nature. The persistent radical effect during NMP can result in a dynamic equilibrium between dormant species and propagation process (Figure

1.2), which is a sign of living radical polymerization.16 2,2,6,6-Tetramethyl-1-piperidinyloxy

(TEMPO) is a well-known structure that works for NMP, while other structure, such as

1,1,3,3-tetraethylisoindolin-N-oxyl and di-t-butyl nitroxide, also serves NMP well and even has higher efficiency.17

Figure 1.2. Mechanism of NMP16

As for RAFT polymerization, it was firstly reported by CSIRO in 1998.18 Chain transfer agent (CTA) is a unique presence for RAFT polymerization to control the polymerization.

Dithiobenzoates was firstly used for most RAFT polymerization. Trithiocarbonates, a more

hydrolytically stable species than dithiobenzoates, was then also developed and used, which gives more possibility on architecture design because either one or two homolytic leaving groups can be attached to the trithiocarbonate group.19 Different from ATRP and

NMP, in the most cases, RAFT polymerization needs external initiator (like AIBN) which may cause the termination, especially when the concentration is high. Though there are some reports about RAFT polymerization without initiator under UV irradiation or high temperature, the polymerization efficiency always becomes low.20-21 During the polymerization, once the free radical attacks the CTA, the R group containing free radical, which can attack other monomers and connect back to CTA to establish the equilibrium, will be cleaved from the CTA. Chain propagation can be finished within such equilibrium process (Figure 1.3).22 For different kinds of monomers, different Z group of CTA will lead to different chain transfer rate which is a critical parameter for RAFT polymerization. With high chain transfer rate, the target product can be approached with narrow molar mass dispersity as well as the high polymerization efficiency.23 Meanwhile, the relative leaving group ability of R radical group, as well as the propagating radical group formed during the polymerization, also has the strong influence of the transfer coefficient and can also determine the polymerization efficiency.24 The controllable feature also contributes RAFT polymerization an excellent tool to construct polymers with particular structure for variable applications.

Figure 1.3. General steps of the RAFT CTA processes occurring in dithioester-mediated radical polymerization22

1.2 Synthesis of polymer brushes via CRP

Thin polymer films on different substrate always play important roles including anti- corrosion, anti-fouling, smart response, lubrication, and etc.25-29 To simply fabricate the polymer films, physical methods like spin coating, dip coating, and spray coating are usually applied to the substrate. However, weak physical interaction, which makes coatings easily to be damaged and peeled from the surface, limits the applications of those polymer films. Furthermore, those three kinds of strategies also have the limitation on substrate’s shape. When small particles or granules are potential targets for the coatings, the operation of these three strategies becomes a little bit difficult. Therefore, chemical modification is desired for functionalization of particles or other substrates.

In most conditions, two strategies, named “graft onto” and “graft from”, for chemical modification to fabricate the polymer brushes on the substrate’s surface are utilized.

“Graft onto” means grafting the existing polymer chains onto modified substrate with forming new chemical bond (Figure 1.4). Due to the nature of this method, which means the existing chains have the relatively larger steric hindrance than monomers, there will be some activated groups that are not grafted with the polymer chains. Hence, normally, the chain density of this method cannot be as high as “graft from” methods.

“Graft from”, on the other hand, usually performs a higher chain density compared with the “graft onto” strategy. Under these circumstances, various kinds of initiators or other functional groups (carbon-carbon double bond, thioester, etc.) will firstly be immobilized onto the surface of the substrate. Then, the polymerization will be conducted directly with monomers under proper conditions.

Figure 1.4. Example of “graft onto” and “graft from”30

In recent years, CRP becomes one of the most important ways to construct brushes with well-defined structure and properties. ATRP, NMP, and RAFT polymerization have all been chosen considering of different conditions and special experimental requirements.31-35

1.2.1 Synthesis of polymer brushes via “graft onto”

The “graft onto” method is a more straightforward route for modifying substrate by polymer brushes. It is well-known that different substrate has different nature which may bring some limitations to the grafting process, especially for some nanoparticles. For example, the gold nanoparticles (AuNPs) are not stable and sensitive to impurities and temperature.36 When dealing with “graft onto” strategy, the polymer chains are firstly synthesized without nanoparticles. Therefore, there is no need to care about the nanoparticles, and the conditions for synthesis can be much more flexible. Consequently, the polymer types and structure can be more complex and diverse.

Several approaches, including esterification, silanation, etc., can be used for “graft onto” strategy. Such methods have been used to immobilize different polymers onto functionalize substrates such as graphene oxide, silica nanoparticles, silica wafer, etc.37-39

However, such conventional reactions always require strict conditions or long reaction 7

time and usually have relatively low efficiency. In recent years, “click” chemistry becomes the other method working well with the “graft onto” strategy. The “click” chemistry is the term describes a series of reactions which can join small units together quickly and reliably.40 The most common and popular “click” reactions are azide-alkyne Huisgen cycloaddition and thiol-ene/thiol-yne reactions.

For azide-alkyne “click” reaction, a copper catalyst is always used to link the azide and carbon-carbon triple bond together with forming pentagonal ring containing three nitrogen atoms at room temperature.41 For example, by using 3- bromopropyltrichlorosilane functionalized silica particles and an alkyne functionalized

RAFT CTA, Brittain et al. successfully grafted the polystyrene (PS), poly(methyl acrylate)

(PMA), and poly(PS-b-PMA) onto the silica’s surface.42 By utilizing ATRP and “click” reaction, Krzysztof Matyjaszewski et al. synthesized well-defined block copolymers and grafted them onto the substrate.31 In this case, after the ATRP, the bromide on the chain end was converted to azido group with the help of sodium azide, which can be further used for coupling with another chain containing alkyne group. However, due to the well- known safety issue of the azido group, the applications of azide-alkyne “click” reaction are limited.

Thiol-ene/thiol-yne is another popular “click” reaction which provides a much safer

method. For thiol-ene reaction, free radical and Michael addition are two different mechanisms that can be utilized, which make “click” reaction more flexible and optional for realistic applications.43 Since RAFT CTA contains thioester group which can be reduced to thiol group by primary amine, polymers synthesized by RAFT polymerization become suitable candidates for thiol-ene/thiol-yne reactions.44

While “graft onto” strategy provides the flexible approach to get polymer brushes with well-defined structure and functions, due to the steric resistance, in particular for polymers with large molecular weight, one main disadvantage for it is the low grafting density. Therefore, it is desired to develop a method which can bring higher grafting density for polymer brushes.

1.2.2 Synthesis of polymer brushes via “graft from”

On the contrary, do not like the “graft onto”, “graft from” provides the possibility to synthesize polymer brushes with higher grafting density. For CRP, the most important step of “graft from” strategy is anchoring carbon-carbon double bond, alkyl halides initiators, chain transfer agents, or alkoxyamine initiators onto the surface of substrate.

The initiators for ATRP are always alkyl halides like alkyl bromides or alkyl chlorides.

One of the primary methods of anchoring is to utilize the hydroxy groups and silane molecules, which is similar to the methods mentioned above.45-47

One of the early examples of “graft from” via ATRP was reported by Timothy E. Patten et al. in 1999.48 By using (2-(4-chloromethylphenyl)ethyl)dimethylethoxysilane (CDES) as the initiator, the polystyrene was grafted from the surface of the nanoparticles in the solvent of ethanol. After the polymerization, the TEM images for nanoparticles prove that the distance between nanoparticles within the domains increased from 10 nm to 40 nm.

One thing important is that the GPC analysis of the cleaved polymer chains shows the dispersity of those grafted polymers can be narrowed down to 1.24 which is not a big difference from the polymers obtained by solution polymerization. In fact, it has been indicated that when polymerizing from the surface of the substrate, the CRP can work well as well as in the solution.49 Being able to re-polymerize and form block copolymers is another essential indication of living polymerization. To further demonstrate the living feature of the “graft from” via ATRP, Matyjaszewski et al. synthesized poly(styrene-b-tert- butyl acrylate) from the silicon surface.50 Eva E. Malmstro ̈m et al. also synthesized poly(methyl acrylate-b- hydroxyethyl methacrylate) from the cellulose fibers via ATRP.34

One advantage of utilizing ATRP for “graft from” strategy is the high conversion of the monomers for grafting process. Since no external initiator is needed for ATRP, all of the

monomers can only be attached to the ATRP initiator on the surface. Therefore, theoretically, nearly all of the polymers can only propagate from the surface. On the other hand, for RAFT polymerization, due to the external initiator and the heterogeneous reaction, it is inevitable to have some free radical polymerizations in solution which can be severe when the concentration of monomer and initiator are high. This competition reaction will waste the monomer and sometimes even prevent the “graft from” due to the gelation of the mixture.

NMP is also a major CRP used for “graft from” method. By tethering the NMP initiator onto the substrate’s surface, the NMP can serve for “graft from” strategy as well.

Beyou et al., in 2003, reported that they successfully generated the core-shell structure nanoparticles by using NMP and “graft from” method.51 The styrene-BEPN was firstly prepared by using an alkoxyamine (DEPN), and then, the styrene-BEPN was connected with a silane molecule for further attachment. After these, the NMP initiator based silane was grafted onto the silica’s surface, which was followed by further polymerization steps under standard NMP conditions.52

Different from the ATRP and NMP, RAFT polymerization employs conventional initiators such as azobisisobutyronitrile (AIBN) and benzoyl peroxide (BPO). Therefore, for the surface-initiated RAFT (SI-RAFT) polymerization, two different approaches named

initiator attachment and CTA attachment are usually used for RAFT polymerization synthesizing polymers from surface (Figure 1.5).

Figure 1.5. Surface initiated RAFT polymerization via (A) initiator attachment (B) CTA attachment

Marina Baum et al. firstly introduced a surface-initiated method for RAFT polymerization from silicate substrate.53 A silane-modified azo-type initiator was firstly immobilized onto the substrate which would then be used for “graft from” in the presence of free CTA and initiator. Due to the selective effect between CTA and monomers and the feed ratio between CTA and initiator, the polymers synthesized by altered monomers shows different molar mass dispersity varies from 1.10 to 1.72. At the same time, sequenced diblock copolymers, PS-b-PDMA and PDMA-b-PMMA, was also synthesized

from the substrate’s surface by using the substrate-initiator. The uniform growth of the polymer films for both the homopolymers and the diblock copolymers shows a linear chain growth from the side. Though using of initiator modified substrate is an effective way to approach “graft from” via RAFT polymerization, the conditions of preparation, the storage are always strict due to the nature of the initiator, which may cause some limitations. Therefore, anchoring of the RAFT CTA becomes an altered approach to modify the substrate. When SI-RAFT is carried out for “graft from” strategy, both R group attachment or Z group attachment can be utilized, which have a slightly different propagation process due to the mechanism of RAFT polymerization.54

As one of the most common materials, silica substrate including silica wafer and particles with different size has been widely used to prepare CTA modified substrate. Due to the large amount of hydroxyl group on the surface, a series of functionalized silane can be used to modify the surface. The RAFT CTA can be connected to the silane either before the silanation or after the silanation of the substrate. Also, the connection between silane and RAFT CTA can be achieved by esterification, amidation, as well as the “click” reactions mentioned above. A number of silica-supported RAFT CTAs for “graft from” strategy have been reported (Figure 1.6).

Figure 1.6. Silica-supported RAFT CTAs. The X can be H, OMe, OEt, or OSi54

It has been mentioned that when RAFT polymerization was used for “graft from” strategy, free initiators are always needed which may lead to potential problems especially when the polymerization is conducted at high temperature with high concentration of initiator and monomer. However, according to the mechanism, high concentration is benefitted for improving the efficiency. In order to overcome this and to satisfy the result,

Kohji Ohno et al. added some free RAFT CTA into the mixture to help control the polymerization in solution. Though the free RAFT polymerization in solution is also a competitor for the SI-RAFT polymerization, it can contribute to exchange the reactions between free polymerization in solution and “graft from” polymerization on substrate.55

As a consequence, the polymers grafted from the nanoparticles’ surface have larger molecular weight and narrower molar mass dispersity than the free polymers in solution. 14

And the grafting density can be as high as 0.3 chains/nm2.

Although most of “graft from” brings higher grafting density than “graft onto”, there is also a potential risk which might cause the brushes less uniform, especially when flat substrate is used, and the designed chain length is long. During the grafting process, all chains are supposed to grow from the bottom to the top and have the same propagation rate. However, in fact, there are always some differences between different chains and make the chain length a little bit different. As a result, the longer chains will have higher chance to meet with monomers and grow faster. Consequently, the longer chains will entirely cover the shorter chains due to the chain expansion and the shorter chains will stop grow even if there is no conventional termination of the polymerization. This phenomenon will not only appear in SI-RAFT polymerization but also can be found in SI-

ATRP and SI-NMP.

To improve this defect, Douglas H. Adamson et al. developed a novel method for

“graft from” strategy which is named “grafting-through”(Figure 1.7).56 To demonstrate their ideal, ATRP initiator was attached to the wall of dialysis tube. The monomers were packed inside the tube. During the dialysis process, the monomers would penetrate the tube and meet the initiator. Therefore, all of the initiators would have chance to react with the monomers. Once there was chain length difference, those shorter chains would have

higher chance to meet monomers and grow faster. By using this continuous-like method, much more uniform polymer brushes were fabricated. Further simulation result also approved their result.

Figure 1.7. Comparison between (A) conventional ATRP from surface and (B) novel “grafting-through” strategy56

Additionally, when “graft from” strategy is employed for synthesis of polymer brushes, another potential problem can be found especially when small particles are used as the substrate. During the grafting process, between every step, a purification procedure is always needed in order to remove any free molecules. Especially when micro- or nanoparticles are selected as the substrate, the washing procedure can take even longer

time which including washing and filtration/centrifuging processes. When sequenced block copolymers are aimed, such purification can drastically increase the time and cost.

Therefore, further research is desired to improve the “graft from” strategy.

1.3 Polymerization in continuous system

Most of the conventional reactions are conducted in a batch reactor like the round bottom flask. However, several disadvantages limit the applications of the batch reactors.

For a certain batch reactor, there is a maximum volume of the reagent for every batch.

Therefore, to increase the output, reactions from batch to batch are needed unless larger reactor is selected. The interval and washing between batch to batch will then waste time and increase the cost which is critical for industrial production. Meanwhile, another significant shortcoming for batch reactor is the poor thermal transmission. The larger a batch reactor is, the lower specific surface area it will have. And the low specific surface area will consequently lead to weak heat transfer efficiency even if the material is a good thermal conductor.

When we are talking about poor thermal transmission, usually, here are two aspects we are meaning. The first aspect is the heating process. The poor thermal transmission will make the time very long for solution to reach the destination temperature. In addition, 17

during the heating process, the temperature of the solution from center to outer ring can varies which makes the reaction inhomogeneous and decrease the efficiency, though stirring can improve this phenomenon. Secondly, during the reaction, most of the reaction is exothermic. Poor thermal transmission would make the reactor lose control of the temperature which may bring negative effect to the reactions. When polymerization is conducted, high viscosity and exothermic effect will generate “hot spots” in the solution and make the polymerization out of control.57 The burst polymerization and gelation can also happen under such conditions and may even cause damage when the reagent volume is large.

In addition, the most of the conventional reactors in lab, like glass round bottom flask, cannot tolerate high pressure which also limits the application for many reactions which require a high pressure. Furthermore, like mentioned in the last section, when solid particles need to be modified in solution, there is always additional purification process between every step for batch reactors. Therefore, it is desired to develop a strategy rather than batch approach to overcome all of the limitation caused by batch reactors.

Recently, using flow reactor and microfluidic system for synthesis applications has been attracting significant attentions. Generally, there are two types of continuous system.

The first type of continuous system can be fabricated on a polydimethylsiloxane (PDMS)

plate. It is a flexible method to fabricate the continuous system since the path of the reaction region can be designed in order to meet the specific demands of the experiment.

Many of the microfluidic systems were formed by using this method.58 Another kind of continuous system utilizes coil-like or tubular container as the reaction region. Coil with different length made by various materials like stainless steel and Teflon can be easily changed for different conditions. For both of the continuous systems, the reaction region is thin tubes or channels with inner diameter varies from several millimeters to micrometers. Due to the small diameter, the specific surface area can reach high and lead to high thermal transmission. Therefore, more homogeneous products are supposed to be produced through those thin tubes. The thin tubes of the flow reactor also contribute to the facile control of reaction temperature and safe operation process.59-60 The continuous feature is also valuable for industrial productions because saving of the intervals between the two batches of production will increase the production efficiency and reduce the manufacturing cost.61 Theoretically, larger amount of product can be produced just by simply prolonging the time or adding parallel tubes. Moreover, for some continuous system, it is also feasible to control the pressure during the reaction.

Considering these superiorities, many organic reactions, as well as polymerization, were already successfully carried out in different kinds of continuous flow systems.62-65

Due to the advantages of flow system, in recent years, an increasing number of 19

studies that using flow system synthesize polymers via controlled polymerization including

CRP, cationic polymerization, and anionic polymerization have been reported.66-69 Most of the studies have demonstrated that flow system possesses the better capability to synthesize well-defined polymers with narrow molar mass dispersity in a short period.

Hideaki Maeda et al. successfully carried out the polymerization of N-carboxy anhydrides in a PTFE tubular reactor with the assistance of a PDMS micromixer.70 Compared with the reactions in batch reactor under the same conditions, this tubular reactor can synthesize polymers with much lower dispersity. Due to the short resistance period and small volume of reaction region, Thomas Junkers et al. even performed cationic polymerization at up to

180 °C.67 The conversion can reach near 100% within just several minutes, which makes it possible to synthesize block copolymers in short period without purification. Meanwhile, the dispersity of the block copolymers can still be kept lower than 1.3. For free radical polymerization, Takeshi Iwasaki and coworkers even tried to keep the system running for several days to produce polymers with stable molecular weight and molar mass dispersity

(Ð), which exhibited great potential for industrial productions.71 When it comes to CRP,

Thomas Junkers et al. reported using both tubular reactor and glass-chip based microreactor to synthesize PMA via ATRP.72 At 15 °C, approximately 90% monomer conversion can be reached within 20 mins under UV irradiation. Meanwhile, the obtained polymers have low molar mass dispersity in the range of 1.1. The kinetic study also

showed linear growth of the polymers during the polymerization. Christian H. Hornung et al. have reported the synthesis of both homopolymer and block copolymers via RAFT polymerization in a continuous system.73-75 Moreover, “click” reaction and photo-initiated

RAFT polymerization was also successfully performed in the flow systems.76-78 They also used continuous flow processing to perform RAFT polymerization of acrylic acid in large scales (up to 90 grams) with stable properties.79 Our group also studied using a commercially available flow reactor to synthesize polymers in aqueous environment via

RAFT polymerization at high temperature,80 which will be discussed in detail in the next chapter.

1.4 “graft from” or “graft onto” strategy in continuous system

There are already some examples using continuous system to functionalize substrate by, but not limited to, “graft from” and “graft onto” strategy. PDMS is a low-cost, non-toxic material used for fabrication of microfluidic instruments which have further potential for biological applications such as sorting of cells, electrophoresis separation of biomolecules, and so on.81-82 However, the hydrophobic property of the PDMS’s surface becomes the issue for such applications. Moreover, due to the adsorption of biomolecules, the original

PDMS can only give poor resolution for the separation and may lose separation efficiency

after being used for several times. Therefore, it is required to get surface modified PDMS with hydrophilic property for such biological applications.

Immersing the PDMS microfluidic instrument into monomer or polymer solution is a possible method to reach the modification target. Nancy Allbritton et al. described a UV irradiation assisted method which can be used to functionalize the microfluidic chips.83

The PDMS microfluidic chips were immersed into a solution which contained the monomers. When UV was applied to the system, the hydrogen would leave the methyl group on silicon atom and form a free radical which can attack the monomers to start the

“graft from” process. However, one potential problem with this method is that the most parts which do not need to be modified will also be grafted. This can increase the cost. As a consequence, only modification of the channels by continuous or segmented method become the feasible methods.

Fred E. Regnier et al. described using a segmented method to modify PDMS separation columns.84 After fabrication and oxidation the chips and finishing the sealing process, which converted the methyl group to hydroxyl group on PDMS’s surface, the solution which contained monomer, catalyst (ammonium cerium nitrate), nitric acid, and solvent was placed into the well of the instrument. The capillary action would then drive the solution to fill all of the channels with 5 µm width. The cerium catalyzed

polymerization can be finished (Figure 1.8 and 1.9). After the grafting, 1 mM carbonate buffer was pumped to wash the channels.

Figure 1.8. Scheme of a separation column used for modification84

Besides the “graft from”, “graft onto” was also employed to modify PDMS’s surface.

Hong-Yuan Chen et al. reported a “graft onto” method for modification of PDMS channels.85 Firstly, they pumped the chitosan solution (pH=6.0, 0.01%, w/v) to pass through the PDMS channel. After keeping flow for 5 mins, a chitosan film could be formed on the channel’s surface. Due to the abundant amine group on chitosan, (O-[(N- succinimdyl)succiny]-o’-methyl-poly(ethylene glycol) was chosen to be pumped into the channel to be grafted onto the chitosan film by amidation reaction. The “graft onto” process was kept for 4 hours at room temperature. After the modification, the hydrophilic

PDMS channels performed good ability to keep stable of electroosmotic flow (EOF) and suppress adsorption of biomolecules.

In-channel ATRP was also utilized to modify the surface of the poly(glycidyl methacrylate)-co-(methyl methacrylate) (PGMAMMA) microfluidic devices, which was reported by Milton L. Lee group.86 The oxidized PDMS channel was firstly functionalized by the 2-bromoisobutyryl bromide which could perform as the initiator for ATRP. The methyl methacrylate (MMA) and MMA-like monomers were then pumped to flow through the channel with the flow rate of 0.5 µL min-1. After modification by monomer solution, the modified channel can be simply flushed by deionized water to remove any unreacted monomer and residual catalyst and ligand. The authors also declared that besides the low EOF and resisted protein adsorption, the in-channel ATRP modification also brought better long-term stability comparing with previous ATRP modification.

Another existent application of the continuous method for grafting is the modification of the monolith. Due to the complex structure, the conventional grafting reaction in batch reactor is tough to modify all of the monolith’s surface thoroughly and homogeneously.

Therefore, using flow method becomes an ideal approach to functionalize the monolith.

Lanqun Mao et al. reported a two-step method to get brushed functionalized poly

(ethylene glycol dimethacrylate) (PEDMA) monolith.87 Since the monolith was synthesized by ATRP method, the bromide group on its surface can be utilized for further modification.

2-(Dimethylamino) ethyl methacrylate (DMAEMA) was chosen as the monomer to finish

the “graft from” process. The polymerization was conducted for 7 h at 35 °C with the flow rate of 3 mL h-1. As a continuous method, simply flushing by using solvent can remove the unreacted monomers and ligand quickly. Prolonging the flow time is supposed to give longer chains on the surface so that the polymer films should have higher retention factor which has been approved in the literature. In addition, due to the PDMAEMA, pH-sensitive properties of the monolith can also be observed after the modification.

1.5 Objective

The goal of this study is to develop a continuous method to synthesize polymers and graft polymer brushes from silica microparticles via RAFT polymerization. With the help of high pressure, the reaction temperature can reach a high level which should increase the efficiency of the polymerization. The free RAFT polymerization will be conducted in aqueous solution to demonstrate the potential advantages, especially for the high efficiency caused by high temperature, of polymerization in this system.

For grafting polymers from microparticles, the silane-modified RAFT CTA will be synthesized in order to complete the “graft from” process on silica microparticles’ surface.

Poly(ethylene glycol) methyl ether methacrylate (PEGMEMA) will be polymerized from the silica’s surface under different conditions including different flow time and monomer 26

concentration, which is supposed to provide the possibility to control the polymer brushes grafted from the surface. To further demonstrate the “living” property, poly(PEGMEMA)- b-poly(N-isopropylacrylamide) will also be synthesized without complicated purification, which should be another major advantage of the continuous system. This method may also provide an easier approach to synthesize sequenced block copolymers.

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Chapter Two Highly-Efficient RAFT Polymerization in Ethanol/Water

via Flow Chemistry

2.1 Experimental section

2.1.1 Materials

Flow reactor (Phoenix Flow Reactor) equipped with an 8 mL stainless steel loop (1mm inner diameter), which works with an HPLC pump and a Valve Module, was supplied by

ThalesNano Nanotechology Inc. 1-Butanethiol (99%), carbon disulfide, Poly(ethylene

glycol) methyl ether methacrylate (PEGMEMA, Mn=300,) and 4,4’-Azobis(4-cyanovaleric acid) (ACVA, >=98%) were purchased from Sigma-Aldrich. 2-Bromopropionic (98%) was purchased from Alfa Aesar. NaOH was purchased from Fisher Scientific. HCl solution was purchased from BDH. Anhydrous ethanol was purchased from Millipore. Deionized (DI) water was produced by Milli-Q water system.

2.1.2 Measurements

The conversion of monomer and the degree of polymerization (DPn) for the polymerization was characterized by 1H nuclear magnetic resonance (1H NMR, Varian

Inova 600 MHz NMR spectrometer) using deuterated water. Multi-detector (RALS, IV, RI) gel permeation chromatography (GPC) measurements were carried out on a Viscotek 270 instrument equipped with two GMHHR-Mand one GMHHR-L mixed bed ViscoGel columns to get the absolute molecular weight. Tetrahydrofuran (THF) was used as the eluent. The operation was carried out at the flow rate of 1.0 mL/min. The GPC system was calibrated using a 170k polystyrene standard. Fourier transform infrared spectroscopy (FTIR, Cary

600 Series FT-IR spectrometer with the scanning range of 400-4000 cm-1 purchased from

Agilent Technologies) was used to determine the infrared (IR) spectra of the polymer product with attenuated total reflection (ATR) method.

2.1.3 Synthesis of 2-(((butylthio)carbonothioyl)thio)propanoic acid chain transfer agent (RAFT-CTA)

In general, the trithioester RAFT-CTA was synthesized following the previous literature.1 18 g of 1-Butanethiol was dissolved in 30 mL of water followed by adding 16 g

of 50%wt NaOH solution and 10 mL of acetone. After stirring for half hour, 13.5 mL of carbon disulfide was added into the mixture to form an orange solution. The mixture was

then stirred for 1 hour. After cooling down the mixture in ice bath, 31.20 g of 2-

Bromopropionic acid was dropped into the solution followed by adding another 16 g of

50%wt NaOH solution. After the exothermic reaction, 80 mL of DI water was added into the mixture. The stirring was kept for 24 h at room temperature. 30 mL of 10M HCl was finally dropped into the solution to afford yellow precipitates under ice bath. The raw product was then recrystallized from hexane to get yellow solid.

2.1.4 Synthesis of poly(PEGMEMA) in flow reactor

A typical procedure for the synthesis of poly(PEGMEMA) in flow reactor is described

as below: 20 mL 50%vol EtOH solution was prepared and purged with nitrogen for 30 min.

The EtOH solution was then degassed with nitrogen and used to purge the flow system with the flow rate of 2 mL min-1 for 8 min. The monomer was treated by a column which contains inhibitor remover and alumina oxide to remove the inhibitor. The certain

amount of purified monomer and RAFT-CTA were then mixed with 50%vol EtOH solution.

For every sample, the monomer concentration was kept as 1 mol L-1. After transferring 10 mL solution into a glass vial and purging for 15 min with nitrogen, a certain amount of

ACVA was added into the vial. Then the mixture was sonicated in ice water for 5 min. After being degassed with nitrogen for another 30 min, this vial was connected to the HPLC 44

pump. The temperature was set to the target value and the pressure was set to 73 bar.

Then the reagent was pumped into the system with a pre-set flow rate. A 20 mL glass vial was used to collect the product from the system. The scheme for synthesis process is described in Figure 2.1. The raw product was purified by dialysis against methanol for 3 days. Poly(PEGMEMA) was finally obtained by evaporating the solvent.

Figure 2.1. Scheme of the instruments and experiment process

2.1.5 Synthesis of poly(PEGMEMA) in batch reactor

A typical procedure for the synthesis of poly(PEGMEMA) in the batch reactor is described as below: The monomer was firstly treated by a column which contains inhibitor remover and alumina oxide to remove the inhibitor. A Certain amount of purified monomer and RAFT-CTA were mixed with 50%vol EtOH solution. For every sample, the monomer concentration was kept as 1 mol L-1. 5 mL solution was transferred into a

Schlenk flask with a magnetic stirrer. After degassing for 15 min, the certain amount of

ACVA was added into the Schlenk flask. Then, the mixture was sonicated in ice water for

5 min and degassed for another 30 min with nitrogen. The reaction was conducted in an oil bath under the nitrogen atmosphere at 80 ℃ for 16 min. Once the time is up, the

Schlenk flask was transferred to an ice bath to terminate the polymerization. The raw product was purified by dialysis against methanol for 3 days. Poly(PEGMEMA) was finally obtained by evaporating the solvent.

2.2 Results and discussion

2.2.1 Comparative RAFT polymerization by flow and batch reactor

Before the RAFT polymerization, the 1H NMR spectrum was used to confirm the successful synthesis of RFAT-CTA (Figure 2.2). Both of the peaks and intigrals of the 1H

NMR spectrum indicate the target product was obtained after the recrystallization.

Figure 2.2. 1H NMR spectrum of 2-(((butylthio)carbonothioyl)thio)propanoic acid

It is well known that the high thermal exchange efficiency of flow reactor not only provide the product with homogeneous properties, but also endows high efficiency to

2-3 polymerization process . Herein, PEGMEMA300 was selected as the monomer for RAFT polymerization in aqueous system due to its unique property and hence broad applications range from biomaterial and energy storage device4-7. Due to the low solubility of RAFT-CTA in pure water, aqueous solution with 50% ethanol was prepared for the polymerization. A series of comparative polymerizations were performed in batch and flow reactors to confirm the presumption. Due to the limitation of the conventional batch reactor, all of the experiments (sample 1, 2, 3, and 4) were performed at 80 °C. The reaction conditions and polymerization results are listed in Table 2.1.

Table 2.1. Comparative RAFT polymerization in flow reactor and batch reactor

Sample 1 to 4 were synthesized at 80 ℃; sample 5 to 13 were synthesized at 100 ℃. All of the samples were prepared with the same monomer concentration (1 mol L-1). All of the reactions performed in flow reactor were undergoing at 73 bar.

[M]:[CTA]:[I]: the feed ratio of monomer, RAFT-CTA, and initiator. The initiator is 4,4’-

Azobis(4-cyanovaleric acid) (ACVA), one kind of thermal initiator.

a) Calculated by Volumeloop/Flow rate. Volumeloop = 8 mL. b) Calculated from the ratiointegration results of 1H NMR spectra. c) Theoretical Mns were calculated from the feed ratio ([M]:[CTA]) and the conversion results.

d) [Mn(NMR)]=[DPn(NMR)]×300+[MW(RAFT-CTA)]. e) Obtained from GPC analysis.

It should be noticed that at 80 °C, only with flow reactor and initiator concentration of 0.33 mmol L-1, polymers can be detected after 16 minutes’ reaction (sample 3). As shown in SI Figure 1, after normalizing the peak integrals of methyl groups (proton a in the polymer and a’ in the monomer) in the 1H NMR spectra, the peak integrals of alkene groups (proton i and i’) in the products (sample 1 and 2) remained the same compared with that of the starting material. This result demonstrated that when using batch reactor under the same reaction condition, negligible monomers were polymerized. Poor thermal transmission may be the primary reason for the low reaction efficiency of the batch reactor. It always needs longer time for the heat transfer process in batch reactors than that in flow reactorsThis effect may become more significant when the total reaction time is only several minutes. Several hours, according to our experience, is necessary for a batch reactor to synthesize polymers via RAFT polymerization. On the other hand, due to the high specific surface area of the thin reaction channel，the heat transfer process in flow reactor can be accomplished with a shorter time and kept stable during the whole process. In addition, another possible reason for the high efficiency of RAFT

polymerization is the high pressure in the flow reactor. Some researchers have studied the pressure effect on the RAFT polymerization, and indicated that high pressure leads to the high propagation rate while keep the termination rate and hence increased polymerization efficiency without affecting the molar mass dispersity8-10. However, since the pressure we used was much lower than most of the pressure reported in the literature, the pressure here may only have minor influence on the polymerization efficiency.

Aside from the favorable performance of thermal transfer process, the capability of maintaining a homogeneous system is another key for the flow reactor to get monodispersed products. Even with the help of a stirring bar, it is difficult to ensure the homogeneity of the solution in batch reactor during the whole reaction process, especially for the high viscous solutions. With the disservice of poor heat dissipation and the occurrence of “hot spots”,3 this situation can be even worse. On the other hand, for flow reactors, because all of the reactants were pumped into the loop gradually by small amounts, each part should be the same during the reaction in flow reactors. As a consequence, the Ð of sample 3 was obtainedas as low as 1.06. When the concentration of initiator was reduced to 0.08 mmol/L, even for the sample synthesized by flow reactor, almost no polymer was obtained. One explanation is that under such conditions there were not enough free radicals to initiate the polymerization within such a short period. 50

2.2.2 High-temperature RAFT polymerization via flow reactor

It has been mentioned that the boiling point of the reaction medium limited the reaction temperature, and even with the flow reactor, the monomer conversion can only reach 7%. Usually, the RAFT polymerization was performed at mild temperature: from 60 to 80 °C, which was limited by the boiling temperature of the solvent. However, in RAFT polymerization, the free radicals are generated from initiator whose decomposition

11 constant (�) increases significantly with the elevation of the temperatures . The boiling

temperature of the mixture solvent (EtOH/H2O=1:1) that we used is around 85°C, which gives the thermal initiator, i.e., 4,4’-Azobis(4-cyanovaleric acid) (ACVA), the half-life of 2 hours. Since the temperature not only influences the initiation stage but also affects other rate constants like propagation rate constant and chain transfer rate constant, the reaction under such conditions in conventional reactors usually takes several hours.

Aside from the initiator decomposition rate, the chain propagation rate is also temperature dependent. The propagation constants of different kinds of monomers at different temperatures have already been studied12-14. Based on those studies, although different monomers have different propagation constants (� ), all of them showed a drastically increasing trend of � when temperature increases. Additionally, both � and � fit well with the Arrhenius equation:

� = � exp − (1)

With the help of the Valve Module, the flow system can be operated under the pressure as high as 100 bar, which makes it possible to perform reactions at elevated temperatures. Many studies have demonstrated that RAFT-CTA may decompose at high temperatures,15-16 which may lead to uncontrolled polymerization and high Ð. At the same time, polymerization with high temperatures may also possess the risk of self- polymerization and hence much higher Ð.17 According to the polymerization result

(sample 13 in Table 1), no self-polymerization was detected at 100 °C. Therefore, 100 °C was selected as the polymerization temperature for the following experiments.

Usually, the half-life of initiator can be used to estimate the reaction time for polymerization. The derived formula of Arrhenius equation was applied to calculate the half-life of the ACVA at high temperatures.

The data of k and half-life for ACVA at 69 ℃ and 80 ℃ are from Sigma-Aldrich.

Substitute the data into the equation, respectively:

lnk = − ∗ T + lnA (2)

Here, k is the decomposition constant number at a certain temperature. A is a constant which varies depending on the order of the reaction. E is the activation

-1 -1 energy for the decomposition. R is the gas constant which is 8.314 JK mol . t/ is the

half-life. k for ACVA at 69 °C (half-life is 10 h) and 80 °C (half-life is 2 h) were obtained from the data sheet of Sigma-Aldrich.

After substituting k and T of ACVA at 69 ℃ and 80 ℃ into equation (2) respectively, E and A of ACVA in water can be determined. Then, this equation can be determined as:

lnk = 0.1414 ∗ T − 59.2502 (3)

Therefore, different k at different temperature can be calculated from equation 3.

And the half-life, t/, can be calculated from equation 4:

t/ = ln2/k (4)

The calculation results were listed in Table 2.2. And the half-life of the ACVA in aqueous solution at 100 °C was determined as 7 min 40 s.

Table 2.2. k and half-life of ACVA in water at different temperatures

Fourier Transform infrared (FT-IR) spectroscopy was firstly utilized to monitor the polymerization process. Compared to the monomers, the raw product (sample 5) exhibited the reduced absorption intensity of the peaks lying at 1637 cm-1 and 657 cm-1 that are corresponding to the stretching and bending vibration of the double bond, which 53

indicate the successful polymerization process (Figure 2.3). The unreacted monomers were removed by dialysis against methanol.

Figure 2.3. FT-IR spectra of (A) PEGMEMA300, (B) raw product after polymerization (sample 5) and (C) purified product (sample 5)

As pointed out earlier, the NMR spectra integrals of the peaks i and i’ corresponding to protons in double bonds and the peaks a and a’ derived from methyl groups were used to determine the monomer conversion (see Figure 2.4A and B). The degree of

1 polymerization (DPn) of the resulting polymers was calculated from the H NMR analysis of the purified product as shown in Figure 2.5, and the calculated values were combined

in Table 2.1. The number average molecular weights (Mns) of the synthesized polymers were obtained from the GPC analysis of the purified products.

Figure 2.4. 1H NMR spectrum of (A) raw product before purification (sample 5), (B) all of the samples before purification

Figure 2.5. 1H NMR spectrum of the polymers synthesized at 100 °C via flow reactor

With the temperature of 100 °C and pressure of 73 bar, the monomer conversion of sample 5 reached 41% within 16 min, which is much higher than that synthesized at 80 °C by flow reactor. This result indicates that increasing the reaction temperature can significantly increase the polymerization efficiency. With the flow reactor, the reaction time can be readily controlled by modifying the flow rate. By adjusting the flow rate to

0.3 mL/min, the prolonged reaction time (26.6 min) increased the monomer conversion to 57% (sample 6). It is worth noticing that the reaction time did not show significant

effect on the Ð of the product. It may be explained by the similar initiator concentration in these two systems at 100 °C.

2.2.3 Optimization of reaction conditions for flow process

Narrow molar mass dispersity is always highly desired for CRP. One problem for sample 5 and 6 is that the Ð was still not narrow enough, and it is still desirable to synthesize polymers with lower Ð. The concentration of generated radicals always plays an important role in the monomer conversion and Ð of the obtained polymer. At the same temperature, higher initiator concentration means higher radical concentration, and it will help reach higher monomer conversion within the same reaction time. It should be noticed that for our system, even for sample 5 and 6, the feed ratio of initiator to RAFT-

CTA was only 0.033 to 1, which is much lower than conventional RAFT polymerization.18-

19 Although RAFT polymerization is one kind of controlled radical polymerization, it is still inevitable to have some propagating polymer chains out of the control of the RAFT-CTA, and the situation can be even worse in high concentration of free radicals. In the current situation (sample 5 and 6), high radical concentration caused by the high temperature at the beginning might be the problem which may increase chance of the termination and cause more “dead” chains.20

Since high temperature is necessary for the high efficiency of both initiation and propagation stage, decreasing the feed ratio of initiator to RAFT-CTA would be a favorable way to lower the Ð. Although some researchers demonstrated the non-initiator polymerization of styrene and methyl methacrylate at high temperatures (more than

125 °C), 100 °C should still be too low for MMA-like monomers to be self-polymerization in such a short period.17, 21 To prove the point, sample 13 was set as a non-initiator trial using the same system. As expected, no polymer was detected after 16 min reaction, which indicated the presence of initiator is necessary. Therefore, RAFT polymerization with reduced initiator concentration was performed (see comparative data of sample 5,

7 and 8), and the Ð decreased from 1.34 to 1.18 and then to 1.12. The results provide a possibility that the flow system has potential capability to synthesize polymers with desired properties. One thing need to be pointed out is that since sample 5, 7, and 8 have different monomer conversion and initiator concentration, it cannot be concluded that the sample 8 performs better than sample 5 and 7. The Ð of the obtained polymer cannot be further reduced within the same time when the feed ratio of initiator to RAFT-CTA

([I]/[C]) reduced from 0.8% to 0.4% (see comparative data of sample 8 and 9) due to pretty low level of the both initiator concentrations. One side effect of decreasing the initiator concentration is the lower monomer conversion. For both sample 8 and 9, the monomer conversion decreased to 19%~18%. It can be explained that lower initiator concentration

rendered lower radical concentration in the flow system, which leads to lower monomer conversion at the same the reaction time. Therefore, moderately decreasing the flow rate can be a feasible solution to improve the monomer conversion via increasing the reaction time. By slightly prolonging the residence time, the monomer conversion can be increased from 19% (sample 8) to 30% (sample 10), and at the same time, the Ð of sample 10 can

be kept as low as 1.12 (Figure 2.6). The actual Mns calculated from the integration results

1 of H NMR spectra are consistent with the theoretical Mns that are obtained from the feed ratio ([M]:[CTA]) and conversion results. Although there is slight difference between

the Mns determined by GPC and NMR, the trend is consistent. The relatively poor solubility of poly(PEGMEMA) in THF might contribute to this difference. Use polystyrene instead of PEG-like polymers as the GPC standard might be another main reason.

Meanwhile, the well-known integration errors of 1H NMR spectroscopy might also cause the difference.

Figure 2.6. GPC trace of sample 10

To further improve the monomer conversion for the samples with initiator concentration of 0.08 and 0.15 mmol L-1, the flow rate was further decreased to 0.2 mL min-1. As expected, higher conversion was reached to 41% and 52%, respectively.

Meanwhile, the molar mass dispersity was slightly increased to 1.18 and 1.24, which is still acceptable for RAFT polymerization. It should be noticed that when comparing sample 11 and 5, narrower dispersity with similar monomer conversion was obtained.

This can be explained by the lower initiator concentration, which decreased the free radical concentration and rendered lower termination rate.

References

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Klumperman, B.; Russell, G. T., Critically evaluated rate coefficients for free-radical polymerization, 3 - Propagation rate coefficients for alkyl methacrylates. Macromol. Chem.

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Chapter Three Continuous Fabrication of Polymer Brushes Grafted

Silica Microparticles and Block Copolymers

3.1 Experimental section

3.1.1 Materials

Flow reactor (Phoenix Flow Reactor) equipped with a stainless steel column (99mm length, 3.8mm inner diameter), which works with an HPLC pump and a Valve Module, was supplied by ThalesNano Nanotechology Inc. (3-Aminopropyl)trimethoxysilane (97%), N-

(3-Dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC, commercial grade),

Poly(ethylene glycol) methyl ether methacrylate (PEGMEMA, Mn=300), N-

Isopropylacrylamide (NIPAM, 97%), 4,4’-Azobis(4-cyanovaleric acid) (ACVA, >=98%), and hydrofluoric acid (HF, 48%) were purchased from Sigma-Aldrich. N-Hydroxysuccinimide

(NHS, 97%) was purchased from Alfa Aesar. HCl solution (37%) was purchased from BDH.

Anhydrous ethanol (EtOH) was purchased from Millipore. Deionized (DI) water was produced by Milli-Q water system. 2-(((butylthio)carbonothioyl)thio)propanoic acid RAFT-

CTA was from the Chapter 2.

3.1.2 Synthesis of silane-modified RAFT CTA

The silane-modified RAFT CTA, butyl (1-oxo-1-((3-(trimethoxysilyl)propyl)amino)prop- an-2-yl) carbonotrithioate (BTPAPC), was synthesized followed the procedure below.

479.3 mg (2.5 mmol) of EDC and 8 mL of dried DMF were firstly added into a 50 mL round bottom flask. 596.5 mg (2.5 mmol) of 2-(((butylthio)carbonothioyl)thio)propanoic acid

(BCPA) was then added to the flask. The mixture was stirred with a magnetic stirrer for several minutes until the clear solution was formed. Then, 287.6 mg (2.5 mmol) of NHS in

1mL of dry DMF was added into the mixture followed by adding 268.9 mg (1.5 mmol) of

(3-Aminopropyl)trimethoxysilane which was also in 1 mL of dry DMF. This mixture was stirred at 40 °C for 24 hours. After that, the final mixture was diluted by dry DMF to 50 mL for future usage without purification. Reversed-phase Silica gel chromatography (MeOH :

DCM = 8 : 2) was used to separate the final product for NMR analysis.

3.1.3 Preparation of silica microparticles for further usage

Silica microparticles were added into a round bottom flask with 10% HCl solution. The mixture was stirred at 90 °C for 5 hours. After washing with DI water, the particles were put in the vacuum oven at 60 °C for 2 days. Those particles were then stored for further usage.

3.1.4 Anchor modified CTA onto silica microparticles’ surface in flow reactor

10 mL of diluted BTPAPC solution was transferred into a 20 mL glass vial without any purification. This vial was then purged with nitrogen for 20 mins. 200 mg of silica microparticles were added into the stainless steel column. After connecting this column to the flow reactor, 25 mL of degassed ethanol was used to purge the whole flow system.

Then, the modified CTA solution was pumped to pass through the column by the HPLC pump with the flow rate of 0.2 mL min-1. During this process, the pressure of the whole system was kept at 80 bar, and the temperature of the column was controlled at 120 °C.

The nitrogen was purged during the whole modification process. After the modification,

30 mL of ethanol was pumped to pass through the system to remove any free molecules.

The CTA modified particles were kept in the column for next procedure without additional purification.

3.1.5 Grafting poly(PEGMEMA) from CTA modified silica microparticles’ surface in flow reactor

In a 50 mL glass vial, the certain amount of PEGMEMA (4.8 g, 2.4 g, or 1.2 g) was

mixed with 15 mL of 50 %vol ethanol solution. The monomer concentration was determined as 0.8 M, 0.432 M, and 0.235 M, respectively. 2.8 mg of ACVA was then added

into this vial. Before every entry, the solution in vial was purged with nitrogen for 30 mins.

After using 25 mL of degassed ethanol to purge the whole system, the monomer mixture in vial was connected to the HPLC pump with the flow rate of 0.2 mL min-1 for different flow time. In order to increase the utilization of the monomers, a closed circular system was formed as the following (Figure 3.1). Once the mixture came out from the waste tube

(after 40 mins from the start), the waste tube was embedded into the original vial to let the mixture flow back. For “graft from”, the process was carried out under the pressure of

80 bar, and the temperature of the column was kept at 125 °C. The nitrogen was purged during the whole modification process. After the modification, 50 mL of ethanol was pumped to pass through the system to remove any free molecules. The particles were then taken out of the column and dried by rotary evaporator and vacuum pump.

Figure 3.1. Scheme of the closed circular flow system

3.1.6 Grafting block copolymers from CTA modified silica microparticles’ surface in flow reactor

In order to synthesize block copolymers from microparticles’ surface, the particles were firstly modified by PEGMEMA for 1 hour following the procedure mentioned above.

After that, a 50 mL glass vial which contained 1 M NIPAM monomer and 2.8 mg of ACVA

- (in 15 mL 50 %vol ethanol) was connected to the HPLC pump with flow rate of 0.2 mL min

1. All of the conditions for grafting of the NIPAM were set as same as the conditions for grafting PEGMEMA. The reaction time for PNIPAM block was also set as 1 hour. After the modification, the particles were taken out of the column and dried by rotary evaporator and vacuum pump. The whole grafting process including the CTA modification process was shown in Figure 3.2.

Figure 3.2. Scheme of the grafting poly(PEGMEMA)-b-PNIPAM from silica microparticles process

3.1.7 Cleave polymer chains from microparticles’ surface

After transferring 100 mg of microparticles into a 20 mL PTFE vial, 5mL 48% HF was added to react with the silica part. The mixture was kept in the hood overnight and then dried with the help of blowing air at 50 °C. After that, THF was used to dissolve all products in PTFE vial and the solution was transferred into a 20 mL glass vial, and dried by rotary evaporator. For GPC analysis, the crude products were dissolved in HPLC THF without further purification. For NMR analysis, the crude products were purified by dialysis against

in methanol for 3 days to get pure products.

3.1.8 Characterization

Purified BTPAPC, were characterized by 1H NMR (Varian Inova 600 MHz NMR spectrometer) using deuterated chloroform. Poly(PEGMEMA) grafted for 2.5 hours, and the block copolymers were characterized by NMR using deuterated water. Multi-detector

(RALS, IV, RI, or UV) GPC measurements were carried out on a Viscotek 270 instrument equipped with two GMHHR-Mand one GMHHR-L mixed bed ViscoGel columns. THF was used as the eluent. The operation was carried out at the flow rate of 1.0 mL min-1. The standard used for GPC was 170K polystyrene. The dn/dc set for poly(PEGMEMA) and poly(PEGMEMA)-block-PNIPAM were 0.076 and 0.091, respectively. The number average

molecular weight (Mn) and the Ð (Mw/Mn) were calculated by the software, OmniSEC 4.1.

FT-IR (Cary 600 Series FT-IR spectrometer with scanning range of 400-4000 cm-1 purchased from Agilent Technologies) was used to recorder the infrared (IR) spectra of the product.

TA instrument, 2050 TGA, was used for thermogravimetric analysis (TGA) to measure the thermal properties of the polymer grafted microparticles. The solid samples were heated up to 800 °C with a heating rate of 10 °C min-1 in the nitrogen atmosphere. Scanning electron microscopy (SEM) was used to see the surface of the pristine and grafted silica

microparticles. Before the imaging, 5 nm-thick gold was coated to the samples by Hummer

6.2 Sputter System from Anatech USA (Alexandria, VA). The SEM micrographs of the samples were then recorded with a JEOL scanning electron microscope (JEOL-JSM-6510LV) using a 30 kV acceleration voltage.

3.1.9 Measurements of water contact angle

For pristine silica microparticles and poly(PEGMEMA) grafted silica microparticles, a piece of double side sticky tape was stuck on a glass slide. The particles were then spread on the sticky tape to form a homogeneous layer. The excess microparticles can be removed by blowing air. Then this slide was used for static water contact angle test with

CAM 200 optical contact angle meter instrument. For poly(PEGMEMA)-b-PNIPAM grafted silica microparticles, a double side sticky tape was stuck on a hot plate instead of the glass slide. The microparticles were then spread on the tape with the same procedure. The static water contact angle tests were conducted at room temperature and 60 °C (plate temperature), respectively.

3.2 Results and discussion

3.2.1 Grafting poly(PEGMEMA) from CTA modified silica microparticles’ surface in flow reactor

BTPAPC was purified by the reversed phase silica gel chromatography. Before the purification, DMF was evaporated under vacuum at 70 °C. The 1H NMR spectrum shows that the target product has been produced (Figure 3.3). After setting the integration value of peaks “i” (0.57 ppm) as 2, the integration results of other peaks “a”, “b”, “c”, “d”, “e”,

“f”, “g”, “h” are consistent with the theoretical value of the designed molecule. However, the integral of peak “j” is smaller than the designed value which should be nine. The decreased integral of peak “j” is reasonable. Since water is the byproduct during the synthesis of silane-modified CTA, during the evaporation procedure, the partial hydrolysis of silane group can happen, which will consume some of the methoxy groups. To avoid the hydrolysis, the silane-modified CTA was used without any purification after the synthesis as mentioned above.

Figure 3.3. 1H NMR spectrum of silane-modified CTA

The FT-IR spectrum demonstrates the successful anchoring of the CTA to the silica microparticles’ surface (Figure 3.4). The new peaks in the dashed region indicates the presence of C-H bond, as well as the amide bond, of the silane-modified CTA. In addition, after the grafting procedure, the particles’ color turned from white to yellow which is due to the modified CTA on the surface. To make the comparison, original RAFT CTA was used to pass through the column with the same procedure and the conditions. On the contrary, no color change was observed after the flow process.

Figure 3.4. FT-IR spectrum of CTA modified silica microparticles and pristine silica microparticles

After grafting poly(PEGMEMA) from the particles’ surface, FT-IR was also carried out for the particles (Figure 3.5). For all of the poly(PEGMEMA) grafted samples, new peaks at

1351 and 1454 cm-1 is due to the stretching vibration of C-H of the polymer chains.

Moreover, the new peak at 2881 cm-1 is corresponding to the C-H stretching vibration of the chains. Meanwhile, the peak of C=O bond at 1728 cm-1 belongs to the ester bond of the poly(PEGMEMA). When the monomer concentration was fixed as 0.8 M, different flow time was chosen for grafting poly(PEGMEMA) from the microparticles’ surface. In order to compare the loading of polymer on the surface, before the TGA analysis, the FT-IR spectrums for different samples were also used for the evaluation. After normalization based on the peak at 794 cm-1 (refers to the vibration of Si-O-Si, not shown in the Figure), which belongs to the pristine silica particles, the obvious increasing trend of peaks at 1351, 75

1454, 1728, and 2881 cm-1 was observed. The peaks’ height increased with the increasing of the flow time which proved that the longer flow time would lead to polymers with higher molecular weight.

Figure 3.5. FT-IR spectrum of silica microparticles grafted by poly(PEGMEMA) within different flow time

In general, increasing of temperature cannot only decrease the half-life of the initiator but can also increase the rate of the propagation process. One of the advantages of our flow system is the high pressure which can increase the boiling temperature of the solvent during the polymerization. Therefore, the grafting of CTA and polymers in 50 % ethanol can be conducted at 125 °C with 80 bar. It should be noticed that after modifying the particles by grafting polymer, a color change trend was observed, which was consistent 76

with the change of the reaction time (Figure 3.6). The longer the flow time was kept, the brighter surface of the particles would be, which reflects the presence of longer chains from the side

Figure 3.6. Silica microparticles grafted by poly(PEGMEMA) within different flow time

TGA curves were used to further determine the grafting amount of the polymers on the surface. For samples prepared with different flow time (prepared with 0.8 M monomer), the weight loss increased from 9.7 % to 25.4 % when the flow time increased from 0.5 hour to 3 hours (Figure 3.7). It is noteworthy that when the reaction time increased from 0.5 hours to 1.5 hours, the weight loss drastically increased from 9.7 % to

22.2 %. Meanwhile, when the reaction time increased from 1.5 hours to 2.5 hours and finally to 3 hours, the weight loss only increased from 22.2 % to 23.8 % and 25.4 %, 77

respectively. The reason for this is possibly due to the concentration change of the circular system. Since after 40 mins, the waste, which contained unreacted monomers, was arranged to flow back to the glass vial, the monomer concentration was diluted. And the monomer concentration would keep decreasing over the whole period. Since the monomer concentration is a key factor influences polymerization efficiency, the propagation rate was decreasing over the time.

To further investigate the molecular weight difference caused by monomer concentration, another two samples were prepared with different monomer concentration. When the concentration of monomer increased from 0.24 M to 0.8 M, the weight loss increased from 9.5 % to 22.2 %. Under the assumption that all the microparticles contain the similar amount of CTA on the surface, the TGA results provide a demonstration that both prolonging of reaction time and increasing of monomer concentration are feasible ways to graft longer polymer chains from particles’ surface via

RAFT polymerization in the flow reactor.

Figure 3.7. TGA results of (A) samples prepared within different flow time and (B) different monomer concentration

To further explore the polymers grafted by flow reactor, the HF was used to cleave polymer chains from the particles’ surface. The NMR result (Figure 3.12A) indicates the successful synthesis of target polymers on the surface. Followed by GPC characterization, the molecular weight and the molar mass dispersity were also determined (Figure 3.8 and

Table 3.1). No matter increasing the flow time or the monomer concentration, the increasing of the molecular weight can be observed. For all of the samples, relatively narrow molar mass dispersity can be observed, which varies from 1.17 to 1.27. This is an evidence that the brushes grafted from the surface are controlled by the RAFT CTA. It also provides a possibility that it is possible to form uniform polymer shell through this method.

However, one thing needs to be noticed that since under current condition, all of the microparticles in the column are compacted together, which means every part of the particle may have different space for growth of polymers. As a consequence, over the

polymerization, some chains may have larger steric hindrance and less chance to meet with the monomers and then become harder to grow. Besides, due to the existence of contacted part, the particles may not be coated perfectly.

Figure 3.8. GPC traces for polymer brushes synthesized with (A) different flow time and (B) monomer concentration

Table 3.1. Molecular weight and molar mass dispersity of polymers cleaved from silica microparticles

Another interesting phenomenon is observed by the SEM images. For pristine silica microparticles, very smooth surface with sharp parts can be observed. After the grafting by poly(PEGMEMA), a rough coating which was formed by the polymer brushes can be observed, which changed the morphology of the particles surface (Figure 3.9). When compare two samples prepared with different flow time, it seems like the thicker coating can be resulted by the longer flow time, which is supposed to be formed by longer polymer brushes. However, further methodology is needed if the actual thickness needs to be determined.

Figure 3.9. SEM images of (A) pristine silica, (B) silica grafted by poly(PEGMEMA) within 3 h, (C) silica grafted by poly(PEGMEMA) with 0.5 h

3.2.2 Grafting poly(PEGMEMA)-b-PNIPAM from CTA modified silica microparticles’ surface in flow reactor

One of the biggest advantages of grafting polymers from particles by continuous method is that the additional purification process is not necessary between every step.

Because the support parts are fixed in the column, the oxygen-free environment can also

be maintained during the whole process. Therefore, after 1-hour fabrication of the first block of the polymer, the second kind of monomer solution, NIPAM, was connected to the system to synthesize the second part of the block copolymers directly. The new peaks at

1367 cm-1 and 1540 cm-1 of FT-IR spectrum indicate the presence of amide that belongs to the PNIPAM as well as the difference of peaks from 2883 to 2977 cm-1 which indicate the different C-H of the polymer chains (Figure 3.10). Meanwhile, TGA analysis also showed a higher weight loss of the polymers, 21.5 % versus 18.0 %, of the block copolymers. Also, the higher decomposition temperature of samples modified by block

copolymers can be observed (Td5 increased from 231.2 to 284.5 °C) as well, which is due to the higher decomposition temperature of the PNIPAM compared with the poly(PEGMEMA) (Figure 3.11).

Figure 3.10. FT-IR spectrum for (A) poly(PEGMEMA) (grafted witn 2.5 h)and poly(PEGMEMA)-b-PNIPAM, (B) zoom-in spectrum of the range for wavenumber between 1300 to 1400 cm-1

Figure 3.11. TGA results for poly(PEGMEMA) (grafted within 1 h) and poly(PEGMEMA)-b- PNIPAM

The block copolymers were also cleaved from the particles with the help of HF and measured by NMR (Figure 3.12B). The new peaks (j, f’, and g’) at 3.71, 1.85, and 0.95 ppm further approved that the PNIPAM blocks have been grafted from the particles’ surface.

Assisted by the GPC, a sample cleaved from the particles, which was prepared with 1 hour flow time, was used to compare with the cleaved block copolymers (Figure 3.13). The larger molecular weight belongs to the longer chains that can only be caused by the

PNIPAM block of the copolymers. It should be noticed that the molar mass dispersity of the block copolymers is 1.12, which is even lower than the dispersity (1.49) of the poly(PEGMEMA) synthesized within 1 hour. This difference is probably caused by the

different entry of the experiment. Meanwhile, since the block copolymers show a higher molecular weight and low dispersity, most of the chains can be considered that they were growing controlled by the RAFT CTA during polymerization.

Figure 3.12. NMR spectrum of (A) cleaved poly(PEGMEMA) (grafted within 2.5 h), (B) cleaved poly(PEGMEMA)-b-PNIPAM 85

Figure 3.13. GPC traces for cleaved poly(PEGMEMA) (grafted within 1 h) and poly(PEGMEMA)-b-PNIPAM

In addition, the static water contact angle tests were also conducted to prove the functionalization of the microparticles’ surface (Figure 3.14). For pristine silica microparticles, due to the large amount of hydroxyl groups, the static water contact angle was detected as 0°. When the particles were functionalized by poly(PEGMEMA) with

0.232 M monomer for 1.5 hours, which is supposed to have shortest chains, the water contact angle increased to 38±3°, which is very similar to the result reported by literature1-2. Meanwhile, when the particles were functionalized by 0.8 M monomer for

0.5 h, the water contact angle increased to 43±5°, which is probably due to the longer backbone of the polymers on the surface. Further increasing the chain length with 3 h of

polymerization, the static water contact angle increased to 60±3°. The reason for the increasing of the water contact angle should be due to the increasing length of the backbone, which increases the hydrophobicity of the surface. When it comes to the poly(PEGMEMA)-b-PNIPAM functionalized microparticles, at room temperature, the static water contact angle further increased to 95±5°, which is already a hydrophobic surface. Considering that both of the poly(PEGMEMA) and PNIPAM should be hydrophilic, besides the increasing of the chain length, another reason for the increasing of water contact angle might be the morphology. Due to the irregular shape of the silica microparticles, the surface of the sticky tape becomes rough, and there are many air traps between the microparticles. This rough surface morphology contributes to the more hydrophobic property and increases the water contact angle even the material is hydrophilic.3-4 As a temperature-sensitive polymer, PNIPAM has potential to become hydrophobic from hydrophilic status due to the lower critical solution temperature (LCST) of around 32 °C.5 As a consequence, the static water contact angle of 116±4° was observed at 60 °C (hot plate set-temperature), which provides the evidence of the hydrophobicity changing and the presence of the PNIPAM block.

Figure 3.14. Static water contact angles of silica microparticles grafted by polymers under different conditions. (A) sample grafted by poly(PEGMEMA) with 0.24 M in 1.5 h. (B) sample grafted by poly(PEGMEMA) with 0.8 M in 0.5 h. (C) sample grafted by poly(PEGMEMA) with 0.8 M in 3 h. (D) sample grafted by poly(PEGMEMA)-b-PNIPAM tested at room temperature. (E) sample grafted by poly(PEGMEMA)-b-PNIPAM tested at 60 °C

3.2.3 Comparison with the batch reactor

In order to compare the flow reactor with the batch reactor. The grafting poly(PEGMEMA) from particles’ surface was also conducted in a batch reactor. To make the conditions same, the silica particles were firstly modified by silane-modified CTA in flow reactor with the same procedure. Then, those particles were mixed with initiator, 0.8

M monomer in a 200 mL round bottom flask with a reflux tube. The temperature of oil bath was also set to 125 °C. Because the pressure was only 1 atm, the mixture became boiling at the temperature of 85 °C. However, even the temperature was only 85 °C, strong gelation happened in less than 1 hour, which prohibits further reactions (Figure 3.15). This is due to the free radical polymerization in solution, which is an inevitable part for RAFT polymerization from substrate. This negative impact can be extremely strong when the concentration of monomer and initiator is high. However, high monomer concentration is a crucial factor for RAFT polymerization with high efficiency. Because the RAFT CTA is only present on substrate’s surface, there will always be some free radical polymerization.

Since all of the monomers were in the flask from the beginning to the end, a large ratio of monomers may contribute to the free radical polymerization but not the RAFT polymerization from the surface, which finally leads to the gelation of the solution. On the contrary, for flow reactor, because all of the monomers only hava short time to stay in the column, the free radical polymerization can be stopped once they leave the column and are cooled down. As a result, the free radical polymerization can be avoided to the minimum under such conditions.

Figure 3.15. Gelation happened in batch reactor

References

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H., Poly(dimethyl siloxane) surface modification by low pressure plasma to improve its characteristics towards biomedical applications. Colloid Surface B 2010, 81 (1), 20-26.

2. Bi, H. Y.; Meng, S.; Li, Y.; Guo, K.; Chen, Y. P.; Kong, J. L.; Yang, P. Y.; Zhong, W.; Liu, B.

H., Deposition of PEG onto PMMA microchannel surface to minimize nonspecific adsorption. Lab Chip 2006, 6 (6), 769-775.

3. Zhu, M. F.; Zuo, W. W.; Yu, H.; Yang, W.; Chen, Y. M., Superhydrophobic surface directly created by electrospinning based on hydrophilic material. J Mater Sci 2006, 41 (12), 3793-

3797.

4. Cao, L. L.; Hu, H. H.; Gao, D., Design and fabrication of micro-textures for inducing a superhydrophobic behavior on hydrophilic materials. Langmuir 2007, 23 (8), 4310-4314.

5. Pelton, R., Poly(N-isopropylacrylamide) (PNIPAM) is never hydrophobic. J Colloid

Interf Sci 2010, 348 (2), 673-674.

Chapter Four Conclusions and Future Work

4.1 Conclusions

Firstly, a highly-efficient RAFT polymerization of PEGMEMA in aqueous solution was conducted in a flow reactor equipped with a pressure controller. At the same reaction temperature, the flow reactor allows the RAFT polymerization performed in a high- efficiency manner compared with the batch reactor due to the high thermal exchange efficiency. With the help of the increased pressure, raising the reaction temperature is an efficient way to increase the monomer conversion within a short reaction time via increasing both of the radical generation rate and other rate constants such as propagation rate constant and chain transfer rate constant. Adjusting the initiator concentration can control the radical concentration and, therefore, limit the termination caused by free radicals, which significantly lowers the Ð. Meanwhile, adjusting the flow rate (increase the residence time) was demonstrated capable to significantly improve the monomer conversion with slightly increased molar mass dispersity.

Grafting poly(PEGMEMA) brushes from silica microparticles’ surface can also be achieved by using this commercially available system. By constructing the closed circular system, extending of reaction time without adding extra monomer solution becomes possible, which increases the utilization of the monomer. With the help of tunable

pressure, the “graft from” procedure can be achieved at 125 °C. Both of prolonging the flow time and increasing the monomer concentration can result in longer brushes.

Comparing with the batch reaction, due to the continuous nature, the free polymerization in solution can be limited, and the purification procedure can be greatly simplified, which saves the time and cost. Moreover, with the similar procedure, poly(PEGMEMA)-b-

PNIPAM was also grafted from the silica microparticles’ successfully, which was confirmed by several techniques including FT-IR, TGA, NMR, GPC, and temperature-controlled static water contact angle.

4.2 Future work

The current work has demonstrated that the diblock copolymers can be grafted from the microparticles’ surface by continuous method. It is also possible and valuable to graft triblock or even sequenced copolymers from the particles’ surface by similar method.

Such method may even have potential to fabricate sequenced copolymers through programmatic procedure controlled by computers.

Besides the RAFT polymerization, the ATRP and NMP are all possible tools to graft polymer brushes from the microparticles’ surface in both aqueous and organic environment. In addition, with the suitable accessories, grafting polymers from 93

nanoparticles’ surface via CRP in continuous method is also a challengeable and attractive goal for the future work.

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