Synthesis of Thermo-responsive Shell Cross-Linked (SCL) Micelles

with Functional Coronas.Laura Pilon, Steve Armes

School of Chemistry, Physics and Environmental Science, University of Sussex, Falmer, Brighton, BN1 9QJ, UK

Steve Rannard, Paul FindlayUnilever Research, Port Sunlight, Bebington, Wirral,

CH63 3JW, UK

Outline.

• Background.• Triblock copolymer and SCL micelle

synthesis.• Triblock copolymer characterisation.• Characterisation of SCL micelles.• Adsorption of cationic corona micelles onto

anionic silica particles.

AB Block Copolymer Micelles

• Micelles are generally formed by AB diblock copolymers in a selective solvent.

• Micelles are in equilibrium with molecularly dissolved chains.• Stimulus-responsive micelles can be synthesised from block

copolymers in which the solubility of one of the blocks is dependent on either temperature or pH.

In a good solvent… In a selective solvent…

Riess, G. Prog. Polym. Sci. 2003, 28, 1107

What are Shell Cross-Linked (SCL) Micelles?

• Permanent nano-particles formed from amphiphilic AB diblock copolymer micelles in THF/water mixtures.

• The block copolymer corona is chemically cross-linked.• Suggested applications include drug delivery, catalysis

and scaffolds for creating ordered inorganic materials.

Bruce Thurmond II, K. et al. J. Am. Chem. Soc. 1996, 118, 7239.

Hydrophobic polystyrene micelle core

Hydrophilic cross-linked poly(4-vinyl pyridine) micelle shell or corona.

SCL Micelles of ABC Triblock Copolymers vs. Dendrimers

Hydrophobic core

Functional corona

• Similar core-shell structure.

• Major difference is in size.

SCL micelle synthesis is considerably more facile than multi-step dendrimer syntheses.

OH

OH

OH

OH

OHOH

OHOHOH

OHOH

OHOH

OHOH

OH

5 - 10 nm

dendrimer

20 – 50 nm

OH

HO

OH

OH

OH

SCL micelleHydrophobic

core

Liu, S.; Armes, S.P. J. Am. Chem. Soc. 2001, 123, 9910

Atom Transfer Radical Polymerisation (ATRP)

• ATRP leads to polymers with controlled molecular weights and narrow molecular weight distributions.

• Use of polar protic solvents allows direct synthesis of highly functional polymers without protecting group chemistry.

(activation)

deactivationP P X

polymer radical

halide-cappeddormant polymer chain

Cu(I)X

Cu(II)X2

Wang, J. S.; Matyjaszewski, K. J. Am. Chem. Soc. 1995, 117, 5614: Kato, M. et al.Macromolecules 1995, 28, 1721: Matyjaszewski, K.; Xia, J. Chem. Rev. 2001, 101, 2921

Thermo-responsive SCL Micelle Synthesis

• poly(propylene oxide) – PPO, thermo-responsive block

• poly(2-(dimethylamino)ethyl methacrylate) – PDMA, cross-linkable block (V. Butun et al., J. Am. Chem. Soc., 1999, 121, 4288).

• poly(glycerol monomethacrylate) – PGMMA, solubilising block and steric stabiliser during cross-linking – prevents micellar fusion (V. Butun et al., Macromolecules, 2000, 33, 1).

• Using different cross-linking chemistry allows the roles of PGMMA and PDMA to be interchanged.

Aqueous solution of molecularly dissolved triblock

copolymer at 5 oC.

Micelles at 40 oC

Selective cross-linking of inner-shell

Permanent nanoparticle

Synthesis of PPO33-DMA20-GMMA50 Triblock Copolymer

• GMMA in methanol added at 98 % conversion.

• Reasonable blocking efficiency.

OBrO

O33

O

ON

CuCl(HMTETA) 60 oC, 60 mins

OO

O33X

OO

N

20

20

O OOH

OH

50

methanol

OO

O33

OO

N

20X

OO

OH

OH

50

X = Br or Cl

in 60 oC

+

Molecular Weight18.8

a)

10.2 11.6 13.1 14.5 15.9 17.4

Triblock, 14,300, 1.26

Diblock,5,900, 1.24

Macro-initiator3,200, 1.19

Synthesis and Quaternisation of the PPO33-b-GMMA20-b-DMA50 Triblock Copolymer

OO

OX

OO O O

33 20 50

OH

OH N

OO

O

33Br

OO

O

OO

33 20X

OH

OHO O

N

+ Cu(I)Cl(bipy)2

O OOH

OH

50 % solids in9:1 IPA/water 20 oC

50 % solids in9:1 IPA/water 20 oC

OO

O

OO O O

33 20

OH

OH N

X

OO

N+

I

5050 x

quaternisationwith methyl iodide in methanol

-x

• DMA in 9:1 IPA/water was added at 98 % conversion of GMMA.

• Reasonable blocking efficiency.

• Copolymers with 0 %, 30 % and 60 % degrees of quaternisationwere targeted.

Synthesis of PPO33-b-GMMA20-b-QDMA50

• Quaternised DMA (QDMA) added at 98 % conversion.

• Permanently cationic.• Cannot directly confirm

blocking efficiency of QDMA from GMMA in this ABC triblock copolymer.

CuCl(bipy) 225 o C

O

O

OO33

X

OO

20

OH

H

OBrO

O33

O O

OH

OH

20

O

OO33

OO

20X

OO

50

OH

OHN

+

Cl

X = Br or Cl

9:1 IPA:water

O O

N+

50

30 % in 1:1IPA/water25 oC

Cl

Cross-Linking Chemistry1) 1,2-bis(2-iodoethoxy)ethane

(BIEE) for DMA cross-linking

OO

II

OO

N

OO

N

OO

OO

N+

OO

N+

aqueous solution 40 oC

II

5 %solids

2) Divinyl sulfone (DVS) for GMMA cross-linking

OO

O

OH

H

OO

OH

OH

OO

OH

O

S

O

O

OO

OH

O

aqueous solution 40 oC, pH 12

S

O

O

+ side-products

5 %solids

Liu, S.; Armes, S. P. J. Am. Chem. Soc.2001, 123, 9910

Liu, S.; Weaver, J. V. M.; Save, M.; Armes, S. P. Langmuir 2002, 18, 8350

Analysis of ABC triblock copolymers

100 %

53 %

33 %

-------------------

-------------------

16,500

18,400

15,500

13,200

12,900

calcd.Mn

4.3--------15,00015,700PPO33-b-GMMA20-b-QDMA50

3.6--------19,60017,400PPO33-b-GMMA20-b-(DMA20-st-QDMA30)

4.3--------18,10015,200PPO33-b-GMMA20-b-(DMA35-st-QDMA15)

5.01.4615,80013,100PPO33-b-GMMA20-b-DMA50

2.01.2512,30013,300PPO33-b-DMA20-b-GMMA50

% N

Degree of quaternisation

(by NMR)

MicroanalysisMw/MnMn, (NMR)

Mn, (theory)

Turbidimetic Studies of Triblock Copolymers.

• Typical critical micelle temperature (CMT) of PPO is a function of molecular weight (~35 oC for 1000 g mol-1).

• Only 2 oC variation in CMT.

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0 5 10 15 20 25 30 35Temp/ oC

Ab

s @

500

nm

12.5 oC

11 oC12 oC

12 oC

13 oC

g PPO33-b-GMMA20-b-DMA50

5 PPO33-b-GMMA20-b-(DMA45-st-QDMA15)

• PPO33-b-GMMA20-b-(DMA20-

st-QDMA30)

• PPO33-b-GMMA20-b-QDMA50

5 PPO33-b-DMA20-b-GMMA50

pH ~ 8

0.5 wt %

Dynamic Light Scattering (DLS) of Micelles Before and After Cross-Linking

0 100 300 400 50050Diameter by DLS/ nm

Unimers at 5 oC (< 5 nm)

Micelles at 40 oC (~30 nm)

Swollen SCL micelles at 5 oC (~50 nm)

Aggregated micelles at 40 oC (~300 nm)

Aggregated SCL micelles at 40 oC (~400 nm)

pH ~ 8

Transmission Electron Microscopy (TEM) of Shell Cross-Linked Micelles prepared using

PPO33-b-GMMA20-b-DMA50• Approximately spherical, polydisperse nanoparticles.

• Similar micelle diameter to that observed by DLS in aqueous solution.

• Variation in shape could be due to drying effects.

100 nm

Variable Temperature 1H NMR Studies on the PPO33-DMA20-GMMA50 Micelles After Shell Cross-

Linking

5 oC 50 oC

0.20.20.40.40.60.60.80.81.01.01.21.21.41.41.61.61.81.82.02.02.22.22.42.4

Variable Temperature 1H NMR Studies on the PPO33-DMA20-GMMA50 Micelles After Shell Cross-

Linking

5 oC 50 oC

0.20.20.40.40.60.60.80.81.01.01.21.21.41.41.61.61.81.82.02.02.22.22.42.4

Variable Temperature 1H NMR Studies on the PPO33-DMA20-GMMA50 Micelles After Shell Cross-

Linking

5 oC 50 oC

0.20.20.40.40.60.60.80.81.01.01.21.21.41.41.61.61.81.82.02.02.22.22.42.4

Adsorption of Cationic Corona SCL Micelles onto Anionic Silica Particles

30 nm cationic SCL micelles

250 nm (or 1 µm) monodispersesilica particles dispersed in

aqueous solution

--

----

---

--

---

+ ++

+++

+ +

+ +++ ++

-

- -- ---

----

--- -

-

-60

-40

-20

0

20

40

60

0 2 4 6 8 10 12pH

Zet

a P

ote

nti

al/ m

VZeta Potential Measurements on SCL

Micelle-Decorated 250 nm Silica Particles

IEP @ pH 3

-60

-40

-20

0

20

40

60

0 2 4 6 8 10 12pH

Zet

a P

ote

nti

al/ m

VZeta Potential Measurements on SCL

Micelle-Decorated 250 nm Silica Particles

IEP @ pH 3

-60

-40

-20

0

20

40

60

0 2 4 6 8 10 12pH

Zeta

Pot

entia

l/ m

VZeta Potential Measurements on SCL

Micelle-Decorated 250 nm Silica Particles

IEP @ pH 9.5

Decorated silica (positively charged)

Bare silica (negatively charged)

-60

-40

-20

0

20

40

60

0 2 4 6 8 10 12pH

Zeta

Pot

entia

l/ m

V

0

500

1000

1500

2000

2500

Par

ticle

Dia

met

er (D

LS)/

nm

Zeta Potential Measurements on SCL Micelle-Decorated 250 nm Silica Particles

5

Bare silica

Decorated silica

Flocculation around IEP

SEM Studies of SCL Micelle-Decorated 250 nm Silica Particles

Bare Monospher 250 nm silica particles.

Micelle-decorated Monospher250 nm silica particles.

200 nm 200 nm actual micelle size

Conclusions• Well-defined multi-functional ABC triblock copolymers can be

readily synthesised by ATRP in protic media at 20 oC.• The micellar self-assembly of these ABC triblock copolymers

in aqueous solution has been studied.• SCL micelles have been successfully synthesised and

characterised from these triblock copolymer precursors.• Cationic corona SCL micelles have been electrostatically

adsorbed onto near-monodisperse silica particles and full characterisation of these new composite particles is under way.

• Cationic corona SCL micelles may offer potential applications for the generic and facile preparation of ‘smart’ stimulus-responsive surfaces.

Acknowledgements• EPRSC and Unilever for an Industrial CASE award.• Röhm, Germany for the donation of the GMMA

monomer.• E. Merck, Germany for the Monospher silicas.• Cognis Performance Chemicals for the donation of

the PPO macro-initiator precursor.• Dr Erica Wanless, University of Newcastle, Australia.• Dave Randall, University of Sussex.• Sussex Polymer Group.