Self-assembly and its inhibition of bolaform amphiphile dendrimers

Jirun Sun and Paul Russo

Chemistry Department &

Macromolecular Studies Group

Louisiana State University

June 15, 2005

What are the bolaform amphiphiles?

They have a dumb-bell shape

hydrophilichydrophilic

hydrophobic

Arborol example: [9]-10-[9] 9 watery hydroxyl groups

10 oily methylene groups

3-D Structure of [9]-10-[9]

Dr. George NewkomeJCS, Chem. Commu. 1986,752

OH

OH

OH

NH

OH

OH

OHNH

OO

O

OH

OH

OH

NH OH

OH

OH

NH

OH

OH

OHNH

OO

O

OH

OH

OH

NH

MW = 1052

Arborol Gels’ Properties

• Dissolve in warm water• Gel on cooling• Apparently, they are “real” gels• Reversible

• Fibers inside the gels • Self-assembly

Why do we care?

Reversible self-assembling system

Small molecule hydrogels

Easy to vary headgroup and core size

Possible applications in:• Porous media• Stationary phase for separations

• Model for studying -amyloid (the protein fragment responsible for Alzheimer’s disease).

Do they look alike?

• We need this method development because arborol fibrils resemble those made by -amyloid -amyloid: $300,000/gram (probably more if we make it!)[9]-10-[9]: $120/gram (make it yourself)

TEM image of Amyloid fibrils after 14-days incubation. A 3x expansion (inset) TEM image of 0.2% [9]-12-[9]

Petkova, Aneta T.; Tycko, Robert et al. PNAS (2002), 99(26), 16742-16747

200 nm100 nm

Yu, Russo, Younger, Henk, Hua, Newkome and Baker J. Polym. Sci. Part B: Polymer Physics, 38, 2787-2793 (1997)

FFTEM of 3% [9]-10-[9]

Confocal imagefrom FM (3% [9]-12-[9])

3% [9]-12-[9] by POM

N N

N

OOH O

OOH

NH

Cl

Cl

5-DTAF

Wet SAXS for Different Concentrations

•They are rods… more so at high concentration

•Diameter from 2D Guinier ~ 54Å does indicate multi-strands in wet gel

0.0 0.2 0.4 0.6

1E-4

1E-3

0.01

0.1

1 ___ 4% [9]-12-[9]___ 3% [9]-12-[9]___ 1.5% [9]-12-[9]

qI(q

) / a

rbitr

ary

q2/ nm-2

cgc

cg

RR

RqqqIqqI

2

3)0(ln)(ln

22

Rcg

R = D/2

In dilute solution

4x4 m AFM for 0.2%[9]-12-[9] on mica

TEM for 0.2%[9]-12-[9]

Inhibition Strategies

Strategy

Wanted to be terminator, settled for governor.

Self-assembly and Inhibition of Arborol Gels

• Inhibitors: One Directional Arborols

OH

OH

OH

NH

OH

OH

OHNH

OO

O

OH

OH

OH

NH

[9]-6, [9]-8 and [9]-10 (One Directional arborols)

3-D Structure of [9]-6

Extruding Arborol FibersFilter

Before Filtering After Filtering

0.2% [9]-10-[9] Filtering

Water

0.02%[9]-60.1% [9]-10-[9]0.01%[9]-6

0.1% [9]-10-[9]

Self-assembly of [9]-10-[9]

Self-assembly of Dilute Arborols—Rh

Changing

0 1 2 3 4

50

100

Rh

/ nm

Number of Days

[9]-10-[9]only [9]-10-[9] plus [9]-6

Rh from linear fit of gamma vs q2 of DLS data at five angles: 40, 50, 60, 70 and 90 degrees.

0.1% [9]-10-[9] only Rh=250 ± 17 nm

0.1%[9]-10-[9] plus 0.01%[9]-6 Rh=161 ± 4 nm

One Month Later:

Size distributionby CONTIN

1E-7 1E-6 1E-5 1E-4 1E-3 0.01 0.1

5th day

4th day

3rd day

2nd day

1st day

Rh/107nm

Amplitude

0.1% [9]-10-[9] in Continuous days

[9]-10-[9] 2/2 Rh/nm Peak(%) 1st Day 0.06 52 ± 2 91 2nd Day 0.14 70 ± 1 93 3rd Day 0.2 92 ± 2 90 4th Day 0.13 102 ± 1 93 5th Day 0.21 127 ± 2 92

CMC for [9]-6

0 2 4 6 8 10 12 1450

55

60

65

70

75

Concentration / (mmol/L)

Sur

face

Ten

sion

/ (

mN

/m)

(CMC = 4.7 mg/ml)TEM for [9]-6 micelles 7mg/ml

Critical Micelles Concentration of [9]-6 at 25 oC

0.1 1 10 100 1000 10000 100000

0.000

0.005

0.010

0.015

0.020

0.025

0.030

21400 nm

304 nm

13 nm

Am

plitu

de

Rg/nm

[9]-6 MicellesCONTIN for [9]-6 micelles 7 mg/ml filter by 450 nm PVDF filter

Rg = 124 ± 9 nmRh = 282 ± 131 nm

Other unidirectional Arborols

0 2 4 6 8 10 12

0

10

20

30

40

Sur

face

Pre

ssur

e /(

mN

/m)

Area/molecular /(Ang2/molecular)

NIMA LB trough

Pressure-area isotherm of [9]-8 at 25 oC

0 2 4 6 8 10 12

0

10

20

30

40

Sur

face

Pre

ssur

e /(

mN

/m)

Area/molecular /(Ang2/molecular)

After 9 conpressions

Pressure-area isotherm of [9]-10

0 2 4 6 8 10 120

5

10

15

20

25

30

35

40

Sur

face

Pre

ssur

e /(

mN

/m)

1st Compression 2nd Compression 3rd Compression 4th Compression 5th Compression 6th Compression 7th Compression 8th Compression 9th Compression 10th Compression 11th Compression

Area/molecular /(Ang2/molecular)

100 m

Crystal structure of [9]-10 in mixture of water and MeOH under POM

Conclusion

• The inhibitor [9]-6 slows down the assembly of arborol fibers.

• The size distribution after filtration is narrow.

• The inhibitor forms micelles.

• Surface properties of [9]-8 and [9]-10 are intriguing.

Acknowledgement

• Russo group• Supported by the National Science

Foundation under Grant DMR-0075810. • Coates travel fund from LSU

Thank You!

Chipmunk atMcMaster University