Self-assembly and its inhibition of bolaform amphiphile dendrimers
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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
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What are the bolaform amphiphiles?
They have a dumb-bell shape
hydrophilichydrophilic
hydrophobic
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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
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Arborol Gels’ Properties
• Dissolve in warm water• Gel on cooling• Apparently, they are “real” gels• Reversible
• Fibers inside the gels • Self-assembly
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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).
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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
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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
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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
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In dilute solution
4x4 m AFM for 0.2%[9]-12-[9] on mica
TEM for 0.2%[9]-12-[9]
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Inhibition Strategies
Strategy
Wanted to be terminator, settled for governor.
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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
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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]
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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:
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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
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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
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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
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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
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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
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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.
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Acknowledgement
• Russo group• Supported by the National Science
Foundation under Grant DMR-0075810. • Coates travel fund from LSU
Thank You!
Chipmunk atMcMaster University