Self-assembly and its inhibition of bolaform amphiphile dendrimers

1. 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

2. What are the bolaform amphiphiles? They have a dumb-bell shape hydrophilic hydrophilic hydrophobic

3. O H H O O H H H O N O H H O O H O N H O O H O O H N H H O N O H H H O H O H O N H O O O O H N H H O O H H O Arborol example: [9]-10-[9] 9 watery hydroxyl groups MW = 1052 10 oily methylene groups Dr. George Newkome JCS, Chem. Commu. 1986,752 3-D Structure of [9]-10-[9]

4. Arborol Gels’ Properties • Dissolve in warm water • Gel on cooling • Apparently, they are “real” gels • Reversible • Fibers inside the gels • Self-assembly

5. 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 b-amyloid (the protein fragment responsible for Alzheimer’s disease).

6. Do they look alike? • We need this method development because arborol fibrils resemble those made by b-amyloid b-amyloid: $300,000/gram (probably more if we make it!) [9]-10-[9]: $120/gram (make it yourself) 200 nm 100 nm 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

7. Confocal image from FM (3% [9]-12-[9]) 3% [9]-12-[9] by POM FFTEM of 3% [9]-10-[9] 5-DTAF Yu, Russo, Younger, Henk, Hua, Newkome and Baker J. Polym. Sci. Part B: Polymer Physics, 38, 2787-2793 (1997)

8. 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 Rcg R = D/2

9. In dilute solution 4x4 mm AFM for 0.2%[9]-12-[9] on mica TEM for 0.2%[9]-12-[9]

10. Wanted to be terminator, settled for governor. InhibitionStrategies Strategy

11. Self-assembly and Inhibition of Arborol Gels • Inhibitors: One Directional Arborols 3-D Structure of [9]-6 [9]-6, [9]-8 and [9]-10 (One Directional arborols)

12. Filter After Filtering Before Filtering Extruding Arborol Fibers Water 0.1% [9]-10-[9] 0.2% [9]-10-[9] Filtering 0.1% [9]-10-[9] 0.01%[9]-6 0.02%[9]-6

13. Self-assembly of [9]-10-[9] Self-assembly of Dilute Arborols—Rh Changing One Month Later: 0.1% [9]-10-[9] only Rh=250 ± 17 nm 0.1%[9]-10-[9] plus 0.01%[9]-6 Rh=161 ± 4 nm Rh from linear fit of gamma vs q2 of DLS data at five angles: 40, 50, 60, 70 and 90 degrees.

14. Amplitude Size distributionby CONTIN 0.1% [9]-10-[9] in Continuous days

15. CMC for [9]-6 Critical Micelles Concentration of [9]-6 at 25 oC TEM for [9]-6 micelles 7mg/ml (CMC = 4.7 mg/ml)

16. [9]-6 Micelles CONTIN for [9]-6 micelles 7 mg/ml filter by 450 nm PVDF filter Rg = 124 ± 9 nm Rh = 282 ± 131 nm

17. After 9 conpressions Other unidirectional Arborols Pressure-area isotherm of [9]-8 at 25 oC NIMA LB trough

18. 100 mm Pressure-area isotherm of [9]-10 Crystal structure of [9]-10 in mixture of water and MeOH under POM

19. 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.

20. Acknowledgement • Russo group • Supported by the National Science Foundation under Grant DMR-0075810.  • Coates travel fund from LSU Thank You! Chipmunk at McMaster University