Macroarea di Scienze M.F.N. Colloqui interdisciplinari Roma, 20 Aprile 2016

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1 Macroarea di Scienze M.F.N. Colloqui interdisciplinari Roma, 20 Aprile 2016 From Nano- to Mesostructures: Governing the hierarchical self-assembly of supramolecular architectures

2 From nano- to mesostructures: Bottom-up approach Hierarchical self-assembly Nano- and mesoscopic structures

3 electrostatic, Van der Waals, HB interactions π-π interaction comparative solvation of monomers and aggregates morphology of the aggregates interfacial phenomena - size and molecular shape

4 Mesoscopic structures from two molecular building blocks: - Steroid porphyrins from the Pavel Drašar porphyrin synthesis lab in Prague - Conformationally constrained peptides from the Claudio Toniolo and Fernando Formaggio peptide synthesis lab in Padua

5 Case study 1: Steroid Porphyrins Pavel Drašar Chem. Eur. J. 2011, 17,

6 H 2 TGS-P Aggregation is complete with 20% of water. J-type aggregates predominate. H 2 DGS-P Aggregation is complete with 40% of water. J- and H-type aggregates are formed.

7 H 2 TGS-P H 2 DGS-P DMAc DMAc H 2 TGS-P H 2 DGS-P 40% H 2 O 100% H 2 O 20% H 2 O DMAc/H 2 O 80/20 (v/v)

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9 H 2 DGS-P tetramer Interaction between the steroid groups make L-handedness the predominant configuration.

10 H 2 DGS-P 0.8 μm H 2 DGS-P 1.6 μm H 2 DGS-P 2.4 μm H 2 TGS-P 2.4 μm

11 Chiral self-assembly Donato Monti Cholic acid Org. Biomol. Chem. 2014, 12,

12 Aggregation occurs with the formation of chiral superstructures. CD pattern suggests the formation of rod-like structures with a regular arrangement of the J aggregates (exciton coupling) A( t) A( ) A1 exp( k1t ) A exp( k t) 2 k 1 = s -1 β 1 = 1.91 k 2 = s -1 β 2 = μm in DMA/H 2 O 58/42 (v/v)

13 A( t) A(0) [ A( ) A(0)][1 exp( kt) ] k = s -1 β = 0.58 A Diffusion Limited Aggregation (DLA) mechanism is operative at this higher concentration! 10 μm in DMA/H 2 O 58/42 (v/v)

14 3μM in DMA/H 2 O 58/42 (v/v) Entangled fibrils! 10μM in DMA/H 2 O 58/42 (v/v) Globules!

15 TSP 1 -OH for each steroid group TSPc 3 -OHs for each steroid group

16 Solvent induced aggregation leads to the formation of chiral supramolecular species TSPc Antonio Palleschi

17 TSPc monomer dimer

18 TSPc octamer

19 Langmuir-Blodgett films Compression isotherm TSP π = 60 mn/m Mma = 80 Å 2 /molecule TSP TSPc π = 55 mn/m Mma = 60 Å 2 /molecule TSPc Expanded vs. condensed liquid phase transition Raffaella Lettieri

20 UV-Vis LB Deposition on quartz Fluorescence TSP TSPc TSPc CD TSP The stereochemical organization of both porphyrin derivatives observed in DMA/H 2 O solution is conserved in the LB film deposited on quartz.

21 Fluorescence Microscopy TSP (multilayer) 20x 20x Fibrils of millimetric length TSPc (multilayer) Thickness: 2.4 ± 0.6 µm

22 Y[µm] Atomic Force Microscopy TSP: LB deposition on silicon wafer nm nm X[µm] Diameter: 130 ± 30 nm Thickness: 80 ± 20 nm

23 Scanning Electron Microscopy TSPc multilayer on glass

24 Case study 2: Peptide Foldamers Foldamers are molecules that have well-defined and predictable folding properties in solution. Claudio Toniolo Fernando Formaggio

25 Blocking the torsional angles by C,α dialkylsubstitution H 3 C CH 3 H 5 C 2 C 2 H 5 NH C CO NH C CO NH C CO Aib Deg D g O H 3 C N CH 3 H 2 C CH 2 H 3 C CH 3 NH C CO NH C CO NH C CO Db 7 g Ac 6 c TOAC

26 C,α -disubstituted aminoacids Ala Aib

27 Aggregation of conformationally constrained model peptides N N N U6N U12N U15N Z Z Z U = Aib; N = Naphthyl; Z = Benzyloxycarbonyl J. Phys. Chem. B 2013, 117,

28 U6N U9N Gianfranco Bocchinfuso U12N U15N For the longer homologues of the series (n 9), unfolding events during the simulation time were not detected.

29 U6N U12N U15N Dotted line: MeOH Dashed line: MeOH/H 2 O 70/30 Continuous line: MeOH/H 2 O 50/50

30 U6N U12N U15N Excimer emission Dotted line: MeOH Dashed line: MeOH/H 2 O 70/30 Continuous line: MeOH/H 2 O 50/50

31 J aggregates K A 7( 1) 10 5 monomer U12N 70/30 v/v MeOH/H 2 O

32 U6N U15N (both from 10μM 70/30 v/v MeOH/H 2 O deposition solution)

33 U12N (from 125 μm 70/30 v/v MeOH/H 2 O deposition solution)

34 U15N Six U15N peptide chains were considered J. Pept. Sci. Special Issue Peptide Materials for Biomedicine and Nanotechnology 2014, 20,

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36 A single Aib vs. Ala substitution inhibits fibrillization of Ala pentapeptides

37 PyA5 PyA3UA U V - V I S PyA5 PyA3UA

38 F L U O R E S C E N C E PyA5 PyA5 PyA3UA PyA3UA adding water adding peptide

39 PyA5 PyA3UA Only PyA5 shows characteristic exciton coupling in the Pyrene absorption region, suggesting aromatic-aromatic interaction at close distances.

40 PyA5 Thioflavine binding assay PyA3UA PyA3UA Infrared Absorption PyA5

41 PyA5 on mica Deposition solution: 10μM in 70/30 MeOH/H 2 O Ernesto Placidi

42 PyA3UA on mica Deposition solution: 10μM in 70/30 MeOH/H 2 O

43 PyA5 equatorial MeOH axial H 2 O equatorial Carlos Aleman (30 years ago) axial

44 PyA3UA equatorial MeOH axial equatorial H 2 O axial

45 David Zanuy Soft Matter (2014) 10,

46 We need a general model for: - hierarchical self-assembly - kinetics of self-assembly We need to fill the gap from molecular aggregates to mesoscopic structures

47 Lab. of Physical Chemistry of Biomolecules Antonio Palleschi, Lorenzo Stella, Gianfranco Bocchinfuso, Emanuela Gatto, Claudia Mazzuca Chemistry Dept. University of Rome Tor Vergata Physical properties of peptide materials Gil Rosenman, Meital Reches, Nurit Ashkenasy Tel Aviv University, Hebrew University, Ben Gurion University Peptide fibrillization and gelification Ian W. Hamley, V. Castelletto Reading University, UK