Title: Ignacio PrezVictoria
1Diffusion NMR Studies of Dynamic Combinatorial
Libraries Involving Self-Assembled Receptors
Based on Hydrogen Bonds
Ignacio Pérez-Victoria
Project leader Aldrik Velders
2Dynamic Combinatorial Chemistry
3Dynamic Combinatorial Chemistry
Nucleic acids Synthetic supramolecular templates ?
4 Double Rosette Assemblies
Chem.Eur.J. 1997, 3, 1823 Angew. Chem. Int. Ed.
Eng. 1996, 35, 1215
36 H-bonds diss. lt 10-4 M
5Characterization of Double Rosette Assemblies
Chem.Eur.J. 2000, 6, 4104
6Rosettes as Endo/Exo Receptors
Endo-receptors
Exo-receptor
7X-Ray structure of the alizarin complex
Top view
Side view
Angew. Chem. Int. Ed. Engl. 2003, 42, 5717
8Rosettes as Multivalent Exo-Receptors
16 binding
stoichoimetry
Org. Biomol. Chem. 2003, 1, 2596
J. Org. Chem. 2005, 70, 8443
9Rosettes as ditopic Exo-Endo Receptors
Angew. Chem. Int. Ed. 2005, 44, 3248
10Dynamic Combinatorial Libraries involving double
rosettes
- As dynamic components of libraries templated by a
suitable guest. Reversible non-covalent chemistry
(hydrogen bond exchange) - As supramolecular templates (receptors) in
dynamic libraries of putative guest molecules.
Reversible covalent chemistry (CN exchange)
Non polar organic solvents toluene, chloroform
11DCL of hydrogen bonded assemblies in toluene-d8
Interexchange of components
Statistical distribution
12DCL of hydrogen bonded assemblies in toluene-d8
Alizarin as template
Chem. Eur. J. 2007, 13, 2377
13New DCL involving Rosettes
Rosettes as the dynamic componets of the library
Simultaneous use of exo and endo templates
Identification amplified rosette challenging
20 possible different assemblies
R exo-binding sites
Endo
Exo
Templates
14New DCL involving Rosettes
Rosettes as the dynamic componets of the library
Simultaneous use of exo and endo templates
Identification of amplified rosette will be
challenging
Desing of suitable exo template by DCC
15New DCL involving Rosettes
Multivalent Rosettes as templates in dynamic
libraries of trivalent guest candidates
16New DCL involving Rosettes
Multivalent Rosettes as templates
Reversible covalent chemistry compatible with
the Rosette assembly
Acid catalysis
Transimination, Imine Metathesis
17New DCL involving Rosettes
J. Org. Chem. 2005, 70, 8443
18New DCL involving Rosettes
Org. Lett. 2000, 2, 4121
19Building blocks
Catalytic TFA
20Titration of rosette with TFA. Regeneration with
excess Et3N
After addition of excess Et3N
21 mM TFA
7 mM TFA
3.5 mM TFA
Starting material (7mM)
21Imine synthesis
Low-yield imine formation after 2 weeks. No
template effect with the rosette
22Imine formation
Building blocks
Building blocks double rosette
23Imine formation
24DOSY analysis
Building blocks
Building blocks double rosette
25DOSY analysis
Building blocks
Building blocks double rosette
26Transimination
27Transimination
Scandium (III) catalysis
Scandium(III) bis(trifluoromethanesulfonate),
polymer-bound Commercially available
Lehn et al., J. Am. Chem. Soc., 2005, 127, 5528
28New DCL involving Rosettes
Identification and characterization of amplified
species by Diffusion NMR
Dmolecule
Drosette
Dcomplex
Dmolecule gtgt Drosette Dcomplex
29DOSY of the double rosette
DR
Et3N
30Nanoparticle fixed templates
Increasing diffusion coefficient differences by
fixing the receptor to nanoparticles
Dguest gtgtgtgt Dnanoparticle
31Nanoparticle fixed templates
Langmuir 2007, 23, 2377
32 Liquid cristalline rosettes
Angew. Chem. Int. Ed. 2006, 45, 7543
33 Liquid cristalline rosettes
Powder XRD pattern of 13DEB6 at 120Â C, and
schematic of the columnar organization in the
Colh phase
POM images of 13 Â (DEB)6 at 120Â C (top) and of
13 Â (BuCYA)6 at 180Â C (bottom).
34New DCL involving Rosettes. Amplification by
template-induced assembly
35New DCL involving Rosettes. Amplification by
template-induced assembly
(S)-MePropCYA
liquid crystalline rosette
typical rosette
Dynamic Library
36Outlook
Synthesis of all the tripodal amines.
Transimination with the phenolic imine (in the
presence and absence of the rosette)
Preparation of nanoparticle fixed rosette. Find
conditions to minimize clustering. Use of these
as templates for the imine library.
Preparation of nanoparticle-fixed ligands (exo)
for functionalized rosette. Study of rosette
complexation with these nanoparticles.
Preparation of DCL of rosettes (hydrogen bond
exchange)
Characterization of the assemblies formed by
complexation of the alizarin with the liquid
cristalline rosette.
37Acknowlegmendts
Dr. Aldrik Velders Prof. David Reinhoudt Dr.
Riccardo Salvio Dr. Alessio Piermattei Ursula
Zomkowska