Ignacio PrezVictoria

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Diffusion NMR Studies of Dynamic Combinatorial
Libraries Involving Self-Assembled Receptors
Based on Hydrogen Bonds
Ignacio Pérez-Victoria
Project leader Aldrik Velders
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Dynamic Combinatorial Chemistry
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Dynamic Combinatorial Chemistry
Nucleic acids Synthetic supramolecular templates ?
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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
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Characterization of Double Rosette Assemblies
Chem.Eur.J. 2000, 6, 4104
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Rosettes as Endo/Exo Receptors
Endo-receptors
Exo-receptor
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X-Ray structure of the alizarin complex
Top view
Side view
Angew. Chem. Int. Ed. Engl. 2003, 42, 5717
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Rosettes as Multivalent Exo-Receptors
16 binding
stoichoimetry
Org. Biomol. Chem. 2003, 1, 2596
J. Org. Chem. 2005, 70, 8443
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Rosettes as ditopic Exo-Endo Receptors
Angew. Chem. Int. Ed. 2005, 44, 3248
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Dynamic 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
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DCL of hydrogen bonded assemblies in toluene-d8
Interexchange of components
Statistical distribution
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DCL of hydrogen bonded assemblies in toluene-d8
Alizarin as template
Chem. Eur. J. 2007, 13, 2377
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New 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
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New 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
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New DCL involving Rosettes
Multivalent Rosettes as templates in dynamic
libraries of trivalent guest candidates
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New DCL involving Rosettes
Multivalent Rosettes as templates
Reversible covalent chemistry compatible with
the Rosette assembly
Acid catalysis
Transimination, Imine Metathesis
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New DCL involving Rosettes
J. Org. Chem. 2005, 70, 8443
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New DCL involving Rosettes
Org. Lett. 2000, 2, 4121
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Building blocks
Catalytic TFA
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Titration 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)
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Imine synthesis
Low-yield imine formation after 2 weeks. No
template effect with the rosette
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Imine formation
Building blocks
Building blocks double rosette
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Imine formation
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DOSY analysis
Building blocks
Building blocks double rosette
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DOSY analysis
Building blocks
Building blocks double rosette
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Transimination
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Transimination
Scandium (III) catalysis
Scandium(III) bis(trifluoromethanesulfonate),
polymer-bound  Commercially available
Lehn et al., J. Am. Chem. Soc., 2005, 127, 5528
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New DCL involving Rosettes
Identification and characterization of amplified
species by Diffusion NMR
Dmolecule
Drosette
Dcomplex
Dmolecule gtgt Drosette Dcomplex
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DOSY of the double rosette
DR
Et3N
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Nanoparticle fixed templates
Increasing diffusion coefficient differences by
fixing the receptor to nanoparticles
Dguest gtgtgtgt Dnanoparticle
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Nanoparticle fixed templates
Langmuir 2007, 23, 2377
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Liquid cristalline rosettes
Angew. Chem. Int. Ed. 2006, 45, 7543
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Liquid cristalline rosettes
Powder XRD pattern of 13DEB6 at 120 C, and
schematic of the columnar organization in the
Colh phase
POM images of 13  (DEB)6 at 120 C (top) and of
13  (BuCYA)6 at 180 C (bottom).
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New DCL involving Rosettes. Amplification by
template-induced assembly
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New DCL involving Rosettes. Amplification by
template-induced assembly
(S)-MePropCYA
liquid crystalline rosette

typical rosette
Dynamic Library
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Outlook
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.
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Acknowlegmendts
Dr. Aldrik Velders Prof. David Reinhoudt Dr.
Riccardo Salvio Dr. Alessio Piermattei Ursula
Zomkowska