3rd International Summer School “Supramolecular Systems in Chemistry and Biology” Lviv, Ukraine

3rd International Summer School “Supramolecular Systems in

Chemistry andBiology”

Lviv, Ukraine

Topology : the science of objects which can be infinitely distorted (totally different from Euclidian geometry)

Chemical Topology : mostly the synthesis and the study of molecular systems whose graphs are non planar (i.e., which can not be represented in a plane without crossing points)

Brevetoxin A or C60 are topologically trivial (sorry!)

Schlegel diagram

a [2]catenane

a [2]rotaxane

Schill & Lüttringhaus could prepare small amounts of such compounds

via elegant but low-yielding and multistep synthetic routes (Angew.

Chem., 1964)

copper(I)-templated synthesis of a [2]catenane

Dietrich-Buchecker et al., Tet. Lett., 1983

gf

gf

"entwining"

"gathering and threading"

Dietrich-Buchecker et al., JACS, 1984

OH (27%)

Dietrich-Buchecker et al., JACS, 1984

(100%)

Dietrich-Buchecker et al. (1983-84) and Pascard et al. (1985)

KCN

[Cu(CH3CN)4][PF6]

Synthesis of Catenanes : "template" methods

➪ Fraser Stoddart and co-workers : stacking and H bonds (1989)

➪ Chris Hunter : H bonding (1992)

➪ Fritz Vögtle et al. : H bonding (1992)

➪ Makoto Fujita et al. : kinetically labile Pd-N bonds and hydrophobic interactions (1994)

... and, later on, many other outstanding research teams

The synthesis of topologicaly non trivial molecules is, in itself, a challenging task

In the course of the last 20 years, many such systems have been made (challenge) and studied (new properties)

the Borromean rings

Strasbourg,1989

UCLA, 2004

the trefoil knot

From catenane to molecular machines

Molecular machines : a very active research area

Catenanes and Rotaxanes are very well adapted to large amplitude motions : pirouetting of a ring

around an axis, translation of a ring along an axis and many other

possible movements

Two examples of biologically essential molecular machines

Kinesin "walking" on a microtubule :

molecular shuttle

ATP-synthase : rotary motor

-e-

+e-

seconds

minutes= Cu(I) = Cu(II)

rotation of a ring within another ring (no directionality): use of the Cu(II)/Cu(I) couple (Livoreil et al., 1994)

+0.67 V

-0.06 V

A molecular "shuttle": the compound is set in motion by modifying the acceptor-donor interaction

a rotaxane dimer is the ideal topology for interconverting a streched structure and a contracted systema synthetic molecular "muscle" (2000 )➠

Maria Consuelo Jiménez (Chelo)...Christiane Dietrich-Buchecker

Towards an artificial molecular press

- +

a)

b)

= Cu(I)

= bipy

= guest molecule

= Zn(II) poprhyrin

= M-30 like macrocycle

= bulky stopper

= bipy

= Cu(I)

= guest molecule

= Zn(II) porphyrin

= coordinating ring

= bulky stopper

A chemically driven molecular machine (2005 ) : ➠from an adjustable receptor to a molecular press : a [3]rotaxane

JACS, 2008 & 2009

Schematic drawing and structure of a complex between GroEs (blue) and GroEL (green), including a cross-section

through the GroEL part.

molecular chaperones

encapsulation, folding and release of proteins

NN

O

O

OO

OO

NN

NN N

NNNZn

34

the organic components of the [3]rotaxane

N

NOO

ON

NN

ONNN

N

N

demetalation of the [3]rotaxane

KCN

CH2Cl2/CH3CN/H2O

95%

Cu...Cu ~ 8 to 8.5 Å

N

NOO

O NNN

ONNN

N N

O

N

N

N

N

R R

R R

N N

N N

Zn

OO

OO

N

N N

O

N

N

N

N

R R

R R

N N

N N

Zn

OO

OO

N

N

N N

OO

N

N

N

N

R R

R R

N N

N N

Zn

N

OO

OO

N

N N

OO

N

N

N

N

R R

R R

N N

N N

Zn

N

OO

OO

OO

2+ , 2PF6-

O NNN

ONNN

Cu Cu

NN

N N

N

NOO

ON

NN

ONNN

N N

O

N

N

N

N

R R

R R

N N

N N

Zn

OO

OO

N

N N

O

N

N

N

N

R R

R R

N N

N N

Zn

OO

OO

N

N N

guest

These values reflect both the adaptability of the [3]rotaxane host

and the respective basicities of the guests

log Kass= 7.5 ± 0.2 log Kass= 6.0 ± 0.2

NN

N N

log Kass= 6.8 ± 0.2 log Kass= 6.8 ± 0.2

N

N N

OO

N

N

N

N

R R

R R

N N

N N

Zn

N

OO

OO

N

N N

OO

N

N

N

N

R R

R R

N N

N N

Zn

N

OO

OO

OO

2+ , 2PF6-

O NNN

ONNN

Cu Cu

destabilisation stabilisation

free rotaxane : log Kass= 7.5 ± 0.2 log Kass= 6.0 ± 0.2

Two-dimensional interlocking arrays (2005 )➠

a natural chain-mail

Topologically linked Protein Rings in the Bacteriophage HK97 Capsid

Wikoff, Liljas, Duda, Tsuruta, Hendrix and Johnson, Science, 2000

a cyclic [2]rotaxane tetramer consisting of two

"filaments" and two bis-macrocycles

Jean-Paul Collin, Julien Frey, Valérie Heitz and Christian Tock – 2006 ➠

N NN NOMeMeO

N

NN

N N

N

O

OO

O

O

O

O

O

O

O

O

O

the bis-macrocycle

the two-chelate rod

the organic fragments

42

2

copper(I)-induced threading of two bis-macrocycles on two rods: a cyclic [4]rotaxane

Jean-Paul Collin, Julien Frey, Valérie Heitz, Efstathia Sakellariou and Christian Tock

= bidentate chelate

= Cu(I)

= spacer

N NN NMeO OMe

NN NNOMeMeO

N

O

OO

N

OO

N

O

OO

N

OO

N N

N

O

OO

N

OO

N

OO

N

OO

N N

O O

O

Cu Cu

CuCu

4PF6

95%

the threading reaction

N NN NMeO OMe

N

OOO

NO

O N

O OO

NO

O

N

N

O

O

4 Cu(CH3CN)4PF6

CH2Cl2 / CH3CN

2

2 7 days / r.t.

X-ray structure : Kari Rissanen

(2008)

A two-porphyrin [4]rotaxane : towards high-control molecular

receptors

-

Trapping

Releasing

from an adjustable receptor to a molecular press : a [4]rotaxanefrom an adjustable receptor to a molecular press : a [4]rotaxane

a [4]rotaxane with 2 porphyrinic plates

preliminary study : the quadruple "gathering-and-threading" step

the axles :

(i) pyridine, 60 °C (45%); (ii) 1) Zn(OAc)2, CHCl3/MeOH, reflux; 2) EDTA, CHCl3/MeOH/H2O, r.t., 24h (quant.).

synthesis of the porphyrinic component

RR

R

RR

R

quantitative copper(I)-driven formation of a [4]pseudorotaxane

24 covalent bonds between the two

chelating fragments

quantitative

“click” chemistry affords the real rotaxane

(95% yield for the quadruple stoppering reaction!)

JACS, 2010

~50 Å

~45 Å

MW ~ 9,000

Chemical structures of guests G1 to G5

(stability constants : logKs)

(7.4) (7.3)

(no "internal" complex) (no "internal" complex)

(weak internal plus external)

host-guest properties of the [4]rotaxane

demetalation leads to a collapsed structure

GuestG

double black arrow : Guest : intramolecular interactions betwwen PZn and a Lewis base

(triazole) of the axis

J.-P. Collin, F. Durola, V. Heitz, F. Reviriego, Y. Trolez, Angew. Chem. IE,

2010

NN NN

NN

OO

OOOO

N

N N

N

NN

O O

NN

OO

OOOO

CuCu

NN NN

NN

OO

OOOO

N

N N

N

NN

O O

NN

OO

OOOO

CuCu

N

N

N

N

N N

NN

N N

NN

Zn

ArAr

ArArN

N

N

N

N N

NN

N N

NN

Zn

ArAr

ArAr

4+ . 4PF6-

KCN

removal of the 4 copper(I) atoms

KCN

ON

O

N

NN

N

N N

NN

NN

NN

NN

NN

NN

NN

Zn

O

O

O

OO

O

Ar

Ar

Ar

Ar

O

N

N

O

NNN

O

N N

NN

NN

NN

NN

NN

NN

NN

Zn

O

O

O

O

O

OO

O

O

O

Ar

Ar

Ar

Ar

NN

N

NNN N

O

OO

O

O NO

N

N

O

formation of a totally collapsed structure :no complexation properties anymore!

The collapsed [4]rotaxane is totally unable to complex an organic guest internally

GuestG

a switchable receptor

the host-guest properties are switched on and off by metalation or demetalation

J.-P. Collin, F. Durola, V. Heitz, F. Reviriego, Y. Trolez, Angew. Chem. IE,

2010

Synthesis and Coordination Chemistry

Laboratoire de Chimie Organo-Minérale (Strasbourg)Christiane Dietrich-Buchecker...Jean-Claude Chambron...

Jean-Marc Kern...Jean Weiss...Abdel Klemiss... Dennis Mitchell... Catherine Hemmert...

Jean-François Nierengarten... Jean-Luc Weidmann...Gwénaël Rapenne...

David Amabilino...Aude Livoreil...Riccardo Carina... Bernhard Mohr...Neri Geum Hwang…Christine Hamann…Benoît

Colasson…Pierre Mobian…Masatoshi KoizumiJulie Voignier…Valérie Heitz

Catenanes and Knots

Claudine Pascard…Michèle Césario (Gif-sur-Yvette)Jean-Fischer…André De Cian…Nathalie Gruber

…Richard Welter (Strasbourg)

X-ray structures

Copper-complexed Catenanes and Rotaxanes in Motion

catenanes in motion : Aude Livoreil...Diego J. Cardenas

translation of a ring along an axle : Jean-Paul Collin... Pablo Gaviña

pirouetting of a ring around the axle: Laurence Raehm...Jean-Marc Kern…

Ingo Poleschak…Ulla Létinois…Jack Beierle...Jean-Paul Collin

towards molecular muscles : Maria Consuelo Jiménez

(Chelo)...Christiane Dietrich-Buchecker

photochemically induced motions (Bologna): Nicola Armaroli...Vincenzo

Balzani...Lucia Flamigni...Francesco Barigelletti...Barbara Ventura

Two-dimensional threaded arrays and adaptable receptor

Tomás Kraus (Strasbourg and Prague), Milos Budesinsky, Josef Cvacka

(Prague)

Jean-Paul Collin*, Julien Frey, Valérie Heitz*, Efstathia Sakellariou, Christian

Tock, Fabien Durola, Yann Trolez, Stéphanie Durot, Valérie Sartor and Benoît

Champin

Bi-isoquinoline ligands and their complexes

Fabien Durola & Oliver Wenger, Pirmin Roesel, David Hanss,

Alexander Prikhod′ko, Jacques Lux

X-ray structures: André De Cian

Kari Rissanen et al. (Jyväskylä, Finland), Lydia Brelot (Strasbourg)

Université de Strasbourg and CNRS

European Communities and Région Alsace

Many, many thanks to our Russian friends:

Professors Aslan Tsivadze and Yulia Gorbunova

Professor Alexander Varnek

Dr Alexandre Martynov

The organisers of this nice Summer School

Professor Volodymyr Novikov and his colleagues

Dr Olena Fedorova