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

1. 3rd International Summer School “Supramolecular Systems in Chemistry and Biology” Lviv, Ukraine

2. Topology : the science of objects which can be infinitely distorted (totally differentfrom 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

3. 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)

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

5. gf gf Dietrich-Buchecker et al., Tet. Lett., 1983 "entwining" "gathering and threading"

6. Dietrich-Buchecker et al., JACS, 1984

7. (27%) OH Dietrich-Buchecker et al., JACS, 1984

8. KCN [Cu(CH3CN)4][PF6] (100%) Dietrich-Buchecker et al. (1983-84) and Pascard et al. (1985)

9. Synthesis of Catenanes : "template" methods ➪ Fraser Stoddart and co-workers : p-p 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

10. The synthesis of topologicaly non trivial molecules is, in itself, a challenging task the trefoil knot Strasbourg,1989 the Borromean rings UCLA, 2004 In the course of the last 20 years, many such systems have been made (challenge) and studied (new properties)

11. 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

12. Two examples of biologically essential molecular machines ATP-synthase : rotary motor Kinesin "walking" on a microtubule : molecular shuttle

13. = Cu(II) = Cu(I) rotation of a ring within another ring (no directionality): use of the Cu(II)/Cu(I) couple (Livoreil et al., 1994) -e- +0.67 V seconds minutes +e- -0.06 V

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

16. a synthetic molecular "muscle" (2000➠) Maria Consuelo Jiménez (Chelo)...Christiane Dietrich-Buchecker

17. a) =bipy =Cu(I) =guest molecule - + =Zn(II) poprhyrin b) =M-30 like macrocycle = bulky stopper A chemically driven molecular machine (2005 ➠) : from an adjustable receptor to a molecular press : a [3]rotaxane Towards an artificial molecular press = bipy = Cu(I) = guest molecule = Zn(II) porphyrin = coordinating ring = bulky stopper JACS, 2008 & 2009

18. molecular chaperones encapsulation, folding and release of proteins Schematic drawing and structure of a complex between GroEs (blue) and GroEL (green), including a cross-section through the GroEL part.

19. the organic components of the [3]rotaxane

20. demetalation of the [3]rotaxane Cu...Cu ~ 8 to 8.5 Å KCN CH2Cl2/CH3CN/H2O 95%

21. guest log Kass= 7.5 ± 0.2 log Kass= 6.0 ± 0.2 These values reflect both the adaptability of the [3]rotaxane host and the respective basicities of the guests

22. log Kass= 6.8 ± 0.2 log Kass= 6.8 ± 0.2 destabilisation stabilisation free rotaxane : log Kass= 7.5 ± 0.2 log Kass= 6.0 ± 0.2

23. Two-dimensional interlocking arrays (2005 ➠)

24. Topologically linked Protein Rings in the Bacteriophage HK97 Capsid Wikoff, Liljas, Duda, Tsuruta, Hendrix and Johnson, Science, 2000 a natural chain-mail

25. a cyclic [2]rotaxane tetramer consisting of two "filaments" and two bis-macrocycles Jean-Paul Collin, Julien Frey, Valérie Heitz and Christian Tock – 2006 ➠

26. the organic fragments the two-chelate rod the bis-macrocycle

27. = spacer = bidentate chelate = Cu(I) 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

28. O O O O O O O O O O M e O O M e O N N N N C u C u 2 M e O O M e N N N N N N N N 4 P F 6 4 C u ( C H C N ) P F 3 4 6 N N N N O C H C l / C H C N O O 2 2 3 O 7 d a y s / r . t . O O N N N 2 N N N N N N O N O O C u O C u O O N N N N O O O M e O O M e O O O O O O O O the threading reaction 95%

29. X-ray structure : Kari Rissanen (2008)

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

31. Trapping - Releasing from an adjustable receptor to a molecular press : a [4]rotaxane from an adjustable receptor to a molecular press : a [4]rotaxane

32. a [4]rotaxane with 2 porphyrinic plates

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

34. the axles :

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

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

37. 24 covalent bonds between the two chelating fragments quantitative

38. “click” chemistry affords the real rotaxane (95% yield for the quadruple stoppering reaction!)

39. JACS, 2010

40. ~45 Å ~50 Å MW ~ 9,000

41. host-guest properties of the [4]rotaxane (weak internal plus external) (7.3) (7.4) (no "internal" complex) (no "internal" complex) Chemical structures of guests G1 to G5 (stability constants : logKs)

42. demetalation leads to a collapsed structure G Guest 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

43. removal of the 4 copper(I) atoms KCN

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

45. a switchable receptor The collapsed [4]rotaxane is totally unable to complex an organic guest internally G Guest 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

46. 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 Koizumi Julie Voignier…Valérie Heitz Catenanes and Knots X-ray structures Claudine Pascard…Michèle Césario (Gif-sur-Yvette) Jean-Fischer…André De Cian…Nathalie Gruber …Richard Welter (Strasbourg)

47. 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

48. 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)

49. 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