1

A few questions

• What are the main supramolecular interactions? What are their properties?

• What is preorganization, complementarity?

• What is a receptor, a carrier?• Example for a receptor for an amino acid.

• How to synthesize a macrocycle? Examples for efficient syntheses of macrocycles.

• How to synthesize a supramolecular cube, a catenane, a rotaxane?

• The properties of dendrimers? • Example for a molecular machine.

2

Wires and Related Systems

• Balzani, V.; Venturi, M.; Credi, A.Molecular Devices and Machines, Chapter 2-6

Host Syntheses

• See on the slide

3

Wires and Related Systems

• Conductivity measurements on single molecule

• Replacement of some octanethiol molecules with 1,8-octanedithiol molecules and incubation with gold nanoparticles

• Observation with an atomic force microscope

• Resistance of a single octanedithiol molecule: 900 MΩ

.

Moore, Science, 2001, 294, 571

4

Photoinduced Electron Transfer

Rate constant: kel α exp(-βelrAB) with

• rAB : distance between A and B

• βel : attenuation factor = ca. 5 Å-1 in vacuum. Less if A and B are separated by matter (ca. 1 Å-1 for saturated compounds and ca. 0.5 Å-1 for oligophenylenes).

• Favorated by a bridge with a low lying LUMO

*A--L--B

A+--L---B

A+--L--B-

Hfe

Hie

E

State diagram illustrating the superexchange interaction between an electron donor A, an acceptor B through a bridge L

5

Photoinduced Electron TransferElectronic WiresFrom Ru(II) to Rh(III) through a 3MLCT

excited state• Exponential decrease of the rate constant

for the homogeneous serie 25+-45+.• 15+ slower due to a higher LUMO of the

bridge.

• 55+ slower due to twisting of the central phenylene unit (sterical reasons).

6

Photoinduced Electron Transfer

1 and 2 : Distance dependant superexchange mechanism (tunneling)

3 – 5 : Bridge assisted hopping dynamics, wire-like (LUMO of the bridge similar to the LUMO of tetracene).

Wasielewski, Nature, 1998, 396, 60. JACS, 2001, 123, 7877.

7

Energy transfer

• Two different mechanisms

8

Energy Transfer

Resonance Mechanism

• Also called trough-space, Förster-Type or Coulombicmechanism.

• Long range mechanism based on dipole-dipole coupling (1/r6

dependence on the distance).

• Efficient when both partners have high oscillator strengths, good spectral overlap, and a correct orientation.

• Förster-Radius (50 % transmission): 4.9 nm for Cyan Fluorescent Protein – Yellow Fluorescent Protein

9

Energy Transfer

Exchange Mechanism

• Also called Dexter-Type or through-bond mechanism.

• Requires orbital overlap, exponentially dependant on distance.

• Spin selection rule: spin conservation in the reacting pair• Efficient for triplet-triplet energy transfer, for example.

10

Energy Transfer

Photonic Wires

• Transfer from Ru(II) to Os(II) by a superexchange mechanism

• Rate constants are higher than the one expected for a resonance mechanism

• Exponential decrease of the rate with increasing length

• A further increase of the number of phenylene unit should lower the triplet state, switching the mechanism to wire-like.

Balzani, JACS, 1999,121,4207.

11

Energy Transfer

12

Energy Transfer

Cascade hopping mechanism

• The transfer can be slowed down (80 times) by oxidation of the anthracene unit.

13

Energy Transfer

• Delocalization in a giant chromophore

• The energy levels of the spacer and the donor are similar mixing occurs.

• The excitation is then trapped by the anthraceneunit.

14

Switches

Definition 1 (strict):

• A device incorporated in a molecular wire that can reversibly interrupt the electron or energy transfer.

Definition 2 (large):

• Any molecular system that can be reversibly interconverted between two (or more) different states. (Definition 1 + molecular devices)

15

Switches

Switching under thermodynamic control

• e.g., temperature change

• Solvent effects

• Changes in electrochemical potential• pH change, (ph indicators)

no barrier, can not be locked in

16

Switches

Switching under kinetic control

• Separated by some kinetic barriers

• Usually controlled photonically (or chemically).

• Ranges from picoseconds (electronic excited states) to years• Exit is usually achieved by a second stimulus

can be locked in

17

Switches

A good switch must be:

• Thermally stable,both isomers should not return to the initial state in the dark

• Fully reversible

• Fatigue resistant1000 cycles can be done with the actual switches, it corresponds to a side reaction quantum yield of ca. 0.001

• Show an important change in its electronic properties

Irie, Chem. Rev. 2000, 100, 1685

18

Switches

The classical, optimized example:The reversible photoisomerization of 1,2-bis-(3-thienyl)ethene derivatives

• OFF: open-ring isomer aπ- electrons are localized in the thiophene ring

• ON: closed ring isomer bπ-electrons are delocalized through the whole unit.The electronic interaction between the X and Y substituents increases.

19

Switches

The stilbene-dihydrophenanthrene system

This parent system is not useful because :

• Returns to stilbene in the dark

• Easily oxidized in the presence of air

20

Switches

Photoelectrochemical switching• No electrochemical process in the open isomer 51a• A reversible reduction wave at –230 mV in the closed form 51b

electron flow can be controlled by photoirradiation

352 nm

662 nm

Irie, Chem. Rev. 2000, 100, 1685

21

Switches

Switching of photoinduced electron transfer

ON OFF

• ON in the open formDirect electron transfer between the substituents.

• OFF in the closed form

The bridge competes successfully for the energy transfer, but further transfer is thermodynamically forbidden.

22

Switches

Switching Energy-Transfer Processes

• Photon inputs

4 different chromophores quite difficult to handle

23

Switches

Switching Energy-Transfer Processes

• Redox inputs• The switch must not be in the

main chain

• Oxidation of MgP to MgP.+ (E = +0.34V) quenches the fluorescence.

• Can also be performed chemically (Ferric perchlorate)

BDPY: Boron-dipyrromethene dye

24

Multistate-Multifunctional Systems

Write-Lock-Read-Unlock-Erase Cycles

25

Computing at the molecular level

Stoddart, Structure and bonding, 2001, 99, 190.

26

Photoinduced Charge Separation

A liposome-based proton pump

Moore, Nature, 1997, 385, 239.

27

Photoinduced Charge Separation

Light-driven Production of ATP

Moore, Nature, 1998, 392, 479.

28

Thiacalixarenes

• A readily accessible cavity, slightly bigger than calix[4]arene

Miyano, Chem. Rev. 2006, 106, 5291

29

Thiacalixarenes

• Rotation can be blocked by substituents bulkier than propyl

Miyano, Chem. Rev. 2006, 106, 5291

30

Thiacalixarenes

• Toward chiral host compounds

Miyano, Chem. Rev. 2006, 106, 5291

31

Dynamic Covalent Synthesis

Warmuth, JACS, 2006, 128, 14120.

• The small capsules are first kinetic products among a mixture of oligomeric(4-9 units) cavitands. (after ca. 1h reaction time).

• No linear oligomersare present; unreactedgroups are disfavored by 4 kcal/mol.

• Slight differences in the solvation lead to different products (a polar solvent lead to a small capsule).

82 %

35 %

65 %

yield

32

Dynamic Covalent Synthesis

Warmuth, JACS, 2006, 128, 14120.

The entropically most favorable capsule:

• Use of the flexible or preorganized diamines 9-14 lead almost quantitatively to the dimer.

• Use of ethylene diamine as a bridge does not lead to dimer formation, probably because it prefers an anti conformation

33

Synthesis of Macrocycles

Macrocyclic Schiff-Base Synthesis

• Aliphatic dicarbonyl compounds low hydrolytic stability• Aromatic and heteroaromatic dicarbonyl compounds hydrolytically stable,

easier to chromatography

• Aliphatic diamines most nucleophilic and most flexible

• Cycloaliphatic diamines nucleophilic and rigid• Aromatic diamines slightly nucleophilic and rigid

e.g., the reaction of o-phenylenediamine can be stopped after one condensation. The second step requires acid catalysis. Ustynyuk, Chem. Rev. 2007, 107, 46.

34

Synthesis of Macrocycles

Macrocyclic Schiff-Base Synthesis• A reversible reaction leading first to a mixture of mainly cyclic oligomers.

• Prolonged stirring lead to the thermodynamically most stable compound(s).• The yields and even the obtained products are strongly dependant of the

reaction conditions (solvent, catalyst, ….): optimization is required

• The dynamic combinatorial library generated requires usually separation by HPLC

• The macrocycles are often reduced to the amine in order to obtain a stable product. After protonation, reversed-phase HPLC may be used.

Often templated by a metal ion

• Pro: really efficient

• Con: The better templates are also difficult to be removed.• Con: Metal ion are small only for small macrocycles

Ustynyuk, Chem. Rev. 2007, 107, 46.

35

Synthesis of Macrocycles

And up to [7+7]Realized under high-dilution conditions

36

Synthesis of Macrocycles

Macrocyclic Schiff-base synthesis without an efficient template:

• [1+1] condensation only if the two reactants are perfectly matched • Orientation of the end groups

• Size of the reactants

• Rigidity

• [2+2] condensation is obtained in the standard case

• The obtained macrocycle is usually already flexible enough to be free of strain

• It is favored by entropy (minimization of the number of molecules implicated)

Ustynyuk, Chem. Rev. 2007, 107, 46.

37

Synthesis of Macrocycles

• [1+1] condensation

y=74-92%

38

Synthesis of Macrocycles

[3+3] condensation

• Trans-1,2-diaminocyclohexane possesses a 60o dihedral (angles).

• Connection with rigid linear rods (180o, edges) leads to formation of a triangle.

39

Synthesis of Macrocycles

[6+6] condensation

• Reaction performed in dichloromethane

• Macrocyclestabilized by theH-bridges

• Product is insoluble and driven out of the equilibrium

MacLachlan, Chem. Commun., 2006, 2480–2482

40

Synthesis of Macrocycles

Anionic template effect

• Usually does not affect the structure of the product nor the yield

• The pyrrol unit is able to build an H-bridge with anions The equilibrium may be shifted.

• But not in MeOH, protic solvents compete for the formation of H-bridges

Ustynyuk, Chem. Rev. 2007, 107, 46

75%

41

Synthesis of Macrocycles

• Anionic template effect; rearrangement in MeCN within 5 days

• Strongly binds sulfate and phosphate in MeCN (but not nitrate nor halogenides)

Ustynyuk, Chem. Rev. 2007, 107, 46

quantitative

42

Synthesis of Macrocycles

Hydrazone Dynamic Combinatorial Chemistry

• Hydrazone exchange is reversible under acidic conditions

43

Synthesis of Macrocycles

Hydrazone Dynamic Combinatorial Chemistry

• Under acidic conditions, the acetal is deprotected and exchange is starting.

Sanders, Org. Biomol. Chem., 2003, 1, 1625.

p

PF

pPF3

44

Synthesis of Macrocycles

Hydrazone Dynamic Combinatorial Chemistry

• Amplification of the trimer by a Li or Na template

• pPF3 is a good host for:Li : 10000 M-1

Na: 19000 M-1

in chloroform/methanol 98/2

Sanders, Org. Biomol. Chem., 2003, 1, 1625.

45

Synthesis of Macrocycles

Hydrazone Dynamic Combinatorial Chemistry

• Acetylcholin (Ach) amplificates a catenane.y = 67%

Sanders, Science, 2005, 308, 667.

46

Synthesis of Macrocycles

Hydrazone Dynamic Combinatorial Chemistry

Sanders, Science, 2005, 308, 667.

• A receptor with a 100 nM affinity for acetylcholine:K = 1.4 x 107 M-1 in CHCl3/MeOH 95/5

47

Synthesis of Macrocycles

• NMR without Ach:Broad signals several conformers slowly interconverting (rotating) on the NMR time scale

• With Ach:Sharp signals Ach selects only one conformation

Sanders, Science, 2005, 308, 667.

Hydrazone Dynamic Combinatorial Chemistry

48

Synthesis of Macrocycles

Hydrazone Dynamic Combinatorial Chemistry

Sanders, Science, 2005, 308, 667.

49

Synthesis of Macrocycles

Disulfide exchange

• Quenched by lowering the pH

• Pro: has the potential to be easily decomposed (metabolized).

50

Synthesis of Macrocycles

Disulfide exchange

51

Synthesis of Macrocycles

Disulfide Dynamic Combinatorial Library (DCL)

• Use of 3 rigid building blocks suitable for cation-pi interactions

• Soluble in water under basic conditions

• Use of high template concentration leads to a preferred amplification of the small oligomers over the higher ones.

Sanders, JACS, 2005, 127, 9392.

52

Synthesis of Macrocycles

Induced-Fit Hosts

• Strong amplification high binding constant (4 x 106 M-1 in borate buffer, pH 9)

• The best host may not be the main product.

Sanders, JACS, 2005, 127, 9392.

53

Synthesis of Macrocycles

Induced-Fit Hosts

Sanders, JACS, 2005, 127, 9392.

Figure 6. a) The host 3 and its guest in an extended conformation, b) the same host and guest in a folded conformation, c) a cartoon representation of b, showing a rationalisation of the observed diastereoisomerism.

54

Synthesis of Macrocycles

Catalysts from DCLsfor a Diels-Alder reaction

• Use of an analogous of the transition state as a template for the host (catalyst) synthesis

• Product = transition state analogue (very roughly)

• The host accelerates the Diels-Alder reaction (10 times)

• But it has a low turn-overreactant: K = 130000 M-1

product: K = 240000 M-1Sanders, Angew. Chem. IE 2003, 42, 1270.

55

Synthesis of Macrocycles

DCL of porphyrin disulfides

• Selective amplification of the dimer, trimer and tetramer by using different templates

• Performed in chloroform

• Templating with neutral molecules remains a difficult task lack of strong interactions

56

Multivalency

Reinhoudt, Langmuir, 2002, 18, 6988. JACS, 2000, 122, 4963.

• The observed rupture forces are multiples of 55 pN.

• The ferrocenesdecomplex and rebind spontaneously on the AFM time scale. (1 ms).

57

Multivalency

58

Molecular Printboards

Multivalency, toward strong interactions• Densely packed SAM due to the reversibility of the interactions

• Kinetically stable assembly, cannot be washed out by CD solutions.

Wolfgang Knoll, Reinhoudt, Langmuir, 2005, 21, 7866.

59

Molecular Printboards

Layer by layer Assembly

• Mean Au particle size: 2.8 nm (TEM)

• Realized at pH 2 protonation of the PPI dendrimers water soluble dendrimers in their extended conformation

Reinhoudt, Chem. Soc. Rev. 2006, 35, 1122.

60

Unidirectional Rotors

An altitudinal rotor on Au(111)

• Molecules immobile over hours as shown by STM.

• Rotates when placed in an alternating electric field. (STM tip)

Michl, JACS, 2004, 126, 4540; Chem. Rev. 2005, 105, 1281.

61

Artificial Motors

Molecular muscles

• Powered with Fe(ClO4)3/ascorbic acid

Stoddart, JACS, 2005, 127, 9745. Balzani, Chem. Soc. Rev., 2006, 35, 1135

62

Artificial Motors

Molecular Muscles• Fixed on a flexible gold coated cantilever

(500 x 100 x 1 µm)

63

Artificial Motors

Single Molecule Force Spectroscopy

• Based on the photoisomerization of cis/trans azobenzenecis-azobenzene: 1.0 nmtrans-azobenzene: 1.1 nm

• Length change: 3% for n= 46

• Can be shortened against a load of 400 pNwith 120 photons of λ = 365 nm Total efficiency = 0.07 %

Gaub, Macromolecules, 2003, 36, 2015.

64

Artificial motors

Crowded-alkene based helical motors

• Light-driven

• Unidirectional

Feringa, JACS, 2006, 128, 5127.Chem. Soc. Rev. 2007, 36, 77.

65

Artificial Motors

• Bulky substituents accelerate the rotation.

• Larger increase of the energy in the ground state than in the transition state. the fastest thus far

66

Nanocars

• Translation perpendicular to the axles1 min per images at 200°C

67

Nanocars

Tour, JACS, 2006, 128, 4854.Chem. Soc. Rev. 2006, 35, 1043.

68

Motorized Nanocars

Con of fullerene wheels:

• Strong absorbption at 365 nm

• Low solubility

• Difficult to connect• Bind strongly to the Au surface

Replacement by p-carborane

69

Molecule Carrier

Anthraquinone as a cargo for CO2

• Transforms the diffusion of CO2 on Cu(111) from isotropic to linear.

• The interaction is mediated by the substrate (0.12 eV).

• 1eV = 96.5 kJ/mol.

Bartels, Science, 2007.

70

Molecule Carrier