Molecular Systems Engineering

1
Molecular Systems Engineering

• Updated 26-March-05
• (with references)

2
Unit Operations

• Reactors
• Material transporters
• Separators
• Mixers/Splitters
• Energy transfer
• Process control elements

3
Molecular Reactors

• Two functional options
• Type 1 Encloses reactants and controls molecular
  interaction/proximity (catalytic effect)
• Type 2 Interacts with reactant molecule and
  directly participates in reaction

4
Type 1 Reactors

• Multi-guest cavitands
• Encloses 2 guest species
• Self-assembly of capsules induced by the presence
  of the guest species

Scarso, A Rebek, J. J. Am. Chem. Soc. 2004, 126,
8956.
5
Type 1 Reactors

• Micellular self-assembly using amphiphilic
  molecules

Lee, M Jang, C Ryu, J. J. Am. Chem. Soc. 2004,
126, 8082.
6
Type 1 Reactors

• Vesicle/Micelle complexes
• Temperature controls permeability of the
  membranes
• Characteristic ordered-fluid phase transition
  temperature (Tt)
• Small unilamellar vesicles (SUVs) and large
  unilammelar vesicles (LUVs) with different Tt
  exhibit controlled release

Bolinger, P Stamou, D Vogel, H. J. Am. Chem.
Soc. 2004, 126, 8594.
7
Type 2 Reactors

• Selective proteolysis
• Peptide bond cleavage (all X-Pro bonds) using
  Pd(H2O)42
• Complex with cyclodextrin to form
  sequence-specific peptidase
• Cyclodextrin recognizes aromatic side chains
  (e.g. Phe, Tyr, Trp)

Synthesis of conjugate
Sequence-selective activity
Milovic, N Badjic, J Kostic, N. J. Am. Chem.
Soc. 2004, 126, 696.
8
Molecular Transporters

• Nanotubes formed through the self-assembly of
  amphiphilic molecules
• Placement may be controlled through
  immobilization methods

Banerjee, I Yu, L Matsui, H. J. Am. Chem. Soc.
2003, 125, 9542.
9
Molecular Transporters

• Seeman (NYU) DNA nano structures/devices

- DNA motors
- DNA gears
Tian, Y Mao, C. J. Am. Chem. Soc. 2004, 126,
11410.
Chen, Y Mao, C J. Am. Chem. Soc. 2004, 126,
8626.
10
Molecular Transporters

• Rotaxanes as molecular shuttles
• (Molecular switch?)

Long, B Nikitin, K Fitzmaurice, D. J. Am. Chem.
Soc. 2003, 125, 15490.
11
Molecular Separators

• Channels, pores, gates, etc.
• Ex) Synthetic catalytic pores (SCPs)
• Channels may transport products or ions
• Stabilized in hydrophobic membranes (biomimetics)

Sakai, N Sorde, N Matile, S. J. Am. Chem. Soc.
2003, 125, 7776.
12
Molecular Separators

• Molecular recognition ion gating membrane
• Pore size controlled by specific ion signal (i.e.
  Ba2 vs. Ca2)
• Membrane grafted with benzo18-crown-6-acrylamide
  (BCAm), which has a crown receptor which
  captures ions whose size fits in the receptor
  cavity

Ito, T Yamaguchi, T. J. Am. Chem. Soc. 2004,
126, 6202.
13
Molecular Separators

• Ion gating (example 2)
• pH-responsive groups at pore outlet

Casasus, R Marcos, M Martinez-Manez, R
Ros-Lis, J Soto, J Villaescusa, L Amoros, P
Beltran, D Guillem, C Latorre, J. J. Am. Chem.
Soc. 2004, 126, 8612.
14
Molecular Separators

• Separate particular molecule for transport and
  delivery
• Separation may depend on noncovalent interactions
• Hydrophobic effect, hydrogen bonding, etc.
• Ex) Tertiary structure of carrier peptides
• EAK16 self-assembles into ?-sheet microstructure
  exhibiting hydrophobic and hydrophilic surfaces.
• EAK16 good carrier of hydrophobic cargo in
  aqueous solution
• Able to transfer cargo to cell-like vesicle
  membranes
• Other molecules can also covalently bind to cargo
  and direct it (e.g. kinesin, myosin, dynein
  motors).

Keyes-Baig, C Duhamel, J Fung, S Bezaire, J
Chen, P. J. Am. Chem. Soc. 2004, 126, 7522.
15
Molecular Energy Transfer

• Biological example ATP,GTP
• Light
• Electricity/Magnetism

16
Molecular Process Control

• External control of molecular environment causes
  drastic changes
• Temperature
• pH
• Solvent content
• Photoelectric effects
• Molecular sensors
• Molecular controllers

17
Molecular Sensors

• Molecular modifications due to environmental
  changes
• Temperature sensors
• Self-complexing pseudorotaxane
• UC/SC equilibrium sensitive to temperature
• Color intensity measured to sense temperature

UC colorless SC purple
Liu, Y Flood, A Stoddard, JF. J. Am. Chem. Soc.
2004, 126,9150.
18
Molecular Sensors

• Product sensors
• AND/OR logic gates for molecular recognition

Yoshizawa, M Tamura, M Makoto, F. J. Am. Chem.
Soc. 2004, 126, 6846.
19
Molecular Controllers

• Flow controller
• Limits available reactant for use in reaction
• Possible response to process feedback
• Ex) Cavitand encapsulation (deactivation)
• Guest-induced self-assembly
• Selective recognition based on size/shape of
  guest molecules

Kobayashi, K Ishii, K Sakamoto, S Shirasaka,
T Yamaguchi, K. J. Am. Chem. Soc. 2003, 125,
10615.
20
Molecular Controllers

• Control through properties of environment
• Ex1) pH-triggered micelle degradation
• Attachment of hydrophobic groups to the surface
  of the core-forming dendrimer block by sensitive
  acetal linkages
• Upon hydrolysis of the acetals, the hydrophobic
  dendrimer periphery becomes hydrophilic micelle
  destabilizes

Gillies, E Jonsson, T Frechet, J. J. Am. Chem.
Soc. 2004, 126, 11936.
21
Molecular Controllers

• Control through properties of environment (cont)
• Ex2) Vesicle structural modifications at variable
  pH
• pH-triggered release
• Vesicle break-down at low pH triggers release of
  previously encapsulated hydrophilic guest
  molecules.
• Reaction rate control
• Reactor vesicle break-down at low pH to decrease
  reactant interactions

Lee, M Lee, S Jiang, L. J. Am. Chem. Soc. 2004,
126, 12724.
22
Environment?

• Many current mechanisms of molecular function are
  influenced by solvent properties or changes in
  solvent properties.
• Environment properties may be an input and/or
  output of molecular systems function.

23
References(updated 23-March-05)
24
Reactors

• Bolinger, P Stamou, D Vogel, H. J. Am. Chem.
  Soc. 2004, 126, 8594. (pH-induced reactions with
  vesicles inside vesicles)
• Purse, B Ballester, P Rebek, J. J. Am. Chem.
  Soc. 2003, 125, 14682. (cavitand molecular
  recognition and reactions)
• Gibson, C Rebek, J. Organic Letters. 2002, 4
  (11), 1887. (cavitand recognition and catalysis)
• Gissot, A Rebek, J. J. Am. Chem. Soc. 2004, 126,
  7424. (cavitand catalysis)
• Yoshizawa, M Tamura, M Makoto, F. J. Am. Chem.
  Soc. 2004, 126, 6846. (and/or bimolecular
  recognition) Reactor or Control (molecular
  sensor)?
• Lee, M Jang, C Ryu, J. J. Am. Chem. Soc. 2004,
  126, 8082. (block copolymer self-assembled
  reactors)
• Milovic, N Badjic, J Kostic, N. J. Am. Chem.
  Soc. 2004, 126, 696. (palladium complex as
  biomimetic peptidase)
• Scarso, A Rebek, J. J. Am. Chem. Soc. 2004, 126,
  8956. (self-assembled coencapsulation)
• Chen, R Bronger, R Kamer, P van Leeuwen, P
  Reek, J. J. Am. Chem. Soc. 2004, 126, 14557.
  (catalyst anchoring on silica binding sites)

25
Scaffolds (Reactors)

• Park, S Yin, P Liu, Y Reif, J LaBean,T Yan,
  H. Nano Lett. 2005. (DNA grid/scaffold)

26
Material Transporters

• Keyes-Baig, C Duhamel, J Fung, S Bezaire, J
  Chen, P. J. Am. Chem. Soc. 2004, 126, 7522.
  (self-assembling oligopeptide carrier delivery
  system) Transporter or Separator or
  Mixer/Splitter?
• Tian, Y Mao, C. J. Am. Chem. Soc. 2004, 126,
  11410. (DNA gears)
• Yamaguchi, T Tashiro, S Tominaga, M Kawano, M
  Ozeki, T Fujita, M. J. Am. Chem. Soc. 2004, 126,
  10818. (3.5 nm coordniation nanotube)
• Chen, Y Mao, C J. Am. Chem. Soc. 2004, 126,
  8626. (DNA nanomotor)
• Banerjee, I Yu, L Matsui, H. J. Am. Chem. Soc.
  2003, 125, 9542. (immobilized nanotubes)
• Sakai, N Sorde, N Matile, S. J. Am. Chem. Soc.
  2003, 125, 7776. (synthetic catalytic pores)
• Perez, E Dryden, D Leigh, D Teobaldi, G
  Zerbetto, F. J. Am. Chem. Soc. 2004, 126, 12210.
  (light-operated rotaxanes) Transport or
  Control?
• Badjic, J Balzani, V Credi, A Silvi, S
  Stoddart, Science, 2004, 303, 1845. (molecular
  elevator)
• Altieri, A Gatti, F Kay, E Leigh, D Martel,
  D Paolucci, F Slawin, A Wong, J. J. Am. Chem.
  Soc. 2003, 125, 8644. (rotaxanes as molecular
  shuttles) Transport or Control?
• Long, B Nikitin, K Fitzmaurice, D. J. Am. Chem.
  Soc. 2003, 125, 15490. (electron transfer
  rotaxanes) Transport or Control?
• Vignon, S Jarrosson, T Iijima, T Tseng, H
  Sanders, J Stoddart, JF. J. Am. Chem. Soc. 2004,
  126, 9884. (rotaxanes as switch) Transport or
  Control?
• Zhu, F Schulten, K. Biophysical Journal. 2003,
  85, 236. (water and proton conduction in carbon
  nanotubes)
• Rothemund, P Ekani-Nkodo, A Papadakis, N
  Kumar, A Fygenson, D Winfree, E. J. Am. Chem.
  Soc. 2004, 126, 16344. (DNA nanotubes)

27
Separators

• Hernandez, R Tseng, H Wong, J Stoddart, JF
  Zink, J. J. Am. Chem. Soc. 2004, 126, 3370.
  (pseudorotaxanes as nanovalves)
• Casasus, R Marcos, M Martinez-Manez, R
  Ros-Lis, J Soto, J Villaescusa, L Amoros, P
  Beltran, D Guillem, C Latorre, J. J. Am. Chem.
  Soc. 2004, 126, 8612. (ionically controlled
  molecular gates)
• Marti-Rujas, J Desmedt, A Harris, K Guillaume,
  F. J. Am. Chem. Soc. 2004, 126, 11124. (selective
  molecular transport)
• Meijer, E van Genderen, M. Nature. 2003, 426,
  128. (dendrimers as delivery systems)
  Separators or Transporters?
• Jeon, Y Kim, H Jon, S Selvapalam, N Oh, D
  Seo, I Park, C Jung, S Koh, D Kim, K. J. Am.
  Chem. Soc. 2004, 126, 15944. (artificial K ion
  channel)

28
Mixers/Splitters
29
Energy Sources or Transfer
30
Process Control Elements

• Kobayashi, K Ishii, K Sakamoto, S Shirasaka,
  T Yamaguchi, K. J. Am. Chem. Soc. 2003, 125,
  10615. (cavitand guest encapsulation)
• Ito, T Yamaguchi, T. J. Am. Chem. Soc. 2004,
  126, 6202. (molecular recognition ion gating
  membrane)
• Saito, S Rebek, J. Bioorganic Medicinal Chem.
  Lett. 2001, 11, 1497. (cavitand selective
  recogntion)
• Liu, Y Flood, A Stoddard, JF. J. Am. Chem. Soc.
  2004, 126,9150. (thermally and electrochemically
  controllable switches)
• Gillies, E Jonsson, T Frechet, J. J. Am. Chem.
  Soc. 2004, 126, 11936. (pH-induced dendritic
  copolymer self-assembly) Control or Separators?
• Lee, M Lee, S Jiang, L. J. Am. Chem. Soc. 2004,
  126, 12724. (pH and temperature controlled
  self-assembly of amphiphilic molecules) Control
  or Reactors or Separators?