Lect 17-18 Self Assembly I_print

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MSE 598/494 Bio-inspired Materials and BiomaterialsMSE 598/494 Bio-inspired Materials and Biomaterials

Instructor: Ximin He

TA: Xiying Chen Email: [email protected]

2014-04-18

Lecture 17-18

Self-assembly I

Self-assembled Structure

What you will learn in the next 75 minutes

Self-assembly

1. Molecular clefts, cages

2. Enzyme mimics

3. Self-assembled liposome-like systems

4. Ion-channel mimics

5. Base pairing structures

6. DNA-DNA structures

7. Bioinspired frameworks (Option for Lit Rev Presentation)

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Self-assembly

Multifunctional building blocks are assembled into larger molecularentities showing considerable sophistication in both their function andform.

Natural self-assembly processes: Protein folding,

the assembly of DNA,

the formation of bilayers, micelles, and vesicless

Synthetic self-assembly: Self-assembly structures prepared by the bottomup approach

Arise from supramolecular chemistry, when it became a subdescipline ofchemistry

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Supramolecular Chemistry

History:

Originate from Weak bonds: 1873, van de Waals force; 1950, Hydrogen bond

DNA : nucleic acid double helix are held together by base pairing

Enzyme: interaction with substrate


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History: In 1894, Herman Fischer:enzyme-substrate interactions a lock and key

the fundamental principles ofmolecularrecognition and host-guest chemistry

Nobel Prize in 1987: D. J. Cram, J.-M. Lehn, andC. J. Pedersen

in particular for the development of selective "host-guest" complexes, in which a host molecule recognizes

and selectively binds a certain guest


Definition:The domain of chemistry beyond that of molecules andfocuses on the chemical systems made up of a discrete number ofassembled molecular subunits or components.

Traditional Chemistry covalent bonds

Supramolecular Chemistrythe weaker and reversible noncovalentinteractions between molecules

Concepts studied:

molecular self-assembly, folding, molecular recognition, host-guest chemistry,

mechanically-interlocked molecular architectures,

dynamic covalent chemistry


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Self-Assembly

Study Subjects: The spontaneous and often selective inclusion of numerous neutral and

charged (both cationic and anionic) guests in the cavities of a wide rangeof cage-like synthetic hosts (often referred to as container molecules orassemblies

Synthetic structures based on noncovalent interactions, suchas micelles and microemulsions

Glue between building blocks:

weaker noncovalent interactions hydrogen bonding (in nature: carbohydrates, amino acids, nucleic acids)

metal coordination,

-stacking, -cation and -anion interactions,

electrostatic interactions (ionion, iondipole, dipoledipole)

Design and Assembly of Supramolecular Systems

Molecular and ioniccomplementarity

Influencing parameters:Steric and electronic informationinherent in molecular/ionicbuilding blocks

Preparation of bioinspiredsystems:

1. fully syntheticcomponents

2. naturally occurringmolecules (DNA, etc)

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1. MOLECULAR CLEFTS, CAPSULES, AND CAGES

Nature uses molecular (and ionic) encapsulation: enzymes, proteasomes, and viral capsids

1. Host: deep cavity-like structures

2. Guest: can be single molecule or large entities

3. Inclusion process associated with combination of Selective guest uptake (sometimes associated with chiral recognition)

Induced high catalytic activity

Concentration and guest storage of particular guests (including toxicspecies)

Molecular/ionic guest transport processes

Alteration of guest reactivity: e.g. a carboxylate group when encapsulatedin lysozymebecomes capable of hydrolyzing a polysaccharide in water

Research Focus: Syntheses for larger cage-like molecules and assemblies (metalor metal-free structures)

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K+

1) Organic Cage Systems

Large variety of cage or cage-like systems:

Simple self-assembling micelles that can act as primitive hosts,

large container systems capable of including a nanoscale guest ormultiple smaller guests

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1. Closed cages: Cryptand, fullerene

2. Fully organic closed and open cagesbased on preformed macrocyclic scaffolds

1) natural cyclodextrins

2) synthetic cyclic derivatives based oncalixarene, resorcinarene, andcurcurbit[n]uril rings


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1) Organic Cage Systems organic synthesis

Trinacrene

High performance:

a suitable host for a range of organic,organometallic, and inorganic guests

Low yield:

prepared in a conventional four-step synthesisstarting from furan and hexabromobenzene in anoverall yield of less than 0.01%!

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1) Organic Cage Systems templating

Cavitand

water soluble

spontaneously forms a self-assembled dimeric capsule in the presenceof different hydrophobic templating guests, i.e. highly complementaryrigid steroids and flexible straight-chain hydrocarbons weak C-H- interactions

hydrophobic effect

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1) Organic Cage Systems reversible imine linkage

Exist in solution in equilibrium with their precursors namely, thecorresponding carbonyl (aldehyde or ketone) and amine derivatives

The equilibrium corresponds to the reversible hydrolysis or solvolysisof the imine linkage

Allow the generation of cages in fewer steps and in higher yield

Dynamic covalent synthesis: imine-linked, fully covalent nanocubes

1) Organic Cage Systems reversible imine linkage

Dynamic covalent synthesis: imine-linked, fully covalent nanocubes

4: diamine (1,4-phenylenediamine or benzidine), in an 8:12 ratio inchloroform containing trifluoroacetic acid as catalyst

90% yield


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2) Metallosupramolecular Cage Systems - Fe

Metal ions are incorporated in the framework of the cage structures Show inclusion behavior that resembles that exhibited by biological

systems

Example: Fe(II) was demonstrated to interact in acetonitrile with thequaterpyridine-derived ligand

the assembly of an 8+charged tetrahedral shaped cation of type[Fe4L6]

8+, which was found to spontaneously encapsulate the polyatomicanions BF4

, PF6, [FeCl4]

from solution.

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cationic metallosupramolecular cage[Fe4L6(FeCl4)]

5+

an [FeCl4] anion occupies the center of thetetrahedron

selective for Fe(III) species, [FeCl4], overFe(II) analog, [FeCl4]

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2) Metallosupramolecular Cage Systems - Fe

enlarged internal volume of 844 3

encapsulate four tetrahydrofuran solvent molecules in the solid state

as opposed to 174 3 volume in the smaller phenylene-spacedanalog which included a single tetrahydrofuran molecule

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neutral metallosupramolecular cage[Fe4L6(THF)4]5+


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2) Metallosupramolecular Cage Systems -Ni or Zn & Fe

[Fe8(M-L)6]16+ (M = Ni)

internal volume=1340 3

uptake 3 coronene molecules

2) Metallosupramolecular Cage Systems Pd, Cu2+

a series of M12L24 spherical assemblies

displays cuboctahedral symmetry(diameter of 2.6 nm)

M24L48 spherical assemblies, mass of>20,000 Da, diameter of 4.0 nm.

nanocage of composition [Pd12L24]24+

Confirmed by X-ray diffraction


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2. ENZYME MIMICS AND MODELS

Substrate selectivity of enzymes

nature of the cavity Dimensions Lipophilicity

The presence or absence of

complementary functional groups

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Goals of synthetic enzyme mimics: as an aid for defining the active site of a natural system & for probing

potential mode of action

to probe the possibility of producing a functioning catalyst system for

application in the real world.

2. ENZYME MIMICS AND MODELS - Carbonic anhydrase

Carbonic anhydrase II is an enzyme that reversibly converts carbondioxide into the bicarbonate ion.

maintain acid-base balance in blood and other tissues and to help transportcarbon dioxide out of tissues

The active site incorporates a zinc ion bound to three histidines and a watermolecule, such that a distorted tetrahedral coordination geometry is present

Feature: pKa = 7 Readily deprotonated under

physiological conditions

Deprotonation is promoted by the Lewis

acidity of the zinc center and bound water(part of a hydrogen bonded network withinthe cavity)

employed to model the active site of carbonicanhydrase


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2. ENZYME MIMICS AND MODELS - Carbonic anhydrase

Most of the studies have focused on the role of the Zn(II)OH

groupfor the hydration of CO2 & the reverse process, the dehydration ofHCO3

Mimics:1. Using tripodal (substituted) tris(pyrazolyl)borate ligand to form complexes

of type [ZnL(OH)]+ (pKa =6.5)

2. Using triaza-macrocycle,1,5,9-triazacyclododecane to form [ZnL(H2O]2+

Catalytic enhancement of both the hydration of CO2 and the dehydration ofHCO3

3. SELF-ASSEMBLED LIPOSOME-LIKE SYSTEMS

Bilayer structures self-assembly process

Importance: the delivery of both therapeutic (drugs, genes) anddiagnostic agents

Bionanoscience: the self-assembly of liposomes and caposomes usingpolymers

demonstration of forming bilayer structures through the use of smallamphiphilic components Various shapes

By cryo-TEM

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an amphiphilic dendrimer with a cross-sectional view of a spherical dendrimersome.


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4. ION CHANNEL MIMICS

The passage of ions across cell membranes

crucial to cellular vitality

Ion Channel Mimics:Self-assembled pyrogalloarene cages and

nanotubes:

With sufficiently long alkyl chainsextending from the metallocage core, theseassemblies display an excellent ability toinsert into phospholipid bilayers and act asprotein channel mimics

conductance measurements to ion channel

behavior greatest selectivity toward Na+among Na+, K+, and Cs+ ions.

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5. BASE-PAIRING STRUCTURES

WatsonCrick base pairing is central to the structure and function of DNA

reliable base-pairing interactions

strength of the double helical structure over nanometer dimensions

Base pairing mimics: a synthetic nucleotide

coordination of Ag+ by the central imidazole nucleosides.

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imidazoleAgimidazole bonds

double helixdetermined through 107/109Ag15N heteronuclear correlation NMR


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6. DNARNA STRUCTURES

Using DNA and RNA as building blocks RNA

stronger interactions between base pairs than DNA and can give morethermally robust structures

slightly more stable to acidic environments than DNA

tRNA and DNA heteroduplex formation to give a triangular unitthat assembles into a large discrete dodecahedron

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6. DNARNA STRUCTURES

(a) Formation of a triangle through base-pairing interactions;

(b) linking strands bringing two units together to form the prism;

(c) reinforcement of the linking strands;

(d) metallation of the prism (Cu+ or Ag+)

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DNA orgigami

developed a computer program to generate a continuous single-stranded DNA sequence that, along with smaller DNA fragments thatact as staples, would self-assemble into the desired shape.

3D2D

Summary

Self-assembly

1. Molecular clefts, cages

2. Enzyme mimics

3. Self-assembled liposome-like systems

4. Ion-channel mimics

5. Base pairing structures

6. DNA-DNA structures

7. Bioinspired frameworks (Option for Lit Rev Presentationand Original Research)

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Reading Sources

Self-assembly for elctronics, drug delivery, etc

Prof. Samuel Stupp, Northwestern Univ

DNA Origami:

Prof. William Shih, Harvard

Prof. Peng Yin, Harvard

Prof. Hao Yan, ASU

Aarhus University Center for DNA Nanotechnology

(Option for Lit Rev Presentation and Original Research)

Documents

Lect 17-18 Self Assembly I_print