Chirality in amorphous and crystalline materials - experimental aspects

David Avnir

Institute of Chemistry, The Hebrew University

Summer School on ChiralityMainz, August, 15-17, 2011, sponsored by

#How is it possible to induce chirality in a material?

# How is it possible to extract chiral activity from a material?

Our main road:

SiO2-based amorphous materials

and crystalline metals

Main general questions to be addressed:

Amorphous silica

The classical approach:

Attach covalently a chiral molecule to the surface of the (porous) material

Often, a silylating reaction

How is it possible to induce chirality in a material?

Photophysical Recognition of Chiral Surfaces

With E. WellnerM. Ottolenghi

J. Am. Chem. Soc., 111, 2001 (1989)

The quencher:

DMP, R-Q or S-Q

The excited chiral surface: Silica derivatized with R- or S-BNP

N

For the R-surface (shown):

S-Q/R-Q = 1.3

For the S-surface:

R-Q/S-Q = 1.2

The S-quencher recognizes better the R-surface

Stern-Volmer quenching analysis

The second, newer approach

Dope the material with a chiral molecule

DOPING OF SILICA IS MADE POSSIBLE

BY THE SOL-GEL POLYCONDENSATION

Si(OCH3)4 + H2O (SiOmHn)p + CH3OH

(unbalanced)

Variations on this theme:

–the metals, semi-metals and their combinations

–the hydrolizable substituent

–the use of non-polymerizable substituents

–organic co-polymerizations (Ormosils)

–non-hydrolytic polymerizations

H+ or OH-

Sol Gel XerogelSol Gel Xerogel

sol-particle

entrappedmolecule

monomer

oligomer

-

Organic functionalization

by physical entrapment of molecules within sol-gel matrices

* Small molecules

* Polymers

* Proteins

* Nanoparticles

Monomers,oligomers

Doping the material with a chiral molecule:

# A chiral catalyst

# A protein

# A chiral surfactant

Entrapment of a chiral catalyst

With

F. Gelman

J. Blum

J. Molec. Catal., A: Chem., 146, 123 (1999)

ee = 78% (BPPM)

The advantages

# Covalent bonding chemistry is not needed

# Working with a hydrophobic catalyst in water

# Recyclability

Doping the material with a chiral surfactant

CHO

HC

CH3

H

N

CH3

CH2(CH2)10CH3

CH3

+

(1R,2S)-(-)-N-dodecyl-N

-methylephedrinium bromide

(DMB)

The experiment:

Inducing Circular Dichroism in Congo-Red

Within Silica Sol

SO3Na

NH2

N

SO3Na

NH2

NNNCHO

HC

CH3

H

N

CH3

CH2(CH2)10CH3

CH3

+

The chiral inducer: DMB The achiral probe: CR

CR-DMB@SG sol (red line) and CR-DMB@OSG sol (blue line)

The ICD spectra of co-entrapped CR-DMB in hydrophilic and hydrophobic silica sols

S. Fireman

-40

-20

0

20

40

60

80

300 400 500 600

Wavelength (nm)

CD

(m

deg)

CR-DMB in solution (blue line) and CR solution (red line)

Has the silica matrix become chiral?

Second experiment with doped surfactant:

NMR detection of diastereomeric interactions

within phenylated-silica sols and gels

With S. FiremanS. Marx

PO

OH

O

O

S-BINAP

CHO

HC

CH3

H

N

CH3

CH2(CH2)10CH3

CH3

+

1R,2S-DMB

The possible interactions:

DMB/S-BINAP

DMB/R-BINAP

SiO

Si

O-

O

Si

Si

O

Si

O

O

Si

O

O-

(H3C)2N

(H3C)2N

O-

CHCH

H3C

CH CH

OHH3C

OH

+

+

OO

POO

CHCH

OH

H3CNH(CH3)2

OO

P OO

Si

+

31P-NMR spectrum of BINAP-DMB diastereomers:Looking inside the sol and the gel of silica

S-BINAP R-BINAP

5.99

5.85.96.06.1ppmppm

5.9 4

S-BINAP interacts better with the chiral surfactant

6.00

5.98

5.85.96.06.1ppmppm

In the gel

In solution

In the sol

5.85.96.06.16.2ppm

6.13

26.

146

Is it possible to induce structural chirality in a material?

Make a hole which is chiral -

imprint the material; make a chiral silicate skeleton

What have we seen so far?

# Covalent attachment of a chiral molecule

# Physical entrapment of a chiral dopant

Dickey, 50’s

With

S. Marx

S. Fireman

General methodology for chiral imprinting of

sol-gel based thin-films

Silica thin-film chiral imprinting

Where is “Smart porosity” needed?

for evaluating ee,

for chiral separations,

for selective sensing,

for chiral catalysis

PropranololPropranolol

OCH2CHCH2NHCHCH3

HOH CH3

The functional monomers

Film thickness: 700 nm

Si

H3CO

H3CO

H3CO

CH3Si

H3CO

H3CO

H3CO

Si

OCH3

H3CO

OCH3

OCH3

TMOS PTMOS MTMOS

Two different cases:

I. Selectivity towards an enantiomer of the imprinting molecule

Chem. Mater. ,15, 3607 (2003)

Immersed in solutions of R or S, for adsorption, and radio-assay; or:

Fluorescencemeasurement

Imprinted films Adsorbed molecules are leached out

The enantioselectivity adsorption experiment

Fluorescence: (ex = 288nm; em= 335 nm)

Radio ligand binding of 3H-S-Propranolol

Enantioselectivity towards Propranolol enantiomers

0

0.05

0.1

0.15

0.2

0.25

0.3

0.35

S imprinted R imprinted Blank

Ads

orpt

ion

(nm

ole)

S solutionR solution

Cu

rren

t /

A

0

0.5

1

1.5

2

2.5

3

3.5

4

L Dopa D Dopa Dopamine Dopac Catechol

L imprinted

D imprinted

Electrochemical detection of enantioselectivity and molecular selectivity in very thin silica films

Cur

rent

(A

)

OH

OH

CH2CHNH2

COOH

OH

OHOH

OH

CH2CO2H

OH

OH

CH2CH2NH2

L-Dopa D-Dopa

70 nm films

The more general case:

Enantioselectivity towards enantiomers of

non-imprinting molecules

Why is that important?

Because a small, recyclable chiral imprinting molecules can be used and reused

S. Fireman

S.Marx

CHO

HC

CH3

H

N

CH3

CH2(CH2)10CH3

CH3

+

CH3O

CH C

O

OH

H3COCH2CHCH2NHCHCH3

HOH CH3

PO

OH

O

O

Silica imprinted with aggregates of DMB

Was capable of separating the enantiomer-pairs of:

BINAP Propranolol Naproxen

0.9

1.2

1.5

1.8

2.1

2.4

Propranolol Anthracene

extracted-DMB@PSG

extracted-CTAB@PSG

Dis

crim

inat

ion

Rat

io

R

R

General enantioselectivity in imprinted thin films

20% phenylated silica, 270nm J. Am. Chem. Soc. 127, 2650 (2005)

PO

OH

O

O

OCH2CHCH2NHCHCH3

HOH CH3

0.9

0.95

1

1.05

1.1

1.15

1.2

1.25

1.3

Dis

crim

inat

ion

Rat

io

S

R R

0.93

1.03

1.13

1.23

1.33

Dis

crim

inat

ion

Rat

io

SR

R

General enantioselectivity in granules:

Comparison of two methods of inducing chirality

Before extraction: Chiral dopant (DMB)

After extraction:

Chiral holes

The recognition handedness changes!

Next:

If an SiO2 material is made chiral by a foreign molecule which either remains there or not, then:

#How are the building blocks of the material affected?

#Is it possible that an SiO4 tetrahedron which is neighboring to the chiral event, becomes chiral itself?

#Is it possible that the material becomes chiral deeper inside?

Nature has already provided an answer -Yes, it is possible!

Quartz

A:P3121 & B:P3221

A:P3121 & B:P3221

31 Right Helix31 Right Helix

32 Left Helix32 Left Helix

SiO4

1. Each of the chiral SiO4 tetrahedra is a single enantiomer event.

#A statistically similar counter enantiomer maybe defined.

2 .Silica is a racemic mixture of chiral SiO4 tetrahedra :

#Half comprise a homochiral left-handed set, and half a right-handed

set.

#This is true for ANY handedness definition; but each definition will

divide the set differently into two equal halves.

Silica is composed of randomly distorted SiO4 tetrahedra. Therefore:

3 .Induction of chirality by any of the methods,

will enrich the chiral population of SiO4 tetrahedra

with one type of handedness.

-6

-5

-4

-3

-2

-1

0

1

2

300 400 500 600

Wavelength (nm)C

D (

mde

g)

The ICD signal of CR adsorbed on DMB@silica

The only possibility is chiral skeletal porosity induced by the doped DMB

Co-doping:CR/DMB@silica

CR adsorbed on DMB@silicaReversal of the ICD signal indicates that the chirality-inducer is different in the two cases.

Inducing chirality in metals

Motivation: Why should one dope metals with organic molecules?

* Hybrid materials of metals and organics have been unknown

* Most elements are metals

* Metals are everywhere – any new methodology of affecting their properties is interesting

* The library of organic compounds is huge; the number of metals is small

* Placing a molecule in a sea of electrons may affect its properties; and the properties of the metal

* Synergetic effects between the metal and the dopant may emerge

Synthetic methods: Reduction in the presence of the dopant

AgNO3

Reducing aqueous solution

Reduction

Doping through metal synthesis

Dopant

Reducing agent

Aggregation and

entrapment

Ag metal

Hanna Behar-Levy et al, Chem. Mater., 14, 1736 (2002)

Ag

CR@Ag1:100 molar

Congo-Red

Noble metals

Coin metals

Scope: The metals

Magnetic metal

Alloys: Cu-Pd, Cu-Pt, Au-Ag

Small molecules, hydrophilic or hydrophobic: Sudan III

Scope: The dopants

Polymers, hydrophobic or hydrophilic: Polyacrylonitrile

Biologicals: D-Tryptophan

Proteins: Alkaline phosphatase

Nanoparticles:Carbon nanofibers

Complexes: [Rh]

Inorganic compounds:H3[P(Mo3O10)4]

Nafion@Ag PSSA@Au CR@Co CR@Cu

The New Materials

Scope: The entrapment range

0.2% (doped metals) - 10% by weight (hybrid materials)

For instance for PSSA@Ag:Molar ratio - PSSA-monomer units : Ag = 1:250Weight ratio - 0.42 carbon w/w%Atomic molar ratio - C : Ag = 1:30

Hierarchical structure: PSSA@Ag

H. Behar-Levy, G. Shter, G. Grader, Chem. Mater., 16, 3197 (2004)

aa bbaa bbbb

First taken after a few secondsFirst taken after a few seconds

Rhodium-Rhodium-complex@silver@silver

Thionin@Ag

Thionin@Ag - Coin

Thionin@Ag - Powder

compression

DMSO

No extraction with water, although water is a solvent of the dye

Adsorption of CR compared to entrapment

Adsorbed Doped

Adsorption on Adsorption on Entrapment in Ag commercial Ag Ag

1% 1% 100%

Starting solution: 6.2x10-4 M

Supernatant after entrapment:3.5x10-

7 M

Thionin@Cu-Pt: Entrapment vs adsorption

Adsorption: 4%

Y. Ben-Efraim

Dopant@metal - the picture of the entrapment

* Aggregated crystallite metal system* Porous material* The dopant is tightly entrapped in narrow pores and cages * The molecules are entrapped intact* Adsorption and entrapment are different processes

Scope: Properties and functionalities

*Affecting the metal properties - conductivity

*Affecting the reactivity characteristics – “acidic metal”

*Affecting the metal structure – chiral metals

*Affecting the catalytic properties of the metal

*Using a metal as a support for heterogeneous catalysis

*Bioapplication: Synergism in antibacterial activity

*Bioapplication: Enzyme entrapment within metals

*Corrosion prevention

*New concept in batteries

Chlorhexidine digluconate@Ag

0 100 200 300 400 500 600 700 800 900

0

20

40

60

80

100

98.8

99.0

99.2

99.4

99.6

99.8

100.0W

eig

ht

(%

)

Temperature (oc)

CHD

CHD@Ag

Racheli Ben-Knaz, Rami Pedahzur, Adv. Funct. Mater., 20, 2324 (2010)

HN

HN

HN

NH

NH

NH

ClNH NH

NH NHCl

O

OH

OH

OH

OH

OH

HO

O

HO

OH

OH

OH

OH

OH

Thermal gravimetric analysis

Enzymatic activity of acid-phospatase@gold

Michaelis-Menten dose-response kinetics is obeyed

Km = 9.3 mM (free enzyme: 1.25 mM )

0 30 60 90 1200.00

0.03

0.06

0.09

0.12

0.15

0.18

0.21A

bso

rbance

at

405 n

m (

a.u

)

Time (min)

AcP@Au AcP Adsorbed on Au Adsorption supernatant

Racheli Ben-Knaz, Biomaterials, 30 126 (2009)

What is chiral doping doing to the metal?Is it inducing chirality in it?

Circularly polarized 193 nm

Laser source

Sample:Chiral gold

Electron beam

Detector

Vacuum chamber

Detection of chirality of metals using photoelectrons

Photoelectrons are emitted from the conducting band with different kinetic energies.

H. Behar-Levy, O. Neumann, Ron Naaman, Adv. Mater. 19, 1207 (2007)

D- or L-Tryptophan

L-Glutathione Quinine (R=COH3)

Entrapped chiral molecules in gold or silver for the photoelectron experiment

Blank: Scattering from undoped Au

0.0 0.5 1.0 1.5 2.0 2.50.0

0.1

0.2

0.3

0.4

cw

ccw

I nte

nsity

(ar

b. u

nits

)

Energy (eV)

Scattering from gold doped with L-quinine

Reversal of scattering behavior by switching between the enantiomers of tryptophan

Silver was made chiral too!

Two enantiomers of gold

Chiral doping of palladium

L. Duran Pachon, I. Yosef, T. Markus, R. Naaman, D. Avnir, G. Rothenberg, Nature-Chemistry, 1, 160 (2009)

N

OH

R

N N

N

R

OH

2: (+)-Cinchonine (CN)

1: (–)-Cinchonidine (CD)

Pd SDS@Pd

Clockwise irradiation, Counterclockwise, Linearly polarized

Photoelectron emission spectroscopy of chirally doped Photoelectron emission spectroscopy of chirally doped palladiumpalladium

CD@PdCN@Pd

What is chiral in the metal?

# The chiral dopant affects the metal molecular orbitals, distorting them chirally

# The geometry of the metal pore around the doped molecule is chiral

These are two different chiral entities!

Doping Doping vsvs chiral imprinting chiral imprinting with with cinchonine

CN@Pd after extractionCN@Pd

Doped Imprinted

Similar but mirror behavior with CD@Pd

CD adsorption on dopant-free PdCN adsorption on dopant-free Pd

CD readsorption on CN imprinted Pd

CN readsorption on CN imprinted Pd

Enantioselectove adsorption on CN-imprinted palladium

N

OH

R

N N

N

R

OH

CD CN

Concentration in solution

Chiral catalysis in the context of metals

α-ketogluterate + NH4+ + NADPH

L-Glu + NADP+ +H2O

L-glutamic dehydrogenase@Au

O

O

O

O

OO

O

NH3

O

O

Level 1: The metal serves as a heterogenization matrix for a chiral catalyst

L. Duran Pachon, I. Yosef, T. Markus, R. Naaman, D. Avnir, G. Rothenberg, Nature-Chemistry, 1, 160 (2009)

Level 2:Level 2: A Catalytic metal is chirally doped A Catalytic metal is chirally dopedHydrogenation of isopreneHydrogenation of isoprene

Isophorone (R)-3,3,5-Trimethyl-cyclohexanone

A Catalytic metal is chirally imprintedA Catalytic metal is chirally imprinted

CN-imprinted Pd

Motivation: Chiral catalysis with a pure metal

A challenge to be met!