Chirality in amorphous and crystalline materials - experimental aspects David Avnir Institute of Chemistry, The Hebrew University Summer School on Chirality Mainz, 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: SiO 2 -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. Wellner M. 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

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(OCH 3 ) 4 + H 2 O (SiO m H n ) p + CH 3 OH (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 -

SolGel Xerogel SolGel Xerogel sol - particle entrapped molecule 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 (1R,2S)-(-)-N-dodecyl-N -methylephedrinium bromide (DMB)

The experiment: Inducing Circular Dichroism in Congo-Red Within Silica Sol The chiral inducer: DMB The achiral probe: CR

sol (red line) and sol (blue line) The ICD spectra of co-entrapped CR-DMB in hydrophilic and hydrophobic silica sols S. Fireman 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. Fireman S. Marx S-BINAP 1R,2S-DMB The possible interactions: DMB/S-BINAP DMB/R-BINAP

31 P-NMR spectrum of BINAP-DMB diastereomers: Looking inside the sol and the gel of silica S-BINAPR-BINAP ppm 5.94 S-BINAP interacts better with the chiral surfactant ppm In the gel In solution In the sol ppm

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

Propranolol The functional monomers Film thickness: 700 nm TMOSPTMOSMTMOS 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: Fluorescence measurement Imprinted filmsAdsorbed molecules are leached out The enantioselectivity adsorption experiment Fluorescence: ( ex = 288nm; em = 335 nm) Radio ligand binding of 3 H-S-Propranolol

Enantioselectivity towards Propranolol enantiomers

Current /  A Electrochemical detection of enantioselectivity and molecular selectivity in very thin silica films Current (  A) 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

Silica imprinted with aggregates of DMB Was capable of separating the enantiomer-pairs of: BINAP Propranolol Naproxen

Discrimination Ratio R R General enantioselectivity in imprinted thin films 20% phenylated silica, 270nm J. Am. Chem. Soc. 127, 2650 (2005)

S R R S R 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 SiO 2 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 SiO 4 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:P & B:P Right Helix3 2 Left Helix SiO 4

1. Each of the chiral SiO 4 tetrahedra is a single enantiomer event. # A statistically similar counter enantiomer maybe defined. 2. Silica is a racemic mixture of chiral SiO 4 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 SiO 4 tetrahedra. Therefore:

3. Induction of chirality by any of the methods, will enrich the chiral population of SiO 4 tetrahedra with one type of handedness.

The ICD signal of CR adsorbed on The only possibility is chiral skeletal porosity induced by the doped DMB CR adsorbed on Reversal 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 AgNO 3 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 1:100 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 : H 3 [P(Mo 3 O 10 ) 4 ]

The New Materials

Scope: The entrapment range 0.2% (doped metals) - 10% by weight (hybrid materials) For instance for Molar ratio - PSSA-monomer units : Ag = 1:250 Weight ratio carbon w/w% Atomic molar ratio - C : Ag = 1:30

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

First taken after a few seconds First taken after a few seconds

- Coin - Powder compressionDMSO 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 Entrapment vs adsorption Adsorption: 4% Y. Ben-Efraim

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

Enzymatic activity of Michaelis-Menten dose- response kinetics is obeyed Km = 9.3 mM (free enzyme: 1.25 mM ) Racheli Ben-Knaz, Biomaterials, (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=COH 3 ) Entrapped chiral molecules in gold or silver for the photoelectron experiment

Blank: Scattering from undoped Au

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) 2: (+)-Cinchonine (CN) 1: (–)-Cinchonidine (CD)

Pd Clockwise irradiation, Counterclockwise, Linearly polarized

Photoelectron emission spectroscopy of chirally doped palladium

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 vs chiral imprinting with Doping vs chiral imprinting with cinchonine after extraction Doped Imprinted Similar but mirror behavior with

CD adsorption on dopant-free Pd CN adsorption on dopant-free Pd CD readsorption on CN imprinted Pd CN readsorption on CN imprinted Pd Enantioselectove adsorption on CN-imprinted palladium CDCN Concentration in solution

Chiral catalysis in the context of metals

α-ketogluterate + NH NADPH L-Glu + NADP + +H 2 O L-glutamic 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: A Catalytic metal is chirally doped Hydrogenation of isoprene Isophorone ( R)-3,3,5-Trimethyl-cyclohexanone

A Catalytic metal is chirally imprinted CN-imprinted Pd Motivation: Chiral catalysis with a pure metal A challenge to be met!