Probing chiral interfaces by infrared spectroscopic methods · 2010-09-23 · investigate...

Probing chiral interfaces by infrared spectroscopic methods

Marco Bieri, Cyrille Gautier and Thomas Burgi*

Received 12th July 2006, Accepted 15th November 2006

First published as an Advance Article on the web 1st December 2006

DOI: 10.1039/b609930k

Biological homochirality on earth and its tremendous consequences for pharmaceutical science

and technology has led to an ever increasing interest in the selective production, the resolution

and the detection of enantiomers of a chiral compound. Chiral surfaces and interfaces that can

distinguish between enantiomers play a key role in this respect as enantioselective catalysts as well

as for separation purposes. Despite the impressive progress in these areas in the last decade,

molecular-level understanding of the interactions that are at the origin of enantiodiscrimination

are lagging behind due to the lack of powerful experimental techniques to spot these interactions

selectively with high sensitivity. In this article, techniques based on infrared spectroscopy are

highlighted that are able to selectively target the chiral properties of interfaces. In particular, these

methods are the combination of Attenuated Total Reflection InfraRed (ATR-IR) with

Modulation Excitation Spectroscopy (MES) to probe enantiodiscriminating interactions at chiral

solid–liquid interfaces and Vibrational Circular Dichroism (VCD), which is used to probe the

structure of chirally-modified metal nanoparticles. The former technique aims at suppressing

signals arising from non-selective interactions, which may completely hide the signals of interest

due to enantiodiscriminating interactions. Recently, this method was successfully applied to

investigate enantiodiscrimination at self-assembled monolayers of chiral thiols on gold surfaces.

The nanometer size analogues of the latter—gold nanoparticles protected by a monolayer of a

chiral thiol—are amenable to VCD spectroscopy. It is shown that this technique yields detailed

structural information on the adsorption mode and the conformation of the adsorbed thiol. This

may also turn out to be useful to clarify how chirality can be bestowed onto the metal core itself

and the nature of the chirality of the latter, which is manifested in the metal-based circular

dichroism activity of these nanoparticles.

Introduction

The origin of biological homochirality has puzzled scientists

since the chiral nature of molecules was discovered by Louis

Pasteur1 more than 150 years ago. On a molecular-level,

homochirality represents an intrinsic property of the building

blocks of life. Although most amino acids can exist in both

left- and right-handed forms, life on earth is made of left-

handed amino acids, almost exclusively. Similarly, many other

bio-molecules are handed: DNA is right-handed, and so are all

the sugars we can use. Several explanations have been put

forward for the origin of homochirality on earth. The simplest

one assumes a random excess of one handedness, which is self-

perpetuating and irreversible.2 Another model proposes chiral

crystal surfaces to have played a decisive role for biochemical

homochirality.3,4 The discovery of an excess of L-amino acids

in meteorites5,6 led to the hypothesis that a preference for

L-amino acids existed in our solar system material before there

was life on earth. Other models propose that the interaction

between chiral molecules and circularly polarized light has

led to the selective destruction of one enantiomer.7 Even

further models make a link between homochirality and the

weak force,8 one of the four fundamental forces in nature.

This force has a handedness (parity violation), which results

in a very small energy difference between enantiomers. The

list of models mentioned above is certainly not complete

and no consensus is found among origin-of-homochirality

researchers.9

As a consequence of the chiral nature of living systems,

metabolic and regulatory processes mediated by biological

systems are sensitive to stereochemistry and different re-

sponses can often be observed for the enantiomers of a chiral

molecule interacting with such systems. Specifically, in order

to develop new therapeutic drugs, the stereoselectivity of many

biological processes has to be taken into account. In fact, very

often only one enantiomer exhibits a specific therapeutic

action, whereas the other has to be considered as ballast,

contributing to side effects, displaying toxicity, or acting as

antagonist.10–13 In this context, thalidomide is a tragic remin-

der of the importance of chirality. In the early 1960s, this drug

was prescribed to pregnant women suffering from morning

sickness. While the left-handed form is a powerful tranquilli-

zer, the right-handed form can disrupt fetal development,

resulting in severe birth defects. Unfortunately, the synthesis

of the drug produced a racemate, as would be expected, and

the wrong enantiomer was not removed before the drug was

marketed in Europe and Canada. There was also an American

Universite de Neuchatel, Institut de Microtechnique, Laboratoire dechimie physique des surfaces, Rue Emile-Argand 11, 2009 Neuchatel,Switzerland. E-mail: [email protected]; Fax: +41 32 718 2511; Tel: +41 32 718 24 12

This journal is �c the Owner Societies 2007 Phys. Chem. Chem. Phys., 2007, 9, 671–685 | 671

INVITED ARTICLE www.rsc.org/pccp | Physical Chemistry Chemical Physics

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http://dx.doi.org/10.1039/B609930K

company that applied to the U.S. Food and Drug Adminis-

tration (FDA) to market the drug. However, due to the

scepticism and concerns of FDA’s Frances Kelsey, the drug

was kept out of American pharmacies.

The scientific and economic relevance of chiral substances

has stimulated processes that can selectively produce one

enantiomer, or that are able to separate enantiomers from a

racemic mixture, as well as the molecular-level understanding

of these methods. The importance of this field of research was

underlined by the Nobel Prize in Chemistry in 2001 awarded

to Knowles, Noyori and Sharpless for their work on chirally-

catalysed hydrogenation and oxidation reactions.

The selective production of enantiomers and the resolution

of a racemic mixture necessitate a chiral environment. For this

purpose, chiral auxiliaries, catalysts or selectors have to be

developed. The formation of the corresponding diastereomeric

species implies an energy difference between them that finally

allows enantiodiscrimination.14

In this context, chiral surfaces and interfaces have received

considerable interest in recent years due to their application in

heterogeneous enantioselective catalysis15,16 and their impor-

tance in the separation17 and sensing18,19 of enantiomers. It

has, for example, been shown that the enantiomers of glucose

are electrooxidized at different rates on intrinsically chiral

Pt(643) electrodes.20 It has also been reported that (R)-3-

methylcyclohexanone desorbs enantiospecifically from the

two enantiomeric forms of the chiral Cu(643) surface21 and

that desorption occurs from the chiral kink sites.22 Despite the

numerous reports on enantiodiscrimination at chiral surfaces,

not much molecular-level information is available on the

relevant intermolecular interactions between surface (selector)

and analyte molecule (selectand). This is because most of the

applied experimental methods merely quantify enantiodiscri-

mination, or in other words, give a value for the difference in

Gibbs free energy between the relevant diastereomeric com-

plexes, without allowing direct molecular-level insight. For

example, in chromatographic methodologies, the separation

factors are derived from different retention times.23–27 Experi-

mental methods like quartz crystal microbalance measure

enantiospecificity via a mass change28�31 and optical techni-

ques detect a change in the thickness of the adsorbed layer.18

Even further methods, such as atomic force microscopy, rely

on force measurements between the surface and the modified

probe tip.19 Another approach makes use of soluble model

systems in order to investigate the relevant intermolecular

interactions by applying bulk techniques.32

A technique to probe enantiodiscrimination at interfaces

should ideally combine (surface) sensitivity with selectivity for

the chiral information. Whereas the former criterion is met by

many powerful surface science tools,33 the latter is an attribute

of chiroptical techniques like circular dichroism,34,35 vibra-

tional circular dichroism36 or Raman optical activity.37 The

combination of both attributes mentioned above is a real

challenge. Non-linear optical techniques may turn out to be

very useful for probing chiral interfaces.38–40 InfraRed (IR)

spectroscopy is a well-established tool for the investigation of

interfaces and it has been used to probe enantiospecific inter-

action at chiral surfaces.22,41 However, conventional IR spec-

troscopy has the disadvantage that non-specific interactions

also give rise to signals. Thus, the adsorption of a chiral

molecule on a chiral surface may result in very similar spectra

for the two enantiomers, the interesting differences being over-

laid by much stronger signals due to non-specific interactions.

In order to overcome these problems, Attenuated Total Re-

flection InfraRed (ATR-IR)42 was recently combined with

Modulation Excitation Spectroscopy (MES).43,44 MES selec-

tively highlights the periodically changing signals stimulated

by an external parameter. For example, by periodically chan-

ging the absolute configuration of the analyte molecule

(selectand) enantiospecific interactions can be spotted, as

has been demonstrated for interactions taking place at

chiral stationary phases45,46 and chiral self-assembled mono-

layers.47,48

In this contribution, we first present the main experimental

techniques—ATR-IR and MES—that allow us to study en-

antiodiscrimination at chiral solid–liquid interfaces. We then

present results for enantiodiscrimination at self-assembled

monolayers of chiral thiols on gold surfaces. In the last part,

we focus on gold nanoparticles covered by chiral thiols, which

are the nanometer size analogues of chiral Self-Assembled

Monolayers (SAMs) on gold surfaces. The chirality of these

particles can be probed by circular dichroism spectroscopy,

both in the infrared49 and the UltraViolet-Visible (UV-Vis)

spectral regions,50 which is shown to be a powerful method for

structure determination of this interesting class of materials

and for elucidating the nature of the chirality imparted on the

gold particles by the chiral thiol. Vibrational Circular Dichro-

ism (VCD) is sensitive to molecular vibrations51 in a similar

way to Raman Optical Activity (ROA)52 and it will be shown

in this article that VCD can be used to probe the ligand shell of

metal nanoparticles. Circular Dichroism (CD or ECD, Elec-

tronic CD)53 probes electronic transitions and, thus, it can

spot the chirality associated with the metal core.54 The com-

bination of both methods may reveal the influence of the

adsorbed chiral thiols on the nature of the chirality of the

metal core.

Attenuated total reflection infrared spectroscopy

The principle of total internal reflection. ATR is a special

mode of conventional IR spectroscopy for the investigation of

interfaces. The ATR method relies on the formation of an

evanescent field between a so-called Internal Reflection Ele-

ment (IRE) and the adjacent medium. Due to the evanescent

field, only a small volume is being probed at the interface

which makes the technique surface sensitive.

Beam propagation in an optically dense medium with

refractive index n1 undergoes total reflection at the interface

of an optically rare medium (n2) when the angle of incidence

exceeds the critical angle yc. Newton’s experiments55 showed,

and it follows from Maxwell’s equations,56 that an electro-

magnetic wave propagates through the optical interface and

generates an evanescent field in the rare medium. The electric

field amplitude of the evanescent field falls off exponentially

with distance z from the surface, i.e.

E ¼ E0e�z=dp ð1Þ

672 | Phys. Chem. Chem. Phys., 2007, 9, 671–685 This journal is �c the Owner Societies 2007

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The depth of penetration dp, defined as the distance required

for the electric field amplitude to decrease to e�1 of its value at

the surface is given by

dp ¼l1

2pffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiffiðsin2y� n221Þ

q ð2Þ

where l1 = l/n1 is the wavelength in the denser medium and

n21 = n2/n1 is the ratio of the refractive indices of the rarer and

denser medium. It is important to note that the depth of

penetration depends on the optical constants of the interface,

the angle of incidence y and also on the wavelength l of the

electric field. In the infrared, dp is about one micron.

Attenuated total reflection spectroscopy. In 1967, Harrick42

showed that the principle of total internal reflection can be

used for spectroscopy. If the rare medium (n2) is absorbing, the

evanescent electric field will be attenuated due to absorption

and less intensity is reflected, resulting in an Attenuated Total

Reflection (ATR). A schematic representation of the basic

ATR-IR experimental setup is given in Fig. 1. A beam emitted

from a light source (left side) is coupled into an IRE (n1). For

the IR, materials like ZnSe (n1 = 2.3), Si (n1 = 3.4) and Ge

(n1 = 4) are commonly used as IREs. On the way to the

detector, the IR beam can undergo multiple internal reflec-

tions, which significantly increases the signal-to-noise ratio.

Due to the evanescent nature of the field the ATR-IR techni-

que surface is a powerful tool for the investigation of solid–

liquid interfaces.57

Modulation excitation spectroscopy

Introduction. Conventional IR spectroscopy is non-specific.

All species that are probed by the IR beam and that have IR

active vibrations will give rise to signals in the spectrum,

whether the species are involved or not in the process of interest.

A conventional approach to partly overcome this problem is

difference spectroscopy.58 However, in order to further extract

important information such as, e.g., the kinetics of surface

reactions, more sophisticated techniques like time-dependent

stimulation may be applied, provided that the system under

observation responds to an external parameter, including con-

centration of reactive species, pH, temperature, and so on.

Practically, there are two methods for external stimulation:

the relaxation technique (parameter jump)59 and the modula-

tion technique (parameter modulation).60 A prerequisite of the

latter is a reversible system response to a periodic stimulation.

Fig. 2 shows the principle of Modulation Excitation Spectro-

scopy (MES). The sample is stimulated periodically by an

external parameter at the stimulation frequency o, which leads

to a periodic system response (reversibility provided).

The theory of phase sensitive detection. If a system is

disturbed periodically by an external parameter, all the species

addressed by the stimulation will also change periodically at

the same frequency as the stimulation or harmonics thereof.43

As is indicated in Fig. 2, there may be a phase lag f between

the stimulation and system response. A phase lag is observed

when the time constant of a process giving rise to a signal is on

the same order as the time constant T = 2po�1 of the

stimulation. After reaching a new quasi-stationary state, at

the beginning of the modulation the system is oscillating at

frequency o around this state. The resulting absorbance

variations A(~n,t) are followed by measuring spectra at different

times during the modulation period T. The set of time-resolved

spectra A(~n,t) is then transformed by means of a digital Phase

Sensitive Detection (PSD), according to eqn (3), to a set of

phase-resolved spectra.

AfPSDk

k ð~nÞ ¼ 2

T

ZT

0

Að~n; tÞ sin ðkotþ fPSDk Þdt ð3Þ

where k = 1,2,3,. . . determines the demodulation frequency,

i.e. fundamental, first harmonic, and so on, T is the modula-

tion period, ~n denotes the wavenumber, o the stimulation

frequency and fkPSD the demodulation phase angle. With a set

of time-resolved spectra A(~n,t), eqn (3) can be evaluated for

different phase angles fkPSD resulting in a series of phase-

resolved spectra AfPSDk

k . Eqn (3) is closely related to a Fourier

analysis.61 According to the Fourier theorem, every periodic

Fig. 1 Schematic representation of the ATR-IR principle. A beam,

emitted from a source depicted on the left, is coupled into an Internal

Reflection Element (IRE) and is undergoing multiple internal reflec-

tions until it is focused on a detector (depicted on the right). At each

total internal reflection, an evanescent electric field is being formed

that penetrates into the rare medium. The depth of penetration

depends on the optical constants of the system but also on the

wavelength of radiation and the angle of incidence.

Fig. 2 Schematic representation of the Modulation Excitation Spec-

troscopy (MES) principle. The system (sample) is periodically stimu-

lated at frequency o by an external parameter of interest (e.g.,

temperature, pH, concentration, absolute configuration). The periodic

sample response is sensed by IR spectroscopy and may exhibit

frequency-dependent amplitude and phase lag f. Selective detection

of the periodic sample responses due to the stimulation is performed

by Phase Sensitive Detection (PSD). See modulation excitation spec-

troscopy section for more details.


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function f(t) can be expressed as a Fourier series in the form

f ðtÞ ¼ a0 þX1k¼1

ak cos ðkotÞ þX1k¼1

bk sin ðkotÞ ð4Þ

where ak and bk are the orthogonal cosine and sine Fourier

coefficients, respectively, and the integer k is the frequency

multiplier, i.e. fundamental, first harmonic, and so on. Now,

the Fourier series represented by eqn (4) can also be expressed

as a sine series with an additional phase angle fk according to

f ðtÞ ¼ a0 þX1k¼1

ck sin ðkotþ fkÞ ð5Þ

with ck ¼ffiffiffiffiffiffiffiffiffiffiffiffiffiffiffia2k þ b2k

qand tan(fk) = akbk

�1. The Fourier co-

efficients of the periodic function described by eqn (5) are

given by

a0 ¼1

T

ZT

0

f ðtÞdt ð6Þ

ck ¼2

T

ZT

0

f ðtÞ sin ðkotþ fkÞdt ð7Þ

By replacing f(t) with A(~n,t) and fk with fkPSD, eqn (7) yields

the demodulation transformation given in eqn (3). In other

words, a demodulated spectrum Akfk

PSD

represents the Fourier

coefficient of the time-varying signal A(~n,t) for a given fre-

quency (usually fundamental, k = 1) and a given user-defined

phase lag fkPSD.

We want to conclude this theoretical section by stating the

main benefits of MES: The signals arising in demodulated

spectra are exclusively related to the stimulation of the ex-

ternal parameter, i.e. MES selectively highlights the species

that are affected by the external parameter. Furthermore,

demodulated spectra are of much higher quality with a better

signal-to-noise ratio (about one order of magnitude compared

to conventional time-resolved spectra). The kinetic informa-

tion of the investigated system is contained in the frequency

dependent amplitude of the response and the phase lag

between stimulation and response (Fig. 2). Consequently,

species with different kinetics can be separated by setting the

demodulation phase angle fkPSD accordingly. An excellent

and exhaustive quantitative analysis of MES can be found in

ref. 43 and more information is given elsewhere.44,60,62–64

Experimental application of modulation excitation spectro-

scopy. In order to use the benefits of MES for ATR-IR, a

special home-built flow-through cell was designed.65 Fig. 3

shows the basic experimental setup for ATR-IR in combina-

tion with MES. The flow-through reactor has two inlet tubes

leading to the interior of the cell and coinciding directly above

the surface of the IRE. Each of the two inlet tubes is

connected, through a Teflon valve, with a bubble tank con-

taining the appropriate solution. By means of a peristaltic

pump situated behind the cell, each of the solutions can be

introduced and continuous flow over the IRE surface is

established. Typical stimulation experiments are modulation

of temperature,66,67 pressure, electric field, light flux, concen-

tration44 and pH.60,68 In order to probe chiral interfaces and

enantiodiscrimination, absolute configuration modulation was

applied,45–48 which consists of periodically flowing the two

enantiomers of the chiral probe molecule (separately stored in

bubble tanks I and II, see Fig. 3) over the chiral interface. This

approach has the advantage that signals due to unspecific

interactions, i.e. interactions with achiral sites, are efficiently

suppressed. The latter may completely hide the relevant

spectral features arising from enantiodiscriminating interac-

tions. Fig. 4 demonstrates this attribute of absolute configura-

tion modulation for the investigation of the

enantiodiscriminating interaction between Ethyl Lactate

(EL) and a Chiral Stationary Phase (CSP), amylase tris[(S)-

a-methylbenzylcarbamate] (Fig. 4a).45 The chiral stationary

phase was fixed on the IRE for measurements and at the inlet

of the ATR-IR flow-through cell a periodic concentration

profile (as shown in Fig. 4b) was applied. In this way, the

concentration of the two enantiomers is by turns high and low,

while the total concentration stays constant throughout the

modulation experiment. Fig. 4c shows demodulated ATR-IR

spectra at different phase angles for two different experiments.

For the top spectra, no chiral stationary phase was present in

the cell. The IR spectra of the dissolved enantiomers are

identical. Since only periodically varying signals are detected

in the experiment, no signals are observed, despite the fact that

the absolute configuration of the probe molecule, EL, was

periodically changed. The spectra of the two enantiomers

remain identical if they adsorb on achiral sites, i.e. sites that

can not distinguish between them, and therefore no signals are

detected after demodulation even though EL adsorbs (for

example on a silica gel).45 In the presence of chiral sites that

can distinguish between the two enantiomers (Fig. 4c, bot-

tom), the spectra of the two enantiomers change slightly and

these slight changes are amplified by the phase sensitive

detection. The result is signals in the demodulated spectra

that contain selectively information on the two diastereomeric

Fig. 3 Flow-through cell specially designed for modulation excitation

spectroscopy. The cell has two inlet tubes leading to the interior of the

cell and coinciding directly above the surface of the Internal Reflection

Element (IRE). Each of the two inlet tubes is connected, through a

Teflon valve, with a bubble tank containing the appropriate solution.

By means of a peristaltic pump situated behind the cell, each of the

solutions can be introduced and continuous flow over the IRE surface

is established.


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complexes formed between the chiral sites on the surface and

the two enantiomers of the chiral probe molecule (EL). These

spectra reveal which functional groups are involved in the

relevant interaction complexes and therefore point towards the

origin of enantiodiscrimination.45 In particular, the demodu-

lated spectra (Fig. 4c, bottom) reveal significant signals at

about 1250, 1540 and above 1700 cm�1, associated with the

amide III, amide II and amide I vibrations, respectively, which

shows that the amide group of the CSP is involved in hydrogen

bonding with EL both as an acceptor and as a donor. Based on

the spectral shifts and in combination with calculations, a

detailed picture can be obtained on the intermolecular inter-

actions at the chiral solid–liquid interface.45

In the next section, the enantiodiscriminating interaction

between chiral SAMs (the selector) and the probe molecule

proline (Scheme 1, the selectand), as investigated by ATR-IR

MES, will be discussed.47,48

Probing enantiodiscrimination between chiral self-assembled

monolayers and proline

Chiral SAMs were prepared from L-glutathione (GSH, g-glu-cys-gly, Scheme 2) and N-acetyl-L-cysteine (NAC, Scheme 3),

respectively. These molecules readily self-assemble on gold

surfaces from ethanol (EtOH) solutions. In order to under-

stand and interpret the spectroscopic results related to enan-

tiodiscriminating interactions, the structure of the adsorbed

molecules in the chiral SAM should be studied first. Therefore,

the investigation of the self-assembly process of GSH and

NAC on gold68–70 by in situ ATR-IR spectroscopy is a

precursor to experiments on enantiodiscrimination.

Enantiodiscrimination between an L-glutathione SAM and

proline. GSH (Scheme 2) is a natural reducing molecule and

ubiquitous. In fact, it is the most abundant non-protein thiol

in mammalian cells71 found in millimolar concentrations. The

molecule has a multitude of physiological functions,72 such as

redox buffering, detoxification, and antioxidant activity.

Furthermore, GSH is cheap, which makes it an attractive

candidate for surface and electrode modification73–86 and the

synthesis of monolayer protected nanoparticles.54,87,88

GSH SAMs undergo reversible conformational changes

induced by acid and base stimuli.89 Part of the adsorbed

molecules interact with the gold surface not only through

the thiol but also through the carboxylic acid group of the

gly moiety, which deprotonates upon adsorption.89 The

ATR-IR MES study presented below shows that similar

conformational changes are induced by the presence of the

amino acid proline and that GSH SAMs can differentiate

between proline enantiomers.

The interaction of each of the proline enantiomers with the

GSH SAMwas studied first. This was experimentally achieved

by ‘‘EtOH vs. D(L)-proline’’ modulation experiments, where

EtOH and the proline enantiomers were allowed to periodi-

cally flow over the chiral GSH SAM while ATR-IR spectra

Fig. 4 Absolute configuration modulation ATR-IR experiment re-

vealing the enantiodiscriminating interactions between a Chiral Sta-

tionary Phase (CSP) and Ethyl Lactate (EL). (a) Structure of CSP and

EL. (b) Schematic concentration profile at the inlet of the ATR-IR cell

(see Fig. 3) for the two enantiomers of EL. (c) Demodulated ATR-IR

spectra for two experiments: In the absence of CSP (top) and in the

presence of CSP (bottom). Adapted with permission from ref. 45.

Copyright (2003) American Chemical Society.

Scheme 1 Structure of proline.

Scheme 2 Structure of L-glutathione, g-glu-cys-gly (GSH).

Scheme 3 Structure of N-acetyl-L-cysteine (NAC).


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were recorded in situ (bubble tank I: EtOH, bubble tank II:

D(L) proline, see Fig. 3).

The time dependence of selected ATR-IR signals for the

‘‘EtOH vs. D(L)-proline’’ modulation experiment is displayed

in Fig. 5. Dashed lines refer to D-proline and solid lines to

L-proline. The upper half of Fig. 5 shows the absorbance as a

function of time of the nas(–COO�) vibration of dissolved

proline at about 1637 cm�1. As is obvious, no significant

differences are apparent between the proline enantiomers,

since the concentration change of dissolved proline within

the ATR-IR flow reactor is forced by convection and diffusion

and does not depend on the absolute configuration. At the

chiral interface, however, significant differences between

D- and L-proline emerge, as can be seen in the lower half in

Fig. 5. The signals shown refer to the GSH n(–COOH)

vibration at about 1725 cm�1, which are affected by proline

adsorption and thus reflect adsorption/desorption kinetics.

During the first half period of modulation, EtOH is flowed

through the ATR-IR cell and removes physisorbed proline

from the GSH interface. As can be seen, the signals for the two

enantiomers fall off at different rates, indicating that D-proline,

which is slower desorbing, is more strongly bound to the chiral

surface (see signals on the left side at the bottom in Fig. 5). The

signals on the right side in Fig. 5, bottom, are related to

proline adsorption on the GSH SAM and show minor differ-

ences between the enantiomers. This example shows that

information on dissolved molecules near the interface and

on adsorbed molecules can be obtained simultaneously by

ATR-IR, provided the spectral response significantly changes

upon adsorption.

In order to correctly quantify the observed differences

between the D(L)-proline interactions and the GSH SAM, a

model based on the finite element method was developed.47

The model couples mass transport of solute species by con-

vection and diffusion to surface reactions. The model has two

adjustable parameters; notably, the rate constants of adsorp-

tion kads and desorption kdes, which were tuned to best fit the

experimental data. The model outputs are included in Fig. 5

and are represented as smooth bold lines (dashed line:

D-proline, solid line: L-proline). Obviously, the model captures

the significant differences between the bulk (top) and surface

(bottom) response well. Deviations from experiment may be

explained by small volumes in the ATR-IR cell (behind inlet

and outlet), where the fluid is almost stagnating.65 Further-

more, the applied model assumes simple Langmuir kinetics,

which may not completely capture the real adsorption/

desorption process.

Extracting the rate constants by fully accounting for mass

transport by convection and diffusion allows one to calculate

DDG0 of adsorption for D- and L-proline according to

DDG0 ¼ �RT ln ðKD

KLÞ ð8Þ

where KD,L = kads(D,L)[kads(D,L)]�1 denote the corresponding

equilibrium constants of D- and L-proline, respectively. Eval-

uating eqn (8) for T = 298 K, we found KD(KL)�1 E 7.5 and

thus DDG0 E �5.0 kJ mol�1. This indicates that the GSH

SAM is able to discriminate between the proline enantiomers,

with D-proline being more strongly bound to the chiral inter-

face. In addition to the quantitative information provided by

the experiments described above, ATR-IR gives some insight

into the mechanism of enantiodiscrimination. In particular,

ATR-IR spectroscopy reveals that a large fraction of (zwitter-

ionic) molecules within the GSH SAM is deprotonated at the

carboxylic acid group of the gly moiety, which is assisted by

surface interaction.68 It was demonstrated that this dynamic

equilibrium between zwitterionic (not surface bound) and

deprotonated (surface bound) molecules within the adsorbate

layer is easily shifted by acid/base stimuli, which finally results

in significant structural changes within the SAM.68 The spec-

troscopic results of the absolute configuration modulation

experiment (data not shown), i.e. the flow of D-proline fol-

lowed by an equally long flow of L-proline over the GSH

SAM, and subsequent phase sensitive detection of the

Fig. 5 Time dependence of ATR-IR signals for a proline concentra-

tion modulation experiment, which characterizes the interaction of

proline with a chiral L-glutathione (GSH) SAM. Signals related to

D-proline are represented as dashed lines, whereas L-proline signals are

depicted as solid lines. The time dependence was obtained by an

‘‘EtOH vs. D(L)-proline’’ modulation experiment (bubble tank I:

EtOH, bubble tank II: D(L)-proline, see Fig. 3). During the first half

period of modulation (indicated by ‘‘EtOH’’ in the left half of the

figure) ethanol was flowed over the GSH SAM and physisorbed

proline is removed from the interface. In the second half period of

modulation (denoted by ‘‘EtOH + Proline’’), an equal long flow of

D(L)-proline over the GSH SAM was established, resulting in proline

physisorption on the chiral surface. The signals in the upper half of the

figure refer to changes in the concentration of dissolved proline,

whereas the signals in the lower half reflect variations in the surface

concentration of proline due to adsorption/desorption on/from the

GSH SAM. The smooth curves in the figure (dashed lines refer to

D-proline and solid lines to L-proline) further show the calculated

response based on a model that considers both mass transport within

the cell and adsorption/desorption as described in detail elsewhere.47

Reprinted with permission from ref. 47. Copyright (2005) American

Chemical Society.


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periodically varying signals, give evidence that similar con-

formational changes are induced by the presence of the amino

acid proline and by changing its absolute configuration.

Enantiodiscrimination between an N-acetyl-L-cysteine SAM

and proline. The interaction of proline with a GSH SAM is

complex, involving structural changes of the relatively flexible

GSH molecules. In this section, we report on enantiodiscrimi-

nation between N-acetyl-L-cysteine (NAC, Scheme 3) SAMs

and proline.48 NAC can be viewed as the anchoring part of

GSH, and it has less conformational freedom than the latter.

On the basis of absolute configuration modulation experi-

ments and Density Functional Theory (DFT) calculations, a

model for the interaction of proline with the chiral NAC SAM

is proposed and it is furthermore shown that the interaction is

significantly different from the GSH case.48

As stated above, a prerequisite for understanding enantio-

discrimination between a chiral SAM and a probe molecule is

the investigation of the structure of the SAM itself. Selected

ATR-IR spectra recorded during the self-assembly process of

NAC from EtOH are depicted in Fig. 6. Spectrum (a) was

recorded at the start of self-assembly whereas spectrum (b)

was recorded about two hours afterwards. As is obvious,

significant spectral differences are apparent and are empha-

sized in the corresponding difference spectrum (b) � (a) at the

bottom of Fig. 6, and that reveal spectral changes within the

adsorbate layer beside bare mass uptake. Specifically, the

growing band intensities at 1590 and 1400 cm�1, associated

with the nas(–COO�) and ns(–COO�) vibrational modes and

the simultaneous decrease of the n(–COOH) mode at 1727

cm�1 indicate a deprotonation of adsorbed NAC molecules at

the carboxylic acid moiety. This deprotonation process is

assisted by the interaction of the carboxylic acid group with

the Au surface, which acts as a proton acceptor.70 On the basis

of the ratio between the integrated intensities of the carboxylic

acid vibrational bands n(–COOH) before and after the depro-

tonation process, we estimate that about 40% of adsorbed

NAC molecules undergo a deprotonation under the applied

conditions. The analysis assumes that the molar extinction

coefficient e of the n(–COOH) vibration is equal for the species

that do and do not undergo deprotonation. As a result, the

NAC adsorbate layer consists of a mixture of neutral and

negatively charged (anionic) molecules. As will be shown

below, mainly the anionic species within the SAM contribute

to enantiodiscrimination, which was further confirmed by

DFT calculations.

At the bottom of Fig. 7, ATR-IR spectra of the interacting

species are shown, notably NAC adsorbed on gold (selector,

bold solid line) and dissolved proline (selectand, thin solid

line). The most prominent vibrational modes for NAC are the

n(–COOH) mode at 1727 cm�1, amide I at 1661 cm�1 and

amide II at 1539 cm�1. The proline ATR-IR spectrum is

dominated by the nas(–COO�) vibrational mode at 1637 cm�1,

with the ds (–NH2) scissoring mode appearing as a shoulder at

1570 cm�1. At the top of Fig. 7, two phase-resolved, i.e.

demodulated, spectra are presented (label ‘‘(D) vs. (L)’’) that

refer to an absolute configuration modulation experiment

performed on different days using different gold surfaces

(gold coated Ge IREs). These phase-resolved ATR-IR spectra

Fig. 6 ATR-IR spectra recorded during N-acetyl-L-cysteine (NAC)

adsorption on gold. Spectrum (a) was recorded at the start of the self-

assembly process whereas spectrum (b) was recorded about two hours

afterwards. The corresponding difference spectrum (b) � (a) empha-

sizes structural changes within the NAC adsorbate layer during

adsorption. M. Bieri and T. Burgi, ChemPhysChem, 2006, 7,

514–523. Copyright John Wiley & Sons Limited. Reproduced with

permission.

Fig. 7 Bottom: ATR-IR spectra of N-acetyl-L-cysteine (NAC, selec-

tor, bold solid line) adsorbed on a gold surface and proline (selectand,

thin solid line, scaled by a factor of 2.7) dissolved in ethanol. Top:

Demodulated, i.e. phase-resolved, signals for experiments performed

on different days using different gold surfaces illustrating the reprodu-

cibility of the absolute configuration modulation experiments. In this

type of modulation experiment, D- and L-proline were periodically

flowed over a chiral NAC SAM after two hours of self-assembly. The

two demodulated spectra highlight the signals arising due to enantio-

specific interaction between NAC and proline. M. Bieri and T. Burgi,

ChemPhysChem, 2006, 7, 514–523. Copyright John Wiley & Sons

Limited. Reproduced with permission.


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highlight the differences in intermolecular interactions be-

tween the two proline enantiomers and the NAC SAM. The

spectra show a rather complex pattern with sharp positive and

negative bands. As a conclusion, the spectral response cannot

be reduced to the strong adsorption of only one enantiomer,

because this would lead to spectra strongly resembling the

proline spectrum. Although the signals are considerably above

the noise level (which is about 5 � 10�6 in the spectral region

around 1700 cm�1), the overall strength of the ATR-IR signals

reveals that the enantiodiscrimination between the NAC SAM

and proline is rather weak.

Dispersive bands in demodulated spectra, such as those

observed for the absolute configuration modulation experi-

ment (Fig. 7, top), can arise due to slight frequency shifts

induced by the stimulation, i.e. the change in absolute config-

uration of proline in this case. In our case, this means that, due

to the different interaction between the enantiomers of proline

and the chiral SAM, the spectrum of the interaction complex

changes slightly. Note that no such changes and therefore no

signals are expected in the demodulated spectra for an abso-

lute configuration modulation experiment over an achiral

surface45 (see, for example, Fig. 4c, top). The position of the

dispersive bands finally suggests frequency shifts of the proline

carboxylate nas(COO�) (possibly also ns(COO�)) and NH2

scissoring d(–NH2) and NAC amide and carboxylate vibra-

tions (compare the spectra of NAC and proline at the bottom

in Fig. 7).

Theoretical investigation of N-acetyl-L-cysteine—proline

intermolecular interactions

In order to further study the origin of the observed enantio-

discrimination, DFT calculations of an NAC–proline complex

were performed using GAUSSIAN03.90 The structures of

isolated NAC and proline were first optimized using the

hybrid functional B3PW9191,92 with a 6-31G basis set.93

Solvent (EtOH) effects were accounted for by performing

optimizations using a Polarizable Continuum Model

(PCM).94 It should be noted that other continuum models

exist, and even methods that explicitly consider solvent mole-

cules for the calculation of zwitterionic species.95 For the

system discussed here, no systematic study of different models

was performed and it is shown that the chosen method gives

satisfactorily results. It is, however, expected that the explicit

inclusion of solvent molecules in the calculation leads to an

improvement of the results.96 Structure optimization was

performed for proline in the zwitterionic form (as it prevails

in EtOH) and NAC in anionic form, since this species mainly

interacts with proline. Finally, the interaction complexes

between NAC (anionic) and the two proline enantiomers were

considered at the same level of theory. The conformational

space of the complex was further probed by a Born–Oppen-

heimer Molecular Dynamics (BOMD)97 using the semi-em-

pirical AM1 Hamiltonian.98 Among different NAC–proline

intermolecular forces, the ionic interaction between the posi-

tively charged proline NH2+ group and the negatively charged

NAC carboxylate COO� turned out to dominate the interac-

tion. Structure optimization was performed for the NAC-(D)-

proline and NAC-(L)-proline diastereomeric complexes and a

pictorial representation is given in Fig. 8, with the (L)-complex

shown in (a) and the (D)-complex shown in (b). For the former,

the partially charged groups are schematically indicated with

corresponding charge clouds. The difference in potential en-

ergy between the two chiral complexes was finally found to be

only about 0.2 kJ mol�1.

In order to compare theory with experiment, normal modes

analyses of the two chiral complexes were performed by

accounting for solvent effects. The phase-resolved spectra at

the top of Fig. 7, i.e. the result of the absolute configuration

modulation experiments, can be viewed as difference spectra

between the NAC-D-proline and the NAC-L-proline com-

plexes. The analogous difference spectrum can also be derived

from the DFT calculations. The result of the vibrational

analysis for the NAC-D-proline complex, denoted by ‘‘(D)’’,

and for the NAC-L-proline complex, denoted by ‘‘(L)’’,

Fig. 8 Pictorial representation of the optimized structures of the

NAC-L-proline (a) and NAC-D-proline (b) complexes. The structure of

the complexes is determined by ionic proline NH2+� � �COO� NAC

intermolecular interactions. In a) the charges are schematically indi-

cated by clouds. For details concerning the calculation method, see

text. M. Bieri and T. Burgi, ChemPhysChem, 2006, 7, 514–523.

Copyright John Wiley & Sons Limited. Reproduced with permission.

Fig. 9 Calculated vibrational spectra of NAC-D-proline (‘‘D’’) and

NAC-L-proline (‘‘L’’) complexes (optimized structures from Fig. 8). A

Lorentzian band shape with g = 10 cm�1 was used to simulate the

spectra from the calculated intensity. The corresponding difference

spectrum ‘‘(L) � (D)’’, scaled by a factor of 5, is presented at the

bottom as bold solid line. Note that the calculated difference spectrum

is experimentally accessible by ATR-IR and corresponds to the phase-

resolved spectra at the top of Fig. 7. M. Bieri and T. Burgi, Chem-

PhysChem, 2006, 7, 514–523. Copyright John Wiley & Sons Limited.

Reproduced with permission.


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together with the corresponding difference spectrum (bold

solid line, ‘‘L � D’’) is displayed in Fig. 9 (the spectra were

calculated by convoluting the IR intensities with a Lorentzian

band shape, using g= 10 cm�1). At first glance, the calculated

spectra of the (D) and (L) complex seem to be almost identical

but the resulting difference spectrum, scaled by a factor 5,

clearly reveals significant dispersive bands that originate from

slight frequency shifts of vibrational bands on the order of one

to several wavenumbers. The calculations thus clearly show

that very small frequency shifts of the complex due to the

change of the absolute configuration of proline results in

significant dispersive features in the corresponding difference

spectrum. This means that absolute configuration modulation

experiments, as performed here, are very sensitive to such

small changes and thus very sensitive to spotting small differ-

ences in diastereomeric interactions. Further, the calculations

are in qualitative agreement with experiment, shown in Fig. 7

(top). In particular, the observed dispersive line pattern be-

tween 1700 and 1550 cm�1 is very well reproduced by the

calculations. The agreement between experiment and theory

finally allows the conclusion that enantiodiscrimination is

dominated by a ‘‘one-point’’ electrostatic interaction between

proline (NH2+) and NAC (COO�). A ‘‘one-point interaction’’

is further consistent with the very small calculated energy dif-

ference between the two diastereomeric complexes, which is

also in agreement with the experiment. Still, even such weakly

enantiodiscriminating interactions lead to detectable signals in

the difference spectrum of the two diastereomeric complexes,

as was revealed by absolute configuration modulation.

In contrast to GSH, the NAC spectra reveal merely slight

frequency shifts only, which indicates that the NAC confor-

mation does not drastically change upon interaction with

proline. The reason for the better enantiodiscrimination of

GSH may therefore be associated with its larger flexibility as

compared to NAC.

Gold nanoparticles stabilized with chiral thiols can be

viewed as the nanometer size analogues of chiral SAMs on

flat gold surfaces formed by adsorption of the same thiols, and

similar surface chemistry may therefore be expected. However,

the investigation of SAMs and nanoparticles relies on rather

different techniques. It is shown below that Vibrational

Circular Dichroism (VCD) is a powerful tool to study chiral

nanoparticles.

Vibrational circular dichroism

Introduction. VCD99–102 is one of two principal forms of

Vibrational Optical Activity (VOA).36,103,104 The other form is

vibrational Raman Optical Activity (ROA).105–109 Both

VCD51,110 and ROA52,111 were discovered in the early 1970s.

VCD and ROA are both chiroptical spectroscopies that probe

the stereochemical structure of chiral molecules through their

vibrational transitions. VCD is simply the extension of tradi-

tional CD arising from transitions in the UV-Vis regions of the

spectrum to the IR. It is defined as the difference in the IR

absorbance A between left and right circularly polarized light

according to the following equation

DA ¼ AL � AR ð9Þ

With technological developments such as lock-in amplifiers,

liquid-nitrogen-cooled semiconductor detectors and IR polar-

ization modulators for the generation of left and right circu-

larly polarized radiation, stable electronic control of

experiments became possible. In 1997, the first commercial

VCD spectrometer based on FT-IR measurement design

became available.112 Nowadays, several manufacturers

provide IR spectrometers with VCD equipment.

Areas of application of vibrational circular dichroism. VCD

spectra contain substantial structural information. First of all,

the technique can be used to determine the absolute config-

uration of a sample without the need to grow single crystals.

Second, and perhaps even more important, the technique

yields information on the conformation of dissolved mole-

cules. This information has to be extracted from the experi-

mental spectrum through comparison with theory. For this,

the possible conformations of the molecule have to be deter-

mined, their structure refined and their VCD spectrum calcu-

lated. Generally, the VCD spectra of different conformations

differ significantly, such that the comparison with experiment

allows the determination of the most abundant confor-

mer(s).113,114 This strategy for structure determination of

dissolved molecules obviously relies on the quality of the

calculation. Today, methods are available, notably relying

on DFT, that have predictive character for VCD spectra. This

is illustrated in Fig. 10, which shows the comparison between

measured (thin traces) and calculated (bold traces) IR (de-

picted in the lower half) and VCD (depicted in the upper half)

spectra of heptahelicene.115 As is obvious, good qualitative

agreement between experimental and theoretical spectra can

be obtained despite the approximations inherent in the calcu-

lations, such as harmonic approximation for the vibrational

analysis and neglect of solvent. It has been realized only very

recently that VCD can be used to study chiral particles.116

Chiral gold nanoparticles

Gold nanoparticles can be prepared by reduction of an

Au(I)–thiol polymer.117,118 The latter is spontaneously formed

when mixing tetrachloroauric acid with the thiol. Upon re-

duction, nanoparticles are formed according to a nucleation,

growth and passivation mechanism. These nanoparticles are

highly soluble, depending on the adsorbate layer, i.e. the

nature of the thiol used for their preparation. This makes

them amenable to bulk techniques like Nuclear Magnetic

Resonance (NMR) and chiroptical spectroscopy, such as CD

or ECD and VCD. The latter two techniques selectively probe

the chirality of the particles. Specifically, CD spectroscopy

addresses electronic transitions in the UV and visible spectral

ranges. For gold nanoparticles, these transitions may be

located in the metal core. In contrast, VCD spectroscopy is

sensitive to vibrational transitions, which allows spotting the

chiral thiols adsorbed on the gold nanoparticles.

We have recently applied, for the first time, VCD spectro-

scopy to study the conformation of chiral thiols adsorbed on

gold nanoparticles.116 Specifically, we have prepared gold

nanoparticles covered with N-acetyl-L-cysteine (NAC)116 and

N-isobutyryl-cysteine (NIC).119 Typically, the particles are


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small with gold core diameters, as determined by transmission

electron microscopy, of about 2 nm and below. Fig. 11 shows

IR and VCD spectra of gold nanoparticles covered by

N-isobutyryl-L-cysteine and N-isobutyryl-D-cysteine, respec-

tively. Whereas the IR spectra are identical for the two

samples, the VCD spectra show mirror image relationship.119

Fig. 12 shows a comparison of calculated and experimental

VCD spectra of NAC protected gold particles. The calcula-

tions were performed for different adsorption modes (confor-

mers) of NAC. Obviously, the calculated spectra strongly

depend on the adsorption mode of the molecule, which shows

that VCD spectra contain detailed information on the con-

formation. In contrast, the structure of the gold particle seems

to have less influence on the VCD spectrum.116 The NAC-

protected nanoparticles that were investigated contain 20–200

gold atoms (1–2 nm core diameters) and up to several tenths of

adsorbed NAC molecules. The entire particle is too large to be

calculated at the required accuracy and therefore a single

molecule adsorbed on small metal clusters was considered.

Such an approximation is justified since molecular vibrations

are a local property. For example, the vibrational spectrum of

molecules adsorbed on a metal surface can very well be

reproduced by calculations that consider only one single

molecule adsorbed on a small cluster of a few atoms.89,120

The comparison in Fig. 12 shows that the VCD spectrum of

one conformer only (the bottom one) is compatible with the

experimental spectrum. The two most prominent bands in the

experimental VCD spectrum—at 1627 and 1595 cm�1—are

associated with the amide I and asymmetric carboxylate

nas(COO�) modes, respectively, which are positive and nega-

tive, respectively, in the spectrum. For the two conformers

shown in Fig. 12, top, both bands are negative. For other

conformers (not shown) the two bands are negative. For the

bottom conformer in Fig. 12, the two bands have the correct

sign. For this conformer, also the rest of the spectrum matches

best with experiment, in particular the two positive bands

around 1425 cm�1 (CH2 scissoring and das(CH3)) and the

negative C–H bending mode at 1330 cm�1. The latter band is

Fig. 10 Comparison between calculated (bold) and experimental

(thin) IR (bottom) and VCD spectra of heptahelicene. Note that the

spectral region of the strongly absorbing solvent is excluded from the

experimental spectra. The calculations were performed at the B3LYP/

6-31G(d,p) level of theory and were performed on the M enantiomer

shown in the Figure (top). The calculated frequencies were scaled by a

factor of 0.97 and the intensity axes of the calculated spectra were

scaled to fit the experimental ones.115

Fig. 11 Infrared (top) and VCD (bottom) spectra of N-isobutyryl-

cysteine-protected gold nanoparticles in NaOH/D2O. The dashed

(solid) lines correspond to the spectra of the particles covered by the

L-enantiomer (D-enantiomer). The IR spectrum of the particles cov-

ered with N-isobutyryl-L-cysteine was offset for clarity. Reprinted with

permission from ref. 119. Copyright (2006) American Chemical

Society.


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clearly negative in the experimental spectrum, whereas for the

calculated conformers it is slightly negative for the bottom

(matching) conformer but positive for the other two confor-

mers (top). The VCD analysis discussed above shows that

NAC adsorbs on the gold particles preferentially in the way

shown for the bottom conformer in Fig. 12. The conformer

that matches best the experimental VCD spectrum is also

calculated to be the most stable one, although some other

conformers are calculated only 3–4 kcal mol�1 higher in

energy.

The adsorption mode as determined by VCD spectroscopy

is characterized by a double interaction between adsorbate and

gold particle. Besides the strong sulfur–gold bond, an addi-

tional carboxylate–gold bond is formed. Evidence for this

double interaction stems further from independent ATR-IR

experiments, where NAC was adsorbed from EtOH on gold

surfaces (see above).70 A VCD study of gold nanoparticles

covered with NIC resulted in an analogous adsorption

geometry.119

A relevant issue that needs to be addressed in future studies

is the importance of low-lying electronic states of the metal

core on the VCD spectra of the adsorbate.121 It has been

shown before that some transition metal complexes reveal

enhanced vibrational optical activity due to interaction with

low-lying electronic states.122 Enhancement effects in vibra-

tional spectroscopy are well-known for adsorbates on metal

surfaces from surface-enhanced Raman123 and surface-

enhanced IR spectroscopy.124

The gold nanoparticles described above are charged due to

the deprotonation of the acid groups in water, and hence they

migrate in an electric field. This property can be used for their

separation according to charge and size in an electrophoresis.

Fig. 13 shows a separation of NIC gold particles in

PolyAcrylamide Gel Electrophoresis (PAGE). The appearance

of separate bands indicates the presence of compounds with

distinct composition, i.e. number of gold atoms and thiol

ligands. Clearly, these different compounds have different

color, which directly reflects the size-dependent electronic

structure of the gold core. This is also reflected in the

UV-Vis spectra (not shown), which exhibit considerable fine-

structure.119 Similar separations were reported for particles

stabilized with GSH (Scheme 2).54,58,125 The latter particles

were analyzed by mass spectrometry, which revealed cores of

10–38 gold atoms. Comparison of the color and UV-Vis

spectra between the NIC and GSH particles indicated similar

core sizes for the two. Therefore, the particles shown in Fig. 13

contain about 10 gold atoms for the smallest compound (the

band on the right) to about 40 gold atoms for the larger

compounds.

Extraction and purification by dialysis yields the different

compounds that can be analyzed by CD spectroscopy. Fig. 14

shows the CD and UV-Vis spectra of compounds 2, 3 and 4

(Fig. 13). The bands are associated with electronic transitions

in the metal core, which shows that the electronic structure of

the gold cores is chiral. A key question emerging from these

studies, which remains to be answered, is whether the structure

of the metal core is intrinsically chiral or whether the CD

signals in the metallic transitions are induced by the chiral

ligands adsorbed on an achiral metal core. The first possibility

has support from theoretical calculations, which indicate that

small metal particles such as Au28 prefer low symmetry chiral

over high symmetry achiral structures.126 This could indicate

that, in general, such small metal particles adopt a chiral

structure. Evidently, the samples would be racemic if covered

by an achiral thiol. In combination with a chiral thiol, how-

ever, one of the two enantiomeric forms of the metal core

might be more stable, and thus favored over the other.

In case of an achiral metal core covered with a chiral thiol,

several mechanisms are possible for the induction of optical

activity in the metallic transitions. These include the chiral

arrangement of the ligands and the influence of the asymmetric

centers of the chiral ligands (through space or through bonds)

Fig. 12 Comparison between calculated (top three) and experimental

(bottom) VCD spectra of N-acetyl-L-cysteine (Scheme 3) adsorbed on

gold particles. Calculations at the B3PW91 level using a 6-31G(d,p)

basis set (LanL2DZ for gold) were performed for N-acetyl-L-cysteine

in different conformations adsorbed on a Au4 cluster. The correspond-

ing structures are shown on the right. The experimental spectrum

(bottom) was obtained form a solution of nanoparticles in

NaOH/D2O. More details can be found elsewhere.116

Fig. 13 PolyAcrylamide Gel Electrophoresis (PAGE) separation of

N-isobutyryl-L-cysteine-protected gold particles. The separated com-

pounds are numbered from 1–8 according to their decreasing electro-

phoretic mobility. Compound 1 is only visible under UV irradiation.

Reprinted with permission from ref. 119. Copyright (2006) American

Chemical Society.


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on the electronic structure of the metal. For example, it has

been demonstrated recently using a dissymmetrically-per-

turbed particle-in-a-box model that CD signals can arise from

chiral adsorbates on symmetric particles.127 Induced CD

occurs when transition dipole moments of optically active

electronic transitions couple to transition dipole moments of

another species, which may be achiral. Induced CD is, for

example, observed for achiral drug molecules interacting with

DNA128 and has also been reported in the IR.129 The coupling

is possible both for electronic and magnetic transition dipole

moments.130

From a more structural point of view, the chirality of the

gold nanoparticles is similar to the one discussed for flat metal

surfaces (Fig. 15),15 which can be intrinsically chiral, such as

the one shown in Fig. 15a.131 Adsorption of molecules on an

achiral surface may lead to a chiral adsorbate pattern of long-

range ordered molecules (Fig. 15b).132,133 Note that, in this

case, the molecule does not have to be chiral.134 In the latter

case, the resulting surface is racemic, consisting of patches on

the surface with opposite chirality. An adsorbed chiral mole-

cule may also induce a chiral distortion of the metal surface

atoms from the equilibrium position that they adopt in the

absence of the adsorbate. The chiral molecule may thus impart

a chiral ‘‘footprint’’ on the surface.135 The model shown in

Fig. 15c holds for adsorption of a chiral thiol that interacts, in

addition to the sulfur, via a carboxylate with a gold surface.

Finally, the chirality may be associated solely with the chirality

of an adsorbed molecule (Fig. 15d). Analogous situations can

occur for monolayer protected gold particles. For example, the

adsorption of NAC may lead to chiral ‘‘footprints’’ on the

(particle) surface similar to that shown in Fig. 15c. The

adsorption mode of NAC as determined by VCD spectroscopy

(Fig. 12) is in agreement with this model.

Fig. 14 CD and UV-Vis spectra of separated compounds 2–4 (see

Fig. 13) of gold particles covered with N-isobutyryl-L-cysteine

(dashed) and N-isobutyryl-D-cysteine (solid line). The UV-Vis spectra

were scaled to 1 absorbance unit at 250 nm. Reprinted with permission

from ref. 119. Copyright (2006) American Chemical Society.

Fig. 15 Different possibilities for chiral metal surfaces: (a) Intrinsi-

cally chiral metal surfaces: Kink sites on a high Miller index single

crystal surface.21 (b) Supramolecular chirality on achiral terraces by

self-assembly of molecules. The example shows adsorbed tartaric acid

on Cu(110).133 The adsorption pattern destroys all symmetry planes of

the underlying metal surface. (c) A chiral ‘‘footprint’’. Adsorption of a

chiral molecule leads to a distortion of the surface atoms to a chiral

arrangement. In the model shown here, a gold surface is distorted by

adsorption of a chiral thiol. Besides the thiol, represented by S, a

carboxylate group, represented by O, interacts with the surface. (d) A

chiral site on a metal surface can be generated by adsorption of a chiral

molecule. The picture shows cinchonidine on a Pt(111) surface.142 The

latter is used to induce enantioselectivity in the hydrogenation of

a-functionalized prochiral ketones to the corresponding alcohol.15


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All of the different possibilities presented above are likely to

lead to a chiral electronic structure of the metal136 and thus

CD signals, although to different extents. The magnitude of

the anisotropy factor g = De/e may thus give a hint on the

likelihood of the different possibilities. Optical activity was

reported for size-selected gold particles protected by GSH,54

penicillamine137 and NIC.119 The anisotropy factors for these

systems are on the order of 1/1000 and thus quite strong. A

comparison with chiral fullerenes is appropriate, as the latter

exhibit delocalized electronic structure, analogous to that

expected in metallic particles. Fullerenes with a different chiral

nature have been reported: intrinsically chiral fullerenes, such

as C76138 and C84,

139,140 fullerenes with chiral functionaliza-

tion patterns (C70),141 and fullerenes with an achiral functio-

nalization pattern but with an attached optically active

group.141 The former two situations lead to large anisotropy

factors, comparable in magnitude to the ones observed for the

gold particles,54 whereas the latter situation leads to consider-

ably weaker anisotropy factors.141 These considerations would

point more towards an intrinsically chiral metal core (or chiral

‘‘footprint’’) or a chiral adsorbate pattern, rather than an

induced CD from a chiral adsorbate on an achiral core with

achiral adsorbate pattern.

Conclusions

Vibrational spectroscopy is a powerful technique to probe

chiral interfaces and their ability to discriminate between

enantiomers. Besides pure quantification of enantiodiscrimi-

nation, considerable molecular-level insight into the origin of

the latter can be obtained. However, this requires adapted

tools that push the limits of conventional infrared spectro-

scopy. The latter is intrinsically non-selective and therefore the

discrimination between important and unimportant species or

between enantiodiscriminating and non-selective interactions

is difficult to make. Attenuated Total Reflection InfraRed

(ATR-IR) combined with Modulation Excitation Spectro-

scopy (MES) is both highly sensitive and selective for the

enantiodiscriminating interactions. By periodically admitting

the two enantiomers of the chiral selectand to the selector

immobilized on the internal reflection element (absolute con-

figuration modulation), and by a phase sensitive detection of

the time-resolved ATR-IR spectra, the relevant enantiodiscri-

minating interactions are spotted, whereas non-specific inter-

actions are suppressed. In addition, the phase sensitive

detection results in an increase in sensitivity, which easily

allows the study of chiral self-assembled monolayers on gold

surfaces. In spite of these advantages the techniques do not

require expensive equipment and the digital phase sensitive

detection is easily performed on a personal computer. The

nanometer-size analogues of chiral SAMs—metal nanoparti-

cles covered by chiral thiols—are amenable to Vibrational

Circular Dichroism (VCD). Again, this technique is very

selective for the chiral structure of the sample under investiga-

tion. VCD spectroscopy is sensitive towards the conformation

of molecules adsorbed on the nanoparticles. It has therefore

the potential to become an important tool for structure

determination of chiral molecules adsorbed on nanoparticles,

also in view of the difficulty to grow single crystals of these

compounds suitable for crystallography. The importance of

structure determination derives from the fact that many

potentially valuable properties of nanoparticles, such as

molecular recognition and self-assembly, are directly affected

by the structure of the adsorbed molecules. In addition, the

adsorbed molecules can bestow chirality to the metal core,

as is directly evident from optical activity in metal-based

electronic transitions.

Acknowledgements

Financial support by the Swiss National Science Foundation

and grants of computer time by the Swiss National Super-

computer Centre (Manno) are kindly acknowledged.

References

1 L. Pasteur, Ann. Chim. Phys., 1848, 24, 442–459.2 A. Saghatelian, Y. Yokobayashi, K. Soltani and M. R. Ghadiri,Nature, 2001, 409, 797–801.

3 R. M. Hazen, T. R. Filley and G. A. Goodfriend, Proc. Natl.Acad. Sci. U. S. A., 2001, 98, 5487–5490.

4 D. A. M. Zaia, Amino Acids, 2004, 27, 113–118.5 E. Rubenstein, W. A. Bonner, H. P. Noyes and G. S. Brown,Nature, 1983, 306, 118–118.

6 J. T. Cronin and S. Pizzarello, Science, 1997, 275, 951–955.7 G. Belavoine, A. Moradpour and H. B. Kagan, J. Am. Chem.Soc., 1974, 96, 5152–5158.

8 A. S. Garay and J. A. Ahlgren-Beckendorf, Nature, 1990, 346,451–453.

9 J. Podlech, Cell. Mol. Life Sci., 2001, 58, 44–60.10 I. W. Wainer, Drug Stereochemistry: Analytical Methods and

Pharmacology: Second Edition, Revised and Expanded, MarcelDekker, New York, 1993.

11 H. Y. Aboul-Enein and I. W. Wainer, The Impact of Stereochem-istry on Drug Development and Use, Wiley, New York, 1997.

12 J. Caldwell, J. Chromatogr., A, 1995, 694, 39–48.13 J. Caldwell, J. Chromatogr., A, 1996, 719, 3–13.14 R. S. Atkinson, Stereoselective Synthesis, John Wiley and Sons,

New York, 1995.15 T. Burgi and A. Baiker, Acc. Chem. Res., 2004, 37, 909–917.16 A. Baiker and H. U. Blaser, in Handbook of Heterogeneous

Catalysis, ed. G. Ertl, H. Knozinger and J. Weitkamp, VCHPublishers, Weinheim, 1997, pp. 2422–2436.

17 S. Ahuja, Chiral Separations by Chromatography, OxfordUniversity Press, Washington, DC, 2000.

18 K. Bodenhofer, A. Hierlemann, J. Seemann, G. Gauglitz, B.Koppenhoefer and W. Gopel, Nature, 1997, 387, 577–580.

19 R. McKendry, M. E. Theoclitou, T. Rayment and C. Abell,Nature, 1998, 391, 566–568.

20 G. A. Attard, J. Phys. Chem. B, 2001, 105, 3158–3167.21 J. D. Horvath and A. J. Gellman, J. Am. Chem. Soc., 2002, 124,

2384–2392.22 J. D. Horvath, A. Koritnik, P. Kamakoti, D. S. Sholl and A. J.

Gellman, J. Am. Chem. Soc., 2004, 126, 14988–14994.23 E. R. Francotte, in Chiral Separations, Applications and Techno-

logy, ed. S. Ahuja, American Chemical Society, Washington, DC,1997, p. 349.

24 E. R. Francotte, Chimia, 1997, 51, 717–725.25 E. R. Francotte, J. Chromatogr., A, 1994, 666, 565–601.26 J. Dingenen and J. N. Kinkel, J. Chromatogr., A, 666, 627–650.27 N.M.Maier, P. Franco andW. Lindner, J. Chromatogr., A, 2001,

906, 3–33.28 T. Nakanishi, N. Yamakawa, T. Asahi, T. Osaka, B. Ohtani and

K. Uosaki, J. Am. Chem. Soc., 2002, 124, 740–741.29 T. Nakanishi, N. Yamakawa, T. Asahi, N. Shibata, B. Ohtani

and T. Osaka, Chirality, 2004, 16, S36–S39.30 J. Huang, V. M. Egan, H. Guo, J.-Y. Yoon, A. L. Briseno, I. E.

Rauda, R. L. Garrell, C. M. Knobler, F. Zhou and B. Kaner,Adv. Mater., 2003, 15, 1158–1161.


Dow

nloa

ded

on 2

3 Se

ptem

ber

2010

Publ

ishe

d on

01

Dec

embe

r 20

06 o

n ht

tp://

pubs

.rsc

.org

| do

i:10.

1039

/B60

9930

KView Online


31 R. Paolesse, D. Monti, L. La Monica, M. Venanzi, A. Froiio, S.Nardis, C. Di Natale, E. Martinelli and A. D’Amico, Chem.–Eur.J., 2002, 8, 2476–2483.

32 N. M. Maier, S. Schefzick, G. M. Lombardo, M. Feliz, K.Rissanen, W. Lindner and K. B. Lipkowitz, J. Am. Chem. Soc.,2002, 124, 8611–8629.

33 D. J. O’Conner, B. A. Sexton and R. S. C. Smart, SurfaceAnalysis Methods in Materials Science, Springer Series in SurfaceScience, Springer-Verlag, Berlin, 1992.

34 A. J. Alder, N. J. Greenfield and G. D. Fasman, MethodsEnzymol., 1973, 27, 675.

35 S. Pagliari, R. Corradini, G. Galaverna, S. Sforza, A. Dossena,M. Montalti, L. Prodi, N. Zaccheroni and R. Marchelli,Chem.–Eur. J., 2004, 10, 2749–2758.

36 L. A. Nafie, Annu. Rev. Phys. Chem., 1997, 48, 357–386.37 W. Hug, S. Kint, G. F. Bailey and J. R. Scherer, J. Am. Chem.

Soc., 1975, 97, 5589–5590.38 J. M. Hicks and T. Petralli-Mallow, Appl. Phys. B: Lasers Opt.,

1999, 68, 589–593.39 N. Ji and Y. R. Shen, Chirality, 2006, 18, 146–158.40 N. Ji, K. Zhang, H. Yang and Y. R. Shen, J. Am. Chem. Soc.,

2006, 128, 3482–3483.41 A. J. Gellman, J. D. Horvath andM. T. Buelow, J. Mol. Catal. A:

Chem., 2001, 167, 3–11.42 N. J. Harrick, Internal Reflection Spectroscopy, Interscience

Publishers, New York, 1967.43 D. Baurecht and U. P. Fringeli, Rev. Sci. Instrum., 2001, 72,

3782–3792.44 T. Burgi and A. Baiker, J. Phys. Chem. B, 2002, 106,

10649–10658.45 R. Wirz, T. Burgi and A. Baiker, Langmuir, 2003, 19, 785–792.46 R. Wirz, T. Burgi, W. Lindner and A. Baiker, Anal. Chem., 2004,

76, 5319–5330.47 M. Bieri and T. Burgi, J. Phys. Chem. B, 2005, 109, 10243–10250.48 M. Bieri and T. Burgi, ChemPhysChem, 2006, 7, 514–523.49 L. A. Nafie, T. A. Keiderling and P. J. Stephens, J. Am. Chem.

Soc., 1976, 98, 2715–2723.50 J. A. Schellman, Chem. Rev., 1975, 75, 323–331.51 L. A. Nafie, J. C. Cheng and P. J. Stephens, J. Am. Chem. Soc.,

1975, 97, 3842–3843.52 W. Hug, S. Kint, G. F. Bailey and J. R. Scherer, J. Am. Chem.

Soc., 1975, 97, 5589–5590.53 J. A. Schellman, Chem. Rev., 1975, 75, 323–331.54 T. G. Schaaff and R. L. Whetten, J. Phys. Chem. B, 2000, 104,

2630–2641.55 I. Newton, Opticks, Dover Publications, New York, 1952.56 M. Born and E. Wolf, Principles of Optics, Pergamon, Oxford,

UK, 1979.57 T. Burgi and A. Baiker, Advances in Catalysis, 2006, 50, 228–283.58 W. Mantele, Biophysical Techniques in Photosynthesis, Kluwer

Academic, Dordrecht, The Netherlands, 1996.59 H. Strehlow and W. Knoche, Fundamentals of Chemical Relaxa-

tion, Verlag Chemie, Weinheim, 1977.60 U. P. Fringeli, D. Baurecht and H. H. Gunthard, in Infrared and

Raman Spectroscopy of Biological Materials, eds. H. U. Gremlichand B. Yan, Dekker, New York/Basel, 2000, pp. 143–192.

61 J. Fourier, The Analytical Theory of Heat, Cambridge universitypress, 1878.

62 A. Urakawa, T. Burgi, H.-P. Schlapfer and A. Baiker, J. Chem.Phys., 2006, 124, 054717.

63 A. Urakawa, T. Burgi and A. Baiker, Chimia, 2006, 60, 231–233.64 A. Urakawa, T. Burgi and A. Baiker, Chem. Phys., 2006, 324,

653–658.65 A. Urakawa, R. Wirz, T. Burgi and A. Baiker, J. Phys. Chem. B,

2003, 107, 13061.66 D. Baurecht, I. Porth and U. P. Fringeli,Vib. Spectrosc., 2002, 30,

85–92.67 M. Muller, R. Buchet and U. P. Fringeli, J. Phys. Chem., 1996,

100, 10810–10825.68 M. Bieri and T. Burgi, Langmuir, 2005, 21, 1354–1363.69 M. Bieri and T. Burgi, Phys. Chem. Chem. Phys., 2006, 8,

513–520.70 M. Bieri and T. Burgi, J. Phys. Chem. B, 2005, 109, 22476–22485.71 T. M. Bray and C. G. Taylor, Can. J. Physiol. Pharmacol., 1993,

71, 746–751.

72 H. Sies, Free Radical Biol. Med., 1999, 27, 916–921.73 K. Takehara, M. Aihara and N. Ueda, Electroanalysis, 1994, 6,

1083–1086.74 H. McCormick, R. McMillan, K. Merrett, F. Bensebaa, Y.

Deslandes, M. A. Dube and H. Sheardown, Colloids Surf., B,2002, 26, 351–363.

75 N. Damrongchai, K. Yun, E. Kobatake and M. Aizawa,J. Biotechnol., 1997, 55, 125–133.

76 S. Kanagaraja, S. Alaeddine, C. Eriksson, J. Lausmaa, P. Teng-vall, A. Wennerberg and H. Nygren, J. Biomed. Mater. Res.,1999, 46, 582–591.

77 C. Fang and X. Zhou, Electroanalysis, 2001, 13, 949–954.78 C. Fang and X. Zhou, Electroanalysis, 2002, 14, 711–714.79 J. Wang and P. Grundler, Electroanalysis, 2003, 15, 1756–1761.80 F. Zhao, B. Zeng and D. Pang, Electroanalysis, 2003, 15,

1060–1066.81 A. Zhou, Q. Xie, Y. Wu, Y. Cai, L. Nie and S. Yao, J. Colloid

Interface Sci., 2000, 229, 12–20.82 M. Hepel and E. Tewksbury, J. Electroanal. Chem., 2003, 552,

291–305.83 B. Zeng, X. Ding and F. Zhao, Electroanalysis, 2002, 14, 651–656.84 J. Wang, B. Zeng, C. Fang and Z. X., Electroanalysis, 2000, 12,

763–766.85 C. Fang and X. Zhou, Electroanalysis, 2003, 15, 1632–1638.86 M. Aihara, F. Tanaka, Y. Miyazaki and K. Takehara, Anal.

Lett., 2002, 35, 759–765.87 T. G. Schaaff, G. Knight, M. N. Shafigullin, R. F. Borkman and

R. L. Whetten, J. Phys. Chem. B, 1998, 102, 10643–10646.88 Y. Negishi, Y. Takasugi, S. Sato, H. Yao, K. Kimura and

T. Tsukuda, J. Am. Chem. Soc., 2004, 126, 6518–6519.89 T. Burgi and M. Bieri, J. Phys. Chem. B, 2004, 108, 13364–13369.90 M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A.

Robb, J. R. Cheeseman, J. A. Montgomery, T. Vreven, K. N.Kudin, J. C. Burant, J. M. Millam, S. S. Iyengar, J. Tomasi, V.Barone, B. Mennucci, M. Cossi, G. Scalmani, N. Rega, G. A.Petersson, H. Nakatsuji, M. Hada, M. Ehara, K. Toyota, R.Fukuda, J. Hasegawa, H. Ishida, T. Nakajima, Y. Honda, O.Kitao, H. Nakai, M. Klene, X. Li, J. E. Knox, H. P. Hratchian, J.B. Cross, C. Adamo, J. Jaramillo, R. Gomperts, R. E. Stratmann,O. Yazyev, A. J. Austin, R. Cammi, C. Pomelli, J. Ochterski, P.Y. Ayala, K. Morokuma, G. A. Voth, P. Salvador, J. J. Dannen-berg, V. G. Zakrzewski, S. Dapprich, A. D. Daniels, M. C. Strain,O. Farkas, D. K. Malick, A. D. Rabuck, K. Raghavachari, J. B.Foresman, J. V. Ortiz, Q. Cui, A. G. Baboul, S. Clifford, J.Cioslowski, B. B. Stefanov, G. Liu, A. Liashenko, P. Piskorz, I.Komaromi, R. L. Martin, D. J. Fox, T. Keith, M. A. Al-Laham,C. Y. Peng, A. Nanayakkara, M. Challacombe, P. M. W. Gill, B.Johnson, W. Chen, M. W. Wong, C. Gonzalez and J. A. Pople,GAUSSIAN03, Inc., Wallingford CT, 2003.

91 A. D. Becke, J. Chem. Phys., 1993, 98, 5648–5652.92 J. P. Perdew, J. A. Chevary, S. H. Vosko, K. A. Jackson, M. R.

Pederson, D. J. Singh and C. Fiolhais, Phys. Rev. B: Condens.Matter Mater. Phys., 1992, 46, 6671–6687.

93 R. Ditchfield, W. J. Hehre and J. A. Pople, J. Chem. Phys., 1971,54, 724–728.

94 M. T. Cances, B. Mennucci and J. Tomasi, J. Chem. Phys., 1997,107, 3032–3041.

95 K. J. Jalkanen, R. M. Nieminen, M. Knapp-Mohammady and S.Suhai, Int. J. Quantum Chem., 2003, 92, 239–259.

96 K. J. Jalkanen, V. W. Jurgensen, A. Claussen, A. Rahim, G. M.Jensen, R. C. Wade, F. Nardi, C. Jung, I. M. Degtyarenko, R. M.Nieminen, F. Herrmann, M. Knapp-Mohammady, T. A. Nie-haus, K. Frimand and S. Suhai, Int. J. Quantum Chem., 2006, 106,1160–1198.

97 T. Helgaker, E. Eggerud and H. J. A. Jensen, Chem. Phys. Lett.,1990, 173, 145–150.

98 M. Dewar and W. Thiel, J. Am. Chem. Soc., 1977, 99, 2338–2339.99 L. A. Nafie and T. B. Freedman, Enantiomer, 1998, 3, 283–297.100 L. A. Nafie, in Encyclopedia of Spectroscopy and Spectrometry,

ed. J. C. Lindon, G. E. Tranter and J. L. Holmes, Academic Press,London, 1999, pp. 2391–2402.

101 L. A. Nafie, in Encyclopedia of Analytical Chemistry: Instrumen-tation and Applications, ed. R. A. Meyers, John Wiley and Sons,Chichester, 2000, pp. 662–676.


Dow

nloa

ded

on 2

3 Se

ptem

ber

2010

Publ

ishe

d on

01

Dec

embe

r 20

06 o

n ht

tp://

pubs

.rsc

.org

| do

i:10.

1039

/B60

9930

KView Online


102 T. A. Keiderling, in Circular Dichroism: Principles and Applica-tions, ed. N. Berova, K. Nakanishi and R. W. Woody, Wiley-VCH, New York, 2000, pp. 621–666.

103 L. A. Nafie, in Circular Dichroism: Principles and Applications, ed.K. Nakanishi, N. Berova and R. W. Woody, Wiley-VCH, NewYork, 2000, pp. 97–131.

104 L. A. Nafie and T. B. Freedman, in Infrared and Raman Spectro-scopy of Biological Materials, ed. H. U. Gremlich and B. Yan,Marcel Dekker Inc., New York, 2001, pp. 15–54.

105 L. D. Barron, L. Hecht, E. W. Blanch and A. F. Bell, Prog.Biophys. Mol. Biol., 2000, 73.

106 L. D. Barron and L. Hecht, in Circular Dichroism: Principles andApplications, ed. N. Berova, K. Nakanishi and R. W. Woody,Wiley-VCH, New York, 2000, pp. 667–701.

107 W. Hug, in Encyclopedia of Spectroscopy and Spectrometry, ed.J. Lindon, G. Tranter and J. Holmes, Academic Press, London,1999, pp. 1966–1976.

108 W. Hug andG. Hangartner, J. Raman Spectrosc., 1999, 30, 841–582.109 L. A. Nafie, in Encyclopedia of Spectroscopy and Spectrometry,

ed. T. Lindon, G. Tranter and J. Holmes, Academic Press,London, 1999, pp. 1976–1985.

110 G. Holzwarth, E. C. Hsu, H. S. Mosher, T. R. Faulkner and A.Moscowitz, J. Am. Chem. Soc., 1974, 96, 251–252.

111 L. D. Barron, M. P. Bogaard and A. D. Buckingham, J. Am.Chem. Soc., 1973, 95, 603–605.

112 L. A. Nafie, F. Long, T. B. Freedman, H. Buijs, A. Rilling, J.-R.Roy and R. A. Dukor, in Fourier Transform Spectroscopy: 11thInternational Conference, ed. J. A. de Haseth, Woodbury, NY,1998, pp. 432–434.

113 L. A. Bodack, T. B. Freedman, B. Z. Chowdhry and L. A. Nafie,Biopolymers, 2004, 73, 163–177.

114 F. Wang and P. L. Polavarapu, J. Phys. Chem. A, 2000, 104,1822–1826.

115 T. Burgi, U. Urakawa, B. Behzadi, K.-H. Ernst and A. Baiker,New J. Chem., 2004, 28, 332–334.

116 C. Gautier and T. Burgi, Chem. Commun., 2005, 43, 5393–5395.117 A. C. Templeton, S. Chen, S. M. Gross and R. W. Murray,

Langmuir, 1999, 15, 66–76.118 M. Brust, M. Walker, D. Bethell, D. J. Schiffrin and R. Whyman,

J. Chem. Soc., Chem. Commun., 1994, 7, 801–802.119 C. Gautier and T. Burgi, J. Am. Chem. Soc., 2006, 128,

11079–11087.120 M. Neurock, Top. Catal., 1999, 9, 135–152.

121 L. A. Nafie, J. Phys. Chem. B, 2004, 108, 7222–7231.122 Y. N. He, X. L. Cao, L. A. Nafie and T. B. Freedman, J. Am.

Chem. Soc., 2001, 123, 11320–11321.123 A. Wokaun, Mol. Phys., 1895, 56, 1–33.124 M. Osawa, K. Ataka, M. Ikeda, H. Uchihara and R. Naba, Anal.

Sci. (Suppl.), 1991, 7, 503–506.125 Y. Negishi, K. Nobusada and T. Tsukuda, J. Am. Chem. Soc.,

2005, 127, 5261–5270.126 I. L. Garzon, J. A. Reyes-Nava, J. I. Rodriguez-Hernandez, I.

Sigal, M. R. Beltran and K. Michaelian, Phys. Rev. B, 2002, 66,73403.

127 M.-R. Goldsmith, C. B. George, G. Zuber, R. Naaman, W. D. H.P. Wipf and D. N. Beratan, Phys. Chem. Chem. Phys., 2006, 8,63–67.

128 S. Allenmark, Chirality, 2003, 15, 409–422.129 T. Burgi, A. Vargas and A. Baiker, J. Chem. Soc., Perkin Trans. 2,

2002, 9, 1596–1601.130 T. Mizutani, T. Ema, T. Yoshida, T. Renne and H. Ogoshi, Inorg.

Chem., 1994, 33, 3558–3566.131 C. F. McFadden, P. S. Cremer and A. J. Gellman, Langmuir,

1996, 12, 2483–2487.132 M. O. Lorenzo, S. Haq, T. Bertrams, P. Murray, R. Raval and C.

J. Baddeley, J. Phys. Chem. B, 1999, 103, 10661–10669.133 M. O. Lorenzo, C. J. Baddeley, C. Muryn and R. Raval, Nature,

2000, 404, 376–379.134 V. Humblot and R. Raval, Appl. Surf. Sci., 2005, 241, 150–156.135 V. Humblot, S. Haq, C. Muryn, W. A. Hofer and R. Raval, J.

Am. Chem. Soc., 2002, 124, 503–510.136 W. A. Hofer, V. Humblot and R. Raval, Surf. Sci., 2004, 554,

141–149.137 H. Yao, K. Miki, N. Nishida, A. Sasaki and K. Kimura, J. Am.

Chem. Soc., 2005, 127, 15536–15543.138 R. Kessinger, J. Crassous, A. Herrmann, M. Ruttimann, L.

Echegoyen and F. Diederich, Angew. Chem., Int. Ed., 1998, 37,1919–1922.

139 T. J. S. Dennis, T. Kai, T. Tomiyama and H. Shinohara, Chem.Commun., 1998, 619–620.

140 J. Crassous, J. Rivera, N. S. Fender, L. Shu, L. Echegoyen, C.Thilgen, A. Herrmann and F. Diederich, Angew. Chem., Int. Ed.,1999, 38, 1613–1617.

141 A. Herrmann, M. Ruttimann, C. Thilgen and F. Diederich, Helv.Chim. Acta, 1995, 78, 1673–1704.

142 A. Vargas, T. Burgi and A. Baiker, J. Catal., 2004, 226, 69–82.


Dow

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Probing chiral interfaces by infrared spectroscopic methods · 2010-09-23 · investigate...

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