Rapid characterization of complex viscous liquids at the molecular level

Article abstract of DOI:10.1002/anie.200902360

Sticky subject: An N₂ stream forms bubbles inside bulk viscous liquids, which create an aerosol sample through a microjetting mechanism (see picture). This aerosol is then analyzed by extractive electrospray ionization (EESI) mass spectrometry (MS). EESI-MS reveals the molecular composition of complex liquids and the kinetics of ongoing processes occurring in the highly viscous liquids without any sample pretreatment.

Full text of DOI:10.1002/anie.200902360

Angewandte
Chemie
DOI: 10.1002/anie.200902360
Mass Spectrometry
Rapid Characterization of Complex Viscous Liquids at the Molecular
Level**
Wai Siang Law, Huanwen Chen,* Jianhua Ding, Shuiping Yang, Liang Zhu, Gerardo Gamez,
Konstantin Chingin, Yulin Ren, and Renato Zenobi*
Mass spectrometry (MS) is the
method of choice for molecular char-
acterization of complex samples,[1–3]
due to its unparalleled ability to
acquire detailed qualitative and
quantitative information as well as
its exceptional sensitivity and specif-
icity. Recent progress in the rapid
characterization of complex samples
by MS has mostly been due to the
rapid development of ambient ion-
ization techniques,[4–18] which require
no or only minimal sample pretreat-
ment. For instance, analytes present
on solid surfaces[5–9] or in liquid
solutions,[10–14] aerosols,[15,16] and
living objects[17,18] have been success-
fully detected at low concentration
levels. However, studies on viscous
complex mixtures remain sparse.
Figure 1. Schematic illustration of the concept and setup of EESI-MS. Inset: compositions and
environment of molecules present in bulk liquid, liquid–gas interface, and headspace. The
temperature of the heated column is 808C.
Herein, we report a simple yet
universal method based on extrac-
tive electrospray ionization mass
spectrometry (EESI-MS) to directly
analyze complex liquid samples of high viscosity.[19,20] As
shown in Figure 1, a stream of nitrogen gas is directed into the
liquid and causes bubble formation under the liquid surface.
Driven by the gas pressure, the emerging bubbles carry
molecules of the bulk sample up to the liquid surface.
Eventually, at the gas–liquid interface (inset of Figure 1 and
Supporting Information, Figure S1), the bubbles burst, creat-
ing microdroplets through a mechanism known as micro-
jetting.[19,20] Several studies have been conducted to inves-
tigate similar processes occurring in highly viscous liquids.
These studies, however, only focused on the bursting kinetics
of microbubbles rather than on the molecular composition of
the microbubbles owing to technological limitations.[21–23]
Unlike previous techniques,[17] EESI-MS is able to analyze
aerosol formed from the bulk liquid, which is representative
of the molecular composition of the bulk liquid. Thus,
microjetting with subsequent EESI-MS analysis provides a
unique opportunity to chemically characterize complex liquid
samples, including highly viscous liquids.
Our first example is the online monitoring of the
conversion of fructose to 5-hydroxymethylfurfural (HMF, a
promising surrogate for petroleum-based chemicals, see the
Supporting Information) at 808C in an ionic liquid, 1-ethyl-3-
methylimidazolium chloride (EMIMCl); chromium chloride
(CrCl2) dissolved in EMIMCl forms the catalyst for this
reaction (see the Supporting Information for reaction con-
ditions).[24,25] At the beginning of the reaction, the mass
spectrum was dominated by peaks at m/z 83 and 129, which
correspond to 1-methylimidazolium (MIM; [C4H7N2]+) and
[*] Dr. H. Chen, J. Ding, S. Yang
Department of Applied Chemistry
East China Institute of Technology
Fuzhou 344000 (China)
Fax: (+86)794-8258-320
E-mail: chw8868@gmail.com
W. S. Law, L. Zhu, G. Gamez, K. Chingin, Prof. Dr. R. Zenobi
Department of Chemistry and Applied Biosciences, ETH Zurich
8093 Zurich (Switzerland)
Fax: (+41)44-632-1292
E-mail: zenobi@org.chem.ethz.ch
J. Ding, Prof. Y. Ren
College of Chemistry, Jilin University
Changchun 130023 (China)
[**] W.S.L. is grateful for financial support from an ETH Fellowship and
from the Eidgenꢀssische Stipendienkommission fꢁr auslꢂndische
Studierende (ESKAS). Partial financial support from MOST (China,
grant no. 2009 DFA41880) is gratefully acknowledged.
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.200902360.
hydrated
1-ethyl-3-methylimidazolium
(EMIM;
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“solvents of the future”,[27] are increasingly used as a
media in research labs and chemical industry, owing to
their negligible vapor pressure, good thermal stability,
recyclability, and the availability of a wide varying of
binary and approximately 1018 ternary ionic liquids.[28]
However, fundamental aspects of chemical reactions in
ionic liquids are not well understood, owing to the lack of
suitable analytical tools. As demonstrated herein, the
EESI-MS is useful for real-time, online monitoring of
chemical processes occurring in viscous ionic liquids,
providing rich information at the molecular level.
Food quality monitoring is of paramount importance
to human health and to the global economy and is another
area where viscous liquids occur frequently. Hence,
experiments were conducted to perform online monitor-
ing of the quality of extra virgin olive oil (EVOO, viscosity
ca. 80 cP) and honey (ca. 8000 cP; see the Supporting
Information for details) to explore the scope of EESI-MS
for molecular profiling of viscous mixtures. Owing to the
intricate matrix of EVOO and its viscosity, solvent
extraction is usually necessary prior to MS analysis.
Consequently, mass spectral profiling of only the
extracted part of the sample is obtained.[29] As shown in
Figure 3, higher peak intensities and a higher peak density
Figure 2. Mass spectra of the fructose dehydration reaction recorded at
a) 0, b) 2.5, and c) 60 min. d) Intensities of protonated HMF (m/z 127),
1-methylimidayolium (m/z 83), 1-ethyl-3-methylimidazolium (m/z 111),
and hydrated 1-ethyl-3-methylimidazolium (m/z 129). Inset in (c) is the
MS/MS (CID) spectrum of HMF.
[C6H11N2·H2O]+), respectively (Figure 2a). The signals of
EMIM (m/z 111) and protonated HMF (m/z 127) were only
observed after 2.5 min (Figure 2b), and their intensities
increased over the duration of the reaction (Figure 2c).
Probably owing to the decrease of the water content in the
reaction mixture as the reaction proceeds, the signal intensity
of EMIM increases, resulting in dominant unhydrated EMIM
(m/z 111; Figure 2c) instead of hydrated EMIM (m/z 129).
This result agrees with previous reports[24,26] that the HMF
yield increases in systems that partition HMF from water.
After a reaction time of 60 min, the intensity of the HMF
signal increased further, while the intensities of the MIM and
hydrated EMIM signals leveled off. The MS/MS spectrum of
HMF is shown in the inset in Figure 2c. A reaction
intermediate with a peak at m/z 149 was also detected and
tentatively interpreted as a lactone/furan-based compound on
the basis of the MS/MS spectrum (data not shown). For
further information on peak assignments, see the Supporting
Information. In the plots of the signal responses versus time
(Figure 2d), the simultaneous reduction in the signals of MIM
and hydrated EMIM with the increase in intensity of the
HMF and EMIM signals as the reaction progressed clearly
show that the reaction kinetics can be monitored in real time.
These preliminary results suggest that the intermediates
formed between CrCl2 and EMIM play key roles in fructose
dehydration and produce a high yield of HMF without
promoting side reactions that form undesired by-products.
More mechanistic details are given in the Supporting
Information. Ionic liquids (viscosity ca. 100 cP), known as
Figure 3. Mass spectra fingerprints of a) extra virgin olive oil b) extra
virgin olive oil extract. c) Score plot of principle component analysis of
the mass spectra obtained from four edible oils. EVOO: extra virgin
olive oil, SSO: sesame oil, RSO: rapeseed oil, and SFO: sunflower oil.
The space described by principal components (PC) 1, 2, and 3 is
shown.
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are observed in the mass spectrum of EVOO compared to an
EVOO extract (a MeOH/water mixture was used for
extraction, see the Supporting Information). Owing to the
intrinsic selectivity of the extraction method, compounds with
m/z 57, 99, 121, 137, and 181 were not detected in the olive oil
extract. Moreover, signals arising from volatile compounds at
m/z 81 and 99 were significantly reduced in intensity in the
mass spectrum of the EVOO extract. The latter compound is
identified as (E)-2-hexenal (Supporting Information, Fig-
ure S5), which contributes to the characteristic fruity/sweet
taste of EVOO.[30] The experimental data clearly confirms
that important molecular information is lost when extraction
of EVOO samples is performed. More interestingly, the major
peaks at m/z 340, 303, 295, 280, and 266 observed in the EESI
mass spectrum of the EVOO extract were also detected in the
pristine EVOO, with similar intensities and relative signal
ratios. This result illustrates that the sensitivity of EESI-MS is
not compromised when samples with intricate matrices are
analyzed; in fact, EESI-MS provides more comprehensive
information on molecular composition than is obtained from
analysis of an olive oil extract.
[M+Na]+ (m/z 129), and potassium [M+K]+ (m/z 145) ions
were observed (Supporting Information, Figure S6) when
ammonium acetate in MeOH/H2O (1:1) solution was used as
the primary spray. In the collision-induced dissociation (CID)
spectrum, the ionic ammonium adduct of DEG (m/z 124)
generated a distinct fragment at m/z 107 (i.e., protonated
DEG), which was used for quantification purposes (Figure 4).
These results show that reactive EESI-MS enables rapid and
specific detection and quantification of analytes in highly
viscous samples.
In conclusion, a simple yet powerful method based on
EESI-MS was developed for rapid characterization of com-
plex liquids with viscosities ranging from a few cP to
300000 cP, without the need for any sample pretreatment.
The results show that EESI-MS is potentially an attractive
tool to study the mechanisms of chemical reactions and to
monitor, characterize, and quantify extremely highly viscous
and complex liquid samples. The present experiments can be
modified to investigate other viscoelastic systems, such as
polymers, gels, and biomaterials.
Using the EESI mass spectral fingerprints, four EVOO
samples (one pure, three adulterated with 5% edible oils), Experimental Section
Method summary: EESI-MS fingerprints of the samples were
which are difficult to differentiate by smell, were successfully
separated with high confidence by principal component
analysis (PCA) score plots (Figure 3c and Supporting Infor-
mation, Figure S5). EVOO adulterated with sun flower oil
(SFO) and rapeseed oil (RSO) are grouped near to each
other, whereas EVOO with 5% sesame oil (SSO), which also
has a distinct smell, is located far from EVOO and SFO/RSO.
Ion–molecule reactions can also be implemented in an
EESI source for highly specific detection.[15] This method is
particularly useful in cases where analytes cannot be proton-
ated because of low proton affinity. In this case, the
quantitative detection of diethylene glycol (DEG) in tooth-
paste (viscosity ca. 300000 cP) is shown as an example of
specific detection by EESI. Abundant signals of DEG
cationized with ammonium [M+NH4]+ (m/z 124), sodium
obtained in positive-ion mode on a quadrupole time-of-flight mass
spectrometer (Q-TOF UltimaTM, Micromass/Waters, Manchester,
UK) with very minor modifications of the source. Typical EESI-MS
conditions were as follows: source temperature 258C, desolvation
temperature 508C, ESI and cone voltages set at + 3.8 kV and + 40 V,
respectively. An electrospray solvent mixture (MeOH/H2O/acetic
acid in a 2:2:1 ratio) was infused at 2 mLminÀ1. As for detection of
DEG in toothpaste, 10 mmolLÀ1 ammonium acetate dissolved in H2O/
MeOH (1:1) was electrosprayed at 5 mLminÀ1. Mass spectra were
acquired over the m/z 50–500 range. MS/MS using collision-induced
dissociation of selected ions was performed with 10–35 units of
collision energy.
The fructose dehydration reaction was conducted according to
reported literature with minor modifications[24] (see the Supporting
Information). Honey, oil, and toothpaste samples were obtained from
local grocery stores. PCA was performed using the EESI-MS data in
TXT. PCA score plots were generated using Matlab (MathWorks,
Inc., Natick, MA, United States).
Received: May 3, 2009
Revised: July 17, 2009
Published online: September 25, 2009
Keywords: complex matrices · high-throughput analysis ·
.
ionic liquids · mass spectrometry · viscous liquids
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