PERSPECTIVES

ings of Korin et al. is that administration

of the aggregates cleared clots induced by
ferric chloride in mouse arteries. Administration of tPA at the same dose (50 ng),
aggregates without tPA, predissociated tPAcoated aggregates, or fused aggregates that
are coated with tPA did not have appreciable
effects. Notably, neither dispersed nanoparticles nor fused aggregates disrupted the
clots. The authors observe that the aggregates bind to the clots and begin dissolution,
leading to further increases in shear stress
and deployment of the nanoparticles to complete clot dissolution.
Korin et al. investigated the tPA-coated
aggregates in several clinically relevant
models of vessel blockages, including a
number of variations on pulmonary emboli
and dosing immediately after clot formation
and 30 min later. Large clots in the lungs are
lethal, and administration of the tPA-coated
aggregates improved survival.
tPA is clearly an effective therapy. The big
question is whether the aggregates reduce
complications. The aggregates are relatively
large (2 to 5 m) and are cleared within minutes of administration. Such large particles
are often considered risky for intravenous
administration because they can cause clots.
The ability of these aggregates to break
apart limits that risk substantially. Still, the
concerns with tPA must be considered, and

the authors note that they are using tPA on

the particles at 1/100th of the concentration
used in the clinic, and no adverse bleeding
events have been seen thus far.
The work by Korin et al. is certainly
exciting, but is still in the early stages. It is
challenging to make very tightly controlled
aggregates of nanoparticles at scale, and that
will be a critical part of moving this technology forward. Streptavidin-biotin chemistry
is very versatile, but as the authors note, it is
associated with immune responses that can
limit translation.
Approximately 800,000 people will
experience a stroke this year in the United
States (8), and worldwide, 5.5 million people will die from stroke-related causes (9).
Pulmonary embolisms and deep vein thrombosis are estimated to be on par with the
number of strokes (10), and heart attacks are
the leading cause of death worldwide (11).
Thus, there is a need for technologies that are
safe, simple and can be easily administered
to break up clots. The use of shear forces to
trigger these aggregates is relatively simple
and very effective, at least in these models,
and is a potentially extremely powerful technique for targeting blocked vessels.
More broadly, the study by Korin et al.
shows that we need to think outside the box
in targeting nanotechnologies in the body.
There has been much focus in the eld on

nding the right, high-afnity molecule or

molecules to target nanoparticles. Leveraging other phenomena such as differences in
shear stresses in the targeting regions may
lead to more successful enrichment of particles at the target site with fewer systemic
complications (12). The authors provide
compelling early data for developing new
treatments for clots, but their work also
marks a change in approach that broadens
the potential of nanomedicine.
References
1. J. Grotta, J. Marler, Surg. Neurol. 68 (suppl. 1), S12
(2007).
2. N. Korin et al., Science 337, 738 (2012); 10.1126/
science.1217815.
3. D. Collen, H. R. Lijnen, Arteriosclerosis 4, 579 (1984).
4. J. M. Wardlaw, V. Murray, E. Berge, G. J. Del Zoppo,
Cochrane Database Syst. Rev. 4, CD000213 (2009).
5. S. S. Wang, N. K. Chou, T. W. Chung, J. Biomed. Mater.
Res. A 91A, 753 (2009).
6. T. W. Chung, S. S. Wang, W. J. Tsai, Biomaterials 29, 228
(2008).
7. C. Balucani, A. V. Alexandrov, Curr. Cardiol. Rep. 12, 34
(2010).
8. V. L. Roger et al., Circulation 125, 188 (2012).
9. D. Mukherjee, C. G. Patil, World Neurosurg. 76 (suppl.),
S85 (2011).
10. M. D. Silverstein et al., Arch. Intern. Med. 158, 585
(1998).
11. A. Kibos, A. Guerchicoff, Acute Card. Care 13, 136
(2011).
12. M. N. Holme et al., Nat. Nanotechnol. 10.1038/
nnano.2012.84 (2012).
10.1126/science.1227097

CHEMISTRY

Low-Temperature Oxidation
of Methane

Catalysts prepared by modular assembly of

subunits into a functionalized support show
exceptional activity and stability for methane
oxidation.

Robert J. Farrauto

ince automobile emissions standards

were written into the U.S. Clean Air
Act of 1970, methane has been absent
from the list of pollutants covered by such
regulations (14) because it is unreactive
in photochemical smog-generating reactions. Today we understand that methane
is a potent greenhouse gas. Future transportation emission standards are therefore
expected to include methane. On page 713
of this issue, Cargnello et al. (5) report a new
approach in catalyst structure that may help
to address methane emissions in the automobile exhaust within the temperature range
Department of Earth and Environmental Engineering,
Columbia University, New York, NY 10027, USA. E-mail:
rf2182@columbia.edu

required for emission control. Low-temperature methane combustion is also important

for catalyst-assisted combustion in gas turbines fueled with natural gas.
The removal of methane from transport
emissions is a major challenge for automakers and catalyst suppliers. In the past four
decades, there has been little progress in
developing catalysts that can initiate methane oxidation at the required temperatures.
Palladium oxide (PdO) supported on various
materials has been shown to initiate oxidation
of methane at about 400C, but the expected
requirement will be <300C in the exhaust
of a lean-burn engine. Furthermore, exhaust
temperatures of 800 to 850C during fast
driving lead to decomposition of PdO to less
active Pd, as well as sintering. The latter is

irreversible even when Pd reverts to more

active PdO at lower temperatures.
Cargnello et al. now report a catalyst
that has low-temperature activity and stability under thermal conditions that simulate an automobile exhaust system. The PdO
is encapsulated in a cerium oxide (CeO2)
matrix, resulting in enhanced performance
relative to the traditional supported PdO catalysts. This raises the potential for a catalytic
solution for removing a powerful greenhouse gas from lean-burn engine exhausts.
This result alone will stimulate new thinking
in catalyst development and system design.
However, the exhaust contains harmful
combustion products, such as sulfur oxides
and oil-additive elements such as compounds of phosphorus, zinc, and calcium,

www.sciencemag.org SCIENCE VOL 337 10 AUGUST 2012

Published by AAAS

659

PERSPECTIVES
Engine exhaust:
Methane
Higher hydrocarbons
CO
Soot
NOx

Urea
Tailpipe emissions:
CO2
N2
H2O

Oxidation of methane, higher

hydrocarbons, and carbon monoxide
with a Pd catalyst

Catalyzed soot filter

Wall-flow filter removes soot

Requirements for the diesel oxidation catalyst. Catalyzed monoliths in the

exhaust of a future diesel engine are likely to comprise a diesel oxidation catalyst, a catalyzed wall ow lter, and a NOx reduction system. The diesel oxidation catalyst must oxidize methane, carbon monoxide, higher hydrocarbons, and

all of which poison most catalysts, especially PdO and CeO2. The presence of 5%
steam in lean-burn engines can also inhibit
catalytic reactions and cause excessive sintering of the catalytic components and their
carriers. Furthermore, catalysts must be prepared cost-effectively in high volumes as a
washcoat on a monolith (6). It remains to be
shown whether Cargnello et al.s catalyst can
survive under these conditions.
The severity of the duty cycle for a typical
exhaust catalyst, together with an expected
lifetime of ~400,000 miles for diesel trucks
in the United States, is challenging for any
catalyst. Clearly this can only be achieved
with enhanced catalysts, an advanced engine
control strategy, and improved fuel quality.
In the diesel engine, the oxidation catalyst
must achieve simultaneous complete oxidation of not just methane but also carbon
monoxide (CO), higher hydrocarbons, and
nitric oxide (NO) to nitrogen dioxide (NO2).
In practice, the diesel oxidation catalyst will
likely be placed in a position near the engine
(see the gure) to elevate the inlet temperature to that required for methane oxidation.
As difcult as these criteria may sound,
the combination of improved catalysts,
engine control strategies, and improved fuel
quality has been successful for the gasoline three-way catalytic converter, which
has been in use in cars since 1981 to reduce
NOx emissions and to oxidize CO to CO2
and higher hydrocarbons to CO2 and H20
(4). The current U.S. standards require this
catalyst to meet stringent emission regulations for 150,000 miles of consumer driving;
matching this requirement is a major technological accomplishment.

660

Selective catalytic reduction

Converting nitrogen oxides with aid of urea
(which hydrolyzes to ammonia) into nitrogen
and water

nitric oxide. Cargnello et al. report a PdO catalyst that shows high activity and
stability, under thermal conditions that simulate an automobile exhaust system
but whether it can be successfully integrated into a catalyzed monolith while
avoiding sintering and poisoning remains unknown.

Natural gasred turbines for power generation would also benet from a catalyst
that can oxidize methane at low temperature. In the early 1970s, Engelhard Corporation (bought by BASF Corporation in 2006)
patented catalyst and process technology
with the promise of low CO, hydrocarbon,
and NO emissions without post-emission
treatment (7). This technology requires the
catalytic oxidation of a mixture of natural gas (mostly methane) and air below the
ammability limits. At a gas temperature
of ~650 to 700C, the mixture becomes
flammable, and complete homogeneous
combustion occurs at gas temperatures
approaching 1300C. The hot combustion
gas is then directed to a turbine for power
generation. The technology would make
mechanical burners obsolete and eliminate
the need for selective catalytic reduction of
NOx. However, no catalyst currently exists
that can convert methane at the required
temperature, and this technology has never
been commercialized.
A major requirement for the catalyst is
that it must light off methane at the air compressor discharge temperature of 340C at
13 atmospheres. The best candidate is PdO
on various carriers, but as discussed above,
it can become deactivated through conversion to Pd and sintering. The temperature
for decomposition of PdO to Pd (~800C at
atmospheric pressure) is much higher than
that at which it is reformed to PdO (550C)
(8, 9). This hysteresis creates a window
of little activity. Cargnello et al.s catalyst
shows very little hysteresis, meaning that
the catalyst reforms active PdO at higher
temperatures than previous catalysts. This

observation suggests that in their catalyst,

O2 is activated by the CeO2 during the cooldown; the dissociated O atoms then react to
form active PdO.
After 40 years of catalyst failures, there
is reason to be hopeful. The low-temperature methane catalyst reported by Cargnello
et al. is an important step toward two main
applications: abatement of methane from
internal combustion engines for emission
control, and catalytically assisted homogeneous combustion. However, demonstration
in real applications will require additional
catalytic and system breakthroughs in sintering and poison resistance required for
long-term performance. I hope others will
take up the challenge to begin addressing
these important issues.
References and Notes
1. U.S. Environmental Protection Agency, Summary of the
Clean Air Act, 42 U.S. Code 7401 et seq. (1970).
2. J. Hightower, Catalytic Converters for Motor VehiclesA
General Overview, paper presented at the 67th meeting of the American Institute of Chemical Engineers, 2
December 1974.
3. J. G. Calvert, J. B. Heywood, R. F. Sawyer, J. H. Seinfeld,
Science 261, 37 (1993).
4. R. M. Heck, R. J. Farrauto, S. Gulati, Catalytic Air Pollution Control: Commercial Technology (Wiley, Hoboken,
NJ, ed. 3, 2009).
5. M. Cargnello et al., Science 337, 713 (2012).
6. Monoliths are parallel channel structures made of
ceramic or metal upon the walls of which the catalyst is
deposited. They are the standard structures in most pollution abatement applications.
7. W. C. Pfefferle, Catalytically-supported thermal combustion, U.S. Patent 3,928,961.
8. R. J. Farrauto, T. Kennelly, E. Waterman, M. Hobson, Appl.
Catal. 81, 277 (1992).
9. R. J. Farrauto, T. Kennelly, E. Waterman, Process conditions for operation of the ignition catalyst for natural gas
combustion, U.S. Patent 4,893,465.

10 AUGUST 2012 VOL 337 SCIENCE www.sciencemag.org

Published by AAAS

10.1126/science.1226310

CREDIT: P. HUEY/SCIENCE

Diesel oxidation catalyst