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Distillation: New Wrinkles
for an Age-Old Technology Gerald Parkinson C onsidering that distillation is
both an entrenched technology
and an integral tool in today’s
chemical process industries, it seems
somewhat surprising that ways to signiﬁcantly improve the operation are
still at large. The current offerings
from purveyors of distillation technology include innovations in extractive distillation (ED), reactive or catalytic distillation, dividing-wall (DW)
columns, and process enhancements,
such as the incorporation of membranes to improve separation efficiency. While some of these basic techniques have been around for decades,
commercial acceptance often takes
time, as many companies are unwilling to risk the installation of a technology until it has been well-proven
in the ﬁeld.
Take the case of DW columns,
which are used to separate threecomponent mixtures, thereby avoiding the expense of a second column.
BASF AG (Ludwigshafen,
Germany; www.basf.com), the
world leader in that ﬁeld, developed
its own captive technology, and installed its ﬁrst DW column in 1985
for the recovery of ﬁne chemicals.
As of ﬁve years ago, there were less
than 20 commercial columns in the
world, practically all which were
built and operated by BASF.
Today, there are nearly 60 DW
columns in operation, 42 of which
are owned by BASF, says Gerd
Kaibel, a research fellow with BASF.
The rest were built by other companies, some with technical support
from BASF, which has been offering
its technology for license in recent
years. Linde AG of Höllriegelskreuth,
Germany (www.linde.de), for example, has tapped BASF know-how to
build three columns, including the
world’s tallest. Standing 107 m tall,
the unit is used by Sasol Ltd.
(Secunda, South Africa; www.sasol.
com) to recover 1-hexene.
10 www.cepmagazine.org July 2005 CEP In the past three years,
BASF has extended DW
technology to four-compoA
nent separation (Figure 1).
Three such columns are in
operation for the recovery
of ﬁne-chemical intermediC
ates. The key to four-component separations, says
Kaibel, is that the chemicals
must have fairly close boilD
ing points in order to limit
the temperature differential
■ Figure 1. BASF’s Dividing-wall columns separation sequence 4between the reboiler and
component mixture (A, B, C, D). In the drawing on the left, the unit
outside the column at the top is a condenser and the one outside
UOP LLC (Des Plaines,
the bottom of the column is a reboiler.
IL; www.uop.com) has
commercialized a DW deDW columns are named after the
sign for its Pacol Enhancement
vertical wall that divides the middle
Process (PEP), a complex separation
section of the column. In a typical opthat is part of UOP’s Pacol process
eration, a three-component mixture is
for the dehydrogenation of longfed to the middle section, toward one
chain paraffins to long-chain oleﬁns
side of the dividing wall. Light and
(Figure 2). The oleﬁns are subseheavy components are recovered, requently alkylated with benzene to
spectively, from the top and bottom of
make linear alkyl benzene (LAB).
the column (as in conventional distilPEP falls between the Pacol and
lation), and the intermediate compoalkylation steps. Its function is to renent is removed through a side draw,
move heavy aromatic byproducts
located on the opposite side of the
from the Pacol effluent. Two streams
column from the feed port.
are created in the PEP, and these are
Given today’s high fuel costs, the
separated in the DW column, producenergy savings achieved with a DW
ing an oleﬁn/paraffin product along
column are 20–45%, says Kaibel. The
with benzene (which is used in the
investment savings are about 30%.
downstream alkylation step).
Another beneﬁt, he adds, is that “we
The ﬁrst commercial PEP plant
obtain higher yields and better prodhas been operated by an undisclosed
uct qualities in the distillation of therU.S. client for 3–4 yr, and three othmally sensitive products, because
er units are under construction in
thermal stress at the hot reboiler survarious parts of the world, according
faces is reduced when two columns
to Michael Schultz, a process reare integrated into one.”
search specialist with UOP.
From its origins in ﬁne-chemical
“Compared with the previous twoseparations, DW technology has
column fractionation system, the
spread to the processing of most orDW design saves about 14% in capiganic chemicals, and ranges from
tal costs and has demonstrated enersimple solvent recovery to separations
gy savings of 50%,” he says. UOP is
with high-purity demands, such as
also working on DW designs for a
electronic-grade chemicals, where imfew other processes, including one
purities are speciﬁed in the ppb range.
for separating high-octane gasoline
Most applications are ﬁnal distillablending components from reactants.
tions, says Kaibel.
A petrochemical technology
director. The units include
A process that comboth grassroots and rebines a DW design with
ED has historically been
(ED) has been commer(Light Paraffin,
limited to the separation of
cialized by Uhde GmbH
close-boiling or azeotropic(Bad Soden, Germany;
forming components withwww.uhde.de). In ED, a
in a narrow boiling range,
nonvolatile, polar solvent
says Gentry. GTC’s
is introduced near the top
(Benzene, Light Paraffin,
Column Sidedraw to
process, in contrast, uses a
of the distillation tower
proprietary solvent mixture
and selectively dissolves
to recover a wide-boiling
the more-polar compoExternal Benzene
range of aromatic products
nent. The solvent is subPentane
— across three carbon numsequently separated from
bers — from various feedthe product and recycled.
stocks (Figure 3). “This exUhde’s development imMiscellaneous Lines
tends the technology to a
proves upon the compabroader spectrum of the
market,” he says.
The conventional way
which employs n-formylto Storage
to extract aromatics from
morpholine (NFM) to ex(Aromatics)
catalytic reformate or pytract high-purity benzene,
rolysis gasoline is liquidtoluene and/or xylenes
■ Figure 2. In UOP’s PEP process, a dividing-wall column saves capital costs and energy
in a complex separation.
liquid extraction (LLE).
from various feedstocks.
GTC’s method uses about
In Uhde’s process, the
20% less energy than LLE
feed is introduced just
and has a 30–40% lower
above the dividing wall
capital cost, depending on
and solvent is injected
the feedstock, says Gentry.
near the top of the colRaffinate
In GTC’s process, BTX
umn. The lighter nonaroAromatics to
are extracted from the feed
matics exit overhead and
in the ED column, then the
the product-laden solvent Hydrocarbon
aromatics are stripped
ﬂows down the column,
from the solvent in a prodon the opposite side of
uct-recovery column. The
the wall from the feed.
solvent is recycled to the
En route, the product is
ED column and BTX are
stripped from the solvent
recovered by fractionation.
and recovered through
The ﬁrst major comthe side draw, while the
■ Figure 3. GTC Technology’s extractive distillation process uses a propriety cocktail of
mercial launched ﬁve years
solvent is recycled.
solvents to remove benzene, toluene and xylene from reﬁnery or petrochemical aromatics
ago at the Yosu, South
The ﬁrst commercial
streams. The nonaromatic hydrocarbons exit the top of the extractive distillation column
Korea, reﬁnery of LGplant to use the DW-ver- (EDC) (1), and the non-condensibles in the overhead stream are the raffinate product.
Caltex Oil Corp. (now GSsion Morphylane process Solvent from the bottom of the EDC is sent to the solvent-recovery column (2) where the
Caltex; Seoul; www.calwas mobilized last fall by aromatics are stripped and then recovered by downstream fractionation.
tex.com). With a capacity
Aral Aromatics AG
Uhde’s aromatics group.
of more than 1.2 million ton/yr, it is
(Bochum, Germany; www.aral.com) in
A newer ED process (without the di“the world’s largest extractive distillaGelsenkirchen, Germany. It is producviding wall) for aromatics recovery, detion plant for aromatics puriﬁcation,”
ing 30,000 metric ton/yr (m.t./yr) of
veloped by GTC Technology Corp.
high-purity toluene using various
(Houston, TX; www.gtchouston.com), is says Gentry. The plant produces BTX
from several types of feedstock. Both
coke-oven light oils as feed. “The savenjoying rapid growth in popularity.
the yield and purity of the products exings in capital costs were about 25%,
“We have licensed 13 units of the GTceed 99.9%. Gentry adds that GTC is
and the energy savings are about 20%
BTX (benzene, toluene and xylene)
compared with a two-column conﬁguprocess, most within the last 18 months,” working on new solvent mixtures for
other product applications.
ration,” says Thomas Diehl, head of
says Joseph Gentry, the company’s CEP July 2005 www.cepmagazine.org 11 Update Reactive distillation
The campaign to remove sulfur from
gasoline has been a boon to Catalyic
Distillation Technologies (CDTech;
Houston; www.cdtech.com), a leader in
the ﬁeld of catalytic or reactive distillation, in which chemical reactions and
distillation are done simultaneously in
the same column. “We have licensed 25
units and 19 plants are in operation, for a
total capacity of about one million bbl/d
of FCC gasoline,” says Kerry Rock, the
company’s director of technology.
In general, the advantage of reactive
distillation is that products are continually separated from the reaction mixture,
thus allowing the reactions to go faster.
However, this is not the case with the
desulfurization process, which is similar
to conventional hydrotreating in that it
uses hydrogen and a standard catalyst to
extract sulfur from FCC gasoline. The
main differences are that the reaction is
carried out in a distillation column and
the pressure is only 250 psig, versus
300–400 psig for traditional hydrotreating. “The hydrogen partial pressure is
lower because we use less than onetenth the amount of hydrogen circulation,” says Rock. He notes that the conventional process requires the
circulation of a large volume of H2 to
prevent oligomers from building up on
the catalyst and fouling it.
CDTech’s process avoids this problem by separating the lighter oleﬁnic
fraction from the heavy, high-sulfur
fraction in a distillation column.
Oligomers, which form from the oleﬁns
at reaction conditions, have a high boiling point and are removed from the bottom of the column. Light oleﬁns collect
in the top part of the column, where the
conditions are less severe and there is
less H2 saturation of the oleﬁns, thus
avoiding octane loss. As for sulfur removal, “in one unit we have reduced the
sulfur content from 1,800 ppm to 10
ppm,” says Rock.
“Capital and operating costs are at
least competitive with those of regular
hydrotreating,” says Rock, “but the
compelling beneﬁt of the process is
longer catalyst life.” CDTech’s ﬁrst
commercial unit has been operating for
ﬁve years, with no loss of catalyst activity. In contrast, Rock points out, the cata- 12 www.cepmagazine.org July 2005 CEP lyst in a ﬁxed-bed process loses all activity and has to be replaced after three
or four years. This interrupts the
FCC’s normal 5-yr cycle between major turnarounds.
Meanwhile, the ﬁrst commercial
plant to use a CDTech process for producing normal 2-butene from a mixed
C4 stream for propylene production was
started up earlier this year by Secco near
Shanghai. The product is subsequently
reacted with ethylene to make propylene. CDTech’s process uses a standard
catalyst to hydrogenate butadiene to
butene, then hydroisomerizes 1-butene
to heavier 2-butene in the same column.
The latter step is critical for the separation of 1-butene from isobutylene,
which has a similar boiling point.
Butene-2 is recovered from the bottom
of the column.
A reactive-distillation process for the
hydrolysis of methyl acetate, developed
by Sulzer Chemtech Ltd. (Winterthur,
Switzerland; www.sulzer.com) in cooperation with Wacker-Chemie GmbH
(Burghausen, Germany; www.wacker.
com), has been commercialized in two
plants. Wacker built a 7,000-m.t./yr
plant ﬁve years ago, while an undisclosed customer started up a 40,000m.t./yr retroﬁt facility two years ago.
“The retroﬁt has increased throughput
by about 25% for the same energy use,
with payback in a little over a year,”
says Claudia von Scala, Sulzer’s applications manager for reactive distillation.
Sulzer has also developed a reactive
distillation process for the continuous
esteriﬁcation of fatty acids in cooperation with an undisclosed Malaysian producer, which started up a 4,000-m.t./yr
plant in 2003. “The plant replaced a conventional semi-batch plant of similar capacity, but it uses only half the energy of
the old plant, and the product is of consistent high quality,” says von Scala.
A signiﬁcant portion of the investment cost was saved by installing a
membrane module to extract water
from the isopropanol-water mixture
that exits the top of the column.
Alternatively, says von Scala, two
more distillation columns would have
been needed to treat the distillate
stream and recover the alcohol.
Sulzer has installed 20–30 membrane systems to treat the overhead from distillation columns. Most of them have been
installed in the past two years, says
Mario Roza, Sulzer’s head of membrane
technology. The majority of these units
are removing water from isopropanol
(IPA) and ethanol, although the company makes a variety of composite polymer membranes to treat alcohols, esters,
ethers and other volatile compounds that
form azeotropes with water and/or
methanol. Separation is achieved by pervaporation (for liquid feed) or vapor permeation, in which a vacuum is applied
to the back of the membrane.
A typical application is debottlenecking a distillation tower, says Roza. “If
you have IPA and you are operating
close to the azeotrope a lot of energy is
required. But if you use pervaporation
and operate a few percent under the
azeotrope, you can save energy, while
increasing the feed rate,” Roza continues. “In IPA applications, we can increase the capacity up to 30%, and in
tetrahydrofuran operations, we can increase it even more.”
A semicontinuous, reactive distillation process has been devised in the
Dept. of Chemical and Biomolecular
Engineering at the Univ. of Pennsylvania (Philadelphia; www.upenn.edu).
“The process is designed for systems
that need production rates higher than
a batch system would support economically, but low enough that a continuous system would be too expensive,”
says researcher Thomas Adams.
The system consists of a continuously stirred-tank reactor (CSTR), a distillation column, and an accumulation tank
for the products. It operates in a cycle
that has two principal modes. In one
mode, reactants from the CSTR are fed
to the column and the resultant product
is collected in the tank. In the next
mode, the column is used to purify products from the accumulation tank. The
concept has been simulated on a computer and the researchers are seeking
support to test it. GERALD PARKINSON is a contributing
editor with over 25 years of experience writing about the chemical process industries. PROCESS TECHNOLOGY
Plasma Recycling Process Debuts
Alcoa’s Brazilian affiliate Alcoa Aluminio S.A (www.alcoa.com.br) has joined Tetra Pak (www.tetrapak.com.br),
Klabin (www.klabin.com.br) and TSL Engenharia Ambiental
(Sao Paulo, Brazil; www.tslambiental.com.br) to inaugurate a
carton-packaging recycling (CPR) facility in Piracicaba,
Brazil, that, for the ﬁrst time, enables the total separation of
aluminum and plastic components from each other and from
the cartons. The enabling technology is a plasma treatment
process developed by TSL Engenharia Ambiental. “It constitutes a signiﬁcant enhancement to the current CPR process,
which, up until now, separated the paper, but kept plastic and
aluminum together,” says Franklin Feder, president of Alcoa
During operation, electrical energy is used to produce a
jet of plasma at 15,000°C, which heats the plastic and aluminum mixture. Plastic is transformed into paraffin and the
aluminum is recovered in the form of high-purity ingot.
Alcoa, which supplies thin-gauge aluminum foil to Tetra
Pak for aseptic packaging, uses the recycled aluminum to manufacture new foils. The paraffin is sold to the Brazilian
Paper that is extracted during the ﬁrst phase of the recycling process is transformed into cardboard by Klabin. TSL
Engenharia Ambiental is responsible for operating this new
facility, which has the capacity to process 8,000 ton/yr of
plastic and aluminum, corresponding to a recycle capacity of
32,000 ton/yr of aseptic packaging. Feder says that the emission of pollutants during material recovery is minimal and
handled in the absence of oxygen without combustion, yielding an energy efficiency rate close to 90%.
Simplify Pharmaceutical Cleaning Validation
High-performance liquid chromatography (HPLC) or total
organic carbon (TOC) are the traditional techniques used for
cleaning validation in pharmaceutical manufacturing.
However, both methodologies have substantial drawbacks.
HPLC requires long setup and analysis times — often requiring one to two days of downtime before processing equipment can be certiﬁed for cleanliness. And while TOC offers
faster processing times, clocking in at a quick three minutes
per sample, the results they give back are non-speciﬁc, only www.cepmagazine.org or Circle No.119
CEP July 2005 www.cepmagazine.org 13 Update indicating that a sample contains organic compounds. This could lead to a
false positive and unnecessary cleaning.
Offering, speed, sensitivity and
speciﬁcity is Smiths Detection’s
(Danbury, CT; www.smithsdetection.
com) IONSCAN-LS, which uses ion
mobility spectrometry (IMS) technology to quickly and simply detect low
levels of organic compounds. “It is an
accepted technology that is used in laptop swabs for explosives at airport security checkpoints, thus demonstrating
its high-speed, accurate capabilities under some of the most challenging environmental operating conditions,” says
John Carroll, applications chemist at
Smiths Detection. Compared to the traditional HPLC equipment, the IONSCAN-LS dramatically drops setup
and analysis times, so that running a set
of samples that may take more than a
day using HPLC can be completed in
just a few hours. It also overcomes the
shortcomings of TOC testing by identifying the exact organic compound in
ppm to ppb levels. “IMS technology is
also economical. It costs just pennies
per sample to analyze,” says Carroll.
Smiths Detection, working in conjunction with the Dober Group
(Midlothian, IL; www.dober-group.
com), have developed IMS methods In this fuel cell system, the fuel and oxidant are
brought together as liquid streams in a microchannel, where they merge and ﬂow laminarly
between the catalyst-covered electrodes without
mixing. The protons and electrons diffuse through
the liquid-liquid interface. for Dober’s Chematic pharmaceutical
detergents. “Cleaning veriﬁcation
methods are generally based on the detergent component that is the most difﬁcult to rinse or the ‘last to leave’,”
notes Rebecca Brewer, director at the
Dober Group. In this particular instance, surfactants, which make up
about 0.5–10% of the detergent formulation, are the “last to leave.” The surfactants are often mixtures of
oligomers of different chain lengths.
With IMS, they can be quantiﬁed and
speciﬁed to very low levels, since they
yield peaks in an IMS plasmagram. Scalable Dendrimer-Based Platform Debuts
endrimers are sphere-shaped nanostructures that can be
engineered to carry molecules (which add functionality or
reactivity) by either encapsulating the compound in an interior
cavity or by attaching it to a surface. The size and shape of the
dendrimer is determined by the spherical shells, called generations, that possess these reactivities and are grown around the
unit’s core. To date, manufacturing methods have required dendrimers to reach a certain generation before other functions can
be added to them. Dendritic NanoTechnologies, Inc. (DNT;
Mount Pleasant, MI; www.dnanotech.com) has commercialized
a family of dendrimer nanostructures that, for the first time, can
be scaled in terms of function/reactivity. Designated Priostar
Generation 3, they significantly improve upon the original PAMAM dendrimers that were invented 25 years ago by DNT
president and chief technology officer Donald Tomalia while he
was at The Dow Chemical Co. (Midland, MI; www.dow.com).
Further, they can be manufactured in high volumes at costs
that are 2–3 orders of magnitude lower than their PAMAM
Generation 3 counterparts.
The PAMAM Generation 3 dendrimers are created in 8
steps and take 1 month of processing time. “In contrast,
Priostar Generation 3 dendrimers require 3 steps and a few
days, thanks to the use of faster, kinetically driven chemistry,
combined with the use of polyfunctional branch-cell reagents
to rapidly and precisely build dendrimer structures in a con- D 14 www.cepmagazine.org July 2005 CEP Fuel Cell Takes a Microfluidic Route
to Reducing Operating Costs
Researchers at the Univ. of Illinois
www.uiuc.edu), working with INI
Power Systems, Inc. (Cary, NC;
designed a microﬂuidic fuel cell that
operates without a solid membrane to
separate the fuel from the oxidant
(Figure, left). “Eliminating the membrane will not only reduce fuel-cell
costs — typically the membrane accounts for 20–30% of the overall cost
— but makes it possible for the fuel
cell to operate with either alkaline or
acidic chemistry,” says Paul Kenis,
professor of chemical and biomolecular engineering and project leader.
The microﬂuidic cell consists of a
Y-shaped channel (1 mm high × 1
mm wide) in which two liquid
streams containing fuel (1 M
methanol or formic acid) and oxidant
(1 M KOH or H2SO4 saturated with
O2) are merged, without mixing, into
the 3-cm-long stem. Because of the
microscale dimensions involved, the
two ﬂuids ﬂow under laminar conditions, and thus remain separated. The
redox reactions occur at the opposing
walls of the stem, which are coated
with catalyst-doped electrodes. For trolled way, generation by generation,” says Tomalia. A unique
aspect of production is the amplification procedure. Priostar
dendrimers’ surface groups increase by a factor of 3 for each
succeeding generation (e.g., G1 = 12 surface groups, G2 = 36
surface groups, G3 = 108 surface groups). The PAMAM surface groups only increase by a factor of 2 for each succeeding
generation (e.g., G1 = 8 surface groups, G2 = 16 surface
groups, etc.). “This allows rapid building of surface functionality
and molecular weight, therefore obtaining container properties
in fewer generations than for PAMAM,” notes Tomalia. The
methodology also requires lower levels of dilution, thereby offering a higher-capacity method that is more easily scaled to
Another interesting characteristic of Priostar the introduction and control of six critical nanostructure design parameters
that may be used to engineer over 50,000 different major variations of sizes, compositions, surface functionalities and interior
nanocontainer spaces that are expected to offer novel properties for use in a wide variety of commercial applications, including drug delivery, sensors, catalysts, surfactants and medical
imaging. These dendrimers also are more thermally stable (approximately 350°C for Priostar versus 130°C for PAMAM).
Initially, Priostar dendrimers will not be made available to the research community. However, DNT plans to establish a limited
number of business partnerships for commercial research that
could lead to direct commercialization. acid (or alkaline) conditions, proton (or OH–) exchange
takes place via diffusion through the liquid-liquid interface.
Work continues at UIUC to improve the performance of
the cell, and to also increase the power by connecting multiple cells into a stack. Depending on the performance of each
cell, about 100–200 cells would be required to operate a laptop computer, says Kenis. Meanwhile, INI Power — a spinoff company formed by Larry Markoshi, the co-inventor of
the Laminar Flow Fuel Cell — has exclusively licensed the
technology from UIUC and is working to commercialize
products by the end of 2006.
Turning a Hydrate Problem into a Self-Serving Solution
Natural gas hydrates — crystal structures in which
methane molecules are trapped in a lattice containing more
than 85% water — often form in oil and gas pipelines under
conditions of medium-to-high pressure (> 500 psig) and low
temperature (< 20°F), causing blockages and holding up production. Conventional treatment methods, including the use
of methanol and glycol to shift the conditions at which hydrates are stable, and kinetic hydrate inhibitors have been
met with limited success. Now, scientists at Heriot-Watt
Univ.’s Centre for Gas Hydrate Research (CGHR;
Edinburgh, U.K.; www.hw.ac.uk) under the leadership of
Bahman Tohidi, director of the GHRC, are proposing a completely different approach. Instead of trying to prevent hydrate formation, they encourage their crystallization into specially designed hydrates that can be transported as a stable,
The patent-pending technology, borne out of a 3-yr,
$685,000 project funded by the U.K. Dept. of Trade and
Industry and four industry partners, comprises a family of
proprietary chemicals that are added to the hydrocarbon ﬂuid
during transport to control the size of the crystals as well as
their tendency to agglomerate. “This cold-ﬂow approach will
reduce the operating and capital cost of pipelines, decrease
the operating pressure, and eliminate the need for insulation
(to prevent hydrate formation),” says Tohidi.
Transporting gas as hydrates offers other advantages.
“For one, when these structures form, methane molecules
are held closer together than they are in their gaseous state,
which increases pipeline capacity,” Tohidi notes. The technique is also safer. “If a pipeline is attacked, hydrates burn
slowly, but do not explode. And, if pipes rupture, large
amounts of gas do not escape.” The additive has been
awarded funds for further testing and development. The molecule shown is an example of the new class of chimeric
peptidomimetic polymers designed by Northwestern Univ. researchers.
It consists of a short anchoring peptide that mimics an adhesive protein from
marine mussels coupled to a chain of N-substituted glycine (peptoid)
oligomer, which provides resistance to protein and cell fouling. (Figure, above) that are mimics of polypeptides (these
mimics are also known as peptoids) and demonstrate both
robust, water-resistant anchorage to biomaterial surfaces
and long-term resistance to fouling in a biological environment (J. Am. Chem. Soc., May 13, 2005). BIOTECHNOLOGY
Novel Biopolymer Coating Boosts Fouling Resistance
Many of the biopolymers proven to be effective at preventing bacteria, cells and proteins in the body from accumulating on the medical devices coated with them do not
last long in-vivo, falling prey to chemical degradation to
the body’s enzymes. Northwestern Univ. (Evanston, IL;
www.northwestern.edu) researchers have developed a
new class of synthetic antifouling macromolecules www.cepmagazine.org or Circle No.120 CEP July 2005 www.cepmagazine.org 15 Update The general design of these
chimeric peptidomimetic polymers is
that of a short functional peptide for adsorption, coupled to a variable-length
N-substituted glycine (peptoid)
oligomer, which prevents biofouling.
When tested on titanium dioxide substrates in environments with fresh
serum and cells, the coatings warded
off deposits for up to ﬁve months,
which, according to Phillip
Messersmith, professor of biomedical
engineering and lead investigator in the
study, is the longest successful in-vitro
Messersmith expects in vivo testing of the new polymer to begin in
about a year. The coatings are believed to hold promise for use on a
variety of medical implants, including
cardiac stents and biosensors, as well
as on water-processing equipment, to
Edible Laser-Marking Wins Patent
Sherwood Technology (Widnes,
Chesire, U.K.; www.sherwoodtech.
com) has been granted a European
patent for a method of laser marking
edible products using its DataLase
Edible color-change technology. This
novel technique, for which Sherwood
was also recently awarded a U.S.
patent, features the deposition of
DataLase — a non-toxic, white inorganic pigment that can be applied by
most common coating and printing
processes or as a masterbatch in the
case of plastic molding — onto pharmaceutical and food products, such as
tablets and fruits. The coating undergoes a safe color-change from white
to black when exposed to the infrared
energy from a low-power CO2 laser,
thereby creating a highly visible, stable image.
Previous methods of marking these
substrates required a mechanical embossing or surface-printing technique,
both of which resulted in a signiﬁcant
number of rejects due to damaged
product, according to Andrew
Jackson, the company’s marketing
manager. Sherwood’s innovation is
now available through licensing
agreements and strategic partnerships.
16 www.cepmagazine.org July 2005 CEP A sample of “smart plastic” (a) is elongated and irradiated with ultraviolet light, forming a temporary shape
(b). Photos (c) and (d) show the plastic recovering its original shape after exposure to UV light of a different
wavelength. Scale is in centimeters. Photo courtesy of GKSS. R&D UPDATE
Intelligent Plastics Change Shape
A new family of polymers that
change their shape when illuminated
with ultraviolet (UV) light and return
to their original shapes when exposed
to light of speciﬁc different wavelengths has been developed by researchers at the GKSS Research
Center (Teltow, Germany;
Institute of Technology (MIT;
Cambridge; www.mit.edu) and the
Institute for Technology and
Development of Medical Devices
(Aachen, Germany), among others
(Nature 2005, 434 (7,035), p. 879).
The innovation may offer advantages
over temperature-responsive, shapememory polymers used in industrial
and medical applications (e.g., sutures
that self-tie into a knot).
The shape-changing capability is
imparted by photosensitive molecules that are grafted onto a copolymer backbone. When the photosensitive ﬁlm is exposed to an external
stress (e.g., stretching) and illuminated with a speciﬁc wavelength of ultraviolet light, the molecules
crosslink. After the light is switched
off, the polymer maintains an elongated structure long after the stress
has been released, even when the
material is heated to 50°C.
Exposure of the polymer to light
of another wavelength cleaves the
new bonds, allowing the material to
spring back to its original shape. “A
corkscrew spiral can be created by
exposing only one side of the stretched sample to light,” notes
Andress Lendlein, director of GKSS.
Uses for the polymers’ photosensitivity are being explored in minimally invasive surgery.
Environmentally Safer Catalyst
Increases Hydrogen Deposition
Engineers at Ohio State Univ.
(OSU; Columbus; www.osu.edu) have
developed a chemical catalyst for water-gas shift reactions that increases
hydrogen production by 25% at the
same temperature and using the same
amount of catalyst as required with
iron-chromium alternatives, when tested on a feed mixture similar to that
produced from coal gasiﬁcation.
Chromium helps to maintain the
pore structure of iron oxide and protect it from sintering during the reaction, speculates Umit Ozkan, professor of chemical and biomolecular
engineering at OSU and project
leader. This led the team to seek out
the components that would have high
thermal and chemical stability, such
as aluminum, silicon, and titanium, to
The speciﬁc way we prepare the
catalyst is key to its superior performance and cost efficacy,” notes
Ozkan. “Both of the promoters are incorporated into the iron matrix using a
modiﬁed sol-gel (MSG) technique,
which can be thought of as a controlled inorganic polymerization.”
Traditional sol-gel techniques are
based on alcoxides and rely on coprecipitation to prepare Fe-Cr catalysts. Ozcan’s group uses an
organometallic iron precursor, but the
other metals are added in the form of inorganic salts. The precursors used in MSG are also less
expensive than the ingredients used in co-precipitation,
notes Ozcan. “For example, Al is less costly than Cr. In addition, the use of nitrate salts is much less expensive than
the use of alkoxides for all ingredients, which is typical of a
sol-gel preparation,” she explains. The team plans to conduct tests to determine whether the catalyst works in the
presence of sulfur.
Bridging the Superconductivity Gap
Superconductivity is a state of matter normally exhibited at temperatures below –450°F in which electrical current ﬂows without resistance through a material as a result
of the material’s electrons acting in pairs. A collaborative
team of scientists from the Univ. of California (UCLA;
Los Angeles; www.ucla.edu), Los Alamos National
Laboratory (Los Alamos, NM; www.lanl.gov) and
Chonnam National Univ. (Gwangju; South Korea;
www.chonnam.ac.kr/english_home) have discovered that
one material, a mixture of plutonium, cobalt and gallium
(PuCoGa5) derived its superconductivity from magnetic
correlations, and exhibits this property at temperatures warmer than –427°F. “Even though that temperature
seems low, PuCoGa5 possesses the highest superconducting transition temperature among actinide based compounds found so far,” says researcher Nicholas Curro.
This new class of magnetically mediated superconductors might encompass materials ranging from metals to
oxides that would be the basis for the dissipation-less ﬂow
of electric current through power lines. Magnetic ﬂuctuations, rather than interactions mediated by tiny vibrations
in the underlying crystal structure, are believed to be responsible for the electron pairing that generates the material’s superconductivity.
Shimmying Molecule Sheds Light on
Cure for the Common Cold
A team of scientists at Purdue Univ. (West Lafayette, IN;
www.purdue.edu) has determined why a prototype antiviral
drug is showing so much promise as a means of neutralizing
rhinoviruses that cause the common cold. Although these
ﬁndings reveal a signiﬁcant characteristic that antiviral compounds must possess in order to be successful, lead investigator, Carol Post, professor of medicinal chemistry and bio- www.cepmagazine.org or Circle No.122
CEP July 2005 www.cepmagazine.org 17 Update logical sciences at Purdue quickly
points out that they are not likely to result in a cure for the common cold on
The antiviral compound is called
WIN (short for 2,6-dimethyl-1-(3-[3methyl-5-isoxazolyl]-propanyl)-4-[4methyl-2H-tetrazol-2-yl]-phenol). Its
key feature, which is deemed an important characteristic for any anti-viral
drug molecule, is a ﬂexible structure
that allows it to shimmy inside the
virus’ complex outer surface, thereby
altering the virus to the point where it
cannot complete the infection process.
The rhinovirus’ outer surface is
made up of proteins organized into
pentagons that form an icosahedral
capsid or protective shell. “Although
our antibodies are designed to destroy
viruses, the rhinovirus may mutate
from a previous cold virus so that our
antibodies can’t recognize the new
one,” she explains. The viral shell also
changes shape during the life cycle of a single rhinovirus particle. These shape
changes seem to depend on a small,
cigar-shaped cavity within the folds of
a protein called VP-1 that forms
around the capsid’s axis of pentameric
(5-fold) symmetry. Post observes that
ﬁlling this cavity appears to stop the
virus from changing shape. WIN is a
prime candidate for the task.
Once the rhinovirus particle penetrates the infected cell, the capsid
opens up, releasing RNA, which instruct the cell to reproduce the rhinovirus particles. “This change is possible because the capsid proteins,
including VP-1, are ﬂexible enough to
allow the release of genetic material,”
notes Post. “Restricting the VP-1 protein motions would prevent the capsid
from opening, thereby preventing the
virus from releasing genetic material,”
One reason why the WIN compound is so effective is that it can
shimmy through a narrow hole into the cigar shaped cavity where VP-1 resides. “It’s all part of the inhibition
mechanism,” explains Post. The wiggling part is important to get into the
cavity. When WIN occupies the cavity,
it has the long-distance effect of preventing the release of RNA by restricting motion at the 5-fold axis.” Unable
to come up with a scientiﬁc explanation, the team hypothesizes that “having a WIN compound in its cavity may
be the VP-1 protein’s equivalent of a
person who has a full stomach not
wanting to move around very much.”
Post and her colleagues are planning additional computer simulations
using the CHARMM molecular mechanics program running in parallel on
fast Linux clusters to identify the underlying cause of the long-distance effects. By understanding WIN’s locking
mechanism, researchers may be able to
design drugs that can lodge themselves
into the virus’ cavity without causing
adverse effects. cludes a cap-and-trade program that states can adopt to
achieve and maintain their Hg-emissions budgets. States may
U.S. Hunkers Down on Power Plants’ Hg Emissions join the trading program by adopting the federal model trading
n March 15, 2005, the U.S. became the first nation to regurule into the state regulations. The states and tribes are not oblate mercury (Hg) emissions from coal-fired power plants
ligated to adopt the EPA administered cap and trade program.
(CFPPs), as the Environmental Protection Agency (EPA;
However, their emission budgets are permanent, regardless of
Washington, DC; www.epa.gov) issued its Clean Air Mercury
growth in the electric sector.
Rule (CAMR) affecting utilities nationwide. The rule, which builds
In the cap-and-trade program, the government allots to each
upon the agency’s Clean Air Interstate Rule (CAIR), aspires to
state and tribe a specific number of Hg allowances. A Hg alreduce utilities’ Hg discharges from the current 48 ton/yr to 15
lowance is equivalent to 1 oz of Hg. Each state allots a number
ton/yr (~70%) by 2018 by establishing standards of performance
of Hg allowances to the affected facilities within the state. Each
that limit Hg emissions from new and existing facilities, and by
affected facility must hold an allowance for each ounce of hg
creating a market-based cap-and-trade program — modeled afthat the facility emits to the atmosphere. If the affected facility
ter EPA’s Acid Rain Program — that reduces Hg emissions in
desires to increase its power output, then it must purchase Hg
allowances from other facilities that have excess allowances,
The first phase caps Hg discharges at 38 ton/yr by 2010,
must install additional air-pollution-control equipment so as to
and will take advantage of co-benefit reductions — i.e., Hg remaintain the same Hg emissions despite the increase in power
ductions achieved by reducing sulfur dioxide (SO2) and nitrooutput, or must come to an agreement with other affected faciligen oxides (NOx) emissions under the CAIR. In the second
ties to decrease the emissions from those other facilities so that
phase, due in 2018, an additional cap will reduce emissions to
the overall Hg emissions do not increase.
15 ton/yr upon full implementation. New coal-fired power plants
EPA says the mandatory declining emissions caps in the
(those that started construction on or after Jan. 30, 2004) must
CAMR, coupled with significant penalties for noncompliance, will
meet stringent new-source performance standards, in addition
ensure that the rule requirements are achieved and sustained.
to complying with the caps.
As with the Acid Rain Program, the flexibility of allowance tradUnder the cap-and-trade system, each state and the two afing should create financial incentives for CFPPs to seek new
fected tribes are assigned an Hg-emissions budget for all of
and low-cost ways to reduce emissions, and improve pollutiontheir fossil fuel-fired electric utility steam generating units.
Other types of entities not listed could be affected. To deterThe final text of the Clean Air Mercury Rule may be found in
mine whether a facility, company, business, organization, etc.,
the Federal Register of May 18, 2005, on pp. 28,605-28,700.
is regulated by the final rule, the owner or operator should examine the applicability criteria in 40 CFR 60.45a of the final
New Source Performance Standards.
Regulatory Update is prepared by William A. Shirley, P.E., J.D.,
a chemical engineer and attorney in private practice in St. Louis, MO;
Each state must submit a state-plan revision detailing how it
Phone: (888) OSHA-LAW; E-mail: [email protected]
will meet this budget for its affected sources. The rule also in- REGULATORY UPDATE O 18 www.cepmagazine.org July 2005 CEP P ATENT UPDATE
The Future of Drug Development
he Hatch-Waxman Act was passed by Congress to encourage
pharmaceutical companies to develop new drugs, while allowing
generic drug manufacturers to bring cheaper versions of drugs to market once patents expire. The Act includes a “safe harbor” provision [35
USC 271(e)(1)] that permits drug makers to perform the experiments
necessary to obtain FDA approval without incurring liability for patent
infringement, even if their activities infringe another’s patent rights. But
the statute’s language is not clear as to which activities it shelters. It
simply states that it is not an act of infringement to use a patented invention “solely for uses reasonably related to the development and
submission of information under a federal law that regulates the manufacture, use, or sale of drugs.”
Until recently, the courts have broadly interpreted the language of
the safe harbor provision. But in Integra Lifesciences v. Merck, the
Federal Circuit took a much narrower view of the exemption. Merck
hired a consulting research group that was working with certain compounds, called RGD peptides, that interact with specific receptors on
cell surface proteins. The researchers were investigating the usefulness of the peptides as potential drug candidates. But Integra held a
patent covering the peptides. At first, Integra offered to license their
use to Merck, but when Merck rejected the proposal, Integra sued for
patent infringement. Merck argued that its activities were exempt from
infringement under the safe harbor provision.
In considering Merck’s argument, the Federal Circuit had to decide
whether the safe harbor reaches back down the chain of experimentation to embrace development and identification of new drugs that will, T in the future, be subject to FDA approval. The court reasoned that the
focus of the exemption is the provision of information to the FDA, not
the hunt for new drugs that may or may not undergo clinical testing for
FDA approval. The court concluded that general biomedical research
to identify new pharmaceutical compounds was not covered by the exemption, and ruled that Merck had infringed Integra’s patent. Merck
appealed its case to the U.S. Supreme Court.
On June 13, 2005 in a unanimous decision, the Supreme Court set
aside the Federal Circuit’s ruling. The Court reasoned that “the use of
patented compounds in pre-clinical studies is protected as long as
there is a reasonable basis for believing the experiments will produce
the types of information that are “relevant” to the FDA approval of a future drug. The decision means that many types of early-stage research would be covered by the safe harbor provision, and pharmaceutical companies are presumably free to use patented technologies
at no cost in drug development programs.
On one hand, since companies at least appear to have a lower
cost of development, the cost to the consumer for an approved drug
should also be lower. However, since the owners of the patented technologies, typically researchers and universities, are now faced with the
shrinking value of their intellectual property, the loss of value could
stunt innovation and lead pharmaceutical firms to perform the research
themselves. This cost would have to be passed on to the consumer as
higher prices for new drugs. The true effect that the Supreme Court
decision will have on drug prices will only be known with time.
This “Patent Update” was written by Frank C. Eymard, P.E., a chemical engineer and patent attorney with Albemarle Corp., Baton Rouge,
LA; Phone: (225) 388-7750; E-mail: [email protected] www.cepmagazine.org or Circle No.121
CEP July 2005 www.cepmagazine.org 19 ...
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This note was uploaded on 12/29/2011 for the course CHE 128 taught by Professor Scott,s during the Fall '08 term at UCSB.
- Fall '08