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Molecular components:
One area which is always important to the advancement of nanotechnology
is the invention or discovery of new molecular components with properties
useful in nanometer scale machinery. The following four papers describe
two types of stiff structural members, an actuator, and a constant force
spring.
Perhaps the most fundamental capability needed in nanotechnology is the
ability to hold objects in place in the presence of thermal motion. The
stiffest connectors that we know of which can restrain this motion are covalent
bonds. F. Diederich and C. Thilgen, writing in [Science 271:
317-323 19Jan96] describe some fullerene reactions which look like an attractive
way to build an extended covalent network. M. Krummenacker, in [Steps
Towards Molecular Manufacturing Chemical Design Automation News
9: 1,29-39 Jan94] described criteria for molecular building blocks,
including stiffness, the presence of at least six connecting links (preferably
with Diels-Alder link reactions), and the presence of sites for introducing
functional groups. C60 is a stiff molecule, with each carbon
atom covalently bonded to three neighbors. Diederich and Thilgen describe
a rich chemistry for C60, notably where it "participates
as the electron-deficient dienophile in a variety of thermal cycloaddition
reactions." Their work appears to show that C60 can satisfy
the other two conditions as well.
In particular, they display a variety of Diels-Alder reactions where C60
reacts at six double bonds, placed at the vertices of an octahedron. From
a lattice building point of view this is ideal. It leaves potential connecting
groups pointed in just the right positions to connect to another C60
and continue the lattice. In particular, compound 22 in the article, a hexa-adduct
of 2,3-dimethylbuta-1,3-diene, is formed directly in 26% yield and has almost
the right properties to form a lattice. The adduct has a single double bond
remaining at each adduct site. If it could be modified so that a pair of
hydrogen atoms could be removed from the terminal methyl groups it would
then be a new diene. This new diene would be properly oriented to react
with additional C60 molecules to form a simple cubic covalent
lattice. Alternate additions of the hexa-adduct and unmodified C60
with an AFM tip look like a plausible means to built up a complex covalent
structure.
These hexa-adducts of C60 look like they ought to be quite stable
to additional, undesirable addition reactions. The substituted C60's
unsaturated skeleton is reduced to a "cubic cyclophane" -- a structure
where the remaining double bonds are restricted to 8 benzene rings, which
would lose their aromatic stability on further addition.
The bridging substituted butadiene groups have 8 hydrogens which are not
involved in the reaction. If modified versions of these were synthesized
with functional groups substituted for these hydrogens, they could be reacted
with C60 before being placed in the lattice, thus incorporating
functional groups into the completed lattice.
The article also describes reactions which effectively add carbenes to double
bonds in C60, forming cyclopropane rings. The authors again display
symmetrical hexa-substituted C60 adducts. In this case, however,
it is not clear whether the reaction can be converted to a lattice forming
one.
The "molecular bottlebrush" achieves high stiffness to resist
thermal motion
The following paper describes a quite different mechanism for controlling
thermal motion. M. Wintermantel, M. Gerle, K. Fischer, M. Schmidt, I. Wataoka,
H. Urakawa, K. Kajiwara, and Y. Tsukhara, writing in [Macromolecules
29: 978-983 29Jan96], describe a new type of stiff polymer, which
relies on long side chains for its stiffness. They synthesized a derivative
of polymethacrylate where each monomer is bound to a long side chain of
polystyrene. They describe their new polymer as a "molecular bottlebrush".
The side chains of polystyrene (up to 500 units long, in their stiffest
sample) make it hard to bend the main chain of their polymer. A measure
of the stiffness of the main chain is the "Kuhn statistical segment
length", a measure of how far the polymer chain extends until thermal
vibrations bend it significantly. For this group's polymers, this length
ranges up to 200 nm. The authors give three possible explanations for the
high stiffness: "(i) simple steric overcrowding, (ii) specific phenyl
ring interaction, i.e. stacking, and (iii) a certain degree of tacticity
caused by the steric requirements during addition of a monomer to the highly
overcrowded radical at the chain end."
These stiff polymers are valuable to nanotechnology as possible compression
members in assemblers or similar structures. Increased stiffness decreases
the positional errors due to thermal noise. One disadvantage of the existing
polymers is that they are formed with a distribution of lengths. For atomically
precise applications, it would be desirable to choose backbone and side
chain composition to allow synthesis of a single species.
Writing in [Science 271: 1558-1560 15Mar96], T. Pascher,
J. P. Chesick, J. R. Winkler, and H. B. Gray describe a probe of protein
folding using photochemically driven electron transfer to investigate some
of the early dynamics of the process. They mixed an unfolded, oxidized form
of the protein cytochrome c with the Ruthenium complex Ru(2,2'-bipyridine)32+.
The Ruthenium complex "was used as a photosensitizer to inject electrons"
into the heme group in the cytochrome c. The authors were able to reduce
the cytochrome c in less than a microsecond, then observed the changes in
the protein's spectrum as it folded. The folding can only be watched for
about a millisecond by this technique, because the oxidized Ruthenium complex
then reoxidizes the cytochrome c back to its initial state.
This technique is useful in nanotechnology for several reasons. First, it
effectively gives us a new high speed actuator at the molecular level. In
addition, the millisecond reoxidation of the cytochrome c essentially resets
the actuator, so it can be used again without requiring addition of other
chemical species. The use of this technique as a probe of fast protein dynamics
may also be important in monitoring mechanical processes in early nanotechnology.
DNA's ability to act as a constant force spring has been demonstrated
Two groups have recently found that DNA can act as a constant force spring.
P. Cluzel, A. Lebrun, C. Heller, R. Lavery, J.-L. Viovy, D. Chatenay, and
F. Caron, writing in [Science 271: 792-794 9Feb96] and
S. B. Smith, Y. Cui, and C. Bustamante, writing in [Science
271: 795-799 9Feb96] have found that double stranded DNA can be stretched
at constant force (about 70 piconewtons) from slightly over its unstretched
length to about 170% of its unstretched length. Both groups attributed the
constant force behavior to a phase change, with the DNA transformed from
normal B-form DNA in its relaxed state to some other structure in its fully
stretched state. A number of possible causes for the transition appear possible,
but the evidence for constant force behavior appears quite clear. From a
machine building perspective, constant force springs are quite useful, allowing
us to gain as large a stroke as possible from an externally driven force
change (as in the acoustically driven Stewart platform design in Drexler's
Nanosystems). It is fortunate that an existing, well known
polymer has proven to have this property, since that takes yet another machine
component from theoretical studies to experimental demonstration.
Building blocks often need to be optimized for some desirable property.
Tension or compression members need to be optimized for stiffness or strength,
adhesive molecules need to be optimized for binding energy and so on. Writing
in [JACS 118: 1669-1676 21Feb96] J. Singh, M. A. Ator,
E. P. Jaeger, M. P. Allen, D. A. Whipple, J. E. Soloweij, S. Chowdhary,
and A. M. Treasurywala describe a novel application of genetic algorithms
to chemical optimization. Typically, genetic algorithms are used to optimize
a design by evaluating candidate designs entirely by computation and repeatedly
combining the successful designs to yield new candidates. In this work,
the evaluation was performed by actually synthesizing the candidate molecules
and performing an assay. The targets sought in this work were hexapeptides,
evaluated as substrates for stromelysin. The assay process synthesized the
peptides so that they were bound to a glass substrate, capped their free
end with a fluorescent tag, cleaved them with stromelysin, then measured
the amount of fluorescence in solution. The optimization process used 5
generations with a "population" of 60 peptides in each generation,
"breeding" them in proportion to their assay results. The best
peptide found by the fifth generation had an activity as stromelysin substrates
roughly triple that of the best peptide in the original generation.
This technique may be helpful in optimizing components in nanoscale machinery
where synthetic methods exist and where assay techniques are more reliable
than simulation. Unlike previous "evolution in a drum" techniques,
this technique is not limited to molecules that can replicate themselves,
and where the assay technique can physically separate the desirable species
from a mixture of similar compounds. On the other hand, this technique is
limited to much smaller populations of trial compounds than those techniques.
Nanotechnology is unusual in that the basic components of its structures,
atoms, are well enough understood and sufficiently uniform (except for small
isotopic effects) that it is reasonable to do extended calculations of the
properties of systems that we cannot yet construct. The following papers
describe recent calculations on nanometer scale systems, ranging from a
calculation on an existing protein complex, through a calculation on unstable
intermediates in cluster chemistry, to calculations on a hypothetical fullerene
tube.
Writing in [Science 271: 997-999 16Feb96], H. Grubmuller,
B. Heymann, and P. Tavan describe the analysis of the mechanical rupture
of a streptavidin-biotin complex by molecular dynamics simulations. Their
simulations agreed well with AFM experiments, both showing rupture forces
of about 250 pN. The simulations showed that the rupture process is quite
complex, with 25 different maxima in the applied force (roughly speaking,
boundaries between two different "structures") between the initial
state and free biotin. Due to computer time constraints, the velocity of
rupture had to be much higher in the simulations than in experiments, the
slowest being 1.5 nm/nsec. The rupture force increased with increasing velocity,
with a frictional term of 20 pN/(m/sec). The authors extrapolated the measurements
from runs at a number of velocities to yield the static rupture force.
In addition to the velocity variation, there was a residual scatter of computed
rupture forces of roughly 35 pN (rms). In AFM experiments the scatter is
comparable, roughly 50 pN. The authors note that the scatter in the AFM
results, while normally attributed to experimental error, may reflect actual
differences in the streptavidin conformations encountered during a series
of experimental trials. The authors note that "That scatter of computational
results is due to a heterogeneity of reaction pathways observed in our simulations
and is related to the known structural microheterogeneity of proteins commonly
described in terms of conformational substates." This is unfortunate
from a technological point of view, since it means that even proteins with
well-defined covalent structures may have considerable scatter in their
dynamical mechanical properties.
K.D. Ball, R.S. Berry, R.E. Kunz, F.-Y. Li, A. Proykova, and D.J. Wales,
writing in [Science 271: 963-966 16Feb96] have described
how dynamics of atomic clusters can be analyzed for tendencies to form glasses
even when the number of locally stable structures that can be formed by
the cluster is too high to explicitly find them all. What they did was to
find a small subset of the possible minima and analyze transitions between
them. The model systems that they worked with were Ar19 and (KCl)32.
The Ar cluster has a much stronger tendency to form a glass than the KCl
cluster did. Simulations of Ar cluster annealing left clusters trapped above
the global minimum when cooling was at 109 K/sec, while leaving
any KCl clusters trapped above the global minimum required cooling faster
than about 1013 K/sec. The energetics of the clusters only differed
by two orders of magnitude, leaving the other two to be explained by structural
factors. The authors show that in tracing local minima down to the global
minimum, the Ar cluster minima have only small differences in energies (except
for the step down to the global minimum), with comparatively large barriers,
giving the path to the minimum a sawtooth profile. In doing a similar trace
for the KCl cluster, they find fairly large differences in energies between
minima (favoring each step) with fairly small barriers, giving the path
a staircase profile.
In terms of atomic configurations, the sequence of minima in the KCl cluster
follows a path where a seed crystal forms and then grows by adding groups
of atoms. The authors suggest that "The funnel-like, staircase topography
of the (KCl)32 surface in Fig 1B is similar to the kind of landscape
that has been proposed recently for the potential surfaces of proteins."
If the analogy proves close, the authors' technique for evaluating the dynamics
from a sparsely sampled cluster may assist in evaluating protein designs,
ensuring that designs will have acceptably fast folding kinetics.
Writing in [Science 271: 1232 1Mar96], R. F. Service
describes how a number of groups have modeled a carbon nanotube that should
act like a metal-semiconductor junction. The two groups, in Berkeley and
Namur, Belgium, modeled tubes where half of the tube had the hexagonal mesh
of carbon atoms rolled up so that the atoms formed closed rings, while the
other half was rolled up so that the atoms formed spirals. In the section
with closed rings "quantum mechanical principles can restrict the energies
of the electrons, explains Cohen [of Berkeley], forcing them to occupy separate
energy levels, like electrons in a semiconductor." In the spiral half
of the tube the structure "can allow the electrons to exist at any
one of a continuous range of energy levels, as in a metal." The joint
between the two portions of the tube had to be carefully crafted. The two
structures couldn't simply be butted together, or else a gap would be left.
Both groups solved this problem by joining the two portions of the tubes
at an angle, with a five-carbon ring and a seven-carbon ring also present
at the joint. Bent tubes have been observed, but thus far they appear to
be multi-walled tubes rather than the single-walled tubes modeled by these
groups. "If nanotube heterojunctions can move from model to reality,
say Martin and others, maybe nanotube electronics could make the move as
well."
One route to atomically precise control of complex systems is the direct
manipulation of individual molecules on surfaces with STMs and other scanning
microscopy probes. The following two papers describe advances in these manipulation
techniques.
T. A. Jung, R. R. Schlittler, J. K. Gimzewski, H. Tang, and C. Joachim,
writing in [Science 271: 181-184 12Jan96] describe the
room temperature placement of molecules with an STM. The molecules, copper
porphyrins with four bulky substituents extending out of the porphyrin's
plane, were carefully designed to allow this positioning. The operation
at room temperature required sufficiently strong bonding to the substrate
(Cu(100)) that thermally activated diffusion would not move the molecules
during positioning or observation. The bonding could not be too strong,
however, or attempts to reposition the molecules on the surface would break
bonds within the molecules. "By evaluating a range of different molecular
systems, we have found that a specific copper porphyrin molecule meets the
criteria for positioning as outlined above. The molecule is Cu-tetra-(3,5
di-tertiary-butyl-phenyl)-porphyrin (Fig. 1A) with four di-tertiary-butyl-phenyl
(DTP) substituents (legs)." On the STM images in the article the four
legs of each molecule are clearly visible. The authors confirmed a match
of the observed STM images to predicted STM images from quantum mechanical
calculations.
The authors were able to displace molecules "in a predefined direction".
For instance, they were able to rearrange the molecules "to form a
hexagonal ring. Such rings do not naturally form upon annealing of the molecule
on the square lattice of Cu(100)." By moving the tip towards and away
from the molecules, the authors showed that the molecules were being pushed
by the tip. The deformations of the molecule during displacement were analyzed
by molecular mechanics methods. The legs were shown to bend individually,
giving "uncorrelated slip-stick action of the individual legs [which]
effectively lowers the barrier for lateral displacement as compared with
that of a rigid molecule -- a crucial aspect of the nanomechanics of movement
for this molecule."
Fairly complex molecules can be designed for positioning by STM
From a nanotechnologist's viewpoint, this work shows that proper design
of a fairly complex molecule, much more complex than the monatomic species
which had previously been manipulated by Eigler's group at IBM Almaden,
can enable its controlled movement with an STM. A desirable next step would
be to design two molecules which can react with each other and to form a
lateral bond between them under STM control.
In the USC [Chronicle v. 15 n. 7 9Oct95] E. Mankin describes
work by L. Dalton, G. Olah and others to build molecules specifically designed
to store information. The molecules that they are building will consist
of a metal or semiconductor core surrounded by a dendrimer insulating layer.
The dendrimer portion of the molecule "will also anchor the molecule
in a specific spot". Information will be read, written and erased "by
a specially configured STM." The funding is coming from DOD which "has
earmarked $6.65 million over the next five years for the interdisciplinary
project..."
Jeffrey Soreff is a researcher at IBM with an interest in nanotechnology.
