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A publication of the Foresight Institute
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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 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.
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."
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.
From Foresight Update 25, originally published 15 July 1996.