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Foresight Update 27 (page 3)

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Table of Contents - Foresight Update 27

Recent Progress: Steps Toward Nanotechnology

by Jeffrey Soreff

Advances in Proximal Probe Techniques

Proximal probes, primarily scanning tunneling microscopes (STMs) and atomic force microscopes (AFMs) are important tools in the development of nanotechnology. They permit an experimenter to probe or modify a precisely chosen location. The following three papers describe recent advances in these techniques.

Writing in [Science 272: 1158-1161 24May96], P.E. Sheehan and C.M. Lieber describe fabrication of a working mechanical lock with a 58 nm wide crystal of MoO3 as one of its moving parts. The authors grew several MoO3 crystals on a MoS2 substrate. They imaged, moved, and machined the crystals with an AFM tip. Each of the crystals has a preferred sliding direction along one of three crystallographically equivalent directions parallel to the surface of the hexagonal MoS2 substrate. The orientation of a particular MoO3 crystal determines which of the three directions is the preferred sliding direction for this particular crystal. The MoS2 substrate effectively locks the MoO3 crystals on to rails of sulfur surface atoms. The locking is so strong that attempts to push the crystals against their sliding directions cut them instead. The ability to cut the crystals was used to cut one into a latch for a second one. The atomic alignment with the substrate (which sets the sliding directions) was an integral part of the operation of this device. The authors write: "By sliding the latch into the notch of crystal 2 (Fig. 4e), we effectively locked the two nanocrystals, because crystal 2 could no longer move along its preferred sliding direction of the MoS2 substrate. Hence, we created a nanometer-scale mechanical lock. ... More generally, we believe that our results represent an important step toward the creation of nanometer-scale devices, because they demonstrate the ability to machine complex shapes and to reversibly assemble these pieces into interlocking structures."

L.A. Bumm et. al., writing in [Science 271: 1705-1707 22Mar96] describe evidence that single conjugated molecules (4,4'-di(phenylene-ethnylene)benzenethiolate) can act as single molecular wires. Electrical wires will be important in many types of subsystems in nanotechnology. There are instabilities that tend to destroy conductivity in one-dimensional systems, so it is important to have experimental bounds on how large these effects are. In this paper, a low concentration of the conjugated molecules was embedded in a self-assembled monolayer of n-dodecanethiol, a much less conductive material. The composite monolayer (on an Au{111} surface) was "probed by scanning tunneling microscopy (STM) and microwave frequency alternating current STM at high junction impedance (100 gigaohms)." The conjugated molecules could be seem extending about 0.7 nm above the rest of the monolayer. There are several lines of evidence that imply that the molecules are isolated. In looking at images of several of these molecules, they appear "with exactly the same shape, size, and orientation, which is indicative of features that are much sharper than the STM tip." Clusters of conjugated molecules only appear at Au step edges, where the monolayer is expected to be distorted. The isolated conjugated molecules are mostly found at monolayer structural boundaries, but only at a small fraction of these boundaries, "which indicates that their insertion into the film is an isolated and improbable event." Finally, the molecules are expected to be isolated because they are not associated in the solution phase. Now that this work shows that isolated conjugated molecules can successfully conduct current through a monolayer, possible extensions might include attempting localized electrochemical fabrication, or coupling an electrically sensitive protein to the wire and changing its conformation.

A longstanding problem in proximal probe work has been the difficulty in determining the detailed geometry of the probe tip, so that this may be accounted for in analyzing information from the probe or in constructing structures with the probe. K.F. Kelly et. al., writing in [J.Vac.Sci.Tech.B 14: 593-596], describe imaging fullerene covered STM tips. The authors' method uses in-situ reverse imaging of the tip (as proposed by Drexler for AFM). In this paper, the sharp objects used to create the image of the STM tip are defects in a graphite substrate produced by argon ion bombardment. While the defects are produced in a vacuum of 10-9 Torr, they were able to use them in air. "Even though these defects are larger than a few angstroms, their apices are narrow enough to enable them to resolve the features of the tip-adsorbed fullerene molecules." The authors propose mounting samples on the ion-bombarded graphite so that a tip can be used for scanning the samples and itself be evaluated by the defects on the portion of the graphite that is not covered by the sample during the same experiment. In the fullerene experiments, the role of the apical atoms on the tips was played by several fullerene molecules adsorbed on the tip. The authors found that "typically, when a single or predominant fullerene molecule is imaged on the tip, clear atomic resolution [by the tip] on graphite is observed. The presence of several fullerene molecules of equivalent height usually corresponds to little or no resolution of the underlying graphite lattice." The authors explain that their technique for imaging tips is preferable to several prior techniques. It is preferable to some prior STM technique work, which had resolution limited to tens of nanometers and had no way to identify the actual tunneling region. It is preferable to field ion microscopy because it is not limited to ultrahigh vacuum, and it allows imaging during tunneling conditions rather than field evaporation conditions.

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Towards Machine Phase Synthesis

The following two papers describe some experiments in solid-state chemistry which have some features in common with the machine-phase synthetic processes. They show the potential speed and specificity of reactions between rigidly held groups.

"...suggests the utility of mechanochemistry at tool tips."

J.J. Gilman, writing in [Science 274: 65 4Oct96], describes an analysis of mechanochemistry, albeit focussing on reactions in sheared crystals rather than at the tool tips of molecular machinery. Gilman emphasizes the importance of the lower symmetry of a sheared system, as opposed to a compressed one. In the case of sheared solids, he writes: "Thus, the minimum (indirect) gap is decreased by shear but is nearly unchanged by isotropic compression." One way to view mechanochemistry at a tool tip is as a very high spatial frequency, low symmetry, strain field. If we view tip chemistry in this way, the enhanced efficacy of shear over compression in producing reactions suggests the utility of mechanochemistry at tool tips. Ideally, one would like to use something like x-ray diffraction of sheared crystals of model compounds to confirm predicted intermediate states in tool tip chemistry. Gilman points out that the detonation of solid explosives is driven mechanochemically, not thermally. This provides an experimental proof of concept for high speed mechanochemical operations.

A different use of the rigidity of the solid state in chemical reactions is described in [C&EN p34 19Aug96]. This article describes a UV-induced carbene rearrangement of a diazo compound which produces 4 isomers when carried out in solution, but produces a single isomer in 96% yield when performed in the solid state. According to the article, "Garcia-Garibay [an assistant professor at UCLA] says that this [the high yield of one isomer] is made possible by the order, homogeneity, and rigidity of the crystal lattice housing the reaction." These conditions are analogous to those expected for machine phase synthetic processes.

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Protein Design and Synthesis

Our best way for generating functional, extended, atomically precise, nonperiodic, 3D structures is currently probably protein synthesis. Our ability to exploit this technique is by limited our ability to predict the folding of proteins into their stable conformations and by the set of amino acids that we have available for use in these proteins. The following four papers describe advances in our ability to synthesize, design, and exploit proteins.

"...broadens the accessibility of unnatural amino acid residues"

M.J. O'Donnell, C. Zhou, and W.L. Scott, writing in [JACS 118: 6070-6071 1996], describe a new method for adding unnatural amino acid residues to peptides. The basic idea is to add a glycine residue using standard peptide chemistry, activate the terminal amine on the glycine by converting the amine into a Schiff base with benzophenone, introduce the unnatural side chain by alkylating the alpha-carbon of the glycine residue, then hydrolyze off the benzophenone, leaving the unnatural amino acid residue bound to the growing peptide. The main advantage of this method is that it adds the special side chain in an alkylation step, which can use a wide variety of alkyl halides. Previous methods had required the separate synthesis of an amino acid before adding it to the peptide. The advantage of this technique to nanotechnologists is that it broadens the accessibility of unnatural amino acid residues, which can assist in building more rigid peptides with more predictable folding. The disadvantage of the technique as it currently stands is that the alkylation isn't stereospecific, so only 50% of each unnatural residue has a particular orientation. Fortunately, the authors "are currently exploring ... incorporation of alpha,alpha-disubstituted residues, and stereoselective UPS [unnatural peptide synthesis]."

M.D. Struthers, R.P. Cheng, and B. Imperiali, writing in [Science 271: 342-345 19Jan96], describe the design of a 23-residue peptide which folds into a stable tertiary structure. It does this without assistance from complexed metal ions or disulfide bridges. This work provides an example of a minimalist rigid peptide structure. In order to build functional structures with well defined geometries from flexible polymers such as peptides, much of the design freedom in selecting the polymer must be used to ensure that it folds into the desired structure. Sufficiently small peptides have so few intramolecular interactions that they can't fold stably at all. The invention of small, stably folding peptides provides structural motifs that can guide the design of functional structures. The smaller and stabler these motifs are, the better they will assist in economizing on how much of the design of a protein much be reserved to ensure its proper folding. The authors' peptide consists of a beta hairpin turn and an alpha helix. The design of the peptide went through five iterations, starting with a sequence extracted from a natural protein. Modifications were introduced to increase the stability of the turn, originally dependent on Zn2+ coordination, but eventually stabilized with a D-proline in the sequence. There is also a second unnatural amino acid, a 1,10-phenanthroline derivative, in the sequence. This is present as a reporter group rather than to drive structure formation in the final peptide. The authors confirmed the 3D structure of the final peptide with NMR.

Writing in [Science 274: 34-35 4Oct96], R.F. Service describes some recent work towards improving the understanding of beta sheet folding in proteins. Both alpha helices and beta sheets are important structural elements in proteins, but the formation of alpha helices is currently easier to predict. The article describes a model compound built by Norwick and coworkers that holds a "beta strand mimic--a rigid, rodlike chemical group that forms hydrogen bonds with its flexible peptide neighbor" together with two peptide strands. The whole assembly forces all three strands into a beta sheet when the proper amino acids are used in the peptide strands. The group is using combinatorial chemistry to build thousands of variations on this structure. Norwich says "this allows us to juxtapose different amino acids next to one another to see how it affects the structure and stability" of the beta sheet folding.

S. Ueyama et. al. at Mitsubishi have built a molecular diode from a modified cytochrome c552 protein [Inside R&D 25: 1-2 6Mar96]. They bound flavin to the cytochrome, and were able to demonstrate rectification with individual molecules imaged between an STM tip and a gold substrate. The current flow goes through both the flavin group and the heme group in the cytochrome. The amino acids in the cytochrome are important in preventing a direct connection between these two groups, thus blocking reverse current flow when the voltage is reversed. This development is helpful because the individual molecule used as a diode contains many amino acid residues, each of which permits a degree of design freedom in tuning the device for improved performance.

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DNA Technology

While proteins currently provide a way to combine 3D structure with inclusion of functional groups, DNA has also been used to construct complex 3D structures. The papers below describe two groups' work in organizing nanoscale particles with DNA.

Two groups have recently described controlled assembly of Au colloidal particles using DNA linkers. The two groups did their experiments in rather different size regimes. C.A. Mirkin et. al, writing in [Nature 382: 607-609 15Aug96], constructed their structures from 13-nm particles, while A.P. Alivisatos et. al., writing in [Nature 382: 609-611 15Aug96] used 1.4-nm clusters.

Mirkin's group attached two different, noncomplementary DNA octomers to two batches of Au colloid. The octomers were attached to the particles with thiol groups. The two sets of DNA-bound colloidal particles were mixed, then a linking DNA strand, complementary to one type of particle on one end and to the other type on the other end, was added. This linked the particles together into a mass which then precipitated. Mirkin's group showed that this linkage is a noncovalent, reversible one. They repeatedly cycled the material between an unlinked state and a linked one by cycling the temperature above and below the dissociation temperature (42C) of the DNA links. In contrast, "Naked Au colloids do not aggregate in this manner under comparable conditions, but rather undergo [irreversible] particle-growth reaction." The aggregation is controlled by the DNA pairing, which is highly specific. "In a control experiment designed to verify that this process was due to oligonucleotide hybridization, a duplex with four base-pair mismatches in each of the 'sticky' ends of the linkers (step 2 in Fig. 1) did not induce the reversible particle aggregation process."

Alivisatos's group, on the other hand, bound a single oligonucleotide strand to each of their clusters. Their structures look more like DNA decorated with Au clusters, where Mirkin's look more like Au clusters covered with DNA. Alivisatos's group built several structures from their DNA-Au cluster conjugates. They constructed several types of unlabelled DNA strands which were complementary to various combinations of Au-bound strands. They built two structures containing two Au clusters in each structure. One of these brought the two clusters together towards the center of the complementary strand, in a "head-to-head" configuration. The other placed one of the clusters towards the center of the complementary strand, while the other was towards the end of the strand. A third structure linked three DNA-linked Au clusters together.

Both groups examined their structures with electron microscopes. Mirkin's group saw particle spacing of around 6nm, while Alivisatos's saw spacings from 2-10 nm, depending on the structure and on the conformation of the structure. One of the comments in Mirkin's article is that "An advantage of the DNA/colloid hybrid materials reported herein is that the assemblies can be characterized easily by transmission electron microscopy (TEM) and/or atomic force microscopy (AFM) as well as spectroscopic methods conventionally used with DNA" in contrast to the more difficult task of proving that a purely DNA structure truly has the intended shape. Both groups expect to extend this technique to other types of colloidal particles. As in Seeman's DNA polyhedra, the specificity of DNA pairing should allow construction of complex geometries using this technique. The addition of colloidal particles can potentially add structural elements which are more rigid than any polymer strand to the set of building blocks for nanometer-scale structures. To take full advantage of this will require particles which are atomically precise and which have several chemically distinct anchoring points on each particle.

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The 1996 Nobel Prize in Chemistry was awarded to R.F. Curl, H.W. Kroto, and R.E. Smalley for their discovery of fullerenes in 1985 (see this issue's lead story and also nanotechnology news story). From the perspective of nanotechnology, fullerenes are potentially useful as stiff building blocks for larger structures. The discovery of fullerenes has led to a wide variety of work on their derivatives and on similar materials. One related material that has attracted attention is "nanotubes". Nanotubes are extended tubes of carbon with radii of roughly 0.7nm. Smalley's lab has recently discovered a method for efficiently producing single-wall nanotubes [C&EN 74: 5-6 29Jul96]. They have also "found a way to use a single nanotube as the tip of an atomic force microscope." If the atomic configuration at the tip is as well-controlled as it is in C60 itself, this would permit precise control of tips for both probing and fabricating molecular structures with the microscope. More generally, the nanotubes are stiff, and have small lateral dimensions, both desirable properties for components for nanoscale machinery.

Another recently discovered material related to the fullerenes is a bowl-shaped molecule, C36H12, discovered by L.T.Scott, M.S.Bratcher, and S. Hagen [C&EN 74: 8-9 16Sep96]. It consists of a 36 carbon fragment of the 60 carbon fullerene structure, with the dangling bonds terminated with hydrogen atoms. Unlike the fullerenes, which are prepared by vaporizing carbon under special conditions, these experimenters prepared their compound from a well-defined precursor (decacyclene, C36H18). All but three of the bonds present in the final compound are already present in the precursor. It seems reasonable that a variety of related structures (borazine-like ones, for instance, with BN pairs substituted for adjacent carbon atoms) might be synthesized via this route. This spectrum of rigid, carbon-rich, well-defined structures could be useful as building blocks for nanostructures.

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In [C&EN 74: 30-37 16Sep96] J.H. Krieger covers a large number of developments in chemical software. A good deal of the article covered WWW and user interface issues, but there were some descriptions of advances in underlying capabilities as well. Tripos introduced a technology called "ChemSpace", which allows searches for compounds with various characteristics which are synthetically accessible. According to the article: "because of the way ChemSpace designs a database, it won't be generating compounds with interesting structures but which are synthetically inaccessible. Because the reaction that builds any compound is known and the reagents are known, it is possible for a company to make the compound using that reaction and those reagents." Since one of the major criticisms of theoretical work in nanotechnology has been that we do not have the synthetic capability to enable experimental tests of the theoretical predictions in the near future, ChemSpace may be helpful in discovering accessible structures which permit some of these experimental tests.

Jeffrey Soreff is a researcher at IBM with an interest in nanotechnology.

Table of Contents - Foresight Update 27

From Foresight Update 27, originally published 30 December 96.
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