Eric Drexler Talks about Self Assembly at Metamodern and Chris Phoenix does the same at CRNano

February 01, 2010

Eric Drexler talks about the current state of self assembly and future possibilities in three recent articles.

1. Eric has been exploring some recent developments in chemical synthesis and self-assembly that suggest attractive possibilities for engineering robust self-assembling molecular systems. (see below) Boronate esters are involved in two ways.

… + 2 H₂O, reversibly

I’ve been exploring some recent developments in chemical synthesis and self-assembly that suggest attractive possibilities for engineering robust self-assembling molecular systems. Boronate esters are involved in two ways.

Two days ago, I sat down to write about this, but then I read further into the literature, and learned substantially more. Yesterday, another cycle of the same. There’s entirely too much relevant information and progress. Maybe tomorrow.

2. Self-assembling nanostructures: Building the building blocks (See below)

Eric Drexler often think in terms of four levels of molecular assembly:

* Specialized covalent chemistry to synthesize monomers
(~1 nm)
* Modular covalent chemistry to link monomers to make oligomers
(~10 nm length)
* Intramolecular self-assembly (folding) to make 3D objects
(< 10 nm diameter) * Intermolecular self-assembly to make functional systems (~10–1000 nm) Recent developments are blurring the first level into the second, however, because new modular chemistries can make complex structures that can serve a monomers at the next level of assembly. Perhaps the most outstanding example comes from Marty Burke’s lab, which has pioneered a new, combinatorial methodology for piecing together small molecules of enormous diversity.

Diverse components

This post is prompted by a set of interrelated advances in chemistry that hold great promise for advancing the art of atomically precise fabrication. In this post, I’ll describe an emerging class of modular synthesis methods for making a diverse set of small, complex molecular building blocks.

The road to complex self-assembled nanosystems starts with stable molecular building blocks, and the more choices, the better. Self-assembly and the folding of foldamers are similar processes: They work when parts fit together well, and in just one way. Having building blocks to choose from at the design stage will typically make possible a better fit, resulting in a denser, more stable structure.

Building blocks for building blocks for building blocks

I often think in terms of four levels of molecular assembly:

• Specialized covalent chemistry to synthesize monomers
  (~1 nm)
• Modular covalent chemistry to link monomers to make oligomers
  (~10 nm length)
• Intramolecular self-assembly (folding) to make 3D objects
  (< 10 nm diameter)
• Intermolecular self-assembly to make functional systems
  (~10–1000 nm)

Recent developments are blurring the first level into the second, however, because new modular chemistries can make complex structures that can serve a monomers at the next level of assembly. Perhaps the most outstanding example comes from Marty Burke’s lab, which has pioneered a new, combinatorial methodology for piecing together small molecules of enormous diversity. From the lab website:

To most effectively harness the potential impact of complex small molecules on both science and medicine, it is critical to maximize the simplicity, efficiency, and flexibility with which these types of compounds can be synthesized in the laboratory.

…the process of peptide synthesis is routinely automated. As a result, this highly enabling methodology is accessible to a broad range of scientists. In sharp contrast, the laboratory synthesis of small molecules remains a relatively complex and non-systematized process. We are currently developing a simple and highly modular strategy for making small molecules which is analogous to peptide synthesis…

Our long term goal is to create a general and automated process for the simple and flexible construction of a broad range of complex small molecules, thereby making this powerful discovery engine widely accessible, even to the non-chemist.

In outline, the Burke group’s method exploits iterative Suzuki-Miyaura coupling, a mild and increasingly general technique in which (in Burke’s approach) carbon-carbon bond formation plays the role of amide bond formation in making peptides. In peptide synthesis, suitably-protected amino acids are iteratively coupled, deprotecting the terminal amine at each step. In Burke’s method, suitably-protected boronic acids play the analogous role.

The key advance is the N-methyliminodiacetic acid (MIDA) protecting group, a trivalent ligand that rehybridizes the boron center from sp² to sp³, thereby filling and blocking access to the open p orbital that makes trivalent boron compounds so wonderfully, gently reactive. The resulting complex is stable to a wide range of aggressive conditions, including powerful oxidants and strong acids. It can be removed, however, by an aqueous base (e.g., sodium bicarbonate in water).

For more information, good places to start are the Burke lab’s research overview page, and the MIDA boronate technology spotlight page at Sigma-Aldrich, which also provides off-the-shelf MIDA-protected building blocks. Sigma-Aldrich offers a larger universe of boronic acids and boronic esters, as does CombiPhos Catalysts. It’s worth looking through one of these documents to get a gut sense of what’s now available. Impressive diversity, compared to the 20 standard amino acid side chains.

(For a general perspective on this direction of development, see “Controlled Iterative Cross-Coupling: On the Way to the Automation of Organic Synthesis”, Angew. Chem. Int. Ed. 2009.)

More than a protecting group

The MIDA boronate ester is an example of a broader class of structures that are important in their own right. The demands of organic synthesis have brought forth a vast range of commercially available boronate esters (see links above), and this investment gives a free ride to scientists aiming to exploit them as building blocks. As linkers for self-assembled structures, boronate esters are both extraordinary and underexploited.

Relying a little less on hydrogen bonds, and a little more on bonds that can hold a self-assembled solid together at 600°C — dull red heat — could increase the robustness of self-assembled products. A fast, reversible, aqueous, biocompatible boron chemistry opens a door.

More later.

[Updated, 5 Feb: The boron chemistry in question opens “a door”, not “the door”]

See also:

• Modular Molecular Composite Nanosystems
• A High-Performance Polymer for Nanosytems Engineering
• CAD for Nanoengineering: DNA, proteins, and search-intensive design

3. Self assembly and nanomachines: Complexity, motion, and computational control (See below)

Regarding readiness to build extended, self assembling structures, yes, I think that the existing fabrication abilities (that is, the range of molecular structures that can be synthesized) are now more than adequate. The bottleneck is design software, including the development of rules that adequately (not perfectly) predict whether a given design satisfies a range of constraints. These include synthesis, stability, solubility, and sufficiently strong net binding interactions.

A commenter on the previous post raised several important issues, and my reply grew into this post. The comment is here, and my reply follows:

@ Eniac — Thanks, you raise several important questions.

Regarding readiness to build extended, self assembling structures, yes, I think that the existing fabrication abilities (that is, the range of molecular structures that can be synthesized) are now more than adequate. The bottleneck is design software, including the development of rules that adequately (not perfectly) predict whether a given design satisfies a range of constraints. These include synthesis, stability, solubility, and sufficiently strong net binding interactions.

As for specifying face combinations that would result in unique binding, this becomes easier with increasing face size, and more difficult with the number of simultaneously exposed faces. Hierarchical assembly can address both of these, but the most practical schemes require the ability to convert reversible binding interactions into irreversible ones. One approach is to introduce covalent linkages after assembly of the intermediate blocks lower in the hierarchy of sizes. There are several ways to do this.

The problem of enabling motion between self-assembled components can be addressed at the level of interactions between assemblies that are held together by (for example) a combination of large-scale complementary shapes and non-contact colloidal binding interactions.

Flexible hinges in self-assembled structures are also practical, as shown by natural systems. Protein engineers have successfully designed structures that undergo conformational switching.

Downstream, there’s a continuum of assembly approaches that spans the range between free Brownian motion, constrained Brownian motion, and more macro-machine-like devices (discussed in “From Self-Assembly to Mechanosynthesis”, and Motors, Brownian Motors, and Brownian Mechanosynthesis).

You are right that the relative sizes of machines for manipulating matter and for manipulating information become similar (or reversed) at the nanoscale, relative to what we are familiar with in today’s macro-machine, micro-computer world. The resulting design constraints can be met by a various combinations of several techniques, including

• Offloading computation to conventional computers that direct what would typically be large numbers of nanosystems (a good early solution).
• The same single-computer / multiple machine approach with nanosystems for both operations.
• Extensive use of hard automation, in which repetitive operations require no computation at all.

Regarding the last point above, this is how high-throughput manufacturing works today. I’ve discussed this in posts with videos of machines in action: “High-Throughput Nanomanufacturing: Small Parts” and “High-Throughput Nanomanufacturing: Assembly,” with a more quantitative discussion of “molecular mills” on E-drexler.com).

Chris Phoenix – of the Center for Responsible Nanotechnology also has been talking self assembly as well.  Chris Phoenix noted that the Foundations of Nanoscience FNANO10: Self-Assembled Architectures and Devices has many interesting topics.

Viral Self-Assembly
Nanoplasmonics & Nanophotovoltaics
Self-Assembly Across Scales
Top-down Meets Bottom-up
Principles and Theory of Self-Assembly

4. Molecular Manufacturing vs. Self-Assembly (See below)

DNA self-assembles very nicely into quite large structures – as big as 100 nanometers, almost bacteria-sized – almost big enough to see with an ordinary microscope.

Molecular manufacturing uses nanoscale tools to guide the fabrication of more tools. Once you can computer-control those tools to make a programmable range of shapes, you can make more tools (both in quantity and variety) than you started with.

Self-assembly is already using templates, and templated self-assembly is pretty darn close to molecular manufacturing. Once the templates become programmable and are built using the same processes and building blocks that they guide… then that is molecular manufacturing.

With so many advances on self-assembly, it seems pretty clear that just a few years from now, we’ll have primitive molecular manufacturing. More steps will be needed, of course, to design a full nanofactory and get it working. But the conceptual and practical hurdles are falling fast.

Molecular Manufacturing vs. Self-Assembly

January 27, 2010

Source: Chris Phoenix &    http://crnano.typepad.com/crnblog/2010/01/molecular-manufacturing-vs-selfassembly.html

Why was I so excited about the FNANO10 conference on self-assembly, given that self-assembly is not molecular manufacturing?

Self-assembly is a way of making large structures out of small pieces, by designing the pieces so that random (“Brownian”) motion will jiggle them into place. DNA self-assembles very nicely into quite large structures – as big as 100 nanometers, almost bacteria-sized – almost big enough to see with an ordinary microscope.

A problem with self-assembly is that the pieces have to use their own structure or other properties to template their assembly. That limits and complicates the design. So templates, created by other means, are sometimes used to guide the self-assembly.

With a template, larger and more intricate structures can be built than by pure self-assembly. For example, self-assembled monolayers, using a flat surface as a template, can produce square centimeters of high-precision arrangements of molecules. Lithographed templates can arrange DNA structures in arbitrary orientations over large areas (this is cutting-edge stuff).

Molecular manufacturing uses nanoscale tools to guide the fabrication of more tools. Once you can computer-control those tools to make a programmable range of shapes, you can make more tools (both in quantity and variety) than you started with.

Self-assembly is already using templates, and templated self-assembly is pretty darn close to molecular manufacturing. Once the templates become programmable and are built using the same processes and building blocks that they guide… then that is molecular manufacturing.

With so many advances on self-assembly, it seems pretty clear that just a few years from now, we’ll have primitive molecular manufacturing. More steps will be needed, of course, to design a full nanofactory and get it working. But the conceptual and practical hurdles are falling fast.

This entry was posted on Sunday 14 February, 2010 at 1:26 pm and is filed under Industry, Machines, Manufacturing, Risk Assessments, Studies. You can follow any responses to this entry through the RSS 2.0 feed.