But as we do not yet have such a technology, naturally the question arises as to what pathways would lead from today's chemistry to the anticipated molecular manufacturing. This problem of putting together a self-contained system from a cruder level of sophistication by hooking up a number of more primitive parts is often encountered in computer science, and is termed "boot-strapping".
As diamondoid materials put many constraints on their synthesis procedure because they are so highly cross-linked and have such a high bond-density, they probably will have to be synthesized with highly reactive carbon species such as radicals and carbenes, and in a local high vacuum, which are conditions rather far from ordinary laboratory chemistry.
So in order to facilitate the boot-strapping process, the first primitive assembler which is able to self-replicate, should be constructed using less dense materials, more comparable to the polymeric species which are traditionally dealt with by liquid-phase chemistry. It has been shown in chapt.16 of [Dre92] that once a primitive assembler which achieves positional control to atomic precision has been constructed, migration pathways can be found that lead to diamondoid machinery through a few generations of increasingly sophisticated assemblers.
A primitive polymer-based assembler is still a large molecular aggregate by most of today's standards, with linear dimensions on the order of 100nm, somewhat larger than a ribosome. A description of what such an assembler might look like can be found in chapt.16 of [Dre92]. This stretches synthetic organic chemistry towards very large structures, while still having to maintain atomic precision. Many techniques like convergent synthesis and convergent self-assembly will have to be applied in well thought out ways to be able to construct a properly functioning molecular aggregate this large. The following discusses a number of available options to meet this formidable yet intriguing and inspiring challenge.
Machinery composed of sub-units
- division into two sub-problems
- rasters and lattices
- functional group classification
- positional control
- link chemistry
- storage of MBBs
- MBB skeletons
- almost no skeleton
- the zeolite-effect
- the current status of research (end of 1993)
- MBB conclusions
Between the Extremes in Design Space
By analyzing the new aspect of chemistry which is dealing with specific intermolecular aggregation, one will learn the design rules by which smaller building-blocks can be assembled into supramolecular entities to achieve a "chemistry beyond the molecule" [Lehn93]. Rewards of this development will be many novel materials with special optical, electrical, and perhaps magnetic properties, which will have uses in their own right. These novel materials most often have fairly simple and regular lattice structures.
But the big payoff will come from using the insight gained from the intermolecular assembly strategies to build parts of molecular machinery, which are entities of distinct sizes and shapes, not just infinitely extended crystals. The goal is to use these machine parts to build a first crude assembler which is able to self-replicate, and to thus boot-strap molecular manufacturing.
Small organic molecules serving as molecular building-blocks have the problem that they are too small to encode significant amounts of information to allow their preprogrammed self-assembly into aggregates with highly idiosyncratic structure. There is a lack of sound and reliable engineering guidelines for designing preprogrammed and autochthonous assembly reactions [Lin91], which is not surprising considering that small molecules provide so little encoded information available for manipulation. Therefore a positional synthesis device is needed which can assemble the materials under external program control.
A promising alternative for obtaining protein sized sub-units is the folding polymer approach, where some amount of the design complexity is mitigated through the use of rigid, non-standard amino-acid-like moieties. A large proportion of the remaining design task is off-loaded to automated design programs which are based on the packing of rotamers, similar in concept as described in [PonRic87]. It is indeed surprising that this existing rotamer approach has so far been used only for understanding natural proteins, instead of extending it for designing new ones. The full arsenal of available methods has not yet been unleashed on the problem of de novo protein engineering and the design of folding polymers. There is reason to believe that a more vigorous effort in this direction will be very successful.
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(Copyright 1993 by IMM. All rights reserved.)v. 1.4 of September 1996