4.1

Kinematic Self-Replicating Machines

Robert A. Freitas Jr., Ralph C. Merkle, Kinematic Self-Replicating Machines, Landes Bioscience, Georgetown, TX, 2004.

4.1 Molecular Self-Assembly and Autocatalysis

There is a wide range of different molecular systems that can self-assemble [1323, 1324], and space does not permit more than a brief review here. Perhaps the best-known self-assembling molecular systems include those which form ordered monomolecular structures by the coordination of molecules to surfaces [1325], called self-assembled monolayers (SAMs) [1326-1328], self-assembling thin films [1328-1330], Langmuir-Blodgett films [1328, 1331], self-assembling lipidic micelles and vesicles [1332-1335], or self-organizing nanostructures [1336, 1337]. In many of these systems, a single layer of molecules affixed to a surface allows both thickness and composition in the vertical axis to be adjusted to 0.1-nm by controlling the structure of the molecules comprising the monolayer, although control of in-plane dimensions to <20 nm remains difficult. Fluidic self-assembly of microscale parts [1345-1351], nanoscale parts [1357, 1972], and the dynamics of Brownian self-assembly [1358] have also been described, and the theory of designable self-assembling molecular machine structures [1546, 1565] and the computational modeling of self-assembly processes [1359] are beginning to be addressed.

A bench chemist would define autocatalysis (Section 4.1.6) very narrowly as the catalysis exhibited by a product of a reaction. Following a standard textbook definition, a catalyst accelerates a reaction while being neither consumed nor produced in the reaction. An autocatalyst, however, is a catalyst that is produced in a reaction. Upon production, an autocatalyst accelerates its own formation, initially leading to an exponential (more generally, nonlinear) increase in the number of autocatalytic molecules. A very simple example of an autocatalytic reaction is the hydrolysis of a carboxylic ester in “neutral” water: RCO₂R’ + H₂O → RCO₂H + R’OH. Ester hydrolysis is known to be catalyzed by acids. Since an acid (RCO₂H) is produced in the reaction, the product feeds back into its own synthesis. One may write: RCO₂R’ + RCO₂H + H₂O → 2 RCO₂H + R’OH to indicate that the process is autocatalytic.

Following Lehn’s “instructed mixture” paradigm [1360] – in which large molecules can store more “information” than small molecules, and in which chemical information is “stored” as constitution (the network of bonds between atoms), configuration (the 3-D arrangement of bonds at “stereogenic” atoms), and long-living conformation (the 3-D orientation of atoms at bonds allowing for internal rotations) – self-replication via autocatalysis means autocatalysis in a bond-making reaction creating chemical information. The usual mechanism to transfer chemical information is templating: The template “instructs” its components in such a way that a specific bond is formed between the components. Templating is based on self-assembly, viz. the “docking” of components by noncovalent interactions.

Examples of chemical systems capable of templating and catalyzing their own synthesis – self-replicating systems – have begun to appear in the chemical literature over the last two decades [1370-1374], starting with the first demonstration of a chemical self-replicating system by von Kiedrowski [1373]. Various template-dependent ligation systems have been devised to study the role of a template in binding and positioning complementary substrates for covalent bond formation [1377-1381]. These have included simple self-replicating systems of the form A + B → T, where A and B are substrates that bind to a complementary template, T, and become joined to form a product molecule that is identical to the template [1373-1376], so that the reaction product has the potential to direct additional reactions [1372]. The system is termed autocatalytic when the newly formed product is able to direct the assembly of additional product (template) molecules.

The self-replicating systems that have been studied through 2004 use template molecules composed of nucleic acids [1366, 1373, 1375], peptides [1384-1387], peptide nucleic acids [1388-1391] or nucleobase amino acids [1392], and small organic compounds [1620-1623]. The nucleic acid-based systems rely on simple Watson-Crick pairing interactions between a short oligonucleotide template and two complementary oligonucleotide substrates [1366, 1373, 1375]. As described by Paul and Joyce [1372], the substrates are bound at adjacent positions along the template and are joined through a reaction involving chemical groups at their opposed ends [1372]. Peptide-based self-replicating systems are similar, except that the components are oligopeptides that can form alpha-helices [1372]. The template is the hydrophobic face of an alpha-helix that interacts with the corresponding face of two peptide substrates [1384-1387]. Unlike nucleic acid systems, where the templating interactions involve all of the nucleotide subunits, peptide replication systems involve only a few amino acid residues in the helix-helix interactions [1372]. The remaining residues are responsible for maintaining the overall fold of the helix, demonstrating that the templating properties of a self-replicating system need not necessarily involve interactions with every residue in the polymer [1372]. Self-replicating systems based on organic compounds further generalize the notion of a template, as these systems are not based on a polymer but rather on a low molecular weight compound that presents a templating surface to bind the two substrates [1620-1622].

In the following discussion we briefly review self-assembling peptides, porphyrins and nucleotides (Section 4.1.1), self-assembling crystalline solids (Section 4.1.2), self-assembling dendrimers (Section 4.1.3), self-assembling rotaxanes and catenanes (Section 4.1.4), self-assembly of mechanical parts and conformational switches (Section 4.1.5), and finally autocatalysis and autocatalytic networks (Section 4.1.6).

Last updated on 1 August 2005