Autocatalysis and organocatalysis with synthetic structures

Abstract

The discovery of ribozymes led to the proposal of an RNA world, where a single type of molecule was supposedly capable of selfreplication and chemical catalysis. We show here that both autocatalysis and organocatalysis can be engineered into a synthetic structure. The compound is shown to selectively accelerate its own formation and catalyze either hydrogenation or nucleophilic addition to α,β-unsaturated aldehydes. The observed reactivity indicates that the components of a purported pre-RNA world conceivably include smaller organic molecules.imidazolidinone catalysis | self-replication | template effects S tudies of prebiotic chemistry raise questions concerning which functions came nearer the origin of life-genetics or metabolism (1). The discovery of the catalytic activity of ribozymes provided an answer in which both functions could be accounted for in an "RNA world" (2). Although no one doubted that RNA could carry genetic information, some 15 years lapsed before an RNA molecule was shown to self-replicate (3), and this type of catalysis has since been developed to an extraordinary level of efficiency (4). Short, self-complementary DNA strands were shown to selfreplicate in 1986 (5), and autocatalysis based on molecular recognition was found in simplified organic molecules (6) and even peptides (7). At the present time, many types of self-replicating structures are known (8). These systems function like their nucleic acid counterparts in that the self-complementary structures operate as templates for their own formation. However, unlike ribozymes, the synthetic self-replicating systems are not known to catalyze other chemical reactions. The wholly synthetic structures act as either organocatalysts or autocatalysts, but published evidence for both activities in a single molecule is limited (9). This research was undertaken to find molecules that could perform in both capacities, and we report here an imidazolidinone-based compound and its properties as a catalyst and autocatalyst. Results and DiscussionTo realize an autocatalytic/organocatalytic molecule, we made modifications in the structure of compound 1, a molecule that bears self-complementary hydrogen-bonding subunits-a diaminotriazine and cyclic imide-that allow for dimerization in noncompeting organic media (Fig. 1). The arrangement of these subunits in 1 was earlier shown to allow its action as an autocatalyst (10): It acts as a template for its own synthesis, gathering two subunits on its surface to facilitate the formation of the amide bond. The insertion of a functional group known to catalyze organic transformations into 1 was a prospect to be explored. We initially inserted a thiourea into the framework of 1 (11). Although the thiourea function is a widely used organocatalyst (12), its applications were limited in the present context: The same hydrogen bonding that accounts for the thiourea's activity requires the use of solvents that also lead to tight dimerization of the template. This effect minimizes the fraction of the monomeric compound t...

The Phylogenomic Roots of Modern Biochemistry: Origins of Proteins, Cofactors and Protein Biosynthesis

“…In vitro evolution studies (Ellington et al 2009) reveal that RNA molecules can serve as catalysts (e.g., Robertson and Scott 2007) and as replicators (Lincoln and Joyce 2009) and proteins in random libraries can be selected to gain structure and function (Keefe and Szostak 2001). Autocatalytic processes of molecular recognition develop in simplified systems of organic molecules (Vidonne and Philp 2009), including autocatalytic hydrogenations and nucleophilic additions to unsaturated aldehydes (Kamioka et al 2010).…”

Self-reproducing catalyst drives repeated phospholipid synthesis and membrane growth

“…However, membrane growth in these systems inevitably leads to dilution of the catalyst and cessation of membrane formation (15,16). Thus, a significant roadblock to synthetic membranes capable of continual phospholipid synthesis has been the lack of a mechanism by which the embedded molecular catalysts that are responsible for membrane expansion are able to repopulate indefinitely (15,17). Here we report on the design of a simplified lipid synthesizing membrane that uses a synthetic, membraneembedded catalyst that is capable of self-reproduction.…”

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