The role of selection pressure in RNA-mediated evolutionary materials synthesis

Evolutionary materials synthesis is a provocative concept that has the potential for the discovery of novel compounds ranging from drugs to inorganic materials. RNA-mediated evolutionary materials synthesis requires aqueous solvent of moderate ionic strength, water-soluble precursors, and an appropriately designed selection pressure. Throughout the selection process, the RNA must be folded, stable, and accessible once it has bound to a target, catalyzed a chemical reaction, or templated formation of a structure. Subsequently, the RNA must be accessible to permit reverse transcriptase to create DNA copies for amplification. A well-designed selection will generate RNAs that can favor growth of a particular crystal habit or catalyze a specific reaction pathway. In this study we rigorously test the assumptions, procedures, and results of the only published example of an RNA-mediated evolutionary materials synthesis. The proof that a particular RNA sequence is responsible for a novel material synthesis must be established by control experiments as outlined in the present study. Furthermore, the product of nanoscale synthesis must be studied using state-of-the-art characterization methods to determine that selection pressure is exerted according to design. Herein, we demonstrate the use of advanced electron microscopy to determine chemical composition and structure as a critical step in analysis of the success of a selection. We conclude that RNA selections should not be carried out in binary solvent systems, such as tetrahydrofuran (THF) and water. A specific example, which is not consistent with rigorous selection of functional RNAs or RNA cognates, is provided by the precipitation of the water-insoluble precursor, tris(dibenzylideneacetone) dipalladium(0) Pd2(DBA)3.