Supramolecular Porous Network Formed by Molecular Recognition between Chemically Modified Nucleobases Guanine and Cytosine

Abstract

The involvement of surfaces in the origin of the first genetic molecules on Earth has long been suggested. Prior to the emergence of nucleic acid polymerases in the prebiotic soup, the self-assembly of primitive nucleobase building blocks may have relied on surface-mediated recognition events which catalyzed the formation of a covalent backbone in prototype oligonucleotides that subsequently may have functioned as templates in a primitive copying mechanism. This initial replication process may have been catalyzed by surfaces or chemical substances in solution—including RNA itself, as postulated in the RNA world hypothesis. Today, the role and the relative importance of the basic, fundamental driving forces for nucleic acid replication such as base pairing, base stacking, and steric effects are still under intense debate. Watson–Crick hydrogen bonding has traditionally been thought to be a prerequisite for high-fidelity DNA replication. However, recent studies on nucleobase analogues with the same size and shape as the natural ones but without relevant hydrogen-bonding groups have revealed that these analogues can recognize each other with high fidelity when incorporated into DNA sequences in vivo. Watson–Crick hydrogen bonding thus seems not to be a requisite for the selectivity of base pairing in DNA replication. However, in the absence of polymerases in the prebiotic soup, Watson– Crick hydrogen bonding may have played a more crucial role in the molecular recognition between the nucleobase building blocks at surfaces and for further polymerization. In support of this postulation, molecular recognition between complementary bases, most likely driven by hydrogen bonding alone, has already been observed both at the liquid/solid (HOPG) interface and on the noble Au(111) surface under extreme ultrahigh vacuum (UHV) conditions. These previous experiments were, however, conducted with nucleobases alone, and hence did not take the presence of deoxyribose into account. It is therefore of utmost importance to explore the role that Watson–Crick hydrogen bonding plays at surfaces in chemical structures that mimic nucleotides so as to address the fundamental question of how the polymerization of nucleotides may have started in the prebiotic soup in the absence of enzymes. The development of the scanning tunneling microscopy (STM) technique has advanced our understanding of supramolecular self-assembly systems on surfaces and has allowed intermolecular interactions to be explored at the submolecular scale. Herein we show by using a combination of high-resolution STM imaging and density functional theory (DFT) that sequential co-deposition of N-aryl-modified nucleobases cytosine (C) and guanine (G) onto the Au(111) surface under UHV conditions results in the formation of highly ordered supramolecular porous networks, where Watson–Crick hydrogen bonding between chemically modified C and G molecules plays the primary role in their stabilization. As the N-arylation of the nucleobases has been performed on the nitrogen atom normally attached to the sugar moiety in DNA or RNA (Scheme 1), these N-aryl-modified nucleobases thus represent two-dimensional (2D) structural mimics of naturally occurring nucleotides. The current results outline a new route for directing the self-assembly of nucleobase-derived nanostructures at the surface. Furthermore, the observed [*] Prof. W. Xu, Dr. M. F. Jacobsen, Dr. M. Yu, Prof. E. Laegsgaard, Prof. I. Stensgaard, Prof. T. R. Linderoth, Prof. J. Kjems, Prof. K. V. Gothelf, Prof. F. Besenbacher Interdisciplinary Nanoscience Center (iNANO) and Center for DNA Nanotechnology (CDNA), Department of Physics and Astronomy, Department of Chemistry, and Department of Molecular Biology, Aarhus University 8000 Aarhus C (Denmark) E-mail: fbe@inano.au.dk