Thermochemical and Structural Analysis of Tautomers of Sulfur and Selenium Modified RNA Nucleobases

Nucleobases (adenine, cytosine, guanine, and uracil), the four molecules that forms RNA, have been found to be useful in probing in the human body when modified because they can emit light. Non-modified nucleobases do not exhibit emissive properties and cannot be used as probes. Some of the modifications include the substitution of nitrogen atoms with sulfur and selenium, and the resulting modified nucleobases give place to the so-called tz- and ts- RNA alphabets, respectively. Therefore, the aim of this project was to provide insights about the viability, from a computational perspective, of using the modified nucleobases as probes, evaluating the differences in thermochemical, structural and emissive properties of the modified nucleobases with respect to the non-modified ones. Nucleobases can coexist with other modified nucleobases or tautomers, molecules that differ due to the change in position of hydrogen atoms in a molecule’s structure and as a result have different physical and chemical properties. The thermochemical properties evaluation mainly consisted in the computation of the relative Gibbs Free Energy (G), which is related to the fraction F, an index of the relative population among tautomers. This was done using Gaussian 09 software by performing geometry analysis and frequency computations on each one of the tautomers. By comparing the equilibrium fractions, it was determined that in both cases, tz- and ts- guanine and cytosine exist principally in the form of one of their tautomers (Cytosine 2 and Guanine 2) as in the case of the non-modified cases. After confirming which tz- and ts- tautomers were the ones with the largest probable population, infrared (IR) and ultraviolet-visible (UV-vis) spectra were obtained. The IR spectra of selenium and sulfur tautomers of guanine and cytosine indicated that the tautomers had peaks at similar frequencies with respect to each other, however, the intensities varied, implying slight structural changes between the tautomers. On the other hand, the UV-vis spectra showed a change in peak positions between the tautomers with sulfur and selenium, suggesting that the change between sulfur and selenium has an effect on the spectra by shifting the peaks from the original molecules’ λmax values. Their relative population fractions show that only the canonical forms of the modified nucleobases exist in a larger extent than the rest of their tautomer forms. In addition, the features in their UV-vis and IR spectra allow these tautomers to be differentiated from each other.

The Stability of a Nanoparticle Diamond Lattice Linked by DNA

The functionalization of nanoparticles (NPs) with DNA has proven to be an effective strategy for self-assembly of NPs into superlattices with a broad range of lattice symmetries. By combining this strategy with the DNA origami approach, the possible lattice structures have been expanded to include the cubic diamond lattice. This symmetry is of particular interest, both due to the inherent synthesis challenges, as well as the potential valuable optical properties, including a complete band-gap. Using these lattices in functional devices requires a robust and stable lattice. Here, we use molecular simulations to investigate how NP size and DNA stiffness affect the structure, stability, and crystallite shape of NP superlattices with diamond symmetry. We use the Wulff construction method to predict the equilibrium crystallite shape of the cubic diamond lattice. We find that, due to reorientation of surface particles, it is possible to create bonds at the surface with dangling DNA links on the interior, thereby reducing surface energy. Consequently, the crystallite shape depends on the degree to which such surface reorientation is possible, which is sensitive to DNA stiffness. Further, we determine dependence of the lattice stability on NP size and DNA stiffness by evaluating relative Gibbs free energy. We find that the free energy is dominated by the entropic component. Increasing NP size or DNA stiffness increases free energy, and thus decreases the relative stability of lattices. On the other hand, increasing DNA stiffness results in a more precisely defined lattice structure. Thus, there is a trade off between structure and stability of the lattice. Our findings should assist experimental design for controlling lattice stability and crystallite shape.