Carbonless DNA†

Abstract

Carbonless DNA was designed by replacing all carbon atoms in the standard DNA building blocks with boron and nitrogen, ensuring isoelectronicity. Electronic structure quantum chemistry methods (DFT(ωB97XD)/aug-cc-pVDZ) were employed to study both the individual building blocks and the larger carbon-free DNA fragments. The reliability of the results was validated by comparing selected structures and binding energies using more accurate methods such as MP2, CCSD, and SAPT2+3(CCD)δ_MP2. Carbonless analogs of DNA components, including cytosine, thymine, guanine, adenine, and deoxyribose, were investigated, showing strong resemblance to the carbon-based versions in terms of spatial structure, polarity, and molecular interaction capabilities. Complementary base pairs of the carbonless analogs exhibited a similar number and length of hydrogen bonds as those found in their carbon-containing counterparts, with binding energies for A–T and G–C analogs remaining comparable. Carbonless DNA fragments containing two and six base pairs were studied, revealing double-helix structures analogous to natural DNA. Structural parameters such as fragment size, hydrogen bond lengths, and rise per base pair were consistent with those observed in unmodified DNA. Docking simulations with a 12 base pair fragment and netropsin as a ligand indicated a slight shift in binding preference for the carbonless DNA through the minor groove, with an approximate 25% increase in binding affinity compared to natural DNA.