Rare Tautomers of Artificially Expanded Genetic Letters and their Effects on the Base Pair Stabilities

In order to expand the existing genetic letters, it is necessary to design robust nucleotides that can function naturally in living cells. Therefore, it is desirable to examine the roles of recently-proposed second-generation artificially genetic letters in producing stable duplex DNA. Herein, a reliable dispersion-corrected density functional theory method is used to shed light on the electronic structures and properties of different rare tautomers of proposed expanded genetic letters and their effects on the base pair stabilities in the duplex DNA. It is found that the rare tautomers are not only stable in the aqueous medium but can also pair with natural bases to produce stable mispairs. Except for J and V, all of the artificial genetic letters are found to produce mispairs that are about 1-7 kcal mol^-1 more stable than their complementary counterparts. They are also appreciably more stable than the naturally occurring G : C, A : T, and G : T pairs. Mainly attractive electrostatic interactions and polarity of the monomers are responsible for the higher base pair stabilities.