In Silico Study of Complex Formation of Nucleic Acid Bases with Conjugated Nitrogenous Heterocycles

We studied in silico in a fragment-to-fragment approach the possibility of the formation of stable [Het- BioM]-complexes between $\boldsymbol{\pi}$ -conjugate nitrogen molecules with nucleic bases by the $\boldsymbol{\pi}$ -stack mechanism and due to hydrogen bonding. The parameter $\varphi_{0}$ is used to quantify the donor-acceptor properties of model heterocycles and NBs. It is established that the possibility of complex formation by different mechanisms depends on the parameter $\varphi_{0}$ of both components, as well as on the nature of their first electron transitions. It has been shown that imidazole-based drugs form stable [Het-BioM] complexes by the $\boldsymbol{\pi}$ -stack interaction, and pyrimidine-based drugs form [Het-BioM] complexes by the mechanism of hydrogen bond formation. The introduction in the uracil of the acceptor sulfo- group stabilizes the [HB]-complex at 2.5 kcal/mol, and the introduction of the chlorine atom at the same position changes the nature of the first electron transition so that such a molecule is characterized by the formation of a $\boldsymbol{[\pi,\pi]}$ -complex instead of [HB]-complex.