A comparative study of the hydrogen-bonding patterns and prototropism in solid 2-thiocytosine (potential antileukemic agent) and cytosine, as studied by ¹H- ¹⁴N NQDR and QTAIM/ DFT

Abstract

A potential antileukemic and anticancer agent, 2-thiocytosine (2-TC), has been studied experimentally in the solid state by ¹H- ¹⁴N NMR-NQR double resonance (NQDR) and theoretically by the quantum theory of atoms in molecules (QTAIM)/density functional theory (DFT). Eighteen resonance frequencies on ¹⁴N were detected at 180 K and assigned to particular nitrogen sites (−NH ₂, –N=, and –NH–) in 2-thiocytosine. Factors such as the nonequivalence of molecules (connected to the duplication of sites) and possible prototropic tautomerism (capable of modifying the type of site due to proton transfer) were taken into account during frequency assignment. The result of replacing oxygen with sulfur, which leads to changes in the intermolecular interaction pattern and molecular aggregation, is discussed. This study demonstrates the advantages of combining NQDR and DFT to extract detailed information on the H-bonding properties of crystals with complex H-bonding networks. Solid-state properties were found to have a profound impact on the stabilities and reactivities of both compounds.

Figure

The experimental 1H-14N NQDR spectrum of 2-thiocytosine obtained at T = 180 K by the solid effect technique (left) and 3d distribution of the electron density Laplacian calculated by DFT (right)