Effects of Chlorine and Methyl Substitution on Structure, IR, and Raman Spectra of the Biomolecule 6-Chloro-3-methyluracil in Isolated and Solid States and in Base-Pair Formation.

The effect of the chlorine atom in the sixth position and methyl group in the third position of the uracil ring on the structural parameters, NBO charge distribution, and molecular properties of the 6-chloro-3-methyluracil (M6CU) biomolecule was analyzed in the isolated state, solid-state arrangement and within a double-stranded RNA microhelix. This effect, which was also compared to those with uracil and several uracil derivatives, leads to higher reactivity and the special properties of this pharmaceutical compound. Several correlations were established using MP2 and several DFT methods. The structural characterization of M6CU and a detailed analysis of the experimental FT-IR and FT-Raman spectra in the solid state was another aim studied in detail. For an accurate assignment, a simple approximation to a crystalline unit cell was optimized using a trimer form and the wavenumbers were subsequently corrected using several scaling procedures. The modified nucleobase M6CU forms base pairs with the complementary adenine and, therefore, it could replace uracil in the helix; based on our calculations, it leads to a noticeable helix deformation. This computational finding suggests its possible potential effect by binding to cancer-related or viral RNA helices. Molecular docking also revealed that M6CU could act as an active ligand within the 1JPW active site of the target β-catenin/Tcf4 protein complex.