Synthesis of [(MeCyt)2H]I—structure and stability of a dimeric threefold hydrogen-bonded 1-methylcytosinium 1-methylcytosine cation

Abstract

Reaction of trimethylsilyl-protected cytosine with methyl iodide afforded N1-methylated product. Subsequent treatment with ethanol resulted in cleavage of the protection group forming [(MeCyt)₂H]I (4). Identity of 4 was confirmed by microanalysis, mass spectrometry, ¹H and ¹³C NMR spectroscopy and by single-crystal X-ray diffraction analysis. Crystals of 4 consist of dimeric [(MeCyt)₂H]⁺ cations and I⁻ anions. These ions are arranged in the crystal such that there is a strong base stacking (mean stacking distance 3,467 Å) and, furthermore, π interactions between I⁻ and cytosine rings (mean distance 3,737 Å). The dimeric [(MeCyt)₂H]⁺ cations are centrosymmetric having three strong hydrogen bonds, namely two terminal N4–H⋯O′ ones (N4⋯O′ 2.815(4) Å) and a central N3–H⋯N3′ (N3⋯N3′ 2.813(4) Å) one. Quantum chemical calculations on the DFT level of theory show that the gas phase structure of the dimeric cation exhibits two different terminal N–H⋯O hydrogen bonds, a stronger (N4⋯O′ 2.722 Å) and a weaker one (N4′⋯O 2.960 Å). The central N3–H⋯N3′ hydrogen bond (N3⋯N3′ 2.852 Å) was characterized to have an unsymmetrically located proton and a typical double minimum potential with a very low activation barrier. The interaction energy between [(MeCyt)H]⁺ and MeCyt yielding [(MeCyt)₂H]⁺ was calculated to be −42.4 kcal mol⁻¹ (ZPE and BSSE corrected). Comparison with the interaction energy (calculated on the same level of the theory) between cytosine and guanine yielding the triply hydrogen-bonded Watson–Crick dimer (−24.2 kcal mol⁻¹) revealed a much higher stability of the hydrogen bonds in [(MeCyt)₂H]⁺.