Syntheses, π-stacking interactions and base-pairings of uracil pyridinium salts and uracilyl betaines with nucleobases

Abstract

Reaction of 6-chlorouracil with 4-(dimethylamino)pyridine, 4-methylpyridine, and pyridin-4-yl-morpholine yielded pyridinium-substituted uracils as chlorides which were converted into pyridinium uracilates by deprotonation. These heterocyclic mesomeric betaines are cross-conjugated and thus possess separate cationic (pyridinium) and anionic (uracilate) moieties. Calculations and X-ray single crystal analyses were performed in order to characterize these systems and to compare the salts with the betaines. ¹H NMR experiments in D₂O proved π-interactions between the uracilyl betaines and adenine, adenosine, as well as adeninium. No π-stacking interactions were detected between the betaines and guanosine. The acidic N8-H group of the uracil pyridinium salts caused acid–base reactions which were observed in parallel to π-stacking interactions. Self-complementarity of the modified uracils was detected by ¹H NMR experiments in DMSO-d₆ and electrospray ionisation mass spectrometry (ESIMS). Ab initio calculations predicted base-pairings of the modified uracils with adeninium, cytosine, and guanine. Several geometries of hydrogen-bonded associates were calculated. Hoogsteen pairings between the uracil-4-(dimethylamino)pyridinium salt and adeninium, as well as associates between the corresponding betaine plus cytosine, and the betaine plus guanine were calculated, and the most stable conformations were determined. In the ESI mass spectra, prominent peaks of associates between the modified uracils and adeninium, cytosine, cytidine, guanosine and d(CpGp) were detected.