Restricted rotation/tautomeric equilibrium and determination of the site and extent of protonation in bi-imidazole nucleosides by multinuclear NMR and GIAO-DFT calculations

The restricted rotation about the conjoining bond in a series of 4″‐substituted bi‐imidazole nucleosides {5‐amino‐4‐[4″‐R‐imidazol‐2″‐yl]‐1‐(β‐d‐ribofuranosyl)‐1H‐imidazole; where R=H, methyl, hydroxymethyl, oxalo, formyl} due to intramolecular hydrogen bonding between N‐3″ and the N‐6 protons concomitant with prototropic tautomerism has been examined using multinuclear (1H, 13C and 15N) experimental NMR. Substitution at the 4″ position causes the interconversion, whilst still an intramolecular process, to yield complex spectra as the dynamic process consists of a two‐site exchange between non‐degenerate tautomeric forms (asymmetric sites). The preferred tautomers were identified experimentally in each case and compared with theoretically determined structures geometry optimized using density functional theory (DFT) at the B3LYP/6–31G(d,p) level of theory on which gauge‐independent atomic orbital‐DFT (GIAO‐DFT) computations at the B3LYP/cc‐pVTZ level of theory were applied to calculate the chemical shifts of the 1H, 13C and 15N nuclei. Both the site and the extent of protonation of the bi‐imidazole nucleosides were also similarly ascertained using the same methodology. Protonation at the pyridine‐type nitrogen (N‐3″) of the outer imidazole ring, the principle site of protonation, effectively eliminated the barrier to rotation about the conjoining bond yielding time‐averaged spectra experimentally. Copyright © 2004 John Wiley & Sons, Ltd. The restricted rotation about the conjoining bond in a series of 4″‐substituted bi‐imidazole nucleosides due to intramolecular hydrogen bonding concomitant with prototropic tautomerism was examined by multinuclear (1H, 13C and 15N) NMR. The preferred tautomers were compared with geometry‐optimized structures using DFT at the B3LYP/6–31G(d,p) level of theory on which GIAO‐DFT computations at the B3LYP/cc‐pVTZ level of theory were applied to calculate the chemical shifts. Protonation at the pyridine‐type nitrogen of the outer imidazole ring effectively eliminated the barrier to rotation yielding time‐averaged spectra.