Creatinine and creatininium cation in DMSO‐d₆ solution. Structure and restricted internal rotation of NH₂ group

Abstract

Investigation of 15N NMR spectra of isotopically enriched creatinine has unequivocally shown that in DMSO-d6 solution it exists as amino tautomer (2-amino-1-methylimidazoline-4-one), which in the presence of acid is protonated at N-3. Free energies of activation of the amino group rotation in creatinine and its cation have been determined to be 56 kJ/mol and 60 kJ/mol, respectively, at 298 K, by performing the simultaneous analysis of the lineshapes of -NH2 proton signals in the whole set of 1H NMR spectra recorded at various temperatures and magnetic fields. These results have been theoretically reproduced by the calculations of molecular structures and energies of creatinine and creatininium cation in their ground states and transition states of the amino group rotation, using DFT (B3LYP) method, involving the influence of the solvent.

Creatinium perchlorate

“…For a related structure, see: Cherouana et al (2003); Berrah et al (2005). For interpretation of the solution acidity effect on NMR chemical shifts, see: Kotsyubynskyy et al (2004). Mo K radiation = 0.45 mm À1 T = 293 (2) K 0.10 Â 0.10 Â 0.10 mm…”

Creatininium benzoate

“…NMR spectroscopic studies and high-level theoretical calculations indicate that the amino tautomer of creatinine is more stable in aqueous solutions (Kotsyubynskyy et al, 2004;Craw et al, 1997). On the other hand, in the gas phase, the imino tautomer is probably more stable (Butler & Glidewell, 1985), while in a sufficiently acidic medium, creatinine is protonated apparently at N3, forming the creatininium cation with strongly delocalized charge (Reddick & Kenyon, 1987;Olofson et al, 1998).…”

Hydrogen bonding in creatininium nitrate

“…In the present study, only the imino group of the imidazolyl moiety (atom N1) in creatinine is protonated, which con®rms the possibility of the existence of creatinine and creatininium cations in various tautomeric forms in aqueous solution. This is discussed and quanti®ed in the light of the interpretation of the solution acidity effect on 1 H, 13 C and 14 N NMR chemical shifts (Kotsyubynskyy et al, 2004).…”