Creatinine: an examination of its structure and some of its reactions by synergistic use of MNDO calculations and nuclear magnetic resonance spectroscopy

MNDO calculations do not predict correctly the tautomer of creatinine (1) present in aqueous solution as deduced from n.m.r. evidence. The reason is substantial hydrogen bonding to the solvent. However, calculations do illuminate the form of protonated creatinine and lead to a semi-quantitative explanation of the higher basicity of glycocyamidines with exocyclic CN, e.g. methylcreatinine (2). Both calculations and spectroscopy show the ring-opening reaction of creatinine in alkaline solution to give creatine (5). The significance of this to the clinical assay of creatinine (the Jaffé reaction) is discussed. In acid solution creatinine undergoes slow ring closure.