Study of creatinine and its 5-alkoxy analogs: Structure and conformational studies in the solid and solution states by X-ray crystallography, NMR, UV, and mass spectrometry

Creatinine (2-amino-1,5-dihydro-1-methyl-4-imidazolone) is a natural by-product of cellular metabolism related to muscular mass. It is excreted in human urine and is necessary for normal kidney function. Urinary secretion of creatinine serves as a bench mark for several clinical measurements. Recently, in our laboratories, during the course of an investigation of the urine of cancer patients for tumor markers, we found some new metabolites of creatinine. These were identified as 5-methoxy and 5-ethoxy creatinine by UV, NMR and Mass spectrometry and their tautomeric structures confirmed by crystal structural investigations of the metabolites. The x-ray crystallographic analysis confirmed the structures of the compound and showed that it exists in the 2-amino form. The spectral characteristics of these new compounds and the generality of the reaction are discussed in this paper. Creatinine, when allowed to react with methanol, ethanol and propanol respectively, in the presence of charcoal and air gave the 5-methoxy, 5-ethoxy and 5-propoxy creatinine derivatives respectively, suggesting a generality of a reaction. The reaction of creatinine with alcohols in the presence of charcoal and air takes place through a free radical reaction mechanism.