Creatine acts as a crucial energy carrier in the cardiac muscle, facilitating the transport of phosphate from mitochondria to myofibrils for ATP regeneration. However, creatine spontaneously undergoes non-enzymatic cyclization to creatinine. The molecular mechanisms of this reaction remain poorly understood, particularly in the presence of calcium ions, which accumulate during myocardial ischemia. We employed quantum chemical calculations using DFT/MN15/Def2-TZVP methodology with PCM solvent modeling to investigate creatine cyclization paths under various conditions: intramolecular, with water molecules, in the presence of Ca
Bachurin et al. (Wed,) studied this question.