We have studied the hydrolysis mechanism of lobaplatin in aqueous medium under neutral and acidic conditions using density functional theory combining with CPCM model. The stationary states located on potential energy surface were fully optimized and characterised. The rate limiting step in neutral conditions, ring opening reaction with an activation energy of 110.21 kJ mol(-1). The completely hydrolysed complex is expected to be the reactive species towards the DNA purine bases. In acidic conditions, ligand detachment is the rate limiting step with an activation energy of 113.82 kJ mol(-1). Consequently, mono hydrated complex is expected to be the species reacting with DNA. (C) 2016 Elsevier B.V. All rights reserved.