Hydrolysis mechanism of anticancer drug lobaplatin in aqueous medium under neutral and acidic conditions: A DFT study

• Published in: Chemical physics letters Vol. 663; pp. 115 - 122
• Main Authors: Reddy B., Venkata P., Mukherjee, Subhajit, Mitra, Ishani, Mahata, Sujay, Linert, Wolfgang, Moi, Sankar Ch
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 16.10.2016
• Subjects: Aqueous medium; DFT; Hydrolysis mechanism; Lobaplatin; Third generation anticancer drug; Lobaplatin; DFT; Hydrolysis mechanism; Aqueous medium; Third generation anticancer drug
• ISSN: 0009-2614; 1873-4448
• DOI: 10.1016/j.cplett.2016.10.004

[Display omitted] •Hydrolysis mechanism of lobaplatin has been studied in aqueous medium under neutral and acidic conditions.•It undergoes complete hydrolysis and fully hydrolysed form is expected reach to DNA, under neutral conditions.•Second aquation being the rate limiting step, lobaplatin is expected to reach the DNA in its monohydrated form under acidic conditions.•Activation barrier heights have been compared with Pt-based anticancer drugs currently used in the medical protocols. 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 110.21kJmol−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 113.82kJmol−1. Consequently, monohydrated complex is expected to be the species reacting with DNA.