A theoretical investigation on decarboxylation mechanism of antibiotic para-aminosalicylic acid to highly toxic form met
- PDF / 842,579 Bytes
- 8 Pages / 595.276 x 790.866 pts Page_size
- 68 Downloads / 175 Views
ORIGINAL RESEARCH
A theoretical investigation on decarboxylation mechanism of antibiotic para-aminosalicylic acid to highly toxic form meta-aminophenol Niloofar Hemati 1 & Farshad Shiri 2,3 & Saba Hadidi 2 & Elham Mohammadi 4 & Rasool Parvizi 1 & Mohammad Hosein Farzaei 5 Received: 24 August 2020 / Accepted: 9 November 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The antibiotic para-aminosalicylic acid (PAS) is decomposed into its decarboxylated product, meta-aminophenol, with a series of toxicity symptoms including hemolytic anemia. The present trial investigates the decarboxylation mechanism of PAS, along with an in-detail assessment of the potential energy profiles, geometries, kinetic, and thermodynamic preference of the process. Further, the effects of solvent and pH on the process have been fully investigated. B3LYP-D3(BJ)/G4MP2 calculations have been executed on the para-aminosalicylic acid decomposition with a view to clarify the aqueous thermal decarboxylation and pH influences on the mechanism. The decomposition process can only be described accurately by the inclusion of solvent not only as a reaction medium but also as an active contributor to the chemical process. We further found an optimal preference with respect to energy barriers for the process with decreasing pH. Also, experiments showed the reduction in PAS absorbance with fall in pH. These together suggested the decrease of rate of decarboxylation with pH increase. Finally, we concluded that increasing pH reduces the reaction rate and in the pH around 10, the reaction rate reaches zero and it completely halts. We assume that this experiment can pave the way for advanced experimental and theoretical researches in the drug degradation mechanisms field and the effect of pH and solvent on the process. Keywords Para-aminosalicylic acid . Decarboxylation . pH effects . Solvent dependence . B3LYP-D3(BJ)/G4MP2
Introduction Highlights 1. PAS is decomposed into its decarboxylation product, metaaminophenol. 2. The solvent is not only as a reaction medium but further it acts as an active contributor in the chemical process 3. The process shows a significant rate reduction by increasing pH. * Mohammad Hosein Farzaei [email protected] 1
Internal Medicine Department, School of Medicine, Kermanshah University of Medical Sciences, Kermanshah, Iran
2
Department of Inorganic Chemistry, Faculty of Chemistry, Razi University, Kermanshah, Iran
3
Medical Biology Research Center (MBRC), Kermanshah University of Medical Sciences, Kermanshah, Iran
4
R.R College of Pharmacy, Bangalore, India
5
Pharmaceutical Sciences Research Center, Health Institute, Kermanshah University of Medical Sciences, Kermanshah, Iran
Para-aminosalicylic acid (PAS) as an available drug to treat extensively drug-resistant tuberculosis is an active agent in the treatment of cancer and inflammatory bowel disease [1]. PAS has also shown modest activity against mycobacterium and influenza virus [2]. The short serum half-life of the compound is a c
Data Loading...
