Theoretical investigation of loratadine reactivity in order to understand its degradation properties: DFT and MD study

  • Stevan Armaković
  • Sanja J. Armaković
  • Biljana F. Abramović
Original Paper


Antihistamines are frequently used pharmaceuticals that treat the symptoms of allergic reactions. Loratadine (LOR) is an active component of the second generation of selective antihistaminic pharmaceutical usually known as Claritin. Frequent usage of this type of pharmaceuticals imposes the need for understanding their fundamental reactive properties. In this study we have theoretically investigated reactive properties of LOR using both density functional theory (DFT) calculations and molecular dynamics (MD) simulations. DFT study is used for collecting information related to the molecule stability, structure, frontier molecular orbitals, quantum molecular descriptors, charge distribution, molecular electrostatic potential surfaces, charge polarization, and local reactivity properties according to average local ionization energy surfaces. Based on these results, N24 atom of pyridine ring and oxygen atom O1 were identified with nucleophilic nature. In order to collect the information necessary for the proposition of degradation compounds we also calculated bond dissociation energies (BDE) for hydrogen abstraction and single acyclic bonds as well. According to BDE, the oxidation is likely to occur in the piperidine and cycloheptane rings. MD simulations were used in order to understand the interactions with water through radial distribution functions (RDF). Based on RDFs the most important interactions with solvent are determined for carbon atom C5, chlorine atom Cl15, and oxygen atom O1. Collected results based on DFT calculations and MD simulations provided information important for suggestion of possible degradation compounds. Covalent and noncovalent interactions between LOR and OH have also been investigated.


Bond dissociation energy (BDE) Degradation intermediates Density functional theory (DFT) Loratadine (LOR) Molecular dynamics (MD) Radial distribution functions (RDF) 



This work has been done thanks to the support received from Schrödinger, Inc. Presented research was done within the framework of projects supported by the Ministry of Education, Science, and Technological Development of Republic of Serbia, grant numbers 172042, 171039, and 34019.

Supplementary material

894_2016_3101_MOESM1_ESM.doc (1.4 mb)
ESM 1 (DOC 1419 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2016

Authors and Affiliations

  • Stevan Armaković
    • 1
  • Sanja J. Armaković
    • 2
  • Biljana F. Abramović
    • 2
  1. 1.University of Novi Sad, Faculty of Sciences, Department of PhysicsNovi SadSerbia
  2. 2.University of Novi Sad, Faculty of Sciences, Department of Chemistry, Biochemistry and Environmental ProtectionNovi SadSerbia

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