Abstract
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•Structure and conformational dynamics of levetiracetam reported.•Significant intermolecular forces found between the drug and water and methanol.•Local energy decomposition provides contribution to each type of interactions.•Solvent dynamics using ab initio molecular dynamics.•Implicit solvation studies reported.
SV2A is a protein necessary for synaptic neurotransmitter release in the brain. Levetiracetam, an antiepileptic medication, binds to SV2A to produce its effects. To halt seizures, Levetiracetam slows down these electrical signals by reducing excitement or increasing inhibition. In this manuscript, we present the theoretical study of the solvation dynamics of this drug with different solvents. We have used for optimizations and other calculations: PBE0-D3/def2-TZVP method and basis set for NBO, NCI, and wavefunction studies; PBE0-D3/def2-TZVP and DLPNO-CCSD(T) for LED, MD, and bond energy of Levetiracetam and its complex with water and methanol. Levetiracetam can produce four fragments: pyrrolidinone, propyl, carbenoxy-, and amine in amide, and the bond (BDE) energy is 358.3581 kcal/mol. The compounds show significant non-covalent interactions with water and methanol. LED shows Levetiracetam with methanol having the lowest and most stable energy is −98.5818 kcal/mol. Levetiracetam with water has the highest energy is −83.6130 kcal/mol, so methanol is a more suitable solvent than water for Levetiracetam. The NBO explains the delocalization energies of electrons in Levetiracetam with solvents, and this assay supports the solvation studies of LED and AIMD assay. AIMD shows that Levetiracetam with water has the highest energy changes depending on time, going to a higher positive sign, and Levetiracetam with methanol has the lowest energy changes depending on time going to a lower positive sign. The implicit solvation assay also shows the same result as LED and AIMD. The solvated system free energy of Levetiracetam with methanol has the lowest dielectric energy (–23.2865 kcal/mol) than Levetiracetam with water system energy (–23.2421 kcal/mol).