Understanding the behavior of a potential anticancer lamotrigine in explicit solvent (water and DMSO) using quantum mechanical tools and abinitio molecular dynamics

Lamotrigine is a medication used to treat epilepsy and help stabilize mood in individuals with bipolar disorder. Epilepsy includes different types of seizures, such as focal seizures, tonic-clonic seizures, and Lennox-Gastaut syndrome, and Lamotrigine is specifically designed to manage this condition. The effectiveness of the drug relies on how it interacts with different liquid environments. In our study, we employed two methods, namely PBE0-D3/def2-TZVP, for optimizations and various calculations. We utilized this approach for NBO, NCI, and wavefunction assay. Additionally, we used PBE0-D3/def2-TZVP and DLPNO-CCSD(T) for analyzing LED, MD, and the bond energy of Lamotrigine in both a vacuum and a complex setting (with water and DMSO). Our findings revealed that Lamotrigine can break down into four fragments: triazine, dichlorophenyl-, 10 amine at the second position in triazine, and 10 amines at the fourth position in triazine. The bond energy for these fragments is measured at 351.84 kcal/mol. NBO provided insights into the electronic transition energies of Lamotrigine in different environments, including a vacuum and with solvents. NCI helped us understand the noncovalent interactions of Lamotrigine in both a vacuum and with water and DMSO (complex) molecules through their two pores: inter and intra interactions. We further explored binding energies and total binding energies of Lamotrigine with water and DMSO. Simulations indicated that Lamotrigine with DMSO pore1 exhibited the highest energy changes over time with a positive sign, while Lamotrigine with water pore2 showed the lowest energy changes over time with a negative sign. In our implicit solvation assay using the SMD model and the CPCM method, we found that Lamotrigine with water had a lower free energy compared to the LamotrigineDMSO system.