A COMPUTATIONAL STUDY ON RELATIONSHIP BETWEEN SOLUBILITY AND MOLECULAR STRUCTURE: LAMOTRIGINE

Lamotrigine as a voltage- gated sodium channel blocker is used in epilepsy and bipolar disorder [1]. Unlike the other antiepileptics, it has fewer side- effects which make it unique among antiepileptic agents. But there is still the solubility problem about it just like not only antiepileptics but also the other drugs, in pharmaceutical industry. It is estimated that 40% of drug agents have low aqueous solubility [2, 3]. We have investigated in detail to give clear explanation the solubility of Lamotrigine according to its relatedphysicochemical properties. In this context, we have performed solvation calculations for global minimum structure to obtain the thermodynamics about it, in different solvent environment. And we also calculated partial atomic charges by MPA, NPA, CHELPG, ESP methods to show electronic properties. Finally, EPT calculations with P3 and OVGF approximations have been employed to calculate energy gap values. All calculations have been performed by using the Gaussian 03W [4] package program. Isodensity version of Polarized Continuum Model is used to obtain solvation energetics from 6-31g* and 6- 311++g** basis sets both HF and DFT methods.