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

Abstract

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.

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