Effect of pH and $\beta$-cyclodextrin on the photophysical properties of lamotrigine

Photophysical properties of lamotrigine (LMT) were investigated at different pH values. Lamotrigine exhibited a broad absorption band at 308 nm that was shifted to 268 nm at pH 2.0 due to protonation (HLMT+). Emission spectra of LMT at different pH values showed a single band at 483 nm except for at pH 2.0, where a second band at 502 nm was observed due to the deprotonation from the singlet excited state. LMT pH profile was used to calculate pK a of LMT in excited and ground states (pKa* = 4.50 and pKa = 5.90). Absorption spectra of LMT at different pH values for LMT in the presence of beta-CD showed an isosbestic point at 290 nm. A significant enhancement in the emission intensity of LMT upon increasing beta-CD (0-7 mmol L-1) was reported. Benesi-Hildebrand analysis showed that LMT / beta-CD and HLMT + / beta-CD complexes have 1:1 stoichiometry, with K11 values anging from 122 at pH 2.0 to 50 at pH 8.0. Thermodynamic parameters showed that complexation process is enthalpy driven (delta H degrees = - 23.1 kJ.mol(-1) at pH 2.0 and -24.1 kJ.mol(-1) at pH 8.0). Molecular mechanical calculations by MM+ force field indicated that LMT is preferentially included within the beta-CD cavity through its diamino-1,2,4-triazine moiety.