Photophysical and photochemical properties of amitriptyline and nortriptyline hydrochloride: a 266 nm nanosecond laser flash and theoretical study

Amitriptyline (AMI) and nortriptyline (NT) hydrochlorides were studied by 266 nm laser transient absorption spectroscopy and quantum theoretical calculations. Both drugs photoionize through a biphotonic mechanism producing a radical cation and the solvated electron. A triplet excited state in a twisted conformation around the exocyclic bond is proposed as the intermediate state in the photoionization process. The solvated electron reacts with the ground state drug molecules with rate constants of 6.5 and 5.5×109 M−1 s−1 to form electron adducts, that absorb in the same wavelength region as the radical cation. Photosensitization experiments using thioxanthone triplet state as the sensitizer demonstrated that AMI or NT quenches this state by a mechanism that depends on the protonation of the amino group in the alkylamine side chain. The protonated species favors energy transfer, while the unprotonated species produces the tricyclic antidepressive radical cation of these drugs and the thioxanthone ketyl radical. These results follow the Rehm–Weller equation for an electron transfer mechanism. Quantum theoretical calculations indicate that ground and excited singlet states photophysical properties of these molecules are determined by the 1,2-diphenylethane system with little participation of the exocyclic double bond. The presence of these primary radicals could explain the reported Type I photodamaging effects for these drugs.