A theoretical study on the enthalpies of homolytic and heterolytic N-H bond cleavage in substituted melatonins in the gas-phase and aqueous solution.

In this paper, the study of melatonin and 60 meta- and ortho-substituted melatonins is presented. The reaction enthalpies related to the hydrogen atom transfer (HAT), single electron transfer - proton transfer (SET-PT) and sequential proton loss electron transfer (SPLET) have been calculated using DFT/B3LYP method in gas-phase and water. Results show that electron-withdrawing substituents increase the bond dissociation enthalpy (BDE), ionization potential (IP) and electron transfer enthalpy (ETE), while electron-donating ones cause a rise in the proton dissociation enthalpy (PDE) and proton affinity (PA). In ortho position, substituents show larger effect on reaction enthalpies than in meta position. In comparison to gas-phase, water attenuates the substituent effect on all reaction enthalpies. Results show that IP and BDE values can be successfully correlated with the indolic N-H bond length after electron abstraction, R(N-H(+*)), and the partial charge on the indolyl radical nitrogen atom, q(N). Furthermore, calculated IP and PA values for meta and ortho substituted melatonins show linear dependence on the energy of the highest occupied molecular orbital (E(HOMO)) of studied molecules in the two environments. SPLET represents the thermodynamically preferred mechanism in water.