Theoretical Prediction for the Possible ESIPT in N‐Protonated Gauche‐Form Histamine in Aqueous Medium

Histamine is a neurotransmitter, and it is available as protonated state at the physiological conditions. We predicted theoretically the possibility of excited state intra‐molecular proton transfer (ESIPT) at the excited state of N‐protonated gauche‐form histamine in aqueous phase. The proton transfer occurs from the ammonium unit of aliphatic chain to the nitrogen of the imidazole ring. The acidity of aliphatic amine (N14) and basicity of imidazole nitrogen (N8) increase only at the excited state, suggesting the possibility of proton transfer at the excited state. The distance between amine proton and acceptor nitrogen in the imidazole ring becomes closer at the excited state (∼3.23 Å changes to ∼1.86 Å) in aqueous phase, which facilitates proton transfer from the amine group to imidazole nitrogen at the excited state. The energy barrier calculated using the potential energy surface scans suggests the low activation energy (∼5.1 kcalmol −1 ) facilitating faster reaction. At pre‐ESIPT state, protonated histamine (gauche form) absorbs light of ∼219 nm and emits at ∼315 nm in aqueous phase, whereas at post‐ESIPT state it emits at ∼407 nm, reflecting a large red‐shifted emission due to ESIPT in protonated histamine. Born‐Oppenheimer Molecular Dynamics studies detected the timescale of the ESIPT reaction as ∼203 fs for protonated histamine in aqueous phase, which correlates well with the experimental ESIPT time scale for other systems reported in literature.