Gas phase protonated nicotine is a mixture of pyridine- and pyrrolidine-protonated conformers: implications for its native structure in the nicotinic acetylcholine receptor

Abstract

The infrared (IR) spectra of gas phase protonated nicotine has been measured in the never-before probed N-H “fingerprint region” (3,200–3,500 cm−1). The protonated molecules generated by an electrospray source are...

Structure of Gas Phase Monohydrated Nicotine: Implications for Nicotine’s Native Structure in the Acetylcholine Binding Protein

“…3,5 Aqueous NOR is known to be protonated also at the pyrro nitrogen (Pyrro-NORH + ), whereas recent investigations of gas-phase NOR suggested that it is almost fully protonated at the pyri nitrogen (Pyri-NORH + ). 18,24 NOR's protomer stability is environment dependent, although the effect of the environment on NOR's protonation site appears to be more extreme than that of NIC.…”

“…While previous gas phase studies 24 have been able to capture protomer distributions at RT, the present experiments are limited by the dissociation process. These previous studies 24 have indicated that kinetic trapping at low temperatures prevents equilibrium, and for this reason the temperature in the present experiments is modulated to achieve thermal equilibrium and to be able to observe the hydrated clusters. The present work focuses on singly hydrated clusters, which can be observed well above any suspected kinetic trapping.…”

“…23 Only recently have experimental and theoretical investigations converged to the result that gas phase NIC is definitively a natural mixture of protonation sites at both the Pyrro-NICH + and the Pyri-NICH + nitrogen atoms at room temperature (RT). 24 Nornicotine (NOR), a natural metabolite of NIC found in tobacco leaves together with other alkaloids, 3 is structurally and functionally similar to NIC. 25 NOR shows affinity to nAChRs as an agonist, albeit it is less addictive than NIC.…”

“…The anharmonic frequencies and intensities closely mirror those from a harmonic analysis. 24 Pyri-NICH + shows an intense peak at 3365 cm −1 (114 km/mol), while Pyrro-NICH + shows a much less intense peak at 3226 cm −1 (25 km/ mol). Since they agree well with the previously reported spectrum, they induce no changes to the ratio of absorption cross sections and subsequently to the previously reported monomer populations.…”

The combination of laser photodissociation, action spectroscopy, and mass spectrometry to identify and separate isomers

“…Cryogenic infrared photodissociation spectra of H 2 tagged nicotineH + ions provide additional spectroscopic evidence for the presence of both nicotineH + protomers. 198 Another example of FAIMS separation of protomer ions is the case of quinazolineH + where two protomers present from ESI in comparable yields. 190 With FAIMS separation, the spectra of both protomers were separately recorded, with a vibronic structure (Fig.…”