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

Abstract

We report a joint experimental−theoretical study of the never reported before structure and infrared spectra of gas phase monohydrated nicotine (NIC) and nornicotine (NOR) and use them to assign their protonation sites. NIC's biological activity is strongly affected by its protonation site, namely, the pyrrolidine (Pyrro-NICH + , anticipated active form) and pyridine (Pyri-NICH + ) forms; however, these have yet to be directly experimentally determined in either the nicotinic acetylcholine receptor (nAChR, no water present) or the acetylcholine-binding protein (AChBP, a single water molecule is present) but can only be inferred to be Pyrro-NICH + from the intermolecular distance to the neighboring residues (i.e., tryptophan). Our temperaturecontrolled double ion trap infrared spectroscopic experiments assisted by the collisional stripping method and high-level theoretical calculations yield the protonation ratio of Pyri:Pyrro = 8:2 at 240 K for the gas phase NICH + •••(H 2 O) complex, which resembles the molecular cluster present in the AChBP. Therefore, a single water molecule in the gas phase enhances this ratio in NICH + relative to the 3:2 for the nonhydrated gas phase NICH + in a trend that contrasts with the almost exclusive presence of Pyrro-NICH + in aqueous solution. In contrast, the Pyri-NORH + protomer is exclusively observed, a fact that may correlate with its weaker biological activity.

Hydration-induced protomer switching in p-aminobenzoic acid studied by cold double ion trap infrared spectroscopy

“…1–4 In addition, some molecules vary their preferred protonation site depending on the surrounding environment such as solvent or counter ion. 5–29 Such protonation site-switching obviously has a huge effect on the chemical reactivity and biological activity of the molecule. 12,28…”

“…5–29 Such protonation site-switching obviously has a huge effect on the chemical reactivity and biological activity of the molecule. 12,28…”

“…Such protonation site-switching obviously has a huge effect on the chemical reactivity and biological activity of the molecule. 12,28 Para-aminobenzoic acid (PABA) is a benchmark molecule for protonation site-switching. [8][9][10][11][13][14][15][16][17][18][20][21][22]29 PABA has two lowenergy protonated isomers, namely the O-and N-protomers resulting from protonation of the carboxy and amino groups, respectively (Fig.…”

Similarity scores of vibrational spectra reveal the atomistic structure of pentapeptides in multiple basins

“…Various systems have been studied to date; for example, ionic liquid, [1][2][3][4] protonated water clusters, [5][6][7][8][9][10] metal oxide clusters, [11][12][13][14][15] and so on. Conformer-selective vibrational spectra of polypeptides [16][17][18][19][20][21][22][23][24][25][26] have been measured with the usage of infrared (IR) and ultraviolet (UV) double resonance spectroscopy and supersonic jet expansions. We have developed cryogenic ion traps [27] combined with an electrospray ion source, [28][29] which efficiently produce peptides and peptide-ligand complexes in the gas-phase.…”

Ion Recognition beyond Size Matching: Cooperative Hydration Effect on the K+ Selectivity of Valinomycin over Na+ Revealed by Cryogenic Double Ion Trap Infrared Spectroscopy

“…In solution-phase experiments, the noncovalent interactions between a solute and a solvent are difficult to characterize due to the spectral interference from solvent molecules that do not participate in the solvation. Solvated clusters are regarded as a model for clarifying the nature of solvation. − One can interrogate the microsolvation effect using this double ion trap technique because the degree of solvation (i.e., number of solvent molecules) can be precisely selected by mass spectrometry. ,− In this study, the hydration effect on the conformation of Na + VM was examined by cryogenic double ion trap IR spectroscopy. We have found a significant hydration effect on the Na + VM conformations (not observed for K + VM), as a function of hydration number.…”