We would like to present a challenge of the gas phase ion spectroscopy to ion recognition mechanism in potassium ion channels. Our systematic studies have been reported (see references) and the relation between the ion permeability and conformation of Ac-Tyr-NHMe (a model for GYG peptide) which is a portion of the selectivity filter in the K+ channel have been revealed. In tis presentation, the permeability of silver ion for the potassium channel is discussed. Silver and silver ions have a long history antimicrobial activity and medical applications. Nevertheless, the activity of Ag+ against bacteria, how it enters a cell, has not yet been established. The K+ channel, a membrane protein, is a possible route. The addition of a channel inhibitor (4-aminopyridine) to modulate the Ag+ uptake could support this view. However, the inhibitor enhances the uptake of Ag+, the opposite result. We have applied cold ion trap infrared laser spectroscopy to complexes of Ag+ and Ac-Tyr-NHMe (a model for GYG peptide) which is a portion of the selectivity filter in the K+ channel to consider the question of permeation. With support from quantum chemical calculations, we have determined the stable conformations of the complex. The conformations strongly suggest that Ag+ would not readily permeate the K+ channel. The mechanism of the unexpected enhancement by the inhibitor is discussed. References 1) S. Tanabe et al., JPCL in press. 2) Y. Suzuki et al., Bull. Chem. Soc. Jpn. in press. 3) Y. Suzuki et al., PCCP, 24, 20803 (2022). 4) Y. Suzuki et al., JPCA, 125, 9609 (2021) (Front Cover). 5) T. Negoro et al.,, PCCP, 23, 12045 (2021) (Inside Back Cover) 6) R. Otsuka et al., ChemPhysChem, 21, 712 (2020) (Front Cover) 7) S. Ishiuch et al., PCCP, 21, 561 (2019) (Cover)

The feasibility of industrial scale electrocatalytic CO₂ reduction requires the development of catalysts that are both selective and efficient, making it imperative to understand the catalytic structure-function relationship to inform the design of improved catalysts. Nickel cyclam is a high-performing CO₂ reduction catalyst, and its derivatives have demonstrated differing catalytic abilities. Here, we present cryogenic gas-phase infrared spectra of a series of transition metal-cyclam derivative complexes of the form [M(II)·TEC]²⁺ (TEC = cyclam with four ethyl acetate substituents) and interpret spectral features using density functional theory calculations. The size and conformational flexibility of these complexes cause spectral congestion that complicates peak assignment. We address this challenge by utilizing the carbonyl stretching bands as spectroscopic reporters of molecular structure.

The symmetric O-H stretching band of the protonated water dimer is re-investigated at high spectral resolution applying the novel action spectroscopic technique leak-out spectroscopy (LOS) in the 22-pole ion trap experiment COLtrap operated at 4 K. Ro-vibrational transitions of Helium buffer gas cooled H₅O₂⁺ are excited using a narrow linewidth optical parametric oscillator prior to collisions with Neon as a second buffer gas. In doing so, part of the internal energy of the previously excited cation is transferred into kinetic energy (V-T-transfer) allowing it to surpass the electrostatic potential at the exit electrode of the 22-pole trap. The amount of cations exiting the trap time during the total trap time is monitored using a quadrupole mass-filter and a Daly-type ion detector. The resulting rotationally resolved spectrum is intrinsically background-free because the parent ground state ions are trapped without loss. The line intensities measured by LOS turn out to be closely related to the line intensities of conventional absorption spectroscopy. The new and extensive spectra are compared to previously presented high-resolution data obtained using a two-color-photodissociation scheme. Basically, the previously observed spectral complexity is confirmed by the novel action spectroscopic technique. The single-color leak-out spectra are more reliable in their actual line intensities as any impact on the dissociation efficiency originating from a variation of the optical overlap between two lasers experiments or power fluctuations are avoided. This improvement further simplifies the identification of Q-branches which can be nicely spotted in the high S/N spectra. Based on the multiplicity of these Q-branches and their separation, the tunneling motions at play for this molecular complex can be deciphered. Our findings challenge the current view on the struture and dynamics of the protonated water dimer.

It is widely believed that in the protonated water dimer the central proton is equally shared between the two water molecules (Zundel structure). This complex is subject to large amplitude motions and tunneling. It is an interesting question which motions are feasible and the answer to this question is tightly related to the underlying molecular symmetry group. For a semi-rigid complex the symmetry group is G₁₆⁽²⁾. But when all five protons can swap places the underlying group is G₂₄₀. For these two situations the nuclear spin statistical weights are different. In a trap experiment where a finite ensemble of cold and mass selected ions is stored, it is now possible to determine the fractions of nuclear spin species by kicking out all ions belonging to one nuclear spin configuration using leak-out spectoscopy (LOS). Results from these measurements are much more reliable than comparing line intensities, which is a traditional approach to determine those fractions. This is because the fractions are directly determined from the temporal evolution of the number of ions in the trap. In this contribution we will present results for such LOS depletion experiments for the protonated water dimer. From a detailed analysis of our findings we infer information on the mobility of the central proton of this fundamental complex.

The impact of electric fields on the structure and function of biomolecules is a well-known, yet not well understood phenomenon. One prominent example are enzymes, where electrostatic preorganization around the active site is thought to be vital for their catalytic function. [1] To shed light on the unique catalytic ability of enzymes, we need a better understanding of the impact of such (local) electric fields. This requires a systematic study of the interplay of the various non-covalent interactions present in biomolecular systems such as electrostatic interactions as well as inter- and intramolecular hydrogen bonding. Due to the structural complexity, however, this is difficult to obtain from studies of the condensed phase. A popular approach is therefore to prepare model complexes in the gas phase, where the individual contributions of different types of interactions can be studied in much greater detail.
In this contribution, we will study the solvation of diglycine complexes with three alkali metal ions (Li⁺, Na⁺, K⁺) with cryogenic ion vibrational spectroscopy scrutinising the interplay of the electrostatic metal ion-peptide and metal ion-water interaction with intra- and intermolecular hydrogen bonding. We observe interesting structural differences in the singly hydrated complexes, which can be related to the potassium selectivity of potassium ion channels. [2] In larger solvated clusters, the competition between intramolecular hydrogen bonding in the peptide backbone and intermolecular hydrogen bonding between water and the peptide increases in favour of the latter, leading to a change in peptide structure as the number of water molecules increases, whereas switching point occurs earlier for the Li⁺ compared to the Na⁺ and K⁺ complexes. Differences in internal hydrogen bond strength between the complexes of the three metal ions decrease in the larger solvated clusters, which is important to consider for comparisons between environments where partial solvation dominates versus the bulk phase.
References: [1] N. G. Léonard, R. Dhaoui, T. Chantarojsiri, J. Y. Yang, ACS Catal. 2021, 11, 10923-10932. [2] Y. Suzuki, K. Hirata, J. M. Lisy, S. Ishiuchi, M. Fujii, Phys. Chem. Chem. Phys. 2022, 24, 20803-20812.

Molecular recognition of ions is important in both the natural world within proteins and the synthetic world of supramolecular chemistry. Therefore, a deeper understanding of ion receptors and binding competitiveness in solution is desirable for the advancement of synthetic hosts for ionic guests. Octamethyl calix[4]pyrrole (omC4P), is a prototypical receptor for halide anions in aqueous solution chemistry. We present cryogenic gas-phase infrared spectra of a series of anion-omC4P complexes of the form [X$^{-}$·omC4P] (X$^{-}$ = fluoride, chloride, bromide), and assign spectral features using density functional theory calculations. The vibrational spectra encode the structures of and intermolecular forces in each complex, revealing the geometry of each complex and the binding motif of halide anions within the omC4P binding pocket. The position of the NH stretching modes depend on the identity of the anion, portraying a clear spectral response to changes in binding properties.

Octamethyl-calix[4]pyrrole (OMC4P) is a prototypical anion receptor, and it has been mainly used to bind halide ions, particularly fluoride and chloride. It is not a good receptor for polyatomic anions without chemical modifications. In the present work, we study the structures of complexes of OMC4P with nitrate and formate, using cryogenic ion vibrational spectroscopy with N₂ messenger tagging. We present the vibrational spectra of these species and obtain structural information by comparison of the experimental spectra with calculated spectra based on density functional theory.

Ionic interactions play a crucial role in ion transport and selectivity to maintain cellular ion homeostasis. For example, the channel is a membrane protein that regulates cation concentration on both sides of the cell membrane. Crystal structure of the Magnesium Transport E channel suggests a transport mechanism for ions involving the motion of hexa-hydrated cations recognized through water-mediated ionic interactions between the cation and the carboxylate groups of the channel interior.Takeda, H.; Hattori, M.; Nishizawa, T.; Yamashita, K.; Shah, S. ; Caffrey, M.; Maturana, A. D.; Ishitani, R.; Nureki, O. Nat. Commun. 2014, 5374.n order to characterize these water-mediated ionic interactions, we investigated clusters. We probed their structures from n = 4 to 17 by measuring cryogenic gas phase infrared spectra, further interpreted by high level quantum chemistry DFT-D calculations of vibrational frequencies. This comparison allowed us to investigate size-selected microhydrated ion pairs. In accordance with previous findings obtained on hydrated calciumDenton, J. K.; Kelleher, P. J.; Johnson, M. A.; Baer, M. D.; Kathmann, S. M.; Mundy, C. J.; Wellen, R. B. A.; Allen, H. C.; Choi, T. H.; Jordan, K. D. Proc. Natl. Acad. Sci. U.S.A. 2019, 116, 14874-14880.nd bariumDonon, J.; Bardaud, J.-X.; Brenner, V.; Ishiuchi, S.; Fujii, M.; Gloaguen, E. Phys. Chem. Chem. Phys. 2022, 24, 12121-12125.cetate clusters, hydration by 6 water molecules is insufficient to induce the ion separation. Nonetheless, partially-separated or separated ion pairs are formed from at least 10 water molecules, and more significantly with 14 water molecules. These results highlight the necessity of a second water-mediated ionic interaction for the transport of within the channel and possibly in cooperation with weaker secondary interactions, such as involving carbonyl groups, as suggested by the crystal structure.

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Footnotes:

Takeda, H.; Hattori, M.; Nishizawa, T.; Yamashita, K.; Shah, S. ; Caffrey, M.; Maturana, A. D.; Ishitani, R.; Nureki, O. Nat. Commun. 2014, 5374.I Denton, J. K.; Kelleher, P. J.; Johnson, M. A.; Baer, M. D.; Kathmann, S. M.; Mundy, C. J.; Wellen, R. B. A.; Allen, H. C.; Choi, T. H.; Jordan, K. D. Proc. Natl. Acad. Sci. U.S.A. 2019, 116, 14874-14880.a Donon, J.; Bardaud, J.-X.; Brenner, V.; Ishiuchi, S.; Fujii, M.; Gloaguen, E. Phys. Chem. Chem. Phys. 2022, 24, 12121-12125.a

We report fully rotationally resolved spectra of the I⁻(H₂O) and I⁻(HDO) ion-molecule complexes measured by predissociation spectroscopy in a 3D cryogenic ion trap. The spectra were obtained by excitation with a single-frequency, cw infrared laser (TOPAS by Toptica Corp.) directly into the trap. The formation of bare iodide photoproducts was observed by first ejecting the bare ion from the trap by excitation at the secular frequency, followed by formation of I⁻ photoproducts on the timescale of 40 ms. The product ions were then detected by injecting the contents of the trap into a time-of-flight mass spectrometer. The spectra reveal a plethora of very sharp transitions associated with overlapping rotational band structures arising from at least three vibrational transitions. Despite the fact that this excitation occurs about 300 cm⁻¹above the dissociation threshold, the lines are very narrow, revealing very long lived (ca. 2 ns) rovibrational levels. Analysis of these patterns quantifies the anharmonic behavior of this system arising from tunneling as well as intramolecular mode coupling involving soft modes and the bending overtone.

Cryptands are 3D molecular cages that initiated the field of supramolecular chemistry. They feature three ether bridges capped on either end by a tertiary amine, leading to a structure in which six oxygens and two nitrogens can bind to cations that fit inside the cage. We incorporate a phenyl ring in one of the ether bridges, forming [2.2.2]benzocryptand, in order to have an ultraviolet chromophore for our studies. Investigated complexes include benzocryptand with metal cations of potassium, barium and ion pair of barium-acetate. We will describe our results on the UV photofragment spectroscopy and IR-UV double resonance spectra that provide single-conformation IR spectra of the complexes under cryo-cooled conditions. In each case, there is a single dominant conformation of the complex. IR spectra in the alkyl CH stretch region are surprisingly sensitive to the ion in the cage, and to an anion binding to this caged cation.