Microsolvation Structures of Protonated Glycine and L-Alanine - The

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Microsolvation Structures of Protonated Glycine and L-Alanine Kaitlyn C. Fischer, Summer L. Sherman, Jonathan M. Voss, Jia Zhou, and Etienne Garand J. Phys. Chem. A, Just Accepted Manuscript • Publication Date (Web): 25 Mar 2019 Downloaded from http://pubs.acs.org on March 25, 2019

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The Journal of Physical Chemistry

Microsolvation Structures of Protonated Glycine and L-Alanine

Kaitlyn C. Fischer, Summer L. Sherman, Jonathan M. Voss, Jia Zhou and Etienne Garand*

Department of Chemistry, University of Wisconsin-Madison, 1101 University Avenue, Madison, WI 53706, United States

*Author to whom correspondence should be addressed email: [email protected]

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Abstract The IR predissociation spectra of microsolvated glycine and L-alanine, GlyH+(H2O)n and AlaH+(H2O)n, n=1-6, are presented. The assignments of the solvation structures are aided by H2O/D2O substitution, IR-IR double resonance spectroscopy, and computational efforts. The analysis reveals the water-amino acid as well as the water-water interactions, and the subtle effects of the methyl side-chain in L-alanine on the solvation motif are also highlighted. The bare amino acids exhibit an intramolecular hydrogen bond between the protonated amine and carboxyl terminals. In the n = 1-2 clusters, the water molecules preferentially solvate the protonated amine group, and we observed differences in the relative isomer stabilities in the two amino acids due to electron donation from the methyl weakening the intramolecular hydrogen bond. The structures in the n = 3 clusters show a further preference for solvation of the carboxyl group in L-alanine. For n = 4-6 clusters, the solvation structure of the two amino acids is remarkably similar, with one dominate isomer present in each cluster size. The first solvation shell is completed at n = 4, evidenced by a lack of free NH and OH stretches on the amino acid, as well as the first observation of H2O-H2O interactions in the spectra of n = 5. Finally, we note that calculations at the DFT level show excellent agreement with the experiment for the smaller clusters. However, when water-water interactions compete with water-amino acid interactions in the larger clusters, DFT results show greater disagreement with experiment when compared to MP2 results.

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I.

Introduction Inter- and intramolecular hydrogen bonding (H-bonding) plays a crucial role in protein

structures in aqueous and physiological environments.1-2 At the larger scale, the multitude of such non-covalent interactions and their cooperative and competitive natures makes teasing out the details of the solvation interactions difficult. Gas phase size-selected clusters provide a systematic approach for disentangling such interactions as well as a clear comparison of how subtle structural differences can influence solvation-related interactions. In this work, we concentrate on the interactions between water molecules and the simplest amino acids: the protonated forms of glycine and L-alanine. Protonated L-alanine differs from protonated glycine in the side chain, where a methyl moiety replaces a hydrogen, giving rise to a chiral center. This substitution represents one of the smallest differences between two amino acids, and it is of interest to examine what effects, if any, such a subtle difference can have on the solvation structures. Previous studies on the structures of microsolvated clusters of protonated amino acids and small peptides have shown that initial solvation interactions predominantly go toward stabilizing the excess charge present in the ion. For example, it was found that the first three water molecules preferentially solvate the protonated amine for several amino acids, with the exception of proline which has the third water molecule in the second solvation shell.3-4 These experimental results are in general agreement with calculations,5-8 but computational results show larger disagreements for the larger clusters. Determining the experimentally observed solvation structures for these larger clusters, with water molecules in the second solvation shell, is a nontrivial task due to the presence of numerous possible energetically low-lying structures. Often, good agreement between calculation and experiment is needed for a conclusive 3 ACS Paragon Plus Environment


assignment, and a complete and systematic computational structural search becomes more timeconsuming and difficult with increasing structural complexity and flexibility as the H-bonding network grows.9 Infrared predissociation (IRPD) spectroscopy is a powerful tool for revealing the intricate details of non-covalent interactions, where well-resolved vibrational spectra of cold and massselected clusters can probe the local chemical environment around each individual oscillator.10-11 Additionally, the cryogenic environment minimizes contributions from multiple isomers, simplifying data analysis. However, even at low (< 50K) temperatures, inherent spectral congestion increases the difficulty of obtaining precise structural information from the IR spectrum. In an earlier letter, we illustrated the capabilities of a temperature-controlled ion trap in forming isotopically-labeled solvated clusters.12 Using the protonated glycine as an example, we showed that it is possible to form a cluster composed of an all-hydrogen GlyH+ surrounded by D2O, with minimal H/D exchange between the solvent molecules and the ion core. Comparison of the IRPD spectra from such H2O/D2O substitutions allows for experimental disentangling of the spectroscopic signatures of the solvent, e.g. H2O, from those of the solute, e.g. GlyH+. This new capability allows for quick rough assessments of solvation structures from the experimental spectra alone and significantly simplifies any computational structural searches by reducing the number of possible structures. In this paper, we present the experimental results, analyses and assignments of the IRPD spectra of GlyH+(H2O)n and AlaH+(H2O)n, n = 0-6, with the aid of H2O/D2O substitution, isomer-specific IR-IR double resonance,13-14 and computational efforts. The good agreements between calculation and experiment provide more conclusive assignments, which allow us to discuss the presence of various solvation isomers and their relative energies, as well as extract 4 ACS Paragon Plus Environment

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general observations that will hopefully facilitate future studies of larger solvated clusters and complex amino acids and peptides. II.

Experimental and computational details All IRPD spectra presented were obtained using our home-built dual cryogenic ion trap

vibrational spectrometer, which has been detailed previously.15 The GlyH+ ions were generated via electrospray ionization of a ~1 mM glycine solution in methanol with trace amounts of formic acid; the AlaH+ ions were generated from a similarly prepared solution of L-alanine. Hexapole ion guides transferred the ions through a series of differentially pumped regions into a linear octupole ion reaction trap, which was held at 80K by a liquid nitrogen cryostat. In this trap, the ions were thermalized by a ~1ms pulse of N2 buffer gas seeded with either H2O or D2O, leading to formation of [ion+](H2O)n or [ion+](D2O)n clusters. The solvated clusters were then transferred to a 3D quadrupole ion tagging trap held at 10K by a closed-cycle helium cryostat, where they were thermalized via collisions with He buffer gas seeded with 10% D2, allowing for D2-tagged adducts to form. The tagged adducts were ejected into a time-of-flight (TOF) mass spectrometer. For the smaller clusters with n ≤ 3, D2 adducts were mass-selected for IRPD experiments; for the larger (n = 4-6) clusters, few D2 adducts formed, and the solvated clusters themselves were mass-selected and either H2O or D2O was used as the messenger. After mass selection, the clusters were intersected with the output of a 10 Hz Nd:YAG pumped OPO/OPA laser (probe laser). The photofragments were separated from the parent clusters inside a twostage reflectron and the yield was monitored as a function of laser wavelength to produce the one-laser IRPD spectra. The IRPD spectra presented here were normalized to the most intense feature in each spectral region, i.e. 1400-2000 cm-1 region was normalized to the C=O stretch while 2400-3800 5 ACS Paragon Plus Environment


cm-1 region was normalized to the most intense OH or NH stretch. To overlay the IRPD spectra of the isotopologues, the D2O spectra were normalized to the H2O spectra to achieve optimal overlap in regions where the two spectra share common features. IR-IR double resonance spectra were obtained by focusing the output of a second Nd:YAG pumped tunable OPO/OPA laser (pump laser) into the 10K tagging trap. The laser was fired ~90ms after the buffer gas was introduced into the trap and 5ms before the ion extraction, such that the solvated clusters cannot re-tag after tag loss. To obtain an ion-burn spectrum, the pump laser was fixed at a frequency resonant with a vibration of the isomer to be removed, and the spectrum containing the vibrations of the remaining isomers was obtained by scanning the probe laser as described above. Analysis of the IRPD spectra was assisted by DFT and MP2 calculations carried out using the Gaussian 16 program.16 For DFT, we utilized the long-range corrected cam-B3LYP functional together with the def2TZVP basis set. This combination has previously provided good agreement with experimental results 14-15, 17-18while not being too computationally taxing for the larger clusters. In addition, we also carried out calculations including the GD3BJ empirical dispersion as well as accounted for basis-set superposition error (BSSE) by counterpoise correction. Optimized geometries and harmonic vibrational frequencies were computed at each DFT level. Optimized geometries were also obtained at the MP2/def2TZVP level for all clusters, and harmonic frequencies were calculated for select clusters. Energetic comparisons between isomers are carried out using unscaled ZPE corrected energies; MP2 energies are ZPE corrected using the cam-B3LYP/def2TZVP/GD3BJ/BSSE vibrations. Harmonic IR spectra are scaled by comparing the carboxyl group OH stretch in the 3500-3600 cm-1 region and C=O stretch around 1800 cm-1 to those in the experimental IRPD spectrum for the n = 0 and 1 clusters. This yielded a factor of 0.968 and 0.9542 for the lower and higher 6 ACS Paragon Plus Environment

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frequency ranges, respectively, for DFT, and 0.9857 and 0.9629 for MP2. Spectra are also Gaussian broadened with the Gaussian areas corresponding to the calculated intensities, and for strong H-bonded features, broader Gaussian widths are used to facilitate comparisons to experimental spectra. Isomer searches for the smaller clusters (n=1-4) were mostly done by chemical intuition. For the larger clusters, additional structure searches were carried out using the molecular mechanics basin hopping program developed by the Hopkins group at the University of Waterloo.19-23 The lowest energy structure of the n = 4 cluster was used as the starting structure within the basin hopping program, adding either one or two waters for n=5 and n=6, respectively. The rotational and translational coordinates of the 5th and 6th waters were iteratively stepped 10,000 times by a random value between ±5° and ±0.2Å, respectively. The resulting structure after each iteration was optimized using the AMBER force field. The output structures were then optimized at the BLYP/3-21g level, and all duplicate structures were rejected. All structures with energy

Microsolvation Structures of Protonated Glycine and L-Alanine - The

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