Cation-Size Dependent Conformational Locking of Glutamic Acid by

Subscriber access provided by UNIVERSITY OF TOLEDO LIBRARIES

Article

Cation-Size Dependent Conformational Locking of Glutamic Acid by Alkali Ions: Infrared Photodissociation Spectroscopy of Cryogenic Ions Johanna Klyne, Aude Bouchet, Shun-ichi Ishiuchi, Masaaki Fujii, and Otto Dopfer J. Phys. Chem. B, Just Accepted Manuscript • DOI: 10.1021/acs.jpcb.7b12601 • Publication Date (Web): 02 Feb 2018 Downloaded from http://pubs.acs.org on February 5, 2018

Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. They are citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors or consequences arising from the use of information contained in these “Just Accepted” manuscripts.

The Journal of Physical Chemistry B is published by the American Chemical Society. 1155 Sixteenth Street N.W., Washington, DC 20036 Published by American Chemical Society. Copyright © American Chemical Society. However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties.

Page 1 of 27 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

The Journal of Physical Chemistry

Cation-Size Dependent Conformational Locking of Glutamic Acid by Alkali Ions: Infrared Photodissociation Spectroscopy of Cryogenic Ions Johanna Klynea, Aude Boucheta,b, Shun-ichi Ishiuchib, Masaaki Fujiib, Otto Dopfera* a) Institut für Optik und Atomare Physik, Technische Universität Berlin, Hardenbergstr. 36, 10623, Berlin, Germany. *E-mail: [email protected] b) Laboratory for Chemistry and Life Science, Institute of Innovation Research, Tokyo Institute of Technology, 4259, Nagatsuta-cho, Midori-ku, Yokohama, Japan.

Abstract Consolidated knowledge of conformation and stability of amino acids and their clusters is required to understand their biochemical recognition. Often, alkali ions interact with amino acids and proteins. Herein, infrared photodissociation (IRPD) spectra of cryogenic metalated glutamic acid ions (GluM+, M=Li-Cs) are systematically analyzed in the isomer-specific fingerprint and XH stretch ranges (1100-1900, 2600-3600 cm-1) to provide a direct measure for cation-size dependent conformational locking. GluM+ ions are generated by electrospray ionization and cooled down to 15 K in a cryogenic quadrupole ion trap. The assignment of the IRPD spectra is supported by density functional theory calculations at the dispersion-corrected B3LYP-D3/aug-cc-pVTZ level. In the global minimum of GluM+, the flexibility of Glu is strongly reduced by the formation of rigid ionic CO…M+…OC metal bridges, corresponding to charge solvation. The M+ binding energy decreases monotonically with increasing cation size from D0=314 to 119 kJ/mol for Li-Cs. Whereas for Li and Na only the global minimum of GluM+ is observed, for K-Cs at least three isomers exist at cryogenic temperature. The IRPD spectra of cold GluM+ ions are compared to IR multiple-photon dissociation (IRMPD) spectra measured at room temperature. Furthermore, we elucidate differences of the impact of protonation and metalation on the structure and conformational locking of Glu.

Revised version submitted to JPC B on 30 January 2018

1 ACS Paragon Plus Environment

The Journal of Physical Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Page 2 of 27

1. Introduction Solvation and metalation effectively influence the reactivity of biomolecules. For example, biochemical recognition of amino acids strongly relies on their charge and solvent dependent conformation. In the 19th century, the protein scientist Franz Hofmeister discovered and classified the effects of salts on the solubility of proteins in water.1 These consistent effects, documented in the Hofmeister series, are believed to depend on changes of the hydrophobic interaction of the protein, most likely by changing the structure of the protein rather than the structure of bulk water.2,3 However, the exact mechanism of the Hofmeister series is still not entirely clear.4–6 The study of isolated protein-ion complexes may shed light on structural changes upon addition of the salt.5,7 Alkali metals cations (Li+-Cs+), also members of the cationic Hofmeister series, are ubiquitous in living organisms because they belong to the most important ions that regulate life.6 For example, K+ and Na+ are required in the inter- and intracellular transport of neurotransmitters such as glutamate.8 L-glutamate, the anion of the natural proteinogenic α-amino acid L-glutamic acid (L-Glu, (S)-2-aminopentanedioic acid) is the principal excitatory neurotransmitter in the vertebrate central nervous system.9,10 A recent spectroscopic study of L-GluM+ showed a strong structure locking effect of Li+, which is relaxed for Cs+.11 However, the mechanism behind this obviously size-dependent structure-controlling effect of M+ is not further examined. Generally, for amino acids, metal binding and interaction strength strongly depend on the size, nature, and charge of the metal cation. For example, the rather small monovalent alkali metal ions Li+ and Na+ are trapped between the amino nitrogen and carbonyl oxygen atoms of canonical glycine.12,13 Yet, larger mono- and divalent metal cations such as K+, Cu2+, and Zn2+ bind to the deprotonated carboxylic group of its zwitterionic form.7,12–17 Herein, we systematically study GluM+ with M=Li-Cs to characterize the underlying intermolecular interaction potential, including binding site and interaction strength. Charged closed-shell protonated and metalated ions are easily accessible in the gas phase by electrospray ionization.11,18–23 Mass spectrometry combined with sophisticated spectroscopic techniques allows the exploration of the structure of the bare ions without any perturbing influence of solvent and counter ions. On the other hand, this approach also enables mimicking solvent effects like self-solvation of charges,24 production of zwitterionic species,25 and stepwise microhydration in a controlled fashion. Elaborate theoretical exploration of the conformational space of neutral Glu yields a total number of 385 isomers within ∆E~75 kJ/mol.26 Five conformers are detected by microwave spectroscopy in a supersonic jet, all exhibiting an intramolecular H-bond between the α-carboxyl group and the amino group via either NH...OC or N…HO interactions.27 Three of them benefit from additional stabilization by an intramolecular H-bond connecting the amino and γ-carboxyl groups. Like most small amino acids, Glu protonates at the amino nitrogen.11,20,26,28,29 The protonation thermochemistry of Glu is well documented.28–32 Protonation induces conformational locking of Glu via strong and cooperative HOCO…(HNH)+…OCOH ionic H-bonds between the protonated amino group and the adjacent carbonyl oxygen atoms, as evidenced by quantum chemical 2 ACS Paragon Plus Environment

Page 3 of 27 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


calculations and infrared multiple-photon dissociation (IRMPD) spectroscopy of room-temperature ions.11,26,33 Recently, based on the analysis of high-resolution IRPD spectra of cryogenic GluH+ ions recorded in the conformer-specific XH stretch range (2600-3600 cm-1) via H2-tagging, we could distinguish the two almost isoenergetic lowest-energy isomers 1-cc and 2-cc and estimate their relative abundance as approximately 2:1. This study emphasizes the importance of cryogenic cooling and single-photon absorption conditions for the identification of biomolecular conformation.33 Entirely different cation-size dependent interaction schemes are predicted for GluM+ (M=Li, Na, and K) by quantum chemical analysis.34 In GluLi+, the flexible alkyl chain is fully contracted with the Li+ cation trapped between both carbonyl oxygen atoms, supported by an additional electrostatic interaction of Li+ and the lone pair of the amino nitrogen. This compact structure was identified as the only gas-phase isomer of GluLi+ by IRMPD spectroscopy at room temperature.11 For M=Na and K, besides a congeneric structure, indeed a zwitterion is stabilized with M+ attached to the deprotonated α-carboxylic group.34 This computational prediction has not yet been proven experimentally. Nonetheless, the tendency for conformational relaxation with increasing cation size becomes evident in IRMPD spectra of GluCs+, which are attributed to two gas-phase isomers coexisting at room temperature.11 However, the process of successive weakening of the interaction in GluM+ for larger M+ is not yet documented. In general, the energetic order of the various predicted GluM+ isomers does not only depend on the M+ ion but also strongly on the theoretical level and on temperature.34 In addition, M+ binding enthalpies measured by mass spectrometric techniques for GluM+ with M=Li-Cs are not sensitive to structure.22,34–39 In contrast to mass spectrometry, IR spectroscopy is sensitive to the conformation of GluM+.34 To this end, herein we systematically probe the impact of metalation of Glu with monovalent cations of the whole series of alkali metals by IRPD spectroscopy of cryogenically cooled GluM+ ions (M=Li, Na, K, Rb, Cs) using H2-tagging. Cryogenic cooling and H2-tagging ensure single-photon absorption conditions, which were found to be important in these kinds of systems.33 Furthermore, the results are compared to IRMPD spectra of GluM+ measured at room temperature. Our experimental work is supported by a systematic computational exploration of the potential energy surface (PES). 2. Experimental and theoretical methods IRPD spectra of GluM+-H2 cluster ions (M=Li-Cs) are recorded in the XH stretch and fingerprint ranges (1100-1900, 2600-3600 cm-1) employing a recently commissioned cryogenic quadrupole ion trap (QIT) tandem mass spectrometer.33,40 L-GluM+ ions are generated in a standard continuous electrospray ionization (ESI) source using 10-4 M of L-Glu and MCl salt dissolved in methanol and water (10:1). Since the two enantiomers of Glu are energetically identical, only L-Glu (Sigma Aldrich, 99% purity) is used without further purification. The ESI-generated ions pass through a glass capillary heated to 60°C before entering vacuum. After a skimmer, GluM+ ions are sizeselected by a quadrupole mass filter, deflected by a quadrupole bender, and guided through an octopole to a gold-coated copper QIT mounted onto the cold head of a closed-cycle cryostat. The 3 ACS Paragon Plus Environment


Page 4 of 27

QIT held at 10 K is filled with He/H2 (80/20) buffer gas through a pulsed nozzle (pulse duration ~100 µs) to form cold GluM+-H2 clusters in the QIT. Recent analysis of the internal temperature of protonated tyrosine results in Tint≈13 K.40 IRPD spectra in the XH stretch range (2600-3600 cm-1) are recorded using the idler output of a pulsed tunable IR optical parametric oscillator (IR-OPO, Laservision) with a bandwidth of 1.7 cm-1 pumped by a nanosecond injection-seeded Nd:YAG laser operating at 10 Hz. To measure IR radiation in the fingerprint range (1100-1900 cm-1), the signal and idler outputs of the OPO are difference frequency mixed in an external AgGaSe2 crystal. Resonant vibrational excitation followed by fast internal vibrational energy redistribution induces dissociation of GluM+-H2. Predominantly, loss of weakly bound H2 is observed. However, in the XH stretch range, also M+ is observed as a fragment ion. The fragment ions are ejected into a linear time-of-flight mass spectrometer and sensed by a dynode converter detector. The fragment ion current is recorded by a fast digitizer as a function of the IR frequency to yield IRPD spectra. The measured spectra are plotted as fragmentation yield R=IF/(IP+IF), where IP and IF refer to the abundances of parent and fragment ions, respectively. IRPD spectra of all fragmentation channels are compared initially. All channels revealed essentially the same IR action spectrum. The binding energies of the metal cations are predicted to be >100 kJ/mol (>8000 cm-1). Hence, absorption of a single IR photon in the XH stretch range (νIR OαOγ-tc > OαNOγ-cc2 > OαOα-ZI > OαOγ-tt) benefit more than compact ones (OαNOγ-tc > OαNOγ-ct > OαNOγ-tt). The same trend observed for ∆E0 is also seen for ∆G. Hence, computationally, the conformational locking is strictly cation-size dependent: the smaller the metal ion, the stronger the bond, and the larger the locking effect. The global minimum structure of GluM+ is the same for all alkali metals, namely OαNOγ-cc1, and relevant structural, vibrational, and energetic properties are given in Table S2 in SI. The M+ ion is trapped between two carbonyl oxygen lone pairs forming a CO…M+…OC bridge, with an additional interaction with the lone pair of the amino nitrogen oriented toward M+. Such a metal chelate coordination is denoted tridendate charge solvation. Both carboxylic groups maintain cis conformation. Binding energies with respect to the most stable neutral Glu isomer (c2),26



Page 6 of 27

evaluated as D0=E0(GluM+ OαNOγ-cc1)–E0(Glu,c2)–E(M+), monotonically decrease from D0=314 (Li) to 119 (Cs) kJ/mol, while the averaged interatomic distances RCO-M (average of RαCO-M and RγCO-M) grow linearly with the inverse ionic radius (1/Rion), accounting for the decreasing Coulomb interaction (Figure 3). The strength of the CO…M+…OC bridge vastly depends on the cation size, and is strongest for Li (RαCO-Li=1.940 Å, RγCO-Li=1.862 Å) and weakest for Cs (RαCO-Cs=3.160 Å, RγCOCs=3.117 Å). Interestingly, the O…O distance between the two CO groups increases from 3.182 (Li) to 4.217 (Cs) Å, as a result of weaker attraction and stronger steric repulsion for the larger M+ ions. At the same time, the distance between the amino nitrogen and M+ increases from RN-M=2.073 (Li) to 3.667 (Cs) Å. Simultaneously, the C=O bonds are shortened, e.g. from rγ-CO=1.2223 (Li) to 1.2119 (Cs) Å, and converge toward the undisturbed bond of neutral Glu(c2) (rγ-CO=1.2056 Å). The successive shortening of rCO results in significant blue shifts of the corresponding carbonyl stretch vibrations (νCO), providing a direct link between intermolecular interaction strength in OαNOγ-cc1 and experimental IR spectra. The formation of the CO…M+…OC bridge results in coupling of the two νCO local modes, leading to symmetric and antisymmetric normal modes (νsCO, νasCO). As a result of the reduced electron transfer from the CO groups to M+ for the larger metals, both νCO modes shift to the blue from Li to Cs, whereby this size-dependent shift is more pronounced for the antisymmetric mode, νasCO=1704 (Li) - 1737 (Cs) cm-1 compared to νsCO=1726 (Li) - 1749 (Cs) cm-1. Similarly, in the XH stretch range, the free νOH modes of OαNOγ-cc1 show such cation-size dependence, arising from the slight elongation of the O-H bonds upon metalation. For GluLi+ and GluNa+, the strong CO…M+…OC bridge leads to coupling of ναOH and νγOH. Two almost degenerate ναOH/νγOH modes are predicted at 3516/3515 and 3527/3526 cm-1, respectively. For the larger metals K-Cs, they decouple and split into ναOH=3541 and νγOH=3534 cm-1 for GluCs+. The properties of the N-H bonds are hardly affected, because they only slightly interact with M+ (Table S2). Finally, the impact of M+ on the remote alkyl chain is also negligible. In addition to bond lengths and vibrational frequencies, the interaction strength in OαNOγ-cc1 is also reflected by the NBO charges. In GluLi+, 83% of the positive charge rests on Li+. Around half of the residual 17% is delocalized over α- and γ-carboxylic groups (q=46 and 41 me, respectively). The amino group (q=106 me) is only marginally less negative than in neutral Glu (q=-112 me for c2), illustrating its minor electrostatic interaction. For GluNa+, the intermolecular interaction is weaker, in line with a smaller charge transfer to Glu (8%). In GluK+ and GluRb+, about 99% of the positive charge is located on M+. Finally, in GluCs+ practically all positive charge remains on Cs+ (q=997 me). Still, Cs+ has a polarizing effect on Glu. Its γ-carboxylic group (q=-14 me) is somewhat more negative than in neutral Glu(c2) (q=2 me), and also its amino group is slightly more negative (q=-121 vs. -112 me). A second isomer of GluM+, OαNOγ-cc2, that differs from the global minimum only by its more extended alkyl chain (see distance between two carbon atoms of COOH groups in Figure 1), is also found to be rather stable in relative energy, particularly for M=K-Cs (∆E0=5.7, 5.1, 5.4 kJ/mol). The same trend of gradual interaction weakening from Li to Cs as found for OαNOγ-cc1, is observed also for OαNOγ-cc2 (Figure 2, Table S1 in SI). The CO…M+…OC bridge is of similar strength as in the global minimum, with RαCO-M=1.932-3.247 vs. 1.940-3.160 Å and RγCO-M=1.866-3.170 vs. 1.8623.117 Å (Table S2). The C=O bonds are slightly less affected than in the global minimum, rγ6 ACS Paragon Plus Environment

Page 7 of 27 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(Li) - 1.2118 (Cs) Å, in line with a comparable charge transfer from M+ to Glu. The comparable impact on the COOH groups is also reflected in their νCO and νOH frequencies. For GluLi+, νsCO and νasCO are predicted at 1724 and 1703 cm-1, only very slightly lower than for OαNOγcc1. For all M+ ions, νγOH and ναOH of OαNOγ-cc2 are decoupled and blue shifted compared to OαNOγ-cc1. This blue shift is furthermore cation-size dependent. For example, νγOH and ναOH are predicted at 3522 and 3513 cm-1 (Li) and 3541 and 3534 cm-1 (Cs), respectively. CO=1.2217

Figure 2 indicates that a third low-energy structure of GluM+ is relevant, namely OαOγ-tc (Figure 1, Table S2 in SI) which becomes more stable than OαNOγ-cc2 for M=K-Cs (∆E0=4.9, 3.9, 2.5 kJ/mol). OαOγ-tc is more extended (C-C distance of 4.04-4.32 Å, Figure 1), and the reduced steric strain may explain its enhanced gain in ∆E0 for larger ions compared to the rather rigid and compact OαNOγ-cc2. Its CO…M+…OC bridge is the strongest of all three isomers shown in Figure 1, with RαCO-M=1.804-3.041 Å and RγCO-M=1.837-3.190 Å, consistent with the largest charge transfer from M+ to Glu. Yet, it lacks any additional interaction of M+ with the NH2 group. In contrast, it benefits from an intramolecular OH…N H-bond between the NH2 group and the α-COOH group in trans configuration. This H-bond induces a strongly red shifted ναOH mode predicted at 3145 (Li) and 3224 (Cs) cm-1. On the other hand, its γ-COOH group is less affected than in OαNOγ-cc1/2. Hence, νγOH occurs somewhat higher at 3523 (Li) and 3541 (Cs) cm-1. The OH…N bond also influences the NH2 group. Its νas/sNH modes shift blue to 3436/3361 (Li) and 3435/3359 cm-1 (Cs), compared to 3373/3310 (Li) and 3383/3316 cm-1 (Cs) for OαNOγ-cc1. In the fingerprint range, OαOγ-tc is distinguishable by its decoupled and separated ναCO and νγCO modes predicted at 1757 and 1726 cm-1 for GluCs+. Finally, all three low-energy GluM+ in Figure 1 are readily distinguishable by their specific IR spectra in the XH stretch and fingerprint ranges (vide infra). 3.2 IRPD spectroscopy Figures 4 and 5 compare relevant parts of the IRPD spectra of GluM+ (M=Li-Cs) in the XH stretch and fingerprint ranges to the linear IR absorption spectra of the respective OαNOγ-cc1 global minima, respectively. Figure 5 contains also the IRMPD spectra (dotted lines). Full measured spectra and solid illustration of the IRMPD spectra are available in Figures S3 and S4 in SI. The positions and widths of the transitions observed in the IRPD spectra are compared in Tables 1 and 2 with calculated frequencies, along with the corresponding vibrational and isomer assignments. The corresponding data for the IRMPD spectra are available in Table S4 in SI. All prominent features of the IRPD spectra of GluLi+ and GluNa+ can fully be explained by the existence of only the OαNOγ-cc1 global minimum. The three major peaks in the XH stretch range (A-C at 3526, 3392, 3333 cm-1 for Li and 3542, 3382, 3327 cm-1 for Na) are readily assigned to να/γOH, νasNH, and νsNH, respectively, with a maximum deviation of 23 cm-1 from the calculated values. Similarly, all major peaks observed in the fingerprint range (G-L) are well reproduced by OαNOγ-cc1, with the largest deviation of 33 cm-1 for peak H (δNH). The most conformation-sensitive modes of OαNOγ-cc1, νs/asCO, occur as bands G1/G2 at 1738/1719 (Li+) and 1743/1719 cm-1 (Na+). 7 ACS Paragon Plus Environment


Page 8 of 27

Hence, we deduce a predominant production and detection of the OαNOγ-cc1 global minima of GluLi+ and GluNa+, although a minor population of higher energy isomers cannot fully be excluded. In any case, the population of such higher energy isomers is small (Na) or below the detection limit (Li) under the current experimental conditions. Obviously, in addition to the predicted blue shifts for νs/asCO of OαNOγ-cc1, the IRPD spectra of GluK+, GluRb+, and GluCs+ exhibit additional features in the νCO range (G1-G4), which cannot be rationalized only by OαNOγ-cc1. Even more striking indicators for the existence of additional isomers of GluM+ for M=K-Cs are the transitions M and N around 1400 cm-1. In this frequency range, the calculated spectra of OαNOγ-cc1 are rather flat, and most likely responsible for peaks I/J at 1450/1420 (Li) and 1451/1420 cm-1 (Na), but certainly not for bands M and N. Figure 4 reveals the same trend in the XH stretch range of GluM+ with M=K-Cs, namely the presence of additional bands D-F and splittings of band A, which are not related to the global minimum and missing (or very weak) for Li and Na. Indeed, the predicted blue shift of 28/26 cm-1 of να/γOH for the OαNOγ-cc1 isomers of Li-Cs is well expressed by the IRPD spectra. However, the να/γOH splitting of 3-4 cm-1 is not sufficient to produce the large spacing of bands A1-A3. Furthermore, H2-tagging is also not responsible for this splitting, because it induces far larger red shifts of νOH (>40 cm-1) when attached to one of the OH groups of OαNOγ-cc1 (Figure S6 in SI). Hence, we assign only the broader component A3 to the unresolved να/γOH doublet of OαNOγ-cc1. In line with above assignments for Li and Na, apart from band A3 only bands B/C at 3382/3321 (K), 3384/3324 (Rb), and 3395/3325 cm-1 (Cs) in the XH stretch range are attributed to OαNOγ-cc1 (νas/sNH). To disentangle the contribution of isomers other than the global minimum, Figure 6 compares the IRPD spectra of GluM+ (M=K-Cs) in the XH stretch range to the linear IR absorption spectra calculated for the three most stable GluM+ isomers OαNOγ-cc1, OαOγ tc, and OαNOγ-cc2 shown in Figure 1. The effect of H2-tagging is exemplary investigated for GluK+ (Figures S6 and S7 in SI). Relevant H2 binding motifs and H2 binding energies (D0) for the three considered isomers are given in Figure S8 in SI. For completeness, Figures S9-S11 in SI compare the IRPD spectra of GluM+ to the linear IR absorption spectra of all higher energy isomers found within a range of ∆E0≈10 kJ/mol. The isomer assignment is based on following considerations. We assume that predominantly the most stable isomers are produced in the employed ESI source. To reproduce the triplet A1-A3, at least OαNOγ-cc1 and OαNOγ-cc2 are necessary. These two isomers differ only by the folding of their alkyl chain. Hence, their coexistence seems plausible based on structure as well as on energy arguments, ∆E0=5.7 (K), 5.1 (Rb), and 5.4 (Cs) kJ/mol. However, both OαNOγ-cc1 and OαNOγ-cc2 cannot explain bands D-F, which can only be rationalized by the second most stable OαOγ-tc isomer, ∆E0=4.9 (K), 3.9 (Rb), 2.5 (Cs) kJ/mol. Still, the measured D1/D2 doublet at 3434/3424 (K) or D1-D3 triplets at 3435, 3428, and 3424 (Rb) and 3433, 3429, and 3423 (Cs) cm-1 are not explained by the calculations of the bare ions, and thus may tentatively be attributed to broadening and splittings arising from various binding sites of the H2 tag. Band E at 3364-3365 cm-1 is readily assigned to the symmetric NH stretch (νsNH) of OαOγ-tc. The broad feature F around 3100 cm-1 is attributed to the bound OH stretch vibration of the same isomer. Its red shift is significantly underestimated by the harmonic calculations, which predict νbOH at 3215, 3223, and 3224 cm-1 for 8 ACS Paragon Plus Environment

Page 9 of 27 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


K-Cs. Yet, the predicted IR cross sections of νbOH no longer seem too high compared to experiment, when considering the large width of F. To reassure the assignment of peak F to νbOH, anharmonic spectra of OαNOγ-cc1, OαOγ tc, and OαNOγ-cc2 are considered in Figure S5 in SI for GluM+ with M=K-Cs. Indeed, νbOH of OαNOγ-cc2 shifts to the red by almost 300 cm-1 down to 2965 (K), 2975 (Rb), and 2995 (Cs) cm-1 by anharmonic effects, and thus is in good agreement with the position of band F in the measured IRPD spectra. The shape of the IR spectra of OαNOγ-cc1 and OαNOγ-cc2 is almost unchanged by anharmonicity. Hence, our vibrational and isomer assignments given above are confirmed. Certainly, the growth of the relative intensities of bands D-F from GluK+ to GluCs+ indicates an increasing population of the OαOγ tc isomer, in line with the thermochemical data. Furthermore, the simultaneous growth of bands A1-A3 emphasizes that for larger alkali metals more isomers contribute to the IRPD spectrum. Thus, the conformational locking of GluM+ is relaxed with increasing size of M. Figure 7 compares the IRPD spectra of GluM+ (M=K-Cs) in the fingerprint range to the linear IR absorption spectra of OαNOγ-cc1, OαOγ-tc, and OαNOγ-cc2. Again, the effect of H2-tagging is exemplary investigated for GluK+ (Figure S7 in SI), and is found to be negligible in this spectral range. Figures S9-S11 in SI show the linear IR absorption spectra of all higher energy isomers calculated within a range of ∆E0≈10 kJ/mol. A superposition of the spectra of the three lowestenergy isomers OαNOγ-cc1, OαOγ-tc, OαNOγ-cc2 covers quite well the quartet G1-G4 at 1771, 1748, 1732, and 1719 cm-1 (K), at 1770, 1753, 1733, and 1718 cm-1 (Rb), and at 1769, 1754, 1733, and 1717 cm-1 (Cs), which cannot be described by a single isomer. The two newly emerging bands in the G1-G4 quartet (not present for Li+ and Na+) are assigned to ναCO and νγCO of OαOγ-tc, respectively. Furthermore, together with CH and OH bending modes (δCH, δOH) of OαNOγ-cc2, the rather intense bound OH bend (δαOH) of OαOγ-tc contributes most of the signal of band M around 1400 cm-1. The broadening and splittings of bands G and M are well modeled by the spectra of all three low-energy GluM+ isomers. In summary, the IRPD spectra of GluM+ reveal a gradual weakening of the conformational locking of Glu from M=Li-Cs. The shape of the PES of GluM+ changes notably at the size of K. For Li and Na, essentially only the OαNOγ-cc1 global minimum is populated at cryogenic temperature, while for KRb at least three isomers coexist with significant abundances. Although it is difficult to quantify the contribution of each of the three individual isomers to the IRPD spectra, it is obvious that the population of less stable local minima increases with alkali size. For example, when considering the relative intensities of the isolated bands B and D characteristic for OαNOγ-cc1 and OαOγ-tc, respectively, which have similar theoretical IR cross sections, then the population ratio of both isomers gets converted when going from Li to Cs. This trend is actually indicated by ∆E0 and predicted by the ∆G values. As a general trend, under the current experimental conditions, only isomers with ∆E0≤6 kJ/mol are needed to assign the observed IRPD spectra. Although several of the higher-energy isomers cannot be completely excluded, it is clear from the IRPD spectra that zwitterionic GluM+ isomers with O-…M+…O- salt bridges (e.g., OαOα-ZI) do not provide a significant contribution (see Figures S9-S11 in SI for K-Cs), in line with their higher B3LYP-D3 energies. This is 9 ACS Paragon Plus Environment


Page 10 of 27

in contrast to theoretical predictions at the MP2 level,34 which predict for several M sizes very low energies for zwitterionic ions. For example, the two most stable structures of GluNa+ are zwitterions at the MP2 level.34 This discrepancy emphasizes the importance of experimental spectra for the determination of the preferential GluM+ isomers. Finally, we note that the binding energies calculated for the OαNOγ-cc1 global minima of GluM+ with D0=314, 222, 155, 136, and 119 kJ/mol are consistent with available experimental bond enthalpies from mass spectrometry, ∆H=280±17 (Li),37 204±838 and 199±522 (Na), 152±7 (K),35 134±8 (Rb),36 and 113±7 kJ/mol (Cs),36 respectively, although the conformation of both GluM+ and Glu cannot be determined in these experiments. 3.3 Temperature effects Comparison of the IRPD spectra of cold tagged ions with IRMPD spectra of room-temperature GluM+ ions in Figure 5 (dotted lines, Figure S4 and Table S4 in SI) illustrates strong differences between linear and nonlinear IR spectroscopy, with respect to spectral resolution, sensitivity, and peak positions. First, the IRPD spectra display rich structure due to detection of narrow, resolved, weak transitions, while the IRMPD spectra only show the three most intense bands with much larger width (FWHM=25-60 cm-1). For example, the doublet (G1/G2) or quartet (G1-G4) structure of νCO is not at all resolved in the IRMPD spectra. Moreover, the IRPD spectra feature peaks (H, K, N), which are not present in the IRMPD spectra or significantly reduced in intensity (L, N for GluCs+). A general characteristics of IRMPD techniques is that fragmentation occurs only after a certain mode-dependent laser intensity threshold is reached.48 Last, the comparison in Figure 5 reveals mode-dependent blue shifts, e.g., band L of GluLi+ (+8 cm-1) and GluNa+ (+10 cm-1), as well as red shifts, e.g. band L of GluK+ (-6 cm-1). Hence, in terms of resolution, peak positions, and detection limit, clearly cryogenic cooling and single-photon absorption conditions (H2-tagging) are essential. These factors may have a notable influence on the isomer assignment. Due to the missing substructure of the most isomer-sensitive νCO modes, the IRMPD spectra of GluM+ (M=KCs) are readily described by only two isomers, namely OαNOγ-cc1 and OαOγ-tc, as done in a previous IRMPD study of GluM+ with M=Li and Cs.11 This different interpretation is not due to temperature effects, as the ∆G values reveal. In general, isomers move closer together in energy, when considering ∆G (298 K, Figure S2 and Table S1 in SI) instead of ∆E0 (0 K) (Figure 2, Table S1 in SI). Indeed, for GluM+ with M=Li-Rb, temperature has (almost) no impact on the energy hierarchy, which is only slightly altered for GluCs+. At room temperature, compact structures which are favored at 0 K become less stable than extended ones that benefit from entropy. Thus, OαOγ-tc of GluCs+ (∆G=-0.2 kJ/mol) becomes more stable than OαNOγ-cc1 (∆G=0) followed by OγOγ-ZI (∆G=1.8 kJ/mol) and OαNOγ-cc2 (∆G=4.4 kJ/mol). Thus, for GluCs+ we would expect to detect more isomers at room temperature than at cryogenic conditions. Unfortunately, the sensitivity and resolution of the IRMPD spectra are insufficient to provide a reliable test of this hypothesis.


Page 11 of 27 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


3.4 Comparison of protonation and metalation Recently, the same dual approach of IRPD spectroscopy and DFT calculations revealed the coexistence of two nearly isoenergetic conformers of GluH+ (1-cc and 2-cc, ∆E0=0.5 kJ/mol).33 Both isomers are protonated at the amino group with bridging CO…(HNH)+…OC ionic H-bonds. Hence, protonation and metalation comparably lock the conformational flexibility of Glu, thereby reducing the number of gas-phase conformers from 5 (Glu) to 2 (GluH+) and 1-3 (GluM+). However, the binding motifs of H+ and M+ are entirely different. While the small H+ binds covalently to the functional group of highest proton affinity (PA) - in Glu the NH2 group - the more bulky M+ is attached by noncovalent, mostly electrostatic forces to nucleophilic lone pairs of O and N atoms. Metalation of Glu leads to strong ionic CO…M+…OC metal bridges stabilized by electrostatic interaction. A corresponding CO…H+…OC proton bridge is highly unfavorable (∆E0≈70 kJ/mol) and thus has not been observed. For GluH+(1-cc), we calculate PA=-∆H=950.7 kJ/mol, in good agreement with literature values.28,29,31,32 In analogy, the metal cation affinity (MCA) of an amino acid (AA), is defined as the enthalpy change during the reaction AAM+ → AA + M+ by breaking the weakest noncovalent M+…AA bond(s). For OαNOγ-cc1 of GluM+, MCA=314, 219, 151, 132, and 114 kJ/mol for Li-Cs, decreasing monotonically with the size of M, and in good agreement with measured enthalpies of ∆H=280±17, 199±5, 152±7, 134±8, and 113±7 kJ/mol,37 respectively. These values compare also well with typical MCA of related AA, like the Li+ affinity of Gly or the Cu+ affinity of Glu measured and calculated as MCA=163-213 and 297 kJ/mol, respectively.49,50 4. Conclusions The gas-phase conformations of GluM+ (M=Li-Cs) are determined by the combination of IR(M)PD spectroscopy and DFT calculations at the B3LYP-D3/aug-cc-pVTZ level. The alkali metal cations are attached to the lone pairs of the carbonyl oxygen atoms in form of strong CO…M+…OC ionic bridges via mostly electrostatic interaction. All intermolecular bond parameters reveal a clear 1/Rion dependence. The global minimum OαNOγ-cc1 is predominant for all alkali metals. The intermolecular interaction is significantly weakened from GluLi+ (D0=314 kJ/mol) to GluCs+ (D0=119 kJ/mol), resulting in the successive relaxation of the rigidity of GluM+ with increasing cation size. In fact, for GluM+ with the larger alkali cations M=K-Cs, (at least) two additional isomers OαOγ-tc and OαNOγ-cc2 are required to explain their IRPD spectra. This result corresponds to an energy cutoff of approximately ∆E0=6 kJ/mol for the significant population of the various isomers under the current experimental conditions. Hence, in addition to previous results from an IRMPD study of GluM+ (M=Li, Cs), we provide herein a systematic quantitative analysis of the cation-size dependence of the PES of GluM+, that changes drastically at the size of K+. Furthermore, our study reveals large differences between IRPD spectra of cold GluM+ ions (M=Li-Cs) and IRMPD spectra of room-temperature ions, which are not related to temperature but rather to multiple-photon effects in IRMPD. This comparison emphasizes the crucial importance of cryogenic cooling and messenger-tagging to reliable determine the various conformations of noncovalent and flexible ions like GluM+. Protonation and metalation induce similar locking effects on the conformation of



Page 12 of 27

Glu. Yet, the conformations of GluH+ and GluM+ are entirely different. Protonation occurs at the amino group, leading to two coexisting GluH+ isomers with bridging CO…(HNH)+…OC ionic H-bonds. In contrast, metalation generates rigid CO…M+…OC bridges in GluM+. Finally, we shed light on the strong size-dependence of the structure making effect of alkali cations on a natural amino acid, hence on the local peptide structure, which may be one of the driving forces behind the cationic Hofmeister series. Like all amino acids (except glycine), Glu is chiral. Interestingly, in the mammalian amino acid metabolism only L-enantiomers are biologically active. The discrimination of the two enantiomers L-Glu and D-Glu relies on chirality recognition. This recognition process is currently investigated in protonated homochiral (LL) and heterochiral (LD) Glu2H+ dimers via the dual approach of IRPD spectroscopy and replica exchange molecular dynamics simulation.51 Supporting Information (1) IRMPD spectra of GluM+; (2) calculated structures, energies, IR spectra of GluM+ and GluK+-H2 isomers; (3) ionic radii of M+. This information is available free of charge via the Internet at http://pubs.acs.org. Acknowledgements This study was supported by Deutsche Forschungsgemeinschaft (DO 729/3-3). The research leading to part of these results has received funding from the European Union’s Seventh Framework Program (FP7/2012-2015) under grant agreement no. 312284 (CLIO project IC 14-019). We thank J.-M. Ortega and the CLIO team for valuable support. A.B. acknowledges the People Program (Marie Curie Actions) of the European Union’s Seventh Framework Program (FP7/20072013) for the funding of an IPODI fellowship under the REA grant agreement no. 600209 (TU Berlin/IPODI), and the Japan Society for the Promotion of Science for the funding of a Postdoctoral Fellowship for Overseas Researchers (grant no. P16035). J.K. is grateful for fellowships of the Elsa Neumann Stiftung and the Studienstiftung des deutschen Volkes. O.D. acknowledges travel support for collaboration from the World Research Hub Initiative (WRHI) of Tokyo Institute of Technology. The work at Tokyo Institute of Technology is supported by a Grant-in-Aid for Scientific Research KAKENHI on Innovative Area (2503) ‘‘Studying the Function of Soft Molecular Systems by the Concerted Use of Theory and Experiment’’, KAKENHI in the priority area ‘‘Molecular Science for Supra Functional Systems’’, a Grant-in-Aid for Young Scientists KAKENHI, the Cooperative Research Program of ‘‘Network Joint Research Center for Materials and Devices’’, from the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan, and the Core-toCore Program 22003 from the Japan Society for the Promotion of Science (JSPS).


Page 13 of 27 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Figure Captions Figure 1. Three relevant isomers of GluM+ along with relative energies (∆E0 in kJ/mol) ordered by cation size (Li, Na, K, Rb, Cs) and lengths of CO…M+ bonds (dotted lines, R in Å for Li-Cs) and distance between two carbon atoms of COOH groups (arrows, R in Å for Li-Cs) calculated at the B3LYP-D3/aug-cc-pVTZ level (Table S2 in SI). Figure 2. Energy hierarchy (∆E0) of GluM+ isomers (M=Li-Cs) obtained at the B3LYP-D3/aug-cc-pVTZ level (Table S1 in SI). The most stable isomer is OαNOγ -cc1 (∆E0=0). Figure 3. Binding energies (D0 in kJ/mol) and intermolecular distances (RCO-M+ in pm) of the GluM+ isomer OαNOγ-cc1 (M=Li-Cs) as a function of the inverse ionic radius (1/Rion in 1/Å, Table S3 in SI) obtained at the B3LYP-D3/aug-cc-pVTZ level. Figure 4. IRPD spectra of GluM+ (M=Li-Cs) in the XH stretch range (3000-3600 cm-1) obtained by H2-tagging compared to linear IR absorption spectra of the OαNOγ-cc1 global minima of GluM+ calculated at the B3LYPD3/aug-cc-pVTZ level (Table 1).

Figure 5. IRPD spectra of GluM+ (M=Li-Cs) in the fingerprint range (1100-1800 cm-1) obtained by H2-tagging compared to the linear IR absorption spectra of the OαNOγ-cc1 global minima calculated at the B3LYPD3/aug-cc-pVTZ level (Table 2). For comparison, IRMPD spectra of GluM+ are plotted as dotted lines (Table S4 in SI).

Figure 6. IRPD spectra of GluM+ (M=K-Cs) in the XH stretch range (3000-3600 cm-1) obtained by H2-tagging compared to linear IR absorption spectra of the three most stable GluM+ isomers OαNOγ-cc1, OαOγ -tc, and OαNOγ-cc2 calculated at the B3LYP-D3/aug-cc-pVTZ level (Table 1).

Figure 7. IRPD spectra of GluM+ (M=K, Rb, Cs) in the fingerprint range (1100-1800 cm-1) obtained by H2tagging compared to linear IR absorption spectra of the three most stable GluM+ isomers OαNOγ-cc1, OαOγtc, and OαNOγ-cc2 calculated at the B3LYP-D3/aug-cc-pVTZ level (Table 2).



Page 14 of 27

Table 1. Positions, widths, and assignments of major bands in the IRPD spectra of GluM+ with M=Li-Cs in the XH stretch range obtained with H2-tagging (Figures 4 and 6) compared to frequencies calculated at the B3LYP-D3/aug-cc-pVTZ level.

complex GluLi+

GluNa+

GluK+

GluRb+

GluCs+

experimentala A 3526 (12)

calculatedb 3516 (108) / 3515 (170)

isomer OαNOγ-cc1

assignment ναOH+νγOH

B 3392 (5) C 3333 (7) A 3542 (15) B 3382 (5) C 3327 (5) A1 3570 (10) A2 3562 (10) A3 3548 (12)

3373 (18) 3310 (16) 3527 (72) / 3526 (182) 3369 (13) 3308 (8) 3537 (105) 3526 (124) 3539 (94) / 3535 (132) 3538 (105)

OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc2 OαNOγ-cc2 OαNOγ-cc1 OαOγ-tc

νasNH νsNH ναOH+νγOH νasNH νsNH νγOH ναOH γ ν OH / ναOH νγOH

3434 (25) 3376 (10) 3359 (9) 3312 (5) 3215 (296) 3540 (99) 3529 (120) 3542 (88) / 3539 (129) 3540 (100)

OαOγ-tc OαNOγ-cc1 OαOγ-tc OαNOγ-cc1 OαOγ-tc OαNOγ-cc2 OαNOγ-cc2 OαNOγ-cc1 OαOγ-tc

νasNH νasNH νsNH νsNH ναOH νγOH ναOH νγOH / ναOH νγOH

3434 (25)

OαOγ-tc

νasNH

3379 (9) 3359 (8) 3314 (4) 3223 (293) 3541 (92) 3534 (117) 3544 (85) / 3541 (123) 3541 (96)

OαNOγ-cc1 OαOγ-tc OαNOγ-cc1 OαOγ-tc OαNOγ-cc2 OαNOγ-cc2 OαNOγ-cc1 OαOγ-tc

νasNH νsNH νsNH ναOH νγOH ναOH νγOH / ναOH νγOH

3435 (24)

OαOγ-tc

νasNH

3383 (9) 3359 (7) 3316 (4) 3224 (294)

OαNOγ-cc1 OαOγ-tc OαNOγ-cc1 OαOγ-tc

νasNH νsNH νsNH ναOH

D1 3434 (5) D2 3424 (10) B 3382 (5) E 3365 (20) C 3321 (20) F 3100 (30) A1 3571 (12) A2 3564 (10) A3 3551 (15) D1 3435 (5) D2 3428 (5) D3 3424 (5) B 3384 (5) E 3364 (20) C 3324 (20) F 3100 (30) A1 3575 (12) A2 3566 (10) A3 3551 (15) D1 3433 (5) D2 3429 (5) D3 3423 (5) B 3395 (5) E 3365 (20) C 3325 (20) F 3100 (30)

a b

Widths of the transitions (FWHM, cm-1) are listed in parentheses. IR intensities (km/mol) are listed in parentheses. The scaling factor is 0.95.


Page 15 of 27 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


Table 2. Positions, widths, and assignments of major bands in the IRPD spectra of GluM+ with M=Li-Cs in the fingerprint range obtained with H2-tagging (Figures 5 and 7) compared to frequencies calculated at the B3LYP-D3/aug-cc-pVTZ level. Complex GluLi+

GluNa+

GluK+

experimentala G1 1738 (5) G2 1719 (10) H 1600 (8) I 1450 (8) J 1420 (5) K 1205 (5) L 1165 (5) G1 1743 (5) G2 1719 (12) H 1602 (8) I 1451 (8) J 1420 (5) L 1162 (8) G1 1771 (15) G2 1748 (20) G3 1732 (10) G4 1719 (8) H 1595 (8)

I 1440 (8) M1 1412 (10) M2 1393 (15) M3 1379 (15) N 1357 (10) L 1156 (10) GluRb+

G1 1770 (15) G2 1753 (20)

G3 1733 (10) G4 1718 (8)

GluCs+

M1 1419 (10) M2 1414 (10) M3 1400 (10) M4 1389 (10) M5 1380 (15) N 1356 (10) L 1156 (10) G1 1769 (15) G2 1754 (20) G3 1733 (10) G4 1717 (8) M1 1411 (10) M2 1399 (15) M3 / M4 1386 (10) / 1382 (10) N 1354 (10) L 1152 (10)

a b

calculatedb 1726 (500) 1704 (166) 1632 (60) 1462 (12) 1422 (74) 1211 (68) 1170 (121) / 1167 (197) 1735 (579) 1718 (73) 1635 (52) 1465 (15) 1412 (38) / 1390 (42) 1164 (202) / 1154 (79) 1751 (516) 1743 (631) 1741 (516) 1717 (207) 1730 (33) 1729 (120) 1633 (49) 1627 (33) 1643 (49) 1449 (17) 1429 (28) 1426 (28) 1410 (59) / 1401 (37) 1397 (483) 1346 (22) 1160 (219) / 1148 (48) 1142 (347) 1754 (517) 1746 (647) 1746 (520) 1722 (208) 1734 (27) 1734 (119) 1429 (25) 1425 (27) 1409 (48) 1398 (46) 1392 (470) 1346 (24) 1159 (204) / 1146 (66) 1757 (525) 1749 (656) 1749 (538) 1726 (212) 1737 (31) 1738 (111) 1431 (23) 1429 (27) 1408 (42) 1399 (43) 1391 (471) 1347 (25) 1158 (195) / 1142 (79)

isomer OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc1 OαNOγ-cc1 OαOγ-tc OαNOγ-cc1 OαNOγ-cc2 OαOγ-tc OαNOγ-cc1 OαNOγ-cc2 OαNOγ-cc1 OαOγ-tc OαNOγ-cc2 OαNOγ-cc1 OαNOγ-cc2 OαOγ-tc OαNOγ-cc2 OαOγ-tc 2 OαOγ-tc 2 OαNOγ-cc1 OαNOγ-cc 3 OαOγ-tc OαNOγ-cc1 OαNOγ-cc2 OαOγ-tc OαNOγ-cc1 OαNOγ-cc2 OαNOγ-cc2 OαOγ-tc OαNOγ-cc2 OαNOγ-cc2 OαOγ-tc OαOγ-tc OαNOγ-cc1 OαOγ-tc OαNOγ-cc1 OαNOγ-cc2 OαOγ-tc OαNOγ-cc1 OαNOγ-cc2 OαNOγ-cc2 OαOγ-tc OαNOγ-cc2 OαNOγ-cc2 OαOγ-tc OαOγ-tc OαNOγ-cc1

assignment νsCO νasCO δNH δCH δαOH + δCH δγOH + δCH δαOH / δγOH νsCO νasCO δNH δCH α δ OH + δCH / δγOH + δCH δαOH / δγOH ναCO νsCO νsCO νγCO νasCO νasCO δNH δNH δNH δCH δCH δCH δαOH + δCH / δγOH + δCH δαOH δCH δαOH / δγOH δαOH + δγOH ναCO νsCO νsCO νγCO νasCO νasCO δCH δCH δαOH + δCH δγOH + δCH δαOH δCH δαOH / δγOH ναCO νsCO νsCO νγCO νasCO νasCO δCH δCH δαOH + δCH δγOH + δCH δαOH δCH δαOH / δγOH

Widths of the transitions (FWHM, cm-1) are listed in parentheses. IR intensities (km/mol) are listed in parentheses. The scaling factor is 0.98.



Page 16 of 27

References (1) Hofmeister, F. Zur Lehre von der Wirkung der Salze. Zweite Mittheilung. Arch. Exp. Pathol. Pharmakol. 1888, 25, 248–260. (2) Kunz, W. Specific ion effects in colloidal and biological systems. Curr. Opin. Colloid & Interface Science 2010, 15, 34–39. (3) Omta, A. W.; Kropman, M. F.; Woutersen, S.; Bakker, H. J. Negligible Effect of Ions on the Hydrogen-Bond Structure in Liquid Water. Science 2003, 301, 347. (4) Jungwirth, P.; Cremer, P. S. Beyond Hofmeister. Nat. Chem. 2014, 6, 261 EP -. (5) Crevenna, A. H.; Naredi-Rainer, N.; Lamb, D. C.; Wedlich-Söldner, R.; Dzubiella, J. Effects of Hofmeister Ions on the α-Helical Structure of Proteins. Biophys. J. 2012, 102, 907–915. (6) Lo Nostro, P.; Ninham, B. W. Hofmeister Phenomena: An Update on Ion Specificity in Biology. Chem. Rev. 2012, 112, 2286–2322. (7) Baldauf, C.; Pagel, K.; Warnke, S.; Helden, G. von; Koksch, B.; Blum, V.; Scheffler, M. How Cations Change Peptide Structure. Chem. Eur. J. 2013, 19, 11224–11234. (8) Platt, S. R. The role of glutamate in central nervous system health and disease – A review. Vet. J. 2007, 173, 278–286. (9) Tapiero, H.; Mathé, G.; Couvreur, P.; Tew, K. II. Glutamine and glutamate. Biomed. Pharmacot. 2002, 56, 446–457. (10) Riedel, G.; Platt, B.; Micheau, J. Glutamate receptor function in learning and memory. Behav. Brain Res. 2003, 140, 1–47. (11) O’Brien, J. T.; Prell, J. S.; Steill, J. D.; Oomens, J.; Williams, E. R. Interactions of Mono- and Divalent Metal Ions with Aspartic and Glutamic Acid Investigated with IR Photodissociation Spectroscopy and Theory. J. Phys. Chem. A 2008, 112, 10823–10830. (12) Bertrán, J.; Rodríguez-Santiago, L.; Sodupe, M. The Different Nature of Bonding in Cu+-Glycine and Cu2+-Glycine. J. Phys. Chem. B 1999, 103, 2310–2317. (13) Moision, R. M.; Armentrout, P. B. Experimental and Theoretical Dissection of Sodium Cation/Glycine Interactions. J. Phys. Chem. A 2002, 106, 10350–10362. (14) Ropo, M.; Schneider, M.; Baldauf, C.; Blum, V. First-principles data set of 45,892 isolated and cation-coordinated conformers of 20 proteinogenic amino acids. Scientific Data 2016, 3, 160009 EP -.


Page 17 of 27 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(15) Ropo, M.; Blum, V.; Baldauf, C. Trends for isolated amino acids and dipeptides: Conformation, divalent ion binding, and remarkable similarity of binding to calcium and lead. Scientific Reports 2016, 6, 35772. (16) Remko, M.; Fitz, D.; Rode, B. M. Effect of metal ions (Li+, Na+, K+, Mg2+, Ca2+, Ni2+, Cu2+ and Zn2+) and water coordination on the structure and properties of L-histidine and zwitterionic Lhistidine. Amino Acids 2010, 39, 1309–1319. (17) Moision, R. M.; Armentrout, P. B. An experimental and theoretical dissection of potassium cation/glycine interactions. Phys. Chem. Chem. Phys. 2004, 6, 2588–2599. (18) Wu, R.; McMahon, T. B. Infrared Multiple Photon Dissociation Spectra of Proline and Glycine Proton-Bound Homodimers. Evidence for Zwitterionic Structure. J. Am. Chem. Soc. 2007, 129, 4864–4865. (19) Wu, R.; McMahon, T. B. Protonation Sites and Conformations of Peptides of Glycine (Gly1−5H+) by IRMPD Spectroscopy. J. Phys. Chem. B 2009, 113, 8767–8775. (20) Wu, R.; McMahon, T. B. An Investigation of Protonation Sites and Conformations of Protonated Amino Acids by IRMPD Spectroscopy. ChemPhysChem 2008, 9, 2826–2835. (21) Atkins, C.; Rajabi, K.; Gillis, E.; Fridgen, T. Infrared Multiple Photon Dissociation Spectra of Proton-and Sodium Ion-Bound Glycine Dimers in the N-H and O-H Stretching Region. J. Phys. Chem. A 2008, 112, 10220–10225. (22) Heaton, A. L.; Moision, R. M.; Armentrout, P. B. Experimental and Theoretical Studies of Sodium Cation Interactions with the Acidic Amino Acids and Their Amide Derivatives. J. Phys. Chem. A 2008, 112, 3319–3327. (23) Veenstra, T. D. Electrospray ionization mass spectrometry in the study of biomolecular noncovalent interactions. Biophys. Chem. 1999, 79, 63–79. (24) Schnier, P. D.; Price, W. D.; Jockusch, R. A.; Williams, E. R. Blackbody Infrared Radiative Dissociation of Bradykinin and Its Analogues: Energetics, Dynamics, and Evidence for Salt-Bridge Structures in the Gas Phase. J. Am. Chem. Soc. 1996, 118, 7178–7189. (25) Forbes, M. W.; Bush, M. F.; Polfer, N. C.; Oomens, J.; Dunbar, R. C.; Williams, E. R.; Jockusch, R. A. Infrared Spectroscopy of Arginine Cation Complexes: Direct Observation of Gas-Phase Zwitterions. J. Phys. Chem. A 2007, 111, 11759–11770. (26) Meng, L.; Lin, Z. Comprehensive computational study of gas-phase conformations of neutral, protonated and deprotonated glutamic acids. Comput. Theor. Chem. 2011, 976, 42–50. (27) Peña, I.; Sanz, M.; López, J.; Alonso, J. Preferred Conformers of Proteinogenic Glutamic Acid. J. Am. Chem. Soc. 2011, 134, 2305–2312. 17 ACS Paragon Plus Environment


Page 18 of 27

(28) Harrison, A. G. The gas-phase basicities and proton affinities of amino acids and peptides. Mass Spectrom. Rev. 1997, 16, 201–217. (29) Bouchoux, G.; Bimbong, R. N. B.; Nacer, F. Gas-Phase Protonation Thermochemistry of Glutamic Acid. J. Phys. Chem. A 2009, 113, 6666–6676. (30) Bouchoux, G. Gas phase basicities of polyfunctional molecules. Part 3: Amino acids. Mass Spectrom. Rev. 2012, 31, 391–435. (31) Bleiholder, C.; Suhai, S.; Paizs, B. Revising the Proton Affinity Scale of the Naturally Occurring α-Amino Acids. J. Am. Soc. Mass Spectrom. 2006, 17, 1275–1281. (32) Sun, W.; Kinsel, G. R.; Marynick, D. S. Computational Estimates of the Gas-Phase Basicity and Proton Affinity of Glutamic Acid. J. Phys. Chem. A 1999, 103, 4113–4117. (33) Bouchet, A.; Klyne, J.; Ishiuchi, S.-i.; Fujii, M.; Dopfer, O. Conformation of protonated glutamic acid at room and cryogenic temperatures. Phys. Chem. Chem. Phys. 2017, 19, 10767–10776. (34) Meng, L.; Lin, Z. Complexations of alkali/alkaline earth metal cations with gaseous glutamic acid. Comput. Theor. Chem. 2014, 1039, 1–10. (35) Heaton, A. L.; Armentrout, P. B. Experimental and Theoretical Studies of Potassium Cation Interactions with the Acidic Amino Acids and Their Amide Derivatives. J. Phys. Chem. B 2008, 112, 12056–12065. (36) Armentrout, P. B.; Yang, B.; Rodgers, M. T. Metal Cation Dependence of Interactions with Amino Acids: Bond Dissociation Energies of Rb+ and Cs+ to the Acidic Amino Acids and Their Amide Derivatives. J. Phys. Chem. B 2014, 118, 4300–4314. (37) Rodgers, M. T.; Armentrout, P. B. Cationic Noncovalent Interactions: Energetics and Periodic Trends. Chem. Rev. 2016, 116, 5642–5687. (38) Kish, M. M.; Ohanessian, G.; Wesdemiotis, C. The Na+ affinities of α-amino acids: side-chain substituent effects. Int. J. Mass Spectrom. 2003, 227, 509–524. (39) N. Andersen, U.; Bojesen, G. The order of lithium ion affinities for the 20 common α-amino acids. Calculation of energy-well depth of ion-bound dimers. J. Chem. Soc., Perkin Trans. 2 1997, 323–328. (40) Ishiuchi, S.-i.; Wako, H.; Kato, D.; Fujii, M. High-cooling-efficiency cryogenic quadrupole ion trap and UV-UV hole burning spectroscopy of protonated tyrosine. J. Mol. Spectrosc. 2017, 332, 45–51. (41) Maı ̂tre, P.; Le Caër, S.; Simon, A.; Jones, W.; Lemaire, J.; Mestdagh, H.; Heninger, M.; Mauclaire, G.; Boissel, P.; Prazeres, R. Ultrasensitive spectroscopy of ionic reactive intermediates


Page 19 of 27 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


in the gas phase performed with the first coupling of an IR FEL with an FTICR-MS. Proceedings of the 24th International Free Electron Laser Conference and the 9th Users Workshop 2003, 507, 541– 546. (42) Lemaire, J.; Boissel, P.; Heninger, M.; Mauclaire, G.; Bellec, G.; Mestdagh, H.; Simon, A.; Le Caer, S.; Ortega, J. M.; Glotin, F. et al. Gas Phase Infrared Spectroscopy of Selectively Prepared Ions. Phys. Rev. Lett. 2002, 89, 273002. (43) M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, et al. Gaussian 09, Revis. D.01; Gaussian, Inc.: Wallingford CT, 2009. (44) Roy, L. E.; Hay, P. J.; Martin, R. L. Revised Basis Sets for the LANL Effective Core Potentials. J. Chem. Theory Comput. 2008, 4, 1029–1031. (45) Reed, A. E.; Weinstock, R. B.; Weinhold, F. Natural population analysis. J. Chem. Phys. 1985, 83, 735–746. (46) Reed, A. E.; Curtiss, L. A.; Weinhold, F. Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint. Chem. Rev. 1988, 88, 899–926. (47) E. D. Glendening, A. E. Reed, J. E. Carpenter, and F. Weinhold. NBO Version 3.1. (48) Parneix, P.; Basire, M.; Calvo, F. Accurate Modeling of Infrared Multiple Photon Dissociation Spectra: The Dynamical Role of Anharmonicities. J. Phys. Chem. A 2013, 117, 3954–3959. (49) Marino, T.; Russo, N.; Toscano, M. Gas-phase metal ion (Li+, Na+, Cu+) affinities of glycine and alanine. J. Inorg. Biochem. 2000, 79, 179–185. (50) BA, C.; C, W. The Relative Copper(I) Ion Affinities of Amino-Acids in the Gas-Phase. J. Am. Chem. Soc. 1995, 117, 9734–9739. (51) Sugita, Y.; Okamoto, Y. Replica-exchange molecular dynamics method for protein folding. Chem. Phys. Lett. 1999, 314, 141–151.



3.71 - 3.93 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46

Page 20 of 27

4.10 - 4.57

1.87 - 3.17

1.94 - 3.16

1.86 - 3.12

1.93 - 3.25

4.04 - 4.32

OαNOγ-cc1

OαNOγ-cc2

ΔE0 = 0, 0, 0, 0, 0

13.5, 8.0, 5.7, 5.1, 5.4

1.80 - 3.04

1.84 - 3.19

OαOγ-tc

ACS Paragon Plus Environment

21.4, 12.3, 4.9, 3.9, 2.5

Page 21 of 27

5 0 4 5 4 0

O γO γ- Z I O αN O γ- t t

O αO γ- c c

3 5 3 0 2 5

O αN O γ- t c O αO γ- t c

2 0

O αN O γ- c t

∆E

0

( k J /m o l)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


1 5

O αN O γ- c c 2

O γO γ- c t

O αO γ- t t O αO α- Z I

1 0

0

5 O αN O γ- c c 1

L i

+

+


N a

K

+

R b

+

C s

+


3 5 0

R b

K

+

N a

+

L i

3 5 0 +

3 0 0

3 0 0

2 5 0

2 5 0

R

D

2 0 0

2 0 0

1 5 0

1 5 0

D 0

R 1 0 0

C O -M

+

1 0 0 0 .6

0 .8

( 1 / Å)

1 .0

1 /R


io n

1 .2

(p m )

0

+

( k J /m o l)

C s

+

C O -M

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

+

Page 22 of 27

I

0 .0 5

+

C s

0

A 3 A 2

A 1

D 3 D 2 E B D 1

F C

R

(a . u .)

2 0 0

( k m /m o l)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


IR

Page 23 of 27

I IR

0

(a . u .)

+

R b

A 1

F

D 3 D 2 E B D 1 C

R

0 .0 5

A 3 A 2

0

( k m /m o l)

2 0 0

I IR

0

K

+

F

R

(a . u .)

0 .0 5

A 3 C

E B

A 2 A 1

0

D 2 D 1

I

0

IR

0 .1

A

N a

+

B C

R

(a . u .)

0

( k m /m o l)

2 0 0

D

I

0

IR

A 0 .2

L i

0

+

B

R

C 0

3 0 0 0

3 2 0 0 3 4 0 0 w a v e n u m b e r (c m ACS Paragon Plus Environment

-1

)

3 6 0 0

( k m /m o l)

2 0 0

(a . u )

( k m /m o l)

2 0 0

R (a. u.)

0 +

0.05

Cs

G2 G1 G3 G4

M4 M3 M2

L

L

N

M1

0

R (a. u.)

500

M5 M4 M3 M2

+

0.05

G1 G2 G3 G4

Rb L

L

N

M1

R (a. u.)

500

M3 M2 M1

+

0.05

IIR (km/mol)

0

0

K L

L

N

I

H

G2 G1 G3 G4

0

R (a. u.)

500

G1

+

Na

J I

L

H

0

G2

R (a. u.)

500

0.2

G1

+

L K

0 1200

J I

0

H


G2

1400 1600-1 wavenumber (cm )

1800

IIR (km/mol)

0

Li

IIR (km/mol)

0

0.15

IIR (km/mol)

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

500

IIR (km/mol)


Page 24 of 27

Page 25 of 27

αN

O

γ-

O

c c 2

2 0 0

I

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


tc

2 0 0 0

αN

γ-

O

G lu C s 0 .0 5

c c 1

2 0 0 0

+

A 1 -A 3

F

E C

B D 1 -D 3

0

R

(a . u .)

O

( k m /m o l)

αO γ-

O

IR

0

αN

O

γ-

O

c c 2

2 0 0

I IR

αO γ-

O

tc

2 0 0 0

αN

γ-

O

G lu R b 0 .0 5

c c 1

2 0 0

+

F C

E B

0

A 1 -A 3 D 1 -D 3

R

(a . u .)

O

( k m /m o l)

0

0

αN

O

γ-

O

c c 2

2 0 0

αO γ-

O

tc

2 0 0 0

αN

(a . u .)

0 .0 5

R

O

0

G lu K

3 0 0 0

F

γ-

O

c c 1

2 0 0 0

+

A 1 -A 3 C

E B

D 2

3 2 0 0 3 4 0 0 -1 w a v e n u m b e r (c m ) ACS Paragon Plus Environment

D 1

3 6 0 0

I IR ( k m / m o l )

0

αN

O

γ-

O

Page 26 of 27

c c 2

5 0 0

I

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


tc

( k m /m o l)

αO γ-

O

IR

0 5 0 0 0 αN

γ-

O

0 .2

c c 1

5 0 0 0

+

G lu C s

M 1 -M 4 L

G 1 -G 4

N

0

R

(a . u .)

O

αN

O

γ-

O

c c 2

5 0 0

I IR

αO γ-

O

tc

5 0 0 0

αN

γ-

O

G lu R b 0 .2

5 0 0

c c 1 0

+

L N

M 1 -M 4

G 1 -G 4

R

(a . u .)

O

( k m /m o l)

0

0

αN

O

γ-

O

c c 2

5 0 0

I IR

αO γ-

O

tc

5 0 0 0

(a . u .)

0 .2

R

O

0

αN

G lu K

γ-

O

c c 1

5 0 0 0

+

L

1 2 0 0

M 1 -M 3 N

1 4 0 0 1 6 0 0 -1 w a v e n u m b e r (c m ) ACS Paragon Plus Environment

G 1 -G 4

1 8 0 0

( k m /m o l)

0

Page 27 of 27 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


+ Cs + Rb OαNOγ-cc2

+ K + Na

OαOγ-tc

+ Li 2600

2800

3000 3200 3400 -1 wavenumber (cm )


3600

OαNOγ-cc1

Cation-Size Dependent Conformational Locking of Glutamic Acid by

Recommend Documents