Water-Induced Zwitterionization of Glycine: Stabilization Mechanism

Subscriber access provided by LAURENTIAN UNIV

Letter

Water-induced Zwitterionization of Glycine: Stabilization Mechanism and Spectral Signatures Ricardo Perez de Tudela, and Dominik Marx J. Phys. Chem. Lett., Just Accepted Manuscript • DOI: 10.1021/acs.jpclett.6b02247 • Publication Date (Web): 28 Nov 2016 Downloaded from http://pubs.acs.org on December 1, 2016

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 free 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 accessible to all readers and 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 Letters 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 18

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 Letters

Water–induced Zwitterionization of Glycine: Stabilization Mechanism and Spectral Signatures Ricardo Pérez de Tudela∗ and Dominik Marx∗ Lehrstuhl f¨ ur Theoretische Chemie, Ruhr-Universit¨ at Bochum, 44780 Bochum, Germany E-mail: [email protected]; [email protected]

∗

To whom correspondence should be addressed

1 ACS Paragon Plus Environment


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

Abstract The question not only of how many water molecules are required to stabilize the physiologically relevant charge–separated zwitterionic form of amino acids upon solvation, but also the stabilization mechanism is still under debate. It is well known that a water bridge connecting the carboxyl with the amino group must be established. Here, we show that this is not yet a sufficient condition to stabilize the zwitterion. Instead, the formation of a bifurcated H-bonded water wire that connects the two charged groups turns out to be the key, which explains why an unexpectedly large number of water molecules of about nine is required to enable zwitterionization of microsolvated glycine. Moreover, this bifurcated wire allows one to pinpoint a frequency window that enables the detection of zwitterionization by spectroscopy. These findings will not only be relevant to probe and rationalize microsolvation–induced zwitterionization of amino acids, but of other acid/base reactions that involve somewhat distant such functional groups within the same molecule.

Graphical TOC Entry

Keywords

Stabilizing the zwitterionic form of glycine by microsolvation requires a bifurcated water wire that connects the two functional groups as schematically depicted.

Glycine, zwitterion, microsolvation, clusters


Page 2 of 18

Page 3 of 18

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


Going back to pioneering laboratory experiments mimicking primordial chemistry 1,2 up to ongoing attempts to detect amino acids such as glycine in the interstellar medium, 3 there has been continued interest in understanding the properties of amino acids being the building blocks of proteins. Yet, their structure at physiological conditions – aqueous solutions at ambient pressure and temperature – is distinctly different from that in the gas phase. In isolation, amino acids are characterized by neutral carboxyl and amino groups, –COOH and –NH2 , whereas the former is deprotonated while the latter is protonated to yield –COO− and –NH+ 3 after solvation in water. Evidently, stepwise solvation of an isolated amino acid molecule by water must eventually lead to a cluster in which its zwitterionic form is energetically favored. Quite some computational effort has been invested to find out the minimum number of water molecules that is necessary to stabilize zwitterionic glycine, being the smallest possible amino acid and thus the computationally most affordable case . 4–13 Although different electronic structure methods, basis sets and solvation models yield somewhat different results, it seems clear that about eight or nine water molecules are needed to stabilize the zwitterion. On the experimental side, there is no similar consensus reached yet 14–18 and much smaller numbers around five or even three waters find some support. Moreover, the very mechanisms by which zwitterionic structures get stabilized depending on the number of microsolvating water molecules is poorly understood. The idea that a bridge made of several water molecules must be built between the carboxyl and amino groups for Grotthuss–like proton transfer 19 to take place is old and has been repeatedly discussed. 12,20–22 Importantly, the feature of an interconnecting water bridge is not only relevant for amino acids and similar systems 23,24 in the microsolvation limit, but also for photo–triggered intramolecular proton transfer in bulk solutions. 25,26 Anticipating our core results, we will demonstrate that in glycine the existence of such a water bridge that directly connects the de/protonable acidic/basic groups is necessary – but not sufficient for the zwitterionization process to occur! A second condition must hold, which we trace back to the formation of what we call a bifurcated water wire: a distinct



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

water molecule that accepts an H-bond from the –NH+ 3 group forms two H-bonded chains, one leading to the –COO− group whereas the other one connects back to –NH+ 3 itself. In other words: zwitterionic glycine is preferred over the non–dissociated state only if this bifurcated wire is present. Clearly, before this specific H-bonded network topology can be established, a considerable degree of solvation of the glycine molecule by many waters n is a prerequisite. Once glycine is zwitterionized, it is shown to feature distinct vibrational spectral resonances due to the presence of the bifurcated wire, which can be used as a unique marker in future experiments. Our starting point are some available Gly•(H2 O)n structures 5,11 in addition to a wealth of both neutral and dissociated structures that we have generated by repeated quenching of high–temperature ab initio molecular dynamics simulations (see SI for details). All these initial structures have been fully optimized (as confirmed by computing the Hessian that is furthermore used to generate the harmonic infrared spectra as well as to assess the harmonic zero–point vibrational energy corrections) using SCS–(RI)–MP2 27,28 in conjunction with the TZVPP basis set 29 as implemented in Turbomole; 30 note that spin-component-scaled MP2 improves molecular properties such as structures subject to non–covalent interactions and vibrational frequencies considerably over plain MP2. 31,32 A key property in the present context is the energy difference between the lowest-energy non-dissociated (N) and zwitterionic (Z) structures, which will be called dZN and dZN+ZPE after adding the zero–point correction. The energy difference dZN between the N and Z forms of microsolvated glycine, see Fig. 1, decreases systematically upon increasing the number of water molecules until the zwitterionic state becomes definitely preferred after as many as nine solvent molecules have been added. Yet, a substructure of dZN as a function of n in terms of three regimes can be distinguished, which can be traced back to distinct changes in the solvation patterns of Z versus N forms. First, the non–dissociated form of glycine is clearly favored over the zwitterion up to n = 4. In this regime, the stable N and metastable Z species are chemically very different: the water molecules in N structures essentially solvate exclusively the carboxyl group so that the amino


Page 4 of 18

Page 5 of 18

group remains naked, whereas an incipient bridge between the deprotonated acidic and the protonated basic group is already observed for Z structures even for n = 2; see Table 1 in the SI for all structures. This regime is followed by a second one, 5 ≤ n ≤ 8, in which both forms are practically isoenergetic, dZN ≈ ±1 kcal/mol, which can be traced back to the fact that in this size window the solvation structure around both forms of glycine is astonishingly similar. This becomes evident upon comparing the N and Z structures compiled in Table 1 in the SI. 12

dZN+ZPE dZN

10 E[Z] - E[N] (kcal/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


8

6 4 2 0

-2 -4 2

3

4 5 6 7 8 Number of water molecules

9

10

Figure 1: Energy difference (see text) between the lowest–energy non–dissociated (N) and zwitterionic (Z) conformers of Gly•(H2 O)n clusters as a function of the number n of water molecules. The neutral/dissociated state of glycine is stable in the upper/lower regions as schematically indicated by the respective glycine n = 0 structures, whereas all optimized microsolvated N and Z structures can be found in Table 1 in the SI.

Most importantly, in the third regime, the zwitterionic state becomes definitely more stable when the 9th water molecule is added, as heralded by a dramatic drop in the stabilization energy dZN of over 3 kcal/mol, whereas not much change is observed after adding yet another water molecule. In Fig. 2, schematic representations of the N and Z global minima are shown for clusters with five and more water molecules (where only the bridging solvent molecules are displayed for clarity). It can be seen that for 5 ≤ n ≤ 8 the nondissociated species (drawn in light colors) display a single water bridge that connects both neutral –COOH and –NH2 functional groups (drawn as a rectangle and a big circle, respectively), while all zwitterionic ones (in dark colors) display two such bridges that connect 5 ACS Paragon Plus Environment


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

separately the charged –COO− and –NH+ 3 groups. This similarity in the solvation structure of both N and Z species implies the same topology of that part of the H-bonded network which connects the two functional groups. In contrast, with the addition of the 9th water

Figure 2: Schematic representation of the zwitterionic (dark colors) and non-dissociated (light colors) global minima for n ≥ 5 where the most stable conformer is located at the bottom of each panel. The carboxyl and amino groups of glycine are represented, respectively, by rectangles and large circles whereas only the bridging water molecules are included using small light blue circles. molecule, a topological rearrangement of the H-bond network takes place around the –NH+ 3 group for Z species, while the non-dissociated species do not change at all. The new more complex topology of the H-bond network comprises a bifurcated water wire which, on one hand, directly connects both charged functional groups and, on the other hand, connects the –NH+ 3 group with itself. Both branches of this bifurcated water wire have a specific water molecule in common, which accepts a H-bond that is donated by the protonated amino group. This observation suggests that it is this distinct topological change in the H-bond network made possible by the addition of the 9th water molecule that might be the key to finally allow for the overriding stabilization of the charge–separated Z state. Quantum– mechanical zero–point motion effects not only significantly smoothen the energy drop upon 6 ACS Paragon Plus Environment

Page 6 of 18

Page 7 of 18

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


adding the 9th water molecule as revealed by Fig. 1, but moreover tend to slightly but systematically destabilize the zwitterionic state. Yet, despite these nuclear quantum effects the same qualitative conclusions as worked out above based on the electronic structure energies still hold. But can it be proven that it is indeed the change in the topology of the H-bond network around the amino group that ultimately stabilizes the zwitterionic state? It is beyond any debate that during the step-wise solvation process, a necessary condition for the mere existence of the zwitterion is the formation of the H–bonded water bridge between the –COOH and –NH2 groups thus allowing for their de/protonation. After the zwitterion is created, due to the proximity of the acidic and basic groups within the glycine molecule, the water bridge remains as the most stable structure. However, in order to show that in addition to the bridge a topological change in the H-bond network is needed, several sets of calculations have been performed where these ingredients are manipulated separately (using the identical computational protocol as before). In order to illustrate the three test sets proposed in this work, schematic figures are presented in Fig. 3 where the initial, modified and final optimized structures are depicted in each panel from top to bottom. For each of these test sets, the final optimized structures along with their energies can be found in the SI. Let us start by unequivocally demonstrating that a water bridge is definitely needed. The fully optimized most stable n = 9 and 10 zwitterionic structures served us to create new conformers by removing one or two water molecules from the water bridge, and placing them somewhere else in an energetically favorable H–bonding situation, while the surroundings of the –NH+ 3 group remain untouched. This procedure generates structures in which the acidic and basic groups are partially solvated by two distinct water clusters. After the optimizations the water bridges healed in all cases (as representatively demonstrated in the left panel of Fig. 3), albeit at the expense of leading to higher energies of these Z conformers (see Table 2 in the SI). Such a high propensity for reconstruction suggests that the existence of a water − bridge that connects the H–bonded –NH+ 3 group to the significantly microsolvated –COO



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 3: Schematic representation of the three test sets (see text): breaking the water bridge (left panel), adding a single dangling (i.e. non-bridging) water molecule to the –NH+ 3 group (central panel) and removing the uttermost water molecule from the bifurcated bridge (right panel). In each panel, the initial (optimized) conformation as well as the modified (uncolored glycine) and the final optimized structures are displayed from top to bottom. group is a general feature of zwitterionic species, irrespective if they are higher or lower in energy compared to the most stable non–dissociated conformer, provided both functional groups are not extremely far away from each other. In previous works it has already been reported 33 that adding a water molecule to bare zwitterionic glycine is energetically more favorable if H–bonded to the –NH+ 3 rather than to the –COO− charged group. Therefore, in the second test set, the lowest–energy zwitterionic Gly•(H2 O)n configurations were taken for n = 2 − 8 and an additional water molecule was H–bonded to any of the free hydrogen atoms of the –NH+ 3 group. The idea is to confirm that H-bonding of an additional water molecules by –NH+ 3 per se does not guarantee zwitterion stabilization if the bifurcated water wire topology involving the –NH+ 3 group is not established. After optimizing the structures with the extra dangling water molecule (see central panel of Fig. 3), this water molecule is found to disconnect from the –NH+ 3 group and subsequently forms an H-bond somewhere else in case of the smaller clusters (n ≤ 5). 8 ACS Paragon Plus Environment

Page 8 of 18

Page 9 of 18

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 extra water can eventually be stabilized in its initial position when using more than five waters, although the bifurcated wire is never present in any of the final optimized structures. This implies that a certain minimum degree of overall solvation seems to be essential before establishing this particular H–bond. But even though H-bonding of an additional water molecule at the –NH+ 3 group is energetically favorable, the resulting optimized Z structures are never more stable than the corresponding N conformers (see Table 3 in the SI) which clearly discloses the relevance of a bifurcated water wire. Finally, for the third test set, additional optimizations have been performed for n = 9 and 10 in order to support the key importance of the bifurcated water wire (see Table 4 in the SI). New initial structures were prepared by removing the uttermost water molecule bound to the –NH+ 3 group and placing it at different H–bonded locations (see right panel of Fig. 3). After optimizing these modified structures, half of the Gly•(H2 O)9 conformers not only recovered the bifurcated wire, but also their energies were always below the reference N conformation (whereas the others remain zwitterionic, but do not form a bifurcated bridge and are found to be higher in energy than the corresponding N species). For n = 10 water molecules, even all of the 15 generated structures recovered the bifurcated wire. This clearly demonstrates the propensity of microsolvated glycine to stabilize itself energetically in the Z state by rearranging the topology of the H-bond network toward establishing a bifurcated water wire. We conclude that it is only the emergence of a bifurcated water wire which provides a mechanism to eventually stabilize the zwitterionic over the non–dissociated form. This requires an unexpectedly large number of water molecules since, initially, all water molecules are “used up” to form a water droplet around the –COOH group whereas the –NH2 group resists to donating H–bonds. In stark contrast, the –NH+ 3 group in the zwitterion must be stabilized by increasing its H–bonding, which is achieved not only by building a bridge to the –COO− group, but also by adding an extra branch to that bridge at a bifurcating water molecule, which provides the necessary extra solvation to the –NH+ 3 group. Obviously, the appearance of this feature requires a considerable change of the H-bond network topology as



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 10 of 18

Figure 4: Infrared spectra for pure glycine (black line) as well as zwitterionic (Z, red lines) and non–dissociated (N, green lines) Gly•(H2 O)n clusters with n = 1 − 10. The minimum energy zwitterionic structures are shown for each n (note that the O atoms belonging to the carboxyl group have been marked in orange and that the uttermost H2 O of the bifurcated wire is highlighted in green for n = 9 and 10). The reported unscaled harmonic SCS– MP2/TZVPP frequencies including those after O and N isotopic substitution are numerically compiled in the SI and therefore can be scaled easily using any preferred scaling factor for quantitative comparisons to experiments. clearly unveiled by the schematic structures in Fig. 2 or by the table of contents graphics. The importance of the bifurcated water wire goes beyond the mere stabilization of the zwitterionic form of glycine. Whether it exists or not has substantial consequences for the IR spectrum of microsolvated glycine clusters as will be discussed. Experimental IR and Raman spectra have been reported for Gly•(H2 O)n species.

15,18,34–36

However, a conclusive assign-

ment of the peaks is yet missing, in particular there is no convincing experimental evidence yet for zwitterion detection using these techniques. Glycine being a bad chromophore, is difficult to study spectroscopically, which is why molecules with aromatic side chains such as Tryptophan or Phenylalanine are preferred. 37 A distinctly different attempt of zwitterionic glycine detection makes use of photoelectron spectroscopy on dipole–bound anions, 14 where 10 ACS Paragon Plus Environment

Page 11 of 18

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


it is assumed that zwitterionic clusters have larger dipole moments than those containing non–dissociated glycine. In line with previous work, 16,17,38–40 our data show that there is not a clear correlation between the magnitude of the dipole moment of the whole cluster and the dissociation state of glycine, see Table 1 in the SI. Thus, although the dipole moment of a bare zwitterion is large, it gets effectively screened by the dipole network of the solvent molecules. In contrast, our findings suggest an alternative approach to face the experimental detection challenge of the zwitterionization transition upon microsolvation of glycine, going beyond the traditional idea of directly comparing computed frequencies to measured values – a practice that can easily lead to misinterpretations. A much more desirable piece of information for experimentalists would be a specific frequency window where only resonances due to zwitterionized glycine would show up. As can be seen in Fig. 4, an IR frequency window can be considered from about 2400 to 2800 cm−1 in which only a single pronounced peak appears in the spectra for Gly•(H2 O)n clusters as highlighted using gray shading. For clusters with up to eight water molecules this peak corresponds to a particular NH+ 3 stretching mode in the case of zwitterionic glycine cores. With the addition of the 9th and 10th water molecules, formation of the bifurcated water wire completely changes the environment around the amino group and therefore the frequencies of the –NH+ 3 stretching modes, pushing the peak of interest outside the frequency window towards the region beyond 3000 cm−1 . However, incidentally, another peak enters this frequency window at n = 9 and 10, which corresponds to the OH stretch of the protonated carboxyl group of non-zwitterionic glycine. Importantly, for each n, only the energetically most favored conformer has been included in the IR spectra shown in Fig. 4. However, all relevant structures within less than 1 kcal/mol above the corresponding global minima share similar features, but have not been included for the sake of cleanness. Structures with higher energies contribute less than 10 % to the IR spectra at 200 K. At this point, isotopic substitution can be employed in order to easily distinguish whether an experimental peak found in the respective frequency window corresponds to either zwit-



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

terionic or non-zwitterionic glycine as follows. Upon substituting

Page 12 of 18

14

N by

15

N a red shift of

consistently ≈ 10 cm−1 occurs for the peak corresponding to the NH+ 3 stretching mode of the zwitterion (all data are provided in the SI). Alternatively, when

16

O is substituted by

18

O

only the peak corresponding to the OH stretch of non–dissociated glycine red–shifts also by approximately 10 cm−1 . Clearly, such shifts can be reliably resolved by current experimental techniques. Therefore, it is proposed to perform nitrogen and oxygen isotopic substitution experiments to correlate if a peak shift in the frequency window is due to the protonated amino group, thus heralding the zwitterionic state, or due to the protonated carboxyl group of non-dissociated glycine. These qualitative trends are based on harmonic frequencies and thus on harmonic isotope effects. Anharmonic effects on IR spectra of non-dissociated and dissociated microsolvated clusters have been studied in detail recently for the HCl•(H2 O)n system. 41,42 For the case of such non-dissociated species, standard anharmonic corrections based on scaling approaches already improve the frequencies significantly. We expect the same to hold in the present case, and provided the limits of the frequency region are corrected accordingly, our conclusions will still hold. For dissociated species, the appearance of the H3 O+ unit introduces a variety of new features in the IR spectrum, in which overtones, combination bands and the like lead to complications. In our case, the protonated –NH+ 3 group might suffer from similar effects. However, only whether or not a signal is observed at all within the highlighted frequency region is important in the present case, regardless if it is a unimodal peak or a more structured feature. Moreover, Fermi resonances typically imply peak splitting and slight changes in both frequency and intensity, which, again, will certainly affect specific frequencies but are not expected to alter the exposed qualitative trends. Thus, our finding regarding the importance of the bifurcated water wire in the stabilization of zwitterionic glycine upon microsolvation might open a new door in the study of other amino acids, as they share the same charged functional groups located at similar distances.


Page 13 of 18

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


Acknowledgement The Cluster of Excellence “RESOLV” (EXC 1069) funded by the Deutsche Forschungsgemeinschaft (DFG) is gratefully acknowledged along with computer time support from HPC-RESOLV, HPC@ZEMOS, BOVILAB@RUB, and RV–NRW.

Supporting Information Available Cartesian coordinates and total energies for all optimized structures; unscaled harmonic frequencies for the global non–dissociated and zwitterionic minima; unscaled harmonic frequencies after O and N isotopic substitutions; isotopes masses.

This material is available

free of charge via the Internet at http://pubs.acs.org/.

References (1) Miller, S. L. A Production of Amino Acids Under Possible Primitive Earth Conditions. Science 1953, 117, 528–529. (2) Parker, E. T.; Zhou, M.; Burton, A. S.; Glavin, D. P.; Dworkin, J. P.; Krishnamurthy, R.; Fernández, F. M.; Bada, J. L. A Plausible Simultaneous Synthesis of Amino Acids and Simple Peptides on the Primordial Earth. Angew. Chem. 2014, 126, 8270– 8274. (3) Jiménez-Serra, I.; Testi, L.; Caselli, P.; Viti, S. Detectability of Glycine in Solar-type System Precursors. ApJ 2014, 787, L33. (4) Jensen, J. H.; Gordon, M. S. On the Number of Water Molecules Necessary To Stabilize the Glycine Zwitterion. J. Am. Chem. Soc. 1995, 117, 8159–8170. (5) Aikens, C. M.; Gordon, M. S. Incremental Solvation of Nonionized and Zwitterionic Glycine. J. Am. Chem. Soc. 2006, 128, 12835–12850.



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

(6) Park, S.-W.; Im, S.; Lee, S.; Desfran¸cois, C. Structure and stability of glycine–(H2 O)3 cluster and anion: Zwitterion vs. canonical glycine. Int. J. Quantum Chem. 2007, 107, 1316–1327. (7) Bachrach, S. M. Microsolvation of Glycine: A DFT Study. J. Phys. Chem. A 2008, 112, 3722–3730. (8) Kim, J.-Y.; Im, S.; Kim, B.; Desfran¸cois, C.; Lee, S. Structures and energetics of Gly– (H2 O)5 : Thermodynamic and kinetic stabilities. Chem. Phys. Lett. 2008, 451, 198–203. (9) Takayanagi, T.; Yoshikawa, T.; Kakizaki, A.; Shiga, M.; Tachikawa, M. Molecular dynamics simulations of small glycine(H2 O)n (n=2–7) clusters on semiempirical PM6 potential energy surfaces. J. Mol. Struct.: THEOCHEM 2008, 869, 29–36. (10) Lee, K. T.; Han, K. Y.; Oh, I.; Kim, S. K. Barrierless pathways in the neutral–zwitterion transition of amino acid: Glycine–(H2 O)9 . Chem. Phys. Lett. 2010, 495, 14–16. (11) Kayi, H.; Kaiser, R. I.; Head, J. D. A theoretical investigation of the relative stability of hydrated glycine and methylcarbamic acid–from water clusters to interstellar ices. Phys. Chem. Chem. Phys. 2012, 14, 4942–4958. (12) Meng, X.-J.; Zhao, H.-L.; Ju, X.-S. Influences of n (2–5) water molecules on the proton transfer in hydrated glycine complexes. Comp. Theor. Chem. 2012, 1001, 26–32. (13) Kim, J.-Y.; Ahn, D.-S.; Park, S.-W.; Lee, S. Gas phase hydration of amino acids and dipeptides: effects on the relative stability of zwitterion vs. canonical conformers. RSC Adv. 2014, 4, 16352–16361. (14) Xu, S.; Nilles, J. M.; H. Bowen Jr., K. Zwitterion formation in hydrated amino acid, dipole bound anions: How many water molecules are required? J. Chem. Phys. 2003, 119, 10696–10701.


Page 14 of 18

Page 15 of 18

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) Ramaekers, R.; Pajak, J.; Lambie, B.; Maes, G. Neutral and zwitterionic glycine.H2 O complexes: A theoretical and matrix-isolation Fourier transform infrared study. J. Chem. Phys. 2004, 120, 4182–4193. (16) Diken, E. G.; Hammer, N. I.; Johnson, M. A. Preparation and photoelectron spectrum of the glycine molecular anion: Assignment to a dipole-bound electron species with a high-dipole moment, non-zwitterionic form of the neutral core. J. Chem. Phys. 2004, 120, 9899–9902. (17) Diken, E. G.; Headrick, J. M.; Johnson, M. A. Photoelectron spectroscopy of the [glycine(H2 O)1,2 ]− clusters: Sequential hydration shifts and observation of isomers. J. Chem. Phys. 2005, 122, 224317. (18) Vyas, N.; Ojha, A. K.; Materny, A. Simulation of the Raman spectra of zwitterionic glycine + nH2 O (n=1, 2, . . ., 5) by means of DFT calculations and comparison to the experimentally observed Raman spectra of glycine in aqueous medium. Vib. Spectrosc. 2011, 55, 69–76. (19) Marx, D. Proton Transfer 200 Years after von Grotthuss: Insights from Ab Initio Simulations. ChemPhysChem 2006, 7, 1848–1870. (20) Rzepa, H. S.; Yi, M. Y. An AM1 and PM3 molecular orbital and self-consistent reactionfield study of the aqueous solvation of glycine, alanine and proline in their neutral and zwitterionic forms. J. Chem. Soc., Perkin Trans. 2 1991, 531–537. (21) Fernández-Ramos, A.; Smedarchina, Z.; Siebrand, W.; Zgierski, M. Z. A directdynamics study of the zwitterion-to-neutral interconversion of glycine in aqueous solution. J. Chem. Phys. 2000, 113, 9714–9721. (22) Yamabe, S.; Ono, N.; Tsuchida, N. Molecular Interactions between Glycine and H2 O Affording the Zwitterion. J. Phys. Chem. A 2003, 107, 7915–7922.



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

(23) Smedarchina, Z.; Siebrand, W.; Fernández-Ramos, A.; Gorb, L.; Leszczynski, J. A direct-dynamics study of proton transfer through water bridges in guanine and 7azaindole. J. Chem. Phys. 2000, 112, 566–573. (24) Chang, T. M.; Chakrabarty, S.; Williams, E. R. Hydration of Gaseous m-Aminobenzoic Acid: Ionic vs Neutral Hydrogen Bonding and Water Bridges. J. Am. Chem. Soc. 2014, 136, 10440–10449. (25) Mohammed, O. F.; Pines, D.; Dreyer, J.; Pines, E.; Nibbering, E. T. J. Sequential Proton Transfer Through Water Bridges in Acid-Base Reactions. Science 2005, 310, 83–86. (26) Mohammed, O. F.; Pines, D.; Nibbering, E. T. J.; Pines, E. Base–Induced Solvent Switches in Acid–Base Reactions. Angew. Chem. Int. Ed. 2007, 46, 1458–1461. (27) Grimme, S. Improved second-order Møller-Plesset perturbation theory by separate scaling of parallel- and antiparallel-spin pair correlation energies. J. Chem. Phys. 2003, 118, 9095–9102. (28) Weigend, F.; Häser, M.; Patzelt, H.; Ahlrichs, R. RI-MP2: optimized auxiliary basis sets and demonstration of efficiency. Chem. Phys. Lett. 1998, 294, 143–152. (29) Weigend, F.; Ahlrichs, R. Balanced basis sets of split valence, triple zeta valence and quadruple zeta valence quality for H to Rn: Design and assessment of accuracy. Phys. Chem. Chem. Phys. 2005, 7, 3297–3305. (30) TURBOMOLE V6.2 2010,

a development of University of Karlsruhe and

Forschungszentrum Karlsruhe GmbH, 1989-2007, TURBOMOLE GmbH, since 2007; available from http://www.turbomole.com. (31) Domin, D.; Benoit, D. M. Assessing spin-component-scaled second-order Møller-plesset theory using anharmonic frequencies. ChemPhysChem 2011, 12, 3383–3391. 16 ACS Paragon Plus Environment

Page 16 of 18

Page 17 of 18

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


(32) Takatani, T.; Sherrill, C. D. Performance of spin-component-scaled MøllerPlesset theory (SCS-MP2) for potential energy curves of noncovalent interactions. Phys. Chem. Chem. Phys. 2007, 9, 6106–6114. (33) Kumar, S.; Rai, A. K.; Singh, V. B.; Rai, S. B. Vibrational spectrum of glycine molecule. Spectrochim. Acta. A. Mol. Biomol. Spectrosc. 2005, 61, 2741–2746. (34) Espinoza, C.; Szczepanski, J.; Vala, M.; Polfer, N. C. Glycine and its hydrated complexes: a matrix isolation infrared study. J. Phys. Chem. A 2010, 114, 5919–5927. (35) Balabin, R. M. The First Step in Glycine Solvation: The Glycine-Water Complex. J. Phys. Chem. B 2010, 114, 15075–15078. (36) Kaufmann, M.; Leicht, D.; Schwan, R.; Mani, D.; Schwaab, G.; Havenith, M. Helium droplet infrared spectroscopy of glycine and glycine-water aggregates. Phys. Chem. Chem. Phys. 2016, 18, 28082–28090. (37) Blom, M. N.; Compagnon, I.; Polfer, N. C.; von Helden, G.; Meijer, G.; Suhai, S.; Paizs, B.; Oomens, J. Stepwise Solvation of an Amino Acid: The Appearance of Zwitterionic Structures. J. Phys. Chem. A 2007, 111, 7309–7316. (38) Gutowski, M.; Skurski, P.; Simons, J. Dipole-Bound Anions of Glycine Based on the Zwitterion and Neutral Structures. J. Am. Chem. Soc. 2000, 122, 10159–10162. (39) Ahn, D.-S.; Kang, A.-R.; Lee, S.; Kim, B.; Kim, S. K.; Neuhauser, D. On the stability of glycine-water clusters with excess electron: Implications for photoelectron spectroscopy. J. Chem. Phys. 2005, 122, 084310. (40) Haranczyk, M.; Gutowski, M. Effect of excess electron and one water molecule on relative stability of the canonical and zwitterionic tautomers of glycine. J. Chem. Phys. 2008, 128, 125101.



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

(41) Mancini, J. S.; Bowman, J. M. Effects of Zero-Point Delocalization on the Vibrational Frequencies of Mixed HCl and Water Clusters. J. Phys. Chem. Lett. 2014, 5, 2247– 2253. (42) Mancini, J. S.; Bowman, J. M. Isolating the spectral signature of H3 O+ in the smallest droplet of dissociated HCl acid. Phys. Chem. Chem. Phys. 2015, 17, 6222–6226.


Page 18 of 18

Water-Induced Zwitterionization of Glycine: Stabilization Mechanism

Recommend Documents