7702
2008, 112, 7702–7705 Published on Web 06/06/2008
Stepwise Hydration of Protonated Proline Catherine Michaux§ and Johan Wouters Laboratoire de Chimie Biologique Structurale, De´partement de Chimie, Faculte´s UniVersitaires Notre-Dame de la Paix, rue de Bruxelles 61, B-5000 Namur, Belgium
Eric A. Perpe`te† and Denis Jacquemin* Laboratoire de Chimie The´orique Applique´e, De´partement de Chimie, Faculte´s UniVersitaires Notre-Dame de la Paix, rue de Bruxelles 61, B-5000 Namur, Belgium ReceiVed: March 17, 2008; ReVised Manuscript ReceiVed: May 8, 2008
Using an ab initio strategy accounting for the basis set superposition error and electron-correlation effects, we have investigated the stepwise hydration of the proline cation. Structures with 0-3 surrounding water molecules have been obtained, and major differences with respect to protonated glycine are highlighted. Several structures with similar energies actually coexist at each step, and we give indications that should help removing experimental doubts. The theoretical enthalpies and entropies meet the experimental observations, though the computed entropic changes when adding the third water molecule are overestimated. The microsolvation of molecules, especially biological systems and metal ions, has recently received great theoretical and experimental attention. The experimental studies generally rely on mass spectrometry (MS), which allows an accurate determination of the thermodynamical complexation parameters but does not provide unambiguous structures. As a consequence, the actual solvation sites often remains unknown.1–3 To obtain the relevant structural information, coupled MS/infrared measurements have been performed.4,5 Still, such procedures require adequate theoretical simulations to allow a pertinent interpretation of the resulting vibrational patterns. In that sense, microsolvation is typically a field in which computer simulations nicely complete experiments to attain relevant chemical insights. Aside from the study of the water effect on metal ions or DNA bases, most of the previous stepwise hydration works concentrated on the equilibrium between the nonionized and zwitterionic forms of amino acids (AA),5–11 while fewer works have considered protonated AA, AAH+.4,12–15 For these systems, experimental stepwise enthalpies are available,1,3 allowing meaningful and straightforward theory/experiment comparisons of the thermodynamic complexation contributions. In a recent investigation dealing with the microhydration of protonated glycine,15 we established that a Darwinian logic is suitable for the prediction of the most stable GlyH+-(H2O)n complexes on the basis of the energetics and structures in the previous generation, that is, the set of GlyH+-(H2O)n-1 compounds. In order to assess the transferability of this methodology, we here * To whom correspondence should be addressed; Research Associate of the Belgian National Fund for Scientific Research. E-mail: denis.jacquemin@ fundp.ac.be. § Post-Doctoral Researcher of the Belgian National Fund for Scientific Research. † Research Associate of the Belgian National Fund for Scientific Research.
10.1021/jp8023155 CCC: $40.75
tackle the microhydration of L-ProH+, which is limited to 0-3 complexing water molecules due to the experimental restrictions.1 All calculations have been performed with the Gaussian03 package,16 using the computational protocol developed14 and tested15 for protonated glycine. In short, full geometry optimizations and vibrational frequency determinations have been analytically achieved at the second-order Møller-Plesset (MP2) level using the 6-311++G(d,p) atomic basis set. Recently, Riley and Hobza have shown that MP2 generally gives an accurate hydrogen bond energy description for protein-like systems and that a triple-ζ atomic basis set including both polarized and diffuse is required.17 The basis set superposition error (BSSE) has been removed by using the well-established counterpoise (CP) procedure.18,19 It is essential to stress that these CP corrections have been fully applied not only to the (internal) complexation energies but also to all geometry optimizations and harmonic vibrational frequency calculations. Following ref 15, we designed the evolution tree of the ProH+-(H2O)n complexes with 0, 1, 2, and 3 water molecules. A description of the 49 resulting structures composing this tree, as well as the discussion of the related energetics, is available in Supporting Information (SI), together with comments about the relative stability of the endo and exo minima. In summary, the most stable complexes belong to the same branch of the tree for all n. For instance, the lowest- (Gibbs free energy) ProH+-(H2O)3 structures possess two water molecules bound to the same sites as those in the most stable ProH+-(H2O)2. The complexes that can be detected under experimental conditions are sketched in Figure 1. The minimal energy conformer of nonhydrated ProH+ (0) presents a ψ angle close to 180°, in agreement with recently determined crystal structures.20–22 The endo-like conformer is more stable than its exo-like counterpart by 0.54 kcal/mol. The structural parameters of ProH+ are compared to Pro23–26 in the SI. It turns out that the most stable 2008 American Chemical Society
Letters
J. Phys. Chem. B, Vol. 112, No. 26, 2008 7703
Figure 1. Sketch of the most stable endo L-ProH+-(H2O)n with n ) 0 (top left), 1 (top right), 2 (middle), and 3 (bottom).
structures of Pro and ProH+ substantially differ as a result of the missing nitrogen lone pair in the latter. For 0, the vibrational frequencies of the most significant hydrogen-stretching modes are 3278/3320 and 3519/3516 cm-1 (ammonium) and 3759/ 3759 cm-1 (carboxylic) for the endo/exo conformers. The first water molecule clearly binds to the ammonium hydrogen not involved in the internal hydrogen bond with the CdO group, leading to structure 1 (see Figure 1), the endo form being favored by 0.50 kcal/mol. In the endo/exo complex, the H-bond length is 1.82/1.81 Å, which is significantly longer than in the corresponding glycine cation structure.14 Going from 0 to 1 induces a drastic frequency decrease of the peak27 related to the N-H · · · OH2 elongation (endo: 3255 instead of 3519 cm-1; exo: 3256 instead of 3516 cm-1), together with a burst of its intensity (×7).28 On the contrary, both other bands undergo smaller variations with frequencies of 3348/3378 (ammonium) and 3764/3764 cm-1 (carboxylic). When adding a second water molecule, three close-in-energy structures can be determined: 2a endo, 2a exo, and 2b endo, the two latter being less stable by about 0.62 and 0.70 kcal/mol under standard temperature and pressure. Under the experimental conditions, the majority of the carboxylic OHs are consequently involved in hydrogen bonds with the aqueous ligands, even when only two water molecules are added. This strongly contrasts with GlyH+(H2O)215 and ValH+-(H2O)2,4 for which only ammonium hydrated structures have been predicted and eventually detected. This difference probably originates in the strong internal
NH+ · · · OdC hydrogen bond in ProH+. In endo/exo 2a, the ammonium intermolecular H-bond slightly lengthens (1.83/1.83 Å), and the corresponding stretching mode remains almost unchanged (3269/3278 cm-1, similar intensity). On the contrary, the (CO)OH stretching mode undergoes a 400 cm-1 red shift (3319/3334 cm-1)28 with an intensity increased by almost an order of magnitude! It is quite the reverse for endo 2b, as the OH elongation vibration has a frequency of 3772 cm-1, almost as in 0, the two intense ammonium stretching modes taking place at 3271 and 3325 cm-1. It is therefore obvious that experimentally tracking the evolution of the vibrational signature of COOH upon stepwise hydration should allow to quickly distinguish 2a from 2b (see the SI for simulated spectra). When a third water molecule is plugged in, four structures are experimentally detected: 3a endo, 3b endo, 3b exo, and 3c endo, the endo forms of 3a and 3b presenting almost the same energy and the two latter being close enough (G ) 0.36 and 0.38 kcal/ mol) to coexist at room temperature. Therefore, second-shell compounds should soon appear for ProH+. For comparison, in GlyH+-(H2O)3, the first second-shell complex appears 1.44 kcal/mol above the first-shell reference15 and remains unobserved. This illustrates how the microhydration process is sensitive to the chemical nature of the AA. Let us underline that the presence of a second-shell complex at the third generation was inferred by Wincel from the evolution of the thermodynamical parameters,1 although his guess was a waterfree structure on the carboxylic side. The length of the initial
7704 J. Phys. Chem. B, Vol. 112, No. 26, 2008
Letters
TABLE 1: Successive Gas-Phase Hydration Enthalpies (in kcal/mol) and Entropies (cal/mol.K) of L-ProH+ Obtained from Experiment (refs 1 and 29 in italics) and Theory (this work)a -∆Hn n
complex
1
1 endo (65%) 1 exo (35%) total 2a endo (55%) 2a exo (23%) 2b endo (22%) total 3a endo (33%) 3b endo (32%) 3a exo (18%) 3c endo (17%) total
2
3
experiment
14.8 ( 0.7; 18.9 ( 1.0
12.0 ( 0.4
8.1 ( 0.2
-∆Sn theoryb 14.14 13.56 13.94 12.04 11.31 10.87 11.61 9.91 10.00 9.54 10.03 9.89
experiment
24.2 ( 1.0; 36.8 ( 3.0
22.2 ( 1.0
14.8 ( 0.7
-∆Gn theoryb
theoryc
23.72 23.46 23.63 25.45 25.03 23.88 25.01 23.61 23.90 23.61 25.26 23.99
22.63 22.35 22.53 25.64 25.20 23.97 25.17 23.47 23.69 23.97 25.12 23.81
experiment
7.7 ( 0.7; 8.1 ( 1.9
5.5 ( 0.7
3.8 ( 0.7
theoryb
theoryc
7.19 6.69 7.02 4.60 3.98 3.87 4.30 2.99 2.99 2.62 2.62 2.86
7.51 7.01 7.34 4.52 3.93 3.85 4.24 3.03 3.06 2.52 2.67 2.89
Following the experiment, all values are calculated for T ) 293 K and P ) 1000 mbar. Boltzmann partitioning (experimental conditions, vibrational scaling factor of 0.95) is applied. b Computed straightforwardly using T ) 293 K and P ) 1000 mbar. c Calculated consistently with the experimental data, that is, (1) considering the ∆Sn at the experimental temperature to be equal to those at 293 K, and (2) applying the G ) H - TS formula at T ) 293 K to compute G. a
ammonium hydrogen bond (1.83 Å) slightly increases for firstshell endo structures (3b: 1.86 Å) but goes down for secondshell compounds (3a: 1.73 Å and 3c: 1.74 Å). This gives very different infrared (harmonic) spectra with all stretching modes close in energy for the former case (3391 cm-1 for the OH mode; 3345 and 3294 cm-1 for the NH modes) and well separated IR absorptions for the latter complexes. The extra intense mode experimentally observed at higher energy (3679 m-1 for 3a and 3690 m-1 for 3b) indicates a stretching vibration between hydrogen-bonded waters, and it should consequently allow the detection of second-shell structures and thus 3a and 3c. For monohydrated proline, two experimental measurements are available,1,29 which significantly differ: by ∼50% for the entropic factor and by ∼25% for the enthalpies (see Table 1). The most recent measurements report ∆Hn, ∆Sn, and ∆Gn corrected for standard conditions, though the measurements are carried out at higher temperature (about 380 K for n ) 1, 345 K for n ) 2, and 310 K for n ) 3) and at low pressure (10 mbar). For all ProH+ complexes, the relative proportion of the various structures has been established using the Boltzmann function. Comparisons between experimental and theoretical stepwise hydration energies and entropies can be found in Table 1. We have systematically determined the ∆Sn at both 293 K and the experimental temperature, and we found they are equivalent, as suggested by Wincel.1 It is obvious that the overall agreement between the theoretical and the experimental values is excellent. For instance, the total ∆H (∆G) for the addition of three water molecules is 34.9 (17.0) kcal/mol experimentally, while our simulations deliver 35.4 (14.5) kcal/mol. This clearly consolidates our structure determinations. In fact, the only striking difference is for ∆S3, which we significantly overshoot. Wincel attributed the small ∆S3 to the development of secondshell structures, whereas as shown in Table 1, we calculate very similar thermodynamic contributions for 3a and 3b. Anyway, it should be noted that Table 1 lists stepwise hydration energies, so that it is awaited that the theoretical errors tend to propagate when going down the column. In summary, using a CP-MP2/6-311++G(d,p) approach, the structures and thermodynamic parameters of microhydrated protonated proline have been determined. It turns out that several complexes do coexist, and in contrast with GlyH+, second-shell compounds (3a and 3c) are likely to be detected in the
experiment. Except for ∆S3, we obtain a very good agreement between computed and measured parameters. Acknowledgment. C.M., E.A.P., and D.J. thank the Belgian National Fund for Scientific Research for their respective positions. The authors are indebted to Profs. J.M. Andre´ and D.P. Vercauteren for their long-lasting continuous support and efficient help. All calculations have been performed on the Interuniversity Scientific Computing Facility (ISCF), installed at the Faculte´s Universitaires Notre-Dame de la Paix (Namur, Belgium), for which the authors gratefully acknowledge the financial support of the FNRS-FRFC and the “Loterie Nationale” for the convention number 2.4578.02 and that of the FUNDP. Supporting Information Available: Full Gaussian reference, discussion of the ProH+ tree of complexes, description of the minima for unhydrated ProH+, Cartesian coordinates for the molecules in Figure 1 (both exo and endo conformers), and representations of the optimized exo complexes. This information is available free of charge via the Internet at http:// pubs.acs.org. References and Notes (1) Wincel, H. Chem. Phys. Lett. 2007, 439, 157–161. (2) Beyer, M. K. Mass Spectrom. ReV. 2007, 26, 517–541. (3) Wincel, H. Int. J. Mass. Spectrom. 2006, 251, 23–31. (4) Kamariotis, A.; Boyarkin, O.; Mercier, S.; Beck, R.; Bush, M.; Williams, E.; Rizzo, T. J. Am. Chem. Soc. 2006, 128, 905–916. (5) Bush, M. F.; Prell, J. S.; Saykally, R. J.; Williams, E. R. J. Am. Chem. Soc. 2007, 129, 13544–13553. (6) Aikens, C. M.; Gordon, M. S. J. Am. Chem. Soc. 2006, 128, 12835– 12850. (7) Derbel, N.; Hernandez, B.; Pfliiger, F.; Liquier, J.; Geinguenaud, F.; Jaidaine, N.; Lakhdar, Z. B.; Ghomi, M. J. Phys. Chem. B 2007, 111, 1470–1477. (8) Costa, D.; Lomenech, C.; Meng, M.; Stievano, L.; Lambert, J. F. J. Mol. Struct.: THEOCHEM 2007, 806, 253–259. (9) Rodziewicz, P.; Doltsinis, N. L. ChemPhysChem. 2007, 8, 1959– 1968. (10) Blom, M. N.; Compagnon, I.; Polfer, N. C.; von Helden, G.; Meijer, G.; Suhai, S.; Paizs, B.; Oomens, J. J. Phys. Chem. A 2007, 111, 7309– 7316. (11) Chuchev, K.; DelBruno, J. J. J. Mol. Struct.: THEOCHEM 2008, 850, 111–120. (12) Ai, H.; Bu, Y. J. Chem. Phys. 2004, 120, 2208–2214. (13) Marino, T.; Toscano, M.; Russo, N.; Grand, A. J. Phys. Chem. B 2006, 110, 24666–24673.
Letters (14) Michaux, C.; Wouters, J.; Jacquemin, D.; Perpète, E. A. Chem. Phys. Lett. 2007, 445, 57–61. (15) Michaux, C.; Wouters, J.; Perpète, E. A.; Jacquemin, D. J. Phys. Chem. B 2008, 112, 2430–2438. (16) Frisch, M. J. Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J. R.; Montgomery, J. A.; Jr. Vreven, T.; Kudin, K. N.; Burant, J. C.; Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.; Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.; Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao, O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken, V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A. J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G. A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.; Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Foresman, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.; Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P. M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian 03, revision D.02; Gaussian, Inc.: Wallingford, CT, 2004. (17) Riley, K.; Hobza, P. J. Phys. Chem. A 2007, 111, 8257–8263. (18) Boys, S. F.; Bernardi, F. Mol. Phys. 1970, 19, 553–566. (19) Simon, S.; Duran, M.; Dannenberg, J. J. J. Chem. Phys. 1996, 105, 11024–11031.
J. Phys. Chem. B, Vol. 112, No. 26, 2008 7705 (20) Subha Nandhini, M.; Krishnakumar, R. V.; Natarajan, S. Acta Crystallogr., Sect. C 2001, 57, 423–424. (21) Rajagopal, K.; Krishnakumar, R. V.; Mostad, A.; Natarajan, S. Acta Crystallogr., Sect. E 2003, 59, o277-o279. (22) Jin, M. Z.; Pan, Y. P.; Hu, M. L.; Shen, M.; Li, M. C. Cryst. Res. Technol. 2003, 38, 1009–1012. (23) Lesarri, A.; Mata, S.; Cocinero, E. J.; Blanco, S.; Lopez, J. C.; Alonso, J. L. Angew. Chem., Int. Ed. 2002, 41, 4673–4676. (24) Czinki, E.; Csaszar, A. G. Chem.s Eur. J. 2003, 9, 1008–1019. (25) Flores-Ortega, A.; Casanovas, J.; Zanuy, D.; Nussinov, R.; Aleman, C. J. Phys. Chem. B 2007, 111, 5475–5482. (26) Aleman, C.; Zanuy, D.; Casanovas, J.; Cativiela, C.; Nussinov, R. J. Phys. Chem. B 2006, 110, 21264–21271. (27) It has to be emphasized that for AAH+-(H2O)n complexes, the hydrogen bond stretching frequencies are very sensitive to anharmonic factors (see ref 14), so that the evolution of the vibrational frequencies (rather than their absolute value) is meaningful. For this reason, no scaling factor has been applied to these values. (28) As anharmonic effects tend to significantly decrease the vibrational frequencies especially for the H-bond elongations, we indeed foresee that the computed harmonic red shifts are underestimated. (29) Meot-Ner, M.; Field, F. H. J. Am. Chem. Soc. 1974, 96, 3168–3171.
JP8023155
