Gas-Phase Spectroscopy of Synephrine by Laser Desorption

ARTICLE pubs.acs.org/JPCA

Gas-Phase Spectroscopy of Synephrine by Laser Desorption Supersonic Jet Technique Shun-ichi Ishiuchi, Toshiro Asakawa, Haruhiko Mitsuda, Mitsuhiko Miyazaki, Shamik Chakraborty, and Masaaki Fujii* Chemical Resources Laboratory, Tokyo Institute of Technology, 4259, Nagatsuta-cho, Midori-ku, Yokahama 226-8503, Japan ABSTRACT: In our previous work, we found that synephrine has six conformers in the gas phase, while adrenaline, which is a catecholamine and has the same side chain as synephrine, has been reported to have only two conformers. To determine the conformational geometries of synephrine, we measured resonance enhanced multiphoton ionization, ultraviolet
ultraviolet hole burning, and infrared dip spectra by utilizing the laser desorption supersonic jet technique. By comparing the observed infrared spectra with theoretical ones, we assigned geometries except for the orientations of the phenolic OH group. Comparison between the determined structures of synephrine and those of 2-methylaminno-1-phenylethanol, which has the same side chain as synephrine but no phenol OH group, leads to the conclusion that the phenolic OH group in synephrine does not affect the conformational flexibility of the side chain. In the case of adrenaline, which is expected to have 12 conformers if there are no interactions between the catecholic OH groups and the side chain, some interactions possibly exist between them because only two conformations are observed. By estimation of the dipole
dipole interaction energy between partial dipole moments of the catecholic OH groups and the side chain, it was concluded that the dipole
dipole interaction stabilizes specific conformers which are actually observed.

1. INTRODUCTION Catecholamines, having a catechol ring and an alkyl amine chain, are some of the most important neurotransmitters and hormones, such as dopamine and adrenaline. In the signaling process, these molecules are recognized by G-protein conjugated receptor (GPCR) proteins. Structural information of the native signalization molecules is an active area of research in the field of chemical physics since the past decade.1 Besides that, it is also important in the field of pharmacology to design and develop new drug molecules by mimicking the molecular structures of the native signalization molecules. In the modern medical industry, it is not too much to say that finding out the fine mimic molecules which have high selectivity and no side effects brings about successful drug synthesis. In addition, molecular level understanding of the interaction between the mimic molecules and receptors is also useful to exploring drug design. Therefore, the elucidation of the interactions between the signalization molecules and their receptors is an intriguing issue not only for molecular science but also for pharmacology. In such host
guest interactions, the receptor protein recognizes the shapes of the flexible signalization molecules. By a binding process, geometric change takes place in the receptor protein, which regulates activities of the G-protein. As demonstrated by such an allosteric effect, one of the essential properties of reactions of biologically relevant molecules is flexibility, i.e., which have a number of stable conformations. Therefore, to elucidate the recognition process at the molecular level, it is r 2011 American Chemical Society

indispensable to know not only conformational geometries but also the flexibility between them. To investigate the conformational geometries of such multiconformational molecules, gasphase optical spectroscopy is a powerful tool.2
4 In previous work, we applied laser desorption supersonic jet laser spectroscopy to Dopa, which is a catecholamine neurotransmitter and a precursor of dopamine, to investigate its conformational geometry, and reported that Dopa has a single conformer while tyrosine and m-tyrosine, which have the same side chain as in Dopa but with one phenolic OH group, have multiple conformers, 8 and 14, respectively.5,6 According to past research of noradrenaline7,8 and adrenaline,9,10 also it was reported that they have tiny numbers of conformers, one and two, respectively. From these results, we can deductively make a hypothesis that the catecholic OH groups are responsible for reducing the number of conformers. To confirm this hypothesis, we took notice of synephrine, which has the same side chain as adrenaline but one phenolic OH at the para position. The relationship between synephrine and adrenaline is the same as that between tyrosine and Dopa. If our hypothesis is correct, multiple conformers will be observed in synephrine. In the previous work, we also investigated the number of conformation of synephrine and found that synephrine has six conformers. Received: June 5, 2011 Revised: August 5, 2011 Published: August 06, 2011 10363

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Figure 1. REMPI spectrum of jet-cooled synephrine.

Table 1. Frequencies of 0
0 Transitions of A
F Conformers Observed in the REMPI Spectrum

Figure 2. REMPI spectrum expanded at origin region (bottom trace) and UV
UV hole burning spectra (top traces) observed by probing bands A
F observed in the REMPI spectrum.

In this paper, we report infrared spectra of each of the six conformers of synephrine and assign those geometries by comparing with quantum chemical calculations. In addition, these geometries are compared with those of 2-methylaminno1-phenylethanol11 and adrenaline9,10 to discuss the effect of phenolic OH group on the side-chain conformation.

2. EXPERIMENTAL SECTION Resonance enhanced multiphoton ionization (REMPI) spectroscopy was employed to measure the electronic excitation spectra. In a REMPI spectrum, the electronic transitions of different conformers are observed simultaneously. Electronic transitions originating from different conformers are discriminated using UV
UV hole burning (HB) spectroscopy.12 The number of conformers contributing to the observed REMPI spectrum is determined by comparing the recorded HB spectra. Once the number of conformers produced in the molecular beam is known, IR dip spectroscopy was applied to measure conformer-selected IR spectra. The principles of these spectroscopies are described elsewhere.6 The experiment was carried out using laser desorption sources which have been described in detail elsewhere.5,6 Briefly, synephrine was mixed with graphite powder and applied to the lateral face of a graphite disk (diameter 60 mm, thickness 4 mm). The disk was rotated at a speed of 1 rev/h to provide fresh material constantly. The sample was desorbed by the 1064 nm radiation of a Nd3+:YAG laser (New Wave, Minilase II) in front of a pulsed nozzle (General Valve), and picked up by a supersonic jet of Ar at a backing pressure of 5 bar. The supersonic jet was

conformer

0
0 transition/cm
1

A

35 616

B

35 639

C

35 693

D E

35 703 35 748

F

35 758

trimmed to a molecular beam by a skimmer of 2 mm diameter. Jet-cooled synephrine molecule in the molecular beam was irradiated by a tunable UV laser in the extraction region of a linear time-of-flight mass spectrometer to measure REMPI spectra. The UV laser was generated by a frequency-doubled dye laser (Lumonics, HD-500; Inrad, AUTOTRACKER III with KDP crystal) pumped by a third harmonic of a Nd3+:YAG laser (Spectra-Physics, INDI-40). Setups for UV
UV hole burning and IR dip spectroscopies were also reported previously.6 A second tunable UV laser was generated by a frequency-doubled dye laser (Lumonics, HD-500; Inrad, AUTOTRACKER III with KDP crystal) pumped by the third harmonic of a Nd3+:YAG laser (Spectra-Physics, GCR-170), and a tunable IR laser was generated by difference-frequency mixing, using the output of a dye laser (Sirah, Cobra Stretch) pumped by 80% output of a second harmonic of a Nd3+:YAG laser (Spectra Physics, LAB 190) and the remaining 20% in a LiNbO3 crystal. The pulsed valve, the desorption laser, and the first UV laser were operated at 20 Hz, while the second UV laser and the IR laser were operated at 10 Hz to obtain a UV-only signal and a two-color signal (UV + UV or UV + IR) alternatively. By dividing the latter by the former, fluctuations of the laser power and the condition of the pulsed valve can be canceled.13 Quantum chemical calculations were performed to determine the probable structures of synephrine. Optimized geometries and theoretical IR spectra of the synephrine were calculated at the B3LYP/cc-pVDZ level by Gaussian 09.14 For comparison of experimental IR spectra with calculated ones, calculated vibrational frequencies were scaled by a scaling factor of 0.968.

3. RESULTS AND DISCUSSION 3.1. REMPI and UV
UV Hole Burning Spectra. The REMPI spectrum of jet-cooled synephrine is presented in Figure 1. A series of sharp bands are observed in the spectrum which ensures the efficient cooling of the sample in the expansion. The REMPI spectrum was scanned in the region 35 400
37 000 cm
1 and no other transitions were observed toward the red side of the lowest energy peak observed at 35 616 cm
1. Different conformers of 10364

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synephrine may exist in the molecular beam under the present experimental conditions. The next step is the conformer specific assignment of the REMPI spectrum. UV
UV hole burning spectra were recorded by probing bands A
F observed in the REMPI spectrum presented in Figure 2 (bottom) to discriminate electronic transitions of different conformers present in the jet. Figure 2 A
F shows HB spectra for A
F transitions. The HB spectra clearly show six mutually exclusive sets of transitions

Figure 3. UV
UV hole burning spectra observed by probing bands A
F in the REMPI spectrum. The horizontal axis represents the relative energy to the origin band.

indicating that at least six conformers coexist under the ultracold condition of the molecular beam. The REMPI spectrum can be reproduced by the superposition of the six HB spectra. Frequencies of 0
0 transitions of each conformer are listed in Table 1. The HB spectra are plotted with respect to the 0
0 transition of each conformer and presented in Figure 3 for easy comparison. It is quite clear from Figure 3 that the HB spectra can be classified into three groups based on spectral similarity. It is concluded from this result that two conformers of each pair are originated from the two different orientations of the phenolic OH group, i.e., cis and trans isomers. This tendency is confirmed in a previous report of tyrosine.15 Therefore, it can be expected that side-chain conformation of jet-cooled synephrine is classified into three groups. The observed vibronic bands can be explained by progressions and combinations of a few low frequency modes, which are presented in Figure 3 and listed in Table 2. The assignments of the observed vibronic bands will be discussed later. 3.2. IR Dip Spectra. Figure 4 (top traces, A
F) shows the IR dip spectra of synephrine recorded by probing bands A
F observed in the REMPI spectrum. All the spectra have a band at 3657 cm
1, which is assigned to the stretching vibration of the phenolic OH group based on the corresponding free OH vibration of phenol.16 The spectra of conformers A
F show intense transitions in the region 3500
3530 cm
1 associated with excitation of the O
H stretching mode. The red shift relative to the free O
H stretch frequency is typical of an intramolecular hydrogen bond in which OH acts as a proton donor. Therefore, these bands are assigned to the OH stretching vibration of the side-chain OH group which forms a hydrogen bond to N atom. Accordingly, a free N
H stretching vibration is expected to be observed in all the conformers, which however was not observed possibly because of its weak transition intensity. The bands observed around 3000 and 2800 cm
1 are assigned to C
H stretching vibrations of the benzene ring and those of the side chain, respectively. The IR dip spectra are classified into three groups based on spectral similarities as discussed in case of the HB spectra. In addition, the frequency of side-chain OH (at 3500
3530 cm
1) is slightly different in the three groups, which reflects the conformational difference in the side chain. Therefore, it is concluded that the six conformers can be classified into three groups according to conformational differences in the side chain,

Table 2. Low Frequency Vibrations Observed in the UV
UV Hole Burning Spectra and Calculated Frequencies in the S0 State (B3LYP/cc-pVDZ) of Each Conformer conformer

modea

A/B

1 2

C/D

E/F

a

obsd/cm
1 36/34 44/44

conformational assignment S-GG-OHN-c/t

calcd/cm
1 38/37 52/52

vibrational assignment torsion (γ
β) bend (out-of-plane)

3

96/95

114/114

torsion (N
α)

4

118/116

135/134

torsion (α
β)

5

168/174

195/195

torsion (N
CH3)

1

40/40

42/40

torsion (γ
β)

2

57/57

63/63

torsion (α
β)

3

61/62

75/74

bend (out-of-plane)

1 2

36/36 52/52

39/37 64/63

torsion (γ
β) bend (out-of-plane)

3

112/111

128/128

torsion (α
β)

S-AG-OHN-c/t

PS-AG-OHN-c/t

Numbers indicated in Figure 3. 10365

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Figure 5. B3LYP/cc-pVDZ structures of the 10 most stable synephrine (S) and pseudosynephrine (amine inversion, PS) conformers. Relative energies in the parentheses are given in kJ mol
1.

Table 3. Observed and calculated (B3LYP/cc-pVDZ) vibrational frequencies of the side-chain OH stretching conformer

obsd/cm
1

conformational assignment

calcd/cm
1

A/B

3515/3514

S-GG-OHN-c/t

3478/3478

C/D

3498/3498

S-AG-OHN-c/t

3468/3467

E/F

3526/3528

PS-AG-OHN-c/t

3488/3487

Figure 4. Comparison of observed IR dip spectra of synephrine with calculated spectra of the six stable conformers. For calculated frequencies, a scaling factor of 0.968 is used.

and each group can be split into two species due to cis and trans orientations of the phenolic OH. 3.3. Theoretical Calculation. Synephrine is a molecule with many single bonds. Hence, it is expected that many different possible conformations in the potential energy surface will be determined by theoretical calculations. The initial guess for the starting geometry of different conformers was obtained from previous work by Simon’s group.7
9,11,17
20 The conformations of syneprhine were considered in the following three phases: (i) Synephrine has a chiral center (the Cβ atom, see Figure 5) and thus occurs in two spectroscopically identical chiral forms (R and S). In addition, the N-methyl group makes the N atom chiral because it is very unlikely that umbrella inversion takes place at the low temperatures of supersonic jet experiments.10 This leads to the existence of two diastereoisomers: (1R,2S/1S,2R) and (1S,2S/1R,2R). According to the custom, the former one is denoted as synephrine (S), and latter one is pseudosynephrine (PS). (ii) Initial geometries were generated through a systematic variation of the four dihedral angles that determine the conformation of the side chain. Starting from the benzene ring side, — Cδ
Cγ
Cβ
Cα was set at 90 since aromatic ethanolamine side chains are generally directed perpendicular to the plane of the aromatic ring approximately,11,17
20 and — Cγ
Cβ
O
H, — Cγ
Cβ
Cα
N, and — Cβ-Cα
N
lp (lp, lone pair) were set to 60, 180, and 300, respectively. The resulting side-chain conformation was identified by the arrangement (anti or gauche) of the Cγ
Cβ
Cα
N and O
Cβ
Cα
N atom chains, respectively, and defined the orientation of the aromatic ring and the chain OH group with respect to the amino group. (iii) Finally, the phenolic OH allowed two alternative orientations: one is where the hydrogen atom of the phenolic OH is

directed toward the side-chain OH, and the other is opposite. The former one is denoted as cis (c), and latter one is trans (t). Obtained initial geometries were optimized at the B3LYP/ccpVDZ level, and the resulting 10 most stable structures are shown in Figure 5. It was already reported in previous studies of related molecules7
9,11,17
20 that the most stable conformers are those which are stabilized by an intramolecular OH f N hydrogen bond in the side chain. The notation AG (GG) means that the aromatic ring lies anti (gauche) and the side-chain OH group lies gauche with respect to the amino group. The AG conformers form extended geometries, while the GG conformers form folded ones as shown in Figure 5. Also in synephrine, only the AG and GG structures bring the OH and N-methyl groups into close proximity to allow OH f N or NH f O hydrogen bonding and all of the (10) most stable structures adopt either AG or GG side-chain conformations. In a third conformation GA structure has the orientation that the side-chain OH group and the N-methyl group lie in opposite positions to each other, where there is no hydrogen bonding between them, and this conformation lies approximately 10 kJ mol
1 above the global minimum. As shown in Figure 5, the conformer with an intramolecular OH f N hydrogen bond is more stable than NH f O hydrogenbonded structures. This is in agreement with the larger polarity of OH compared to that of NH, as well as the relative hydrogenbonding abilities of oxygen and nitrogen in different hydrogenbonding environments.21
24 3.4. Assignments of Conformers. It is clear from IR dip spectra that all observed conformers form intramolecular OH f N hydrogen bonds, so S-AG-NHO-c and S-AG-NHO-t can be eliminated as the candidates. In the remaining eight conformers, PS-GG-OHN-c and PS-GG-OHN-t are less stable than the others. It is unlikely that these two species exist in the supersonic 10366

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Figure 6. Conformational evolution from 2-methylamino-1-phenylethanol (MAPE) to adrenaline. Conformational geometries of MAPE and adrenaline have been already reported by Simons and co-workers.9,11 In adrenaline, A-AG-cR and PA-AG-cR conformers were reported to be observed in the gas phase.

jet and they are ruled out. Figure 4 shows a comparison of the observed IR dip spectra with calculated ones for the six stable conformers. In the region 2800
3100 cm
1 (C
H stretching vibration of the benzene ring and side chain), spectra are complicated presumably because of anharmonic couplings and are inconsistent with calculated spectra, so this region was neglected for any detailed assignment. In addition, the N
H stretch vibrations were not observed in this experiment. Herein, the most useful information to elucidate the conformation and assign their IR spectra is the frequency of side-chain OH in terms of red shift from free OH. Table 3 shows a comparison of the experimental and calculated vibrational frequencies of synephrine. According to a correspondence relation, conformer A/B is assigned to the S-GG group, conformer C/D is assigned to the S-AG group, and conformer E/F is assigned to the PS-AG group. These conformational assignments are confirmed by assignments of the vibronic bands observed in the HB spectra. The observed vibronic bands were assigned by comparing with the calculated vibrational frequencies in the S0 state, which are listed in Table 2, on the basis of an assumption that the observed vibrational modes in the S1 state are not so different from calculated modes in the S0 state. 3.5. Comparison with 2-Methylamino-1-phenylethanol and Adrenaline. As mentioned in the Introduction, synephrine is an adrenaline analogue. Adrenaline has neighboring two phenolic OH groups, while synephrine has one. If the phenolic OH had no effect on the conformation of the side chain, two times the number of conformations observed in synephrine would be observed for adrenaline (see the following discussion), which was however reported to give only 2 and not 12 conformers.9 This result means that a strong interaction exists between the catecholic OH groups and the side chain. In order to elucidate the reduction of the conformation in adrenaline, we compared the structures of synephrine with those of adrenaline and 2-methylamino-1-phenylethanol (MAPE), which has no phenolic OH. Also MAPE has been investigated by the Simons group and the conformational structures were assigned.11 According to their report, MAPE has three conformers, MAPE-AG, MAPE-GG, and PMAPE-AG (Figure 6), where the notation of the conformation is the same as that of synephrine. In the case of synephrine, due to the different two orientations of the phenolic

OH, which are denoted by “c” and “t”, each three conformations observed in MAPE generate two conformations. Thus the coexistence of six conformers is expected and is observed in fact. This conformational evolution means that the interaction between the phenolic OH and the side chain is weak. On the other hand, adrenaline, which has one more phenolic OH than synephrine, was reported to give two conformers, A-AG and PA-AG, where the notation is the same as that of MAPE and synephrine (Figure 6).11 In principle, three conformations can be thought of for the orientation of the catecholic OH groups, cis
trans (isoenergetic to trans
cis), cis
cis, and trans
trans forms, where cis and trans represent the OH orientation with respect to another OH group. In catechol, only the cis
trans form is, however, observed in the supersonic jet because of its specific stability by formation of an intramolecular hydrogen bond.9 Similarly, the orientation of the OH group in adrenaline is expected to be in the same manner as that in catechol. By introducing an OH group to the next position of the p-OH of synephrine in such a way that they adopt the cis
trans formation, for which there are two possible ways whether the additional OH group is introduced to left or right position of the p-OH, respectively denoted by “L” and “R”, each of the six conformers of synephrine generates two conformers. If the interaction between the catecholic OH groups and the side chain is weak similarly to synephrine, the number of conformers of adrenaline is expected to be two times larger than synephrine, i.e., 12. These 12 conformers can be classified into three families based on the conformations of the side chain, and each family has four conformers according to the different orientations of catecholic OH groups, cL, cR, tL, and tR. However, the observed (reported) conformers are only A-AG-cR and PA-AG-cR. This result clearly demonstrates that some interactions exist between the catecholic OH groups and the side chain. In previous work on adrenaline,9 C-arc-abal and co-workers considered differences of the evaporation techniques, laser desorption or traditional heating, for the difference of observed conformers in the gas phase. However, in this work the laser desorption technique was employed for synephrine, which is the same as in the case of adrenaline. Hence, the reduction in the number of conformers observed for adrenaline does not depend on the evaporation method, but is an intrinsic property of the adrenaline molecule. 10367

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Figure 7. Dipole
dipole interaction energies of the expected 12 conformers of adrenaline.

As described above, both A-AG and PA-AG forms adopt one orientation of catecholic OH groups, that is, cR, in which m-OH is oriented to the side chain and p-OH acts as a hydrogen donor to the m-OH. These structures evoke the existence of hydrogenbond-like interactions between the m-OH and the side-chain OH. However, the distance between the hydrogen atom of the m-OH and the oxygen atom of the side-chain OH is too far (∼4.72 Å) to form a normal hydrogen bond. Thus, direct interaction, such as a hydrogen bond, must be impossible. Then, to explain the reason why the cR orientation is favorable, dipole
dipole interaction energies between partial dipole moments of the catecholic OH groups and the side chain were estimated, as described in our previous paper.6 For the estimation of the partial dipole of each domain, μ1 and μ2, natural bond orbital (NBO) analysis was carried out on the optimized structures to obtain the charge distribution (population) by utilizing Gaussian 09. A charge center is assumed as the representative point of each domain, represented by r1 and r2. The difference between the each vector is represented by r = r1
r2. The dipole
dipole interaction energy E11(cm
1) is given as E11 ¼
ð1:161  105 Þ 1 f2ðμ1 3 rÞðμ2 3 rÞ
ðμ1  rÞ 3 ðμ2  rÞg r5 where units of length and dipole moment are angstroms and debyes, respectively. The calculated interaction energies E11 of each conformer are shown in Figure 7. As shown in Figure 7, the dipole
dipole interaction energy of the cR orientation is the largest within each family. The secondary stable orientation is cL; however, it is less stable by 500
600 cm
1 than the cR orientation. Therefore, it was confirmed that the favorability of the cR orientation is derived from the dipole
dipole interaction between the catecholic OH groups and the side chain. However, the question remains of why the A-GG-cR conformer is not observed in adrenaline, while the A-GG conformer of MAPE is the most populated.11 Reexaminations of the assignments of the structures of adrenaline, including the number of conformers, might be necessary. Reassignments of the conformers of adrenaline are now in progress, and we will present them soon elsewhere.

4. CONCLUSION REMPI, UV
UV hole burning, and IR dip spectra of synephrine were measured by utilizing the laser desorption supersonic jet technique. By comparing the REMPI and the UV
UV hole

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burning spectra, it was found that synephrine has six conformers under the ultracold condition. Similarity of spectral features of the UV
UV hole burning spectra leads to the conclusion that the conformation of the side chain of synephrine can be classified into three types, PS-AG-OHN, S-GG-OHN and S-AG-OHN, and each of them has two orientations of the phenolic OH group. Relative energies and theoretical IR spectra of presumable conformers were calculated to determine their conformational geometries. The conformational geometries were successfully assigned except for the orientation of the phenolic OH group by comparing the experimental and theoretical IR spectra. The conformational assignments were supported by the assignments of low frequency vibrational modes observed in the UV
UV hole burning spectra. On the basis of the determined structures, the conformational correlation among synephrine, MAPE, and adrenaline was investigated. MAPE has three conformers, MAPE-AG, MAPE-GG, and PMAPE-AG, which completely correspond to the three type conformers of synephrine mentioned above. By deduction of this conformational evolution, adrenaline is expected to have two times the number of conformers with synephrine, that is, 12, because an additional OH group can be introduced to the left or right position of p-OH to form an intramolecular hydrogen bond and each of the six conformers of synephrine generates two conformers. However, only two conformers, A-AG-cR and PA-AG-cR, are reported in adrenaline. This conformational evolution clearly demonstrates that the accumulated OH groups in the catechol ring do enhance an interaction between the catecholic OH groups and the side chain. By the estimation of the dipole
dipole interaction energies between the partial dipole moments of the catecholic OH groups and the side chain, it was found that the stability of observed conformers is derived from such an interaction.

’ AUTHOR INFORMATION Corresponding Author

*E-mail: [email protected]. Phone/fax: +81-45-924-5250.

’ ACKNOWLEDGMENT This study was supported in part by a Grant-in-Aid for Scientific Research KAKENHI in the priority area “Molecular Science for Supra Functional Systems” from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) Japan, and the Industrial Technology Research Grant Program in 2006. ’ REFERENCES (1) Shermann, J. P. Spectroscopy and Modeling of Biomolecular Building Blocks; Elsevier Science: New York, 2007. (2) Chin, W.; Piuzzi, F.; Dimicoli, I.; Mons, M. Phys. Chem. Chem. Phys. 2006, 8, 1033. (3) Robertson, E. G.; Simons, J. P. Phys. Chem. Chem. Phys. 2001, 3, 1. (4) Simons, J. P. Mol. Phys. 2009, 107, 2435. (5) Mitsuda, H.; Miyazaki, M.; Nielsen, I. B.; C-arc-abal, P.; Dedonder, C.; Jouvet, C.; Ishiuchi, S.; Fujii, M., J. Chem. Phys. Lett. 2010, 1, 1130. (6) Ishiuchi, S.; Mitsuda, H.; Asakawa, T.; Miyazaki, M.; Fujii, M. Phys. Chem. Chem. Phys. 2011, 13, 7812. (7) Snoek, L. C.; Van Mourik, T.; C-arc-abal, P.; Simons, J. P. Phys. Chem. Chem. Phys. 2003, 5, 4519. (8) Snoek, L. C.; Van Mourik, T.; Simons, J. P. Mol. Phys. 2003, 101, 1239. 10368

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dx.doi.org/10.1021/jp205267c |J. Phys. Chem. A 2011, 115, 10363–10369