Exploration of the full conformational landscapes of gaseous aromatic

amino acid phenylalanine: An ab initio study

Zhijian Huang, Wenbo Yu, Zijing Lin *

Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, China

Received 7 September 2005; received in revised form 29 October 2005; accepted 31 October 2005

Available online 27 December 2005

Abstract

Systematic ab initio calculations have been employed to characterize the conformational topology of gaseous aromatic phenylalanine (Phe). A

total of 37 local minima were located by geometry optimization of all possible trial structures at the B3LYP/6-311CCG(d,p) level of theory. The

relative energies, dipole moments, rotational constants, harmonic frequencies, and vertical as well as adiabatic ionization energies of all the

conformers were determined. The comparison of the theoretical and experimental ionization energies supports the conformational assignments

through the UV rotational band contour analysis of the resonantly enhanced two-photon ionization (R2PI) spectrum by [Y. Lee, J. Jung, B. Kim, P.

Butz, L. C. Snoek, R. T. Kroemer, J. P. Simons, J. Phys. Chem. A 108 (2004) 69]. The transition states among the nine lowest energy conformers

were searched at the MP2/6-311G(d) level of theory and used to explain the absence of conformers 4 and 8 in the R2PI spectrum of jet-cooled Phe

experiment. The conformational distributions of gaseous Phe at various temperatures were calculated according to the principle of the statistical

mechanics and correlated the experimental observation reasonably well. In addition to the discussion by the geometric criteria, the intramolecular

hydrogen bonding interactions of the conformers were also analyzed by the atoms in molecules (AIM) theory based upon the B3LYP/6-311CC

G(d,p) electron density.

q 2006 Elsevier B.V. All rights reserved.

Keywords: Phenylalanine conformer; Conformational distribution; Hydrogen bond; Ionization energy; Transition state.

1. Introduction

As the biological function of a protein or peptide is often

intimately dependent upon the conformation that the molecule

can adopt, there have been a lot of theoretical and experimental

studies on multi-conformer biomolecular systems in the gas

phase [2,3]. The attraction of gas-phase conformation lies in

the opportunity to study their intrinsic properties free of the

solvent environment. Of the 20 common amino acids, only

tryptophan, tyrosine, phenylalanine and histidine have

aromatic UV chromophores. Their side chains with big pfaces are frequently involved in catalysis and in ligation of

essential metal ions and each conformer is an especially

important model for developing the understanding of biologi-

cally interesting cation/p interactions [4–6]. Consequently,

aromatic amino acids have been the subject of most laser

spectroscopic studies on amino acids so far [1,7–16].

0166-1280/$ - see front matter q 2006 Elsevier B.V. All rights reserved.

doi:10.1016/j.theochem.2005.10.043

* Corresponding author. Tel.: C86 551 3607614; fax: C86 551 3606348.

E-mail address: zjlin@ustc.edu.cn (Z. Lin).

Over 10 years ago, Levy’s group first measured the

electronic spectra of Phe in a supersonic jet using laser-

induced fluorescence (LIF) spectroscopy and identified five

different conformers, labeled A, B, C, D and E, stabilized in the

low-temperature environment [11]. A sixth conformer, labeled

X, which was not detected in the fluorescence emission but

which appeared strongly in the R2PI spectrum, was later

identified by Simons and co-workers [14]. Based on the UV

and IR ion-dip spectroscopy results, the six conformers, A, B,

C, D, E and X, were structurally assigned respectively to the six

most stable conformers V, III, VI, II, IV and I located by ab

initio geometry optimization of 58 guess structures [14].

However, Kim and co-workers [15] investigated Phe and its

hydrated clusters excitation spectra in supersonic expansion by

R2PI and found that the weakly populated conformer E did not

exhibit a hydrogen-bonded (OH/N) structure of conformer

IV. The theoretical ionization energy of conformer E, assuming

the structure of conformer IV, also showed an unusual

deviation from that of the experimental photo-ionization-

efficiency curves [17,18] and Kim et al. suggested the need to

reassign conformer E. Subsequently, Lee et al. [1] provided a

new structural assignment based upon comparisons between

the partially resolved rotational band contours of the R2PI

Journal of Molecular Structure: THEOCHEM 758 (2006) 195–202

www.elsevier.com/locate/theochem

Z. Huang et al. / Journal of Molecular Structure: THEOCHEM 758 (2006) 195–202196

spectrum and simulations based upon ab initio geometries of

nine conformers and argued that conformers A and E should be

assigned to conformers VII and IX. By measuring the S1

lifetime of the six conformers, they also explained that the

inability of LIF to detect the lowest-lying conformer X was due

to the ultra short lifetime of the conformer.

To further the understanding of the conformational land-

scape of gaseous Phe, this work provides a thorough theoretical

search using reliable computational techniques to ascertain all

conformers are located. The conformation-dependent ioniz-

ation energies were computed and used to independently verify

the existing structural assignments by the rotational band

contours. In order to explain the missing of some low energy

conformers in the experiments, the transition states for relevant

conformers were calculated. To more reasonably estimate

the conformer compositions at various experimental tempera-

tures, the conformational distributions were calculated accord-

ing to the statistical principle, instead of the Boltzmann

distribution assumed previously based on the sum of the

conformer electronic energy and zero point energy [14].

Furthermore, the intramolecular hydrogen bonds of gaseous

Phe conformers were classified according to the conventional

geometry criteria and further analyzed using the atoms in

molecules (AIM) theory [19,20].

R=phenyl ring

2. Computational details

The DFT/B3LYP method [21,22] was used in the search of

Phe conformers as it was known to provide accurate molecular

structures and the associated vibrational frequencies and

infrared intensities [23–25]. As the MP2 theory [26,27]

provided better estimate of the conformational energy than

that of DFT/B3LYP when stacking interaction was involved

[28,29], MP2 electronic energies were used when discussing

the relative stabilities of the conformers. The B3LYP and MP2

calculations were performed with the GAUSSIAN 98 program

package [30], using various basis sets, e.g., 6-311G(d) and

6-311CCG(d,p).

The conformational space of Phe was explored through a

systematic variation of four dihedral angles in the molecular

side chain and of the fifth torsion about the bond connecting the

aromatic ring with the aliphatic moiety, i.e. the C4–N12, C4–C3,

C3–O1, C4–C5 and C5–C6 bonds (see Fig. 1). A series of trial

structures were generated by allowing for all combinations of

Fig. 1. Schematic planar structure and atom numbering for the phenylalanine

molecule.

internal single-bond rotamers, as shown in Fig. 2, leading to a

total of 648 possible structures for the Phe molecule. These

possible geometries were optimized at the B3LYP/6-311G(d)

level of theory, and a set of 43 unique conformers were located

in the calculations. These structures were subjected to further

geometry optimization at the B3LYP/6-311CCG(d,p) level of

theory in order to ascertain the structural accuracy and stability,

and 37 unique conformers remained. The structures of the 37

conformers are virtually identical at the B3LYP/6-311CCG(d,p) and B3LYP/6-311G(d) levels of theory. The zero-point

energies and harmonic frequencies of these conformers were

subsequently calculated. No imaginary frequency was

observed, further confirming that the optimized structures

were true local minima. Single-point energy calculations were

then performed for these conformers at the MP2/6-311CCG(d,p) level.

The conformational distributions at various temperatures

were calculated according to the statistical principle with the

accurate ab initio data. Specifically, the molecular partition

function was factorized into its translational, rotational,

vibrational, electronic, and nuclear parts with the Born-

Oppenheimer approximation and neglecting vibro-rotational

coupling, i.e., qZqtransqrotqvibqelecqmucl. The translational and

nuclear partition functions are identical for all of the species

and are irrelevant for the equilibrium distribution. The

expressions for the calculations of the rotational, vibrational

and electronic partition functions can be found in Ref. [31].

Using the respective data for the various conformers, i.e.,

rotational constants, vibrational frequencies, and ground-state

electronic energies, the gas- phase Phe partition functions can

be calculated for a given temperature. Consequently, the

equilibrium distribution of various conformers at a set

temperature can be determined. The rotational partition

functions depended only on the molecular structures and

their computations were straightforward for any given

geometries. The electronic partition functions were calculated

with the MP2/6-311CCG(d,p) energies as they reflected the

conformational energies better than that of B3LYP/6-311CCG(d,p) when stacking interaction was involved [28,29]. The

vibrational partition functions were computed using the

B3LYP/6-311G(d) vibrational frequencies scaled by a factor

a 2-fold : 0, 180

b 6-fold : 30, 90, 150, 210, 270, 330

c 3-fold : -120, 0, 120

d 6-fold : -120, -60, 0, 60, 120, 180

e 3-fold : 60, 120, 180

Fig. 2. Schematic illustration of the rotational degrees of freedom of

phenylalanine molecule. a, b, c, d and e refer to various internal single-bond

rotamers.

Z. Huang et al. / Journal of Molecular Structure: THEOCHEM 758 (2006) 195–202 197

of 0.96 as this approach provided good matches between

theoretical and experimental results [23–25,32].

These neutral structures were also used to calculate the

energies of cations by setting the charge and the spin

multiplicity equal to C1 and C2, respectively. The vertical

ionization energy was taken as the energy difference at the

B3LYP/6-311CCG(d,p) level between the cationic and

neutral Phe at the neutral conformation. The vertical ionization

energies of the six most stable conformers obtained were also

calculated at the B3LYP/6-311CG(d,p) and B3LYP/6-

311CCG(2df,p) levels of theory. For computing the adiabatic

ionization energies, optimizations of the cationic Phe geometry

were performed at the B3LYP/6-311G(d) level of theory, and

the single-point energies were calculated at the B3LYP/6-

311CCG(d,p) level of theory.

The transition states between any two conformers of the

nine lowest conformers were explored employing the

Synchronous Transit-Guided Quasi-Newton (STQN) [33,34]

method at the MP2/6-311G(d) level, which provided adequate

estimates of the barrier heights and was much less CPU

demanding than that of MP2/6-311CCG(d,p). To study the

electronic properties and the intramolecular hydrogen bonds,

the B3LYP/6-311CCG(d,p) densities of the optimized

structures were analyzed by the AIM2000 program [35], as

described in the AIM theory.

3. Results and discussion

3.1. Conformers and energies

After geometry optimizations of all possible 648 trial

structures, a total of 37 unique conformers of the gaseous Phe

have been located in our B3LYP/6-311CCG(d,p) calcu-

lations. Table 1 shows the relative energies by both B3LYP and

MP2/6-311CCG(d,p) calculations, relative zero-point

vibrational energies, rotational data and the components of

permanent dipole moment obtained for these stable con-

formers. The structures of the ten lowest energy isomers are

shown in Fig. 3.

Eight of the nine most stable conformers we obtained are the

same as those obtained by Simons and co-workers [14],

indicating a suitable selection of a limited guess structures with

accurate computational method is more effective in locating

the lowest energy conformers than that by first scanning the

complete set of trial structures with some low level theory and

then followed by more accurate calculations of the scanned

structures [36,37]. Conformer 8 was newly found here and

absent in the previous limited search and further MP2/6-311G*

geometry optimization of conformer 8 produced little

structural change. The conformer VIII found at the MP2/6-

311G(d,p) level in Ref. [14] corresponds to conformer 14

found here. Overall, the relative energies of the conformers

(relative to conformer 1) have some slight change by affiliating

diffuse function to the basis set.

The relative energies of the Phe conformers are determined

by the interplay of the different types of hydrogen bonds, the

interaction between the amino group and the phenyl ring plane,

the interaction between the carboxyl and the phenyl ring plane,

the steric strain and the repulsion of lone pairs on the nitrogen

and oxygen atoms and of the p electrons on the phenyl ring.

The energies of the 37 conformers obtained vary by

w10.8 kcal/mol at the MP2/6-311CCG(d,p) level of theory

due to various kinds of intramolecular H-bonding interactions.

According to the geometric criteria (using a distance of 2.80 A

as a cutoff for near-atom interactions) of judging the

intramolecular H-bond and analyzing all the stable conformers

obtained, in all we find 4 types of H-bonds, i.e. (1) OH/N

(conformers 1, 3–4, 17, 21, 34); (2) NH/OCOH (conformers

2, 6–10, 14, 22–24, 25–33); (3) NH/OHCO (conformers 5,

11–13, 15–16, 18–20, 36); (4) OH/OaC (conformers 2, 5–16,

18–20, 22–23). In addition, the p-electron cloud of the phenyl

ring can form a strong intramolecular H-bond with the amino

group or the hydroxyl group and consequently lower the

conformational energy. Conformer 1 is found to be the global

minimum at both the B3LYP/6-311CCG(d,p) and MP2/6-

311CCG(d,p) levels and is stabilized by H-bonding inter-

action of the type OH/N and through a favorable interaction

between the NH2 group and the phenyl ring (Cartesian

coordinates of conformer 1 can be found in the section

‘Appendix A’).

Conformer 2 has a bifurcated (NH2/OCOH) H-bond

and conformer 5 has a bifurcated (NH2/OHCO) H-bond.

Conformers 2 and 5 differ only in that the carboxyl plane

rotates 180 degree around the linking bond. Their separation

can be attributed to the relative weakness of the interaction

between the amino group and the hydroxyl rather than the

carbonyl oxygen atom.

3.2. Vertical ionization energies (VIE) and adiabatic ionization

energies (AIE)

B3LYP calculations with high-quality basis sets are known

to give good results for molecular ionization energies [17]. The

experimental VIE value of 9.25 eV for benzene [38] is close to

that of 9.00 eV for Phe [17,18], suggesting that the first

ionization of Phe is the detachment of a delocalized p-electron

of the phenyl ring. The calculated values of VIE and AIE for all

the 37 conformers of Phe at the B3LYP/6-311CCG(d,p) level

of theory are listed in Table 1. As can be seen later, the

theoretical VIEs for Phe conformers are not sensitive to the

basis set used.

As shown in Table 1, when the positively charged hydrogen

end of the amino or the carboxyl group interacts with the

phenyl group, such as conformers 1, 3, 4 and 24, these

conformers possess large VIEs. This can be ascribed to that the

attractive interaction between the positively charged hydrogen

and p-electron system of the aromatic ring becomes a repulsive

one upon ionization due to the newly formed positive charge on

the phenyl ring, as noted before [18]. On the other hand, when

the lone-pair electrons of the oxygen or nitrogen atom have a

direct interaction with the p-electron system, such as

conformers 10, 16 and 20 (about 8.40 eV), these conformers

possess much lower VIEs. In these conformers, when

detaching a delocalized p-electron upon the aromatic ring,

Table 1

Relative energies, relative zero-point vibrational energies (ZPVE), vertical ionization energies, adiabatic ionization energies and rotational data and dipole moments

for phenylalaninea

Conformer Relative energies Relative Rotational constants

B3LYP MP2 ZPVEs VIEs AIEs A B C Dipole (D)

1 0.00 0.00 0.00 8.73 8.23 1.691 0.616 0.547 5.49

2 1.21 0.44 K0.42 8.58 8.14 1.614 0.639 0.561 1.34

3 0.03 0.60 K0.16 8.86 8.48 2.458 0.455 0.419 6.03

4 0.27 1.40 K0.27 8.74 8.47 2.450 0.448 0.416 5.82

5 1.94 1.45 K0.31 8.48 8.18 1.624 0.634 0.559 1.61

6 1.53 1.63 K0.56 8.55 8.13 1.710 0.590 0.529 1.49

7 1.47 1.92 K0.54 8.55 8.13 2.421 0.459 0.418 2.56

8 3.16 2.17 K0.62 8.49 8.07 1.623 0.647 0.567 2.45

9 1.72 2.32 K0.63 8.52 8.12 2.468 0.458 0.412 2.09

10 2.61 2.34 K0.62 8.46 8.09 1.738 0.592 0.531 2.06

11 2.33 2.39 K0.56 8.57 8.07 1.719 0.582 0.527 1.55

12 2.21 2.63 K0.59 8.60 8.12 2.509 0.443 0.417 2.47

13 2.37 2.70 K0.63 8.56 8.12 2.442 0.457 0.419 2.87

14 1.62 2.71 K0.57 8.47 8.12 2.344 0.466 0.407 1.38

15 3.61 2.82 K0.52 8.51 8.08 1.604 0.655 0.576 2.34

16 3.70 3.44 K0.74 8.43 8.02 1.742 0.584 0.527 2.94

17 3.19 3.46 K0.34 8.57 8.11 1.918 0.566 0.492 5.35

18 2.81 3.86 K0.60 8.65 8.09 2.371 0.460 0.408 1.87

19 3.75 4.01 K0.58 8.55 8.01 1.831 0.549 0.482 2.61

20 4.55 4.43 K0.71 8.42 8.04 1.581 0.639 0.573 2.45

21 3.17 4.82 K0.13 8.56 8.10 2.036 0.517 0.437 5.35

22 4.67 4.90 K0.61 8.63 7.97 1.771 0.561 0.504 1.69

23 4.45 5.05 K0.74 8.53 8.01 1.965 0.537 0.470 1.93

24 5.31 5.41 K0.75 8.83 8.29 1.916 0.565 0.498 4.17

25 6.49 6.20 K0.78 8.73 8.25 1.893 0.577 0.517 5.27

26 7.03 6.20 K0.65 8.82 8.26 1.632 0.638 0.561 3.44

27 6.22 6.67 K0.84 8.82 8.26 1.966 0.550 0.489 5.25

28 7.42 7.04 K0.37 8.75 8.39 1.858 0.601 0.527 4.69

29 7.17 7.76 K0.81 8.68 8.28 2.412 0.459 0.418 5.20

30 8.89 8.02 K0.81 8.61 8.17 1.658 0.640 0.562 4.74

31 7.19 8.40 K0.75 8.88 8.27 2.314 0.467 0.406 3.60

32 7.62 8.49 K0.94 8.69 8.26 2.457 0.459 0.411 4.72

33 8.88 8.64 K0.56 8.73 8.16 1.721 0.601 0.570 4.68

34 9.03 9.81 K1.13 8.62 7.89 1.870 0.567 0.493 4.20

35 9.30 9.88 K0.80 8.66 7.86 1.712 0.573 0.514 3.81

36 9.76 10.11 K1.02 8.80 8.09 2.505 0.436 0.424 5.54

37 9.53 10.81 K0.74 8.68 8.31 2.351 0.444 0.415 3.88

a Geometries optimized at the B3LYP/6-311CCG(d,p) level and relative energies in kcal/mol at the B3LYP/6-311CCG(d,p) (B3LYP) and MP2/6-311CC

G(d,p) (MP2) levels. Relative ZPVE in kcal/mol at the B3LYP/6-311G(d) level, Rotational constants in GHZ and dipole moment (D) at the MP2/6-311CCG(d,p)

level. The vertical ionization energies (VIEs) and adiabatic ionization energies (AIEs) in eV were computed at the B3LYP/6-311CCG(d,p) level with the zero-

point energy corrections at the B3LYP/6-311G(d) level. Note that the zero-point energies have been scaled by the factor 0.96.

Z. Huang et al. / Journal of Molecular Structure: THEOCHEM 758 (2006) 195–202198

the repulsive interaction between the lone-pair electrons of the

heavy atom and the p-electron system becomes an attractive

one.

Only 15 conformers of cationic Phe were obtained after the

B3LYP/6-311CCG(d,p) geometry optimization of the 37

neutral Phe conformers. The cationic conformer minimizes its

energy with the geometry optimization and the AIE is lower

than the corresponding VIE by an amount between 0.27–

0.88 eV, as shown in Table 1. Some of the AIEs cannot be

taken literally due to that the large structural changes involved

in the optimization process may not reflect the true geometry

relaxation paths.

Fig. 4 shows the VIEs of the six Phe conformers determined by

the photo-ionization-efficiency experiment [17,18] and B3LYP

calculations with various basis sets. The 6-311CG(d,p),

6-311CCG(d,p) and 6-311CG(2df,p) basis sets gave virtually

the same VIE results. If the six observed conformers were

assigned to the six theoretical lowest energy conformers as

suggested initially [14], the experimental and theoretical VIE

pattern did not match, as noted before [17]. Based upon UV

rotational band contour analysis, Lee et al. pointed out the

conformers E and A should be reassigned to conformers 7 and 9,

respectively [1]. Following the later assignment, the theoretical

and experimental VIE variation patterns agree well. Therefore,

our VIE results provide an independent evidence in support of the

structural assignment made by Lee et al.

3.3. Conformational distribution and transition state

The conformational distributions at the various temperatures

are shown in Table 2. At 85 K, only three most stable conformers

may be observable in the equilibrium distribution. In fact,

Fig. 3. The ten lowest lying conformers of phenylalanine located at B3LYP/6-311CCG(d,p) level of theory. The three sets of numbers in parentheses (in kcal/mol)

are respectively the relative conformer energies by MP/6-311CCG(d,p), B3LYP/6-311G(d) and B3LYP/6-311CCG(d,p) calculations. As discussed in the text,

the experimentally detected conformers X, C, A, B, D, and E correspond respectively to conformers 1, 6, 7, 3, 2 and 9.

Fig. 4. Experimental and theoretical vertical ionization energies of the six phenylalanine conformers, X, C, A, B, D, and E. Curve a is the experimental results [17].

Curves b, c, and d, are B3LYP results with the basis set of 6-311CG(d,p), 6-311CCG(d,p), and 6-311CG(2df,p), respectively, following the previous assignment

of X, C, A, B, D, and E to conformers 1, 6, 5, 3, 2 and 4. The comparison between the experimental and theoretical patterns questions the assignment of A and E.

Curve e is the B3LYP/6-311CCG(d,p) results by reassigning A and E to conformers 7 and 9, respectively, as suggested by UV rotational band contour analysis [1].

Table 2

Equilibrium distributions (%) of Phenylalanine conformers at various temperatures

Conformer 85 K 198 K 298 K 398 K 418 498 K

1 86.8 42.2 21.6 11.8 10.6 7.1

2 9.5 28.5 25.5 19.2 18.1 14.3

3 3.6 16.8 15.8 11.8 11.1 8.6

4 – 3.0 5.7 6.0 6.0 5.4

5 – 2.5 5.0 5.7 5.7 5.4

6 – 4.3 11.6 15.1 15.4 15.5

7 – 0.7 2.3 3.3 3.4 3.6

8 – 0.3 1.4 2.2 2.3 2.6

9 – 0.3 1.5 2.5 2.7 3.1

10 – 0.4 2.4 4.2 4.4 5.2

Z. Huang et al. / Journal of Molecular Structure: THEOCHEM 758 (2006) 195–202 199

Table 3

The lowest energy barriers (in kcal/mol) among the nine most stable conformers

Transition

state

T2/1 T3/1 T4/3 T5/2 T6/2 T7/6 T8/2 T9/6

Energy barrier 15.97 4.24 0.34 3.27 3.98 1.96 0.94 2.88

TA/B denotes the transition state between the conformer A and the conformer B. The energy barriers were corrected by the zero-point vibrational energies at the

B3LYP/6-311G(d) level and scaled by the factor 0.96.

Z. Huang et al. / Journal of Molecular Structure: THEOCHEM 758 (2006) 195–202200

concentration of conformer 3 may be too low to be detectable.

Conformer 1 is the dominant isomer in the gas phase with more

than 87% concentration at 85 K. There is a big difference between

the dipole moments of conformers 1 and 2, of 5.49D and 1.34D,

respectively. Therefore, the theoretical distribution can be easily

verified by the permanent electric dipole moment measurement

[36]. As shown in Table 2, the concentration of the lowest energy

conformer decreases and that of the other stable conformers

increase rapidly with increasing temperature. At room tempera-

ture, conformers 1, 2, 3, and 6 are the primary isomers. The

concentration of the conformer 2 (w25%) is higher than that of

conformer 1 (w22%) due to favorable vibrational contribution.

At 418 K, conformer 2 has a concentration higher than that of

conformer 1 by over 50%, in agreement with the experimental

estimation [14].

The relative populations of jet-cooled Phe conformers may

not be consistent with the calculated conformational distri-

butions at the resource temperature [36,39–40], because of

collisional relaxation and the disposition of energy barriers on

the conformational potential energy surface. The transition

states among the nine lowest energy conformers were explored

Fig. 5. Contour maps of the B3LYP/6-311CCG(d,p) electron density for conforme

of the phenyl ring. The circles indicate that the atoms are in the plane and the triangle

outer most contour is r(r)Z0.001 au, and the remaining contours increase in the o

employing the 7-point STQN search at the MP2/6-311G(d)

level. The lowest energy barriers found are listed in Table 3.

The low transition barrier height of 0.34 kcal/mol between

conformer 4 and conformer 3 explains the missing of

conformer 4 in the jet-cooled Phe experiment as conformer 4

can easily go across the energy barrier and relax into conformer

3. The calculated population of conformer 8 is low at the

experimental temperature and the energy barrier between

conformers 2 and 8 is only 0.94 kcal/mol. It is easy to

understand that conformer 8 cannot be detected in the jet-

cooled experiment. However, the missing of conformer 5 has

no good explanation so far. This is likely due to the limitation

of the computational technique. Perhaps there could also be

some other reason to be revealed later, in analogue to the

missing of conformer 1 in the original experiment.

3.4. Intramolecular hydrogen bond

To describe intramolecular H-bonding properties in a more

theoretical way, we perform an AIM analysis of the B3LYP/6-

311CCG(d,p) electron charge density (r(r)) topology.

rs 1–6 in the plane containing the alphatic moiety and the C6, C8 and H20 atoms

s indicate that the atoms are out of the plane. Crosses indicate critical points. The

rder of 2!10n, 4!10n and 8!10n, with nZK3, K2, K1 and 0.

Table 4

Property analysis of the bond critical points (BCPs) between H-bond acceptors and H-bond donors for the ten most stable phenylalanine conformers at the B3LYP/6-

311CCG(d,p) level of theorya

Conformer BCP rb P2rb l1 l2 l3 3 Dc

1 OH/N 0.0375 0.1090 K0.0525 K0.0467 0.2082 0.1256 0.98

CaO/HC(r)b 0.0076 0.0249 K0.0059 K0.0048 0.0356 0.2346 1.26

2 HO/HC(r) 0.0043 0.0157 K0.0025 K0.0014 0.0196 0.7583 0.55

3 OH/N 0.0364 0.1075 K0.0503 K0.0445 0.2023 0.1310 0.96

4 OH/N 0.0362 0.1078 K0.0500 K0.0439 0.2017 0.1369 0.96

5 CaOLHC(r) 0.0055 0.0192 K0.0036 K0.0020 0.0248 0.7557 0.83

a Conformers are not shown in the table if no corresponding BCPs were found. rb and P2rb in atomic units are the electron density and its Laplacian at the BCP.

l1, l2 and l3 in au are the eigenvalues of the Hessian matrix of the electron density. 3 is the ellipticity.b r indicates that the C atom is on the phenyl ring.c D in A is the distance between the BCP and the corresponding RCP.

Z. Huang et al. / Journal of Molecular Structure: THEOCHEM 758 (2006) 195–202 201

The eight AIM criteria proposed by Popelier for the existence

of H-bond [20,41–42] have been systemically applied in order

to find the true intramolecular H-bonds.

The ten lowest energy conformers were emphasized here as

they involve all the 4 types of H-bonds by the geometric

criteria. The bond critical point (BCP) and ring critical point

(RCP) were found for the H-bonds of OH/N, CaO/HC(r)

and HO/HC(r) (r indicates that the C atom is on the phenyl

ring). However, no BCP and RCP were found for the H-bonds

of NH/OCOH, NH/OHCO or OH/OaC by the geometric

criteria, indicating these types of interactions are not true

H-bonds by the AIM theory. Note that no H-bond is found for

conformers 6–10. r(r) is plotted for the six most stable

conformers in the plane indicated in Fig. 5.

Table 4 lists values of the electron density and its Laplacian,

rb and P2rb, the bond ellipticity, 3, and three eigenvalues l1,

l2 and l3 of the Hessian of the density at the H-bond critical

point and the distance between the BCP and the corresponding

RCP. As shown in Table 4, all H-bonds are typical close-shell

interactions, the value for P2rb lying in the proposed range of

0.014–0.139 au [41]. rb and P2rb are the biggest and 3 is the

smallest in the OH/N H-bonds. This suggests that the OH/N

H-bond is the strongest among the three types of H-bonds and

the N atom is the best H-bond acceptor. According to the data

for rb and P2rb in Table 4, the CaO/HC(r) H-bond is very

weak, and the H-bond in conformer 1 is slightly stronger than

that in conformer 5. As shown in Table 4, the distances

between the BCPs and the RCPs in the OH/N and CaO/HC(r) H-bonds are reasonably large, indicating true intra-

molecular H-bonds. However, in the HO/HC(r) H-bond of

conformer 2, the distance between the BCP and RCP is very

small and the corresponding values of rb and P2rb are also

very small, both features show that the HO/HC(r) H-bond is

very weak and unstable [19]. As to the criterion of mutual

penetration of hydrogen and acceptor atom, it is fulfilled in all

the cases where there are BCPs and RCPs, as partially

displayed in Fig. 5.

From the above discussion, two types of interactions

between the H-bonding acceptors and H-bonding donors

(OH/N and CaO/HC(r)) well satisfy the eight AIM criteria.

The phenyl ring may act as H-bonding donor as found in Ref.

[14]. However, the N3H/OCOH, N3H/OHCO and OH/OaC H-bonds by the geometric criteria have not been found in

the AIM study, indicating that the AIM criteria for H-bond is

much more stringent than that of the conventional geometric

criteria, consistent with previous finding [43,44]. Though AIM

is theoretically more rigorous, the geometric criteria for

H-bond is still of supplemental use for explaining the relative

conformer stabilities as AIM indicates only a weak HO/HC(r)

H-bond for conformer 2.

4. Summary

37 gaseous Phe conformers have been found by the full

conformational space exploration at the B3LYP/6-311CCG(d,p) level of theory. Their relative energies, dipole moments,

zero-point vibrational energies, rotational constants, vertical

and adiabatic ionization energies are presented. The confor-

mational distributions at various temperatures are also obtained

based on the MP2/6-311CCG(d,p) electronic energies and

B3LYP/6-311G(d,p) rotational constants and frequencies. The

comparison between the theoretical and experimental VIEs

shows that peaks E and A in the R2PI spectrum should be

assigned to conformers 9 and 7, respectively, consistent with

the result through rotational band contour analysis in Ref. [1].

The results of the transition state calculations show that

conformer 4 (or 8) may easily go across the energy barrier and

relax into conformer 3 (or 2) and conformers 4 and 8 cannot be

located experimentally, explaining the jet-cooled experiments

well.

Four types of H-bonds, OH/N, NH/OCOH, NH/OHCO

and OH/OaC, were found in the 37 conformers by the

geometric criteria with a cutoff distance of 2.8A. The most

stable structure, conformer 1 is stabilized by H-bonding

interaction (OH/N) and through a favorable interaction

between the NH2 group and the phenyl ring, a common

feature of the gaseous conformations of all aromatic amino

acids. This feature is characteristically different from that of the

aliphatic amino acids with the global minima involving the

bifurcated NH/OCOH bonds, suggesting a significant effect

of the side chain on the relative stabilities of amino acid

conformers.

The intramolecular H-bonding properties of the ten most

stable conformers have also been investigated by AIM theory

with the B3LYP/6-311CCG(d,p) densities. Only two types of

H-bonds, namely, OH/N and CaO/HC(r) were found in

Z. Huang et al. / Journal of Molecular Structure: THEOCHEM 758 (2006) 195–202202

these conformers. The OH/N bond is strong while the

CaO/HC(r) bond is weak. Similar to the previous finding in

the other amino acid systems, the H-bond types of NH/O-

COH, NH/OHCO and OH/OaC by the geometric criteria

fail to meet the AIM test. The geometric criteria for H-bond is

still of supplemental use when considering the relative

conformer stabilities.

Acknowledgements

ZL thanks the financial support of the National Science

Foundation of China (Grant No. 10574114) and the Chinese

Science Academy through the Hundred Talent Program.

Appendix. The Cartesian Coordinates of the most stable

conformer (the structure parameters of all the 37

conformers discussed in this paper can be obtained by

contacting the authors)

Coordinates (A)

Number Atomic X Y Z

1 O K1.701190 K2.184325 1.304755

2 O 0.433718 K1.969591 1.935280

3 C K0.400336 K1.987969 1.068402

4 C K0.064150 K1.843136 K0.435787

5 C 1.118130 K0.874402 K0.673639

6 C 0.768208 0.585109 K0.479337

7 C 0.417943 1.386620 1.573016

8 C 0.763739 1.163215 0.797569

9 C 0.070048 2.726106 1.401471

10 C 0.417941 2.500882 0.970345

11 C 0.068175 3.286576 K0.127039

12 N K1.303183 K1.555107 K1.175320

13 H K0.197801 4.329714 0.010414

14 H K1.446834 K0.552389 K1.258272

15 H K2.141805 K2.116522 0.427574

16 H 0.263036 K2.845270 K0.736966

17 H 1.919850 K1.166633 0.007331

18 H 1.486429 K1.030287 K1.692475

19 H 0.438701 0.964015 K2.574408

20 H 1.031514 0.556533 1.655647

21 H K0.190462 3.331417 K2.264102

22 H 0.425298 2.931770 1.966494

23 H K1.284059 K1.943273 K2.110439

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