Journal of Spectroscopy

Journal of Spectroscopy / 2013 / Article

Research Article | Open Access

Volume 2013 |Article ID 369342 |

Mustafa Karakaya, Fatih Ucun, Ahmet Tokatlı, "Density Functional Theory Study on Conformers of Benzoylcholine Chloride", Journal of Spectroscopy, vol. 2013, Article ID 369342, 10 pages, 2013.

Density Functional Theory Study on Conformers of Benzoylcholine Chloride

Academic Editor: Nicolae Leopold
Received21 Jun 2012
Accepted09 Aug 2012
Published13 Sep 2012


The optimized molecular structures and vibrational frequencies and also gauge including atomic orbital (GIAO) 1H and 13C NMR shift values of benzoylcholine chloride [(2-benzoyloxyethyl) trimethyl ammonium chloride] have been calculated using density functional theory (B3LYP) method with 6-31++G(d) basis set. The comparison of the experimental and calculated infrared (IR), Raman, and nuclear magnetic resonance (NMR) spectra has indicated that the experimental spectra are formed from the superposition of the spectra of two lowest energy conformers of the compound. So, it was concluded that the compound simultaneously exists in two optimized conformers in the ground state. Also the natural bond orbital (NBO) analysis has supported the simultaneous exiting of two conformers in the ground state. The calculated optimized geometric parameters (bond lengths and bond angles) and vibrational frequencies for both the lowest energy conformers were seen to be in a well agreement with the corresponding experimental data.

1. Introduction

The determination of the minimum energy conformers of acetylcholine has been subject by many theoretical works [13]. Marino et al. have investigated the conformational behavior and molecular motion of acetylcholine in vacuum and aqueous solution [4]. They have calculated five low lying conformers by molecular mechanics computing. The ab initio data of acetylcholine has indicated that the most stable conformer is the transgauche arrangement of the two essential torsion angles (; C-C-O-C and ; N-C-C-O) [5, 6]. The observed conformer of acetylcholine is transgauche ( = −166.9 and = 84.7°) in the crystal of its chloride [7, 8], gauche-gauche ( and = 78.4°) in the crystal of its bromide [9], and gauche-gauche ( = ±83 and 89°) in the crystal of its iodide [10].

In this study we wish to report the IR, Raman (R), NMR, and NBO analysis of benzoylcholine chloride (BzChCl) to obtain the lowest energy conformer in the ground state by means of density functional theory (B3LYP) method.

2. Computational Details

The optimized structure parameters and vibrational frequencies of BzChCl were calculated by density functional theory B3LYP method at 6-31++G(d) basis set level. All the computations were performed by using Gaussian 03 package [11] and Gauss-View molecular visualization programs [12] on the personal computer. The calculated vibration frequencies have been scaled with a scale factor of 0.9614 [13]. The chemical shifts of 1H and 13C NMR in vacuum for all the conformers of the compound were calculated by GIAO method [14] using the same set level of the theory which is routinely used for NMR chemical shift calculations on fairly large molecules [15, 16]. In the chemical shift calculations tetramethylsilane (TMS) was used as reference molecule.

3. Results and Discussion

3.1. Ground State Conformers

The molecular structures of all the calculated optimized conformers of BzChCl can be seen in Figure 1. In calculations firstly the potential energy surface (PES) of the compound was scanned around the torsion angle of Cl(34)-C(11)-N(19)-C(4) from −180° to 180° at increments of 20° with an ClN distance of around 3.60 Å at B3LYP/6-31 G(d,p). The PES showed four minimum-energy structures (Figure 2). The barrier height between the conformer I and II is 9.6 kcal/mol while those between the conformer I and III or I and IV is bigger than 13 kcal/mol. These structures were chosen as initial geometry to obtain the further ones. The conformers of the compound are defined by five essential torsion angles as given in Table 1. For comparison, the experimental data being available for a similar molecule, acetylcholine chloride, are also shown in the table.

Torsion Angles (°)Exp. [6]Conformer I
Conformer II
Conformer III
Conformer IV

𝜏 𝟏 [C(21)-O(20)-C(1)-C(4)] 167.9 115.02 83.64 −179.64 136.13
𝜏 𝟐 [O(20)-C(1)-C(4)-N(19)] 84.7 −81.83 −153.87 −179.83 −87.70
𝜏 𝟑 [C(1)-C(4)-N(19)-C(11)] 171.4 −172.97 −49.28 −61.10 174.13
𝜏 𝟒 [C(1)-C(4)-N(19)-Cl(34)] −112.83 −105.05 −179.75 −166.48
𝜏 𝟓 [O(22)-C(21)-O(20)-C(1)] 5.2 −9.68 −0.87 0.00 −3.70

The electronic energies, relative energies, and mean vibrational deviations for all the conformers of the compound are given in Table 2. The relative energy values and calculated mean vibrational deviations in the table are respect to the lowest energy conformer I of the compound. As seen the mean vibrational deviation increases while the relative energy increases. Therefore, we state that the more different the molecular structures of the two conformers are the higher the relative energy is between them, and so, a bigger mean vibrational deviation occurs. This comment has also been given for pyridine carboxaldehyde and difluorobenzaldehyde molecules in our previous studies [17, 18]. From Table 2 we also see that the relative energies and mean vibrational deviations between the conformers I and II are fairly low while the others are fairly high. Therefore, we take into account only the conformers I and II after this part of the study.

Conformer I
Conformer II
Conformer III
Conformer IV

Energy (Hartree/part.) −1133.243575 −1133.242015 −1133.239145 −1133.238584
Relative energy (kcal/mol) 0.00 0.978 2.778 3.130
Vib. deviations | | | | Δ 𝜈 a v e 0.00 6.219688 9.875208 6.393542

3.2. Vibrational Frequencies

The calculated vibrational frequencies and proposed vibrational assignments for the two lowest energy conformers I and II of BzChCl are given in Table 3. In the table are also given the experimental vibrational frequencies (IR and R) of the compound [19]. The linear correlation coefficients (), mean absolute error (MAE) and the root mean square errors (RMSE) were also given in the last lines of the table. The RMSE is defined by the following where and are the calculated and experimental chemical shifts of atom i, respectively, and n denotes the number of atoms. According to these values it can be stated that the calculated vibrational frequencies are in a good agreement with the experiment data. The calculated vibrational frequencies are slightly higher than the observable values for the majority of the normal modes. Two factors may be responsible for this discrepancy. The first is the environmental change of the molecule in the experimental medium and the second is that the calculated frequencies are harmonic while the experimental ones are anharmonic.

Mode no.AssignmentsExperimental frequencies Calculated frequencies
(cm−1) BzChCl [19](cm−1) B3LYP 6-31++G(d)
IRRConformer I Conformer II

96Ring ν(CH)sym 31073109
95Ring ν(CH)sym 3091vw31003098
94Ring ν(CH)asym 30863086
93Ring ν(CH)asym 30853078
92ν(CH3)asym 3073s30773076
91Ring ν(CH)asym 3068sh30663065
90ν(CH3)asym 3065w30653058
89ν(CH3)asym 30533053
88ν(CH3)asym 30503048
87ν(CH3)asym + ν(CH2)asym3037w30463044
86ν(CH2)asym + ν(CH3)asym3034vw3023m30263024
85ν(CH3)asym + ν(CH2)asym30183018
83ν(CH3)sym + ν(CH2)sym2979m29882980
82ν(CH2)sym + ν(CH3)sym2956.2927vs2951m29722975
81ν(CH3)sym + ν(CH2)sym2932m29192920
80ν(CH3)sym + ν(CH2)sym2871sh2892w29062904
79ν(CH2)sym + ν(CH3)sym2855vs2836vw28092887
78ν (C=O)1725vs1726vs16871688
77Ring ν (C=C) + Ring δ(CH) 1598m1601s15881589
76Ring ν (C=C) + Ring δ(CH)1583w1584w15691569
75γ(CH3) + δ(CH2)14981493
74γ(CH3) + δ(CH2)1486m1489vw14851479
73δ(CH2) + γ(CH3) + Ring δ(CCH)14811476
72Ring δ(CCH) + δ(CH2) + γ(CH3)1471sh14751474
71γ(CH3) + δ(CH2)14661464
70γ(CH3) + δ(CH2)14641458
69δ(CH3) + δ(CH2)1459, 1451s1455m14581455
68Ring δ(CH) + γ(CH3) + δ(C–CH2) + δ(CH2)1443w14451448
67δ(CH2) + γ(CH3)14371444
66γ(CH3) + δ(CH3)14351434
65Ring δ(CH) + ν(Ring) + δ(CCC)1434sh14341434
64δ(CH3) + δ(C–CH2)1411w1413vw14131412
63δ(CH3) + δ(C–CH2)1404vw14021402
62δ(CH3) + δ(C–CH2)1385vw13941391
61δ(C–CH2) + δ(CH3)1381ms13741362
60δ(C–CH2) + δ(CH3) + δ(CH) + ν(Ring)1341w1346w13381319
59δ(C–CH2) + δ(CH3) + δ(CH)1311m1311w13141314
58δ(CH) + δ(CCC)1283m12991300
57δ(N–CH3) + δ(C–CH2) + ν(N–CH2)1280.1261s1269sh12721281
56δ(C–CH2) + δ(N–CH3)1249sh1261m12591262
55δ(C–CH2) + δ(CH) + ν(C–O)
+ Ring ν(C–C) + δ(CC=O)
54δ(N–CH3) + δ(C–CH2) + ν(N–CH3)1219vw1221w12311227
53δ(N–CH3) + δ(C–CH2)12061209
48δ(CCC) + ν(CO) + δ(NCH)1103w1089vw10931094
46τ(HCCH) + δ(NCH)1041vw10581060
44δ(NCH) + Ring ν(CC)1018m10111026
43δ(CCH) + ν(O–C)1002s10031012
42δ(Ring) + ν(O–CH2) + δ(NCH)992vw983979
41 𝜏 (HCCH)979978
40 𝜏 (HCCH)978976
39 𝜏 (HCCH)951ms959, 953w961961
38ν(N–CH3) + δ(NCH)929940
37 𝜏 (Ring)927927
36δ(CCH) + ν(N–CH3)902m903w906924
35ν(N–CH3) + δ(NCH)869w871w861883
34Ring γ(CH)836m835835
33δ(N–CH3) + δ(Ring) + δ(OC=O)812vw811vw828825
32 𝜏 (HCCH) + Ring γ(CH) + γ(OC=O)793788
31 𝜏 (HCCH) + Ring γ(CH) + γ(OCC)785778
30Breathing (choline)714s724m698717
29Ring γ(CH) + γ(CC=O)688vw680m673699
27δ(Ring) + δ(COC)657663
25δ(N–CH3) + δ(NCC) + δ(OCC)544w544vw526516
24δ(N–CH3) + δ(NCC) + δ(OCC)474w495vw471465
23δ(N–CH3) + δ(N–CH2)476w454459
21γ(Ring) + γ(OC=O)423w431434
18δ(N–CH3) + 𝜌 𝑟 (CH2) 369w369374
17 𝜌 𝑟 (CH2) + 𝜌 𝑟 (CH3) 356357
16 𝜌 𝑟 (CH3) out of plane 344329
15 𝜌 𝑟 (CH3) out of plane324322
14 𝑤 (CH3)303293
13 𝜌 𝑟 (CH3) out of plane 261w266266
12 𝜌 𝑟 (Ring) + 𝑤 (CH3)255236
11 𝜌 𝑟 (CH2) + 𝑤 (Ring) 209m236226
10ν(N–Cl) + 𝜌 𝑟 (CH3) out of plane 185177
9 𝑤 (Ring) + ν(N–Cl)166w166161
8 𝜌 𝑟 (CH3) + 𝜌 𝑟 (CH2) 138149
7 𝜌 𝑟 (CH2) + 𝑤 (Ring)132130
6 𝜌 𝑟 (CH2) + 𝜌 𝑟 (CH3)111w106114
5 𝑤 (CH2) + 𝑤 (C=O) 8472
4 𝜌 𝑟 (Ring) + 𝑤 (CH2) + 𝜌 𝑟 (CH3)6354
3 𝑤 (Ring) + 𝑤 (C=O) + 𝑤 (Cl) 3833
2 𝑤 (Ring) + 𝜌 𝑟 (CH3) out of plane 2526
1 𝜌 𝑟 (Ring) out of plane + 𝑤 (CH3) 1920

     𝑅 2 0.99980.9998



w: weak, m: medium, s: strong, v: very, sh: shoulder, and br: broad.

The assignments in the table are similar those done for a choline derivative molecule, acetylcholine bromide, which is available in literature [21].

3.3. Geometric Structures

BzChCl consists of a benzene ring and a choline group. The calculated optimized structure parameters for the lowest energy conformers I and II of BzChCl are summarized in Table 4, in accordance with the atom numbers in Figure 1. Since the X-ray analysis of the compound could not be reached the theoretical optimized structures were compared with those of acetylcholine chloride for which the crystal structure has been solved [5]. The , MEA, and RMSE values between the calculated and experimental geometric parameters are given in the last lines of the table and they show a well agreement for the two conformers.

Parameters Experimental [6]Calculated B3LYP [6-31++G(d)]
Bond lengths (Å)Conformer I Conformer II


     𝑅 2 0.9990.9414




     𝑅 2 0.76230.8597



3.4. Chemical Shifts

The experimental and calculated 1H and 13C NMR chemical shifts (with respect to TMS) for the lowest energy conformers I and II of BzChCl are given in Table 5. The experimental chemical shifts have been obtained from Spectral Database for Organic Compounds Web Page [20]. Since the experimental 1H chemical shift values of individual hydrogens are not available we have found the average values of 1H chemical shifts for the CH2 and CH3 hydrogen atoms. These are shown as bold in the table. For comparison the average chemical shift values of the two conformers are also given in the table. The , MEA, and RMSE values between the experimental and theoretical chemical shifts are obtained, and given in the last two lines of Table 5. According to these values one important observation is that the calculated results for the average chemical shifts values of the two conformers have a better agreement with the experimental data relative to the individual conformers.

Atom Experimental (ppm) (in DMSO-d6) [20]Calculated B3LYP/6-31++G(d) GIAO
Conformer I Conformer II Average


       𝑅 2 0.99670.99730.9985



 H29 8.3738.2578.315
 H33 8.1408.2308.185
 H30 7.4587.4687.463

       𝑅 2 0.92900.97130.9665



3.5. NBO Analysis

The role of hyperconjugative interactions in the stabilization of the conformers of the compound was investigated by NBO analysis [2225]. Here, the hyperconjugative represents the transfer of an electron from the lone pair (LP Cl) to an antibonding orbital since the molecular structures of the conformers are only changed by the location of the Cl anion. Table 6 consists of hyperconjugative interactions (kcal mol−1) for the two lowest energy conformers of the compound calculated by using the B3LYP/LANL2DZ method. As seen the total hyperconjugative energies determined relative to only the location of the Cl anion for the two conformers are very near. This supports that the two conformers of the compound should have close optimized energies.

Donor NBOAcceptor NBOCalculated B3LYP/6-31++G(d)
Conformer I Conformer II

LP (Cl)σ * C1H20.09
σ * C4H50.120.20
σ * C4H615.0310.26
σ * C7H97.54
σ * C11H1310.07
σ * C11H147.51
σ * C11N190.08
σ * C15H186.92

Total 30.2027.62

Relative energy2.580.00

3.6. Spectral Analysis

The calculated IR and R spectra of the lowest energy conformers I and II of the compound are given in Figures 3(a) and 3(b), respectively. The powder experimental spectra of the compound are also given in the figures, as labeled (d). As seen the experimental IR or R spectrum does fit well to none of the calculated spectra for the two conformers, individually. The experimental spectra show the peaks splinted doublets or triplets, and thus, have more spectral lines than the calculated ones. Since the relative energy values and barrier height between the two conformers of the compound are very low we think that the spectra of these two conformers can simultaneously exist in one experimental spectrum. So, we have drawn the sum of the calculated spectra (IR or R) of these conformers, and obtained the spectra in Figure 3(c). By confronting them to the experimental ones (Figure 3(d)) it can be seen that they fit very well to each other. Therefore, we state that the title compound simultaneously contain these two optimized lowest energy conformers of the compound in the ground state.

When we investigate the relationship of the experimental and calculated chemical shifts by taking into consideration the , MAE, and RMSE values we see from Table 5 the agreement between them are better for the average chemical shift values of the two conformers. This also confirms the simultaneous presence of the two conformers, regarding one experimental NMR spectrum for the two conformers since of their fast motions in the solution phase. Since of these, we state that the title compound simultaneously contains the two optimized energy conformers in the ground state. This is maybe because of highly deliquescent of choline compounds.

4. Conclusion

The optimized molecular structures (bond lengths and bond angles), vibrational frequencies, and chemical shifts of all the conformers of benzoylcholine chloride have been calculated using B3LYP method at 6-31++G(d) basis set level. The comparison of the experimental and calculated IR, R, and NMR spectra of the compound have shown that the experimental spectra are formed from the superposition of the spectra of two optimized energy conformers of the compound. So it was concluded the compound simultaneously exits in two optimized energy conformers in the ground state.


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