Abstract
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 [1–3]. 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 Cl…N 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.
(a)
(b)
(c)
(d)
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.
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.
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.
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.
3.5. NBO Analysis
The role of hyperconjugative interactions in the stabilization of the conformers of the compound was investigated by NBO analysis [22–25]. 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.
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.