Density Functional Theory Study on Conformers of Benzoylcholine Chloride

e optimized molecular structures and vibrational frequencies and also gauge including atomic orbital (GIAO) H and C NMR shi 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.e 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.e 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.


Introduction
e determination of the minimum energy conformers of acetylcholine has been subject by many theoretical works [1][2][3].Marino et al. have investigated the conformational behavior and molecular motion of acetylcholine in vacuum and aqueous solution [4].ey have calculated �ve low lying conformers by molecular mechanics computing.e ab initio data of acetylcholine has indicated that the most stable conformer is the transgauche arrangement of the two essential torsion angles ( 1 ; C-C-O-C and  2 ; N-C-C-O) [5,6].e observed conformer of acetylcholine is transgauche ( 1 = −166.9and  2 = 84.7 ∘ ) in the crystal of its chloride [7,8], gauche-gauche ( 1 = 78.9 and  2 = 78.4∘ ) in the crystal of its bromide [9], and gauche-gauche ( 1 = ±83 and  2 = ±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.

Computational Details
e 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.e calculated vibration frequencies have been scaled with a scale factor of 0.9614 [13].e chemical shis of 1 H and 13 C 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 shi calculations on fairly large molecules [15,16].In the chemical shi calculations tetramethylsilane (TMS) was used as reference molecule.seen in Figure 1.In calculations �rstly 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).e PES showed four minimumenergy structures (Figure 2).e 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.ese structures were chosen as initial geometry to obtain the further ones.e conformers of the compound are de�ned by �ve essential torsion angles as given in Table 1.

Results and Discussion
For comparison, the experimental data being available for a similar molecule, acetylcholine chloride, are also shown in the table.e electronic energies, relative energies, and mean vibrational deviations for all the conformers of the compound are given in Table 2. e 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.erefore, 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.is comment has also been given for pyridine carboxaldehyde and di�uorobenzaldehyde molecules in our previous studies [17,18].From Table 2 we also see that the relative energies and mean vibrational where  calc  and  exp  are the calculated and experimental chemical shis 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.e 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.e �rst 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.
e assignments in the table are similar those done for a choline derivative molecule, acetylcholine bromide, which is available in literature [21].

Geometric Structures.
BzChCl consists of a benzene ring and a choline group.e 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].e  2 , 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.5.According to these values one important observation is that the calculated results for the average chemical shis values of the two conformers have a better agreement with the experimental data relative to the individual conformers.

NBO Analysis. e role of hyperconjugative interactions
in the stabilization of the conformers of the compound was investigated by NBO analysis [22][23][24][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.is supports that the two conformers of the compound should have close optimized energies.
3.6.Spectral Analysis.e 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.e powder experimental spectra of the compound are also given in the �gures, as labeled (d).As seen the experimental IR or R spectrum does �t well to none of the calculated spectra for the two conformers, individually.e 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 �t very well to each other.erefore, 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 shis by taking into consideration the  2 , MAE, and RMSE values we see from Table 5 the agreement between them are better for the average chemical shi values of the two conformers.is also con�rms 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.is is maybe because of highly deliquescent of choline compounds.

Conclusion
e optimized molecular structures (bond lengths and bond angles), vibrational frequencies, and chemical shis of all the conformers of benzoylcholine chloride have been calculated using B3LYP method at 6-31++G(d) basis set level.e comparison of the experimental and calculated IR, R, and NMR T 5: eoretical and experimental 13   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.

3. 1 .F 1 :F 2 :
Ground State Conformers.e molecular structures of all the calculated optimized conformers of BzChCl can be Optimized molecular structures of four conformers of BzChCl.T 1: Five essential torsion angles for all the conformers of BzChCl.Torsion Angles ( Potential energy surface (PES) scan of BzChCl.

F 3 :
Calculated IR and R spectra of conformers I and II of BzChCl as labeled (a) and (b), respectively.(c) shows the sum of (a) and (b); (d) shows experimental spectrum [19].

T 2 :
Electronic energies, and relative energies and mean calculated vibrational deviations between the conformers of BzChCl.
[19]+ (CH 3 ) 1381ms 1374 60 (C-CH 2 ) + (CH 3 ) + (CH) + (Ring) 1341w 1346w 1338 59 (C-CH 2 ) + (CH 3 ) + (CH) 1311m 1311w 1314 58 (CH) + (CCC) 1283m 1299 57 (N-CH 3 ) + (C-CH 2 ) + (N-CH w: weak, m: medium, s: strong, v: very, sh: shoulder, and br: broad.deviations between the conformers I and II are fairly low while the others are fairly high.erefore,wetakeintoaccountonly the conformers I and II aer this part of the study.3.2.VibrationalFrequencies. e calculated vibrational frequencies and proposed vibrational assignments for the two lowest energy conformers I and II of BzChCl are given in Table3.In the table are also given the experimental vibrational frequencies (IR and R) of the compound[19].e linear correlation coefficients ( 2 ), mean absolute error (MAE) and the root mean square errors (RMSE) were also given in the last lines of the table.e RMSE is de�ned by 1H and13C NMR chemical shis (with respect to TMS) for the lowest energy conformers I and II of BzChCl are given in Table5.e experimental chemical shis have been obtained from Spectral Database for Organic Compounds Web Page [20].Since the experimental 1 H chemical shi values of individual hydrogens are not available we have found the average values of 1 H chemical shis for the CH 2 and CH 3 hydrogen atoms.ese are shown as bold in the table.For comparison the average chemical shi values of the two conformers are also given in the table.e  2 , MEA, and RMSE values between the experimental and theoretical chemical shis are obtained, and given in the last two lines of Table T 4: Calculated optimized geometric parameters for two lower-energy conformers of BzChCl.
C and 1 H isotropic chemical shi (with respect to TMS, all values in ppm) for two lower-energy conformers of BzChCl.Calculated hyperconjugative interactions (kcal mol −1 ) for two lower-energy conformers of BzChCl.