3.1 X-ray diffraction study
Parallelepiped shaped transparent crystals of new semiorganic material 2,4-dichloroanilinum perchlorate, (C6H6Cl2N)ClO4 (I) were obtained from an acidic reaction of 2,4-dichloroaniline treated with an equivalent amount of perchloric acid. Crystal data, data collection and refinement of (I) are exhibited in Table 1.
Table 1
Crystallographic data and structure refinement of [C6H6Cl2N] ClO4
Chemical formula
|
C6H6Cl3NO4
|
Formula weight (g.mol− 1)
|
262.48
|
Temperature (K)
|
183
|
Crystal System
|
Orthorhombic
|
Space group
|
Pbca
|
Unit cell dimensions
|
a = 10.4483 (8) Å
b = 7.6093 (7) Å
c = 23.558 (3) Å
|
|
Z
|
8
|
Cell volume (Å3)
|
1873.0 (3)
0.96
0.30 × 0.30 × 0.30
|
Absorption coefficient µ (mm− 1)
|
Crystal dimensions (mm3)
|
Color, shape
|
colorless, Block
|
Diffractometer
|
Mercury CCD System (Rigaku)
|
θ range (°)
|
θmin = 3.4°,θmax = 27.5°
|
Index range (h, k, l)
|
h = − 13→13, k = − 9→8, l = − 30→21
|
No. of measured, independent and observed with I > 2σ(I) reflections
|
12421, 2125, 1927
|
Rint
|
0.039
|
Absorption Correction: Integration
|
Tmin = 0.611, Tmax = 0.749
|
Radiation type
|
Mo (Kα) λ(Å) = 0.71075
|
R, wR2
|
0.054, 0.132
|
Goodness-of-fit on F2
|
1.15
|
Δρmax, Δρmin (e Å−3)
|
0.44, −0.70
|
The crystallographic investigation reveals that the asymmetric part of the unit cell contains a 2,4-chloroanilinium cation and a perchlorate anion (Fig. 1). The protonation on the N site of the cation is confirmed from the elongated C-N bond distance [1.467 (4) Å] and deprotonation from the anion is confirmed from the Cl-O bond distances and O-Cl-O angles as listed in Table 2.
Table 2
Selected bond lengths and bond angles of (ClO4)− anion in [C6H6Cl2N]ClO4.
Bond length (Å)
|
X-ray
|
M062X
|
Bond angles (°)
|
X-ray
|
M062X
|
(ClO4)− anion
|
|
|
|
|
|
Cl1—O4
|
1.422 (2)
|
1.425
|
O4—Cl1—O2
|
110.49 (16)
|
111.7049
|
Cl1—O2
|
1.440 (2)
|
1.4486
|
O4—Cl1—O3
|
111.26 (17)
|
112.2647
|
Cl1—O3
|
1.442 (2)
|
1.4437
|
O2—Cl1—O3
|
109.53 (15)
|
108.8559
|
Cl1—O1
|
1.454 (2)
|
1.4968
|
O4—Cl1—O1
|
109.64 (15)
|
109.8553
|
|
|
|
O2—Cl1—O1
|
107.98 (16)
|
106.9794
|
|
|
|
O3—Cl1—O1
|
107.85 (15)
|
106.9205
|
RMSD
|
|
0.0218
|
|
|
0.8991
|
[C6H6Cl2N]+ cation
|
|
|
|
|
|
Cl2—C6
|
1.729 (3)
|
1.706
|
C1—C6—C5
|
119.8 (3)
|
121.8662
|
Cl3—C4
|
1.732 (3)
|
1.7138
|
C1—C6—Cl2
|
121.4 (2)
|
119.4101
|
N1—C1
|
1.467 (4)
|
1.3118
|
C5—C6—Cl2
|
118.8 (2)
|
118.7237
|
C2—C1
|
1.382 (4)
|
1.361
|
C2—C1—C6
|
120.6 (3)
|
119.5495
|
C2—C3
|
1.388 (5)
|
1.4339
|
C2—C1—N1
|
118.2 (3)
|
119.3973
|
C6—C1
|
1.386 (4)
|
1.4047
|
C6—C1—N1
|
121.1 (3)
|
122.2661
|
C6—C5
|
1.392 (4)
|
1.4007
|
C2—C3—C4
|
118.3 (3)
|
118.3366
|
C3—C4
|
1.391 (5)
|
1.4367
|
C5—C4—C3
|
122.1 (3)
|
120.665
|
C4—C5
|
1.378 (4)
|
1.366
|
C5—C4—Cl3
|
118.5 (3)
|
120.665
|
|
|
|
C3—C4—Cl3
|
119.4 (3)
|
118.9033
|
|
|
|
C4—C5—C6
|
118.8 (3)
|
119.1256
|
|
|
|
C1—C2—C3
|
120.3 (3)
|
120.4567
|
RMSD
|
|
0.0579
|
|
|
1.2667
|
The atomic arrangement of (I) can be divided into an organic and an inorganic parts. The inorganic section is composed of corrugated layers of [ClO4]− anions and NH3+ groups that extend along the b-axis direction, held together by N-H···O hydrogen bonds (Fig. 2). Two such layers cross the unit cell at z = (2n + 1)/4 (Fig. 3). The residues of the organic groups are located between these layers (Fig. 4, Fig. 5).
Two Cl-O bond distances are shorter [1.422(2) and 1.440(2) Å] and two others are in slightly longer [1.442(2) and 1.454(2) Å]. The elongated Cl-O bond distances is due to the two N-H…O hydrogen bonds between the cation and anion (Table 2). This shows the possible charge transfer between donor N and acceptor O atoms. The O-Cl-O bond angles also vary from a minimum of 107.85(2) to a maximum of 111.26(2), which is deviated from a free ion value of 109.5.
The analysis of the hydrogen bonding network reveals that three O atoms of the perchlorate anion are participated in hydrogen bonds (as acceptors) with the -NH3+ group of the dichloroanilinium cation, forming multiple graph set motifs (Table 3, Fig. 6). Stabilization in the crystal structure of (I) occurs through N-H…O hydrogen bonds, augmented by moderate N-H…Cl (Table 3, Fig. 4), C-H…π interactions (Fig. 7) and electrostatic interactions.
Table 3
Selected hydrogen bonds (Å, °) parameters in [C6H6Cl2N]ClO4
D—H···A
|
D—H
|
H···A
|
D···A
|
D—H···A
|
N1—H3···O1i
|
0.89 (5)
|
2.05 (5)
|
2.885 (4)
|
156 (4)
|
N1—H1···Cl2
|
0.94 (5)
|
2.56 (5)
|
3.054 (3)
|
113 (3)
|
N1—H1···O3
|
0.94 (5)
|
2.51 (5)
|
2.854 (4)
|
102 (3)
|
N1—H1···O1ii
|
0.94 (5)
|
2.12 (4)
|
3.000 (4)
|
155 (4)
|
N1—H2···O2iii
|
0.87 (5)
|
2.02 (5)
|
2.892 (4)
|
176 (5)
|
N1—H2···O3
|
0.87 (5)
|
2.58 (5)
|
2.854 (4)
|
99 (4)
|
Symmetry codes: (i) x, y + 1, z; (ii) − x + 1, y + 1/2, −z + 3/2; (iii) − x + 1/2, y + 1/2, z. |
3.2. Hirshfeld surface analysis
Hirshfeld analysis helps to analyze the molecular contributions towards the packing crystal and as such summarizes information on all intermolecular contacts. This analysis is supported through an enrichment ratio concedes assessing the propensity of elaborated compound to form particular interactions. The topology molecular surfaces in terms of dnorm surface (D), shape index (S) and curvedness (C) the title molecules is as shown in Figure 8.
2D Fingerprint plots evincing the occurrence of intermolecular contacts are shown in Fig. 9. Taking into account the 2-D fingerprint plots analysis, the O···H/H···O contributions are prominently evident comprising 43.5% of the overall Hirshfeld surfaces. The enrichment ratio value of 1.76 clearly suggests a fully enriched interaction as being favoured in the crystal assembly, which are portrayed as deep red spots in dnorm surface (Fig. 10). The latter contacts, provide evidence for the formation of N-H…O hydrogen bond, are mainly due to the interaction between ClO4 and C6H6Cl2N generating ring motifs. Intertwined emerge H···Cl/H···Cl interactions comprising 20.3% of the total Hirshfeld surfaces, indicating the presence of intramolecular N–H···Cl interactions, thus, influencing the molecular conformations. It is clearly visible from the enrichment ratios listed in Table. 4 that these contacts, with EH…Cl = 1.24 higher than unity, are recognized as being highly favoured. Importantly, intermolecular Cl···O interactions are remarkable contributors into the molecular surface with a percent 13.4% to the Hirshfeld surface. These contacts adopt an enrichment ratio E Cl…O = 1.02. The solid-state structure exhibit C···H interactions standing at 11.8% to the surface area are characteristic way for C–H⋯π interactions, which plays a crucial role in building three-dimensional network. Interestingly, this contact is over-represented expressed by EC…H = 1.75 in the crystal packing, as result of most proportion SH of hydrogen atoms (39.3%) at the molecular surface. The relative contribution in terms of C···Cl interactions (Fig. 5) is reflected 3.2% of the total surface area from C–Cl⋯π interactions, which are slightly favoured since the EC···Cl = 0.89 is less than unity. Hydrophobic H…H, O···O and Cl···Cl self-contacts are significantly impoverished, which imply that these last-mentioned possess a repulsive character. The C···O contacts are practically avoided with smaller enrichment ratio EC…C = 0.16, as they are derived from less important interactions with contributions 0.9% in the Hirshfeld surface. Even though, the remaining rare C···C contacts with 0.6% are recognized as under-represented showing EC…C = 0.82 lower than unity, indicating the absence of π···π stacking interactions. It is apparent to note that these contacts have reasonable contribution and are responsible for the formation of three-dimensional networks. From this analysis, we have concluded that O···H and H···Cl followed by C···H contacts have major percentage in the crystal structure.
Table. 4
Contacts, enrichment ratio, chemical proportions on the Hirshfeld surface of (C6H6Cl2N)ClO4.
|
H
|
O
|
C
|
Cl
|
% Surface
|
39.3
|
31.3
|
8.55
|
20.85
|
Enrichment
|
|
|
|
|
H
|
0.68
|
|
|
|
O
|
1.76
|
0.24
|
|
|
C
|
1.75
|
0.16
|
0.82
|
|
Cl
|
1.24
|
1.02
|
0.89
|
0.55
|
% Contacts
|
O….H
|
H…Cl
|
O…Cl
|
C…H
|
|
43.5
|
20.3
|
13.4
|
11.8
|
|
C…Cl
|
Cl…Cl
|
O…O
|
H…H
|
|
3.2
|
2.4
|
2.4
|
1.5
|
|
O…C
|
C…C
|
|
|
|
0.9
|
0.6
|
|
|
3.3 Optimization of the chlorate ion
Prior to synthesis and X-ray crystallographic validation of the obtained crystal structure, the structure as obtained from X-ray crystallography was used for computational studies. The first approach in computational structural analysis is to ensure the stability of the considered molecule and test which computational methodology best describes the crystallographic structure. Based on this notion, several computational methods encompassing the highly parameterized M06-2x functional and the highly accurate PWPB95 with D3BJ dispersion corrected functional which are more reliable methods for predicting the molecular properties of main group organic molecules were utilized in combination with the 6-311 + + G(2df, 2pd), aug-cc-PVTZ and def2-TZVP basis in gas and solution set to espy the various molecular electronic properties of the synthesized compound including its geometrical properties in comparison to the crystallographic data. The obtained bond length and angle for selected bonds and angles is presented in table two alongside the X-ray data, while the detailed computational geometrical properties of the molecule in gas and solution are presented in Table S of supporting information. To accurately and statistically estimate the extent of deviation of the modeled structure from the crystallographic structure, correlational analysis based on the root mean square deviation (RMSD) was used to compare the crystallographic and optimized structure. The obtained results are presented along the bond lengths in Table 2. The computed values of RMSD affirms the absolute concordance of the optimized structure to the experimental structure. The RMSD for the bond lengths of the anionic fragment was calculated to be 0.0218 while the cationic moiety had an RMSD value of 0.0579 for all the functionals, while the RMSD for angle deviation was observed to be 0.8991 Å for the anion and 1.2617 Å for the cationic fragment. The calculated C11-O1, C11-O2, C11-O3, C11-O4 bond lengths for the chlorate fragment were 1.4968, 1.4486, 1.442, and 1.425 Å respectively while the experimental bond lengths were observed to be 1.454, 1.440, 1.442, and 1.422 Å. The calculated C-C bond lengths for the [C6H6Cl2]+ fragment was calculated to be in the range of 1.366 to 1.7138 Å. Specifically, C2-C1, C4-C5 and N1-C1 had the lowest calculated bond length of 1.361, 1.366, and 1.312 Å while the experimental bond lengths were equally observed to be low with values of 1.382, 1.378 and 1.467 Å respectively. The O-C-O bond angles of the anion (ClO4)- fragment was computed to be in the range of 106.92 to 111. 71 Å while the experimental bond angles were observed at 107.85 to 110.49 Å. In the same vain, the C-C-C bond angles of the cation [C6H6Cl2N]+ moiety were computed to be in the range of 118.90 to 121.87 Å while the experimental bond lengths were observed to range from 119.8 to 121.4 Å. The results disclosed both the calculated bond lengths and angle to be in good agreement with the experimental. Thus, the chosen computational methods replicate the crystallographic structure well. Also, to further appraise the stability of the structure in solution, the geometrical parameters were assessed in gas, polar and non-polar solvents (water and Benzene) to assess the possible changes in properties and behaviour due to solvation. The obtained results as presented in the supporting information file shows that all the computed bond angles and lengths falls in the same range as no dramatic changes were observed in going from gas to solvents thus, prompting considerable stability irrespective of the electronic environment. The calculated RMSD in going from gas to non-polar solvent (benzene) is 0.031 while the calculated RMSD in going from gas to water (polar solvent) was observed to be 0.073 when computed at the M06-2X/6-311 + + G(d,p) level whereas, the calculated RMSD at the aug-cc-PVTZ was 0.068. therefore, the M06-2x/aug-cc-pVTZ level of theory was selected for further studies based on its ability to reproduce the crystal structure to a higher extent.
3.4 Vibrational Characterization
Molecular vibrational spectroscopy has been successfully utilized in the qualitative and quantitative structural elucidation of several organic and inorganic molecules. The uniqueness of this approach lies in the fact that molecular vibrations are specific to individual molecules and as such the structure-property relationship in molecules can easily be explicated. As a result of the lack of higher symmetry in the considered structure, the vibrational attributes of the compound are well pronounced in both infrared and Raman spectrum. The computational simulations of the vibrational specificities of the studied compound were attained at the M06-2X/6-311 + + G (2df, 2pd) level of computations. 56 fundamental vibrational moods are noticeable based on the n-6 rule [44–45]. For comparison with the experimental data, statistical analysis based on regression coefficient R2 was utilized to effectively assess the level of coherence of the optimized structure with the experimental data. The superposition of the experimental and theoretical vibrational frequencies is presented in Fig. 11. It is evident from literature and several reported data on related structures that theoretical vibrational frequencies are overestimated due to anharmonicity and disparities arising from experimental conditions. Thus, several scaling factors have been proposed to assuage this incongruity, based on this notion, the computed vibrational frequencies were scaled by a factor of 0.967 for better concordance with the experimental values. The FTIR spectrum is segmented into two sections, the first section being the region from 4000 to 2900 cm− 1 wavenumbers which is characterized by low and broad intensity bands mainly attributed to the O-H and C-H stretching vibrations, while the second region (dominated by several intense bands) is characterized between 1617 to 1025 cm− 1 wavenumbers. The experimental spectrum is characterized by three bands of medium intensity at 3566, 3492 and 3423 cm− 1 which corresponds to the NH2 stretching vibrations. These peaks appear to be broad due to the possible hydration of the NH2 groups as a result of hydrogen bond formation with the chlorate ion, thus the formation of the third peak at 3423 cm− 1 is an affirmation of this reality. OH- groups usually have their characteristic absorbance in this region, the peak at 3423 cm− 1 is assigned to the hydrogen bonded O—H band between the anion and cation fragments. The absence of the OH group in the structure indicates that the hydrogen bond between the anion and the cation fragment is strong enough to cause the formation of a pseudo OH absorption peak at this frequency. In the theoretical spectrum these absorptions are quite distinct in gas phase calculations as only two peaks of equal intensity are observed for the NH2 group, therefore affirming the hydrated nature of the NH2 group as evident in the experimental spectrum and computational calculations in solution. The absorption bands are calculated at 3526 and 3435 cm− 1 wavenumbers respectively. To further confirm this observation, the theoretical spectrum as observed in solution shows an increased intensity for the NH2 group which could also be attributed to the presence of intermolecular hydrogen bonding. The experimental spectrum also shows two peaks at 3070 and 3172 cm− 1 which corresponds to the absorptions of the C-H group. The positions of these peaks are due to the aromatic nature of the CH groups which are sp2 hybridized. In the theoretical spectrum, the C-H absorption bands are observed between 3134 to 3140 cm− 1. These peaks overlap with the N-H anti-symmetric stretching absorptions at 2937–2785 cm− 1 which causes the increased intensity of the peak as observed in the spectrum.
The second region in the FTIR spectrum is characterized by deformation bands and NH bending vibrations. The peak at 1617 cm− 1 in the experimental spectrum is assigned to the NH2 scissoring vibration, this peak overlaps with the C = C band at 1572 cm− 1 thus, resulting to the broad nature of the peak. The theoretical spectrum shows this peak at 1708 and 1646 cm− 1 respectively for the NH2 scissoring and C = C stretching vibration. The characteristic peak at 1532 cm− 1 corresponds to the in-plane rocking motion of the NH2 group which overlaps with the aromatic stretching bands, the calculated absorption is assigned at 1543 cm− 1. Other prominent interactions as observed in the experimental spectrum are the bands at 1161, 1116, and 1025 cm− 1 which correspond to the NH, O-Cl, and CH rocking, stretching and CH rocking deformations respectively. The peak at 1025 cm− 1 in the experimental spectrum is assigned to the asymmetric O-Cl stretching and twisting deformation. All these vibrations are well reproduced in the computed spectrum, thus indicating the accuracy of the computational method. The overall resistance to changes in dipole moment as a result of NH stretching is an indication of molecular stability, hence the studied structure maintains a stable geometry. To further assess the exact extent of deviation of the computed wavenumbers with the experimental, the correlation analysis based on R2 values were considered. The result as depicted in Fig. 12 shows an R2 value of 0.9944 which is very high and therefore affirms the absolute correspondence of the computed wavenumbers to the experimental data, also the scale factor employed greatly reduces the computational incongruity arising from basis set and method of computations.
3.5 Electronic Properties
The understanding of molecular electronic properties of molecules is highly important in computation studies, several approaches exist for the computations of such properties however, the famous Koopman’s hypothesis is utilized herein to afford such properties. Molecular descriptors which span through the ionization potential (IP), electron affinity (EA), chemical potential (µ), Chemical hardness (η), and electrophilicity index (ω) are considered. these properties are each unique and tends to unveil a specific electronic property of the studied compound. Table 5 list the various descriptors as computed with the M06-2X/6-311 + + G(2df,2pd and aug-cc-pVTZ basis set. in line with the notion of Koopmans’ ionization potential and electron affinity are absolute values of the negative of HOMO and LUMO respectively [46] thus, the ease of electron acceptance or donation is very much dependent on these two parameters and higher or lower tendencies of charge transfer is also appraised by increased or decreased values of IP and EA respectively [31]. The inference from the results in table is that the compound possesses high probability for electron acceptance and a considerable aptitude for electron donation, this assertion is affirmed by the high IP value and low EA value which are computed to be 9.3515 eV and 1.5532 eV respectively. Molecules with high HOMO or IP values are generally less stable compared to species with low HOMO values due to the less amount of energy required for electronic transitions thus, the studied compound is more prone to accept charge density than donate. The energy gap is conceivably the most significant of these molecular descriptors, reasons that it holistically explicates molecular stability and kinetic reactivity by mere considerations of the difference in quantized quantum states peculiar to electronic transitions from the HOMO to the LUMO and vice versa. Thus, molecular species are considered stable if the energy gap is high enough, such that electronic transition from HOMO to LUMO is not easily assessable, and on the other hand, species are considered reactive if these transitions are highly feasible with less amount of energy. Based on these concepts, the studied compound could be regarded as being considerably stable due to its energy gap which is computed to be 7.7983 eV. This value is comparable with the energy gap suggested for conductors and insulator materials which should be above 5.56 eV [47–48]. However, due to the paramagnetic nature of the studied compound due to unpaired electrons, the most feasible transitions within the studied compound results form the singlet occupied molecular orbital and the singlet unoccupied molecular orbital thus confirming its high potential to accept electrons as revealed by the IP value. Therefore, the compound could be termed as species with less propensity to exchange electron density with eminent environment and could display high tendencies of reactivity towards hard bases. The influence of solvation on these molecular properties was also considered and the results likewise discloses that solvent polarity affected the electronic properties to a minimal extent as only slight changes in energy gap is observed to occur. The exact increase in energy gap due to solvation is observed to be 1.05% and 0.64% in water and benzene respectively. The localization of frontier molecular orbitals were also determined for the (C6H6Cl2N)ClO4 structure (Fig. 13a). it is apparent that, the HOMO is located on the lone pairs of Cl atoms in the cation, while the LUMO is localized over the entire aromatic ring and the NH group. The proximate localization of these molecular orbitals is directly related to the nature of the feasible inter- and intra-molecular interactions within the perchlorate cluster and thus, aid the quantization of orbital density leading to the understanding of the energetics of the studied system. The energy distribution is depicted in Fig. 13b.
Table 5
Calculated quantum descriptors of (C6H6Cl2N)ClO4
|
EG
|
IP
|
EA
|
-µ
|
χ
|
η
|
ω
|
|
|
|
|
M06-2X/6-311 + + G(2df,2pd)
|
|
|
|
Gas
|
7.7983
|
9.3515
|
1.5532
|
-5.4524
|
5.4524
|
3.8991
|
3.8122
|
Water
|
8.8445
|
9.7477
|
0.9032
|
-5.3254
|
5.3254
|
4.4223
|
3.2065
|
Benzène
|
8.4396
|
9.6829
|
1.2433
|
-5.4631
|
5.4631
|
4.2198
|
3.5364
|
|
|
|
|
M06-2X/aug-cc-pVTZ
|
|
|
|
Gas
|
7.8301
|
9.3858
|
1.5557
|
-5.4707
|
5.4707
|
3.9154
|
3.8219
|
Water
|
8.8565
|
9.7490
|
0.8925
|
-5.3208
|
5.3208
|
4.4283
|
3.1966
|
Benzène
|
8.4875
|
9.7278
|
1.2403
|
-5.4841
|
5.4841
|
4.2438
|
3.5434
|
3.6 Natural Bond Orbitals Analysis and Charge Delocalization
Molecular stabilization catalysed by charge density transfer or the delocalization of electrons can be described by considering the second order perturbation theory analysis of the Lewis and non-Lewis’s donor and acceptor interactions existing within the (C6H6Cl2N)ClO4 molecule in different solvents respectively. Such interactions do not only show the preferred stabilization mechanism but also elucidates the exact interactions of each set of molecular charge transfer or excitations within each quantum state of the investigated molecule. Charge transfer or delocalization of electrons within molecular systems is affected by differences in the electronic medium for which the compound exists and as such plays a role in the stability of the investigated molecule [19]. The second order perturbation energy of the investigated complex is presented in Table 6. The most important contributions to molecular stability are the interactions resulting from the delocalization of electrons density from the perchlorate (ClO4) anion to the benzene ring. These interactions are prompted by charge transfer from oxygen lone pairs of the ClO4 fragment to the sigma antibonding orbitals of nitrogen and hydrogen atoms of the cationic moiety (C6H6Cl2N) and account for a greater stabilization enthalpy in the range of 11.39 kcal/mol to 30.25 kcal/mol in gas phase. This interactions resulted from LP(3)O16 \(\to\) σ*(N12-H14), LP(3) Cl11 \(\to\) LP*(1) C6 and σ*C3-C4 \(\to\) σ*C1-C2 with stabilization enthalpies of 23.87 kcal/mol, 30.25 kcal/mol, and 31.91 kcal/mol respectively. The influence of solvation on the observed stabilization enthalpy was carefully observed so as to further appraise the differences in molecular behaviour and stability in polar and non-polar solvents. The results of the stabilization energies in different solvents reveals substantial differences in the E2 energy. The total calculated stabilization energies in gas phase are quite higher than the computed energies in solvent phases, the total charge density delocalization between the lone pairs and pi-antibonding orbitals is calculated to 43.13 kcal/mol in gas phase and this is observed to slightly decrease by 0.06% in water and 0.34 % n benzene. The total change in electron transfer (ΔETLP-σ*) was also, observed to be favoured for the lone pair excitation to sigma bonds than the pi-bonds. The total ΔETLP-σ* charge density delocalization from lone pairs to sigma bonds was calculated to 83.07 kcal/mol in gas phase which is the highest intermolecular stabilization interactions observed. These results suggest that the studied compound is mostly stabilized by charge transfer delocalization via pi back-donation from theClO4 anionic group to the aromatic ring. LP → σ* delocalization of electron density is also observed to be the most dominant interaction observed and plays the major role in stabilizing the molecule than π→π*, and σ→σ* charge transfer in both gas and solution.
Table 6
Resulting Energies of Donor-Acceptor Interactions as revealed by the Natural Bond Orbital Analysis in gas and solvent phases
Gas
|
|
Water
|
|
|
Benzène
|
|
Donor (i)
|
Acceptor (j)
|
E(2)a [kcal/mol]
|
E (j) – E(i)b [a.u.]
|
F (i.j)c [a.u.]
|
E(2)a [kcal/mol]
|
E (j) – E(i)b [a.u.]
|
F (i.j)c [a.u.]
|
E(2)a [kcal/mol]
|
E (j) – E(i)b [a.u.]
|
F (i.j)c [a.u.]
|
LP*(1)C6
|
π*C1-C2
|
11.39
|
0.21
|
0.098
|
11.57
|
0.20
|
0.100
|
11.35
|
0.21
|
0.099
|
|
π*C4-C5
|
18.08
|
0.17
|
0.105
|
17.42
|
0.17
|
0.105
|
17.69
|
0.17
|
0.013
|
LP(3)Cl10
|
π*C4-C5
|
13.66
|
0.43
|
0.097
|
14.08
|
0.42
|
0.098
|
13.75
|
0.43
|
0.097
|
ΔETLP-π*
|
|
43.13
|
|
|
43.07
|
|
|
42.79
|
|
|
LP(2)O17
|
σ*Cl15-O18
|
10.26
|
0.66
|
0.104
|
7.50
|
0.66
|
0.090
|
7.50
|
0.68
|
0.091
|
|
*Cl15-O19
|
10.80
|
065
|
0.107
|
10.48
|
0.65
|
0.106
|
10.70
|
0.65
|
0.107
|
LP(2)O18
|
σ*Cl15-O19
|
12.06
|
0.65
|
0.114
|
11.94
|
0.66
|
0.114
|
12.47
|
0.66
|
0.116
|
LP(2)O19
|
σ*ClO17
|
11.62
|
0.66
|
0.112
|
9.22
|
0.66
|
0.100
|
10.18
|
0.66
|
0.105
|
LP(3)O17
|
σ*Cl15-O16
|
14.46
|
0.58
|
0.117
|
11.97
|
0.63
|
0.111
|
12.25
|
0.61
|
0.111
|
LP(3)O16
|
σ*N12-H14
|
23.87
|
0.82
|
0.180
|
5.58
|
0.87
|
0.090
|
12.81
|
0.85
|
0.135
|
ΔETLP-σ*
|
|
83.07
|
|
|
56.69
|
|
|
65.91
|
|
|
LP(3)Cl11
|
LP*(1)C6
|
30.25
|
0.24
|
0.124
|
32.91
|
0.24
|
0.127
|
31.81
|
0.24
|
0.126
|
π*C3-N12
|
π*C4-C5
|
6.75
|
0.05
|
0.08
|
28.39
|
0.02
|
0.081
|
41.55
|
0.01
|
0.81
|
πC1-C2
|
LP*(1)
|
43.08
|
0.18
|
0.126
|
34.96
|
0.20
|
0.118
|
38.92
|
0.19
|
1.122
|
3.7. Molecular Electrostatic Potential analysis
The visualization of molecular electrostatic potential surfaces is highly essential for the wholistic comprehension of bio-interaction, hydrogen bonding interactions as well as the detection of potential reactive sites in molecules. Regions of high electron densities are explicated by low values of electrostatic potential and high ESP values often expresses the relative absence of electron density [42]. To understand and predict the most susceptible regions of both nucleophilic and electrophilic reactions, the ESP isosurface plot is obtained from the M06-2X/6-311 + + g(2df,2pd) optimized geometry. The MEP isosurface is presented in Fig. 14. It clearly shows that the negative areas are located on oxygen atoms of the perchlorate anion and on the aromatic ring, while the positive zone is located on the hydrogen bonded to nitrogen, in accordance with the Mulliken charges (Table 7). Regions of low electrostatic potential density are designated in blue while the red shows negative ESP regions respectively. The ESP isosurface clearly shows that regions of high electron density which could act as nucleophilic sites are localized on the oxygen atoms of the perchlorate anion whereas, the region with the strongest attraction potential is the red-coloured surface on the aromatic ring and thus, high propensity for electrophilic attack. Positive ESP regions are clearly explicated on the hydrogen atoms of the NH group as clearly revealed in white color.
3.8. Mulliken population analysis
The atomic charge was employed to elucidate the processes of charge transfer in chemical reactions. The Mulliken charge distribution of all atoms is given in Table 7. The atoms of the organic molecule are numbered as follows (Fig. 15):
The atomic charge distribution shows that, for the [ClO4]- anion, the Cl ion have positive charge, the most negative atoms being the oxygen (Table 7), in agreement with the previous MEP results (Fig. 14). For the organic entity, the nitrogen atom is negatively charged, while carbon atoms C1, C2 and C5 have positive charges. The C3, C4 and C6 have negative charges, while the Cl7 and Cl9 are positively charged. All hydrogen atoms carry positive charge (Table 7). These results show an electronic charge transfer of 0.13 e from the anion to the cation.
Table 7
Mulliken charge distribution in the organic cations of (C6H6Cl2N)ClO4
Atom
|
Charge distribution
|
Cl
|
1.477516
|
O
|
-0.543718 ; -0.701627 ; -0.557709 ; -0.550857
|
C1
|
0.078734
|
C2
|
1.037627
|
C3
|
-0.658953
|
H(C3)
|
0.198147
|
C4
|
-0.475237
|
H(C4)
|
0.222445
|
C5
|
0.279696
|
C6
|
-0.808516
|
H(C6)
|
0.241466
|
Cl7
|
0.226077
|
N8
|
-1.275117
|
H(N8)
|
0.495817 ; 0.598678 ; 0.484233
|
Cl9
|
0.231298
|
Cation charge
|
0.87
|
Anion charge
|
-0.87
|
3.9 Visual study of weak interactions
Non-covalent interactions based on the reduced density gradient (RDG) is perhaps one of the most frequently utilized method to study weak interactions especially interactions occurring in low density regions [49] non-covalent interaction offers profound information regarding diverse condensed phase behaviour of molecules as well as their special orientation in biological systems. The exact type of intermolecular interaction existing within molecules could be accounted for by analysing their eigenvalue sign which exemplifies density fluctuations and distinguishes stabilizing and non-stabilizing interactions. However, if the eigenfunction (sign (λ2) ρ is less than zero λ2 < 0, such interaction is described as non-covalent interaction, similar implication is applicable for eigenfunction (sign (λ2) ρ greater than zero λ2 > 0, which primed such interaction to be repulsive in nature. The non-covalent interaction plot for the studied compound is presented in Fig. 16 along with the colour code. it is apparent from the figure that Van der Waals and steric repulsive interaction constitute the predominant forces of intermolecular interactions within the studied compound. The blue colour signifies hydrogen bond, whereas the green and red denotes Van Der Waals and steric cyclic effect respectively. The crystal structure also indicates the presence of hydrogen bond between N-H…O and N-H…Cl. The sign of their eigenvalues (λ2*ρ) ranges from − 0.020 to -0.010 Å in the fingerprint plot indicating significant steric contributions from the aromatic ring to molecular stability. The brightly intense green colour in the RDG isosurface confirms the presence of strong VDW interactions and suggest the compound to be stabilized by these forces of interaction.
3.10 Molecular docking
Molecular docking approach has evolved as an essential computational approach to quickly assess molecular interactions between compounds and biological enzymes, as well as predict possible binding mechanisms in biological process [23, 24]. This approach has been utilized herein to evaluate the bio-activity profile of the studied perchlorate ion cluster. The autodock vina tools and corresponding visualizers were deployed for this purpose. Figure 17 depicts the 3D and 2D interactions of the studied compound with the chosen receptor proteins in comparison with a conventional antispasmodic agent (benzodiazepine) From Fig. 17 (a-b), the interaction of (1) with 4MS3 indicated a binding affinity of -3.2 kcal.mol-1, due to a very close H-bond interaction which is close and strong enough to be considered a covalent interaction at a distance of 1.89Å between the N-atom of (1) and the SER-A:131 residue. Also, a pi-alkyl hydrophobic interaction was observed between the pi-electrons in the aromatic (benzene) ring system of (I) and PRO-A:105 residue at an extracellular distance of 5.26 Å. The interaction between DZP and 4MS3 receptor protein indicated a binding affinity of 12.6 kcal.mol-1, which is poor and attributed to more unfavourable bump-repulsive ionic interactions compared to the weak favourable hydrophobic ones, between the DZP and 4MS3 receptor. The interaction indicated unfavourable bump at a distance of 2.18, 2.23, 2.16, 2.45, 2.32 and 2.46 Å between THR-A:199 and the aromatic ring of DZP and 2.03Å. The favourable interactions were Pi-Sulphur with sulphur in CYS-A:103 and the pi-electrons in the DZP ring system at distance of 5.52Å and Alkyl and pi-alkyl interactions with VAL-A:201. This unfavourable bump, greatly reduced the binding affinity. Figure 17 (b) showed that DZP is not located in the Venus flytrap extracellular module, so it’s not a potential agonist for GABAB receptor the management of spasmodic activity associated with CNS disorder. The interaction between the studied compound (1) and 4MS3 occupied the Venus flytrap extracellular cavity of the GABAB receptor just as described by Zhu, et al., and therefore, may share similar mechanism with benzodiazepines [50]. Therefore, this study provides a template for understanding the bioactivity of (1) and will assist rational approaches to its therapeutic application as a muscle relaxant (antispasmodic) and associated neurological disorders and mental illness by targeting GABAB receptor protein.