Theoretical Investigations on the π-π Stacking Interactions in Phenol-Water Complexes

Non covalent interactions are quite common in all kinds of π-systems, such as π-π interactions, long range/short range van der waal force of interactions, ion-π interactions etc. Ab initio calculations are well established and account well for the experimental long range interaction energies for small clusters of aromatic molecules and most of the calculations were carried out using the MPn methods. If a reasonably large basis set is used to calculate the stacking interaction energies for a cluster (dimer, trimer etc.) of aromatic molecules then the electron-electron correlation energy may be properly calculated. Moreover, ab initio calculations for aromatic π-systems show that the calculated stacking interaction energies highly depend on the basis set used and the electron correlation energy. In this investigation, the electron correlation of the stacked hydrated phenol systems has been accounted at MP2 level of calculations. We have calculated the π-π stacking interaction energies of the hydrated phenolic systems with different conformations.


Introduction
Intermolecular interactions involving aromatic rings are common in many areas of chemistry and biology. In proteins, π-π stacking has been the subject of systematic search in crystal structures, showing that aromatic side chains preferentially interact in a parallely-displaced orientation [1]. The stacking interaction for different aromatic molecules can also be easily estimated from the extent of the dispersion forces, very short range exchange repulsion forces and electrostatic interactions among the molecules of the system, while the extent of intermolecular electron correlation between aromatic rings is the core factor for cal-How to cite this paper: Sharma, S., Bezbaruah, M.J., Ali, I., Choudhury, M. and Bezbaruah, B. (2018) Theoretical Investigations on the π-π Stacking Interactions in DOI: 10.4236/cc.2018. 62002 16 Computational Chemistry culating the dispersion forces. However, it is often found that the less accurate force field methods, and even density functional methods have been successfully applied to large molecular systems [2] [3] [4]. The T-shaped structure, shown to arise as well in biomolecules, was found from high level ab initio calculations to be less stable than the parallel arrangement [5]. Moreover, the ab initio calculations with the inclusion of correlation effect at least at the MP2/6-31G* level of theories have been found successfully in some cases. cule with one to four water molecules by using various levels of ab initio theory and it revealed that for phenol complex with two, three, and four water molecules, the most stable complex was a planar phenol ring [23]. A second-order Møller-Plesset (MP2) perturbation theoretic study using interaction-optimized polarization basis set has revealed the existence of three different minima in the phenol-water complex [24]. Benoit and Clary have studied phenol-water clusters using rigid-body diffusion quantum Monte Carlo method [25] [26]. Earlier studies suggested that the interaction involved in phenol-water clusters is similar in strength to the σ-hydrogen bond [27]. Ab initio calculations have also been carried out for the electronic ground state and the lowest excited state of phenol and complexes of phenol with water and ammonia and the corresponding cations [28]- [40].
The latter complex is highly interesting as the structure of the dimer is characterized by two different types of non-covalent interactions: The phenol water hydrogen bonding and the stacking of two aromatic rings. The hydrogen bonding is mainly of an electrostatic origin while the aromatic stacking is mainly due to London dispersion interactions, both of which participate in determining the equilibrium structure [41]. Phenol may serve as a basic unit of larger molecules, e.g., tyrosine residues in proteins. The hydrogen-bonded phenol complexes with simple solvent molecules are important models for investigation of H-bonding and proton transfer in proteins and nucleic acids [42]. The study of ionic hy-  [45]. In this study, we have investigated the π-π interactions of hydrated phenol systems with different conformations in gas and aqueous phase.

Computational Methodology
The most effective method for studying the non-covalent long range interactions of simple aromatic systems is the ab initio method. The study of π-π stacking interactions has now become much easier due to the quantum mechanical theo-

Result and Discussion
In this research work, the non-covalent π-π stacking interactions of water assisted phenolic dimers have been studied for different conformations in gas phase and aqueous phase. All the conformations for phenol water stacked systems were prepared with different dihedral angles-0˚, 60˚, 120˚ and 180˚. The eclipsed conformation, with dihedral angle 0˚ was prepared by placing one phenol ring parallely over the other ring with an internal separation of 3.6 Å. Then one water assisted phenol ring has been horizontally shifted along either X, Y or Z-axis (from positive to negative direction), keeping the other ring at constant position, to get the most favored minimized stacked model. In this case, the horizontal shifting for the stacked model was investigated along X-axis from −3 to +3 Å. Similarly, all the staggered conformations for the stacked models of phenol water systems were also prepared with dihedral angles 60˚, 120˚ and 180˚ respectively.
The relative changes for the π-π stacking interaction energies in gas phase, with MP2 methods for different stacked hydrated phenol conformations are shown in Table 1 and certain stable structures are located from the local minima in the potential energy curves shown in Figure 2 and  Table 1). The more negative stacking    interaction energy values represent the most stable conformation and effective calculation of electron-electron correlation and dispersion forces. On the other hand, the π-π stacking interaction energy for the staggered conformation with dihedral angle 120˚ is found to be −27.3121 kcal/mol (Table 1). Figure 2 shows the minimized stacked models for all the hydrated phenol systems with different dihedral angles. The computed stacking energies of optimum structures with various levels of calculations in gas phase are summarized in Table 1.
Above studies for hydrated phenol stacking interactions, show effective π-π interaction and they are quite well stacked at a dihedral angle of 0˚ and 120˚. In gas phase at 0˚ dihedral angle the minimized energy shows the most negative value (−27.4314 kcal/mol) at a horizontal shifting of −1.5 Å, it is because of the water molecules of one phenol are far apart from the other which shows minimum electron-electron repulsion, but without any horizontal shifting (at 0 Å) it show maximum repulsion. On the other hand, at 120˚ dihedral angle, the minimized stacked model shows more negative value (−27.3121 kcal/mol) at a horizontal shifting of −1.5 Å which represents the minimum repulsion between the phenol water stacked model. However, towards the positive horizontal shifting, the repulsive forces are maximum and therefore they show less negative values. Similar investigations were also done for stacked hydrated phenol systems with dihedral angle of 60˚ and 180˚. These models shows almost same results and they are less stable as compared to the 0˚ and 120˚ dihedral angle. We also computed the Mulliken Charges for both gas phase and aqueous phase for minimized stacked models as well as the unstacked phenol system to compare the change in electron charge density of phenol ring. Since, the electron charge density is greatly affected by the -OH group of the phenol ring both in staked and unstacked models, hence we have investigated the variations of Mulliken charges only for the -OH group ( Table 2 and Table 3).
It also gives an idea about how effectively it shows the π-π stacking interaction. Although, we have done our calculations for π-π stacking interaction both in gas and aqueous phase, but the results reveal that no such major changes have been found in the stability of the stacked models for hydrated phenol as shown in the plots Figure 3 and Figure 4.

Conclusion
Among the different stacked hydrated phenol systems, it has been observed that minimized π-π stacking interaction energy of the eclipsed conformation (dihedral angle 0˚) gives more negative interaction energy values as shown in Table 1 and Table 2. It has been observed that most of the phenolic systems give effective π-π stacking interaction (since all the stacked models give negative stacking interaction energies). Although, some phenolic systems are not always structurally symmetric, but they show effective π-π stacking between aromatic phenol rings. Therefore, in hydrated phenolic system, eclipsed conformation (dihedral angle = 0˚) of stacked models show better π-π stacking interaction than that of other staggered (dihedral angle 60˚, 120˚ and 180˚) models and it happens due to less repulsive forces. Again, among all the staggered models, stacking models with dihedral angle 120˚ shows better π-π stacking interaction.