The Investigation of Different Properties of Clonidine Drug Binding to Carbon Nanotube: A Theoretical Study

Z. Yousefian

Department of Chemistry, Science and Research Branch, Islamic Azad University, Tehran, Iran.

DOI : http://dx.doi.org/10.13005/ojc/300428

ABSTRACT:

In this study, we investigated the binding of Clonidine Drug (C₉H₉Cl₂N₃) with zigzag single walled Carbon Nanotubes (SWCNTs) (5, 0) and a length of 5^ᵒA by theoretical methods of theory (NMR,NBO, HOMO- LUMO Gap energy,…calculations) using Gaussian _­09 software package. Then, Simulation was done in MM⁺, AMBER and OPLS force fields by Monte Carlo method in HyperChem. Three important energy parameters – Potential Energy, Kinetic Energy and Total Energy-calculated in five different simulating temperatures (308, 310, 312, 314 and 316 Kelvin) were used for computation and good results were obtained.

KEYWORDS:

Carbon Nanotube; Clonidine Drug; Different Properties

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Methodology

In our model, the firstly, Clonidine Drug was attached covalently to Carbon Nanotube(SWCNTs) with (5, 0) structure and a length of 5^ᵒA.

All calculations were performed using Gaussian 09 software package. Geometrical optimizations of Drug, single point calculation and NMR parameters were carried out in gas phase with the Hartee -Fock method coupled to 6-31 g* basis set for all atoms.

The most common type of ab initio calculation is called a Hartee- Fock calculation (abbreviated HF), in which the primary approximation is called the central field approximation. A method, which avoids making the HF mistakes in the first place, is called Quantum Monte Carlo (QMC).  These methods work with an explicitly correlated wave function and evaluate integrals numerically using a Monte Carlo integration [11, 12]. In general, ab initio calculations give very good qualitative results and can give increasingly accurate quantitative results as the molecules in question become smaller [13]. There are three steps in carrying out any quantum mechanical calculation in Hyper­Chem. 7.0 program package [14].

First, prepare a molecule with an appropriate starting geometry. Second, choose a calculation method and its associated options. Third, choose the type of calculation

with the relevant options. For example we calculated H, C, N, Cl NMR spectral parameters for the interaction of Clonidine Drug with SWCNT in gas phase by the HF/6-31g*method.

(σ₁₁ ≤ σ₂₂ ≤ σ₃₃                        ­(1

The values of the shielding tensor are frequently expressed as the isotropic and anisotropic parts (σ_iso and σ_aniso) and the shielding asymmetry (η)_. [15, 16]

Geometrical optimizations of Drug were carried out with the Hartee -Fock   method coupled to 6-31g basis sets for all atoms. Also, in this study we use chem Office software (chem3D and chem draw) and hyper chem at the end data will be presented as tables and figs. Simulation was done in MM⁺, AMBER and OPLS force fields.  Molecular Mechanics calculations were assessed by Monte Carlo method [17]. Three important energy parameters – Potential Energy, Kinetic Energy and Total Energy- in five different simulating temperatures (308, 310, 312, 314 and 316 Kelvin) were used for computation.

Results and Discussion

Molecular Geometry

Fig. 1, Shows the graphical representations of the optimized geometry of Drug–SWCNT. In the figure, the Cl atoms are shown by green colors, white spheres are H atoms, blue sphere is N and gray sphere is C. Selected geometrical parameters for Clonidine Drug SWCNT are also shown in Fig.1.a.

 

Fig1: Optimized geometries of a)Clonidine, b) Clonidine­ Drug-SWCNT obtained at HF/6-31g level.   Click here to View figure

 

Nuclear Magnetic Resonance Parameters

NMR is based on the quantum mechanical property of nuclei. The chemical shielding refers to the phenomenon, which is associated with the secondary magnetic field created by the induced motions of the electrons that surrounding the nuclei when in the presence of an applied magnetic field [18]. In general, the electron distribution around a nucleus in a molecule is more spherically symmetric. Therefore, the size of the electron current around the field, and hence the size of the shielding, will depend on the orientation of the molecule within the applied field B₀.

In the present paper, total dipole moments of Drug interaction with SWCNT in gas phase have been explored and NMR computations were done by Gaussian 09 suite of programs. The calculated magnetic shielding tensor (σ ,ppm), shielding asymmetry (η) and the chemical shift tensor (δ) calculated  for C, H, N and Cl nuclei in the active site of Clonidine Drug and for carbon atoms of the open end of a SWCNT system in gas phase are presented in Table 1. Also, the graphs of calculated isotropic magnetic shielding constants σ_iso (ppm), anisotropic magnetic shielding tensors σ_aniso (ppm), Chemical shifts δ (ppm) and shielding asymmetry (η)  versus the number of atomic centers for selected atoms of Drug -SWCNT system are displayed in Figs. 2a-c respectively.

As was expected, the NMR shielding tensors of H, C, N, and Cl nuclei are drastically affected by the atom to which they are bonded and by the type of the bond to the neighboring atom. The results obtained give strong evidence that intermolecular interactions play a very important role in determining the H, C, N and Cl NMR chemical shielding tensors. Some systematic trends appeared from the analysis of the calculated values.

According to Figure2a, it is obvious that one atom in Drug-SWCNT system has maximum value in compare to the other atoms of this structure and this value belongs to 33Cl. Anisotropic chemical shielding is one of the other parameters that were checked in this work. From Figure 2b it has been found that the maximum value of σ_aniso in Drug-SWCNT system is related to 16C. The results of investigating chemical shift tensor indicate that 32Cl have been shown to be the largest value of (δ) in system as Drug interacted with SWCNT and our knowledge about Drug interacted to SWCNT has been specified that C number 31 show the largest intermolecular effects in (η) component (Fig. 2d).

 

Table1: Components of the magnetic shielding tensor (σ, ppm), shielding asymmetry (η) and the chemical shift tensor (δ) calculated for C, H, N and Cl nuclei in the active site of Clonidine Drug and for carbon atoms of the open end of a SWCNT in gas phases at HF level with the 6-31G* basis set.  Click here to View table

 

Fig2: The graphs of a) , b) σaniso ,  c) δ ,  d) η  of propose atoms of Drug binding to SWCNT in gas phases at the HF/6-31G* basis set.   Click here to View figure

 

Natural Bond Orbital (NBO) Analysis

The concepts of natural atomic orbital NAO and NBO analyses are useful or distributing electrons into atomic and molecular orbitals used for the one-electron density matrix to define the shape of the atomic orbitals in the molecular environment and then derive molecular bonds from electron density between atoms. In NBO analysis, the input atomic orbital basis set is transformed via natural atomic orbitals (NAOs) and natural hybrid orbitals (NHOs) into natural bond orbitals (NBOs). The NBOs obtained in this fashion corresponds to the widely used Lewis picture, in which two-center bonds and lone pairs are localized [19, 28].

The NAOs will normally resemble the pure atomic orbitals and may be divided into a natural minimal basis, corresponding to the occupied atomic orbitals for the isolated atom and a remaining set of natural Rydberg orbitals based on the magnitude of the occupation numbers. The minimal set of NAOs will normally be strongly occupied, while the Rydberg NAO usually will be weakly occupied. There are as many NAOs as the size of the atomic basis set and the number of Rydberg NAOs thus increases as the basis set is enlarged.

Natural orbitals are used in computational chemistry to calculate the distribution of electron density on atoms and in bonds between atoms. NBOs include the highest possible percentage of the electron density, ideally close to 2.000 [20-22]. This is carried out by considering all possible interactions between filled donor and empty acceptor NBOs and estimating their energetic importance by second-order perturbation theory. For each donor NBO (i) and acceptor NBO (j), the stabilization energy E ² associated with electron delocalization between donor and acceptor is estimated as

 

Where q_i is the orbital occupancy, ε_i, ε_j are diagonal elements and F_{i, j} is the off-diagonal NBO Fock matrix element [21].

The aim of the present work is to investigate the nature of bonding in ClonidineDrug- SWCNT using natural bond orbital (NBO) analysis. We have shown that the results from NBO calculations can provide the detailed insight into the electronic structure of molecule. The results of NBO analysis at HF/6-31G* level of theory are listed in Table2.

These tables summarize the second-order perturbative estimates of ‘donor- acceptor’ interactions. This analysis is carried out by examining all possible interactions between ‘filled’ (donor) Lewis-type NBOs and ’empty’ (acceptor) non-Lewis NBOs, and estimating their energetic importance by 2nd-order perturbation theory. Since these interactions lead to loss of occupancy from the localized NBOs of the idealized Lewis structure into the empty non-Lewis orbitals (and thus, to departures from the idealized Lewis structure description), they are referred to as ‘delocalization’ corrections to the zeroth-order natural Lewis structure. For each donor NBO (i) and acceptor NBO (j), the stabilization energy E ² associated with delocalization (“2e-stabilization”) is estimated.

According to Table2, it is obvious that one σ bond in Drug-SWCNT system has maximum Occupancy value in N37-C38.

Also, F _{(i, j)}, E² and E _(j)-E _(i)define Correlation Energy and Coefficients Hybrids is one of the other parameters that are checked in this work.Also, strongest interaction in these compounds are identified for the interaction of BD (1)  → BD^* (1) in Drug-SWCNT system.

 

Table2: NBO analysis of Drug binding to SWCNT in gas phases at HF level with the 6-31G*basis set.  Click here to View table

 

Electromagnetic Hyperfine Parameters

In this section, the major point is embedded in the investigation of the electrostatic interaction of Clonidine Drugwith the open end of a SWCNT in gas phase by the HF/6-31g*method. Length bonds, total atomic charges, Electric Potential in different bonds of Drug and Drug-SWCNT system are reported in Tables3, 4. Also, graphs of calculated electric potential in different bonds of Drug and Drug-SWCNTsystem in Figs. 3, 4.The calculations were performed in two methods and different electrostatic properties.

 

Table3: Electric potential in different bonds of Drug at HF /6-31G* basis set.  Click here to View table

 

Fig3: The graph of calculated electric potential in different bonds of Drug at the HF/6-31G* basis set.  Click here to View figure

 

Table4: Electric potential in different bonds of Drug-SWCNT system at HF/6-31G* basis set.  Click here to View table

 

Fig4: The graph of calculated electric potential in different bonds of Drug-SWCNT system at the HF/6-31G* basis set.   Click here to View figure

 

HOMO, LUMO and HOMO- LUMO Gap energy

Table 5 shows the values of HOMO, LUMO, HOMO–LUMO Gap energyfor  Drug and Drug-SWCNTsystem using HF with 6-31G* basis set. Table 5 demonstrates that From HOMO–LUMO Gap energy calculation, it can be seen that HOMO- LUMO Gap energy of decrease in the order: Clonidine Drug>Clonidine Drug-SWCNT system and by decreasing of HOMO- LUMO Gap energy, would be more stable compound. So, Clonidine Drug beside SWCNT can act better as an electron donor and probably all of its biochemical and molecular functions can be accounted for by this function [21-24].

 

Table5: HOMO, LUMO and HOMO- LUMO Gap energy for Drug and Drug-SWCNT system.  Click here to View table

 

Calculation of Binding Energies for Clonidine­ Drugto SWCNT

Binding parameters such as binding energy, Enthalpy, Free Gibbs energy and Entropy are calculated for Clonidine­ Drug and Clonidine­ Drug to SWCNT. The results are shown in table 6. According to the frequency calculation at the HF/6-31G* level of theory, connection of SWCNT to Clonidine­ Drug is a weak connection. Also, results in Table 6 indicate that energy (ΔE) and enthalpies (ΔH) values as well as free Gibbs energies (ΔG) obtained are negative, signifying that such interaction  is  favorable thermodynamically.

 

Table6: Binding energies for ­ Drug to SWCNT at the HF/6-31G* level.  Click here to View table

 

Therefore, force fields are a series of functional energy parameters that evaluate performance and calculate the Potential Energy of molecule in various positions of its constituent atoms and bonds [29].

MM⁺ is a proper parameter for attaining vibration motion of atoms, related bond stretching potential, and angles bending. AMBER force field has extensive application for proteins and nucleic acids. It assigns all conformational energies and treats with hydrogen bond energy, and torsion term [30]. Like AMBER, OPLS is designed for computation of proteins and nucleic acids. In this force field bonded potentials are similar to AMBER and its non-bonded potentials involve vander Waals and electrostatics. Similar to AMBER and OPLS it has been designed to study macromolecules.

Clonidine Drug to Carbon Nanotube was simulated in mentioned force fields in 5 different temperatures (308K, 310K, 312K, 314K and 316K). To elucidate the effect of Clonidine Drug to Nanotube energy on molecular mechanic calculation, the most usual expression for total potential energy is given by the following equation:

E ^total is the sum of bonded and non-bonded interactions

E ^bond is stretching bond energy between two atoms

E^angle is energy of bending an angle

E ^torsion is torsion energy of rotation around a bond

E ^{electrostatic} and E ^{van der Waals} are two energies which are exponent distribution, and repulsion or attraction between non-bonded atoms, respectively.

The other two calculated energy quantities are kinetic and total energy values. In symbols the total energy equals:

From a statistical point of view, the obtained valuable data for three basis sets of thermodynamic parameters (E _potential, E _kinetic, E _total), analyzed under the different simulation procedure, various temperatures values every 10 (PS) span are listed in tables7, 8 and 9.

 

Table7: Computed Drug to Carbon Nanotube Potential Energy (kcal/ mol), belong to AMBER; MM+ and OPLS force fields in five different temperatures.  Click here to View table

 

According to results observed in table 7, amount of minimum potential energy calculated by MM+ force filed have been reported. Minimum potential energy level in normal body temperature (310K) was 316.2 for MM+force filed. Also,comparisons  of  potential energy levels in different temperatures are displayed in Figs. 5a-c.

Fig5: The graphs of Drug-SWCNT Potential Energy  a)MM+, b) OPLS,  c) AMBER in Monte Carlo method. Click here to View figure

 

Table8: Computed Drug to Carbon Nanotube Kinetic Energy (Kcal/ mol), belong to AMBER, MM+ and OPLS force fields in five different temperatures.  Click here to View table

 

It is known that to have optimum function in biologic system, the energy levels must be in the minimum level. According to results observed in Table 8and Fig.6, for kinetic energy in different time steps and various force fields were constant and the maximum and minimum quantity observed in 310K, 285.5Kcal/mol and in 308K, 123.7 Kcal/mol, respectively.

 

Fig6: The graphs of Clonidine Drug-SWCNT Kinetic Energy  a)MM+, b) OPLS,  c) AMBER in Monte Carlo method.  Click here to View figure

 

Table9: Computed Drug-SWCNT Total energy(kcal/ mol), belong to AMBER, MM+ and OPLS force fields in five different temperatures.  Click here to View table

 

Also, data analysis of table 4 exhibited that total energy quantities were affected by increasing temperature that energy increase leads to molecular instability. According to results observed in Table 9and Fig.7 maximum quantity total energy in different temperature was 312K, 673.4Kcal/mol in amber method.

 

Fig7: The graph of Clonidine Drug-SWCNTTotal Energy  a)MM+, b) OPLS,  c) AMBER in Monte Carlo method.  Click here to View figure