Journal of Nano Chemical Agriculture , Vol(1) , No(3) 94
The investigation of NMR parameter of drug binding to Single Wall Carbon Nanotube
Z.Yousefian1, 2*, N. Shadmani3
1* Department of Chemistry, Shahre-Rey Branch, Islamic Azad University, Tehran, Iran
2Young Researchers and Elite Club, Shahre-Rey Branch, Islamic Azad University, Tehran, Iran 3Young Researchers and Elite Club, Rasht Branch, Islamic Azad University, Rasht, Iran
*Corresponding author’s E-mail:[email protected]
Abstract
At the present study, Clonidine drug were added to zigzag single walled carbon nanotubes (CNT) with (5,
0) structure and a length of 50A. Then NMR different parameters of Drug-CNT complex such as magnetic
shielding tensor (σ ,ppm), shielding asymmetry (η), magnetic shielding constants (σ iso), anisotropic magnetic
shielding tensors (σaniso), Chemical shifts (δ) was studied in theory level of HF/6-31G* in gas phase. The
results obtained from a comparison between tables and charts came up for discussion and analysis.
Keyword
Single walled carbon nanotube (CNT) , Clonidine, Drug , NMR
Introduction
Carbon nanotubes were discovered almost 15
years ago. The first report by Iijima [1] was on the
multi wall form, coaxial carbon cylinders with a
few tens of nanometers in outer diameter. Two
years later single walled nanotubes were
reported [2, 3]. They are typically between 1 and
1.5 nm in diameter, but several microns in length.
After a slow start in the mid 90’s the field
suddenly exploded two years ago. A first
application – displays made out of field emitting
multiwall tubes – is planned to be commercially
available during the next years. Other proposed
applications include, e.g., nanotubes in
integrated circuits, nanotubes actuators, or
nanotubes for hydrogen storage [4-8]. From a
physics point of view they are probably the
best realized example of a one-dimensional
system.
Nano technology is an advancing method with
many ways for unlocking problems, especial in
medical science. By performing more research on
this technology, treat can be found for diseases
that have no cures until now. Therefore,
nanotechnology can effect on life like are
volution. One of the exciting classes of nano
materials is carbon nanotubes (CNTs), which
possess characteristics suitable for many
applications as delivery vehicles of biologically
important molecules in view of possible
biomedical applications, such as vaccination and
gene or drug delivery. Scientists from different
fields of science are just beginning to solve my
steries and hypo the size about CNT-gen
complexes. A useful devise to achievement these
purposes is theoretical methods. [9, 10]
Ideally, the nanotubes will locate to a specific
site in the body, through its functionalized
surface, and release its contents. The major
advantage with this form of targeted drug
delivery is the possibility of reducing the many
adverse side effects experienced by patients [11-
16] hence throughout various field of science and
technology, a push towards the use of Nano-
95 The investigation of NMR parameter
scale technology such as Single wall carbon
nanotubes is on the move. One area where CNTs
work is already well under way is within the field
of drug delivery. CNTs make possible bonding to
drugs [17].
The primary goal of this study was to examine the
binding of Clonidine drug with zigzag single
walled carbon nanotubes (CNTs) with (5, 0)
structure and a length of 50A.
The secondary goal of this study was to
investigate NMR parameter of Drug-SWCNT
complex. [18]
Methodology
In our model, Clonidine drug was attached
covalently to carbon nanotube (CNTs) with (5, 0)
structure and a length of 50A.
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 and B3LYP methods coupled to
6-31g* and 6-31g basis sets 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). There are
several flavors of QMC variational, diffusion and
Green's functions. These methods work with an
explicitly correlated wave function and evaluate
integrals numerically using a Monte Carlo
integration [19, 20]. In general, ab initio
calculations give very good qualitative results and
can give increasingly accurate quantitative results
as the molecules in question become smaller
[21].There are three steps in carrying out any
quantum mechanical calculation in Hyper Chem.
7.0 program package [22]. 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 CNT in gas phase by the HF/6-31g*method.
The chemical shielding tensor describes how
the shielding varies with the molecular
orientation. The three principal components of
this tensor are often given by:
σ11 ≤ σ22 ≤ σ33
The values of the shielding tensor are frequently
expressed as the isotropic and anisotropic parts
(σiso and σaniso) and the shielding asymmetry (η) .
[23, 24]
Results and Discussion
Molecular Geometry
Fig. 1, Shows the graphical representations of
the optimized geometry of drug–CNT. 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 CNT are also
shown in Fig.1.
Journal of Nano Chemical Agriculture , Vol(1) , No(3) 96
Fig.1.Optimized geometries of Clonidine and Clonidine drug-CNT obtained at HF/6-31G level
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 [25]. 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 CNT 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 CNT system in gas phase are
presented in Table 1. Also, the graphs of
calculated isotropic magnetic shielding constants
σiso (ppm), anisotropic magnetic shielding tensors
σaniso (ppm), Chemical shifts δ (ppm) and shielding
asymmetry (η) versus the number of atomic
centers for selected atoms of drug -CNT 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-CNT 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 σaniso in
drug-CNT 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 CNT and our knowledge about drug
interacted to CNT has been specified that C
number 31 show the largest intermolecular
effects in (η) component (Fig. 2d).
97 The investigation of NMR parameter
Conclusion
NMR chemical shielding tensors in the
methods framework makes it possible to study
the chemical shift of carbon nanotubes. The
calculated parameters reveal that Cl57 and H83
atoms have the largest and smallest anisotropic
magnetic shielding (σaniso) constants among the
other nuclei, respectively.
The Cl57 has the largest but N62 has the
smallest chemical shift (δ) constants among the
other atoms, respectively. The diagrams consist
of σiso, σaniso and η show all shielding values but
∆σ, δ show more negative shielding values at the
HF in 6-31G* basis set.
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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 CNT in gas phases at HF level with the 6-31G* basis set
σ11 σ11
Atoms σ22 η Atoms σ22 η
33 δ 33 δ
-637.903 -205.081
16C -146.819 2.1718 0.39 37N 18.9341 60.7706 0.62
833.1764 195.2738 -491.084 406.1945 201.1131 -224.016
-27.4424 -81.4283
26C 62.3164 76.5701 0.68 38C 37.2258 83.3807 0.61
165.2638 137.8214 89.7588 191.1532 109.7249 -118.654
-21.4359 -129.917
27C 74.3248 60.7113 0.75 39N 92.7911 191.107 0.11
205.135 183.6991 109.3743 347.1001 217.1832 -222.708
-31.3291 20.6434
30C 59.2903 70.0129 0.76 48H 25.4223 25.8038 0.84
170.5161 139.187 -90.6194 9.1762 29.8196 -4.7789
-15.762 19.6648
31C 72.2245 74.2898 0.95 51H 28.6523 29.4006 0.83
173.9076 158.1456 -87.9865 17.2266 36.8914 -8.9875
663.5445 14.176
32Cl 816.6251 719.4868 0.22 52H 23.5228 21.6918 0.67
403.2994 1066.844 250.2188 20.5244 34.7004 11.1776
687.0149 22.7438
33Cl 829.9645 740.9236 0.23 53H 26.5296 26.1305 0.59
374.9403 1061.955 231.9907 7.9708 30.7146 5.6926
151.9829 22.9016
34N 201.0279 206.7937 0.76 54H 27.3878 26.1813 0.57
92.3243 244.3072 -49.045 10.1788 33.0804 5.696
82.2142 14.1398
35C 145.1186 158.8151 0.56 55H 31.1369 32.9595 0.78
112.1122 194.3264 -62.9044 32.1716 46.3114 -16.9971
97.5868 -6.546
36C 138.4438 132.6744 0.75 56H 17.6022 9.8818 0.51
87.4834 185.0702 46.6264 56.0167 49.4707 31.8685
99 The investigation of NMR parameter
(a)
(b)
(c)
(d)
Figure2. The graphs of a) , b) σaniso , c) δ , d) η of propose atoms of drug binding to CNT in gas phases
at the HF/6-31G* basis sets.
0
0.2
0.4
0.6
0.8
1
-200
0
200
400
600
800
1000
16
C
26
C
27
C
30
C
31
C
32
Cl
33
Cl
34
N
35
C
36
C
37
N
38
C
39
N
48
H
51
H
52
H
53
H
54
H
55
H
56
H
σ iso
-600
-400
-200
0
200
400
16
C
26
C
27
C
30
C
31
C
32
Cl
33
Cl
34
N
35
C
36
C
37
N
38
C
39
N
48
H
51
H
52
H
53
H
54
H
55
H
56
H
δ
-200
0
200
400
600
800
1000
16
C
26
C
27
C
30
C
31
C
32
Cl
33
Cl
34
N
35
C
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C
37
N
38
C
39
N
48
H
51
H
52
H
53
H
54
H
55
H
56
H
σaniso
0
0.2
0.4
0.6
0.8
1
16
C
26
C
27
C
30
C
31
C
32
Cl
33
Cl
34
N
35
C
36
C
37
N
38
C
39
N
48
H
51
H
52
H
53
H
54
H
55
H
56
H
η