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Molecular optmization study of gentamicine drug

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 عباس عبد علي دريع الصالحي 25/02/2018 08:29:04
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JOURNAL OF MULTIFUNCTIONAL MATERIALS & PHOTOSCIENCE
8(1), June 2017, pp. 1-11
Abbas A-Ali Drea* and Marwa Kamil Jalil
University of Babylon, College of Science, department of Chemistry, Hilla-Iraq
Abstract: Molecular optimization have been carried out in vacuumed to investigate the energetic
properties of geometry optimized structure of Gentamicin drug. Theoretical methods like, Semi
empirical methods and Density functional method have been performed to estimate the chemical
reactivity through calculations of Energy gap, Binding energy, Heat of formation and Zero
point energy. The reactivity of the molecule has been investigated using Surface potential energy
calculations through PM3-Single point Configuration Interaction (3*3), Microstate method to
examination chemical bound stability of main bounds in Gentamicin drug molecule through
bond angle, bond length and torsion angle. The vibration spectrum and electronic spectrum
have been calculated by semi empirical CNDO method and DFT (Minimal STO-3G level). The
best conformations of Gentamicin molecule has been studied through rotation of most reactive
bound torsion angle C19-N26-C27-H62.
They found, the energetics values of total energy , MP2 Correlation Energy, Egap and Zero point
according to DFT(Minimal STO-3G level of theory) are equal to -298643.889, -1553.812,
1.37284,and -3763.39691 respectively at kCal/mol units. The N26-C19 bond in Gentamicin
represented the most probable to break down and shared in various reactions than other duo
to the lowest bond dissociation energy value (75.734 kCal/mol). The conformations has most
stable energy through energetic value equal to -6835.4145 kCal/mol.
Key words: Gentamicin, potential energy surface, Geometry optimization, Single point
calculations, DFT, Semi-empirical.
Introduction
Gentamicin is the antibiotic of first choice for treatment serious bacterial infections in
bone, respiratory, skin, urinary tract, stomach, soft tissue, blood and heart in form of
injection, ointment, cream, suspension and also used in Veterinary Medicine in many
developed and industrialized countries[1-3]. Gentamicin has been discovered in 1963 by
Marvin Weinstein’s set at Schering Plough through isolated from various species of the
micro mono sporia echinospora [4, 5]. Gentamicin is a commonly used as aminoglycoside
antibiotics [6]. Gentamicin has been designed from three rings purpose amine, 2-deoxy
strep amine and gentos amine or garos amine ring [7], since the major compounds of
*Corresponding author: aadreab22@yahoo.com
Gentamicin are differ in purpose amine component. The four major compounds of complex
mixture for Gentamicin are C, C1a and C2a, a 6´-C-epimer of C2 [8, 9]. The other minor
compounds that present include Gentamicin’s A,A1,A2,A3,C2a,C2b,A4,B,B1and X2, and
JI-20A,JI-20B,Sisomicin and G-418 have been described which are other antibiotics
structurally related to Gentamicin.[10,11]. It was one of few antibiotics thermally-stable
that remains active until after sterilization process [12]. Gentamicin drug fundamentally
acts by binding to the 30S subunit of the bacterial ribosome stopping the continuous
progress of protein synthesis [13].The two hydroxyl groups of deoxystreptamine(2-DOS)
linked to Garosamine (3-methyl amino-3-deoxy-4-C-methyl-??-L-arabinose) and
purpurosamine (2,6-diamino-2,3,4,6,7_pentadeoxyheptopyranose) amino sugars by
glycosides’ bonds, the amino groups in the two surges attached to (2-DOS) profoundly
influence on the biological activity but presence or absence of hydroxyl groups not have a
clear effect on the activity of aminoglycosides antibiotics. Figure 1. Show two dimensional
view of the Gentamicin molecule [14-16].
Figure 1: Two dimensional view of the Gentamicin molecule [14-16]
They found several types of Gentamicin with different chemical activities due their
structures, that’s related to energetics properties and energy gaps for each of these
stractures. The aim of the present work tend to find the molecular optimized structure
towards the chemical activity of Gentamicin. The quantum mechanics calculation methods
have been used, since different methods of semi-empirical and DFT- STO-3G at level of
theory, to estimate the geometry optimization, heat formation, total energy,
HOMO&LUMO, Energy gap, vibration spectrum, and electronic spectrum. Also Surface
potential energy was used to investigate the reactivity of main chemical bonds that’s
consistent gentamicin molecule structure [17].
Computational Details
Computations have been done using quantum methods that’s implemented at Hyperchem
program version 8.0.2 [18-20]. DFT, Minimal STO-3G at level of theory have been used to
find out Geometrical properties, likes electrostatic potential, total charge density, HOMO
and LUMO energy, Zero point energy, vibration spectrum and electronic spectrum [21].
Semiempirical calculation have been performed using several methods like MNDO,
CNDO, INDO, MNDO3, AM1 and RM1 and to estimate energetic properties, that’s
followed by using DFT, Minimal STO-3G at level of theory for the same manner[22].
Potential energy stability of bond length, bond angle and torsion angle have been examined
using PM3 method CI (3*3) Microstate to estimate the chemical reactivity of main bound
in Gentamicin drug[23].
Results and Discussion
The Geometry optimization structure of gentamicin molecule is represented in figure 1.
They found that properties such electrostatic potential and their molecular orbitals are
distributed at different active sites. The chemical structure is consisted from three different
sugar rings and chemical reactivity of the substituted functional groups on these ring are
differ at different orientations due their different induced field effect, such amine groups,
hydroxyl groups, and methyl amine . Table 1. Involved energetic values of optimized
gentamicin, the total energy value with full MP2 -300197.701 kCal mol-1 is comes due
geometry optimization process in vacuumed. Zero point energy (ZPE) value is calculated
as a result of vibrational spectrum data that’s equal to -3763.39691 kCal mol-1 is much
stabilized structure and relax molecules due to this low value of ZPE. The cost time of
calculus is 542 hours, 54 mints and 31 second. The red color regions of electrostatic potential
that observed in figure 1&2 show high electron density on oxygen atoms due to the high
electronegativity, while the green color reigns represented the low electron density of
carbon atoms. The HUMO and LUMO energies have been appeared in red and green
color, the negative part of wave function has been given by red color (subject attacked by
an electrophile) and the green color represented the positive part of wave function (subject
attacked by nucleophile ), this behavior determine chemical effectiveness of Gentamicin
molecule toward the substitution reaction [24-27].
Table 1
Energetic properties of Gentamicin molecule calculated at DFT Minimal STO-3G at
level of theory
Total energy (kCal/mol) -298643.889
Total energy with MP2 (kCal/mol) -300197.701
MP2 Correlation Energy (kCal/mol) -1553.812
LUMO (eV) 55.92773
HOMO (eV) 54.55486
Energy gap (eV) 1.37284
Zero point energy (kCal/mol) -3763.39691
Time of calculus (hr.min.sec) 542:54:31
Figure 2: Geometrical optimization properties of Gentamicin molecule calculated by DFT, Minimal STO-3G
at level of theory
Surface Potential energy calculation have been used to investigated the stability of
bond length and bond angle for the bounds of Gentamicin molecule through PM3
Configuration Interaction microstate (3*3), as shown in Table. They found that’s bonds of
C14-O28 and C18-O30 were more stable than other bonds with 108.354 and 104.548 kCal/mol
respectively of dissociation energy values than other bounds. From other view Figure 2.
Shows the four bond with lowest chemical stability than other chemical bounds of
Gentamicin molecule, since the red color on C14-O28 and C18-O30 bonds appears their higher
Geometry optimization Electrostatic potential
LUMO at three dimensions HOMO at three dimensions
Total charge density
stability than other two bonds C19-N26 and C10-C21 bonds in yellow color. The lowest
chemical stability due to the induced effect field of substituted functional groups that
found in the molecule (N atom have electronegativity less than O atom, leads to weak
hydrogen linkage in the amines group compared with a hydroxyl group and thus easily
broken and shared in important reactions).
Table 2
Surface Potential energy calculation of chemical bonds Semiemprical-PM3
method CI (3*3) Microstate
Bonds *Equilibrium **Equilibrium *Dissociation **Dissociation *Energy
energy bond length energy bond length difference
C2-O13 -6835.467 1.927 -6751.963 2.326 83.504
C7-O13 -6835.302 1.427 -6751.080 2.826 84.222
C5-O20 -6835.450 1.427 -6748.511 2.627 86.939
C17-O20 -6835.146 1.427 -6737.786 2.327 97.36
C21-N23 -6834.811 1.527 -6753.967 2.627 80.844
C6-N32 -6834.801 1.527 -6754.999 2.627 79.802
C3-N31 -6834.985 1.527 -6754.030 2.627 80.955
C12-N24 -6834.914 1.527 -6742.434 2.827 92.48
C19-N26 -6834.991 1.527 -6759.257 2.627 75.734
C10-C21 -6835.109 1.527 -6759.148 2.827 75.961
C14-O28 -6835.449 1.427 -6727.095 2.427 108.354
C18-O30 -6835.181 1.427 -6730.633 2.427 104.548
C1-O25 -6835.192 1.427 -6737.128 2.827 98.064
C21-C22 -6835.439 1.527 -6747.763 2.827 87.676
C14-C29 -6835.394 1.527 -6752.386 2.827 83.008
N26-C27 -6834.412 1.527 -6751.304 2.527 83.108
* kCal/mol units. ** Angstrom units
Figure 3: The lowest chemical stability bonds of Gentamicin molecule (active bonds)
Figure 4. Illustrates the potential energy stability of bonds at Gentamicin molecule.
The C2-O13 bond is lowest stable and more active toward the reactions than other bond,
since bond length equal to 1.927 ?. The difference in the stability of the bonds depends on
the nature of substituted functional groups (tendency to donate or draw electrons) and
also their steric effects of each bond in the bulk structure.
Figure 4: Potential energy stability curves of bond length in Gentamicin molecule calculated at semi emprical
PM3 CI.Microstate (3*3)
Table 3. Show the calculation of bound angle stability toward the torsion energy stresses
and their related equilibrium configuration as active site at Gentamicin structure. Comperes
between all the chemical bounds described that, bond angle O13-C7-C11 angle is more stable
than other bond angles due their dissociation energy value of 615.711 kCal/mol [28].
Table 3
Surface Potential energy investigation of Gentamicin bond angle calculated at semi
empirical –PM3, CI (3*3) Microstate
*Energy
difference
**Broking
bond angle
*Dissociation
bond energy
**Equilibrium
bond angle
*Equilibrium
bound energy
Bond angle
C21-C10-C9 -6834.4438 110 -6807.3588 140 27.085
C21-C10-C11 -6834.2270 120 -6806.6005 140 27.627
N23-C21-C10 -6835.4672 110 -6800.2763 140 35.191
C29-C14-C28 -6835.3413 110 -6790.5341 140 44.807
N26-C19-C18 -6834.5932 110 -6803.9326 140 30.661
N26-C19-C14 -6834.7910 110 -6805.7739 140 29.017
C27-N26-C19 -6834.9833 120 -6822.2983 140 12.685
O30-C18-C19 -6835.3989 110 -6803.3569 140 32.042
O30-C18-C17 -6834.8481 110 -6810.2363 140 24.612
N23-C21-C22 -6834.7915 110 -6789.6723 140 45.119
C19-C14-C28 -6835.1088 110 -6803.7934 140 31.315
C29-C14-C15 -6835.4667 110 -6801.0942 140 34.373
N32-C6-C4 -6834.6279 110 -6813.6079 140 21.02
N32-C6-C5 -6835.4580 110 -6802.7153 140 32.743
O25-C1-C5 -6835.4526 110 -6794.6425 140 40.810
O25-C1-C2 -6833.9047 120 -6810.5952 140 23.309
N31-C3-C4 -6835.3852 110 -6796.5888 140 38.796
N31-C3-C2 -6835.4658 110 -6804.6333 140 30.833
N24-C12-C7 -6835.4399 110 -6804.6567 140 30.783
C2-O13-C7 -6834.901 120 -6820.601 140 14.300
C17-O20-C5 -6834.779 110 -6819.388 140 15.392
C18-O17-C20 -6835.323 110 - 6806.133 140 29.19
O20-C17-O16 -6835.0009 100 -6775.118 140 59.882
O20-C5-C6 - 6835.164 110 -6787.224 140 47.94
C3-C2-O13 -6835.416 110 -6730.334 140 105.082
O13-C2-C1 -6834.943 110 -6783.069 140 51.875
O13-C7-C11 -6835.456 100 -6219.745 130 615.711
O13-C7-C12 -6833.747 120 -6811.620 140 22.127
O20-C5-C1 -6835.466 110 -6803.631 140 31.835
Table 4 shows the Potential energy stability of the mean torsion angles in Gentamicin
molecule. The bound angle C2-O13-C7-C12 is represented more stable bound than other
bounds due to their requirements for 3037.6617 kCal/mol to break down, also the
dissociation energy value of the bound angle C19-N26-C27-H62 is equal to 3.231 kCal/mol,
so that it’s represented the lowest stable than other angles of gentamicin [29]. Figure 5
Show comparison between these two bonds, the high stable bond defined in red color
and the lowest stable in yellow color.
Table 4
Potential energy stability and dissociation of Gentamicin Torsion angle by
Semiemprical-PM3 method CI(3*3)
*Dissociation
energy of angle
**Broking
Torsion angle
*Dissociation
energy
**Equilibrium
Torsion angle
*Equilibrium
energy
Bond Torsion
angles
C6-C5-O20-C17 -6834.7261 120 -6736.3330 180 98.3931
C18-C17-O20-C5 -6834.9556 130 -6829.4888 180 5.4668
C2-O13-C7-C12 -6834.5577 90 -3796.8960 180 3,037.6617
C1-C5-O20-C17 -6831.0410 180 -6752.6841 60 78.3569
C7-O13-C2-C1 -6803.3691 180 -6118.7456 100 684.6235
C22-C21-C10-C9 -6834.4434 170 -6829.2099 110 5.2335
C3-C2-O13-C7 -6834.0347 110 -6444.9834 180 389.0513
C11-C7-O13-C2 -6821.1719 180 -5192.0469 70 1,629.125
O16-C17-O20-C5 -6826.2759 180 -6761.5801 90 64.6958
C27-N26-C19-C18 -6832.7802 140 -6820.0845 180 71.2001
N23-C21-C10-C9 -6834.4331 130 -6824.4809 100 9.9522
N23-C21-C10-C11 -6834.3843 160 -6828.9585 110 5.4258
C27-N26-C19-C14 -6834.3779 60 -6828.5972 150 5.7807
C22-C21-C10-C11 -6832.6406 60 -6828.61377 180 4.02683
C19-N26-C27-H62 -6835.4145 180 -6832.1835 140 3.231
C19-N26-C27-H63 -6833.7505 60 -6829.4551 140 4.2954
C19-N26-C27-H64 -6834.4927 60 -6830.1133 140 4.3794
The C19-N26-C27-H62 torsion angle represented the more stable from other in Potential
energy stability value by -6835.4145 kCal/mol in 180? due to the functional groups that
found in the molecule. Different optimized structures (configurations) can be occurs at
Gentamicin through different transitions torsion angle states into C19-N26-C27-H62 angle.
Figure 5 Show that the torsion angle of C19-N26-C27-H62 in Gentamicin molecule includes
the presence of several cases of branches transition to vibrate bond chemical angle in
different energies for getting the best situation stabilizing steric optimum , it’s have several
stationary point such as A, C and E are minimal . Points such as B and D are maximum
energetic states. Only structures at points A, C and E represented the stable conformations
for this torsion angle. the lowest energy conformation was the anti-conformation in
structure E, it was the most stable from other by -6835.4145 kCal/mol in 180? due to the
molecule arranged its groups to adopt the alleviated torsional strain and reduced the
electron repulsion in the torsion angle [31].
CONCLUSIONS
• The Energetic properties of Gentamicin molecule have been found by using several
semi empirical methods and DFT calculations.
• The chemical reactivity of the molecule appeared the N26-C19 bond length the most
probable to break down by using S.P.E calculations duo to the less value of bond
dissociation energy (75.734kCal/mol)of functional group (methyl amine ) at
Garosamine.
• The bond angle O13-C7-C11 angle is more stable than other bond angles due their
dissociation energy value of 615.711 kCal/mol.
• The bound angle C2-O13-C7-C12 is more stable bound than other bounds due to their
requirements for 3037.6617 kCal/mol to break down.
• The C19-N26-C27-H62 is the most stable angle than others in Gentamicin with Potential
energy stability value of -6835.4145 kCal/mol in 180?.
References
[1] W. Lesniak, W. R. Harris, J. Y. Kravitz, J. Schacht, and V. L. Pecoraro , Solution Chemistry of Copper(II)-
Gentamicin Complexes: Relevance to Metal-Related Aminoglycoside Toxicity, Inorg. Chem., 42(2003),
1420-1429, DOI: 10.1021/ic025965t
Figure 5: Surface potential energy curve of torsion angle C19-N26-C27-H62 of Gentmicine
[2] S.M. Dizaj, F. Lotfipour, M. Barzegar-Jalali, M.-H. Zarrintan, K. Adibkia, Physicochemical characterization
and antimicrobial evaluation of gentamicin-loaded CaCO3 nanoparticles prepared via microemulsion
method, J.Drug Delivery Science and Technology. (2016), DOI: 10.1016/j.jddst.2016.05.004.
[3] N. C. Megoulas, Mi. A. Koupparis, Development and validation of a novel LC/ELSD method for the
quantitation of gentamicin sulfate components in pharmaceuticals, J. Pharmaceutical and Biomedical
Analysis. 36 (2004) 73–79, DOI:10.1016/j.jpba.2004.05.018.
[4] J. E. Davies, ”Aminoglycosides: Ancient and Modern”, J. Antibiot. 59(2006) 529–532.
[5] Ch. Chen, Y. Chen, P. Wu, B. Chen, Update on new medicina applications of gentamicin: Evidencebased
review, J .the Formosan Medical Association 113 (2014) 72-82, http://dx., DOI.org/10.1016/
j.jfma.2013.10.002.
[6] A. MansoorInasab, A. Morsali, M.M. Heravi and S. A. Beyramabadi, Quantum Mechanical Study on the
Adsorption of Drug Gentamicin onto ?-Fe2O3 nanoparticles,.J.chem.3 (2015) 1509-1513, http://dx.doi.org/
10.13005/ojc/310329.
[7] G. Hariprasad & M. Kumar & K. Rani &P. Kaur & A. Srinivasan, Aminoglycoside induced nephrotoxicity:
molecular modeling studies of calreticulin-gentamicin complex, J .Mol Model .18 (2012) 2645–2652, DOI
10.1007/s00894-011-1289-8.
[8] Yawen Gu, Xianpu Ni, Jun Ren, Huiyuan Gao, Da Wang, and Huanzhang Xia, Biosynthesis of Epimers
C2 and C2a in the Gentamicin C Complex, ChemBioChem .16 (2015)1933 – 1942, http://dx.doi.org/10.1002/
cbic.201500258.
[9] G. Seidl, H. P. Nerad, Gentamicin C: Separation of C1, C1 a, C2, C2a and C2b Components by HPLC
Using Isocratic Ion-Exchange Chromatography and Post-Column Derivatisation, Chromatographi .3
(1988). DOI: 10.1007/BF02316439.
[10] J. Berdy, J. Kadar Pauncz, ZS. Mesfalvivajna, Gy. Horvath, J. Gyimesi and I. KOCZKA, Metabolites of
Gentamicin-Producing Micromonospora species 1. Isolation and identifiction of metabolites, J. antibiotic.
11(1977), DOI: 10.7164/antibiotics.30.945.
[11] R.T Testa and B.C. Tilley, Biotransformatio , A new Approach to Aminoglycoside biosynthisis:: ??
Gentamicin, Antibiotic .2(1976), DOI: 10.7164/antibiotics.29.140.
[12] A. Mansoorinasab, A. Morsali, M. M. Heravi, and S. A. Beyramabadi, Quantum Mechanical Study on
the Noncovalent Adsorption of DrugGentamicin Onto Pristine and COOH Functionalized Carbon
Nanotubes, J. Comput. Theor. Nanosci .12(2015), 4935–4941, DOI:10.1166/jctn.2015.4462.
[13] S. Yoshizawa, D. Fourmy, and J.D. Puglisi, Structural origins of gentamicin antibiotic action, The EMBO
J.22 (1998) 6437-6448, DOI: 10.1093/emboj/17.22.6437.
[14] M. Himabindu and A. Jetty, Microbial Biosynthesis and Applications of Gentamicin A Critical Appraisal,
Biotechnology .Rev.28 (2008)173–212, DOI: 10.1080/07388550802262197.
[15] A. Chmielewsiu, A. Konowae, and A.Zamojski, The Synthesis of Racemic purpurosamine B, Carbohydrate
Research, 70 (1979) 275-282.
[16] R. Benveniste and J. Davies, Structure-Activity Relationships among the Aminoglycoside Antibiotics:
Role of Hydroxyl and Amino Groups, Antimicrobial agents and chemotherapy, 4(1973) 402-409.
[17] Aqyl. Alaa -Hussein, and Abbas. A-Ali Drea, Theoretical investigations of photolysis for Halon-2402 in
stratospheric layer, Basra Journal of Science (C) 30 (2012) 132-146.
[18] Abbas A- Ali Drea, Theoretical study to synthesis 1, 3, 5,-triglycerol benzene using Semi empirical and
Ab-Initio calculation methods, National Journal of Chemistry, 39(2010) 481- 498.
[19] Aqyl. Alaa Hussein, and Abbas A-Ali Drea, Theoretical investigation study of Bromine radical reaction
with ozone stratospheric layer, J. Applicable Chemistry, 1(2012) 453-459.
[20] HyperChem 8.0.2. 2, Hypercube Inc.
[21] Duaa. Muayad, Saudon. A. Aowda and A.A-Ali Drea, Simulation Study of Oxidation for Oleic acid by
KMnO4 Using Theoretical Calculations. Applicable Chemistry. 2 (2013) 42-49.
[22] Abbas. A-Ali Drea, Photolysis of Raxil DS2 in aqueous solution by sun light through transition state
computational study National Journal of Chemistry, 37(2010), 86 -100.
[23] Fathel. O. Essa, Kathtem. J. Kadhum, and Abbas. A-Ali Drea , Estimation of transition state and Synthesis
of Barbituric Acid with their derivatives of 1,3,4-Thiadiazole, J. Applicable Chemistry, 1(3)(2012)344-
351.
[24] Abbas. A-Ali Drea and Raua -Hussien, Simulation study of ozone depletion through photolysis
mechanism of HCFC-124, 7 (2016) 99-110.
[25] Hyffa. Adnan, Saudon. A. Aowda and Abbas A-Ali Drea, Simulation Study of alkylation reaction of
resorcinol, 3 (2014) 2365-2371.
[26] Hyfa. T. Mohammed, and A. A-Ali Drea, Prodrug Design methods to treat Parkinson’s disease, 7(2)(2016)
111-117.
[27] Raual-Hussein, Theoretical Investigation of Photolysis Reactions Mechanisms for Halo-Hydrocarbon
Compounds in Stratospheric Layer, MSC thesis, 2017.
[28] Abbas A-Ali Drea and Aqyel Hussein Alkhaffagi, Theoretical Study of Reaction Mechanism for Ozone
with Light Halohydrocarbons , MSC thesis, 2012.
[29] H. T. Mohammed, and Abbas A-Ali Drea, Prodrug Design methods to treat Parkinson’s disease, 7(2)(2016)
111-117.
[30] [29] Abbas A-Ali Drea and Aqyel Hussein Alkhaffagi, Theoretical Study of Reaction Mechanism for
Ozone with Light Halohydrocarbons , MSC thesis, 2012.
[31] Abbas A-Ali Drea and Aqyel Hussein Al-khaffagi, Theoretical Study of Reaction Mechanism for Ozone
with Light Halo hydrocarbons, MSC thesis, 2012.

  • وصف الــ Tags لهذا الموضوع
  • Gentamicin, potential energy surface, Geometry optimization, Single point calculations, DFT, Semi-empirical.

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