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SpectroscopicandInterMolecularStudiesofAntiAIDSDrug:3'Azido2'deoxythymidine
Y.P.Singha*andRatneshDasb
aDepartmentofPhysics,Govt.WomensPolytechnicCollege,Sagar(MP)470001
INDIA,.Email:Y_P_S_2k@Yahoo.com
bDepartmentofChemistry,Dr.H.S.GourUniversity,Sagar(MP),INDIA,470001,
Email:ratnesh_das@breakthru.com
ABSTRACT
The vibrational absorption spectra of 3'Azido2'deoxythymidine (Zidovudine) have been studied. The
spectrawereanalysedbasedonsemiempiricalquantummechanical(AM1)and(PM3)calculations.AssumingCs
point symmetry, vibrational assignments for the observed frequencies have been proposed. The spectra exhibit
distinct features originating from low frequency vibrational modes caused by intermolecular motion. Normal
modeshavebeencalculatedandanassignmentoftheobservedspectrahasbeenproposed.
Keywords:Zidovudine,FTIRSpectra,Antiaidsdrug,HIV,AM1andMP2calculations
INTRODUCTION
1988.InthesolidstateAZTformsahydrogenbond
network4.
Thestudyofdrugcomplexeshaveassumed
Thereareanumberofdrugsthathavebeen
consideredastobeantiHIV.Thedrugslike3'Azido
2'deoxythymidine (AZT) and ribavirin appear most
promising because both cross the bloodbrain
barrierandcanbetakenorally,andinearlytraities
theydonotcauseserioussideeffects.
viewforachievimgbetterunderstandingofAIDS,its
causes, symptoms, mode of spreading, diagnostic
treatment and possible cure. Spectroscopis studies
of antiAIDS drug have made a significant
contribution of this noble endeavor of striving to
eliminatethefearofthisdreadfuldisease.
AZTZidovudine,wasthefirstdrugapprovedforthe
treatment of AIDS and HIV infection. Jerome
2
Thecalculationofvibrationalfrequenciesby
spetraofmoleculesintheirgroundelectronicstates
8
werepredictedbymolecularorbitaltheory .
estimatedtobewithin3cm1andtheresolutionwas
betterthan2cm1throughtheentirespectra.
79
O17
C1
N2
H30
O15
studyofthedipolepolarizabilityofAZTdrug.
H31
H20
H29
C13
H24
O9
H 2 5H 2 8
N16
H26
N 32
H27
C6
C12
N14
Thusthepresentstudyhasbeenundertakenwitha
H23
C5
N4
O 19
C8
C7
C3
H22
H21
H18
3'Azido2'deoxythymidineorZidovudine
EmpiricalFormula
C10H13N5O4
MolecularWeight
267.24
andMOPACmethod.
Thus the present study has been
Figure1:StructureandFormulaofZidovudine
RESULTSandDISCUSSIONS
Zidovudineisoneofthecomplexstructured
drugs. The infra red spectrum of this drug is
presentedinfigure2.
Wecangetinformationfromcomputational
ACKNOWLEDGEMENTS
alsocalculatedonthebasisofAM1andPM3precise
set of MOPAC as shown in table 3. 3'Azido2'
deoxythymidinecontains32atomssothatithas90
normal modes. The calculated normal modes are
distributed among 60 a and 30 a species of Cs
symmetrygroup.
The table 3 also shows that PED
1.
2.
3.
4.
5.
6.
7.
8.
CONCLUSIONS
Theoretical
semiempirical
quantum
9.
10.
due
to
intermolecular
interactions,
anharmonicityandcomputationalbasisset.
11.
DossierP,AIDSandThirldWorld,ThePanon
InstituteofLondon(1988)
Yarchoan R, Mitsuya H, Broder S. AIDS
therapies.SciAm,259(4):1109,(1988)
AlanHowie,r.a.howie@abdn.ac.uk,
www.abdn.ac.uk/chemistry/research/rah/r
ah.hti,(2006)
I.D.Dyer,J.N.Low,P.T.Tollin,H.R.Wilsonand
R. Alan Howie; Structure of 3'Azido2'
deoxythymidine, AZT; Acta Crystal,; C44,
767769,(1988)
A.P.Scott, L.J.Radom,; Harmonic vibrational
frequencies: An evaluation of HF, MP,
Quadratic configuration Interaction, DFT
and Semiempirical scale factors; J. Phys
ChemA;;100,1650216513,(1996)
M.W.Wong;
Vibrational
frequencies
predictionusingDFT;ChemPhys.Lett;;256,
391399,(1996)
M. Sabio, S. Topiol; A conformational
analysis of 3'Azido2'deoxythymidine; J.
Comput.Chem,13,478491,(1992).
M. T. Baumgartner, M. I. Motura, R. H.
Contreras, A. B. Pierini, M. C. Brin;
Conformational
studies
of
novel
antiretroverial analogs of Zidovudine;
Nucl.eos. Nucleot. & Nucleic Acids, 22, 45
62,(2003).
H. Xinjuan, H. Mingbao, Y. Dayu; Density
functionof3'Azido2'deoxythymidine;Sci.
China Serie B: Chemistry, 45, 470474,
(2002).
Javier Hernndez, Humberto Soscn,and
Alan Hinchliffe, The dipole polarazibility of
the most stable conformation of 3'Azido
2'deoxythymidine; Internet Electronic
Journal of Molecular Design, Volume 2,
Number9,Pages589598,(2003).
M. Szafran, J. Koput, Z. Dega, A. Katrusiak ,
M.PankowskiandK.Stobiecka;Xray,MP2,
DFTstudiesofthestructureandvibrational
spectraoftrigonelliniumchloride;Chemical
Physics,289,201219,(2003)
12. V.P. Roey, J.M. Salerno, W.L. Duax, C.K.Chu,
M.K.Ahn, R.F. Schinazi; Solid state
conformation
of
anti
human
Fig2:I.R.Spectraof3'Azido2'deoxythymidine/Zidovudine(AZT)
Table1.Optimizedbonddistances(inAngstrom),bondanglesandtorsionangles(indegrees)ofAZT.
BondAngle(Degree)
Bondlength(A )
14
Bond
Experimental
AM1
Calculation
PM3Calculation
C1N2
N2C3
C3N4
C5N4
C5C7
C7C1
C1O17
C7C8
C8H21
N2H18
C3O19
C5H20
N4C10
C10O9
C10C6
C6C12
C12C11
C11O9
C11C13
C13O15
C12N14
N14N16
N16N32
N32N14
1.384
1.368
1.372
1.386
1.332
1.197
1.503
1.201
1.463
1.391
1.535
1.529
1.414
1.515
1.405
1.467
1.231
1.100
1.391
1.391
1.391
1.391
1.391
1.391
1.107
1.542
1.694
1.095
1.095
1.095
1.456
1.401
1.598
1.581
1.946
1.511
1.591
1.483
1.492
1.316
1.245
1.729
1.391
1.391
1.391
1.391
1.391
1.391
1.113
1.557
1.703
1.109
1.116
1.115
1.498
1.451
1.603
1.608
1.993
1.549
1.612
1.506
1.507
1.359
1.281
1.937
Table2:CartesianCoordinates
BondAngle
C1N2C3
C1N2H18
N2C1O17
N2C3O19
C3N4C5
C7C8H21
H21C8H22
C7C5H20
C5N4C10
N4C10H27
N4C10O9
H27C10C6
C11O9C10
C10C6C12
C10C6H26
O9C11C12
C11C12C6
C11C13O15
C13O15H31
H30C13O15
C6C12N14
C5C7C1
C5C7C8
C13C11O9
N4C10C6
N14N16N32
N16N32N14
N32N14N16
N2C3N4
Experimental14
AM1Calculation
PM3Calculation
130.4
123.1
119.1
117.9
107.8
110.2
98.8
104.7
105.6
113.5
111.1
120.0
120.0
120.4
162.3
113.0
120.000
120.000
120.000
120.000
120.000
77.245
69.517
120.000
118.953
120.269
108.329
77.519
111.538
99.157
106.681
103.184
105.995
114.382
141.357
39.462
113.346
121.634
119.924
120.996
160.534
57.165
69.378
56.00
110.0
120.000
120.000
120.010
120.00
120.060
78.058
70.349
121.658
119.359
121.647
109.264
76.927
112.327
100.062
106.992
104.194
104.367
115.216
140.581
40.421
114.624
120.347
120.068
120.624
159.458
58.619
70.058
55.0274
111.621
AM1
NO.ATOMXYZ
1C.0000.0000.0000
2N1.4008.0000.0000
3C2.10061.2117.0000
4N1.40022.4246.0000
5C.00102.4250.0000
6C4.20362.5236.7786
7C.69941.2119.0000
8C1.80251.2121.0000
9O4.71451.14461.2160
10C5.09833.52911.5247
11C6.22871.36731.3141
12C6.33432.73961.9949
13C5.8960.02701.3141
14N7.21374.13691.9949
15O6.58821.00341.3141
16N6.48515.24081.9949
17O.5515.9553.0000
18H1.9522.9554.0000
19O3.20371.2117.0000
20H.55043.3804.0000
21H2.3927.3261.0000
22H2.93861.4685.0000
23H2.71412.1686.0000
24H7.14331.61331.3141
25H5.84772.2723.3594
26H5.10782.5105.3594
27H5.29264.39521.5247
28H3.66863.8305.7786
29H5.1802.85741.3141
30H4.9213.25901.3141
31H7.92811.60391.3141
32N5.00706.08411.9949
Table3
PM3
NO.ATOMXYZ
1C.0000.0000.0000
2N1.4008.0000.0000
3C2.10061.2117.0000
4N1.40022.4246.0000
5C.00102.4250.0000
6C2.24673.4319.8402
7C.69941.2119.0000
8C1.80251.2121.0000
9O2.83232.28891.6796
10C3.46684.2561.3927
11C4.13311.9632.9355
12C4.69623.3511.5971
13C4.57361.1318.9355
14N5.34583.6474.5971
15O5.5266.6188.9355
16N5.10564.8577.5971
17N4.54774.4753.5971
18O.5515.9553.0000
19H1.9522.9554.0000
20O2.70781.1640.0000
21H.55043.3804.0000
22H1.7139.0315.0000
23H2.3664.4990.0000
24H2.08731.9235.0000
25H4.73432.5012.9355
26H3.99692.8504.5971
27H3.08753.5391.2340
28H3.85124.6240.3927
29H2.66793.9207.8402
30H3.7636.7315.9355
31H5.29041.4621.9355
32H6.4823.6999.9355
Experimental,CalculatedFrequenciesandPotentialDistributioninZidovudine(AZT)
Assignment
Experimental
Frequencies
(incm
MOPACCalculatedFrequencies(incm
AM1
PM3
PotentialEnergy
Distributionb
AtomPair/Energy
Contribution
a
(in%)
Speciesa
1
2
3
4
5
3468.99
3451.41
3331.98
3190.12
3143.81
3485.70
3356.85
3294.36
3166.24
3087.32
6
7
8
3142.39
3094.79
3084.79
3077.40
3073.82
3069.05
9
10
3072.90
3055.24
2993.62
2988.79
11
3039.39
2907.71
12
3020.78
2805.41
13
3015.48
2639.90
14
2512.86
2622.94
15
16
2170
1887
2162.78
1842.68
2163.94
1949.16
17
1801
1811.70
1894.66
18
1725
1728.36
1720.75
19
1623
1653.82
1605.83
20
1552.48
1543.15
21
1549.01
1532.50
22
1539.82
1500.53
23
1483
1479.92
1472.42
24
1476.10
1469.10
O15H31(99.5)
N2H18(99.3)
015H31(99.5)
C10H27(97.7)
C8H22(32.9)
C8H21(29.2)
C8H23(24.7)
C5H20(86.0)
C11H24(54.9)
C6H26(70.1)
C6H28(28.4)
C13H29(92.1)
C8H22(55.8)
C8H21(39.2)
C8H23(66.4)
C8H21(26.5)
C11H24(38.8)
C6H28(68.4)
C6H26(29.8)
N16N32(71.7)
N14N16(28.0)
C12N14(23.6)
C10H27(42.2)
C12N14(16.7)
C11C12(15.5)
C5C7(21.7)
C3C5(15.7)
C3N4(10.7)
C3N4(19)
C3O19(14.1)
C3N4(14.8)
C3O19(18.1)
s(HydroxylGroup)
a(ThymineRing)
a(HydroxylGroup)
a(AzideRing)
s(ThymineRing)
s(ThymineRing)
s
s(FurancoseRing)
s(HydroxylGroup)
s(ThymineRing)
a(ThymineRing)
a(FurancoseRing)
a(FurancoseRing)
a(AzideRing)
s(FurancoseRing)
s+s+s
(FurancoseRing)
s+s+s
(ThymineRing)
s+s
(ThymineRing)
a+a
(ThymineRing)
N4C5(24.1)
C5C7(15.6)
O15H31(50.3)
C13H29(11.5)
C13O15(11.1)
C12N14(35.3)
N14N16(29.4)
C13O15(22.6)
C11C13(18.4)
C13H29(15.5)
s+s
(ThymineRing)
s+s+s
(HydroxylGroup)
s+s
(AzideRing)
a+a+a
(HydroxylGroup)
C7C8(25.7)
C1C7(15.0)
C5C7(13.2)
s+s+s
(ThymineRing)
25
1460.51
1451.15
C6H26(20.1)
C6C10(16.8)
C6H28(15.8)
N2H18(29.2)
N2C3(10.4)
C11C12(21.5)
C1C7(13.1)
C8H22(10.7)
N2H18(10.6)
C6H28(12.5)
C6H26(12.4)
26
1437.58
1425.70
27
28
1414
1436.61
1412.89
1419.17
1429.43
29
1395.64
1382.55
30
1384.84
1377.64
C11H24(17.9)
31
1377.14
1370.14
C11H24(14.9)
32
1376.39
1364.90
33
34
1324
1372.71
1320.69
1360.08
1330.35
35
1318.57
1316.84
36
1286.42
1280.66
37
1281.31
1278.95
38
1275.97
1269.91
39
1172.30
1174.33
40
1151
1171.21
1169.71
41
1118.52
1112.05
42
1106
1103.83
1110.50
43
1072.51
1062.79
44
1058.95
1049.28
45
1050.84
1034.86
46
1013
1012.02
1006.45
47
1001
966.26
976.38
48
49
927
922.03
854.58
931.15
863.26
C8H22(34.9)
C8H23(21.5)
C3O19(11.5)
C13H29(25.1)
C11C13(13.8)
C1N2(30.0)
C1O17(13.3)
C1C7(12.6)
C5H20(28.1)
N2C3(12.7)
N4C5(11.7)
C13H29(17.6)
C12N14(14.2)
C6H28(23.8)
C13H29(22.6)
C13H29(19.6)
C6H28(10.0)
C11H24(16.9)
C11C13(14.0)
C11C13(18.9)
C11H24(17.8)
C5H20(22.5)
C1N2(14.4)
C3N4(14.3)
C8H23(36.6)
C8H21(21.0)
C8H22(17.3)
C8H23(11.5)
C8H21(24.7)
C8H22(26.8)
C6C10(19.5)
C10H27(10.6)
C6C10(18.6)
C6H26(17.2)
C6H28(15.9)
C11H24(24.1)
C11C12(19.2)
C1C7(12.9)
C5C7(13.6)
50
694.90
715.21
C6C10(11.0)
s+s+s
(FurancoseRing)
s+s
(ThymineRing)
s(FurancoseRing)
s+s+s
(ThymineRing)
s+s
(FurancoseRing)
s(FurancoseRing)
a(FurancoseRing)
U(ThymineRing)
s(ThymineRing)
s+s
(HydroxylGroup)
s+s+s
(ThymineRing)
s+s+s
(ThymineRing)
s(HydroxylGroup)
s(AzideRing)
s(FurancoseRing)
s(HydroxylGroup)
a(FurancoseRing)
a(HydroxylGroup)
s(FurancoseRing)
s(HydroxylGroup)
a(HydroxylGroup)
a(FurancoseRing)
s+s+s
(ThymineRing)
s+s+s
(ThymineRing)
a+a+a
(ThymineRing)
s+s
(FurancoseRing)
s+s+s
(FurancoseRing)
s+s
(FurancoseRing)
s(ThymineRing)
a(ThymineRing)
s(FurancoseRing)
51
574
574.24
562.87
52
53
54
55
56
57
482
311
490.62
456.07
417.19
367.44
322.41
305.67
450.83
417.07
402.02
354.55
362.60
317.91
58
236.18
225.89
59
144.79
15.47
60
112.24
77.84
Assignment
Experimental
Frequencies
(incm
C13O15(18.7)
C11C13(16.2)
C1C7(10.5)
O15H31(22.4)
N14N16(11.8)
C3015(37.0)
N14N16(21.9)
C6C10(14.5)
C6H28(21.1)
C6H26(18.9)
C6C10(24.5)
C6H28(20.1)
C6H26(19.9)
C6C10(13.4)
C10H27(13.0)
C7C8(24.5)
C8H21(21.2)
C8H22(20.5)
MOPACCalculatedFrequencies(incm
AM1
PM3
rocking
(HydroxylGroup)
s(ThymineRing)
s(HydroxylGroup)
s(AzideGroup)
s(HydroxylGroup)
a(AzideGroup)
s+s+s
(FurancoseRing)
a+a+a
(FurancoseRing)
s+s
(FurancoseRing)
a+a
(ThymineRing)
PotentialEnergy
Distribution
AtomPair/Energy
Contribution(in%)
Speciesa
1
1387
1381.07
1373.55
1350.60
1363.73
1246.77
1274.74
1191
1213.16
1206.15
5
6
7
914
817
944.84
857.71
815.85
981.27
885.26
813.62
741
752.51
797.30
696.64
699.38
10
11
607
696.22
624.34
671.40
647.93
12
563.95
562.70
C8H21(47.9)
C8H23(35.4)
C6H28(17.3)
C6H26(15.0)
C13H29(54.1)
O15H31(12.7)
C6H26(27.1)
C10H27(11.8)
C13H29(11.8)
C5H20(65.0)
C6C10(11.9)
C10H27(24.8)
C6H26(13.9)
C6H28(13.7)
C1C7(31.7)
C1N2(21.6)
C1O17(21.5)
C3N4(27.3)
N2C3(21.3)
C3O19(20.8)
N2H18(80.2)
C1N2(21.1)
N2C3(14.8)
C1C7(13.8)
C3C5(14.5)
13
537.38
555.47
C6C10(11.6)
s(ThymineRing)
s(FurancoseRing)
s+s(Hydroxyl
Group)
a(FurancoseRing)
a(HydroxylGroup)
s(ThymineGroup)
s(FurancoseRing)
s(Furancosering)
s(ThymineGroup)
s(ThymineGroup)
s(ThymineGroup)
a(ThymineGroup)
Rocking(Thymine
Ring)
a(FurancoseRing)
14
486.23
489.36
C11H24(11.3)
15
461.91
453.46
16
441
448.37
432.65
17
406
427.19
412.02
C12N14(12.0)
C11C12(10.2)
N16N32(52.0)
N14N16(41.6)
N14N16(11.8)
18
355
344.89
394.32
19
337.41
377.95
20
180.47
191.89
21
167.09
183.81
22
106.61
116.5
23
24
81.07
50.97
71.33
47.41
25
38.55
33.11
26
29.21
27.21
27
28.56
26.8
28
17.86
18.42
29
30
12.50
10.10
13.6
10.8
O15H31(21.8)
N14N16(13.2)
C7C8(20.5)
N4C5(13.0)
O9C110(12.1)
O9C11(11.4)
C1N2(20.3)
N2C3(20.0)
N2H18(17.7)
C11C12(21.4)
C11C13(20.6)
C11H24(18.8)
C3O19(13.6)
C13O15(19.0)
C11C13(16.2)
O15H31(11.9)
C13O15(17.5)
C11C13(12.9)
C7C1(19.8)
C7C5(17.3)
C7C8(12.6)
C10O9(18.6)
C10C6(16.5)
C10H27(12.9)
C8H21(15.6)
C8H23(14.9)
C8C7(11.60
sScissoring
(FurancoseRing)
aScissoring
(FurancoseRing)
sScissoring
(AzideRing)
aScissoring
(AzideRing)
s(HydroxylGroup)
s(AzideRing)
s(ThymineRing)
s(FurancoseRing)
a(ThymineRing)
s(FurancoseRing)
s(ThymineRing)
a(HydroxylGroup)
Rocking
(HydroxylGroup)
Rocking
(ThymineRing)
Rocking
(AzideRing)
Rocking
(ThymineRing)
Twisting
Twisting
Onlycontributions>10%arelisted
=stretching,=inplanebending,=outofplanebending,s=symmetric,a=asymmetric
Fig3:CorrelationDiagramforExperimentalVsCalculatedFrequencies(AM1method)
Fig:4CorrelationDiagramforExperimentalVsCalculatedFrequencies(PM3method)