Journal of Chemical and Pharmaceutical Research (ISSN : 0975-7384)

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Original Articles: 2022 Vol: 14 Issue: 11

Ab initio and DFT Study of Thymine and Water Complexes

Brijesh Kumar Sharma, AchchheLal, Devendra Kumar Singh*

Department of Physics, Udai Pratap (Autonomous) College, Varanasi, Uttar Pradesh, India

Corresponding Author:
Devendra Kumar Singh
Department of Physics
Udai Pratap (Autonomous) College
Varanasi, Uttar Pradesh, India

Received: 20-Apr-2022, Manuscript No. JOCPR-22-68172; Editor assigned: 23-Apr-2022, PreQC No. JOCPR-22-68172 (PQ); Reviewed: 07-May-2022, QC No. JOCPR-20-68172; Revised: 21-Sep-2022, QI No. JOCPR-22-68172, Manuscript No. JOCPR-22-68172 (R); Published: 19-Oct-2022

Abstract

The optimized geometries of thymine and all the three isomers of thymine-water complex, isomer-I, isomer-II and isomer-III have been obtained using Ab initio method MP2 and DFT methods B3LYP, X3LYP and B3PW91 with 6- 311++G (d,p) basis set. Structural parameters of the optimized geometries, total energies and the APT charges of thymine and all the three isomers of the thymine-water complex have been computed. Frequency calculations are carried out on each optimized structure using DFT methods and their IR and Raman spectra have been discussed. The calculated frequencies of the thymine are found to be in good agreement with the experimental values in most of the cases. We show that addition of water molecules in thymine, the strength of the binding energy decreases i.e. stability increases.

Keywords

Thymine, MP2, DFT, B3LYP, Optimized geometry

Introduction

Adenine, cytosine, guanine and thymine are the nucleobase that form the Nucleic Acid (NA) base pairs (guanine with cytosine, adenine with thymine) in DNA. Thymine is one of the pyrimidine bases, along with cytosine that makes hydrogen bonds with adenine (6-amino purine) in normal Waston-Crick base pairing. The pair wise creation of the bases occurs due to the formation of hydrogen bonds. The building by minor tautomers of NA bases of non-standard base pairs may lead to changes in the genetic code [1,2]. The perusal of the dynamics of these molecules and molecular structure can help to understand and explain some processes in biological systems. Recently, there has been an increasing interest in studying DNA damage, which may cause various diseases such as cancer [3-7]. This intellect is of great interest due to its importance for developing pharmacological substances and developing therapies against viral infections, cancer, mol formations and so on. In a recent work, the proton affinity of the two oxygen atoms and the deprotonation enthalpies of the two NH bonds of thymine have been computed using the DFT methods employing B3LYP, X3LYP and B3PW91 functional in conjunction with 6-311++G (d,p) basis set. It has been suggested that the energies of the three stable thymine-water complexes depend not only on the proton accepting ability of the oxygen atom but also on the ability of NH groups to donate proton [8]. To establish more general correlations between the acidity and basicity of an amphoteric molecule and its hydrogen bonding ability, the energy of the thymine-water complexes are computed in this work using the DFT (B3LYP) and a 6-311++G (d,p) basis set. Use of an suitable DFT functional combined with an appropriate basis set reproduces the energy of the complex very well; in fact, the energy and the intermolecular distance obtained for the thymine-water interaction are comparable with thymine calculated at the DFT (B3LYP) and a 6-311++G (d,p) basis set. For proper use of the vibrational spectra of nucleic acid bases in biophysical research, authentic knowledge of the normal mode of each vibration for each relevant IR or Raman band is essential. Three stable structures for the thymine-water complex have been studied in this work. The three thymine water isomers obtained here have been reported earlier by Chandra, et al. [9]. Optimized geometries of all the three isomers of thymine-water complex have been obtained at MP2/6-311++G (d,p), B3LYP/6-311++G (d,p), X3LYP/6-11++G (d,P) and B3PW91/6-11++G (d,p) levels of theory. Structural parameters of the optimized geometries, total energies and the APT charges of the thymine-water complex have been computed. The optimized bond length and bond angles are in agreement with the corresponding experimental results. In this work a study of change in structures and spectra of possible hydrogen bonded thymine-water complexes have been done and these have been compared with that of free thymine. We show that addition of water molecules in thymine, the strength of the binding energy decreases i.e. stability increases.

Materials and Methods

The vibrational spectra and ground state geometries for free thymine and its hydrogen bonded complexes with molecules of water have been optimized using the Ab initio method: (i) MP2 and hybrid Density Functional Theory (DFT) methods (ii) B3LYP which uses parameter Becke’s functional three with nonlocal correlation provided by Lee-Young-Parr expression with 6-311++G (d,p) basis set [10-14]. The total energies, structural parameters of the optimized geometries and the APT charges of isomers have been computed using DFT methods only. For all computational calculations, we have used Gaussian 09 package of programs [15]. Initially, Ab initio calculations were done at MP2/6-311++G (d,p) level. The optimized geometry at the MP2/6-311++G (d,p) level was taken as the input structure for the DFT calculation using B3LYP/6-311++G (d,p) level. Similarly, the optimized geometry at the B3LYP/6-311++G (d,p) level was used as the input structure for the calculation at the X3LYP/6-11++G (d,p) and B3PW91/6-11++G (d,p) level. The geometries were optimized by minimizing the energies without imposing any constraint on the geometry. It is widely accepted that this level of theory is sufficient to reliably predict molecular geometries of the hydrogen bonded systems. The optimized structures of free thymine and three isomers at B3LYP/6-311++G (d,p) along with atomic numbering have been shown in Figures 1 and 2a-c respectively.

Figure 1: Optimized structure of free thymine at B3LYP/6-311++G (d,p).

Figures 2a-c: Optimized structures of three stable isomers of thymine-water complexes obtained at B3LYP/6-311++G (d,p) level. (Red: Oxygen; Blue: Nitrogen; Grey: Carbon; White: Hydrogen).

Results and Discussion

Optimized Geometry of Thymine

The geometry optimization and charge distribution of thymine have been calculated in their ground state, at various levels of theory using the Gaussian 09 computer code. The total energy of thymine at MP2/6-311++G (d,p), B3LYP/6-311++G (d,p), X3LYP/6-311++G (d,p) and B3PW91/6-311++G (d,p) levels are found to be -453.05193380 a.u., -454.27574640 a.u., -454.08723750 a.u. and -454.09637532 a.u. respectively as listed in Table 1.

Molecular Geometry

The calculated optimized molecular energies, dipole moments, zero point vibrational energies and thermodynamic function using Ab initio method MP2 and DFT methods B3LYP, X3LYP and B3PW91 method with 6-311++G (d,p) basis set for thymine and all the three isomers of thymine-water, viz. isomer-I, isomer-II and isomer-III are shown in Table 1. The isomer-I is most stable having least optimized energy while isomer-II and isomer-III are found to have higher energies in all cases. The dipole moment of isomer-I is least and that of isomer-III is largest therefore isomer-III is more polar than the other two isomers.

S.
No.
Species Total energies
 E (hartree)
Zero point
vibrational
energy (J/mol)
Dipole
moment
(Debye)
Volume molar
heat capacity
(C,) (cal/mol K)
Entropy
S (cal/mol K)
MP2/6-311++G (d,p)
1 Thymine -453.05193380 297752.5 4.3179 28.762 87.289
Thymine-water
1 Isomer-I -529.34490302 - 4.2550    
2 Isomer -II -529.34196051 - 5,1000 - -
3 Isomer-III -529.34231448 - 4.7639 - -
B3LYP/6-311++G (d,p)
1 Thymine -454.27574640 299866.2 4.5316 29,465 87,205
Thymine-water
1 Isomer-I -530.75078380 364093.0 3.7693 37.143 99.359
2 Isomer -II -530.74788215 364685.1 4.8116 39.195 102.130
3 Isomer-III -530.74849881 364839.0 4.5653 39.053 101.965
X3LYP/6-311++G (d,p)
1 Thymine -454.08723750 300512.5 4.5392 29.398 87.140
Thymine-water
1 Isomer-I -530.53364363 364902.4 3.7786 37.048 99.182
2 Isomer -II -530.53070011 365495.0 4.8088 39.103 101.945
3 Isomer-III -530.53131129 365634.9 4.5609 38.965 101,803
B3PW91/6-311++G (d,p)
1 Thymine -454.09637532 301184.1 4.4971 29.388 87,239
Thymine-water
1 Isomer-I -530.53995348 365616.3 3.7575 37,047 99,321
2 Isomer -II -530.53714789 366327.8 4.8611 39,058 101,941
3 Isomer-III -530.53782868 366607.7 4.6350 38,868 101,567

Table 1: Calculated energies, dipole moment, zero point vibrational energy and thermodynamic functions obtained at different levels.

Structural Parameters

The optimized geometrical parameters namely bond length (Å) and bond angles (in degree) of the thymine and all the three isomers of thymine-water, isomer-I, isomer-II and isomer-III computed using Ab initio method MP2 and DFT method B3LYP, X3LYP and B3PW91 functional with 6-311++G (d,p) basis set are reported along with corresponding experimental value in Tables 2-5. We see that the calculated bond lengths are very close to experimental values while calculated using B3PW91/6-311++G (d,p) and bond angles are very close to experimental values while calculated using B3LYP/6-311++G (d,p).

Parameters Experimental Free
thymine
Isomer 1 Isomer 2 Isomer 3
Bond length
C1-N2 1.413 1.404 1.407 1.405 1.396
N2-C3 1.345 1.387 1.382 1.378 1.387
C3-N4 1.314 1.386 1.377 1.382 1.389
N4-C5 1.408 1.380 1.379 1.382 1.378
C5-C6 1.369 1.357 1.358 1.356 1.357
C6-C7 1.522 1.499 1.499 1.498 1.499
C1-O8 1.193 1.223 1.223 1.222 1.232
C3-O9 1.246 1.218 1.228 1.227 1.217
N2-H10 - 1.015 1.015 1.024 1.024
N4-H11 - 1.010 1.020 1.010 1.011
C5-H12 - 1.086 1.086 1.086 1.086
C7-H13 - 1.093 1.093 1.093 1.093
C7-H14 - 1.094 1.094 1.093 1.093
C7-H15 - 1.094 1.094 1.093 1.093
O16-H17 - - 0.97 0.968 0.959
O16-H18 - - 0.959 0.959 0.969
H11-O16 - - 1.937 - -
O9-H17 - - 1.983 2.003 -
O16-H10 - - - 1.982 1.97
O8-H17 - - - - 1.974
Bond angles
O9-C3-N4 122 123 124 122 123
O9-C3-N2 121 124 123 124 124
N4-C3-N2 118 112 113 113 113
C3-N4-C5 123 123 123 123 124
N4-C5-C6 120 122 123 122 122
C5-C6-C7 112 123 124 124 124
C5-C6-C1 119 118 118 118 118
C7-C6-C1 119 118 118 118 118
C6-C1-N2 114 114 114 115 115
C6-C1-O8 125 124 125 124 123
O8-C1-N2 121 120 120 121 121
C1-N2-C3 126 128 128 127 127
H17-O16-H18 - - 105 105 105
N4-H11-O16 - - 145 - -
H11-O16-H17 - - 86 - -
O16-H17-O9 - - 141 140 -
H17-O9-C3 - - 108 109 -
N2-H10-O16 - - - 144 144
H10-O16-H17 - - - 87 138
O16-H17-O8 - - - - 142
C1-O8-H17 - - - - 111

Table 2: Optimized bond lengths (Å) and bond angles (in degree) of free thymine and thymine-water complexes at MP2/6-311++G (d,p) level.

Parameters Experimental Free thymine Isomer 1 Isomer 2 Isomer 3
Bond length
C1-N2 1.413 1.407 1.409 1.407 1.396
N2-C3 1.345 1.384 1.379 1.375 1.384
C3-N4 1.314 1.387 1.378 1.382 1.391
N4-C5 1.408 1.380 1.377 1.381 1.376
C5-C6 1.369 1.349 1.351 1.348 1.350
C6-C7 1.522 1.500 1.499 1.499 1.500
C1-O8 1.193 1.217 1.217 1.216 1.229
C3-O9 1.246 1.213 1.225 1.225 1.212
N2-H10 - 1.013 1.012 1.023 1.024
N4-H11 - 1.009 1.019 1.009 1.009
C5-H12 - 1.083 1.083 1.083 1.083
C7-H13 - 1.091 1.092 1.092 1.092
C7-H14 - 1.093 1.093 1.093 1.093
C7-H15 - 1.093 1.093 1.093 1.093
O16-H17 - - 0.974 0.973 0.975
O16-H18 - - 0.96 0.961 0.961
H11-O16 - - 1.939 - -
O9-H17 - - 1.946 1.965 -
O16-H10 - - - 2 1.98
O8-H17 - - - - 1.933
Bond angles
O9-C3-N4 122 123 123 122 123
O9-C3-N2 121 124 123 124 124
N4-C3-N2 118 112 113 114 113
C3-N4-C5 123 123 123 123 124
N4-C5-C6 120 122 123 122 122
C5-C6-C7 112 123 124 124 124
C5-C6-C1 119 118 118 118 118
C7-C6-C1 119 118 118 118 118
C6-C1-N2 114 114 114 115 116
C6-C1-O8 125 125 125 125 124
O8-C1-N2 121 120 120 120 120
C1-N2-C3 126 128 128 127 127
H17-O16-H18 - - 108 107 107
N4-H11-O16 - - 143 - -
H11-O16-H17 - - 88 - -
O16-H17-O9 - - 140 142 -
H17-O9-C3 - - 110 110 -
N2-H10-O16 - - - 142 143
H10-O16-H17 - - - 86 84
O16-H17-O8 - - - 143
C1-O8-H17 - - - 112

Table 3: Optimized bond lengths (Å) and bond angles (in degree) of free thymine and thymine-water complexes at B3LYP/6-311++G (d,p) level.

Parameters Experimental Free thymine Isomer 1 Isomer 2 Isomer 3
Bond length
C1-N2 1.413 1.406 1.407 1.405 1.395
N2-C3 1.345 1.383 1.378 1.374 1.383
C3-N4 1.314 1.386 1.377 1.380 1.389
N4-C5 1.408 1.379 1.376 1.381 1.375
C5-C6 1.369 1.348 1.350 1.347 1.349
C6-C7 1.522 1.499 1.499 1.498 1.499
C1-O8 1.193 1.216 1.216 1.215 1.228
C3-O9 1.246 1.212 1.224 1.224 1.212
N2-H10 - 1.012 1.012 1.023 1.024
N4-H11 - 1.008 1.019 1.008 1.009
C5-H12 - 1.083 1.083 1.083 1.083
C7-H13 - 1.092 1.091 1.092 1.092
C7-H14 - 1.093 1.093 1.093 1.093
C7-H15 - 1.093 1.093 1.093 1.093
O16-H17 - - 0.974 0.973 0.974
O16-H18 - - 0.959 0.960 0.960
H11-O16 - - 1.930 - -
O9-H17 - - 1.938 1.955 -
O16-H10 - - - 1.990 1.970
O8-H17 - - - - 1.924
Bond angles
O9-C3-N4 122 123 123 122 123
O9-C3-N2 121 124 123 124 124
N4-C3-N2 118 112 113 114 113
C3-N4-C5 123 123 123 123 124
N4-C5-C6 120 122 123 122 122
C5-C6-C7 112 123 124 124 124
C5-C6-C1 119 118 118 118 118
C7-C6-C1 119 118 118 118 118
C6-C1-N2 114 114 114 115 116
C6-C1-O8 125 125 125 124 124
O8-C1-N2 121 120 120 120 121
C1-N2-C3 126 128 128 127 127
H17-O16-H18 - - 108 107 107
N4-H11-O16 - - 143 - -
H11-O16-H17 - - 88 - -
O16-H17-O9 - - 140 142 -
H17-O9-C3 - - 110 110 -
N2-H10-O16 - - - 142 143
H10-O16-H17 - - - 86 84
O16-H17-O8 - - - - 143
C1-O8-H17 - - - - 112

Table 4: Optimized Bond lengths (Å) and Bond angles (in Degree) of free thymine and thymine-water complexes at X3LYP/6-311++G (d,p) level.

Parameters Experimental Free thymine Isomer 1 Isomer 2 Isomer 3
Bond length
C1-N2 1.413 1.402 1.404 1.402 1.391
N2-C3 1.345 1.380 1.374 1.371 1.380
C3-N4 1.314 1.383 1.374 1.377 1.387
N4-C5 1.408 1.375 1.372 1.376 1.371
C5-C6 1.369 1.349 1.350 1.347 1.350
C6-C7 1.522 1.494 1.494 1.494 1.495
C1-O8 1.193 1.215 1.215 1.214 1.227
C3-O9 1.246 1.211 1.223 1.22 1.211
N2-H10 - 1.012 1.012 1.024 1.025
N4-H11 - 1.008 1.020 1.008 1.008
C5-H12 - 1.084 1.084 1.084 1.084
C7-H13 - 1.092 1.092 1.092 1.092
C7-H14 - 1.094 1.094 1.094 1.094
C7-H15 - 1.094 1.094 1.094 1.094
O16-H17 - - 0.973 0.972 0.974
O16-H18 - - 0.958 0.959 0.959
H11-O16 - - 1.914 - -
O9-H17 - - 1.933 1.951 -
O16-H10 - - - 1.976 1.954
O8-H17 - - - - 1.916
Bond angles
O9-C3-N4 122 123 123 122 123
O9-C3-N2 121 124 123 124 124
N4-C3-N2 118 112 113 114 113
C3-N4-C5 123 123 123 123 124
N4-C5-C6 120 122 123 122 122
C5-C6-C7 112 123 124 124 124
C5-C6-C1 119 117 118 118 118
C7-C6-C1 119 118 118 118 118
C6-C1-N2 114 114 114 115 116
C6-C1-O8 125 125 125 124 124
O8-C1-N2 121 120 120 120 121
C1-N2-C3 126 128 128 127 127
H17-O16-H18 - - 108 107 107
N4-H11-O16 - - 143 - -
H11-O16-H17 - - 88 - -
O16-H17-O9 - - 141 143 -
H17-O9-C3 - - 110 109 -
N2-H10-O16 - - - 143 143
H10-O16-H17 - - - 85 84
O16-H17-O8 - - - - 143
C1-O8-H17 - - - - 112

Table 5: Optimized Bond lengths (Å) and Bond angles (in Degree) of free Thymine and Thymine-Water complexes at B3PW91/6-311++G (d,p) level.

Atomic Polar Tensor (APT) charges

The Atomic Polar Tensor (APT) charges for the thymine and thymine-water complexes computed at using DFT method B3LYP, X3LYP and B3PW91 method with 6-311++G (d,p) basis sets are collected in Tables 6-8 for atomic numbering scheme, see Figure 1 and Figure 2a-c respectively. In terms of the charge ofelectron 1e=1.602188 × 10-19 C from Tables 6-8, we see that due to high negativity of the respective atomscompared to the other atoms result enhancement of the bond length. In free thymine, we see that the bondlength of magnitudes of the bond lengths between the pair (C1-O8) and (C3-O9) are found to be differed dueto O9 is more negative than the O8. Thus O9 attracts more to C atoms than O8 which gives difference intheir bond lengths. Hence the bond length of (C3=O9) is shorter than the bond length of (C1=O8) similarly,with the help of APT (Atomic Polar Tensor) charges we can explain the difference in the bond length ofothers pairs e.g. C1-N2 and N2-C3; C3-N4 and N4-C5; C5-C6 and C6-C7.

Atoms Free thymine Isomer I Isomer II Isomer III
C1 1.134 1.135 1.139 1.153
N2 -0.727 -0.727 -0.789 -0.786
C3 1.335 1.337 1.351 1.339
N4 -0.737 -0.791 -0.747 -0.733
C5 0.459 0.488 0.439 0.459
C6 -0.296 -0.305 -0.279 -0.32
C7 0.086 0.086 0.083 0.0893
O8 -0.837 -0.85 -0.827 -0.927
O9 -0.922 -1.01 -1.005 -0.912
H10 0.219 0.221 0.346 0.348
H11 0.244 0.38 0.245 0.244
H12 0.053 0.055 0.052 0.053
H13 -0.008 -0.008 -0.01 -0.009
H14 -0.001 -0.003 -0.001 -0.002
H15 -0.001 -0.003 0.001 -0.001
O16 - -0.723 -0.669 -0.682
H17 - 0.288 0.399 0.272
H18 - 0.43 0.273 0.416

Table 6: APT charges at various atomic sites of free thymine molecule and thymine- water complexes at B3LYP/6-311++G (d,p) level.

Atoms Free thymine Isomer I Isomer II Isomer III
C1 1.140 1.140 1.145 1.160
N2 -0.731 -0.731 -0.794 -0.791
C3 1.341 1.343 1.357 1.345
N4 -0.742 -0.796 -0.752 -0.738
C5 0.462 0.492 0.442 0.462
C6 -0.299 -0.308 -0.282 -0.323
C7 0.085 0.085 0.082 0.088
O8 -0.841 -0.853 -0.831 -0.932
O9 -0.926 -1.015 -1.009 -0.916
H10 0.221 0.222 0.349 0.351
H11 0.245 0.383 0.246 0.245
H12 0.054 0.0558 0.053 0.054
H13 -0.008 -0.007 -0.01 -0.008
H14 -0.001 -0.002 0.001 -0.001
H15 -0.001 -0.002 0.001 -0.001
O16 - -0.728 -0.674 -0.687
H17 - 0.290 0.401 0.274
H18 - 0.432 0.275 0.418

Table 7: APT charges at various atomic sites of free thymine molecule and thymine- water complexes at X3LYP/6-311++G (d,p) level.

Atoms Free thymine Isomer I Isomer II Isomer III
C1 1.128 1.128 1.132 1.146
N2 -0.725 -0.724 -0.793 -0.790
C3 1.329 1.331 1.344 1.333
N4 -0.737 -0.793 -0.745 -0.732
C5 0.454 0.483 0.433 0.454
C6 -0.294 -0.303 -0.276 -0.318
C7 0.069 0.069 0.065 0.071
O8 -0.833 -0.845 -0.822 -0.927
O9 -0.919 -1.010 -1.004 -0.908
H10 0.222 0.223 0.357 0.360
H11 0.247 0.390 0.248 0.247
H12 0.247 0.057 0.054 0.056
H13 -0.004 -0.003 -0.005 -0.004
H14 0.004 0.001 0.005 0.002
H15 0.004 0.001 0.005 0.004
O16 - -0.731 -0.675 -0.689
H17 - 0.291 0.402 0.274
H18 - 0.434 0.274 0.421

Table 8: APT Charges at various atomic sites of free thymine molecule and thymine- water complexes at B3PW91/6-311++G (d,p) level.

Thermodynamic Properties

Few calculated thermo dynamical parameters such as the Zero Point Vibration Energies (ZPVE) the molar capacity at constant volume, the entropy and dipole moment are listed in table in the previous section. The variations in the ZPVES (Zero Point Vibration Energies) seem to be insignificant. Changes in the total entropy and the molar capacity at constant volume of thymine and thymine-water at DFT method B3LYP, X3LYP and B3PW91 method with 6-311++g (d,p) basis set are also marginal only.

Conclusion

The optimized geometries of thymine and three isomers of thymine-water complexes have been calculated employing Ab initio method MP2 and DFT method B3LYP, X3LYP and B3PW91 method with 6-311++G (d,p) basis set using Gaussian 09 program. Most of the geometrical parameters for thymine-water complexes remain the same as thymine except for the geometry of the site of the water bonded atom. Structural parameters of the optimized geometries, total energies and the APT charges of the thymine-water complex have been discussed in detail. From this analysis, it is noted that the theoretically calculated optimized bond lengths are comparatively larger than the experimental values because the theoretical calculations refer to isolated molecules in the gas phase while it is in the solid state for experimental results. We show that addition of water molecules in thymine, the strength of the binding energy decreases i.e. stability increases. The optimized bond length and bond angles are in agreement with the corresponding experimental results.

Acknowledgement

The authors are grateful to Secretary and Principal, Udai Pratap Autonomous College for providing the necessary facilities.

References

http://sacs17.amberton.edu/

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