Computational study on Phosphorylation of Nucleosides and Nucleotides by Austin Model-1 method

doi:10.21203/rs.3.rs-2469598/v1

Download PDF

Research Article

Computational study on Phosphorylation of Nucleosides and Nucleotides by Austin Model-1 method

https://doi.org/10.21203/rs.3.rs-2469598/v1

This work is licensed under a CC BY 4.0 License

Version 1

posted

You are reading this latest preprint version

Phosphorylation of Nucleosides and Nucleotides play essential function for the enzymatic synthesis of DNA and RNA to participate in energy transfer processes, intracellular signalling, and the regulation of proteins’ biological activity. The changing of the base sequence is to cause chromosomal mutations which are sometimes useful and occasionally harmful. Phosphorylation of Nucleosides and Nucleotides have been optimized and evaluated by semi-empirical molecular orbital AM1 method. In this connection, the heats of formation (∆H_f^o), dipole moment (µ), energies of frontier molecular orbitals (E_HOMO and E_LUMO) and quantum chemical descriptors have been performed. It is observed that stability of nucleosides in DNA (deoxythymidin > deoxycytidine > deoxyguanosine > deoxyadenosine) as per heats of formation (∆H_f^o) data. The dipole moment (µ) of nucleosides are investigated in DNA (deoxythymidin > deoxycytidine > deoxyadenosine > deoxyguanosine). Furthermore, the dipole-dipole interactions take part a critical role during the sequencing and replication of DNA has been discussed.

Phosphorylation

quantum chemical descriptors

Nucleosides

Nucleotides

Heat of Reaction

Phosphorylation of Nucleosides and Nucleotides play vital roles in various biological processes. These are basic building blocks for the synthesis of DNA and RNA to participate in energy transfer processes, intracellular signalling, and the regulation of proteins’ biological activity [1]. Scientists have interested in synthetic nucleotide analogs to study of complex biological systems, potential therapeutic and diagnostic value [2]. Literature survey is indicated on the related topics [3]. However, the presence of multiple reactive centres in nucleotide derivatives is still a challenging task for developing efficient synthetic protocols. Synthesis of nucleoside di- and triphosphates [4] were developed for the preparation of nucleoside-5’-triphosphates. However, due to many drawbacks, e.g., the significant formation of side-products, low yields, and synthetic inconveniences, these approaches have not found wider application. But, it is possible to synthesize a number of di- and tri-phosphates of naturally occurring nucleosides [5] (adenosine, uridine, guanosine, thymidine, and deoxycytidine) in isolated yields of 25–35% by using the N,N’-dicyclohexylcarbodiimide (DCC). In this connection, the advanced technology of genetic engineering for the synthesis of genes and discovery of miracle enzymes are required to cure many diseases [6] and continuation of research work [7]. Austin Model-1 (AM1) is one of the semi-empirical methods of quantum chemistry which uses experimental parameters and extensive implication of Schrödinger’s equation (HΨ = EΨ) to optimize molecules for calculation of various thermodynamic properties [8].

In this context, the present research focuses on the thermodynamic properties of Phosphorylation reactions of deoxyadenosine I (Scheme-1, a to c), deoxyguanosine II (Scheme-2, a to c), deoxycytidine III (Scheme-3, a to c) and deoxythymidine IV (Scheme- 4, a to c) have been determined by full optimization calculations (MOPAC2016 (Version: 22.234w)), by using semi-empirical molecular orbital Austin Model-1 (AM1) method.

Computational methods [8]

Semi-empirical molecular orbital calculations were performed using the AM1 (Austin Model 1) method included in the using MOPAC2016 (Version: 22.234w) program. Geometry calculations in the ground state (keywords: CHARGE = 0, GNORM = 1, AIGOUT, DEBUG, PRECISE, GEO-OK, and MMOK to correct the increase in the barrier to rotation of the amide linkage) were completely optimized until the lowest energy conformation was found. The position of the atom in the molecule is mentioned as subscript (as shown in Figure – 1).

Magnitude of the induction effect (µ_ind) [9]

The electronegative hetero-atoms cause displacement of electrons in the molecule that induces an additional dipole moment. The magnitude of the induction effect (µ_ind) can be estimated with corresponding reactant and product at the time of reaction by using Eq. (1).

Induction effect (µ_ind) = µ(Product) - µ(Reactant) ----------- (1)

Heat of reaction (∆H in kcal/mol)

Heat of Reaction is the difference between the sum of the enthalpies of Products and the sum of the enthalpies of Reactants.

Heat of reaction (Enthalpy of chemical reaction) ΔH = ∑H-Products - ∑H-Reactants ---- (2)

Quantum Chemical Descriptors [10]

Various descriptors are being developed to identify drugs or toxins and applied for the chemical reactivity, especially in the prediction of toxicity, biological activities, chemical reactive site, group identification, molecular reactivity’s and cost-effective process. Chemical, agrochemical, pharmaceutical and biotechnology branches of science require extensive input from both bioinformatics and chemo-informatics. These were used for development of QSAR and QSPR for different applications.

The optimized electronic structure of Phosphorylation of Nucleosides and Nucleotides of deoxy ribonucleic acid (DNA) (a to c) are shown in Scheme- 1 to 4. The calculated values of Heat of formation (∆H_f^O in kcal/mol), dipole moment (µ in Debye), frontier molecular orbital energy (HOMO & LUMO) (Table-I), quantum chemical descriptors (Table-II), Calculation of Heat of Reaction (∆H_r) (Table-III), Induction effect(µ_ind),Cosmo area (Sq.Ang) and Cosmo volume (Cu.Ang) (Table-IV) are included.

Phosphorylation of deoxyadenosine (I), as per Scheme – 1, and calculated values are incorporated in Table – I. It is observed the stability in the order of 3’5’-ADP > 3’AMP > 5’AMP > deoxyadenosine as per Heat of formation data. The dipole moment depends on the nature of the atoms and bonds comprising the molecules and on their arrangement. It is also found that the dipole moment has increased in the order of deoxyadenosine < 3’AMP < 5’AMP < 3’5’-ADP.

Table-I - IHeat of formation (∆H_f^Oin kcal/mol), dipole moment (µ in Debye), frontier orbital energy (HOMO & LUMO), Cosmo area and Cosmo volume for nucleosides (I to IV) and nucleotides (a to c) of DNA from AM1 calculation

Comp No.	DNA Nucleotides	ΔH_f^O (Kcal/mol)	Dipole moment (Debye)	HOMO (ev)	LUMO (ev)	Cosmo Area (Sq.Ang)	Cosmo volume (Cu.Ang)	Mol wt
	H₃PO₄	-238.1240	5.8959	-11.716	+ 0.598	100.39	82.58	97.9951
	H₂O	-59.2499	1.8602	-12.463	+ 4.412	42.61	26.03	18.0152
I	deoxyadenosine	+ 60.6205	4.1752	-7.176	-1.807	280.64	297.10	251.2444
Ia	3’-AMP	-170.8813	5.0619	-8.616	-0.492	351.76	362.93	331.2243
Ib	5’-AMP	-131.0727	5.3107	-8.184	-1.037	352.60	361.92	331.2243
Ic	3’,5’-ADP	-384.3956	9.3849	-6.338	-1.424	383.30	416.70	411.2041
II	deoxyguanosine	-24.7427	3.8273	-8.585	-0.742	305.74	319.85	267.2438
IIa	3’-GMP	-176.1358	6.0821	-8.341	-0.634	359.47	377.44	347.2237
IIb	5’-GMP	-284.8335	6.1391	-8.754	-0.744	363.77	382.68	347.2237
IIc	3’,5’-GDP	-480.0820	2.5209	-8.975	-0.808	401.50	435.94	427.2035
III	deoxycytidine	-52.6407	4.6162	-7.524	-2.021	272.69	280.78	227.2194
IIIa	3’-CMP	-272.7677	8.3389	-8.758	-0.748	309.41	335.30	307.1993
IIIb	5’-CMP	-257.1856	3.4799	-6.591	-1.091	313.53	331.79	307.1993
IIIc	3’,5’-CDP	-498.8033	7.1174	-9.135	-1.154	384.63	403.02	387.1791
IV	deoxythymidine	-112.9364	6.6805	-7.714	-2.058	263.41	291.83	242.2310
IVa	3’-TMP	-288.6573	8.4049	-8.731	-0.683	314.81	330.36	307.1993
IVb	5’-TMP	-257.1517	3.4015	-6.605	-1.097	313.51	333.14	307.1993
IVc	3’,5’-TDP	-498.3798	7.4077	-9.035	-1.051	387.14	401.64	387.1791

The heats of reactions are calculated and values incorporated in Table – III. It is investigated that Heat of Reaction (∆H_r) is in the order of 4 > 1 > 3 > 2 as per Scheme – 1. A reaction can occur spontaneously only if the change in free energy is negative. Free energy is a measure of capacity of a system to do useful work at the constant temperature and pressure.

Table- II - Quantum Chemical descriptors i.e. Energy gap or Electron excitation energy (ΔE, in eV), Ionization Potential (IP), Electron Affinity (EA), Electro Negativity(EN) (χ) , Global hardness (ƞ), Softness (s) , Chemical potential (μ⁰) and Electrophilicity Index (w) for nucleosides ( I to IV) and nucleotides (a to c) of DNA are calculated from frontier molecular orbital energy (HOMO & LUMO)

Comp. No.	DNA Nucleotides	HOMO eV	LUMO eV	Energy gap (ΔE) eV	IP eV	EA eV	EN eV	Global Hardness	Softness	Chemical Potential	Eletro philicity Index
	H₃PO₄	-11.716	0.598	12.314	11.716	-0.598	5.559	6.157	1.903	-5.559	2.510
	H₂O	-12.463	4.412	16.875	12.463	-4.412	4.026	8.438	1.477	-4.026	0.960
I	deoxyadenosine	-7.176	-1.807	5.369	7.176	1.807	4.492	2.685	2.673	-4.492	3.757
a	3’-AMP	-8.616	-0.492	8.124	8.616	0.492	4.554	4.062	2.121	-4.554	2.553
b	5’-AMP	-8.184	-1.037	7.147	8.184	1.037	4.611	3.574	2.290	-4.611	2.974
c	3’,5’-ADP	-6.338	-1.424	4.914	6.338	1.424	3.881	2.457	2.580	-3.881	3.065
II	deoxyguanosine	-8.585	-0.742	7.843	8.585	0.742	4.664	3.922	2.189	-4.664	2.773
a	3’-GMP	-8.341	-0.634	7.707	8.341	0.634	4.488	3.854	2.165	-4.488	2.613
b	5’-GMP	-8.754	-0.744	8.010	8.754	0.744	4.749	4.005	2.186	-4.749	2.816
c	3’,5’-GDP	-8.975	-0.808	8.167	8.975	0.808	4.892	4.084	2.198	-4.892	2.930
III	deoxycitidine	-7.524	-2.021	5.503	7.524	2.021	4.773	2.752	2.735	-4.773	4.139
a	3’-CMP	-8.758	-0.748	8.010	8.758	0.748	4.753	4.005	2.187	-4.753	2.820
b	5’-CMP	-6.591	-1.091	5.500	6.591	1.091	3.841	2.750	2.397	-3.841	2.682
c	3’,5’-CDP	-9.135	-1.154	7.981	9.135	1.154	5.145	3.991	2.289	-5.145	3.316
IV	deoxythymidine	-7.714	-2.058	5.656	7.714	2.058	4.886	2.828	2.728	-4.886	4.221
a	3’-TMP	-8.731	-0.683	8.048	8.731	0.683	4.707	4.024	2.170	-4.707	2.753
b	5’-TMP	-6.605	-1.097	5.508	6.605	1.097	3.851	2.754	2.398	-3.851	2.692
c	3’,5’-TDP	-9.035	-1.051	7.984	9.035	1.051	5.043	3.992	2.263	-5.043	3.185

The study of heat is produced from the system to surroundings are termed as exothermic process and Heat of Reaction (∆H_r) is negative (-ve). When heat is observed by the system from the surroundings is termed as endothermic process and Heat of Reaction (∆H_r) is positive (+ ve). All reactions are exothermic and their Heat of Reactions (∆H_r) are negative (-ve).

Table - III - Calculation of Heat of Reaction (∆H_r) as per Schemes (1 to 4) from AM1 Method.

Reactions as per Schemes (1 to 4)			Heat of Reaction (∆H_r) (k.cal/mol)
Scheme − 1	1	deoxyadenosine + H₃PO₄ → 3’-AMP + H₂O	-52.6277
	2	deoxyadenosine + H₃PO₄ → 5’-AMP + H₂O	-12.8191
	3	3’-AMP + H₃PO₄ → 3’5’-ADP + H₂O	-34.6402
	4	5’-AMP + H₃PO₄ → 3’5’-ADP + H₂O	-74.4488
Scheme − 2	1	deoxyguanosine + H₃PO₄ → 3’-GMP + H₂O	+ 27.4810
	2	deoxyguanosine + H₃PO₄ → 5’-GMP + H₂O	-81.2167
	3	3’-GMP + H₃PO₄ → 3’5’-GDP + H₂O	-125.0721
	4	5’-GMP + H₃PO₄ → 3’5’-GDP + H₂O	-16.3744
Scheme − 3	1	deoxycytidine + H₃PO₄ → 3’-CMP + H₂O	-41.2529
	2	deoxycytidine + H₃PO₄ → 5’-CMP + H₂O	-25.6708
	3	3’-CMP + H₃PO₄ → 3’5’-CDP + H₂O	-47.1615
	4	5’-CMP + H₃PO₄ → 3’5’-CDP + H₂O	-62.7436
Scheme − 4	1	deoxythymidine + H₃PO₄ → 3’-TMP + H₂O	+ 3.1532
	2	deoxythymidine + H₃PO₄ → 5’-TMP + H₂O	+ 34.6588
	3	3’-TMP + H₃PO₄ → 3’5’-TDP + H₂O	-30.8484
	4	5’-TMP + H₃PO₄ → 3’5’-TDP + H₂O	-62.3540

The strong kind of dipole-dipole attractions make hydrogen bonding in the formation of the double helix of DNA and these are important in determining the nature of the hydrogen bonding in nucleic acids⁴. It is expected that the dipole moment has increased in the conversion of deoxyadenosine (a to c) due to the induction effect. So that the magnitude of the induction effect¹¹ (µ_ind) can be estimated as per Eq. (1). The electronegative nitrogen atoms cause displacement of elections in the π-frame work to induce an additional dipole moment in the conversion of one to another. The order of induction effect is found and incorporated values in Table – IV. It is also observed in the case of Cosmo area has increased and Cosmo volume has decreased as 3’-AMP > 5’-AMP

Table-IV - Change of Induction effect, Cosmo area (Sq.Ang) and Cosmo volume (Cu.Ang) in the formation of nucleotides.

Conversions	Induction effect (µ_ind)	Cosmo area (Sq.Ang)	Cosmo volume (Cu.Ang)
Deoxyadenosine → 3’-AMP	0.8867	71.12	65.83
Deoxyadenosine → 5’-AMP	1.1355	71.96	64.82
Deoxyadenosine → 3’5’-ADP	5.2097	102.64	119.60
Deoxyguanosine → 3’-GMP	2.2548	53.73	57.59
Deoxyguanosine → 5’-GMP	2.3118	58.03	62.83
Deoxyguanosine → 3’5’-GDP	-1.3064	95.76	116.09
Deoxycytidine → 3’-CMP	3.7227	36.72	54.52
Deoxycytidine → 5’-CMP	-1.1363	40.84	51.01
Deoxycytidine → 3’5’-CDP	2.5012	111.94	122.24
Deoxythymidine → 3’-TMP	1.7245	51.10	38.53
Deoxythymidine → 5’-TMP	-3.2789	50.10	41.31
Deoxythymidine → 3’5’-TDP	0.7273	123.73	109.81

Phosphorylation of deoxyguanosine (II) as per Scheme – 2, and calculated values are incorporated in Table – I. It is observed the stability in the order of 3’5’-GDP > 5’-GMP > 3’-GMP > deoxyguanosine as per Heat of formation data. The dipole moment depends on the nature of the atoms and bonds comprising the molecules and on their arrangement. It is also found that the dipole moment has increased in the order of 3’5’-GDP < deoxyguanosine < 3’-GMP < 5’-GMP. The heats of reactions are calculated and values incorporated in Table – III. It is investigated that Heat of Reaction (∆H_r) is in the order of 3 > 2 > 4 > 1 > as per Scheme – 2.

The dipole moment has increased in the conversion of deoxyguanosine (a to c) due to the induction effect. So that the magnitude of the induction effect¹¹ (µ_ind) can be estimated as per Eq. (1). The order of induction effect is found and incorporated values in Table – IV. It is also observed that Cosmo area and Cosmo volume have increased as 3’-GMP < 5’-GMP. The study of heat is produced from the system to surroundings are termed as exothermic process and Heat of Reaction (∆H_r) is negative (-ve). When heat is observed by the system from the surroundings is termed as endothermic process and Heat of Reaction (∆H_r) is positive (+ ve). All reactions are exothermic and their Heat of Reactions (∆H_r) are negative (-ve) except Scheme – 2, reaction − 1 is endothermic process as in Table – III.

Phosphorylation of deoxycytidine (III) as per Scheme – 3, and calculated values are incorporated in Table – I. It is observed the stability in the order of 3’5’-CDP > 3’-CMP > 5’-CMP > deoxycytidine as per Heat of formation data. The dipole moment depends on the nature of the atoms and bonds comprising the molecules and on their arrangement. It is also found that the dipole moment has in the order of 5’-CMP < 3’5’-CDP < deoxycytidine < 3’-CMP. The heats of reactions are calculated and values incorporated in Table – III. It is investigated that Heat of Reaction (∆H_r) is in the order of 4 > 3 > 1 > 2 as per Scheme – 3. All reactions are exothermic and their Heat of Reactions (∆H_r) are negative (-ve).

The dipole moment has increased in the conversion of deoxycytidine (a to c) due to the induction effect. So that the magnitude of the induction effect (µ_ind) can be estimated as per Eq. (1). The order of induction effect is found and incorporated values in Table – IV. It is also observed that Cosmo area has increased (3’-CMP < 5’-GMP) and Cosmo volume have decreased as 3’-CMP > 5’-GMP.

Phosphorylation of deoxythymidine (IV) as per Scheme – 4, and calculated values are incorporated in Table – I. According to the heat of formation (∆H_f^o) data, the stability is found in the increasing order of 3’5’-TDP > 3’-TMP > 5’-TMP > deoxythymidine as per Heat of formation data. The dipole moment depends on the nature of the atoms and bonds comprising the molecules and on their arrangement. It is also found that the dipole moment has increased in the order of 5’-TMP < deoxythymidine < 3’5’-TDP < 3’-TMP.

The heats of reactions are calculated and values incorporated in Table – III. It is investigated that Heat of Reaction (∆H_r) is in the order of 4 > 3 > 1 > 2 as per Scheme – 4. The dipole moment has increased in the conversion of deoxythymidine (a to c) due to the induction effect. So that the magnitude of the induction effect (µ_ind) can be estimated as per Eq. (1). The order of induction effect is found and incorporated values in Table – IV. It is also observed that Cosmo area has decreased (3’-TMP > 5’-TMP) and Cosmo volume increased (3’-TMP < 5’-TMP). The study of heat is produced from the system to surroundings are termed as exothermic process and Heat of Reaction (∆H_r) is negative (-ve). When heat is observed by the system from the surroundings is termed as endothermic process and Heat of Reaction (∆H_r) is positive (+ ve). As per Scheme – 2, reactions 1 and 2 are endothermic process and reactions 3 and 4 are exothermic process as in Table – III.

Naturally occurring nucleosides and nucleotides are basic building blocks for the synthesis of DNA and RNA. The presence of multiple reactive centres in nucleotide derivatives, the advanced technology of genetic engineering for the synthesis of genes and discovery of miracle enzymes are required to cure many diseases. Austin Model-1 (AM1) is one of the semi-empirical methods of quantum chemistry which uses experimental parameters and extensive implication of Schrodingers’ equation (HΨ = EΨ) to optimize molecules for calculation of various thermodynamic properties like heats of formation (∆H_f^o), dipole moment (µ), the energies of frontier molecular orbitals (E_HOMO and E_LUMO) and quantum chemical descriptors. Further, the utility of theoretical predictions is important to determine the sequence of bases with mutation and genetic diseases.

Disclosure statement

No potential conflict of interest was reported by the author.

Funding

The author received no financial support for the research work, and publication of this article.

Author’s contribution

The author has participated in conception, design, analysis, interpretation of the data, drafting the article, and approval of the final version

(a). Rachwalak, M.; Romanowska, J.; Sobkowski, M.; Stawinski, (2021) J. Nucleoside Di- and Triphosphates as a New Generation of Anti-HIV Pronucleotides. Chemical and Biological Aspects. Appl. Sci., 11, 2248. https:// doi.org/10.3390/app11052248. (b). Berg, J.M.; Tymoczko, J.L.; Gatto, G.J.; Stryer, L. (2019) Biochemistry, 9th ed.; Palgrave Macmillan: London, UK.
(a). Depaix, A.; Peyrottes, S.; Roy, B. (2018) One-pot synthesis of nucleotides in water medium. Phosphorus Sulfur Silicon Relat. Elem. 194, 335–336. (b). Burgess, K.; Cook, D. (2000) Syntheses of Nucleoside Triphosphates. Chem. Rev. 100, 2047–2059.
(a). Hollenstein, M. (2012) Nucleoside Triphosphates—Building Blocks for the Modification of Nucleic Acids. Molecules, 17, 13569–13591.(b). Hou, S.; Qu, Z.; Tang, L.; Shuhua, Q.Z.H. (2014) Advances in the Synthesis of Organic Pyrophosphate. Chin. J. Org. Chem. 34, 54. (c). Sherstyuk, Y.V.; Abramova, T.V. (2015) How to Form a Phosphate Anhydride Linkage in Nucleotide Derivatives. Chembiochem Eur. J. Chem. Biol., 16, 2562–2570. (d). Tanaka, H. (2015) Recent Approaches to the Chemical Synthesis of Sugar Nucleoside Diphosphates. Trends Glycosci. Glycotechnol. 27, 99–110. (e). Ahmadipour, S.; Miller, G.J. (2017) Recent advances in the chemical synthesis of sugar-nucleotides. Carbohydr. Res. 451, 95–109. (f). Kaczynski, T.P.; Chmielewski, M.K. (2017) Mini-Review of the Phosphate Center Activation Strategy in Nucleoside Triphosphate Preparation. Mini Rev. Org. Chem. 14, 448–452. (g). Camarasa,M. (2018)-J. Prodrugs of Nucleoside Triphosphates as a Sound and Challenging Approach: A PioneeringWork That Opens a New Era in the Direct Intracellular Delivery of Nucleoside Triphosphates. ChemMedChem, 13, 1885–1889. [PubMed]
(a). Baddiley, J.; Michelson, A.M.; Todd, A.R. (1949) Nucleotides. Part II. A Synthesis of Adenosine Triphosphate. J. Chem. Soc. 582–586. (b). Baddiley, J.; Michcelson, A.M.; Todd, A.R. (1948) Synthesis of Adenosine Triphosphate. Nat. Cell Biol. 161, 761–762.
(a). Khorana, G.; Todd, A.R. (1953) Studies on Phosphorylation. XI. The Reaction Between Carbodi-imides and Acid Esters of Phosphoric Acid—A New Method for the Preparation of Pyrophosphates. J. Chem. Soc. 2257–2260. (b). Baddiley, J.; Hughes, N.A. (2006) The Synthesis of Nucleotide Coenzymes. In Advances in Enzymology and Related Areas of Molecular Biology;Wiley: Hoboken, NJ, USA, Volume 22, pp. 157–203. (c). Smith, M.; Khorana, H.G. (1958) Nucleoside Polyphosphates. VI. An Improved and General Method for the Synthesis of Ribo- and Deoxyribonucleoside 5’-Triphosphates. J. Am. Chem. Soc. 80, 1141–1145. (d). Chambers, R.W.; Khorana, H.G. (1958) Nucleoside Polyphosphates. VII. The Use of Phosphoramidic Acids in the Synthesis of Nucleoside-5’-Pyrophosphates. J. Am. Chem. Soc. 80, 3749–3752. (e). Moffatt, J.G.; Khorana, H.G. (1958) Nucleoside Polyphosphates. VIII. New and Improved Syntheses of Uridine Diphosphate Glucose and Flavin Adenine Dinucleotide Using Nucleoside-5’-Phosphoramidates. J. Am. Chem. Soc. 80, 3756–3761. (f). Clark, V.M.; Kirby, G.W.; Todd, A.R. (1957) Studies on Phosphorylation. Part XV. The Use of Phosphoramidic Esters in Acylation. A New Preparation of Adenosine-5’-Pyrophsphate and Adenosine-5’-Triphosphate. J. Chem. Soc. 79, 1497–1501. (g). Moffatt, J.G. (1964) A General Synthesis of Nucleoside 5’-Triphosphates. Can. J. Chem. 599–604.
(a). Watson JD, (1976) Molecular biology of the Genes, 3^rd Edn (WA Benjamin, New York). (b). Levin B L, (1983) Genes ( John Wiley & Sons Inc, New York).
(a). Rajeshwar Rao B, (2003) Study of [1,3]Sigmatropic hydrogen migration in cytosine and cytidine by AM1 method, Indian J. Chem, 42B(12), 3081-3088. (b). Rajeshwar Rao B, (2006) Study of [1,3]Sigmatropic hydrogen migration in uracil, uridine and uridylic acid by AM1 method, Indian J. Chem, 45B(9), 2083-2090. (c). Rajeshwar Rao B, (2009) Study of [1,3]sigmatropic hydrogen migration in thymine, thymidine and thymidylic acid by AM1 method., Indian J. Chem, 48B (10), 1411- 1415. (d). Rajeshwar Rao B, (2012) Study of [1,3]sigmatropic hydrogen migration in adenine and guanine by AM1 method, Int J Res Pharmaceutical and Biomed Sci.,3(1), 275-281. www.ijrpbsonline.com. (e). Rajeshwar Rao B, (2022) Critical Review on computational study of [1,3]sigmatropic hydrogen migration in pyrimidines and purines of nucleic acids by Austin Model-1 Method. World J Pharmacy and Pharmaceutical Sciences., 11(4), 904-926. www.wjpps.com.
(a). Dewar MJS, Zeobisch EG, Healy EF, Stewart JJP, (1985) AM1: a new general purpose quantum mechanical molecular model, J am chem soc, 107, 3902-9, (b). Stewart J J P, (1988) MOPAC, A general molecular orbital package, QCPE 455, 5^th edn,. (c). MOPAC2016 (Version: 22.234w).
Paperno T Y A, Pozdnyakov V P, Smirnova A A, Elagin L M, (1979) Physico-Chemical Laboratory Techniques in Organic and Biological Chemistry (Translated from Russian by Oleg Glebov), (MIR Publishers, Moscow).
(a). Tomasz Puzyn, Jerzy Leszczynski, Mark T.D. Cronin, (2009) edited, Recent Advances in QSAR Studies-Methods and Applications, DOI 10.1007/978-1-4020-9783-6, Springer Dordrecht Heidelberg London New York,. (b). Hansch C, Hockman D, Leo A, Wininger D, Selassic C, (2002) Chem Rev, 102,783.

Schemes are available in the Supplementary Files section.

No competing interests reported.

Download PDF

Version 1

posted

You are reading this latest preprint version

Computational study on Phosphorylation of Nucleosides and Nucleotides by Austin Model-1 method

Status:

Version 1

Abstract

Figures

Introduction

Results And Discussions

Conclusions

Declarations

References

Schemes

Additional Declarations

Supplementary Files

Status:

Version 1