Evaluation of the Effect of Doxy-Ribose and Phosphate Substituents on the Strength of Hydrogen Bonds between Adenine-Thymine base Pair

Document Type : Research Article


Department of Chemistry, Faculty of Science, University of Sistan and Baluchestan, Zahedan, I.R. IRAN


In this study, using density functional theory, atoms in molecules and natural bonding orbital’s analyses, the strength of individual hydrogen bonds and the total interaction energy in the thymine-adenine (TA) base pair containing deoxyribose(d) and phosphate(p) substituents, was evaluated. The results of the absolute electron energies show that the structures containing the substituents are more stable than the TA base pair. In addition, according to the results of the hydrogen bonding energy, the binding of deoxyribose to adenine increase the total hydrogen bond strength more than binding this substituent to thymine. In all structures, deoxyribose binding increases N-H…N hydrogen bond strength and decreases N-H…O bond strength. While phosphate group modulates the additive effect of deoxyribose on hydrogen bond strength. It is interesting to note that the C-H...O bond is weaker than the other hydrogen bonds, but the mentioned substituents affect this hydrogen bond more than others. Also, the hydrogen bond of N-H ...N is stronger than the other hydrogen bonds and the highest of the energy value of this bond belongs to the TA-d structure. It also has the highest total hydrogen bond energy. Moreover, four parameters were introduced as suitable descriptors for evaluating the hydrogen bonding of this system.


Main Subjects

[2] Harding S.E., Channell G., Phillips-Jones M.K., The Discovery of Hydrogen Bonds in DNA and a Re-Evaluation of the 1948 Creeth Two-Chain Model for Its Structure. Biochem. Soc. Trans., 46(5): 1171–1182 (2018).
[3] Acosta-Reyes F.J., Alechaga E., Subirana J.A., Campos J.L., Structure of the DNA Duplex d (ATTAAT) 2 with Hoogsteen Hydrogen Bonds. PLoS One10(3): e0120241 (2015).
[4] Akbari F., Foroutan M., Molecular Investigation of Evaporation of Biodroplets Containing Single Strand DNA on Graphene Surface, Phys. Chem. Chem. Phys., 20(7): 4936-4952 (2018).
[5] Park T., Zimmerman S.C., Interplay of Fidelity, Binding Strength, and Structure in Supramolecular Polymers, J. Am. Chem. Soc., 128(44): 14236–14237 (2006).
[7] Riley K. E., Hobza P., Noncovalent Interactions in Biochemistry. Wiley Interdiscip. Rev. Comput. Mol. Sci., 1(1): 3–17 (2011).
[8] Yurenko Y.P., Zhurakivsky R.O., Samijlenko S.P., Hovorun D.M., Intramolecular CH… O Hydrogen Bonds in the AI and BI DNA-like Conformers of Canonical Nucleosides and Their Watson-Crick Pairs. Quantum Chemical and AIM Analysis. J. Biomol. Struct. Dyn., 29(1): 51–65 (2011).
[9] Brovarets O.O., Yurenko Y. P., Dubey I. Y., Hovorun D.M., Can DNA-Binding Proteins of Replisome Tautomerize Nucleotide Bases Ab Initio Model Study, Journal of Biomolecular Structure and Dynamics, 29(6): 1101–1109 (2012).
[10] Samijlenko S.P., Yurenko Y.P., Stepanyugin A.V, Hovorun D.M., Tautomeric Equilibrium of Uracil and Thymine in Model Protein− Nucleic Acid Contacts. Spectroscopic and Quantum Chemical Approach. J. Phys. Chem. B, 114(3): 1454–1461 (2010).
[11] Yurenko Y.P., Zhurakivsky R.O., Ghomi M., Samijlenko S.P., Hovorun D.M., How Many Conformers Determine the Thymidine Low-Temperature Matrix Infrared Spectrum? DFT and MP2 Quantum Chemical Study. J. Phys. Chem. B, 111(32): 9655–9663 (2007).
[12] Lu H., Wang Y., Wu Y., Yang P., Li L., Li S., Hydrogen-Bond Network and Local Structure of Liquid Water: An Atoms-in-Molecules Perspective. J. Chem. Phys., 129(12): 124512 (2008).
[13] Poole P.H., Sciortino F., Grande T., Stanley H.E., Angell C.A., Effect of Hydrogen Bonds on the Thermodynamic Behavior of Liquid Water. Phys. Rev. Lett., 73(12): 1632-1635 (1994).
[14] Méndez J., Stillman B., Perpetuating the Double Helix: Molecular Machines at Eukaryotic DNA Replication Origins. Bioessays, 25(12): 1158–1167 (2003).
[15] Rohs R., West S.M., Sosinsky A., Liu P., Mann R.S., Honig B., The Role of DNA Shape in Protein–DNA Recognition. Nature, 461(7268): 1248-1253 (2009).
[17] Isaacs E.D., Shukla A., Platzman P.M., Hamann D.R., Barbiellini B., Tulk C.A., Covalency of the Hydrogen Bond in Ice: A Direct X-Ray Measurement. Phys. Rev. Lett., 82(3): 600 (1999).
[18] Ragot S., Gillet J.-M., Becker P.J., Interpreting Compton Anisotropy of Ice I h: A Cluster Partitioning Method. Phys. Rev. B, 65(23): 235115 (2002).
[22] Scheiner S., Contributions of NH... O and CH… O Hydrogen Bonds to the Stability of β-Sheets in Proteins. J. Phys. Chem. B, 110(37): 18670–18679 (2006).
[23] Dong H., Hua W., Li S., Estimation on the Individual Hydrogen-Bond Strength in Molecules with Multiple Hydrogen Bonds. J. Phys. Chem. A, 111(15): 2941–2945 (2007).
[24] Kawahara S., Uchimaru T., Taira K., Sekine M., An Ab Initio Study of the Hydrogen Bond Energy of Base Pairs Formed between Substituted 9-Methylguanine Derivatives and 1-Methylcytosine. J. Phys. Chem. A, 106(13): 3207–3212 (2002).
[28] Meng F., Liu C., Xu W., Substituent Effects of R (R= CH3, CH3O, F and NO2) on the A: T and C: G Base Pairs: A Theoretical Study. Chem. Phys. Lett., 373(1–2): 72–78 (2003).
[29] Meng F., Wang H., Xu W., Liu C., Theoretical Study of GC+/GC Base Pair Derivatives. Chem. Phys., 308(1–2): 117–123(2005).
[30] Frisch M.J., Trucks G.W., Schlegel H.B., Scuseria G.E., Robb Ma., Cheeseman J.R., Scalmani G., Barone V., Mennucci B., Petersson G.A.,” Gaussian 09”, Revision D. 01, Gaussian. Inc. Wallingford, CT 201 (2009).
[31] Becke A.D., Density‐functional thermochemistry. III. The role of exact exchange J. Chem. Phys, 98(7): 5648 (1993).
[33] Hehre W.J., Radom L., Schleyer P.V.R., Pople J.A.,” Ab initio Mol. orbital theory “, John Wiley; New York 63–101(1986).
[34] Štrajbl M., Florián J., Density Functional Calculations of the Pseudorotational Flexibility of Tetrahydrofuran. Theor. Chem. Acc., 99(3): 166–170 (1998).
[35] Brovarets O.O., Yurenko Y.P., Hovorun D.M., Intermolecular CH··· O/N H-Bonds in the Biologically Important Pairs of Natural Nucleobases: A Thorough Quantum-Chemical Study. J. Biomol. Struct. Dyn., 32(6): 993–1022 (2014).
[36] Lozynski M., Rusinska-Roszak D., Mack H.-G., Hydrogen Bonding and Density Functional Calculations: The B3LYP Approach as the Shortest Way to MP2 Results. J. Phys. Chem. A, 102(17): 2899–2903 (1998).
[38] Biegler Konig F.W., Schonbohm J., Bayles D., Software News and Updates AIM2000. J Comput Chem, 22(5): 545–559 (2001).
[39] Glendening E.D., Reed A.E., Carpenter J.E., Weinhold F., NBO, Version 3.1; University of Wisconsin: Madison, WI. (1992).
[40] Popelier P.L.A., Aicken F.M., O’Brien S.E., Chemical Modelling: Applications and Theory. R. Soc. Chem. Spec. Period. Rep., 1: 143–198 (2000).
[43] Rozenberg M., Jung C., Shoham G., Low-Temperature FTIR Spectra and Hydrogen Bonds
in Polycrystalline Adenosine and Uridine
. Spectrochim. Acta Part A Mol. Biomol. Spectrosc., 61(4): 733–741 (2005).
[44] Bader R.F.W., A Bond Path: A Universal Indicator of Bonded Interactions. J. Phys. Chem. A., 102(37): 7314–7323 (1998).
[45] Bader R.F.W., A Quantum Theory of Molecular Structure and Its Applications. Chem. Rev., 91(5): 893–928 (1991).
[47] Bader R.F.W., A Quantum Theory of molecular structure and its applications, Chem. Rev., 91(5): 893-928 (1991).
[48] Koch U., Popelier P.L.A., Characterization of CHO Hydrogen Bonds on the Basis of the Charge Density. J. Phys. Chem., 99(24): 9747–9754 (1995).
[49] Koritsanszky T.S., Coppens P., Chemical Applications of X-Ray Charge-Density Analysis. Chem. Rev., 101(6): 1583–1628 (2001).
[50] Stash A.I., Tsirelson V.G., Modern Possibilities for Calculating Some Properties of Molecules and Crystals from the Experimental Electron Density. Crystallogr. Reports., 50(2): 177–184 (2005).
[51] Ranganathan A., Kulkarni G.U., Rao C.N.R., Probing the Hydrogen Bond through Experimental Charge Densities. J. Mol. Struct., 656(1–3): 249–263 (2003).
[52] Poater J., Visser R., Sola M., Bickelhaupt Hydrogen–Hydrogen Bonding in Planar Biphenyl, Predicted by Atoms‐In‐Molecules Theory, Does Not Exist, FM. Chem. Eur. J., 12(10): 2889-2895 (2006).
[53] Cioslowski J., Mixon S.T., Fleischmann E.D., Electronic Structures of Trifluoro-, Tricyano-, and Trinitromethane and Their Conjugate Bases. J. Am. Chem. Soc., 113(13): 4751–4755 (1991).
[54] Abramov Y.A., On the Possibility of Kinetic Energy Density Evaluation from the Experimental Electron-Density Distribution. Acta Crystallogr. Sect. A Found. Crystallogr, 53(3): 264–272 (1997).
[55] Alabugin I.V., Manoharan M., Peabody S., Weinhold F., Electronic Basis of Improper Hydrogen Bonding: A Subtle Balance of Hyperconjugation and Rehybridization. J. Am. Chem. Soc., 125 (19): 5973–5987 (2003).
[57] Curtiss L.A., Pochatko D.J., Reed A.E., Weinhold F., Investigation of the Differences in Stability of the OC⋅⋅⋅ HF and CO⋅⋅⋅ HF Complexes. J. Chem. Phys., 82(6): 2679–2687 (1985).
[58] Weinhold F., Reed AE., Curtiss LA., Weinhold F., For a Deeper Discussion of This Approach, Chem. Rev., 88: 899 (1988).
[59] Fonseca Guerra C., Bickelhaupt F.M., Charge Transfer and Environment Effects Responsible for Characteristics of DNA Base Pairing. Angew. Chemie. Int. Ed., 38(19): 2942–2945 (1999).
[60] van der Wijst T., Guerra C.F., Swart M., Bickelhaupt F.M., Performance of Various Density Functionals for the Hydrogen Bonds in DNA Base Pairs. Chem. Phys. Lett., 426(4–6): 415–421 (2006).
[61] Ida R., De Clerk M., Wu G., Influence of N-H⋯O and C-H⋯O Hydrogen Bonds on the 17O NMR Tensors in Crystalline Uracil: Computational Study. J. Phys. Chem. A, 110(3): 1065–1071 (2006).
[62] Torrent M., Mansour D., Day E.P., Morokuma K., Quantum Chemical Study on Oxygen-17 and Nitrogen-14 Nuclear Quadrupole Coupling Parameters of Peptide Bonds in α-Helix and β-Sheet Proteins. J. Phys. Chem. A, 105(18): 4546–4557 (2001).
[63] گلوی ثانی م.، بهلولی م.، غفاری مقدم م.، خرسندی خ.، شهرکی س.، برهمکنش DNA با رنگ زرد دایرکت 42 توسط روش‌های طیف سنجی، نشریه شیمی و مهندسی شیمی، (3)38: 201 تا 209 (1398).
[64] اسمعیل زایی ز.، صبوری ع.ا.، منصوری ترشیزی ح.، سعیدی فر م.، دیوسالار ع.، مطالعه برهمکنش کمپلکس‌های نیکل (اا) دارای لیگاندهای آروماتیک مسطح با DNA غده تیموس، نشریه شیمی و مهندسی شیمی، (2)32: 1 تا 13 (1392).