MP2 study on the hydrogen-bonding interaction between 5-fluorocytosine and DNA bases: A,C, G,T

The 5-fluorocytosine (5-FC) is a fluorinated cytosine analog that is used as an antifungal agent. In this work, we present the hydrogen-bonding base pairs involving 5-FC bound to the four bases in DNA: adenine (A), cytosine (C), guanine (G), and thymine (T). Full geometry optimizations have been performed for the studied complexes by MP2 method. The interaction energies were corrected for the basis set superposition error, using the full Boys–Bernardi counterpoise correction scheme. Hydrogen-bonding patterns of these base pairs were characterized using NBO analysis and AIM analysis. According to the calculated binding energies and structural parameters, the stability of the base pairs decreases in the following order: 5-FC:G > 5-FC:C > 5-FC:A > 5-FC:T.     

MP2 study on the hydrogen-bonding interaction between 5-fluorouracil and DNA bases: A,C,G,T

The 5-fluorouracil is a pyrimidine analog effective in the treatment of cancer. In this work, we present the hydrogen-bonding base pairs involving 5-FU bound to the four bases in DNA: adenine, cytosine, guanine, and thymine. Full geometry optimizations have been performed for the studied complexes by MP2 method. The interaction energies were corrected for the basis-set superposition error, using the full Boys-Bernardi counterpoise correction scheme. Hydrogen-bonding patterns of these base pairs were characterized using NBO analysis and AIM analysis. According to the calculated binding energies and structural parameters, the stability of the base pairs decrease in the following order: 5-FU:A > 5-FU:G > 5-FU:T > 5-FU:C.     

Ab initio quantum chemistry studies on the coding properties of cytosine derivatives generated by hydroxyl radical in aerobic conditions

The coding properties of four free radicals derived cytosine modifications were characterised by ab initio quantum chemistry method. The dimers geometry was optimised without any restrictions. The analysis was focused on the pairs consisting of a standard DNA base and one of the following cytosine derivatives: 5,6-dihydroxycytosine (1); 5,6-dihydroxyuracil (2); uracil glycol (3); and isodialuric acid (4). The presented data allow to conclude that all studied derivatives are able to form the most stable pairs with guanine. However, other pairs are also possible. In non-polar conditions the 5,6-dihydroxycytosine (1) pair with cytosine in addition to a normal pairing with guanine. This may stand for CG transversion. The significant impact of the environment polarity on the dimers stabilisation energy was observed. The potential mispairing is enriched in the polar conditions The 5,6-dihydroxyuracil (2) and isodialuric acid (4) may form stable pairs also with adenine. This may lead to CT transition. The mispairing of uracil glycol (3) was found as insignificant.     

MP2 study on the hydrogen-bonding interaction between O 4-methylthymine and DNA bases: A,C, G,and T

The O ⁴-methylthymine (m⁴T) is a nucleobase lesion induced by the action of ionizing radiation on thymine residue in DNA. In this study, we present the hydrogen-bonding base pairs involving m⁴T bound to the four bases in DNA: adenine (A), cytosine (C), guanine (G), and thymine (T). Full geometry optimizations have been performed for the studied complexes by MP2 method. The interaction energies were corrected for the basis-set superposition error, using the full Boys–Bernardi counterpoise correction scheme. Hydrogen-bonding patterns of these base pairs were characterized using NBO analysis and AIM analysis. According to the calculated binding energies and structural parameters, the stability of the base pairs decrease in the following order: m⁴T:G > m⁴T:A > m⁴T:C > m⁴T:T.     

DFT and MP2 investigations on the hydrogen bonding interaction between 5,6-dihydrothymine and dna bases: A, C, G, T

5,6-Dihydrothymine (DHT) is a nucleobase lesion induced by the action of ionizing radiation on thymine residue in DNA. In this work, we present the hydrogen bonding base pairs involving 5,6-dihydrothymine bound to four bases in DNA: adenine (A), cytosine (C), guanine (G), and thymine (T). Full geometry optimizations are performed for the studied complexes by the B3LYP method. Interaction energies are corrected for the basis set superposition error, using the full Boys-Bernardi counterpoise correction scheme. Hydrogen bonding patterns of these base pairs are characterized using NBO and AIM analysis. According to the calculated binding energies and structural parameters, the stability of the base pairs decrease in the following order: DHT:G ～ DHT:A > DHT:C > DHT:T.     

MP2 study on the hydrogen bonding interaction between 5-hydroxy-5-methylhydantoin and DNA bases: A,C, G,T

The 5-hydroxy-5-methylhydantoin (5-OH-5-Me-dHyd) is a nucleobase lesion induced by the action of ionizing radiation on thymine residue in DNA. In this study, we present the hydrogen bonding base pairs involving 5-OH-5-Me-dHyd bound to the four bases in DNA: adenine (A), cytosine (C), guanine (G), and thymine (T). Full geometry optimizations have been performed for the studied complexes by MP2 method. The interaction energies were corrected for the basis-set superposition error (BSSE), using the full Boys–Bernardi counterpoise correction scheme. Hydrogen bonding patterns of these base pairs were characterized using NBO analysis and AIM analysis. According to the calculated binding energies and structural parameters, the stability of the base pairs decrease in the following order: 5-OH-5-Me-dHyd:G>5-OH-5-Me-dHyd:A>5-OH-5-Me -dHyd:C~5-OH-5-Me-dHyd:T.     

Hydrogen-bonding interaction of 5,6-dihydrouracil with RNA bases: DFT and MP2 studies

5,6-Dihydrouracil (DHU) is a rare pyrimidine base naturally occurring in tRNAs, it differs from the base uracil due to the saturation of the C₅–C₆ bond. This work presents the interaction energies of complexes formation involving DHU bound to the natural RNA bases adenine (A), uracil (U), guanine (G), and cytosine (C). Full geometry optimization has been performed for the studied complexes by B3LYP/6-31+G(d,p) and MP2/6-31+G(d,p) calculations. The interaction energies were corrected for the basis-set superposition error (BSSE), using the full Boys–Bernardi counterpoise correction scheme. We find that the stability order is DHU:G > DHU:A > DHU:C  DHU:U.     

MP2 study on the hydrogen-bonding interaction between 5-hydroxymethyl-uracil and DNA bases: A,C, G,T

The 5-hydroxymethyl-uracil (HmU) is a product of oxidative attack on the methyl group of thymine in DNA. In this work, we present the hydrogen bonding complexes formation involving HmU bound to the four bases in DNA: adenine (A), cytosine (C), guanine (G), and thymine (T). Full geometry optimizations have been performed for the studied complexes by MP2 method. The interaction energies were corrected for the basis-set superposition error (BSSE), using the full Boys-Bernardi counterpoise correction scheme. Hydrogen bonding patterns of these base pairs were characterized using NBO analysis and AIM analysis. According to the calculated binding energies and structural parameters, the stability of the base pairs decrease in the following order: HmU:A > HmU:G > HmU:C > HmU:T.     

Methylation of DNA bases by methyl free radicals: mechanism of formation of C8-methylguanine

The C8-methylguanine (C8mG) lesions are reported to be produced in vivo due to methylation of guanine base of DNA by methyl free (·CH₃) radicals derived from the carcinogen 1,2-dimethylhydrazines and tert-butylhydroperoxide. It is believed that C8mG lesions can induce G to T and G to C transversion mutations and deletions. However, the mechanisms of reactions of ·CH₃ radicals with DNA bases leading to formation of C8mG and other methylated DNA bases and their biological implications are not properly understood. In the present contribution, we have carried out density functional theory (DFT) calculations to ascertain the various stable methylated derivatives of all the four DNA bases that are formed by the attack of ·CH₃ radicals on DNA bases as well as to understand the mechanism of formation of C8mG due to reaction of ·CH₃ radicals with the C8 site of guanine. Our calculations reveal that ·CH₃ radical would form stable methylated products at the C8 sites of purine bases (guanine and adenine) and at the C5 and C6 sites of pyrimidine bases (cytosine and thymine) by directly attacking to bases. The C8mG is the most stable. This is in agreement with experimental observation. Further, we have found that in absence of any external agents, the C8mG is formed preferably by direct addition of a ·CH₃ radical to the C8 site of guanine followed by abstraction of the H8 hydrogen atom by another ·CH₃ radical. The barrier energies for these two steps are found to be 18.16 (18.73) and 16.05 (18.54) kcal/mol, respectively, as determined at the M06-2X/6-311+G(d,p) level of theory in gas phase (aqueous media). Thus, the present study explains the mechanism of formation of C8mG.     

Regulation of one-electron oxidation rate of guanine by base pairing with cytosine derivatives

Effects of base pairing on the one-electron oxidation rate of guanine derivatives, guanine, 8-bromoguanine, and 8-oxo-7,8-dihydroguanine have been studied. The one-electron oxidation rate of guanine derivatives was determined by triplet-quenching experiments, using N,N'-dibutylnaphthaldiimide (NDI) in the triplet excited state (3NDI*) and fullerene (C(60)) in the triplet excited state ((3)C(60*)) as oxidants. In all three guanine derivatives studied here, acceleration of the one-electron oxidation was observed upon hydrogen bonding with cytosine, which demonstrates lowering of the oxidation potential of guanine derivatives by base pairing with cytosine. When a methyl or bromo group was introduced to the C5 position of cytosine, acceleration or suppression of the one-electron oxidation relative to the guanine:cytosine base pair was observed, respectively. The results demonstrate that the one-electron oxidation rate of guanine in DNA can be regulated by introducing a substituent on base pairing cytosine.     

Oligonucleotide cross-linking with copper ions. Spectral and quantum chemical study

Copper(II) complexes with synthetic oligonucleotides consisting of repeating adenine–thymine and guanine–cytosine complementary base pairs have been studied by UV spectroscopy and simulated by DFT quantum chemical calculations at the B3LYP/6-311G++(d,p) level of theory with inclusion of solvation (hydration) effects. The obtained data suggest selective interaction of copper(II) ions with guanine–cytosine complementary pairs, followed by DNA cross-linking at those sites.     

Prototropic changes in cationic base-pair adducts. II. Guanine methylation

AM 1 calculations have been used to study the effects of CH attachment on the structures, energies, and, in some cases, proton transfer reactions of guanine cytosine base pairs. Methylation of both the guanine 3- and O⁶-positions is predicted to lead to chemically significant concentrations of intermediate base pairs arising from proton transfer from the guanine 1- to the cytosine 3-position. The possible biological implications of such intermediates in nucleic acids is discussed in relation to the formation of either doubly abasic sites or abasic sites opposite potentially miscoding DNA lesions. © 1992 John Wiley & Sons, Inc.     

Prototropic changes in cationic base-pair adducts. I. Guanine protonation

AM 1 calculations have been used to study the effects of protonation on the structures, energies, and, in some cases, proton transfer reactions of guanine cytosine base pairs. Protonation at the guanine O⁶-position, or at various ring sites, leads to a relatively facile conversion to a surprisingly stable complementary base pairs following proton transfer to the cytosine 3-position. In the case of O⁶-protonation, this constitutes a direct route to guanine enolization. It is suggested that the spontaneous formation of apyrimidinic sites in nucleic acids take place via prior protonation of guanine moieties in the opposite strand. © 1992 John Wiley & Sons, Inc.     

Calculation of the stabilization energies of oxidatively damaged guanine base pairs with guanine

DNA is constantly exposed to endogenous and exogenous oxidative stresses. Damaged DNA can cause mutations, which may increase the risk of developing cancer and other diseases. G:C-C:G transversions are caused by various oxidative stresses. 2,2,4-Triamino-5(2H)-oxazolone (Oz), guanidinohydantoin (Gh)/iminoallantoin (Ia) and spiro-imino-dihydantoin (Sp) are known products of oxidative guanine damage. These damaged bases can base pair with guanine and cause G:C-C:G transversions. In this study, the stabilization energies of these bases paired with guanine were calculated in vacuo and in water. The calculated stabilization energies of the Ia:G base pairs were similar to that of the native C:G base pair, and both bases pairs have three hydrogen bonds. By contrast, the calculated stabilization energies of Gh:G, which form two hydrogen bonds, were lower than the Ia:G base pairs, suggesting that the stabilization energy depends on the number of hydrogen bonds. In addition, the Sp:G base pairs were less stable than the Ia:G base pairs. Furthermore, calculations showed that the Oz:G base pairs were less stable than the Ia:G, Gh:G and Sp:G base pairs, even though experimental results showed that incorporation of guanine opposite Oz is more efficient than that opposite Gh/Ia and Sp.     

Ab initio base-pairing energies of an oxidized thymine product, 5-formyluracil, with standard DNA bases at the BSSE-free DFT and MP2 theory levels

Oxidation of the thymine methyl group produces two stable products, non-mutagenic 5-hydroxymethyluracil and highly mutagenic 5-formyluracil. We have calculated the interaction energy of base-pair formation involving 5-formyluracil bound to the natural DNA bases adenine (A), cytosine (C), guanine (G), and thymine (T), and discuss the effects of the 5-formyl group with respect to similar base-pairs containing uracil, 5-hydroxyuracil, thymine (5-methyluracil), and 5-hydroxycytosine. The interaction geometries and energies were calculated four ways: (a) using density functional theory (DFT) without basis set super-position error (BSSE) corrections, (b) using DFT with BSSE correction of geometries and energies, (c) using M?ller-Plesset second order perturbation theory (MP2) without BSSE correction, and (d) using MP2 with BSSE geometry and energy correction. All calculations used the 6-311G(d,p) basis set. Notably, we find that the A:5-formyluracil base-pair is more stable than the precursor A:T base-pair. The relative order of base-pair stabilities is A:5-Fo-U > G:5-Fo-U > C:5-Fo-U > T:5-Fo-U.     

MP2 study on the hydrogen-bonding interactions between 4-thiouracil and four RNA bases

The 4-thiouracil (s⁴U) is a sulphur-containing analog of uracil, a natural component of RNA. In this work, we present the interaction energies of complexes formation involving s⁴U bound to the four bases in RNA: adenine (A), uracil (U), guanine (G), and cytosine (C). Full geometry optimizations have been performed for the studied complexes by MP2 method. The interaction energies were corrected for the basis-set superposition error (BSSE), using the full Boys–Bernardi counterpoise correction scheme. Hydrogen bonding patterns of these base pairs were characterized using NBO analysis and AIM analysis. We find that the order of stability for the base pairs is s⁴U: G > s⁴U: A > s⁴U: U ~ s⁴U: C.     

Properties of the optimal environment inducing tautomerization of complementary base pairs

The optimal environment charge configurations are predicted for the tautomerization of complementary base pairs into their corresponding rare forms, and vice versa. Results indicate that cations approaching the N₃ guanine site may induce tautomerization of the normal guanine—cytosine (G---C) base pair into its rare form. The reverse process requires that the cation approach the O₂ thymine site of the rare adenine*—thymine* pair (A*---31T*) or the O₆ guanine site of rare guanine*—cytosine* base pair (G*---C*). Possible mutagenic and antimutagenic roles of metal cations approaching base pairs are also discussed.     

Binding of anticancer drug Ru(η 6 -C6H5(CH2)2OH)Cl2(DAPTA) to DNA purine bases and amino acid residues: a theoretical study

The hydrolyzed Ru(η ⁶ -C₆H₅(CH₂)₂OH)Cl₂(DAPTA) (DAPTA = 3,7-diacetyl-1,3,7-triaza-5-phosphabicyclo[3.3.1]nonane) binding to guanine(G), adenine (A), cytosine(C), cysteine (Cys), and histidine (His) residues were explored using the B3LYP hybrid functional and IEF-PCM solvation models. The computed activation barriers for the reactions of diaqua complex were lower than those of chloroaqua complex except for binding to cytosine. For the chloroaqua complex, the activation free energy was lowest when binding to cytosine (10.5 kcal/mol). Whereas, the substitution reaction of diaqua complex binding to cysteine showed the lowest activation free energy with 10.1 kcal/mol, closely followed by histidine (15.8 kcal/mol), adenine (20.1 kcal/mol), cytosine (20.7 kcal/mol), and guanine (24.4 kcal/mol) by turns. It could be deduced that the completely hydrolyzed Ru(η ⁶ -C₆H₅(CH₂)₂OH)Cl₂(DAPTA) compounds might preferentially bind to amino acids residues in vivo. In addition, to simulate the protein and DNA environment in vivo, a detailed investigation of the activation free energies for the substitution reactions in dependence of the dielectric constant ε (4, 24, and 78.39) was systematically performed as well. The calculated results demonstrated that the environmental effect had a little impact on these substitution reactions.     

Rapid evaluation of the binding energies between peptide amide and DNA base

The binding energies and the equilibrium hydrogen bond distances as well as the potential energy curves of 20 hydrogen‐bonded amide–base dimers are evaluated from the analytic potential energy function established in our laboratory recently. The analytic potential energy function is used to calculate the N? H···N, N? H···O?C, C? H···N, and C? H···O?C dipole–dipole attractive interaction energies and C?O···O?C, N? H···H? N, and N? H···H? C dipole–dipole repulsive interaction energies in the 20 dimers composed of DNA bases adenine, guanine, cytosine, or thymine and peptide amide. The calculation results show that the potential energy curves obtained from the analytic potential energy function are in good agreement with those obtained from MP2/6‐311+G** calculations by including the basis set superposition error (BSSE) correction. For all the 20 dimers, the analytic potential energy function yields the binding energies of the MP2/6‐311+G** with BSSE correction within the error limits of 0.50 kcal/mol for 19 dimers, only one difference is larger than 0.50 kcal/mol and the difference is only 0.61 kcal/mol. The analytic potential energy function produces the equilibrium hydrogen bond distances of the MP2/6‐311+G** with BSSE correction within the error limits of 0.030 Å for all the 20 dimers. The analytic potential energy function is further applied to four more complicated DNA base‐peptide amide systems involving amino acid side chain and β‐sheet. The values of the binding energies and equilibrium hydrogen bond distances obtained from the analytic potential energy function are also in good agreement with those obtained from MP2 calculations with the BSSE correction. These results demonstrate that the analytic potential energy function can be used to evaluate the binding energies in hydrogen‐bonded peptide amide–DNA base dimers quickly and accurately. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011