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.     

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.     

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 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.     

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.     

带电组氨酸侧链与DNA碱基间非键作用强度的理论研究

采用MP2方法和6-31+G(d,p)基组优化得到了带有一个正电荷的组氨酸侧链与4个DNA碱基间形成的18个氢键复合物的气相稳定结构, 从文献中获取了组氨酸侧链与DNA碱基间形成的12个堆积和T型复合物的气相稳定结构, 使用包含基组重叠误差(BSSE)校正的MP2方法和aug-cc-pVTZ基组及密度泛函理论M06-2X-D3方法和aug-cc-pVDZ基组计算了这些复合物的结合能. 研究结果表明, 包含BSSE校正的M06-2X-D3方法和aug-cc-pVDZ基组能够给出较准确的结合能; 气相条件下, 组氨酸侧链与同种DNA碱基间的离子氢键作用明显强于堆积作用和T型作用, 组氨酸侧链最易通过离子氢键与胞嘧啶C和鸟嘌呤G作用形成氢键复合物, 组氨酸与胞嘧啶C和鸟嘌呤G间的T型作用强于与腺嘌呤A和胸腺嘧啶T间的离子氢键作用; 水相条件下, 组氨酸侧链与同种DNA碱基间的离子氢键作用仍明显强于堆积作用和T型作用, 组氨酸侧链更易与胞嘧啶C和鸟嘌呤G相互作用形成氢键复合物, 但是最强的组氨酸侧链与胞嘧啶C间的T型作用明显弱于与腺嘌呤A和胸腺嘧啶T间的离子氢键作用, 说明水相条件下组氨酸侧链与DNA碱基间主要通过离子氢键作用形成氢键复合物.     

Spectral, magnetic, thermal, antimicrobial, and eukaryotic DNA studies on acetone [N-(3-hydroxy-2-naphthoyl)]hydrazone complexes

Abstract  

Acetone [N-(3-hydroxy-2-naphthoyl)] hydrazone (H₂AHNH) has been prepared and its structure confirmed by elemental analysis and ¹H NMR spectroscopy. It has been used to produce diverse complexes with Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and U(VI)O₂ ions. The complexes obtained have been investigated by thermal analysis, spectral studies (¹H NMR, IR, UV–visible, ESR), and magnetic measurements. IR spectra suggest that H₂AHNH acts as a bidentate ligand. The electronic spectra of the complexes and their magnetic moments provide information about geometries. The ESR spectra give evidence for the proposed structure and the bonding for some Cu(II) complexes. Thermal decomposition of the Ni(II) and Cu(II) complexes afforded metal oxides as final products. Kinetic data were obtained for each stage of thermal degradation of some of the complexes using the Coats–Redfern method. The formation of complexes in solution was studied pH-metrically and the order of their stability constants (log K) was found to be U(VI)O₂ > Cu(II) > Zn(II) > Ni(II) > Cd(II) > Co(II). Antimicrobial and eukaryotic DNA studies were carried out.     

A theoretical study of the interactions between N,N-dimethylformamide and xylenes

The ab initio and density functional (DFT) methods were performed on binary systems of N,N-dimethylformamide (DMF) with xylenes (o-, or m-, or p-xylene), and seven stable configurations were obtained with no imaginary frequencies. To obtain the interaction energies of these complexes, single-point energy calculations with basis set superposition error (BSSE) correction were carried out at B3LYP/6-31G* and MP2/6-31G* levels. The structures, Chelpg (charges from electrostatic potentials using a grid-based method) charge distribution and bond characteristics of the mentioned complexes were calculated. The results indicated the presence of double C–H···O hydrogen bonds between DMF and xylenes in these complexes and the interaction energies of hydrogen bonding between DMF and xylene systems decreased in the following sequence: DMF–o-xylene: a1 > DMF–m-xylene: b1 > DMF–p-xylene: c1.     

Spectral,magnetic, thermal,antimicrobial, and eukaryotic DNA studies on acetone [<Emphasis Type="Italic">N</Emphasis>-(3-hydroxy-2-naphthoyl)]hydrazone complexes

Abstract  Acetone [N-(3-hydroxy-2-naphthoyl)] hydrazone (H₂AHNH) has been prepared and its structure confirmed by elemental analysis and ¹H NMR spectroscopy. It has been used to produce diverse complexes with Co(II), Ni(II), Cu(II), Zn(II), Cd(II), and U(VI)O₂ ions. The complexes obtained have been investigated by thermal analysis, spectral studies (¹H NMR, IR, UV–visible, ESR), and magnetic measurements. IR spectra suggest that H₂AHNH acts as a bidentate ligand. The electronic spectra of the complexes and their magnetic moments provide information about geometries. The ESR spectra give evidence for the proposed structure and the bonding for some Cu(II) complexes. Thermal decomposition of the Ni(II) and Cu(II) complexes afforded metal oxides as final products. Kinetic data were obtained for each stage of thermal degradation of some of the complexes using the Coats–Redfern method. The formation of complexes in solution was studied pH-metrically and the order of their stability constants (log K) was found to be U(VI)O₂ > Cu(II) > Zn(II) > Ni(II) > Cd(II) > Co(II). Antimicrobial and eukaryotic DNA studies were carried out. Graphical abstract        

Ab initio and DFT theory studies of interaction of thymine with formaldehyde

In this article, the interaction of formaldehyde (FA) with thymine is theoretically investigated by computational chemistry methods. The optimization geometries and vibrational frequencies of FA, thymine and three complexes between thymine and FA have been calculated by using the density functional theory and ab initio methods at the B3LYP/6-311G(d, p) and MP2/6-311G(d, p) levels. The NBO and AIM methods are used to analyse interaction as well. Conformers (A), (B) and (C) are cyclic structures with C–H***O and N–H***O hydrogen bonds on a common plane. The corrected complex interaction energies of cyclic structures (A), (B) and (C) at MP2/6-311G(d, p) levels are −38.41, −26.94 and −26.01 kJ/mol, respectively. The order of stability is (A) > (B) > (C).     

Chromium‐metformin ternary complexes: Thermal,DNA interaction and Docking studies

Three chromium ternary complexes with metformin (met) as a primary ligand and bipyridine (bipy) or ortho‐phenylenediamine (opda) or ortho‐phenanthroline (phen) as secondary ligand were synthesized. These complexes [Cr (Cl)₂(Hmet)(bipy)]‐( 1 ), [Cr (Cl)₂(Hmet)(opda)]‐( 2 ) and [Cr (Cl)₂(Hmet)(phen)]‐( 3 ) were characterized by LC–MS, elemental analysis, molar conductance, thermal analysis, infrared spectroscopy, electronic spectroscopy. The geometrical structures have been found to be octahedral. Degradation pattern of the compounds is shown by thermal studies. The Kinetic parameters‐ energy of activation (E_a), enthalpy (ΔH), entropy (ΔS) and free energy changes (ΔG) have been determined by thermogravimetric data. Coats‐Redfern integration method with thirteen kinetic models was used to calculate the kinetic and thermodynamic parameters for the degradation of all the complexes. The stabilities of the complexes were obtained from their molecular orbital structures from which the quantum chemical parameters were calculated using the HOMO‐LUMO energies. UV–Visible absorption, fluorescence, and viscosity measurements have been conducted to assess the interaction of the complexes with CT DNA. The complexes showed absorption hyperchromism in its UV–Vis spectrum with DNA. The binding constants K_b from UV–Vis absorption studies were 3.1x10⁴, 4.4x10⁴, 5x10⁴ M^?1 for 1, 2, 3 respectively and Stern–Volmer quenching constants (K_sq) from fluorescence studies were 0.137, 0.532, 0.631 for 1, 2, 3 respectively. Finally, viscosity measurements revealed that the binding of the complexes with CT‐DNA could be surface binding, mainly due to groove binding. The activity of complexes towards DNA cleavage decrease in the order of 3 > 2 > 1.The light switching properties of the complexes were also evaluated. The complexes were docked in to B‐DNA sequence, 5′(D*AP*CP*CP*GP*AP*CP*GP*TP*CP*GP*GP*T)‐3′ retrieved from protein data bank (PDB ID: 423D), using Discovery Studio 2.1 software.     

A Comparative Study of Hydrogen Bonding Using Density Functional Theory

The hydrogen‐bond energies of water dimer and water‐formaldehyde complexes have been studied using density functional theory (DFT). Basis sets up to aug‐cc‐pVXZ (X=D, T, Q) were used. It was found that counterpoise corrected binding energies using the aug‐cc‐pVDZ basis set are very close to those predicted with the aug‐cc‐pVQZ set. Comparative studies using various DFT functionals on these two systems show that results from B3LYP, mPW1PW91 and PW91PW91 functionals are in better agreements with those predicted using high‐level ab initio methods. These functionals were applied to the study of hydrogen bonding between guanine (G) and cytosine (C), and between adenine (A) and thy mine (T) base pairs. With the aug‐cc‐pVDZ basis set, the predicted binding energies of base pairs are in good agreement with the most elaborate ab initio results.     

True stabilization energies for the optimal planar hydrogen-bonded and stacked structures of guanine...cytosine, adenine...thymine, and their 9- and 1-methyl derivatives: complete basis set calculations at the MP2 and CCSD(T) levels and comparison with experiment

Planar H-bonded and stacked structures of guanine...cytosine (G.C), adenine...thymine (A...T), 9-methylguanine...1-methylcytosine (mG...mC), and 9-methyladenine...1-methylthymine (mA...mT) were optimized at the RI-MP2 level using the TZVPP ([5s3p2d1f/3s2p1d]) basis set. Planar H-bonded structures of G...C, mG...mC, and A...T correspond to the Watson-Crick (WC) arrangement, in contrast to mA...mT for which the Hoogsteen (H) structure is found. Stabilization energies for all structures were determined as the sum of the complete basis set limit of MP2 energies and a (DeltaE(CCSD(T)) - DeltaE(MP2)) correction term evaluated with the cc-pVDZ(0.25,0.15) basis set. The complete basis set limit of MP2 energies was determined by two-point extrapolation using the aug-cc-pVXZ basis sets for X = D and T and X = T and Q. This procedure is required since the convergency of the MP2 interaction energy for the present complexes is rather slow, and it is thus important to include the extrapolation to the complete basis set limit. For the MP2/aug-cc-pVQZ level of theory, stabilization energies for all complexes studied are already very close to the complete basis set limit. The much cheaper D-->T extrapolation provided a complete basis set limit close (by less than 0.7 kcal/mol) to the more accurate T-->Q term, and the D-->T extrapolation can be recommended for evaluation of complete basis set limits of more extended complexes (e.g. larger motifs of DNA). The convergency of the (DeltaE(CCSD(T)) - DeltaE(MP2)) term is known to be faster than that of the MP2 or CCSD(T) correlation energy itself, and the cc-pVDZ(0.25,0.15) basis set provides reasonable values for planar H-bonded as well as stacked structures. Inclusion of the CCSD(T) correction is essential for obtaining reliable relative values for planar H-bonding and stacking interactions; neglecting the CCSD(T) correction results in very considerable errors between 2.5 and 3.4 kcal/mol. Final stabilization energies (kcal/mol) for the base pairs studied are very substantial (A...T WC, 15.4; mA...mT H, 16.3; A...T stacked, 11.6; mA...mT stacked, 13.1; G...C WC, 28.8; mG...mC WC, 28.5; G...C stacked, 16.9; mG...mC stacked, 18.0), much larger than published previously. On the basis of comparison with experimental data, we conclude that our values represent the lower boundary of the true stabilization energies. On the basis of error analysis, we expect the present H-bonding energies to be fairly close to the true values, while stacked energies are still expected to be about 10% too low. The stacking energy for the mG...mC pair is considerably lower than the respective H-bonding energy, but it is larger than the mA...mT H-bonding energy. This conclusion could significantly change the present view on the importance of specific H-bonding interactions and nonspecific stacking interactions in nature, for instance, in DNA. Present stabilization energies for H-bonding and stacking energies represent the most accurate and reliable values and can be considered as new reference data.     

The effect of methylation on the hydrogen-bonding and stacking interaction of nucleic acid bases

Methylated nucleosides play an important role in DNA/RNA function, and may affect republication by interrupting the base-pairing and base-stacking. In order to investigate the effect of methylation on the interaction between nucleic acid bases, this work presents the hydrogen-bonding and stacking interactions between 5-methylcytosine and guanine (G), cytosine (C) and G, 1-methyladenine and thymine (T), as well as adenine and T. Geometry optimization and potential energy surface scan have been performed for the involved complexes by MP2 calculations. The interaction energies, which were corrected for the basis-set superposition error by the full Boys–Bernardi counterpoise correction scheme, were used to evaluate the interaction intensity of these nucleic acid bases. The atoms in molecules theory and natural bond orbital analysis have been performed to study the hydrogen bonds in these complexes. The result shows that the methyl substitute contributes the stability to these complexes because it enhances either the hydrogen bonding or the staking interaction between nucleic acid bases studied.     

Factors determining the deriving force of DNA formation: geometrical differences of base pairs, dehydration of bases, and the arginine assisting

The mechanism of the fidelity synthesis of DNA associated with the process of dGTP combination to the DNA template was explored. The exclusion of water molecules from the hydrated DNA bases can amplify the energy difference between the correct and incorrect base pairs, but the effect of the water molecules on the Gibbs free energy of formation is dependent on the binding sites for the water molecules. The water detachment from the incoming dNTP is not the only factor but the first step for the successful replication of DNA. The second step is the selection of the DNA polymerase on the DNA base pair through the comparison between the correct DNA base and the incorrect DNA base. The bonding of the Arg668 with the incoming dNTP can enlarge the Gibbs free energies of formation of the base pairs, especially the correct base pairs, thus increasing the driving force of DNA formation. When the DNA base of the primer terminus is correct, the extension of the guanine and the adenine is quicker than that of the cytosine and the thymine because of the hydrogen bonding fork formation of Arg668 with the minor groove of the primer terminus and the ring oxygen of the deoxyribose moiety of the incoming dNTP. Because of the geometry differences of the incorrect base pairs with the correct base pairs, the effect from the DNA polymerase is smaller on the incorrect base pair than on the correct base pair, and the extension of a mispair is slower than that of a correct base pair. This decreases the extension rate of the base pair and thus allows proofreading exonuclease activity to excise the incorrect base pair. Arg668 cannot prevent the extension of the GT mispair, as well as the GC correct base pair, and GA and GG mispairs. This may be attributed to the small geometry difference between the GT base pair and the correct AT base pair.     

Binding interactions of mixed ligand copper(II) amino acid Schiff base complexes with biological targets: Spectroscopic evaluation and molecular docking

Three mixed ligand copper(II) complexes [Cu(o ‐vanillin‐l ‐tryptophan Schiff base)(diimine)] (diimine =2,2′‐bipyridine ( 1 ), 1,10‐phenanthroline ( 2 ) and 5,6‐dimethyl‐1,10‐phenanthroline( 3 )) were synthesized and characterized using analytical and spectral methods. The molecular structures of 1 – 3 were optimized using density functional theory (DFT) at B3LYP/LanL2DZ levels in the gas phase. Spectral and DFT studies suggest a distorted square pyramidal geometry around the copper ion. Binding interactions of 1 – 3 with calf thymus DNA and bovine serum albumin protein were studied using UV–visible and fluorescence spectroscopies, viscometric titrations and cyclic voltammetry and also using molecular docking analysis. Studies of the binding of the complexes with calf thymus DNA reveal intercalation, which is supported by molecular docking simulation. The DNA cleavage nature of 1 – 3 with pUC19 DNA shows that the complexes can cleave DNA without any external agents, and the efficiency follows the order 1  >  3  >  2 . Synchronous and three‐dimensional fluorescence spectral studies suggest that the secondary structures of the protein are altered by the complexes. Antioxidant studies reveal that the complexes have significant radical scavenging activity against DPPH. In vitro cytotoxic activity of the complexes was evaluated against breast cancer cells (MCF‐7), revealing that complex 2 exhibits higher cytotoxicity than the other complexes. Nuclear chromatin condensation and fragmentation were observed with DAPI staining assay. The mitochondrial membrane potential damage was studied by FITC staining assay. Flow cytometric analysis suggests that all the metal complexes induce cell apoptosis.     

Biocomplementary interaction behavior in DNA‐like and RNA‐like polymers

A series of nucleobased polymers and copolymers were synthesized through atom transfer radical polymerization (ATRP). Biocomplementary DNA‐ and RNA‐like supramolecular complexes are formed in dilute DMSO solution through nucleobase recognition. ¹H NMR titration studies of these complexes in CDCl₃ indicated that thymine‐adenine (T‐A) and uracil‐adenine (U‐A) complexes form rapidly on the NMR time scale with high association constants (up to 534 and 671 M^–1, respectively) and result in significant T_g increase. WAXD and differential scanning calorimetry analyzes in the bulk state indicate the presence of highly physical cross‐linked structures and provide further details into the nature of the self‐assembly of these systems. Furthermore, this study is of discussion on the difference in the hydrogen bond strength between T‐A and U‐A base pairs within polymer systems, indicating that the strength of hydrogen bonds in RNA U‐A pairs is stronger than that in DNA T‐A base pairs. © 2009 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 47: 6388–6395, 2009     

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.     

Structure–affinity relationships for the binding of actinomycin D to DNA

Molecular models of the complexes between actinomycin D and 14 different DNA hexamers were built based on the X-ray crystal structure of the actinomycin–d(GAAGCTTC)2 complex. The DNA sequences included the canonical GpC binding step flanked by different base pairs, nonclassical binding sites such as GpG and GpT, and sites containing 2,6-diamino- purine. A good correlation was found between the intermolecular interaction energies calculated for the refined complexes and the relative preferences of actinomycin binding to standard and modified DNA. A detailed energy decomposition into van der Waals and electrostatic components for the interactions between the DNA base pairs and either the chromophore or the peptidic part of the antibiotic was performed for each complex. The resulting energy matrix was then subjected to principal component analysis, which showed that actinomycin D discriminates among different DNA sequences by an interplay of hydrogen bonding and stacking interactions. The structure–affinity relationships for this important antitumor drug are thus rationalized and may be used to advantage in the design of novel sequence-specific DNA-binding agents.