Thymine Complexes Research Articles

High-resolution electron spectroscopy and structures of lithium-nucleobase (adenine, uracil, and thymine) complexes

Li complexes of adenine, uracil, and thymine were produced by laser vaporization of rods made of Li and nucleobase powders in a metal-cluster beam source and studied by pulsed-field-ionization zero-electron-kinetic-energy (ZEKE) spectroscopy and density functional theory calculations. The ZEKE measurements determined the adiabatic ionization energies of the three neutral complexes and frequencies of several vibrational modes for the metal-adenine and -uracil ions. The measured spectra were compared with spectral simulations to determine the preferred metal binding sites. For adenine, the most stable structure is formed by Li/Li(+) bidentately binding to both the N7 atom of the imidazole ring and the NH(2) group of the pyrimidine ring. For uracil and thymine, the ideal site for Li/Li(+) coordination is the O4 atom. Although it has only a small effect on the geometries of uracil and thymine, lithium coordination forces the rotation of the NH(2) group out of the adenine plane. The adiabatic ionization energies of the three complexes follow the trend of uracil (33910+/-5 cm(-1))>thymine (33386+/-5 cm(-1))>adenine (32240+/-5 cm(-1)), whereas their metal-ligand bond dissociation energies are about the same, (92-97) +/-6 kJ mol(-1). For all three complexes, the neutral bond energies are smaller than those of the corresponding ions due to a weaker electrostatic interaction and stronger electron repulsion.

Ion-induced DNAzyme switches

The activities of Mg(2+)-dependent DNAzymes are reversibly switched by ion stimuli using the thymine-Hg(2+)-thymine complexes or cytosine-Ag(+)-cytosine complexes.

DFT study on the intermolecular interactions between Au n ( n = 2–4) and thymine

The interaction between small gold clusters and thymine was studied using density functional method (DFT). Geometries of neutral thymine with Au n ( n = 2–4) clusters were optimized using the B3LYP method. The 6-31G+(d,p) basis set was used for thymine and the Stuttgart/Dresden effective core potential (ECP) basis set SDD was employed for the gold atom. Structural parameters and energy properties were discussed for the optimized complexes stabilized with the Au O anchoring bond and the nonconventional Au···H N hydrogen bond. The calculated interacting energy results show that the binding of Au n is the most strong at thymine (H1,O2) site, whereas its binding at (H3,O2) displays relatively weaker stability. Furthermore, analysis of the charge distributions of the optimized complexes by using the natural bond orbital analysis indicates charge is transferred from the lone pair of oxygen in thymine to the n* and σ* orbitals of Au during the interaction. The calculated second-order perturbation stabilization energies show that the Au O anchoring bond plays an important role in forming the Au n ·Thymine complexes.

A novel electrochemical method to detect mercury (II) ions

A novel and sensitive electrochemical method for determination of mercury (II) ions (Hg 2+) based on the formation of thymine–Hg 2+–thymine complexes and gold nanoparticle-mediated signal amplification is reported. Two 5′ end thiolated complementary oligonucleotides containing six strategically placed thymine–thymine mistakes were introduced in this work. One of the two oligonucleotides was immobilized on a gold electrode and the other one on gold nanoparticles (AuNPs). Due to six thymine–thymine mistakes the two oligonucleotides were not able to be hybridized, so AuNPs could not be immobilized onto the electrode surface after the electrode was immersed in the DNA–AuNPs solution. However, if Hg 2+ existed, T–Hg 2+–T complexes could be formed and AuNPs could be immobilized onto the electrode surface. Meanwhile, large numbers of [Ru(NH 3) 6] 3+ molecules as electrochemical species could be localized onto the electrode surface. The Hg 2+ detection limit of this assay could be as low as 10 nM, which is the US Environmental Protection Agency (EPA) limit of Hg 2+ for drinkable water. This method is proven to be simple, convenient, high sensitive and selective.

Convergence of the CCSD(T) Correction Term for the Stacked Complex Methyl Adenine-Methyl Thymine: Comparison with Lower-Cost Alternatives.

We have performed large-scale calculations for the interaction energy of the stacked methyl adenine-methyl thymine complex at the CCSD(T)/aug-ccpVXZ (X = D,T) levels. The results can serve as benchmarks for the evaluation of two methods, MP2.5, introduced recently, and the widely used ΔCCSD(T) correction defined as the difference between the CCSD(T) and MP2 energies. Our results confirm that the ΔCCSD(T) correction converges much faster toward the complete basis set (CBS) limit than toward the MP2 or CCSD(T) energies. This justifies approximating the CBS energy by adding the ΔCCSD(T) correction calculated with a modest basis set to a large basis MP2 energy. The fast convergence of the ΔCCSD(T) correction is not obvious, as the individual CCSD and (T) contributions converge less rapidly than their sum. The MP2.5 method performs very well for this system, with results very close to CCSD(T). It is conjectured that using a ΔMP2.5 correction, defined analogously to ΔCCSD(T), with large basis sets may yield more reliable nonbonded interaction energies than using ΔCCSD(T) with a smaller basis set. This would result in important computational savings as the MP3 scales computationally much less steep than CCSD(T), although higher than SCS-MP2, a similar approximation.

Thermal decomposition study on mixed ligand thymine complexes of divalent nickel(II) with dianions of some dicarboxylic acids

Abstract Thermal decomposition of mixed ligand thymine (2,4-dihydroxy-5-methylpyrimidine) complexes of divalent Ni(II) with aspartate, glutamate and ADA (N-2-acetamido)iminodiacetate dianions was monitored by TG, DTG and DTA analysis in static atmosphere of air. The decomposition course and steps of complexes [Ni(C5H6N2O2)(C4H5NO4)2−(H2O)2]·H2O, [Ni(C5H6N2O2)(C5H7NO4)2−(H2O)2]·H2O and [Ni(C5H6N2O2)(C6H8N2O5)2−(H2O)2]·1.5H2O were analyzed. The final decomposition products are found to be the corresponding metal oxides. The kinetic parameters namely, activation energy (E*), enthalpy (ΔH*), entropy (ΔS*) and free energy change of decomposition (ΔG*) are calculated from the TG curves using Coats–Redfern and Horowitz–Metzger equations. The stability order found for these complexes follows the trend aspartate > ADA > glutamate.

Interaction of Adenine Adducts with Thymine: A Computational Study

The existence of DNA adducts bring the danger of carcinogenesis because of mispairing with normal DNA bases. 1,N6-ethenoadenine adducts (epsilonA) and 1,N6-ethanoadenine adducts (EA) have been considered as DNA adducts to study the interaction with thymine, as DNA base. Several different stable conformers for each type of adenine adduct with thymine, [epsilonA(1)-T(I), epsilonA(2)-T(I), epsilonA(3)-T(I) and EA(1)-T(I), EA(2)-T(I), EA(3)-T(I)] and [epsilonA(1)-T(II), epsilonA(2)-T(II), epsilonA(3)-T(II) and EA(1)-T(II), EA(2)-T(II), EA(3)-T(II)], have been considered with regard to their interactions. The differences in their geometrical structures, energetic properties, and hydrogen-bonding strengths have also been compared with Watson-Crick adenine-thymine base pair (A-T). Single-point energy calculations at MP2/6-311++G** levels on B3LYP/6-31+G* optimized geometries have also been carried out to better estimate the hydrogen-bonding strengths. The basis set superposition error corrected hydrogen-bonding strength sequence at MP2/6-311++G**//B3LYP/6-31+G* for the most stable complexes is found to be EA(2)-T(I) (15.30 kcal/mol) > EA(1)-T(II) (14.98 kcal/mol) > EA(3)-T(II) (14.68 kcal/mol) > epsilonA(2)-T(I) (14.54 kcal/mol) > epsilonA(3)-T(II) (14.22 kcal/mol) > epsilonA(3)-T(II) (13.64 kcal/mol) > A-T (13.62 kcal/mol). The calculated reaction enthalpy value for epsilonA(2)-T(I) is 10.05 kcal/mol, which is the highest among the etheno adduct-thymine complexes and about 1.55 kcal/mol more than those obtained for Watson-Crick A-T base pair and the reaction enthalpy value for EA(1)- T(II) is 10.22 kcal/mol, which is highest among the ethano addcut-thymine complexes and about 1.72 kcal/mol more than those obtained for Watson-Crick A-T base pair. The aim of this research is to provide fundamental understanding of adenine adduct and thymine interaction at the molecular level and to aid in future experimental studies toward finding the possible cause of DNA damage.

Reaction force and electron localization function analysis of the metal chelation process in Mg(II)–thymine complex

The reaction force and the electron localization function (ELF) have been used to investigate the mechanism that promote the metal chelation in the formation of the Mg(II)–thymine enol bi-coordinated complex. Energy and reaction force profiles together with ELF isosurfaces reveal that the intramolecular hydrogen transfer activates the metal chelation process through a concentration of electron population in the monosynaptic valence basin associated to the hydrogen donor atom. Moreover, the ELF analysis suggest that the metal chelation proceeds via electrostatic interaction and the new Mg–N bond in the product complex being of ionic character.

Antiproliferative activity of Pt(II) and Pd(II) phosphine complexes with thymine and thymidine

Oxidative addition reactions between [M(PPh 3) 4] (M = Pt and Pd) and N1-methylthymine (t)/3′,5′-di- O-acetylthymidine (T) were carried out to give [M(II)(PPh 3) 2Cl t (or T)] complexes, in which the metal is coordinated to the N3 of the base. All complexes were characterized by spectroscopic analyses (IR, NMR) and Fast Atom Bombardment mass spectrometry (FAB-MS); X-ray data for the thymine complexes and elemental analysis for the thymidine complexes are reported. The antiproliferative activity of the complexes was tested on human chronic myelogenous leukaemia K562 cells. Arrested polymerase-chain reaction analysis was carried on to correlate antiproliferative activity and inhibition of DNA replication. All Pd and Pt complexes exhibit antiproliferative activity, Pd complexes resulting always more active than Pt complexes. Arrested PCR data are strongly in agreement with the effects on cell growth, suggesting that inhibition of the DNA replication by the synthesized compounds is the major basis for their in vitro antiproliferative activity.

Microsolvation effects on the electron capturing ability of thymine: Thymine-water clusters

The effects of solvation on the stability of thymine and its negative ion have been investigated by explicitly considering the structures of complexes of thymine with up to five water molecules and the respective anions at the B3LYP/DZP++ level of theory. The vertical detachment energy of thymine was predicted to increase gradually with the hydration number, consistent with experimental observations from a photodetachment-photoelectron spectroscopy study J. Schiedt et al., [Chem. Phys. 239, 511 (1998)]. The adiabatic electron affinity of thymine was also found to increase with the hydration number, which implies that while the conventional valence anion of thymine is only marginally bound in the gas phase, it may form a stable anion in aqueous solution.

Potential Energy Surfaces of the Microhydrated Guanine⋅⋅⋅Cytosine Base Pair and its Methylated Analogue

A complete scan of the potential and free-energy surfaces of monohydrated and dihydrated guanine...cytosine and 9-methylguanine...1-methylcytosine base pairs was realized by the molecular dynamics/quenching technique using the force field of Cornell et al. implemented in the AMBER7 program. The most stable and populated structures localized were further fully reoptimized at the correlated ab initio level employing the resolution of identity Møller-Plesset method with a large basis set. A systematic study of microhydration of these systems using a high-level correlated ab initio approach is presented for the first time. The different behavior of guanine...cytosine and adenine...thymine complexes is also discussed. These studies of nucleic acid base pairs are important for finding binding sites of water molecules around bases and for better understanding of the influence of the solvent on the stability of the structure of DNA.

Nanostructuring organo-silicas: combination of intermolecular interactions and molecular recognition properties to generate self-assembled hybrids with phenylene or adenine⋯thymine bridging units

Owing to hydrophobic interactions, silyl linkers containing long alkylene chains allowed the synthesis of self-organised hybrids. Lamellar organo-silicas with phenylene or a hydrogen-bonded adenine⋯thymine complex as the bridging units are reported.

Excess Electron Attachment Induces Barrier-Free Proton Transfer in Anionic Complexes of Thymine and Uracil with Formic Acid

The anionic complexes of formic acid with uracil and thymine reveal broad features in photoelectron spectroscopy (PES) experiments with maxima at 1.7 and 1.1 eV, respectively. The results of quantum chemical calculations suggest that electron vertical detachment energies (VDE) of 1.6−1.9 eV correspond to anionic structures in which a proton has been transferred from the carboxylic group of the formic acid to the O8 atom of uracil or thymine. Smaller values of VDE (0.8 to 1.3 eV) correspond to chemically untransformed complexes, in which anionic uracil or thymine interacts through two hydrogen bonds with the carboxylic group of the intact formic acid. The recorded spectra and the results of quantum chemical calculations suggest that both nucleic acid bases undergo barrier-free proton transfer in anionic complexes with formic acid. The difference in experimental spectra of UF- and TF- provides an indication that the methyl group of thymine could make a difference in the intermolecular proton transfer.

Metabolic and Pharmacological Characteristics of the Bicyclic Nucleoside Analogues (BCNAs) as Highly Selective Inhibitors of Varicella—Zoster Virus (VZV)

AbstractFor Abstract see ChemInform Abstract in Full Text.

Hydrogen-bonded binding of DNA pyrimidine bases to copper(ii) cations co-ordinated by polymethylene linked bis(amidino-O-alkylurea) ligands to form supramolecular architectures

Co-crystallisation of 1,2-bis(amidino-O-methylurea)ethanecopper(II) tetrafluoroborate [CuL][BF4]2 with cytosine or thymine leads to compounds with 1 ∶ 2 or 1 ∶ 1 molar ratios of [CuL]2+ to DNA pyrimidine base, respectively. As both the DNA bases and the cation, which comprises a copper(II) centre co-ordinated by a tetradentate 1,2-bis(amidino-O-methylurea)ethane ligand, are planar species with considerable hydrogen-bonding potential, both products adopt 2-D sheet architectures. A structural building block common to both compounds comprises a pair of cations linked through pairs of DNA bases by diverse hydrogen-bonded contacts. In the cytosine compound, the building blocks are linked by pairs of DNA bases to form a 1-D linear chain with 1 ∶ 2 [CuL]2+ ∶ cytosine molar ratio; in the thymine compound, the building blocks are linked by pairs of water molecules and tetrafluoroborate anions to generate a 1-D linear chain with 1 ∶ 1 [CuL]2+ ∶ thymine molar ratio. Tetrafluoroborate-mediated hydrogen-bonded assemblies serve to connect the chains into sheets. The stacking of the sheets also involves tetrafluoroborate-mediated hydrogen-bonded assemblies as well as very weak co-ordinate Cu⋯O interactions for the cytosine complex and O–H⋯F water–tetrafluoroborate hydrogen-bonded contacts for the thymine complex.

Spectral, thermal and electrical properties of some new azo complexes

Cobalt(II), nickel(II) and copper(II) acetates react with thymine compound (H 2L) to form complexes having the general formula [MH 2L(OAC) 2(H 2O) 2] nH 2O. However, the interaction of iron(III) chloride with thymine in acetic acid–water medium yields a new complex of the type [FeH 2L(OAC) 2H 2O]OAC.H 2O. All the thymine complexes have been characterized by elemental analyses, spectral and magnetic studies where thymine acts as a neutral ligand and the acetate ion behaves as a strong nucleophile during complexation. 6-aryl and thiazolylazo thymine compounds and their metal complexes were synthesized and characterized where the ligands act as a bidentate dibasic. The azo group is not involved in the structure. Thermal decomposition studies of the azo complexes were explained to give more information on the structure of the investigated materials. The effect of some transition metal cations such as Co II, Ni II and Cu II on the electrical behaviour of 6-(2-thiazolylazo)thymine compound is studied. The data obtained obeyed the relation σ= σ° exp (− E/2 kT) over the temperature range 30–150°C. The observed conductivities of the different complexes follow the order Co<Ni<Cu. It is clear that this trend is depending on the decreasing of the ionic radii and the increasing stability of metal complexes. The calculated mobility of charge carriers is ranged from 10 −5 to 10 −9cm 2/V s suggesting that the conduction of the studied complexes takes place by hopping mechanism.

Modeling of the Hydration Shell of Uracil and Thymine

The molecular geometry of complexes of uracil and thymine with 11 water molecules was calculated using the density functional theory with the B3LYP functional. The standard 6-31G(d) basis set has been employed. It was found that the arrangement of water molecules forming a locked chain around the nucleobases significantly differs for uracil and thymine. The presence of a methyl group in thymine results in strong non-planarity of the hydrated shell. The existence of C-H...O hydrogen bonds between the water molecules and the hydrophobic part of the nucleobases is established. Interactions with water molecules cause some changes in the geometry of uracil and thymine which can be explained by the contribution of a zwitter-ionic dihydroxy resonance form into the total structure of the molecules.

Hydration at the TD Damaged Site of DNA and its Role in the Formation of Complex with T4 Endonuclease V

An analysis of the distribution of water around DNA surface focusing on the role of the distribution of water molecules in the proper recognition of damaged site by repair enzyme T4 Endonuclease V was performed. The native DNA dodecamer, dodecamer with the thymine dimer (TD) and complex of DNA and part of repair enzyme T4 Endonuclease V were examined throughout the 500 ps of molecular dynamics simulation. During simulation the number of water molecules close to the DNA atoms and the residence time were calculated. There is an increase in number of water molecules lying in the close vicinity to TD if compared with those lying close to two native thymines (TT). Densely populated area with water molecules around TD is one of the factors detected by enzyme during scanning process. The residence time was found higher for molecule of the complex and the six water molecules were found occupying the stabile positions between the TD and catalytic center close to atoms P, C3′ and N3. These molecules originate water mediated hydrogen bond network that contribute to the stability of complex required for the onset of repair process.

Structural Effects on the Stability of Some Hydrogen‐Bonded Complexes with Nucleobases

The effect that additional groups flanking the hydrogen bond donor/acceptor arrays have on the association constants (Ka) of complexes of chloroform-soluble thymine and adenine derivatives has been investigated by NMR shift titration. Constants for thymine and 2,6-diaminoacyl pyridine derivatives, in which the acyl group bears either (CH2)nR or some other substituent, vary greatly. The peak value of Ka = 1130 M–1 occurs for n = 2 and R = phenyl. Computer modeling with CHARMm suggests that this is due to a weak additional stabilization by a C–H-π interaction; in line with this the complex shows small upfield NMR shifts for the terminal methyl groups. Four other receptors were prepared which could, in principle, form hydrogen bonds with all donor/acceptor sites of adenine; NMR titrations, however, showed very low complexation energies, probably due to deviations from the ideal hydrogen bond geometry necessary to form stronger complexes.

In-situ infrared spectroscopic studies of thymine adsorption on a Au(111) electrode

We have investigated the adsorption of thymine on Au(111) with in-situ infrared spectroscopy. Using IR spectroscopy we have been able to probe the structure and bonding of the ‘chemisorbed’ thymine phase. IR bands in the 1800–1550 cm−1 region, which have a major contribution from stretching vibrations of the carbonyl groups of thymine, exhibit large spectral shifts between thymine in aqueous solution and the chemisorbed phase. By contrast, ‘physisorbed’ thymine shows no IR bands in the spectral region studied, which is consistent with a flat-lying adsorbate. In-situ IR spectroscopy provides compelling evidence for the orientational change of adsorbed thymine occurring concomitantly with the most pronounced anodic current peak in the voltammogram. We have compared the in-situ IR spectra for chemisorbed thymine with IR spectra of metal co-ordination complexes of thymine and uracil. These comparisons provide evidence that chemisorbed thymine bonds to the Au(111) surface through both carbonyl functionalities and a deprotonated N3.