Understanding the mechanisms underlying the assembly of nucleobases is a great challenge. The ability to deeply understand how nucleobases interact with themselves as well as with other molecules will allow us to gain...Understanding the mechanisms underlying the assembly of nucleobases is a great challenge. The ability to deeply understand how nucleobases interact with themselves as well as with other molecules will allow us to gain valuable insights into how we might be able to harness these interesting biological molecules to construct complex nanostructures and materials. Uracil and thymine derivatives have been reported for use in biological applications and in self-assembling triple hydrogen bonded systems. Either uracil or thymine possesses three binding sites （Site 1, Site 2, and Site 3） that can induce strong directional N-H...O=C hydrogen bonding interaction. In this paper, theoretical calculations are carded out on the structural features and binding energies of hydrogen-bonded dimers and trimers formed by uracil and thymine bases. We find that the hydrogen bonds formed through Site 1 are the strongest, those formed through Site 3 are next, while those formed through Site 2 are the weakest. The atoms in molecules analysis show that the electron densities at the bond critical points and the corresponding Laplacians have greater values for those hydrogen bonds formed through Site 1 than through Site 2. All these results indicate that a uracil （or thymine） would interact with another uracil or thymine most likely through Site 1 and least likely through Site 2. We also find that a simple summation rule roughly exists for the binding energies in these dimers and trimers.展开更多
Pentachlorophenol, a widespread environmental pollutant that is possibly carcinogenic to humans, is metabolically oxidized to tetrachloroquinone （TCBQ） which can result in DNA damage. We have investigated the photoc...Pentachlorophenol, a widespread environmental pollutant that is possibly carcinogenic to humans, is metabolically oxidized to tetrachloroquinone （TCBQ） which can result in DNA damage. We have investigated the photochemical reaction dynamics of TCBQ with two pyrimidine type nucleobases （thymine and uracil） upon UVA （355 ran） excitation using the technique of nanosecond time-resolved laser flash photolysis. It has been found that 355 nm excitation populates TCBQ molecules to their triplet state 3TCBQ＊, which are highly reactive towards thymine or uracil and undergo two parallel reactions, the hydrogen abstraction and electron transfer, leading to the observed photoproducts of TCBQH. and TCBQ.- in transient absorption spectra. The concomitantly produced nucleobase radicals and radical cations are expected to induce a series of oxidative or strand cleavage damage to DNA afterwards. By characterizing the photochemical hydrogen abstraction and electron transfer reactions, our results provide potentially important molecular reaction mechanisms for understanding the carcinogenic effects of pentachlorophenol and its metabolites TCBQ.展开更多
Photon-induced dissociation pathways of thymine are investigated with vacuum ultraviolet photoionization mass spectrometry and theoretical calculations. The photoionization mass spectra of thymine at different photon ...Photon-induced dissociation pathways of thymine are investigated with vacuum ultraviolet photoionization mass spectrometry and theoretical calculations. The photoionization mass spectra of thymine at different photon energy are measured and presented. By selecting suitable photon energy, exclusively molecular ion m/z=126 is obtained. At photon energy of 12.0 eV, the major ionic fragments at m/z=98, 97, 84, 83, 70, and 55 are obtained, which are assigned to C4H6N2O＋, C4H5N2O＋, C3H4N2O＋ （or C4H6NO＋）, C4H5NO＋, C2NO2＋, and C3H5N＋, respectively. With help of theoretical calculations, the detailed dissociation pathways of thymine at low energy are well established.展开更多
The reaction mechanisms of carcinogenic methylating agent iodomethane （MeI） with keto and enol tautomers of thymine （K- and E-thymine） were studied by using the B3LYP/6-311＋G （d, p） method in water phase. The s...The reaction mechanisms of carcinogenic methylating agent iodomethane （MeI） with keto and enol tautomers of thymine （K- and E-thymine） were studied by using the B3LYP/6-311＋G （d, p） method in water phase. The solvent effects were examined using the polarizable continuum model （PCM）. Specifically, PCM single-point calculations at the same level of theory were performed in acetone and CCl4 that represent a range in nonpolarity. The calculated results show that the reaction of K-thymine with MeI is a two-step mechanism, whereas that of E-thymine is a one-step mechanism. Our calculations reveal that K-thymine is appreciably more stable than the enol form in the water phase or in the two solvents. The K- and E-form reaction barriers are 135.6 and 222.1 kJ/mol, respectively in water phase. These findings indicate that the reactions mentioned above could not occur efficiently in biological media in the absence of catalyst. Our conclusions are in agreement with the previous studies on the reactions of guanine with methyl chloride and methyl bromide.展开更多
The synthesis of peptoid nucleic acid bearing thymine as nucleobase has been achieved. This modified oligonucleotide showed good hybridization with DNA.
A series of novel mono- and di-terpyridine derivatives with purinyl and pyrimidyl group were obtained from the reaction of 4′-p- bromomethylphenyl-2,2′：6,2″-terpyridine with 6-mercaptopurine, 2,6-dimercaptopurine ...A series of novel mono- and di-terpyridine derivatives with purinyl and pyrimidyl group were obtained from the reaction of 4′-p- bromomethylphenyl-2,2′：6,2″-terpyridine with 6-mercaptopurine, 2,6-dimercaptopurine and thymine, respectively. The active hydrogens on these alkaloids could be abstracted stepwise using different bases, which made the addition controllable.展开更多
The interacting patterns and mechanism of the catechin and thymine have been investigated with the density functional theory Becke＇s three-parameter nonlocal exchange functional and the Lee, Yang, and Parr nonlocal c...The interacting patterns and mechanism of the catechin and thymine have been investigated with the density functional theory Becke＇s three-parameter nonlocal exchange functional and the Lee, Yang, and Parr nonlocal correlation functional （B3LYP） method by 6-31＋G＊ basis set. Thirteen stable structures for the catechin-thymine complexes have been found which form two hydrogen bonds at least. The vibrational frequencies are also studied at the same level to analyze these complexes. The results indicated that catechin interacted with thynfine by three different hydrogen bonds as N-H…O, C-H…O, O-H…O and the complexes are mainly stabilized by the hydrogen bonding interactions. Theories of atoms in molecules and natural bond orbital have been adopted to investigate the hydrogen bonds involved in all systems. The interaction energies of all complexes have been corrected for basis set superposition error, which are from -18.15 k J/mol to -32.99 kJ/mol. The results showed that the hydrogen bonding contribute to the interaction energies dominantly. The corresponding bonds stretching motions in all complexes are red-shifted relative to that of the inonomer, which is in agreement with experimental results.展开更多
The crystal structure of the title compound （C34H47NTO9, Mr = 697.79） has been determined by single-crystal X-ray diffraction. The crystal belongs to monoclinic, space group P21 with a = 9.000（8）, b = 11.360（10）...The crystal structure of the title compound （C34H47NTO9, Mr = 697.79） has been determined by single-crystal X-ray diffraction. The crystal belongs to monoclinic, space group P21 with a = 9.000（8）, b = 11.360（10）, c = 17.841（15.）/k, β = 97.083（14）°, V = 1810（3）A^3, Z = 2, F（000） = 744, D,.= 1.280 g/cm^3,/t = 0.094 mm^-1, the final R = 0.0721 and wR = 0.1942 for 2479 observed reflections with I 〉 2σ（I）. The two methyl groups attached to the cyclobutane ring are cis oriented. An intramolecular hydrogen bond （N（6）-H（6）…O（8）） introduces rigidity into the title molecule and the crystal structure is stabilized by intermolecular N-H…O hydrogen bonds.展开更多
The main purpose of this study is a better comprehension of the non-bonded interaction between an anticancer drug apalutamide and deoxyribonucleic acid(DNA).In the prese nt work,the in teraction between an ticancer dr...The main purpose of this study is a better comprehension of the non-bonded interaction between an anticancer drug apalutamide and deoxyribonucleic acid(DNA).In the prese nt work,the in teraction between an ticancer drug apalutamide and one of the DNA bases called 2,-deoxythymidine 5,-monophosphate(thymine)by Density Functional Theory(DFT)calculations in the solvent water has been investigated for the first time.The non-bonded interaction effects of the molecule apalutamide with thymine on the electronic properties,chemical shift tensors and natural charges have been also detected.The natural bond orbital(NBO)analysis was performed for determining the role of electron donor and acceptor of the molecules apalutamide and thymine at the complex thymine/apalutamide.Both Electron location function(ELF),localized orbital locator(LOL)and quantum theory of atoms in molecules(QTAIM)analysis were carried out in order to determine the chemical bond nature in the investigated compounds.The values of ELF and LOL parameters for the selected bonds are small,which confirms the non-covalent character of these bonds in nature.The electronic spectra of the apalutamide drug,thymine and complex thymine/apalutamide in solvent water were calculated by Time Dependent Density Functional Theory(TD-DFT)for the investigation of interaction effect;Non-bonded interaction between the compound apalutamide and thymine has changed the value of λmax.展开更多
The photolysis of thymine in phosphate-buffered saline (PBS, pH 8.0) under the irradiation of medium pressure mercury lamp (MPML) produces a novel compound C5H7N2O6P. The composition and structure of the compound hav...The photolysis of thymine in phosphate-buffered saline (PBS, pH 8.0) under the irradiation of medium pressure mercury lamp (MPML) produces a novel compound C5H7N2O6P. The composition and structure of the compound have been identified by elemental analysis, EI-MS, UV, IR, 1H, 13C, 31P-NMR.展开更多
As a well known DNA photolesion product, the special UV induced pyrimidine dimmer called spore photoproduct （SP）, has aroused strong research interests. The SP formation was reported solely between two adjacent thym...As a well known DNA photolesion product, the special UV induced pyrimidine dimmer called spore photoproduct （SP）, has aroused strong research interests. The SP formation was reported solely between two adjacent thymidine residues. It remains unclear in pervious experimental observations why there is an absence of the cytosine-derived SP-like photoprod- uct formation at the cytosine containing DNA strand, although the cytosine residue holds great similarity to thymine in terms of molecular structure. From a theoretical perspec- tive, we have explored this issue in this work by means of density functional theory at the B3LYP/6-311＋＋G（d,p） //B3LYP/6-31G（d,p） level for the DNA dinucleotide fragment, cy- tosine phosphate thymine （CpT）. Key factors blocking the formation of the SP-like product between two adjacent cytosine and thymidine residues are revealed. Instead of undergoing photochemical SP reaction, a photophysical deactivation pathway back to the ground state turns out to be favorable for the CpT dinucleotide fragment.展开更多
A new type of HPLC stationary phase containing thymine derivative was successfully prepared.It was found to give selective separation of nucleic acid bases and several purine derivatives,such as caffeine and theophyll...A new type of HPLC stationary phase containing thymine derivative was successfully prepared.It was found to give selective separation of nucleic acid bases and several purine derivatives,such as caffeine and theophylline.The retention behaviour and elution order of the solutes were interpreted in terms of molecular structure.展开更多
Objective: To observe the effect of anciclovir (ACV) treatment on tumors induced by inoculation of TK gene-transfected human pulmonary adenocarcinoma A549 cells in nude mice. Methods: A recombinant plasmid containing ...Objective: To observe the effect of anciclovir (ACV) treatment on tumors induced by inoculation of TK gene-transfected human pulmonary adenocarcinoma A549 cells in nude mice. Methods: A recombinant plasmid containing TK gene was constructed and transfected into A549 cells by electroporation. The sensitivity of the transgenic cells (A549-TK) to ACV was examined by MTT assay in vitro and for in vivo observation, inoculation of A549-TK and A-549 cells into nude mice was separately performed to induce tumor growth, the response of which to ACV treatment was observed, and the tumor tissues were pathologically examined. Results: A recombinant plasmid containing TK gene was successfully constructed and transfected into A549 cells. The sensitivity of A549-TK cells to ACV was 43 times higher than that of A549 cells. The tumors induced by A549-TK cells showed no significant increase in size after ACV treatment (P>0. 05) , and light microscopy revealed local tissue necrosis, karyoklasis, and nuclei disappearance. Conclusion: A549-TK cells acquires sensitivity to ACV both in vitro and in vivo, and ACV can inhibit the growth of tumors induced by A549-TK cell inoculation in nude mice.展开更多
The advanced oxidation processes were examined toward the degradation of thymine （CsH6N202）, a type of nucleic acid from the pyrimidine family. As observed, the photodegradation of thymine over TiO2 photocatalyst wa...The advanced oxidation processes were examined toward the degradation of thymine （CsH6N202）, a type of nucleic acid from the pyrimidine family. As observed, the photodegradation of thymine over TiO2 photocatalyst was rapid and significant in aqueous solution under UV irradiation. Different parameters were studied, including the adsorption of thymine onto TiO2 photocatalyst, the kinetics of degradation, and the effect of pH on the photocatalytic properties of thymine degradation. Additionally, the mineralization of the products obtained upon thymine photodegradation was studied. The disappearance and mineralization rates of thymine during the photocatalytic process were also compared and discussed. The mineralization of nitrogen was also investigated, and the identification of the intermediate products was established. Finally, electronic density calculations were used to propose possible chemical pathways for the photodegradation of thymine over TiO2 photocatalyst under UV irradiation.展开更多
Polymerase-tautomeric model for untargeted delayed base substitution mutations is proposed.Structural analysis of bases insertion showed that any canonical bases may be inserted opposite rare tautomeric forms of thymi...Polymerase-tautomeric model for untargeted delayed base substitution mutations is proposed.Structural analysis of bases insertion showed that any canonical bases may be inserted opposite rare tautomeric forms of thymine T3*,adenines A2*and A4*so that between them hydrogen bonds are formed.Canonical adenine and cytosine can be incorporated opposite canonical thymine only.Canonical thymine and guanine can be incorporated opposite canonical adenine only.If in the synthesis of DNA containing rare tautomeric forms of thymine T3*,adenines A2*and A4*,involved DNA polymerases with relatively high fidelity of synthesis,mutations not appear.However,if further DNA synthesis will involve DNA polymerases having a low fidelity of synthesis,there may be base substitution mutations.It was shown that the conclusion made in the Tomasetti and Vogelstein cancer risk model that the formation of about 67%of all mutations was not caused by exposure to any mutagens is erroneous.展开更多
Significant effort has been invested into unraveling the structure-property relationship of DNA-AgNCs using relatively short DNA sequences.Due to the limited sequence length,two or more strands are often required to s...Significant effort has been invested into unraveling the structure-property relationship of DNA-AgNCs using relatively short DNA sequences.Due to the limited sequence length,two or more strands are often required to stabilize a DNA-AgNC.Therefore,functionalization inherently introduces multiple reactive sites,hindering the implementation of single-site linking strategies.Here,we exploit the concept of using a thymine linking segment to connect two small DNA strands to develop a single-stranded version of DNA_(2)-[Ag_(16)Cl_(2)]^(8+).Our results demonstrate that these redesigned constructs preserve the core AgNC structure and photophysical properties while enabling future single-site functionalization.Furthermore,this approach allows for experimental verification that the DNA linking segments do not interfere with AgNC formation.展开更多
Silver cations(Ag^(+))exhibit site-specific coordination with the natural nucleobases,which can be exploited within DNA nanostructures.Understanding the thermodynamics of formation and organization of DNA complexes fo...Silver cations(Ag^(+))exhibit site-specific coordination with the natural nucleobases,which can be exploited within DNA nanostructures.Understanding the thermodynamics of formation and organization of DNA complexes formed by these interactions is essential for rationally designing Ag^(+)-mediated DNA nanostructures.In this study,we use temperature controlled circular dichroism(CD)spectroscopy,isothermal titration calorimetry(ITC),Förster resonance energy transfer(FRET),and cryogenic-transmission electron microscopy(cryo-TEM)to investigate the formation stoichiometry and resulting morphology of Ag^(+)-mediated duplexes of oligo-dA and oligo-dT homonucleotide strands.CD shows that duplex formation occurs at room temperature and is sensitive to solution phase conditions.ITC reveals that 0.5[Ag^(+)]/[base]is required to form thermodynamically stable dA–Ag^(+)–dT structures with one Ag^(+)per base pair.FRET experiments show that dA–Ag^(+)–dT duplexes maintain anti-parallel strand orientation,even with excess Ag^(+),and cryo-TEM shows that dA–Ag^(+)–dT duplexes adopt morphologies similar to WCF duplexes.Despite these similarities,dA–Ag^(+)–dT duplexes exhibit significantly greater thermal stability compared to their WCF counterparts.These findings provide new insights into dA–Ag^(+)–dT duplex formation and structure that are essential for the development of programmable Ag^(+)–DNA nanostructures.展开更多
E.coli AlkB is a direct DNA/RNA repair protein that oxidatively reverses N1 alkylated purines and N3 alkylated pyrimidines to regular bases.Previous crystal structures have revealed N1-methyl adenine(1-meA)recognition...E.coli AlkB is a direct DNA/RNA repair protein that oxidatively reverses N1 alkylated purines and N3 alkylated pyrimidines to regular bases.Previous crystal structures have revealed N1-methyl adenine(1-meA)recognition by AlkB and a unique base flipping mechanism,but how the AlkB active site can accommodate bulky base adducts is largely unknown.Employing a previously developed chemical cross-linking technique,we crystallized AlkB with a duplex DNA containing a caged thymine base(cagedT).The structure revealed a flexible hairpin lid and a reorganized substrate recognition loop used by AlkB to accommodate cagedT.These observations demonstrate,at the molecular level,how bulky DNA adducts may be recognized and processed by AlkB.展开更多
Repair activities of thymine radical anion by echinocoside, isolated from Pedicularis plicata. were studied using pulse radiolysis technique. The thymine radical anion was produced by the reaction of hydrated electron...Repair activities of thymine radical anion by echinocoside, isolated from Pedicularis plicata. were studied using pulse radiolysis technique. The thymine radical anion was produced by the reaction of hydrated electron with thymine. Echinocoside. one of the polyphenols of phenylpropanoid glycoside, was added to the thymine aqueous solution saturated with N2. Kinetic analysis by transient absorption spectrum showed that thymine radical anion was formed at first, and then after several decades of microseconds of pulse radiolysis. the spectrum of thymine radical anion was changed to that of echinocoside radical anion. The evidence indicated that thymine radical anion was repaired through one-electron-transfer between the DNA base radical anion and echinocoside. The rate constant of electron transfer by echinocoside was 1.45× 109 dm3 · mol1 · s 1.展开更多
基金supported by the National Natural Science Foundation of China (20973088)the Educational Department of Liaoning Province (2007T091, 2008T106)
文摘Understanding the mechanisms underlying the assembly of nucleobases is a great challenge. The ability to deeply understand how nucleobases interact with themselves as well as with other molecules will allow us to gain valuable insights into how we might be able to harness these interesting biological molecules to construct complex nanostructures and materials. Uracil and thymine derivatives have been reported for use in biological applications and in self-assembling triple hydrogen bonded systems. Either uracil or thymine possesses three binding sites （Site 1, Site 2, and Site 3） that can induce strong directional N-H...O=C hydrogen bonding interaction. In this paper, theoretical calculations are carded out on the structural features and binding energies of hydrogen-bonded dimers and trimers formed by uracil and thymine bases. We find that the hydrogen bonds formed through Site 1 are the strongest, those formed through Site 3 are next, while those formed through Site 2 are the weakest. The atoms in molecules analysis show that the electron densities at the bond critical points and the corresponding Laplacians have greater values for those hydrogen bonds formed through Site 1 than through Site 2. All these results indicate that a uracil （or thymine） would interact with another uracil or thymine most likely through Site 1 and least likely through Site 2. We also find that a simple summation rule roughly exists for the binding energies in these dimers and trimers.
基金This work was supported by the National Natural Science Foundation of China （No.20903104, No.2107320L and No.20733005） and the Chinese Academy of Sciences.
文摘Pentachlorophenol, a widespread environmental pollutant that is possibly carcinogenic to humans, is metabolically oxidized to tetrachloroquinone （TCBQ） which can result in DNA damage. We have investigated the photochemical reaction dynamics of TCBQ with two pyrimidine type nucleobases （thymine and uracil） upon UVA （355 ran） excitation using the technique of nanosecond time-resolved laser flash photolysis. It has been found that 355 nm excitation populates TCBQ molecules to their triplet state 3TCBQ＊, which are highly reactive towards thymine or uracil and undergo two parallel reactions, the hydrogen abstraction and electron transfer, leading to the observed photoproducts of TCBQH. and TCBQ.- in transient absorption spectra. The concomitantly produced nucleobase radicals and radical cations are expected to induce a series of oxidative or strand cleavage damage to DNA afterwards. By characterizing the photochemical hydrogen abstraction and electron transfer reactions, our results provide potentially important molecular reaction mechanisms for understanding the carcinogenic effects of pentachlorophenol and its metabolites TCBQ.
基金This work was supported by the Chinese Academy of Sciences and the National Natural Science Foundation of China （No.10805047）. Authors appreciate the kind help from Dr. Yang Pan in experiments.
文摘Photon-induced dissociation pathways of thymine are investigated with vacuum ultraviolet photoionization mass spectrometry and theoretical calculations. The photoionization mass spectra of thymine at different photon energy are measured and presented. By selecting suitable photon energy, exclusively molecular ion m/z=126 is obtained. At photon energy of 12.0 eV, the major ionic fragments at m/z=98, 97, 84, 83, 70, and 55 are obtained, which are assigned to C4H6N2O＋, C4H5N2O＋, C3H4N2O＋ （or C4H6NO＋）, C4H5NO＋, C2NO2＋, and C3H5N＋, respectively. With help of theoretical calculations, the detailed dissociation pathways of thymine at low energy are well established.
基金Supported by the National Natural Science Foundation of China (No. 20763007)
文摘The reaction mechanisms of carcinogenic methylating agent iodomethane （MeI） with keto and enol tautomers of thymine （K- and E-thymine） were studied by using the B3LYP/6-311＋G （d, p） method in water phase. The solvent effects were examined using the polarizable continuum model （PCM）. Specifically, PCM single-point calculations at the same level of theory were performed in acetone and CCl4 that represent a range in nonpolarity. The calculated results show that the reaction of K-thymine with MeI is a two-step mechanism, whereas that of E-thymine is a one-step mechanism. Our calculations reveal that K-thymine is appreciably more stable than the enol form in the water phase or in the two solvents. The K- and E-form reaction barriers are 135.6 and 222.1 kJ/mol, respectively in water phase. These findings indicate that the reactions mentioned above could not occur efficiently in biological media in the absence of catalyst. Our conclusions are in agreement with the previous studies on the reactions of guanine with methyl chloride and methyl bromide.
基金Authors thank the National NatUral Science Foundation of China for financial support !(29672047).
文摘The synthesis of peptoid nucleic acid bearing thymine as nucleobase has been achieved. This modified oligonucleotide showed good hybridization with DNA.
基金the Natural Science Foundation for colleges and University in Jiangsu province (No.07KJD320013)the Natural Science Foundation of Huaihai Institute of Technologe(Nos.Z2006006,Z2007043)for financial support.
文摘A series of novel mono- and di-terpyridine derivatives with purinyl and pyrimidyl group were obtained from the reaction of 4′-p- bromomethylphenyl-2,2′：6,2″-terpyridine with 6-mercaptopurine, 2,6-dimercaptopurine and thymine, respectively. The active hydrogens on these alkaloids could be abstracted stepwise using different bases, which made the addition controllable.
文摘The interacting patterns and mechanism of the catechin and thymine have been investigated with the density functional theory Becke＇s three-parameter nonlocal exchange functional and the Lee, Yang, and Parr nonlocal correlation functional （B3LYP） method by 6-31＋G＊ basis set. Thirteen stable structures for the catechin-thymine complexes have been found which form two hydrogen bonds at least. The vibrational frequencies are also studied at the same level to analyze these complexes. The results indicated that catechin interacted with thynfine by three different hydrogen bonds as N-H…O, C-H…O, O-H…O and the complexes are mainly stabilized by the hydrogen bonding interactions. Theories of atoms in molecules and natural bond orbital have been adopted to investigate the hydrogen bonds involved in all systems. The interaction energies of all complexes have been corrected for basis set superposition error, which are from -18.15 k J/mol to -32.99 kJ/mol. The results showed that the hydrogen bonding contribute to the interaction energies dominantly. The corresponding bonds stretching motions in all complexes are red-shifted relative to that of the inonomer, which is in agreement with experimental results.
基金This work was supported by the National Natural Science Foundation of China (Nos. 30470444, 20672106)
文摘The crystal structure of the title compound （C34H47NTO9, Mr = 697.79） has been determined by single-crystal X-ray diffraction. The crystal belongs to monoclinic, space group P21 with a = 9.000（8）, b = 11.360（10）, c = 17.841（15.）/k, β = 97.083（14）°, V = 1810（3）A^3, Z = 2, F（000） = 744, D,.= 1.280 g/cm^3,/t = 0.094 mm^-1, the final R = 0.0721 and wR = 0.1942 for 2479 observed reflections with I 〉 2σ（I）. The two methyl groups attached to the cyclobutane ring are cis oriented. An intramolecular hydrogen bond （N（6）-H（6）…O（8）） introduces rigidity into the title molecule and the crystal structure is stabilized by intermolecular N-H…O hydrogen bonds.
基金supported by the National Academy of Sciences of Belarus
文摘The main purpose of this study is a better comprehension of the non-bonded interaction between an anticancer drug apalutamide and deoxyribonucleic acid(DNA).In the prese nt work,the in teraction between an ticancer drug apalutamide and one of the DNA bases called 2,-deoxythymidine 5,-monophosphate(thymine)by Density Functional Theory(DFT)calculations in the solvent water has been investigated for the first time.The non-bonded interaction effects of the molecule apalutamide with thymine on the electronic properties,chemical shift tensors and natural charges have been also detected.The natural bond orbital(NBO)analysis was performed for determining the role of electron donor and acceptor of the molecules apalutamide and thymine at the complex thymine/apalutamide.Both Electron location function(ELF),localized orbital locator(LOL)and quantum theory of atoms in molecules(QTAIM)analysis were carried out in order to determine the chemical bond nature in the investigated compounds.The values of ELF and LOL parameters for the selected bonds are small,which confirms the non-covalent character of these bonds in nature.The electronic spectra of the apalutamide drug,thymine and complex thymine/apalutamide in solvent water were calculated by Time Dependent Density Functional Theory(TD-DFT)for the investigation of interaction effect;Non-bonded interaction between the compound apalutamide and thymine has changed the value of λmax.
基金supported by the National Natural Science Foundation of China (No:20171038)
文摘The photolysis of thymine in phosphate-buffered saline (PBS, pH 8.0) under the irradiation of medium pressure mercury lamp (MPML) produces a novel compound C5H7N2O6P. The composition and structure of the compound have been identified by elemental analysis, EI-MS, UV, IR, 1H, 13C, 31P-NMR.
文摘As a well known DNA photolesion product, the special UV induced pyrimidine dimmer called spore photoproduct （SP）, has aroused strong research interests. The SP formation was reported solely between two adjacent thymidine residues. It remains unclear in pervious experimental observations why there is an absence of the cytosine-derived SP-like photoprod- uct formation at the cytosine containing DNA strand, although the cytosine residue holds great similarity to thymine in terms of molecular structure. From a theoretical perspec- tive, we have explored this issue in this work by means of density functional theory at the B3LYP/6-311＋＋G（d,p） //B3LYP/6-31G（d,p） level for the DNA dinucleotide fragment, cy- tosine phosphate thymine （CpT）. Key factors blocking the formation of the SP-like product between two adjacent cytosine and thymidine residues are revealed. Instead of undergoing photochemical SP reaction, a photophysical deactivation pathway back to the ground state turns out to be favorable for the CpT dinucleotide fragment.
文摘A new type of HPLC stationary phase containing thymine derivative was successfully prepared.It was found to give selective separation of nucleic acid bases and several purine derivatives,such as caffeine and theophylline.The retention behaviour and elution order of the solutes were interpreted in terms of molecular structure.
文摘Objective: To observe the effect of anciclovir (ACV) treatment on tumors induced by inoculation of TK gene-transfected human pulmonary adenocarcinoma A549 cells in nude mice. Methods: A recombinant plasmid containing TK gene was constructed and transfected into A549 cells by electroporation. The sensitivity of the transgenic cells (A549-TK) to ACV was examined by MTT assay in vitro and for in vivo observation, inoculation of A549-TK and A-549 cells into nude mice was separately performed to induce tumor growth, the response of which to ACV treatment was observed, and the tumor tissues were pathologically examined. Results: A recombinant plasmid containing TK gene was successfully constructed and transfected into A549 cells. The sensitivity of A549-TK cells to ACV was 43 times higher than that of A549 cells. The tumors induced by A549-TK cells showed no significant increase in size after ACV treatment (P>0. 05) , and light microscopy revealed local tissue necrosis, karyoklasis, and nuclei disappearance. Conclusion: A549-TK cells acquires sensitivity to ACV both in vitro and in vivo, and ACV can inhibit the growth of tumors induced by A549-TK cell inoculation in nude mice.
基金supported by The French Institute of Tunisia and University of Gabes,Tunisia (Scientific Stay High Level 2015)
文摘The advanced oxidation processes were examined toward the degradation of thymine （CsH6N202）, a type of nucleic acid from the pyrimidine family. As observed, the photodegradation of thymine over TiO2 photocatalyst was rapid and significant in aqueous solution under UV irradiation. Different parameters were studied, including the adsorption of thymine onto TiO2 photocatalyst, the kinetics of degradation, and the effect of pH on the photocatalytic properties of thymine degradation. Additionally, the mineralization of the products obtained upon thymine photodegradation was studied. The disappearance and mineralization rates of thymine during the photocatalytic process were also compared and discussed. The mineralization of nitrogen was also investigated, and the identification of the intermediate products was established. Finally, electronic density calculations were used to propose possible chemical pathways for the photodegradation of thymine over TiO2 photocatalyst under UV irradiation.
文摘Polymerase-tautomeric model for untargeted delayed base substitution mutations is proposed.Structural analysis of bases insertion showed that any canonical bases may be inserted opposite rare tautomeric forms of thymine T3*,adenines A2*and A4*so that between them hydrogen bonds are formed.Canonical adenine and cytosine can be incorporated opposite canonical thymine only.Canonical thymine and guanine can be incorporated opposite canonical adenine only.If in the synthesis of DNA containing rare tautomeric forms of thymine T3*,adenines A2*and A4*,involved DNA polymerases with relatively high fidelity of synthesis,mutations not appear.However,if further DNA synthesis will involve DNA polymerases having a low fidelity of synthesis,there may be base substitution mutations.It was shown that the conclusion made in the Tomasetti and Vogelstein cancer risk model that the formation of about 67%of all mutations was not caused by exposure to any mutagens is erroneous.
基金funding from the Villum Foundation(VKR023115)the Independent Research Fund Denmark(0136-00024B)+7 种基金the Novo Nordisk Foundation(NNF22OC0073734)MAX IV Laboratory for time on Beamline Biomax under Proposal 20240265 allocated to Leila Lo LeggioResearch conducted at MAX IV,a Swedish national user facility,is supported by the Swedish Research Council under contract 2018-07152the Swedish Governmental Agency for Innovation Systems under contract 2018-04969Formas under contract 2019-02496MicroMAX is funded by the Novo Nordisk Foundation under grant number NNF17CC0030666.the Danish Agency for Science,Technology,and Innovation for funding the instrument center DanScatt,supporting travel and sample shipping to synchrotronsfunded by the Independent Research Fund Denmark(Natural Sciences)under grant 3103-00279Bthe Research Support Project for Life Science and Drug Discovery(Basis for Supporting Innovative Drug Discovery and Life Science Research(BINDS))from AMED under Grant Number JP23ama121014.
文摘Significant effort has been invested into unraveling the structure-property relationship of DNA-AgNCs using relatively short DNA sequences.Due to the limited sequence length,two or more strands are often required to stabilize a DNA-AgNC.Therefore,functionalization inherently introduces multiple reactive sites,hindering the implementation of single-site linking strategies.Here,we exploit the concept of using a thymine linking segment to connect two small DNA strands to develop a single-stranded version of DNA_(2)-[Ag_(16)Cl_(2)]^(8+).Our results demonstrate that these redesigned constructs preserve the core AgNC structure and photophysical properties while enabling future single-site functionalization.Furthermore,this approach allows for experimental verification that the DNA linking segments do not interfere with AgNC formation.
基金supported by AFOSR FA9550-21-1-0163 and AFOSR DURIP FA9550-22-1-0206supported in part by the National Science Foundation Materials Research Science and Engineering Center program through the UC Irvine Center for Complex and Active Materials(DMR-2011967).
文摘Silver cations(Ag^(+))exhibit site-specific coordination with the natural nucleobases,which can be exploited within DNA nanostructures.Understanding the thermodynamics of formation and organization of DNA complexes formed by these interactions is essential for rationally designing Ag^(+)-mediated DNA nanostructures.In this study,we use temperature controlled circular dichroism(CD)spectroscopy,isothermal titration calorimetry(ITC),Förster resonance energy transfer(FRET),and cryogenic-transmission electron microscopy(cryo-TEM)to investigate the formation stoichiometry and resulting morphology of Ag^(+)-mediated duplexes of oligo-dA and oligo-dT homonucleotide strands.CD shows that duplex formation occurs at room temperature and is sensitive to solution phase conditions.ITC reveals that 0.5[Ag^(+)]/[base]is required to form thermodynamically stable dA–Ag^(+)–dT structures with one Ag^(+)per base pair.FRET experiments show that dA–Ag^(+)–dT duplexes maintain anti-parallel strand orientation,even with excess Ag^(+),and cryo-TEM shows that dA–Ag^(+)–dT duplexes adopt morphologies similar to WCF duplexes.Despite these similarities,dA–Ag^(+)–dT duplexes exhibit significantly greater thermal stability compared to their WCF counterparts.These findings provide new insights into dA–Ag^(+)–dT duplex formation and structure that are essential for the development of programmable Ag^(+)–DNA nanostructures.
基金supported by the National Institute of Health(GM071440 to C.H.)Data collection was performed at GM/CA-CAT Beamline 23-ID-B at the Advanced Photon Source at Argonne National Laboratorysupport for this beamline comes from the National Institute of Health and the United States Department of Energy
文摘E.coli AlkB is a direct DNA/RNA repair protein that oxidatively reverses N1 alkylated purines and N3 alkylated pyrimidines to regular bases.Previous crystal structures have revealed N1-methyl adenine(1-meA)recognition by AlkB and a unique base flipping mechanism,but how the AlkB active site can accommodate bulky base adducts is largely unknown.Employing a previously developed chemical cross-linking technique,we crystallized AlkB with a duplex DNA containing a caged thymine base(cagedT).The structure revealed a flexible hairpin lid and a reorganized substrate recognition loop used by AlkB to accommodate cagedT.These observations demonstrate,at the molecular level,how bulky DNA adducts may be recognized and processed by AlkB.
基金Project supported by the National Natural Science Foundation of China, Doctoral Programme of State Education Commission and Open Laboratory of Radiation Chemistry,the Chinese Academy of Sciences.
文摘Repair activities of thymine radical anion by echinocoside, isolated from Pedicularis plicata. were studied using pulse radiolysis technique. The thymine radical anion was produced by the reaction of hydrated electron with thymine. Echinocoside. one of the polyphenols of phenylpropanoid glycoside, was added to the thymine aqueous solution saturated with N2. Kinetic analysis by transient absorption spectrum showed that thymine radical anion was formed at first, and then after several decades of microseconds of pulse radiolysis. the spectrum of thymine radical anion was changed to that of echinocoside radical anion. The evidence indicated that thymine radical anion was repaired through one-electron-transfer between the DNA base radical anion and echinocoside. The rate constant of electron transfer by echinocoside was 1.45× 109 dm3 · mol1 · s 1.
