Selective conformer detection of short-lived base pair tautomers: A computational study of the unusual guanine-cytosine pairs using ultrafast resonance Raman spectroscopy

Base pair mismatch has been regarded as the main source of DNA point mutations, where minor shortlived tautomers were usually involved. However, the detection and characterization of these unnatural species pose challenges to existing techniques. Here, by using systematic structural and ultrafast resonance Raman(RR) spectral analysis for the four possible conformers of guanine-cytosine base pairs, the prominent marker Raman bands were identified. We found that the hydrogen bonding vibrational region from 2300 cm^(-1) to 3700 cm^(-1) is ideal for the identification of these short live species. The marker bands provide direct evidence for the existence of the tautomer species, thus offering an effective strategy to detect the short-lived minor species. Ultrafast resonance Raman spectroscopy would be a powerful tool to provide direct evidence of critical dynamical details of complex systems involving protonation or tautomerization.

Mapping out the reaction network of humin formation at the initial stage of fructose dehydration in water

The formation of humins hampers the large-scale production of 5-hydroxymethylfurfural(HMF)in biorefinery.Here,a detailed reaction network of humin formation at the initial stage of fructose-to-HMF dehydration in water is delineated by combined experimental,spectroscopic,and theoretical studies.Three bimolecular reaction pathways to build up soluble humins are demonstrated.That is,the intermolecular etherification of β-furanose at room temperature initiates the C12 path,whereas the C-C cleavage of a-furanose at 130-150℃ leads to C11 path,and that of open-chain fructose at 180℃ to C11' path.The successive intramolecular dehydrations and condensations of the as-formed bimolecular intermediates lead to three types of soluble humins.We show that the C12 path could be restrained by using HCl or AlCl_(3) catalyst,and both the C12 and C110 paths could be effectively inhibited by adding THF as a co-solvent or accelerating heating rate via microwave heating.

Interaction of Cisplatin Adducts with Guanine Tautomers： A Theoretical Study of Metalated Tautomeric Forms

The influence of binding of cisplatin adducts on tautomeric equilibrium of guanine was investigated using quantum chemical method. The monoaqua adduct [Pt（NH3）2Cl（H2O）]^＋ and the diaqua adduct [Pt（NHa）2（H2O）2]^2＋ were chosen for coordination to the N（7） site of guanine tautomers. The results demonstrate that the platinum adducts influence moderately on tautomeric equilibrium, but do not change the relative stability of tautomers whether in gas phase or in aqueous solution. The keto form having H atom at N（1） and N（9） was always the predominant structure when cisplatin adducts were bound to guanine. However, other forms could coexist in water. Meanwhile, our calculations suggest that the tautomeric equilibrium should be via the same intermediate.

Analysis of keto-enol tautomers of curcumin by liquid chromatography/mass spectrometry

Keto-enol tautomers of curcumin were confirmed by reversed-phase liquid chromatography（RPLC）/ hybrid quadrupole ion trap/time-of-flight mass spectrometry（QIT/TOFMS）.Tautomers gave different MS/MS spectra in negative mode.Different mass spectra were also obtained by hydrogen/deuterium exchange LC/MS/MS in positive mode.Our results suggest that enol form is the major form in the solution（water/acetonitrile）.

Theoretical Study of the Intramolecular Proton Transfer in the Tautomers of Cytosine Assisted by Water

Ab initio MP2 and DFT studies on the tautomers of cytosine and the related hydrated tautomers have been carried out. The ground-state structures of four tautomers of cytosine and related transition states were fully optimized. The vibrational frequency analysis was performed on all the optimized structures. Detailed intrinsic reaction coordinate （IRC） calculations were carded out to guarantee the optimized transition-state structures being connected to the related tautomers. We obtained the relative stability order for the tautomers of cytosine and the related hydrated tautomers. In the isolated and hydrated condition, the bond types of C（2）--O（7） and C（4）--N（8） greatly affect the stability of the cytosine tautomers. Moreover, we have explored the influence of the water molecules on the intramolecular proton transfer between the keto and enol forms of the cytosine tautomers. The first water molecule obviously decreases the isomerization activation energy for the monohydrated cytosine tautomers. It is shown that the isomerization energy barrier changes only a little when the second and third water molecules are added in the reaction loop. The solvent effects have an obvious influence on the proton-transfer barrier of the isolated cytosine. However, the solvent effects seem to be insignificant for the isomerization energy barriers of the monohydrated, dihydrated and trihydrated cytosine. The water molecule in these complexes can be looked on as the explicit water. Therefore, the explicit water model may be more credible to explore the intramolecular proton transfer, in comparison with the PCM which is the implicit water model.

Theoretical Study on Reaction Mechanism of Tautomerization of Indazole and 3-halogeno-indazole

The molecular structures of indazole and 3-halogeno-indazole tautomers were calculated by the B3LYP method at the 6-311G^＊＊ level, both in the gaseous and aqueous phases, with full geometry optimization. The geometry and electronic structure of the tautomers of indazole, 3-halogeno-indazole and their transition states were obtained. The Onsager solvate theory model was employed for the aqueous solution calculations. The results of the calculation indicated that the N1-H form of the studied molecule is more stable than that of the N2-H form. The influences of the different 3-halogeno and solvent effects on the geometry, energy, charge and activation energy were discussed. The reaction mechanism of the tautomerization of indazole and 3-halogeno-indazole was also studied and a three-membered cyclic transition state of the tautomer reaction has been obtained.

A Study on 4,4′-Diaminobenzene Sulfonanilide(DABSA) and the Properties of Dyes Derived from DABSA

A single crystal of 4,4′ diaminobenzene sulfonanilide(DABSA) was determined by X ray diffraction method. It is shown that the two benzene rings are non planar with an angle of 55 1°. Owing to the non planar configuration, the dyes derived from DABSA possess a lower substantivity on fiber but better permeability in substrate, the color of these azo dyes could be matched by two individual azo dyes locating on both sides of the DABSA molecule.

Theoretical Study on Enol-keto Tautomerism of α-Fluorine-β-diketones

Density Functional Theory method is applied to investigate the enol-keto tautomerism of both acyclic and cyclic α-fluorine-β-diketones. It is shown that, for acyclic cases, α-fluorine could improve the relative stability of keto tautomer by lessening intramolecular hydrogen bond of enol form, whereas the relative stability of cyclic enol could be attributed to two factors： destabilization of keto and stabilization of enol. Furthermore, the relative stabilities of all enol tautomers are improved in THF to different extents.

Theoretical Study by Density Functional Theory Method (DFT) of Stability, Tautomerism, Reactivity and Prediction of Acidity of Quinolein-4-One Derivatives

A theoretical study of the reactivity of quinoline-4-one derivatives is undertaken in order to understand the involved mechanisms. The calculations were carried out in gas phase and in N, N-Dimethylformamide (DMF) solution. The Density Functional Theory (DFT) with B3LYP functional associated to 6-311G (d) and 6-311+G (d) bases is used to perform these calculations. The results of the thermodynamic parameters showed that there is an equilibrium relation between the different tautomers. This equilibrium can be used to explain the failure to obtain tetrahydroquinoline from 5,8-dimethoxy-quinolin-4-one. Reactivity analysis from Frontier Molecular Orbitals theory and Fukui function calculations revealed that ketone forms are less reactive than enol ones. The methoxyl substituent decreases the acidity of the nitrogen and oxygen atoms of quinolin-4-one while the bromine increases the acidity of the same sites. These results foresee that nitrogen deprotonation in the case of the brominated compound is easier than in the case of methoxylated ones.

Tautom ycetin与Leptom ycin B联用协同抑制乳腺癌细胞增殖的作用及机制

目的研究Tautomycetin(TMC)和Leptomycin B(LMB)联用对乳腺癌细胞增殖的协同抑制作用及机制。方法采用MTT、Western blot和免疫荧光等方法检测TMC和LMB对乳腺癌细胞增殖、Bcl-2家族等蛋白的表达与细胞定位等方面的影响。结果 LMB处理24 h后再加TMC对乳腺癌细胞增殖的协同抑制作用最强。与单独用药相比,采用该方式联合用药,TMC和LMB的用量仅为单独用药时的23.8%和17.7%,即可达到相同的半数抑制效应。TMC与LMB联用可促进Bcl-2蛋白表达的下调;并增强对Bad、Akt和FKHR磷酸化的下调作用,促进FKHR的细胞核聚集。结论 TMC与LMB联用对乳腺癌增殖具有显著的协同抑制作用,其机制可能是促进FKHR细胞核定位。

Ab initio Study on Ionization Energies of 1-Methyl-hypoxanthine

Six low-lying tautomers of 1-methyl-hypoxanthine have been studied at the B3LYP/aug-cc- pVDZ level. Two tautomers NTH and N9H with the comparable energies are far more stable than the others. The vertical ionization energies of the tautomers calculated with ab initio electron propagator theory in the P3/aug-cc-pVDZ approximation are in agreement with the experimental data from photoelectron spectroscopy. According to the calculated relative energies and the comparison between the simulated and the experimental photoelectron spectra, it demonstrates that there are at least two tautomers of 1-methyl-hypoxanthine in the gas-phase experiments.

Solid and liquid state characterization of tetrahydrocurcumin using XRPD, FT-IR, DSC, TGA, LC-MS, GC-MS, and NMR and its biological activities

Tetrahydrocurcumin(THC)is one of the major metabolites of curcumin(CUR),an ancient bioactive natural polyphenolic compound.This research article describes both the solid and liquid state characterization of THC using advanced spectroscopic and thermo-analytical techniques.Anti-inflammatory,anti-oxidant,and neuroprotective activities of THC were investigated using in vitro cell lines.Liquid chromatography-mass spectrometry analysis revealed that our sample comprised 95.15%THC,0.51%tetrahydrodemethoxycurcumin(THDC),3.40%hexahydrocurcumin,and 0.94%octahydrocurcumin.Gas chromatography-mass spectrometry analysis indicated the presence of 96.68%THC and 3.32%THDC.THC in solution existed as keto-enol tautomers in three different forms at different retention time,but the enol form was found to be dominant,which was also supported by nuclear magnetic resonance analysis.THC was thermally stable up to 335.55
C.THC exhibited more suppression of cytokines(TNF-a,IL-1b,and MIP-1a)than CUR in a concentration-dependent manner in mouse splenocytes,while NK-cell and phagocytosis activity was increased in macrophages.THC showed a significant reduction of free radicals(LPO)along with improved antioxidant enzymes(SOD and catalase)and increased free radical scavenging activity against ABTSt radicals in HepG2 cells.THC displayed higher protection capability than CUR from oxidative stress and neuronal damage by improving cell viability against H2O2 induced HepG2 cells and MPPt induced SH-SY5Y cells,respectively,in a concentration-dependent manner.Thus,a variation of the biological activities of THC might rely on its keto-enol form and the presence of other THC analogs as impurities.The present study could be advantageous for further research on THC for better understanding its physicochemical properties and biological variation.

Potential Energy Surface of Cytosine and Tunneling Between Its Normal and Trans-imino Tautomer

The potential energy surface of H（13） proton in base cytosine of the DNA molecules is calculated at the Caussian 98 MP2/6-311C（d,p） level. Two potential wells are found. One corresponds to the normal cytosine, while the other corresponds to its trans-imino tautomer. The estimated tunneling probability of the H（13） proton from one well to another well shows that the life time of the proton staying in one of these wells is about 600 yrs. It is too long to let tautomers of cytosine be in thermodynamical equilibrium in a room temperature gas phase experiment.

Exogenous bridge and tautomer effects on magnetic interaction of binuclear copper(II) complexes of μ-phenolato Schiff bases

<正> Four enol-form binuclear copper complexes with different exogenous bridges, [Cu2(L)(μ-Cl)] (1), [Cu(L)(μ-N3)]· DMF (2), [Cu2(L)(μ-OCH3)] (3) and [Cu2(L)(μ-C3H3N2)]· 1/2C2H5OH (4), where L is the trivalence anion of binucleating ligand 2,6-diformyl-4-methylphenol di(tenzoylhydrazone), have been synthesized and characterized. Crystal data for complex (3) are as follows: space group P1- , a=0.8294(1), 6=0.9333(3), c= 1.473 6(6) nm, α=79.51(3)°, β=80.93(2)°,γ=81.32(2)°, Z=1. The magnetic measurements indicated that the effect of exogenous bridging ligands on magnetic interaction is corresponding to that in spectrochemical series. The effect of enol- and keto-form tautomer on magnetic interaction was explained from the point of view of structural factors and electron effects by using molecular mechanks and quantum chemistry calculations.

A new method for the synthesis of 3-hydroxymethylbenzofuran

A new one-step synthesis of 3-hydroxymethylbenzofuran, based on intramolecular cyclization of 2- （methoxymethyl）-2-（2＇-methoxymethyl-4＇-methylphenyl）-butanone I under diluted hydrochloric acid in THF, was developed. The mechanism for this process was investigated via chemical equilibrium shift of tautomer in acidic conditions. The applicability of this new method was studied further in this paper.