Organocatalytic asymmetric destruction of 1-benzylated Reissert compounds catalysed by quaternary cinchona alkaloids

The enantiomeric enrichment of racemic 1-benzylated Reissert compounds under organocatalytic biphasic conditions is presented. The enrichment is the consequence of an asymmetric destruction of the racemic compounds resulting in the formation of the corresponding 1-benzylated isoquinolines. The highest selectivity has been achieved using quaternary cinchona alkaloids as phase-transfer catalysts. The resolution of a number of racemic 1-benzylated Reissert compounds reveals a significant substrate dependence and a proposal for the mechanism of the reaction is presented.     

Ultrafast excited-state dynamics of adenine and monomethylated adenines in solution: implications for the nonradiative decay mechanism

The DNA base adenine and four monomethylated adenines were studied in solution at room temperature by femtosecond pump-probe spectroscopy. Transient absorption at visible probe wavelengths was used to directly observe relaxation of the lowest excited singlet state (S(1) state) populated by a UV pump pulse. In H(2)O, transient absorption signals from adenine decay biexponentially with lifetimes of 0.18 +/- 0.03 ps and 8.8 +/- 1.2 ps. In contrast, signals from monomethylated adenines decay monoexponentially. The S(1) lifetimes of 1-, 3-, and 9-methyladenine are similar to one another and are all below 300 fs, while 7-methyladenine has a significantly longer lifetime (tau = 4.23 +/- 0.13 ps). On this basis, the biexponential signal of adenine is assigned to an equilibrium mixture of the 7H- and 9H-amino tautomers. Excited-state absorption (ESA) by 9-methyladenine is 50% stronger than by 7-methyladenine. Assuming that ESA by the corresponding tautomers of adenine is unchanged, we estimate the population of 7H-adenine in H(2)O at room temperature to be 22 +/- 4% (estimated standard deviation). To understand how the environment affects nonradiative decay, we performed the first solvent-dependent study of nucleobase dynamics on the ultrafast time scale. In acetonitrile, both lowest energy tautomers of adenine are present in roughly similar proportions as in water. The lifetimes of the 9-substituted adenines depend somewhat more sensitively on the solvent than those of the 7-substituted adenines. Transient signals for adenine in H(2)O and D(2)O are identical. These solvent effects strongly suggest that excited-state tautomerization is not an important nonradiative decay pathway. Instead, the data are most consistent with electronic energy relaxation due to state crossings between the optically prepared (1)pipi* state and one or more (1)npi* states and the electronic ground state. The pattern of lifetimes measured for the monomethylated adenines suggests a special role for the (1)npi* state associated with the N7 electron lone pair.     

Insights into the role of Val45 and Gln182 of Escherichia coli MutY in DNA substrate binding and specificity

Background  

Escherichia coli MutY (EcMutY) reduces mutagenesis by removing adenines paired with guanines or 7,8-dihydro-8-oxo-guanines (8-oxoG). V45 and Q182 of EcMutY are considered to be the key determinants of adenine specificity. Both residues are spatially close to each other in the active site and are conserved in MutY family proteins but not in Methanobacterium thermoautotrophicum Mig.MthI T/G mismatch DNA glycosylase (A50 and L187 at the corresponding respective positions).     

A new kind of intermolecular stacking interaction between copper (II) mixed chelate complex (Casiopeína III-ia) and adenine

Casiopeínas® are Cu (II) mixed chelate complexes that have shown cytotoxic, genotoxic and antineoplastic activity. In order to understand the interaction of these complexes with biomolecules, we have studied in this work the interaction of Casiopeína III-ia [CAS 223930-33-4] with adenine, cytosine, thymine and guanine. X-ray diffraction analysis shown the molecular structure of an adduct {[Cu(dmbipy)(acac)(H₂O)]NO₃(adenine)₂·2H₂O} where dmbipy = 4,4′-dimethyl-2,2′-bipyridyne and acac = acetylacetonate, which is an example of intermolecular interaction between a ternary Cu (II) compound and adenine. Adduct is stabilized by hydrogen bonds, which include water molecules and adenines, and by π-π and C-H?π interactions between the ligands attached to the copper ion and the adenines. DFT calculations shown charge transfer between complex ligands and adenines being the former the acceptor and the latter the donor; these results reproduce very well the weak interactions found in the crystalline structure. DFT results shown the same behavior for thymine and guanine, meanwhile, cytosine has shown a direct coordination to metal center.     

Consecutive adenine sequences are potential targets in photosensitized DNA damage

Based on direct spectroscopic measurements of hole transfer in DNA and quantification of the yield of DNA oxidative damage, consecutive adenine sequences were found to be a good launching site for photosensitizers to inject a hole in DNA, where the following rapid hole transfer between adenines causes a long-lived charge-separated state leading to DNA oxidative damage. According to the results, the essential requisites for an efficient and/or harmful photosensitizer are determined as follows: to be able to oxidize adenine to trigger hole transfer between adenines, and react rapidly with molecular oxygen following its reduction, avoiding charge recombination and making the reaction irreversible. These results will greatly help us to classify photosensitizers harmful to human health, and to design an improved photosensitizer for biochemical applications.     

New Long‐Chain Esters and Adenine Analogs from the Leaves of Formosan Bridelia balansae

Six new compounds, including the two long‐chain esters balansenate I (=6,8,11‐trimethyldodecanoic acid (2E)‐3‐methylhexadec‐2‐enyl ester; 1 ) and balansenate II (=10,12,15‐trimethylhexadedecanoic acid (2E)‐3‐methylhexadec‐2‐enyl ester; 2 ), the eburicane‐like triterpenoid bridelone (=hexadecahydro‐4,4,10,13,14‐pentamethyl‐17‐(5‐methyl‐1,4‐dimethylenehexyl)‐3H‐cyclopenta[a]phenanthren‐3‐one; 3 ), the ‘deimino‐xanthine', bridelonine (=5‐(3‐methylbut‐2‐enyl)pyrrolo[3,4‐d]imidazole‐4,6(1H,5H)‐dione; 6 ), and the two adenine analogs 9‐(3‐methylbut‐2‐enyl)adenine ( 7 ) and 1‐(3‐methylbut‐2‐enyl)adenine ( 8 ), besides three known compounds, i.e., N⁶‐(3‐methylbut‐2‐enyl)adenine ( 4 ), 3‐(3‐methylbut‐2‐enyl)adenine ( 5 ), and adenine ( 9 ), were isolated from the leaves of Formosan Bridelia balansae. The novel skeleton of 6 consists of a fused pyrrolidine‐2,5‐dione and imidazole moiety. The already known adenines 7 and 8 were isolated for the first time from a plant. The structures of the isolated compounds were elucidated by spectroscopic analyses.     

Bis-phenanthridinium–adenine conjugates as fluorescent and CD reporters for fine structural differences in ds-DNA/RNA and ss-RNA structures

Two structurally similar bis-phenanthridinium–adenine conjugates (equipped with one or two adenines, respectively), exhibiting strong ds-DNA/RNA groove binding, revealed ratiometric fluorescent recognition of alternating AT-DNA with respect to other ds-DNA/RNA and ss-RNA. Further, CD spectra pattern of adenine–bis-phenanthridinium conjugate/polynucleotide complexes strongly depended on polynucleotide secondary structure. Attached adenine was essential for spectrophotometric recognition response, ds-DNA stabilisation and orientation of compounds regarding chiral DNA helix.     

Bonded excimer in stacked adenines:Semiclassical simulations

The nonradiative decay of a π-stacked pair of adenine molecules,one of which was excited by an ultrafast laser pulse,is studied by semiclassical dynamics simulations.This simulation investigation is focused on the effect of the formation of bonded excimer in stacked adenines on the mechanism of ultrafast decay.The simulation finds that the formation of the bonded excimer significantly lowers the energy gap between the LUMO and HOMO and consequently facilitates the deactivation of the electronically excited molecule.On the other hand,the formation of the chemical bond between two stacked adenines restricts the deformation vibration of the pyrimidine of the excited molecule due to the steric effect.This slows down the formation of the coupling between the HOMO and LUMO energy levels and therefore delays the deactivation process of the excited adenine molecule to the electronic ground state.     

A Study on the Intramolecular Mitsunobu Reaction of N6‐(ω‐Hydroxyalkyl)adenines

The cyclization of N ⁶‐(ω‐hydroxyalkyl)adenines with a N⁶H‐group leads to N⁶,N1 ring closure regardless of the method of the cyclization that was used. Five‐membered to eight‐membered rings were obtained using NBS/PPh₃; however, under Mitsunobu conditions, the eight‐membered fused purine was not formed. Surprisingly, the cyclization of N ⁶‐methyl‐N ⁶‐(4‐hydroxybutyl)adenine only leads to N⁶,N7 ring closure using both methods.     

Protonation‐Dependent Base Flipping at Neutral pH in the Catalytic Triad of a Self‐Splicing Bacterial Group II Intron

NMR spectroscopy has revealed pH‐dependent structural changes in the highly conserved catalytic domain 5 of a bacterial group II intron. Two adenines with pK_a values close to neutral pH were identified in the catalytic triad and the bulge. Protonation of the adenine opposite to the catalytic triad is stabilized within a G(syn)–AH⁺(anti) base pair. The pH‐dependent anti‐to‐syn flipping of this G in the catalytic triad modulates the known interaction with the linker region between domains 2 and 3 (J23) and simultaneously the binding of the catalytic Mg²⁺ ion to its backbone. Hence, this here identified shifted pK_a value controls the conformational change between the two steps of splicing.     

Recognition of homo-polynucleotides containing adenine by a phenanthridinium bis-uracil conjugate in aqueous media

Among novel bis-nucleobase-phenanthridinium conjugates bis-uracil analogue stabilized significantly more effective poly-dA-poly-dT and poly-AH(+)-poly-AH(+) than adenine analogue and reference compound . For the alternating poly-dAdT-poly-dAdT however, the binding preference is lost, pointing to the importance of specific interactions of uracils of with homopolynucleotides containing consecutive adenines.     

Der Einfluss des anomer verknüpften Adeninrestes auf die 13C-chemischen Verschiebungen von Pyranosen

The influence of the anomeric attached adenine residue on the ¹³C chemical shifts of aldopyranose carbons is discussed for a series of pyranosyl adenines. The anomeric carbons with an axially oriented heterocycle always resonate at higher field than the corresponding ones with an equatorial orientation. This rule can be used for the determination of the pyranose conformation. Substituting the anomeric hydroxyl group by an adenyl residue causes deshielding on C-5 of the pyranose residue.     

Novel heterocycles derived from 3-acyloxy- and 3-acetamidoquinuclidines

New quinuclidine derivatives with 3-spiro annelated oxathioline, furanone, and pyrrolinone heterocycles have been synthesized from 3-mesyloxy-, 3-acetoxy-, and 3-acetamidoquinuclidine-3-carbonitrile, respectively, by treatment with base. Treatment of 3-acetamidoquinuclidine-3-carbonitrile ( 3 ) with potassium hydride resulted in decyanation whereas alkyllithium reagents attacked the cyano group in 3 to produce the corresponding imines. Oxidative cyclization of the N-benzylated derivative of 3 with palladium acetate gave the tetracyclic compound 5-acetyl-1,4-ethano-1,2,3,4,5,6-hexahydrobenzo[c]-1,5-naphthyridine.     

Synthesis of Fully O-Benzylated N-Linked Core Pentasaccharide Glycosyl Azide

The fully O-benzylated pentasaccharide glycosyl azide representing the common core structure of N-glycans was synthesized. The β-mannosidic linkage was created by C-2 epimerization of the initially introduced β-d- gluco-unit via DMSO/Ac₂O oxidation followed by stereoselective reduction with tetrabutylammonium borohydride.     

Theoretical study of proton-catalyzed hydrolytic deamination mechanism of adenine

Water-assisted proton-catalyzed hydrolytic deamination of adenine to produce hypoxanthine has been studied using density functional theory method. Because adenine could be protonated at N1, N3, N7 and N10, four pathways initiated from the four different protonated adenines have been investigated. The first step of the four pathways is the nucleophilic attack of water with an assistant water to form a tetrahedral structure complex, and this is the rate-determining step. Including solvent effects decreased the relative energies of stationary points but have little effect on the structures. Pathway A is preferred due to the lowest energy barrier, and the relative free energy is 28.9 kcal/mol in vacuo. The outcomes show that adenine deamination under acidic condition is much easier to occur than under neutral condition due to lower energy barriers. The total atomic charge of C5 in the initial intermediate is correlated with the ease of deamination reaction. The more positive C5 atom is, the easier the deamination reaction is.     

Direct Arylation of Adenine by Fluoro- and Chloronitrobenzenes: Effect of Microwaves

Direct arylation of adenine with fluoro- and chloronitrobenzenes leads to mixtures of N9 and N7 substituted adenines. After separation by column chromatography, the individual isomers can be efficiently hydrogenated on Pd to give the corresponding aminophenyladenines. A significant enhancement of the reaction rate by microwave irradiation was observed. This two-step procedure was found to be a feasible route to otherwise hardly available 7-aminophenyladenines. Correlation between calculated shielding constants and experimental values of chemical shifts in ¹³C and ¹⁵N NMR was used for assignment of the site of substitution.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Mechanism of charge separation in DNA by hole transfer through consecutive adenines

To investigate the mechanism of charge separation in DNA with consecutive adenines adjacent to a photosensitizer (Sens), a series of naphthalimide (NI) and 5-bromouracil ((br)U)-modified DNAs were prepared, and the quantum yields of formation of the charge-separated states (Phi) upon photo-excitation of the Sens NI in DNA were measured. The Phi was modulated by the incorporation site of (br)U, which changes the oxidation potential of its complementary A through hydrogen bonding and the hole-transfer rates between adenines. The results were interpreted as charge separation by means of the initial charge transfer between NI in the singlet excited state and the second- and third-nearest adenine to the NI. In addition, the oxidation of the A nearest to NI leads to the rapid charge recombination within a contact ion pair. This suggests that the charge-separation process can be refined to maximize the Phi by putting a redox-inactive spacer base pair between a photosensitizer and an A-T stretch.     

O-Alkylation of a lignite humic acid by phase-transfer catalysis

A mild phase-transfer catalytic reaction has been conducted to O-alkylate the acidic functions of a lignite humic acid (HA), using tetrabutylammonium hydroxide as the phase-transfer catalyst. The HA acidic functional groups were made to react, in tetrahydrofuran, by nucleophilic substitution with several alkyl halides—methyl iodide, and ethyl, propyl, and butyl, and benzyl bromide. The occurrence of the O-alkylation reaction was assessed by elemental analysis and ¹H NMR, CPMAS ¹³C NMR, and FTIR spectroscopy. Bonding of alkyl groups increased the carbon and hydrogen content and the H/C ratios of all the humic reaction products. Increased nitrogen in the reaction products suggested incomplete removal of the phase-transfer catalyst after purification of the alkylated HA. ¹H NMR and CPMAS ¹³C NMR spectra of alkylated products provided evidence of the successful occurrence of the alkylation reactions. Infrared spectra confirmed the NMR results, revealing the characteristic absorption of newly formed alkyl and aryl ethers and esters in the alkylated products and C–H stretching in the aromatic ring of the benzylated derivative. These findings indicate that humic matter can be successfully alkylated with several different alkylating groups by catalysed phase-transfer reaction. This O-alkylation reaction has the advantage of being mild, versatile, and high-yielding compared with traditional methylation reactions applied to HA. The possibility of introducing different alkyl groups into the HA by a mild phase-transfer reaction may become useful by enabling improved fractionation of humic supramolecular associations and further understanding of the molecular nature of humic substances.     

分子动力学模拟研究A1408G突变对核糖体16S rRNA片段的影响

利用分子动力学模拟方法, 研究了原核生物核糖体小亚基中的16S rRNA片段与氨基糖苷类抗生素巴龙霉素复合物结构的柔性. 结果表明, 16S rRNA片段中的1408位点的腺嘌呤(A)突变为鸟嘌呤(G), 改变了与tRNA中反密码子环识别相关的2个腺嘌呤A1492和A1493的空间构象, 阻碍了氨基糖苷类抗生素与核糖体的结合, 从而影响原核生物蛋白转录过程. 模拟结果与实验测定的晶体结构相吻合, 可为基于核糖体16S rRNA的药物分子设计提供较可靠的结构信息.