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1.
Guanosine and 9-methylguanine treated with epoxides in glacial acetic acid are hydroxyalkylated stereoselectively at the N7 position of the guanine moiety. Previously unreported 7-(hydroxyalkyl)guanosinium acetates from the reactions of six epoxides with guanosine and 7-(hydroxyalkyl)-9-methylguaninium acetates from the reactions of two epoxides with 9-methyl guanine in glacial acetic acid have been prepared and characterized by their pmr spectra. By using an excess of epoxide, quantitative conversion of guanosine or 9-methylguanine to the corresponding 7-hydroxyalkylguanosinium or 7-hydroxyalkyl-9-methylguaninium acetate was achieved. Comparisons of the pmr spectra of the 7-(hydroxyalkyl)guanosinium acetates in DMSO-d6 to the spectrum of guanosine reveal that the H8 and amino group proton absorptions common to guanosine are shifted to a lower field, the absorptions of the H1 proton is absent, and the coupling constant of the H′1-H′2 protons of the ribosyl group is decreased from about 5.7 ± 0.1 Hz in guanosine to about 3.5 ± 0.1 Hz in the products. The use of the pmr spectral features of 7-(hydroxyalkyl)-9-methylguaninium compounds in characterizing 7-hydroxyalkylguanosinium compounds is discussed. Evidence is presented which suggests that extensive delocalization of positive charge exists in both the pyrimidine and imidazole rings of N7-hydroxyalkylated guanosine and N7-hydroxyalkylated-9-methylguanine. The possible effects of charge delocalization upon the hydrogen bonding potential of 7-hydroxyalkylated guanine moieties in DNA is discussed. 相似文献
2.
S-Alkylation of 2-acetamido-9-(2-acetoxyethoxymethyl)-6-oxo-8-thioxopurine was used to synthesize its novel S- and N(7)-substituted derivatives. We have established the effect of the structure of the alkylating agent on the reaction conditions and its regioselectivity. We have shown that the synthesized guanine derivatives can be modified further. 相似文献
3.
9-[[2-Hydroxy-1-(aminomethyl)ethoxy]methyl]guanine (1a), an amino analogue of 9-[[2-hydroxy-1-(hydroxymethyl)-ethoxy]methyl]guanine (I) which is a potent antiviral agent, has been synthesized a multistep-synthesis. 相似文献
4.
顺铂化合物与鸟嘌呤异构体相互作用的理论研究 总被引:1,自引:0,他引:1
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. 相似文献
5.
Adrian Carpov Cornelia Luca Virgil Brboiu 《Journal of polymer science. Part A, Polymer chemistry》1984,22(1):269-275
The chlorometylation of linear and crosslinked polystyrene with 1,4-bis(chloromethoxy) butane was studied, and the behavior of 1,4-bis(chloromethoxy)butane in the presence of chloromethylation catalysts was also established by 1H-NMR spectroscopy. 相似文献
6.
Manuel G. Basallote Rosario Vilaplana Francisco González-Vílchez 《Transition Metal Chemistry》1986,11(6):232-235
Summary Reaction of [MCl2(H4Y)] or (H6Y)[MCl4] compounds (M = Pd or Pt; Y = EDTA, PDTA or CDTA) with guanine (Gu-H) in 0.5 M HCl yields new complexes MCl2(Gu-H)(H2O which have been characterized by elemental analyses in conjunction with electronic, i.r. and n.m.r. spectra. A dimeric structure with two bridging chloride ligands, including coordination of guanine through atom N(9), is proposed for both compounds.Abbreviations used in the paper EDTA
1,2-diaminoethane-N,N,N,N-tetraacetate
- PDTA
1,2-diaminopropane-N,N,N,N-tetraacetate
- CDTA
trans-1,2-diaminocyclohexane-N,N,N,N-tetraacetate
- Gu-H
guanine
- 9-EtGu-H
9-ethylguanine 相似文献
7.
9-(4-Hydroxy-3-hydroxymethylbutyl) guanine (Penciclovir) is a potent and selective inhibitor of members of the herpes virus family. A new convenient synthesis of fluorinated Penciclovir analogues 9-(4-fluoro-3-hydroxymethylbutyl) guanine (FHBG) and 2-amino-6-fluoro-9-(4-hydroxy-3-hydroxy-methylbutyl) purine (6-Fluoropenciclovir) were described. The structures of the products were characterized by UV, IR, 1H NMR, 19F NMR spectra and MS. 相似文献
8.
Metallo-guanines of the type [M(G)2·2H2O] [M = NiII, FeII, CuII and UO2
II; G = anionic guanine], [M(G)2(GH)· H2O] (M = CoII and MnII; GH = neutral guanine), [Pd(G)2]·2H2O and [Zn(G)Cl]2 have been isolated and characterised. Anionic guanine functions as a bidentate ligand and links through N(3) and N(9). E.p.r. data indicate that the CuII complex has a highly distorted octahedral structure. The magnetic susceptibility data suggest that the CoII and NiII complexes possess pseudooctahedral geometry. Neutral guanines are probably unidentate and coordinate either through N(3) or N(9). The isolated guanosine complexes are of the types: [M(Gs)2·H2O] [M = NiII and CuII, Gs = anionic guanosine] [Pd(Gs)2]·2H2O and [UO2(Gs)2]. I.r. data indicate that guanosine also functions as a bidentate ligand, but coordinates through N(1) and C2 — NH2. The electronic absorption spectra of the complexes indicate that guanine is a stronger ligand than guanosine. 相似文献
9.
The synthesis of the guanine derivative (±)-2-amino-1,9-dihydro-9-[(1′α,2′β,3′β,4′α)-(2′,3′,4′-trihydroxy-1′-cyclopentyl]-6H-purin-6-one ( 2 ) is described. This compound is viewed as the carbocyclic ribofuranoside guanine nucleoside analogue lacking the 5′-methylene. 相似文献
10.
11.
Edward Rosenberg Fabrizio Spada Brooke Martin Luciano Milone 《Journal of organometallic chemistry》2004,689(25):4729-4738
The water-soluble triosmium cluster [Os3(CO)9(μ-η2-(4-CHO)C9H5N)(μ-H)(P(OCH2CH2N(CH3)3I)3)] (4) was tested for its reactivity with plasmid DNA. In contrast to the band retardation previously observed with a related series of positively charged clusters, an intensification and retardation of three discrete bands was observed with increasing cluster concentration. In order to further investigate the apparent modification of DNA by 4, its interaction with a 22-oligomer (sequence 5′-AGT TGT GGT GAC TTT CCC AGG C-3′) was examined. Incubation with this oligonucleotide (pH 7.4 in Tris-HCl buffer and 100 mM NaCl) followed by HPLC analysis revealed the formation of three dose dependent products assigned as covalent modifications at three sites of the oligonucleotide. Incubation of 4 with 32P-ATP labeled oligonucleotide at the 5′-end followed by treatment with piperidine and comparison with the standard Maxam-Gilbert sequencing protocol products revealed only general background cleavage, indicating that the modification products are piperidine labile and suggesting that the modification involved formation of a Schiff base. An alternative approach was then pursued which involved annealing the 4-oligonucleotide products with their complementary strand and treatment of the resulting duplex DNAwith the exonuclease, Exo III. This assay indicated three exonuclease stops, consistent with the three products observed by HPLC whose electrophoretic mobility approximately matched guanine containing fragments when compared with the Maxam-Gilbert sequencing lanes. Reduction of the 4-oligonucleotide products with borohydride reducing agents, followed by treatment with piperidine, resulted in the formation of one product (by HPLC) with the same electrophoretic mobility as the AGTT fragment based on comparison with the Maxam-Gilbert sequencing lanes. This product most likely results from reduction of an initially formed Schiff base adduct (to the corresponding amine) with the guanine of the TGT fragment of the oligonucleotide, and corresponds to the most stable of the three Schiff base adducts detected by HPLC and by incubation with the exonuclease. The other two products are less stable and competitive reduction of the free aldehyde functionality on the cluster in equilibrium with these adducts precludes their detection after treatment with the reducing agents. The formation of the Schiff base adduct is further corroborated by the model reaction of [Os3(CO)10(μ-η2-(4-CHO)C9H5N)(μ-H)] (4′) with acetylated guanine in nonaqueous solvents where disappearance of the aldehyde resonance and the appearance of several new resonances in the 6-9 ppm region of the 1H NMR of the reaction mixture is noted. 相似文献
12.
G. A. Smirnov P. B. Gordeev S. V. Nikitin G. V. Pokhvisneva T. V. Ternikova O. A. Luk’yanov 《Russian Chemical Bulletin》2016,65(12):2879-2886
Reactions of 1-alkoxy-3-(2-hydroxyethyl)triaz-1-ene 2-oxides and 1-chloromethoxytriaz1-ene 2-oxides with chloromethoxy derivatives of 3-alkyl-3-(2-acetoxyethyl)- and 3,3-bis(2-acetoxyethyl)-1-hydroxytriaz-1-ene 2-oxides result in very complex product mixtures with the major product comprising the starting salt fragments linked by a methylene bridge. In these products, the central methylene group bridges either two oxygen atoms or two nitrogen atoms, or one oxygen and one nitrogen atom. The synthesized compounds contain from two to four 2-hydroxyethyl moieties. 相似文献
13.
Formation of 8‐oxoguanine (8OG) from guanine in biological systems is known to cause lethal mutation and cancer. It has been suggested earlier, on the basis of experimental studies, that the oxygen molecule in its lowest singlet excited state (1O2) plays an important role in the formation of 8OG. In order to understand the possible mechanisms in this context, B3LYP/6‐31+G* and MP2/6‐31+G* calculations were carried out on the structures and stabilities of different molecules and complexes involved in the formation of 8OG. All the molecules, complexes, and transition states studied in the present report were solvated in aqueous media. Guanine has been found to make a strong complex with 1O2 with the latter species located above the imidazole ring plane, and the complex of guanine with 3O2 is much weaker than that with 1O2. Transition state calculations were carried out to study formation of 7,8‐dihydro,8‐hydroxyguanine (8OHG) and 2‐oxo‐imidazole. It has been shown that 8OG can be formed in two different ways: (i) due to interaction of the radical cation of guanine with O where 8OHG complexed with 1O2 would occur as an intermediate, and (ii) due to interaction of guanine with 1O2 leading to the formation of guanine hydroperoxide that would react with a water molecule in the presence of two 1O2 molecules serving as a source of energy to overcome the barrier. It is shown that because the interaction strengths of 3O2 and 1O2 with other molecules, e.g., guanine, are very different, a crossing of their potential energy surfaces takes place in both gas phase and aqueous media, as a result of which the lifetime of 1O2 is strongly decreased. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2005 相似文献
14.
Hydrogen trioxide (HOOO) radical and other polyoxides of general formula, ROnR (where R stands for hydrogen, other atoms or groups and n?≥?3), are believed to be key intermediates in atmospheric chemistry and biological oxidation reactions. In this contribution, DFT calculations using M06-2X density functional and the 6-31G(d,p) and 6-311+G(d,p) basis sets have been carried out to study different reactions of HOOO radical with guanine such as addition of HOOO radical at the C2, C4, C5, and C8 sites of guanine, abstraction of hydrogen atoms (H1, H2a, and H8) of guanine, and the mechanisms of oxidation of guanine with HOOO radical yielding 8-oxoguanine(a highly mutagenic derivative of guanine) and its radical in gas phase and aqueous media. The polarizable continuum model (PCM) has been used for solvation calculations in aqueous media. Our calculations reveal that the C8 site of guanine is the most reactive site for addition of HOOO radical, and adduct formed at this site would be appreciably stable. The rate constant (\( =\frac{K_bT}{h}{e}^{-\frac{\Delta {E}^b}{RT}} \)) at the C8 site is found to be 6.07?×?107 (2.89?×?107) s?1 at the M06-2X/6-311+G(d,p) level of theory in gas phase (aqueous media). The calculated barrier energy and heat of formation of hydrogen abstraction reactions show that HOOO radical would not abstract hydrogen atoms of guanine. Oxidation of guanine with HOOO radical can occur following two schemes (Scheme 1 and Scheme 2). It is found that formation of 8-oxoguanine radical via Scheme 1 would predominate over formation of 8-oxoguanine via Scheme 2, in a reaction of HOOO radical and guanine. Thus, HOOO radical can be treated as a member of reactive oxygen species (ROS) which play key roles in biological oxidation reactions, in agreement with previous literature reports. 相似文献
15.
在B3LYP/6-311++G**水平上用极化连续介质模型(PCM)系统研究了金属离子(M+/2+=Na+,K+,Ca2+,Mg2+,Zn2+)和十三种鸟嘌呤异构体形成的配合物GnxM+/2+(n为鸟嘌呤异构体的编号,x表示M+/2+与鸟嘌呤异构体的结合位点)在气(g)液(a)两相中的稳定性顺序.着重探讨了液相中配合物的稳定性差异,并且从溶质-溶剂效应、结合能、形变能及异构体的相对能量等几个方面分析了造成稳定顺序发生变化的原因.报道了溶液中这五种金属离子与鸟嘌呤异构体结合形成的六种基态配合物:aG1N2,N3Na+,aG1N2,N3K+,aG1O6,N7Ca2+,aG1N2,N3Mg2+(aG1O6,N7Mg2+),aG2N3,N9Zn2+.可以看出,除了在Zn2+配合物中鸟嘌呤异构体为G2外,构成其余四种金属离子配合物的鸟嘌呤异构体都是G1,但结合位点不同.同时对气相中各类配合物稳定性也进行了系统的排序,并报道了几种较稳定的配合物,如:gG3N1,O6K+,gG5N1,O6K+,gG3N1,O6Ca2+/Mg2+,gG4O6,N7Ca2+/Mg2+. 相似文献
16.
A number of antitumor-active octahedral organotin complexes of the type R2SnX2L2, where R=ethyl or phenyl, X = chloride or bromide, and L2 = o- phenanthroline or 2-(2-pyridyl)benzimidazole, have been shown to exhibit in vitro antiherpes activity towards both herpes simplex virus types 1 and 2 (HSV-1 and HSV-2). In addition, a series of mono-, di-, and tri-organotin halides (alkyl and phenyl) demonstrated weak antiherpes activity in the same viral assay system. Selectivity indexes for the tin compounds were calculated and compared with those available in the literature for a number of well-characterized and commercially important antivirals, e.g. adenine-9-β-D-arabinofuranoside (ara-A), cytosine-β-D-arabinofuranoside (ara-C), 5-iodo-2′-deoxyuridine (IDU) and 9-(2-hydroxyethoxymethyl)guanine (acyclovir, ACY). Although the organotin complexes are less effective in vitro than either ACY or IDU, as determined by their selectivity indexes, they are comparable in activity with both ara-A and ara-C in this particular assay. With few exceptions, most notably (C2H5)2SnBr2(o-phen), the organotin compounds examined in this study are more active against HSV-1 (F strain) than HSV-2 (MS strain). The results presented here represent the first study of the potential antiviral properties of organotin compounds. 相似文献
17.
A molecular orbital geometry optimization study of the potential surface of guanine, guanine? O2, and guanine? O2? water reaction products in the ground state has been carried out. The origin of the asymmetric double-well potential surface of guanine suggested earlier on the basis of experimental observations has been explained. The most stable binding of O2 with guanine (G) is found to occur at the C4C5 double bond of the latter molecule. In the case of G? O2? water reaction product (HOO? G? OH), the groups ? OOH and ? OH bind at C4 and C8, respectively. The possiblity of a polymeric reaction product of the type R1? (G? O? O? G)n? R2 (R1, R2 = H, OH) has also been suggested. These results are broadly supported by experimental observations. The mechanism of spectral oscillations observed in UV-irradiated guanine solutions has been discussed. 相似文献
18.
Ointment-like poly(ortho esters) were synthesized for the first time from the reaction of 3,9-bis(methylene)-2,4,8,10-tetraoxaspiro[5. 5] undecane with poly(ethylene glycol)-400, N,N-bis(2-hydroxyethyl)-n-hexadecylamine and N,N-bis(2-hydroxyethyl) palmitamide, respectively. The obtained polymers were characterized by 1H NMR spectra, 13C NMR spectra, elemental analyses, light scattering, and measurements of intrinsic viscosity. The influence of catalyst on the intrinsic viscosity of polymers was investigated. The 9-[(1,3-dihydroxy-2-propoxy) methyl] guanine controlled release profiles of hydrophobic ointment-like polymers such as polymer PII in vitro were also discussed. 相似文献
19.
Ruohola AM Koissi N Andersson S Lepistö I Neuvonen K Mikkola S Lönnberg H 《Organic & biomolecular chemistry》2004,2(13):1943-1950
Reactions of 9-ethylguanine, 2'-deoxyguanosine and guanosine with bromomalondialdehyde in aqueous buffers over a wide pH-range were studied. The main products were isolated and characterized by (1)H and (13)C NMR and mass spectroscopy. The final products formed under acidic and basic conditions were different, but they shared the common feature of being derived from glyoxal. Among the 1 : 1 adducts, 1,N(2)-(trans-1,2-dihydroxyethano)guanine adduct (6) predominated at pH < 6 and N(2)-carboxymethylguanine adduct (10a,b) at pH > 7. In addition to these, an N(2)-(4,5-dihydroxy-1,3-dioxolan-2-yl)methylene adduct (11a,b) and an N(2)-carboxymethyl-1,N(2)-(trans-1,2-dihydroxyethano)guanine adduct (12) were obtained at pH 10. The results of kinetic experiments suggest that bromomalondialdehyde is significantly decomposed to formic acid and glycolaldehyde under the conditions required to obtain guanine adducts. Glycolaldehyde is oxidized to glyoxal, which then modifies the guanine base more readily than bromomalondialdehyde. Besides the glyoxal-derived adducts, 1,N(2)-ethenoguanine (5a-c) and N(2),3-ethenoguanine adducts (4a-c) were formed as minor products, and a transient accumulation of two unstable intermediates, tentatively identified as 1,N(2)-(1,2,2,3-tetrahydroxypropano)(8) and 1,N(2)-(2-formyl-1,2,3-trihydroxypropano)(9) adducts, was observed. 相似文献
20.
Dr. Barbara Müller Dr. Wei‐Zheng Shen Dr. Pablo J. Sanz Miguel Dr. Francisca M. Albertí Dr. Tushar van der Wijst Dr. Marc Noguera Dr. Luis Rodríguez‐Santiago Prof. Mariona Sodupe Prof. Bernhard Lippert 《Chemistry (Weinheim an der Bergstrasse, Germany)》2011,17(36):9970-9983
The preparation and X‐ray crystal structure analysis of {trans‐[Pt(MeNH2)2(9‐MeG‐N1)2]} ? {3 K2[Pt(CN)4]} ? 6 H2O ( 3 a ) (with 9‐MeG being the anion of 9‐methylguanine, 9‐MeGH) are reported. The title compound was obtained by treating [Pt(dien)(9‐MeGH‐N7)]2+ ( 1 ; dien=diethylenetriamine) with trans‐[Pt(MeNH2)2(H2O)2]2+ at pH 9.6, 60 °C, and subsequent removal of the [(dien)PtII] entities by treatment with an excess amount of KCN, which converts the latter to [Pt(CN)4]2?. Cocrystallization of K2[Pt(CN)4] with trans‐[Pt(MeNH2)2(9‐MeG‐N1)2] is a consequence of the increase in basicity of the guanine ligand following its deprotonation and Pt coordination at N1. This increase in basicity is reflected in the pKa values of trans‐[Pt(MeNH2)2(9‐MeGH‐N1)2]2+ (4.4±0.1 and 3.3±0.4). The crystal structure of 3 a reveals rare (N7,O6 chelate) and unconventional (N2,C2,N3) binding patterns of K+ to the guaninato ligands. DFT calculations confirm that K+ binding to the sugar edge of guanine for a N1‐platinated guanine anion is a realistic option, thus ruling against a simple packing effect in the solid‐state structure of 3 a . The linkage isomer of 3 a , trans‐[Pt(MeNH2)2(9‐MeG‐N7)2] ( 6 a ) has likewise been isolated, and its acid–base properties determined. Compound 6 a is more basic than 3 a by more than 4 log units. Binding of metal entities to the N7 positions of 9‐MeG in 3 a has been studied in detail for [(NH3)3PtII], trans‐[(NH3)2PtII], and [(en)PdII] (en=ethylenediamine) by using 1H NMR spectroscopy. Without exception, binding of the second metal takes place at N7, but formation of a molecular guanine square with trans‐[(Me2NH2)PtII] cross‐linking N1 positions and trans‐[(NH3)2PtII] cross‐linking N7 positions could not be confirmed unambiguously, despite the fact that calculations are fully consistent with its existence. 相似文献