- Symmetric bis-benzimidazoles: New sequence-selective DNA-binding molecules
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A series of bis-benzimidazole compounds with a head-to-head orientation have been designed as sequence-specific DNA binders; crystallographic analysis of oligonucleotide complexes has been combined with DNase I footprinting to confirm that the predicted optimal site for the core bisbenzimidazole motif is the four-base-pair sequence 5'-AATT; this sequence specificity results in inhibition of transcription at A/T sites and may be responsible for the cytotoxic and antitumour effects shown by these head-to-head bis-benzimidazoles.
- Neidle, Stephen,Mann, John,Rayner, Emma L.,Baron, Anne,Opoku-Boahen, Yaw,Simpson, Ian J.,Smith, Nicola J.,Keith R, Fox,Hartley, John A.,Kelland, Lloyd R.
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Read Online
- Absolute Configuration Assignment from Optical Rotation Data by Means of Biphenyl Chiroptical Probes
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A non-empirical approach for the assignment of the absolute configuration of chiral 2-alkyl-substituted carboxylic acids and primary amines by [α]D measurements has been developed. The method requires the conversion of the chiral acids or amines into the corresponding 4,4′-disubstituted biphenylamides or biphenylazepines, respectively. In these derivatives a central-to-axial chirality transfer induces a preferred torsion in the biphenyl moiety revealed by the sign of the biphenyl A band in the ECD spectrum. By 4,4′-substitution on the biphenyl moiety a redshift of the A band is obtained, leading to an increase of its relative contribution to optical rotation. This allows to reliably establish a direct correlation between the [α]D sign, the biphenyl twist and, then, the substrate absolute configuration. This approach thus constitutes a really practical and reliable method to assign the absolute configuration of chiral carboxylic acids and primary amines by simple and straightforward [α]D measurement, readily obtainable by a routine instrumentation like the polarimeter.
- Vergura, Stefania,Scafato, Patrizia,Belviso, Sandra,Superchi, Stefano
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supporting information
p. 5682 - 5690
(2019/03/17)
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- Eco-friendly, catalyst and solvent-free, synthesis of acetanilides and N-benzothiazole-2-yl-acetamides
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An expeditious and green synthesis of acetamides in a solvent-free simple way is described, without catalyst or additives, and in good yield by an instantaneous reaction of anilines or 2-aminothiazoles and acetic anhydride without external heating, and with simple purification. Sixteen substituted acetanilides and four N-benzothiazole-2-yl-acetamides were formed, but aliphatic amines of low molecular weight were not as effective as aromatic ones, and only cyclohexylamine and the enaminone ethyl 3-amino-2-butenoate afforded the corresponding acetamides in good yield.
- Cunha, Silvio,De Santana, Louren?o L. B.
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p. 1137 - 1144
(2017/05/01)
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- Homocoupling of iodoarenes and bromoalkanes using photoredox gold catalysis: A light enabled Au(III) reductive elimination
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The formation of homocoupled alkane byproducts have been identified in the reduction of bromoalkanes via photoredox gold catalysis with dimeric Au(I) complexes. This prompted further investigation into the mechanism of formation of these byproducts and the diversity of C-X bonds amenable to this transformation. Examples were found when considering bromoalkanes while a wide variety of iodoarenes underwent this process in good to excellent yields. The light enabled homocoupling of iodoarenes made possible by photoredox gold catalysis is reported.
- Tran, Huy,McCallum, Terry,Morin, Mathieu,Barriault, Louis
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supporting information
p. 4308 - 4311
(2016/09/09)
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- Pd(OAc)2/PPh3-catalyzed desulfonylative homocoupling of arylsulfonyl chlorides
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The Pd-catalyzed homodimerization with respect to arylsulfonyl chlorides as an efficient method for the synthesis of biaryls has been developed. This desulfonylative reaction which was performed at reflux in 1,4-dioxane for 4 h under air afforded the desired products in good to excellent yields. The Pd(OAc)2/PPh3-catalyzed desulfonylative homodimerization of arenesulfonyl chlorides as an efficient method for the synthesis of biaryls was described. The corresponding products were obtained in good to excellent yields.
- Zhao, Qiao,Chen, Liangshun,Lang, Hongyue,Wu, Shengying,Wang, Limin
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p. 535 - 538
(2015/05/27)
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- Iterative double cyclization reaction by SRN1 mechanism. A theoretical interpretation of the regiochemical outcome of diazaheterocycles
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In this report, we present a synthetic and mechanistic study of novel iterative double cyclization intramolecular SRN1 reactions from diamides bearing two aryl iodide moieties. This cyclization affords aromatic diazaheterocyclic compounds in good yields. Two synthetic strategies were employed for their preparation: intramolecular SRN1 and Homolytic Aromatic Substitution. The mechanism is non-trivial and we propose that radicals are intermediates. The regiochemistry was studied using computational calculations, employing the DFT method and the B3LYP functional. It was found that the distribution of products depends on the cyclization activation energies, proportion of neutral conformers, and the type of the electron transfer reaction.
- Peisino, Lucas E.,Camargo Solorzano, Gloria P.,Budén, María E.,Pierini
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p. 36374 - 36384
(2015/05/05)
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- Design, synthesis, and anti-tumor evaluation of novel symmetrical bis-benzimidazoles
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A novel symmetrical bis-benzimidazole was designed as DNA minor groove binder. Molecular modeling study showed that it could dock into the minor groove of DNA. Several derivatives were synthesized and confirmed by IR, MS, and 1H NMR. All these novel compounds were screened for cytotoxic activity on SKOV-3, HeLa, and BGC-823 cell lines in vitro. Some compounds showed IC50s in the single-digit micromolar range for cytotoxicity in several tumor cell lines.
- Yang, Yan-Hui,Cheng, Mao-Sheng,Wang, Qing-He,Nie, Han,Liao, Na,Wang, Jian,Chen, Hong
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experimental part
p. 1808 - 1812
(2009/06/28)
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- Electrochemical oxidation of organic compounds in fluorosulfonic acid. XIII. Oxidative reaction of aromatic compounds in acidic systems based on FSO3H and CF3COOH
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Basing on the common scale of electrochemical potentials for superacids and acetonitrile, on diagnostic criteria of structural changes in depolarizers at their one-electron oxidation in superacids, and also on identification of conjugate chemical reactions data are presented on the structure, reactivity and pathways of kinetically retarded transformations of cationic intermediates into transition and final oxidation products of aromatic compounds generated in acidic media of wide range of acidity function H0 -22÷-3.
- Rudenko,Pragst
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p. 1589 - 1626
(2007/10/03)
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- The role of acetylation in benzidine metabolism and DNA adduct formation in dog and rat liver
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To determine whether benzidine is acetylated in dog, like rat, the metabolism of benzidine was assessed with dog and rat liver slices. Slices were incubated with 0.05 mM [3H]benzidine for 4 h. Media and cellular DNA were analyzed for acetylated benzidine metabolites and adducts. In rat, benzidine was rapidly converted to acetylated metabolites. At 1 h, benzidine, N-acetylbenzidine, and N,N'-diacetylbenzidine represented 5%, 23%, and 54%, respectively, of the total radioactivity in media. Within 2 h, 75% of the radioactivity was N,N'-diacotylbenzidine. In dog, 45% of the radioactivity was present in metabolites more polar than benzidine by 4 h. No N-acetylated metabolites were observed in dog liver slice media. To identify acetylated benzidine DNA adducts, N-(deoxyguanosin-8-yl)-N,N'-diacetylbenzidine was prepared and identified by FAB MS. This nucleoside adduct was used to synthesize N-(deoxyguanosin-8-yl)-N-acetylbenzidine and N'-(deoxyguanosin-8- yl)-N-acetylbenzidine. Nucleoside adducts from slices incubated with [3H]benzidine were analyzed by HPLC. With this method of analysis, the 3H- material did not correlate with the synthetic adduct standards. To improve sensitivity and identify liver adducts, a 32P-postlabeling method was developed. 2'-Deoxyguanosine 3'-monophosphate adduct standards of acetylated benzidine were prepared. 32P-Postlabeling analysis demonstrated that rat liver contained only N'-(3'-monophosphodeoxyguanosine-8-yl)-N-acetylbenzidine after a 1- or 4-h exposure to benzidine. In contrast, no acetylated adducts were detected in dog. Results indicate that dog is a nonacetylator with respect to benzidine. The availability of acetylated benzidine nucleotide standards allowed unambiguous identification of N'-(3'- monophosphodeoxyguanosin-8-yl)-N-acetylbenzidine as the adduct present in rat liver slices. These nucleotide adduct standards will be useful in subsequent studies in animals and human.
- Lakshmi,Zenser,Goldman,Spencer,Gupta,Fong Fu Hsu,Davis
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p. 711 - 720
(2007/10/03)
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- ortho-Substituent effects on the in vitro and in vivo genotoxicity of benzidine derivatives
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Benzidine and its 3,3'-diamino, 3,3'-dimethyl, 3,3'-dimethoxy, 3,3'-difluoro, 3,3'-dichloro, 3,3'-dibromo, 3,3'-dicarbomethoxy and 3,3'-dinitro derivatives together with 2-nitrobenzidine and 3-nitrobenzidine were compared for their in vitro and in vivo genotoxicity. Relative mutagenicity was established with Salmonella strains TA98, TA98/1,8-DNP6 and TA100 with and without S9 activation. All the derivatives in the presence of S9 were more mutagenic than benzidine with 3,3'-dinitro- and 3-nitro-benzidine having the greatest mutagenicity. Mutagenicity in all 3 strains with S9 activation could be correlated to electron-withdrawing ability of substituent groups, as measured by the basicity of the amines. This correlation was explained on the basis that electron-withdrawing groups could favor the stability of the mutagenic intermediate N-hydroxylamine and also enhance the reactivityof the ultimate mutagenic species, the nitrenium ion. Mutagenicity was also correlated to the energy of the lowest unoccupied molecular orbitals (E(LUMO)). Hydrophibicity was found to have very limited effect on the relative mutagenicity of our benzidine derivatives. The in vivo endpoint was chromosomal aberrations in the bone-marrow cells of mice following intraperitoneal administration of benzidine and its derivatives. In contrast to the in vitro results, while all the amines were genotoxic in vivo, only the 3-nitro derivative had a significant increase in toxicity over benzidine.
- You,Brezzell,Das,Espadas-Torre,Hooberman,Sinsheimer
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- Models for intramolecular exchange in organic π-conjugated open-shell systems: A comparison of three non-kekule biphenyldinitrenes
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The important effect of connectivity upon the nature of intramolecular exchange coupling of unpaired electrons by the biphenyl group was investigated by cryogenic matrix photolysis of diazide precursors expected to yield biphenyl-3,4′-dinitrene (1), biphenyl-3,3′-dinitrene (2), and biphenyl-4,4′-dinitrene (3). System 1 was predicted by parity-based qualitative models to exhibit a high-spin ground state. By Curie law analysis of its electron spin resonance (ESR) spectrum at cryogenic temperatures in frozen 2-methyltetrahydrofuran solution, 1 was found to be a quintet ground-state dinitrene with zero field splitting (zfs) parameters of |D/hc| = 0.153 cm-1, |E/hc| = 0.003 cm-1. System 2 was predicted to be disjoint with nearly-degenerate high-spin and low-spin states. Cryogenic frozen solution ESR spectroscopy showed no ESR-active dinitrene 2 upon extended photolysis of its appropriate diazide precursor, although the related mononitrene with zfs of |D/hc| = 0.996 cm-1 was clearly visible. We presume that system 2 was produced in this experiment, but that it acts either as a singlet ground-state dinitrene or as a pair of isolated mononitrenes. A biradical ESR spectrum was found for photolysis of the diazide precursor to 3, with zfs of |D/hc| = 0.189 cm-1 and |E/hc| -1. The thermal dependence of this biradical spectrum shows it to be an excited state, consistent with quinonoidal dinitrene 3 having a singlet ground state and a triplet excited state ca. 0.6 kcal/mol higher in energy. The results for dinitrenes 1-3 were compared to related work on dicarbene molecules described by others, and it was found that the dinitrenes and dicarbenes exhibit similar electron exchange coupling behavior.
- Minato, Masaki,Lahti, Paul M.,Van Willigen, Hans
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p. 4532 - 4539
(2007/10/02)
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