Evaluation of alkaloids binding to the parallel quadruplex structure [d(TGGGGT)]4 by electrospray ionization mass spectrometry

In this study, electrospray ionization mass spectrometry (ESI‐MS) was used to investigate the binding interaction of six alkaloids with parallel intermolecular G‐quadruplex [d(TGGGGT)]₄, and five alkaloids including berberine, jatrorrhizine, palmatine, tetrandrine, and fangchinoline showed complexation with the target DNA. Relative binding affinities were estimated on the basis of mass spectrometric data. The slight differences in chemical structures of berberine, jatrorrhizine, and palmatine had little influence on their binding affinities to [d(TGGGGT)]₄. Tetrandrine and fangchinoline selectively bound to [d(TGGGGT)]₄ versus duplex DNA. Collision‐induced dissociation (CID) experiments showed that the complexes with berberine, jatrorrhizine, and palmatine dissociated via strand separation and ligand retaining in the strand while the complexes with tetrandrine and fangchinoline were dissociated via ligand elimination. A comparison of dissociation patterns in CID experiments of complexes with the alkaloids to those with the traditional G‐quadruplex DNA binders suggested an end‐stacking binding mode for tetrandrine and fangchinoline and an intercalation binding mode for berberine, jatrorrhizine, and palmatine to the target DNA. The current work not only provides deep insight into alkaloid/[d(TGGGGT)]₄ complexes and useful guidelines for design of efficient anticancer agents but also demonstrates the utility of ESI‐MS as a powerful tool for evaluating interaction between ligand and quadruplex DNA. Copyright © 2012 John Wiley & Sons, Ltd.     

Structural and thermodynamic studies of the interaction of distamycin A with the parallel quadruplex structure [d(TGGGGT)]4

The complex between distamycin A and the parallel DNA quadruplex [d(TGGGGT)]4 has been studied by 1H NMR spectroscopy and isothermal titration calorimetry (ITC). To unambiguously assert that distamycin A interacts with the grooves of the quadruplex [d(TGGGGT)]4, we have analyzed the NMR titration profile of a modified quadruplex, namely [d(TGGMeGGT)]4, and we have applied the recently developed differential frequency-saturation transfer difference (DF-STD) method, for assessing the ligand-DNA binding mode. The three-dimensional structure of the 4:1 distamycin A/[d(TGGGGT)]4 complex has been determined by an in-depth NMR study followed by dynamics and mechanics calculations. All results unequivocally indicate that distamycin molecules interact with [d(TGGGGT)]4 in a 4:1 binding mode, with two antiparallel distamycin dimers that bind simultaneously two opposite grooves of the quadruplex. The affinity between distamycin A and [d(TGGGGT)]4 enhances ( approximately 10-fold) when the ratio of distamycin A to the quadruplex is increased. In this paper we report the first three-dimensional structure of a groove-binder molecule complexed to a DNA quadruplex structure.     

High-resolution structure of an extended A-tract: [d(CGCAAATTTGCG)]2

The crystal structure of [d(CGCAAATTTGCG)]2 has been determined to 1.5 A resolution, representing the first high-resolution structure of this DNA fragment. The ion interactions are novel. A spermine molecule replaces a Mg2+ observed in analogous structures. Unlike lower-resolution structures, the minor groove is narrow and the major groove lacks extra Watson-Crick hydrogen bonds. In addition, a monolayer of solvent sites, including a "spine of hydration", is visible in the minor groove. The crystal of [d(CGCAAATTTGCG)]2 was grown from a solution containing spermine, magnesium, and lithium. The conformation recapitulates that of "monovalent-minus" DNA.     

d6 and d8 Metal Carbonyl Complexes of 7,7-Dimethoxy-5,6-dimethylidenebicyclo[2.2.1]hept-2-ene. Stereoselective Hydroformylation of an [Fe(CO)4(olefin)] Complex

Reaction of 7,7-dimethoxy-5,6-dimethylidenebicyclo[2.2.1]hept-2-ene ( 2 ) with various metal carbonyls and their derivatives gave the η²-M(CO)₄ (M = Fe ( 17 ), Ru ( 18 )), η⁴-M(CO)₃ (M = Fe ( 19x, 19n ), Ru ( 20n )), and η²-M(CO)₅ and η⁶-M(CO)₃ (M = Cr, Mo, W) complexes. The trigonal bipyramidal η²-M(CO)₄ complexes present an exceptional C_3v symmetry at the metal with the C,C-double bond in an axial position. In all the η²-complexes, this double bond is stereospecifically coordinated by its exo-vs. endo-η⁴-Fe(CO)₃ configuration was established by chemical correlation (hydrolysis, hydrogenation) with the corresponding complexes ( 24x, 24n ) of 7,7-dimethoxy-2,3-dimethylidenebicyclo[2.2.1]heptane ( 5 ). The relative rates of hydrolysis (AcOH/H₂O 2:1, 50°C) of ligands 2 and 5 and of complexes 19x, 19n, 24x , and 24n to the corresponding ketones showed an acceleration effect only when the metal is coordinated to the exo-face. This was attributed to an F-strain effect on the leaving group of the substrate. Compound 17 was further metallated by [Fe₂(CO)₉] giving the bimetallic isomers 21xn and 21xx . The endocyclic C,C-double bond of the latter can be stereospecifically hydroformylated (1 atm CO, AcOH/H₂O, 25°C) giving 29x (49%). Hydroformylation of 17 gave the corresponding uncoordinated aldehydes 30x/30n in better yields (76%) but with lower selectivity (3:1). These are the first examples of hydroformylation of an isolated [Fe(CO)₄(olefin)] complex.     

Formation of an interlocked quadruplex dimer by d(GGGT)

A tetranucleotide sequence d(GGGT) has been shown to self-assemble into an interlocking quadruplex dimer. UV-melting studies indicated the existence of two species that each showed distinct quadruplex melting transitions, a low-T(m) species, Q(l), and a high-T(m) species, Q(h). Conditions were controlled to favor the formation of either Q(l) or Q(h). Q(l) and Q(h) each showed circular dichroism spectra characteristic of parallel quadruplexes. Negative ion nano-electrospray ionization mass spectrometry confirmed that Q(l) was a tetrameric complex, d(GGGT)(4), and Q(h) was an octameric complex, d(GGGT)(8). High-resolution (1)H NMR spectroscopy evidenced that d(GGGT)(4) was a C(4)-symmetric parallel tetramolecular quadruplex. The (1)H NMR spectrum of d(GGGT)(8) was consistent with a structure formed by the dimerization of a parallel, "slipped" tetramolecular quadruplex that has its diagonal strands staggered by one base. This "slippage" results in two guanine bases at the 5' end of the quadruplex being presented diagonally that are not involved in tetrads. Two such "slipped" quadruplexes dimerize via these free G-bases at the 5' ends by forming an extra G-tetrad. Each "slipped" quadruplex contributes two guanine bases to this extra G-tetrad. The formation of a novel GTGT tetrad is also observed at both the 3' ends of the interlocked quadruplex dimer.     

Synthesis and crystal structure of the deuterated organic conductor, (d8-ET)4[Hg2(SCN)4Cl2]

On the basis of completely deuterated bis(ethylenedithio)tetrathiafulvalene (d₈-ET), new organic conductors, (d₈-ET)₄[Hg₂(SCN)₄Cl₂] and (d₈-ET)₂[Hg(SCN)₂Br] have been synthesized and studied by X-ray structural analysis. Unlike nondeuterated organic metalsk-(ET)₂[Hg(SCN)_3–n X _n ] (X = Cl or Br;n=1 and 2), the crystal structure of (d₈-ET)₄[Hg₂(SCN)₄Cl₄] exhibits -type packing of the d₈-ET radical cations in the conducting layer and a polymeric structure of anions, in which both the SCN groups and the Cl atoms are involved in the bridging bonds. The crystals of (d₈-ET)₂[Hg(SCN)₂Br] and the nondeuterated form (ET)₂[Hg(SCN)₂Br] are isostructural.Translated fromIzvestiya Akademii Nauk. Seriya Khlmicheskaya, No. 5, pp. 905–909, May, 1995.This work was financially supported by the International Science Foundation (Grant RE1 000), the Scientific Council on the Problems of High-Temperature Superconductivity (Project No. 93030), and the Russian Foundation for Basic Research (Project No. 94-03-09950).     

IR-Untersuchungen an B-Tris (dimethylamino) boroxin und B-Tris[dimethylamino (d6)] boroxin

Zusammenfassung In B-Tri(dimethylamino)boroxin zeigt — im Gegensatz zum B-Trimethoxyboroxin — die B–O-Hauptbande nur geringe Kopplung mit CH₃-Deformationsschwingungen. Die B–N-Valenzbande tritt hingegen mit _sCH₃ in Wechselwirkung, wodurch Banden mit gemischtem Schwingungscharakter entstehen. In der deuterierten Verbindung liegt BN verkoppelt mit BO bei 1461 cm^–1

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In B-Tri(dimethylamino)boroxin coupling between the B–O ring stretching main-band and CH₃ is weak in contrast to B-trimethoxyboroxine. Interference between BN and CH₃ leads to bands of mixed character, one of them is above 1500 cm^–1. In [(CD₃)₂NBO] BN coupled with BO is at 1461 cm^–1.

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Mit 2 Abbildungen     

Unexpected reduction pathway of a Co(2+) salt to [HCo(CO)(4)] via [Co(2)(CO)(8)] in an ionic liquid

In the 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ionic liquid ([BMI][NTf(2)]), [Co(NTf(2))(2)] is reduced under 5.5 MPa of H(2)-CO to [Co(2)(CO)(8)] prior to [HCo(CO)(4)], provided a pyridine ligand is present in the medium.     

4-Oxatricyclo[5.2.1.0(2,6)]decan-10-one and 4-oxatricyclo[5.2.1.0(2,6)]dec-8-en-10-one. Experimental and DFT investigations of the pi-selectivities.

Ab initio MO and experimental pi-selectivities of hydride additions to 4-oxatricyclo[5.2.1.0(2,6)]decan-10-one and 4-oxatricyclo[5.2.1.0(2,6)]dec-8-en-10-one are described. The interactions of sigma(C1-C2) and sigma(C6-C7) with pi(C=O), on one hand, and those of sigma(C1-C9) and sigma(C7-C8) with pi(C=O), on the other hand, support anti-selectivities for both. This is in full accordance with the experiments. The arguments that are based on electrostatic interactions and electron donation from the ring oxygen do not apply.     

沙漏型砷钼酸盐(NH_4)_7[AsMo_8O_(30)]的水热合成,结构和性质(英文)

利用水热合成法制备了一种新的沙漏型砷钼酸盐化合物(NH_1)_7[AsMo_8O_(30)](1),借助X射线单晶衍射、X射线粉末衍射、红外光谱(IR)、紫外光谱(UV)和热分析研究了化合物的结构和性质.结果表明,化合物1属于正交晶系,Cmcm空间群,晶胞参数为:a=0.848 3(4)nm,b=2.322 3(10)nm,c=1.559 1(7)nm,V=3.071(2)nm~3,Z=4,R_1[I>2σ(I)]=0.0431,ωR_2[I>2σ(I)]=0.123 6.X射线单晶衍射分析结果表明,化合物1包含沙漏型的砷钼酸盐阴离子[AsMo_9O_(30)]~(7-).     

Al掺杂对尖晶石型Li[Mn(Al)]2O4结构的影响

采用共沉淀法按不同Al掺杂比例x[x=n(Al)∶n(Mn+Al)=0, 0.025, 0.050, 0.100, 0.150, 0.200]制得了Al(OH)3和Mn3O4混合物, 将其与LiNO3按一定比例混合, 在空气中于700 ℃烧结得Li[Mn(Al)]2O4样品. X射线衍射和Raman光谱结果表明, 在0≤x≤0.20范围内均得到了单相的尖晶石型样品, 随着x的增加, 晶胞参数减小, 晶格振动能量增加, Mn(Al)-O的结合增强, 结构稳定性增强.     

含有两个簇阴离子[As_8V_(14)O_(42)(SO_4)]~(6-)的金属-氧簇合物(H_2en)_6[As_8V_(14)O_(42)(SO_4)]_28H_2O的水热合成与晶体结构

合成了一种新的砷-钒-氧簇合物(H2en)6[As8V14O42(SO4)]28H2O(en为乙二胺),用元素分析、IR和TG-DTA等手段进行了表征,并用X射线衍射法测定了晶体结构。结果表明, 该晶体属单斜晶系,P21/c空间群,晶胞参数a = 20.9235(4),b = 11.9382(2),c = 43.5783(6) 牛琤 = 102.13,V = 10642.1(3) ?,Z = 4,Mr = 4678.01,Dc = 2.920 g/cm3,F(000) = 8944,m = 7.437 mm-1,R = 0.0735,wR = 0.1361。结构测定表明,结构中2个簇阴离子{[As8V14O42(SO4)]6-}与有机铵阳离子[H2en]2+之间靠静电作用相结合,同时与H2O通过氢键构成无限的三维骨架结构。     

The NMR structure of [Xd(C2)]4 investigated by molecular dynamics simulations

The i‐motif tetrameric structure is built up from two parallel duplexes intercalated in a head‐to‐tail orientation, and held together by hemiprotonated cytosine pairs. Two topologies exist for the i‐motif structure, one with outermost 3′ extremities and the other with outermost 5′ extremities, called the 3′E and 5′E topology, respectively. Since the comparison of sugar and phosphate group interactions between the two topologies is independent of the length of the intercalation motif, the relative stability of the 3′E and 5′E topologies therefore should not depend on this length. Nevertheless, it has been shown that the 3′E topology of the [d(C2)]4 is much more stable than the 5′E topology, and that the former is the only species observed in solution. In order to understand the reason for this atypical behavior, the NMR structure of the [Xd(C2)]4 was determined and analyzed by molecular dynamics simulations. In the NMR structure, the width of the narrow groove is slightly smaller than in previously determined i‐motif structures, which supports the importance of phosphodiester backbone interactions in the structure stability. The simulations show that the stacking of cytosines, essential for the i‐motif stability, is produced by a similar and non‐negative twisting of the phosphodiester backbones. The twisting is induced by an interaction between the backbones; the [Xd(C2)]4 in 5′E topology, exhibiting very limited interaction between the phosphodiester backbones, is thus unstable. Copyright © 2002 John Wiley & Sons, Ltd.