Spindle-inhibiting effects of organotin compounds. II. Induction of chromosomal supercontraction by di- and tri-alkyl and -aryl compounds

Spindle-inhibiting effects of chemical compounds may be studied indirectly by quantitation of chromosomal contraction. The effects of the trimethyltin (TMT), dimethyltin (DMT), tributyltin (TBT), dibutyltin (DBT), triphenyltin (TPhT) and diphenyltin (DPht) moieties as the chloride on chromosomal contraction was studied by measurement of the average length of chromosome No. 1 from asynchronous cultures of human peripheral lymphocytes. TMT, TBT, TPhT and DPhT appear to be very strong inducers of chromosomal supercontraction, indicating that these compounds conceivably are spindle inhibitors, whilst DMT and DBT seem to be ineffective. The different effects of aryl versus alkyl and trivalent versus divalent organic substituents of tin on chromosome length may relate to different modes of action.     

Dealkylation of organotin compounds by biological dithiols: toward the chemistry of organotin toxicity

In this Communication, we report evidence for the dealkylation of trialkyltin compounds by a short linear peptide extracted from a small membrane protein (stannin) involved in cellular apoptosis and containing a CXC motif. We show that (a) organotin binding induces the formation of a beta-turn in the linear peptide, (b) both cysteines are necessary for the dealkylation reaction, and (c) stable 1:1 complexes are formed between the peptide and diorganotins that can be observed by ESI-MS. Organotin degradation by biological dithiols may be responsible for both the delayed activity of these toxins in humans and the organotin resistance mechanisms in bacteria.     

Structural and solvent effects on the 13C and 15N NMR chemical shifts of indoloquinoline alkaloids: experimental and DFT study

Indoloquinoline alkaloids represent an important class of antimalarial, antibacterial and antiviral compounds. They have been shown to bind to DNA via intercalation preferentially at GC-rich sequences containing nonalternating CC sites. The stability of complexes formed with biological macromolecules depends on noncovalent binding. In the present study, the ability of indoloquinolines to form intermolecular interactions with solvents was investigated by using NMR spectroscopy and density functional theory (DFT) (B3LYP/6-31G**) calculations. NMR data measured for indoloquinoline bases and the corresponding hydrochlorides are discussed in relation to the structure. DFT calculations of shielding constants in vacuo and in solution allowed the investigation of the influence of the environment on the NMR parameters. Calculations incorporating solvent effects indicated significant changes in the anisotropy of the electron distribution, reflected in the span of the chemical shielding tensor (Omega = sigma11 - sigma33). Solvent effects on the span of the 13C and 15N shielding tensor depended on the type of atom and the data indicated a significant influence of solute-solvent interactions.     

三苯基锡芳氧乙酸酯的合成和表征

三苯基锡芳氧乙酸酯的合成和表征刘宝殿，包明，张景萍（东北师范大学化学系、东北师范大学分析测试中心，长春，１３００２４）关键词芳氧乙酸，三苯基锡芳氧乙酸酯，合成，生物活性三苯基醋酸锡和三苯基氢氧化锡是防治甜菜褐斑病的有效药剂［１］．芳氧乙酸及其酯也具有...     

Rapid and direct speciation of methyltins in seawater by an on-line coupled high performance liquid chromatography-hydride generation-ICP/MS system

A novel on-line coupled HPLC-hydride generation (HG)-ICP/MS system was developed for rapid, direct and sensitive speciation of methyltins in seawater without any pretreatment step. Methyltin compounds were separated by reversed phase HPLC, and then on-line reacted with potassium borohydride and acetic acid to generate volatile hydride products. The volatile derivatization products were separated in the spray chamber of ICP/MS and then introduced into ICP/MS by argon gas for detection. Monomethyltin (MMT), dimethyltin (DMT) and trimethyltin (TMT) were baseline separated in less than 15 min by reversed phase HPLC. The influence of KBH₄ concentration and type of acid on the system performance was investigated and optimized. Calibration curves, based on peak heights against concentration, were linear in the range of 0.5-50 ng (Sn) mL⁻¹ of methyltins with correlation coefficients of 0.9990, 0.9990 and 0.9996 for MMT, DMT and TMT, respectively. The relative standard deviations measured at 10 ng (Sn) mL⁻¹ for these three methyltins were in the range of 0.6-1.4% (n = 5), and the calculated detection limits (S/N = 3) for MMT, DMT and TMT were 0.266, 0.095 and 0.039 ng (Sn) mL⁻¹, respectively. This method was successfully applied to the speciation of methyltins in seawater with spiked recovery in the range of 95.4-106.9%. MMT and DMT were detected in all the seawater samples with concentrations in the range of 1.0-1.5 and 0.30-0.57 ng (Sn) mL⁻¹ for MMT and DMT, respectively.     

The determination of sulfoxide configuration in five-membered rings using NMR spectroscopy and DFT calculations

Cyclic five-membered ring sulfoxides and sulfones were prepared by a stepwise in situ oxidation of the corresponding sulfides with meta-chloroperbenzoic acid in an NMR tube. The oxidation was followed by NMR and both ¹H and ¹³C NMR data were collected. The geometries of all of the compounds were optimized using the DFT B3LYP/6-31G⁷ method and the ¹³C and ¹H chemical shifts were calculated for geometry-optimized structures with the DFT B3LYP/6-31++G⁷ method. The calculated ¹³C chemical shifts induced by oxidation (Δδ values) were in very good agreement with the experimental data and could be used to determine the oxidation state of the sulfur atom (–S–, –SO–, –SO₂–). The characteristic differences of the induced oxidation chemical shifts of the carbon atoms in the α-position and β-position to sulfur were successfully used to distinguish between the diastereoisomeric sulfoxides and allowed configuration determination.     

Sequestration of organometallic compounds by natural organic matter. binding of trimethyltin(IV) by fulvic and alginic acids

The binding capacity of fulvic and alginic acids towards trimethyl tin(IV) cation was quantitatively determined in order to evaluate the sequestering ability of toxic organometallic compounds by natural organic matter. Investigations were performed in the pH range of natural waters (5–8.5) where the carboxylate groups, largely present in both sequestering agents, are the main binding sites. A chemical interaction model, according to which both the protonation of polyelectrolyte ligands and the hydrolysis of the organotin cation in NaCl aqueous solution were considered, was used to define the speciation of the systems under investigation. Measurements performed at different ionic strength values (0.1, 0.25, 0.5 and 0.7 mol L^?1, NaCl) allowed us to consider the dependence of stability constants on the ionic strength, and to calculate the formation constants at infinite dilution. Results obtained show the formation of the complex species TMT(L), TMT(L)₂ and TMT(L)(OH) for L = fulvic acid and TMT(L) for L = alginic acid, respectively. In order to compare the strength of interaction of these natural poly electrolytes with other analogous synthetic polyelectrolytes, measurements were also carried out on the trimethyltin(IV)–polyacrylate (5.1 kDa) system, and in this case the formation of TMT(L), TMT(L)₂ and TMT(L)(OH) species was found. Results show the following trend of stability for the species TMT(L) in the systems investigated: TMT–fulvate ≈ TMT–polyacrylate > TMT–alginate. On the basis of the stability data obtained, the lowest concentration of fulvic and alginic acids, able to act as sequestering agents towards triorganotin(IV) cation in the conditions of natural waters, was also calculated. Copyright © 2006 John Wiley & Sons, Ltd.     

Reduction of inner sulfonium salts, thioethers, and sulfones derived from closo-[B12H12]2- by lithium in methylamine: a new route to mercaptododecaborates

Anions [Me2SB12H11]- (2) and [MeSB12H11]2- (3) can be reduced by excess lithium in methylamine at -15 degrees C to yield [HSB12H11]2- (1) after workup. Such behavior toward this reducing system is similar to that of alkyl aryl sulfides. The sulfone [MeSO2B12H11]2- (12) also yields 1 as a major boron product upon reduction, while alkyl aryl sulfones produce the corresponding arenes under the same conditions. Similarly, isomers of (Me2S)2B12H10 (4-6) are reduced by lithium in methylamine yielding dithiols [(HS)2B12H10]2- (7-9). The tetrabutylammonium salts of 1 and 7-9 are obtained in 80-90% yields and characterized by multinuclear NMR and mass spectrometry, the latter three compounds being isolated and characterized for the first time. The reduction reaction provides access to dithiols 7-9 for biological evaluation and use in synthesis. Thus, 2 and 4-6 can be easily converted to [R2SB12H11]- and (R2S)2B12H10 in a two-step reduction-alkylation procedure. 1,2-(Bn2S)2B12H10 (13) obtained by alkylation of the reduction product of 4 by benzyl chloride was characterized by single-crystal X-ray diffraction analysis. Crystal data for 1,2-(Bn2S)2B12H10.CD3CN: C2/c (No. 15), a = 13.666(1) A, b = 16.978(1) A, c = 14.667(1) A, beta = 91.08(1) degrees, Z = 4.     

The synthesis of new cyclic thioquinone derivatives

New bis(thio)substituted, S‐,O‐substituted, and S‐,S‐substituted benzoquinone compounds were synthesized from the reaction of p‐chloranil ( 1 ) with S‐,O‐substituted thiols, dithiols, and monothiols. The ¹³C NMR spectra and the IR spectra of heterocyclic compounds 3 , 4 and 7 , 8 showed different behavior; that of 3 , 7 showed a carbon signal and a >CO group band for the carbonyl group and that of 4 , 8 showed two carbon signals and split bands for the carbonyl group. The structures of the novel compounds were characterized by microanalysis, FT‐IR, ¹H NMR, ¹³C NMR, MS, and UV–vis spectroscopy. The crystal structure of 2,3,5,6‐tetrakis(4‐fluorobenzylthio)cyclohexa‐2,5‐diene‐1,4‐dione ( 15 ) was determined by the X‐ray diffraction method. © 2010 Wiley Periodicals, Inc. Heteroatom Chem 21:446–452, 2010; View this article online at wileyonlinelibrary.com . DOI 10.1002/hc.20634     

三苯基锡—O,O—二芳基二硫代磷酸酯的合成和结构表征

本文合成了13种三苯基锡-O,O-二芳基二硫代磷酸酯,测定了它们的IR、~1H、~(31)C、~(119)SnNMR,MS和元素分析,结果表明该类化合物具有单体的四面体四价锡结构。     

Solution structure of R(2)Sn(IV)-beta-N-acetyl-neuraminate (R = Me, Bu) complexes in D(2)O and DMSO-d(6): experimental NMR and DFT computational study

Two diorganotin(IV)-NANA complexes (NANA (1) = beta-N-acetyl-Neuraminic Acid = 5-amino-3,5-dideoxy-D-glycero-beta-D-galactononulosic acid) with formula Me(2)Sn(iv)NANA (2) and Bu(2)Sn(IV)NANA (3) were synthesized and characterized by (1)H, (13)C and (119)Sn NMR spectroscopy, both in D(2)O and DMSO-d(6) solutions. The experimental data in DMSO suggested the monosaccharide bidentate chelation via O1 carboxylate and vicinal O2 alkoxide atoms, which, in D(2)O, can be dynamically extended to a third binding site (O8 atom) of the pendant chain. Coordination at the tin atom is discussed on the basis of experimental NMR data and DFT calculation.     

Crystallographic and Dynamic Aspects of Solid‐State NMR Calibration Compounds: Towards ab Initio NMR Crystallography

The excellent results of dispersion‐corrected density functional theory (DFT‐D) calculations for static systems have been well established over the past decade. The introduction of dynamics into DFT‐D calculations is a target, especially for the field of molecular NMR crystallography. Four ¹³C ss‐NMR calibration compounds are investigated by single‐crystal X‐ray diffraction, molecular dynamics and DFT‐D calculations. The crystal structure of 3‐methylglutaric acid is reported. The rotator phases of adamantane and hexamethylbenzene at room temperature are successfully reproduced in the molecular dynamics simulations. The calculated ¹³C chemical shifts of these compounds are in excellent agreement with experiment, with a root‐mean‐square deviation of 2.0 ppm. It is confirmed that a combination of classical molecular dynamics and DFT‐D chemical shift calculation improves the accuracy of calculated chemical shifts.     

51V solid-state magic angle spinning NMR spectroscopy and DFT studies of oxovanadium(V) complexes mimicking the active site of vanadium haloperoxidases

A series of 11 oxovanadium(V) complexes mimicking the active site of vanadium haloperoxidases have been investigated by (51)V magic angle spinning NMR spectroscopy and density functional theory (DFT). The MAS spectra are dominated by the anisotropic quadrupolar and chemical shielding interactions; for these compounds, C(Q) ranges from 3 to 8 MHz, and delta(sigma) is in the range 340-730 ppm. The quadrupolar coupling and chemical shielding tensors as well as their relative orientations have been determined by numerical simulations of the spectra. The spectroscopic NMR observables appear to be very sensitive to the details of the electronic and geometric environment of the vanadium center in these complexes. For the four crystallographically characterized compounds from the series, the quadrupolar and chemical shielding anisotropies were computed at the DFT level using two different basis sets, and the calculated tensors were in general agreement with the experimental solid-state NMR data. A combination of (51)V solid-state NMR and computational methods is thus beneficial for investigation of the electrostatic and geometric environment in diamagnetic vanadium systems with moderate quadrupolar anisotropies.     

The unexpected isolation of CTP-431, a novel thiopyrone from the sponge Cacospongia mycofijiensis

A reinvestigation of a Fijian collection of Cacospongia mycofijiensis has yielded the known mycothiazole and a novel heterocyclic, CTP-431 (1). Its structure including absolute configuration as 8R,9R,10S,13S was established using NMR data, calculated DFT (13)C chemical shifts and results from X-ray crystallography. It is possible that the tricyclic skeleton of CTP-431 (1) is biosynthetically related to the macrolide latrunculin A, however the thiopyrone moiety of 1 has no previous precedent in natural products chemistry.     

Spectroscopic,electrochemical, theoretical characterization and biological evaluation of a ferrocenyl-substituted unsymmetric azine ligand and its Cu(II) complex

Ferrocenyl-substituted unsymmetrical azine and its Cu(II) complex were prepared. The redox active ferrocene-based azine was obtained by condensation of 1-[(E)-hydrazono]-5-bromo-2-hydroxybenzene with ferrocene carboxaldehyde. The ferrocenyl ligand and its Cu(II) complex were characterized by IR, UV–vis, NMR, X-ray, magnetic susceptibility, molar electrical conductivity measurements, and TG techniques. The redox behaviors of the ferrocene compounds were investigated by cyclic voltammetry. Structural parameters and spectroscopic properties of the ligand and the Cu(II) complex were calculated by employing density functional theory (DFT) and time-dependent DFT and compared with available experimental data. We found slightly stronger binding ability for Cu(II) complex than the free ligand. DNA binding abilities for ferrocenyl-substituted unsymmetrical azine ligand and its Cu(II) complex are higher than some reported ferrocene compounds. We also studied DNA cleavage, superoxide and DPPH radical scavenging abilities of the compounds. Furthermore, the synthesized organometallic compounds can be bound to DNA through an intercalative mode.     

Solid-state and high-resolution liquid 119Sn NMR spectroscopy of some monomeric, two-coordinate low-valent tin compounds: very large chemical shift anisotropies

High-resolution liquid- and solid-state 119Sn NMR spectroscopy was used to study the bonding environment in the series of monomeric, two-coordinate Sn(II) compounds of formula Sn(X)C6H3-2,6-Trip2 (X = Cl, Cr(eta 5-C5H5)(CO)3, t-Bu, Sn(Me)2C6H3-2,6-Trip2; Trip = C6H2-2,4,6-i-Pr3). The trends in the principal components of the chemical shift tensor extracted from the solid-state NMR data were consistent with the structures determined by X-ray crystallography. Furthermore, the spectra for the first three compounds displayed the largest 119Sn NMR chemical shift anisotropies (up to 3798 ppm) of any tin compound for which data are currently available. Relaxation time based calculations for the dimetallic compound 2,6-Trip2H3C6Sn-Sn(Me)2C6H3-2,6-Trip2 suggests that the chemical shift anisotropy for the two-coordinate tin center may be as much as ca. 7098 ppm, which is as broad as the 1 MHz bandwidth of the NMR spectrometer.     

三(2-甲基-2-苯基丙基)锡芳氧乙酸酯的合成

三（２－甲基－２－苯基丙基）锡芳氧乙酸酯的合成刘宝殿,宁志刚,朱东升,包明（东北师范大学化学系,长春,１３００２４）关键词三（２－甲基－２－苯基丙基）锡芳氧乙酸酯,三（２－甲基－２－苯基丙基）氢氧化锡,芳氧乙酸,杀螨活性１９６６年Ｒｅｉｃｈｌｅ［１］...     

The determination of sulfoxide configuration in six-membered rings using NMR spectroscopy and DFT calculations

Cyclic six-membered ring sulfoxides and sulfones were prepared by a stepwise in situ oxidation of the corresponding sulfides with meta-chloroperbenzoic acid in an NMR tube. The oxidation was followed by NMR spectra and the ¹H and ¹³C NMR data were collected. The geometries of all of the compounds were optimized using the DFT B3LYP/6-31G^∗∗ method and the ¹³C and ¹H NMR chemical shifts were calculated for geometry-optimized structures with the DFT B3LYP/6-31++G^∗∗ method. The calculated ¹³C NMR chemical shifts induced by oxidation (Δδ values) are in very good agreement with the experimental data and can be used to determine the oxidation state of the sulfur atom (-S-, -SO-, -SO₂-). The characteristic differences of the induced oxidation chemical shifts of carbon atoms at the α- and β-position to sulfur were successfully used for distinguishing between the diastereoisomeric sulfoxides.     

Conformational Properties of New Thiosemicarbazone and Thiocarbohydrazone Derivatives and Their Possible Targets

The structure assignment and conformational analysis of thiosemicarbazone KKI15 and thiocarbohydrazone KKI18 were performed through homonuclear and heteronuclear 2D Nuclear Magnetic Resonance (NMR) spectroscopy (2D-COSY, 2D-NOESY, 2D-HSQC, and 2D-HMBC) and quantum mechanics (QM) calculations using Functional Density Theory (DFT). After the structure identification of the compounds, various conformations of the two compounds were calculated using DFT. The two molecules showed the most energy-favorable values when their two double bonds adopted the E configuration. These configurations were compatible with the spatial correlations observed in the 2D-NOESY spectrum. In addition, due to the various isomers that occurred, the energy of the transition states from one isomer to another was calculated. Finally, molecular binding experiments were performed to detect potential targets for KKI15 and KKI18 derived from SwissAdme. In silico molecular binding experiments showed favorable binding energy values for all four enzymes studied. The strongest binding energy was observed in the enzyme butyrylcholinesterase. ADMET calculations using the preADMET and pKCSm software showed that the two molecules appear as possible drug leads.     

Molecular structure and spectroscopic studies on novel complexes of coumarin-3-carboxylic acid with Ni(II), Co(II), Zn(II) and Mn(II) ions based on density functional theory

Novel Ni(II), Co(II), Zn(II) and Mn(II) complexes of coumarin-3-carboxylic acid (HCCA) were studied at experimental and theoretical levels. The complexes were characterised by elemental analyses, FT-IR, (1)H NMR, (13)C NMR and UV-Vis spectroscopy and by magnetic susceptibility measurements. The binding modes of the ligand and the spin states of the metal complexes were established by means of molecular modelling of the complexes studied and calculation of their IR, NMR and absorption spectra at DFT(TDDFT)/B3LYP level. The experimental and calculated data verified high spin Ni(II), Co(II) and Mn(II) complexes and a bidentate binding through the carboxylic oxygen atoms (CCA2). The model calculations predicted pseudo octahedral trans-[M(CCA2)(2)(H(2)O)(2)] structures for the Zn(II), Ni(II) and Co(II) complexes and a binuclear [Mn(2)(CCA2)(4)(H(2)O)(2)] structure. Experimental and calculated (1)H, (13)C NMR, IR and UV-Vis data were used to distinguish the two possible bidentate binding modes (CCA1 and CCA2) as well as mononuclear and binuclear structures of the metal complexes.