Organometallic SERMs (selective estrogen receptor modulators): Cobaltifens, the (cyclobutadiene)cobalt analogues of hydroxytamoxifen

The McMurry coupling of (tetraphenylcyclobutadiene)cobalt(cyclopentadienyl) ketones, (C₄Ph₄)Co[C₅H₄C(O)R], where R = Me, 3a, or Et, 3b, with a range of substituted benzophenones furnished a series of cobaltifens, organometallic analogues of tamoxifen whereby a phenyl ring has been replaced by an organo-cobalt sandwich moiety. These systems of the general formula (η⁴-C₄Ph₄)Co[η⁵-C₅H₄C(R)C(Ar)Ar′], where R = Me or Et, and Ar = Ar′ = p-C₆H₄X where X is OH, 2a and 2b, OMe, 2c and 2d, OBn, 2e and 2f, or O(CH₂)₂NMe₂, 12a and 12b, and where Ar = C₆H₄OH and Ar′ = C₆H₄O(CH₂)₂NMe₂, 2g and 2h, have been characterised by NMR spectroscopy and/or X-ray crystallography. The effect of 2a and 2b, 2g and 2h, and 12a and 12b on the growth of MCF-7 (hormone-dependent) and MDA-MB-231 (hormone-independent breast cancer cells) was studied. The dihydroxycobaltifens 2a and 2b exhibit a strong estrogenic effect on MCF-7 cells while the aminoalkyl-hydroxycobaltifens, 2g and 2h, were found to be only slightly cytotoxic on MDA-MB-231 cells (IC₅₀ = 27.5 and 17 μM); surprisingly, however, the bis-(dimethylaminoethoxy)cobaltifens, 12a and 12b were shown to be highly cytotoxic towards both cell lines (IC₅₀ = 3.8 and 2.5 μM).     

Top quark spin correlations at the Tevatron and the LHC

Spin correlations of top quarks produced in hadron collisions have not been observed experimentally with large significance. In this Letter, we propose a new variable that may enable demonstration of the existence of spin correlations with 3–4 σ$3\text{–}4\sigma$ significance using just a few hundred dilepton events both at the Tevatron and the LHC. Such number of dilepton events has been observed at the Tevatron. At the LHC, it will become available once integrated luminosity of a few hundred inverse picobarns is collected.     

Lipidated ras and rab peptides and proteins--synthesis, structure, and function

Chemical biology can be defined as the study of biological phenomena from a chemical approach. Based on the analysis of relevant biological phenomena and their structural foundation, unsolved problems are identified and tackled through a combination of chemistry and biology. Thus, new synthetic methods and strategies are developed and employed for the construction of compounds that are used to investigate biological procedures. Solid-phase synthesis has emerged as the preferred method for the synthesis of lipidated peptides, which can be chemoselectively ligated to proteins of the Ras superfamily. The generated peptides and proteins have solved biological questions in the field of the Ras-superfamily GTPases that are not amendable to chemical or biological techniques alone.     

Structure Elucidator: a versatile expert system for molecular structure elucidation from 1D and 2D NMR data and molecular fragments

StrucEluc is an expert system that allows the computer-assisted elucidation of chemical structures based on the inputs of a series of spectral data including 1D and 2D NMR and mass spectra. The system has been enabled to allow a chemist to utilize fragments stored in a fragment database as well as user-defined fragments submitted by the chemist in the structure elucidation process. The association of fragments in this way has been shown to dramatically speed up the process of structure generation from 2D NMR data and has helped to minimize or eliminate the need for user intervention thereby further enabling the vision of automated elucidation. The use of fragments has frequently transformed very difficult 2D NMR elucidation challenges into easily solvable tasks. A strategy to utilize molecular fragments has been developed and optimized based on specific challenging examples. This strategy will be described here using real world examples. Experience gained by solving more than 150 structure elucidation problems from a variety of literature sources is also reviewed in this work.     

Introducing negative charges into bis-p-phenylene crown ethers: a study of bipyridinium-based [2]pseudorotaxanes and [2]rotaxanes

This paper describes novel host-guest systems comprising viologen cations (guests) and the derivatives of bis-para-phenylene-34-crown-10 (hosts) with anionic groups COO(-) or SO(3)(-). The structure of the resulting charge-compensated host-guest complexes, their association constants and their electrochemical behaviour have been studied. In the solid state, the viologen cations thread the negatively charged crown ethers forming electroneutral zwitterion-like [2]pseudorotaxane salts; in solution this threaded geometry is preserved. The association constants of [2]pseudorotaxane salts incorporating the 1,1'-diethylviologen moiety in solution are significantly higher than those of previously reported analogues. The extrapolated association free energies in non-aqueous media exceed -40 kJ mol(-1) at 25 degrees C. This significant increase of the interaction free energy makes these compounds stable even in aqueous solutions. The association constants of [2]pseudorotaxane salts incorporating sterically more hindered 1,1'-diethyl-3,3'-dimethylviologen moieties are significantly lower. Structurally related [2]rotaxane salts, in which the oppositely charged ionic components are mechanically interlocked, have been prepared in good yields. It has been shown that [2]rotaxane salts incorporating anti-isomers of bisfunctionalised crown ethers are cycloenantiomeric. In both [2]pseudorotaxane and [2]rotaxane salts, the electrostatic interactions between the viologen moieties and the negatively charged crown ethers lead to very significant negative shifts of viologen reduction potentials up to 450 mV. The findings of the present study are valuable for the design of nanoscale molecular electronic devices.     

Kinetics of D,L–Lactide Polymerization Initiated with Zirconium Acetylacetonate

The kinetic of D,L-lactide polymerization in presence of biocompatible zirconium acetylacetonate initiator was studied by differential scanning calorimetry in isothermal mode at various temperatures and initiator concentrations. The enthalpy of D,L-lactide polymerization measured directly in DSC cell was found to be ΔH=−17.8±1.4 kJ mol⁻¹. Kinetic curves of D,L-lactide polymerization and propagation rate constants were determined for polymerization with zirconium acetylacetonate at concentrations of 250–1000 ppm and temperature of 160–220 °C. Using model or reversible polymerization the following kinetic and thermodynamic parameters were calculated: activation energy E_a=44.51±5.35 kJ mol⁻¹, preexponential constant lnA=15.47±1.38, entropy of polymerization ΔS=−25.14 J mol⁻¹ K⁻¹. The effect of reaction conditions on the molecular weight of poly(D,L-lactide) was shown.     

Empirical and DFT GIAO quantum‐mechanical methods of 13C chemical shifts prediction: competitors or collaborators?

The accuracy of ¹³C chemical shift prediction by both DFT GIAO quantum‐mechanical (QM) and empirical methods was compared using 205 structures for which experimental and QM‐calculated chemical shifts were published in the literature. For these structures, ¹³C chemical shifts were calculated using HOSE code and neural network (NN) algorithms developed within our laboratory. In total, 2531 chemical shifts were analyzed and statistically processed. It has been shown that, in general, QM methods are capable of providing similar but inferior accuracy to the empirical approaches, but quite frequently they give larger mean average error values. For the structural set examined in this work, the following mean absolute errors (MAEs) were found: MAE(HOSE) = 1.58 ppm, MAE(NN) = 1.91 ppm and MAE(QM) = 3.29 ppm. A strategy of combined application of both the empirical and DFT GIAO approaches is suggested. The strategy could provide a synergistic effect if the advantages intrinsic to each method are exploited. Copyright © 2010 John Wiley & Sons, Ltd.     

Rapid annulation of tropolone units via a pyrylium ylide 1,3-dipolar cycloaddition reaction

The tropolone subunit of the naturally occurring alkaloid rubrolone aglycon is synthesized via a short reaction sequence starting with a 1,3-dipolar cycloaddition of a pyrylium ylide and indenone, followed by enone oxidation, oxygen-bridge elimination and finally hydroxy group oxidation.     

Application of 57Co emission Mössbauer spectroscopy to studying biocomplexes in frozen solutions

Emission Mössbauer spectroscopy with the ⁵⁷Co isotope was used to study very dilute rapidly frozen aqueous solutions of cobalt(II) complexes with low-molecular-weight biomolecules (aromatic amino acids – anthranilic acid and L-tryptophan) and within a sophisticated biopolymer, bacterial glutamine synthetase, a key enzyme of nitrogen metabolism. The appearance of after-effects of the ⁵⁷Co→⁵⁷Fe nuclear transformation as well as the coordination properties of the cation and the ligands in the complexes are discussed on the basis of their Mössbauer parameters.