A Phosphine‐Coordinated Boron‐Centered Gomberg‐Type Radical

The P‐coordinated boryl radical [Ph₂P(naphthyl)BMes]^. (Mes=mesityl) was prepared by (electro)chemical reduction of the corresponding borenium salt or bromoborane. Electron paramagnetic resonance (EPR) analysis in solution and DFT calculations indicate large spin density on boron (60–70 %) and strong P–B interactions (P→B σ donation and B→P negative hyperconjugation). The radical is persistent in solution and participates in a Gomberg‐type dimerization process. The associated quinoid‐type dimer has been characterized by single‐crystal X‐ray diffraction.     

Interactions of halichondrin B and eribulin with tubulin

Compounds that modulate microtubule dynamics include highly effective anticancer drugs, leading to continuing efforts to identify new agents and improve the activity of established ones. Here, we demonstrate that [(3)H]-labeled halichondrin B (HB), a complex, sponge-derived natural product, is bound to and dissociated from tubulin rapidly at one binding site per αβ-heterodimer, with an apparent K(d) of 0.31 μM. We found no HB-induced aggregation of tubulin by high-performance liquid chromatography, even following column equilibration with HB. Binding of [(3)H]HB was competitively inhibited by a newly approved clinical agent, the truncated HB analogue eribulin (apparent K(i), 0.80 μM) and noncompetitively by dolastatin 10 and vincristine (apparent K(i)'s, 0.35 and 5.4 μM, respectively). Our earlier studies demonstrated that HB inhibits nucleotide exchange on β-tubulin, and this, together with the results presented here, indicated the HB site is located on β-tubulin. Using molecular dynamics simulations, we determined complementary conformations of HB and β-tubulin that delineated in atomic detail binding interactions of HB with only β-tubulin, with no involvement of the α-subunit in the binding interaction. Moreover, the HB model served as a template for an eribulin binding model that furthered our understanding of the properties of eribulin as a drug. Overall, these results established a mechanistic basis for the antimitotic activity of the halichondrin class of compounds.     

Design, synthesis, and biological evaluation of diminutive forms of (+)-spongistatin 1: lessons learned

The design, synthesis, and biological evaluation of two diminutive forms of (+)-spongistatin 1, in conjunction with the development of a potentially general design strategy to simplify highly flexible macrocyclic molecules while maintaining biological activity, have been achieved. Examination of the solution conformations of (+)-spongistatin 1 revealed a common conformational preference along the western perimeter comprising the ABEF rings. Exploiting the hypothesis that the small-molecule recognition/binding domains are likely to comprise the conformationally less mobile portions of a ligand led to the design of analogues, incorporating tethers (blue) in place of the CD and the ABCD components of the (+)-spongistatin 1 macrolide, such that the conformation of the retained (+)-spongistatin 1 skeleton would mimic the assigned solution conformations of the natural product. The observed nanomolar cytotoxicity and microtubule destabilizing activity of the ABEF analogue provide support for both the assigned solution conformation of (+)-spongistatin 1 and the validity of the design strategy.     

Recombinant cellulose crosslinking protein: a novel paper-modification biomaterial

Cellulose-binding domains have been isolated from various cellulases, and proteins, which lack hydrolytic activity. The hypothesis that a cellulose-binding domain can be used to alter surface and mechanical properties of paper was tested. Two cellulose-binding domains from Clostriium cellulovorans were fused to form a cellulose crosslinking protein (CCP). The recombinant bifunctional cellulose-binding protein was expressed in E. coli, appliedby immersion onto Whatman cellulose filter paper, and its mechanical properties were tested. The purified protein improved the treated paper's mechanical properties (tensile strength, brittleness, Young's modulus and energy to break). In addition, cellulose crosslinking protein treatment was shown to transform filter paper into a more water-repellent paper. The binding of cellulose-binding domains to cellulose under a wide range of envi-ronmentalconditions, without the need for chemical reactions, and its biodegradability make them attractive moieties for the design of a new class of paper-modification materials.p>     

Amphiphilic maleic acid-containing alternating copolymers—2. Dilute solution characterization by light scattering,intrinsic viscosity,and PGSE NMR spectroscopy

The dilute solution behavior of several alternating copolymers of maleic acid has been characterized by static and dynamic light scattering, intrinsic viscosity, and pulsed-gradient spin-echo NMR spectroscopy. The copolymer of maleic acid–sodium salt and isobutylene (IBMA-Na, M_w ∼350 kg/mol) dissolves readily in concentrated aqueous salt solutions. Changes in chain dimensions with ionic strength and pH are similar to those of the lesser salt solution-soluble poly(acrylic acid-sodium salt). The hydrophobically modified (with n-butyl, n-hexyl, n-octyl, and phenethyl amines) copolymers of maleic acid–sodium salts and isobutylene (IBMA-NHR-Na) show no sign of large intermolecular aggregation in 0.1 N sodium acetate (NaAc). However, the sizes of the copolymers are relatively small compared to that of the ionized parent copolymer (IBMA-Na, M_w ∼350 kg/mol), suggesting intramolecular aggregation of the alkyl side-chain groups along the polymer backbone. The copolymer modified with the longer chain n-decyl, on the other hand, forms stable large intermolecular aggregates containing 33 chains/aggregate. The copolymers of maleic acid–sodium salt and styrene (SMA-Na) appear to have no signs of aggregation, despite being a hydrophobic polyelectrolyte. The copolymer of maleic acid–sodium salt and di-isobutylene (DIBMA-Na) has a similar salting-out concentration as SMA-Na. The radius of gyration measurements by static light scattering suggest that at least some fraction of the DIBMA-Na chains form large intermolecular aggregates. The copolymers of maleic acid–sodium salt with n-alkenes (n-C_mMA-Na) in 0.1 N NaAc form small intermolecular aggregates (three to five chains/aggregate). In contrast to these static light scattering results, PGSE NMR diffusion measurements for the above aggregated systems indicate only one diffusion coefficient consistent with the motion of single isolated chains. A plausible explanation for this discrepancy is that the population of the aggregates is too small to be sufficiently detected in the PGSE NMR experiment. Furthermore, it is likely that the aggregate has a larger relaxation rate than the nonaggregate, and therefore has a comparatively reduced signal in the PGSE NMR experiment. © 2004 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 42: 3584–3597, 2004     

Mass spectrometric investigation of polyfluorinated C60. Evidence for the existence of C60F2n (n = 0–30)

Electron-capture negative ion chemical ionization (EC-NICI) and field desorption (FD) mass spectrometric techniques were utilized to examine polyfluorinated C₆₀. Two different samples from the same preparation, one prior to sublimation and the other sublimed material, were investigated. From the raw non-sublimed product in EC-NCI six series of ions corresponding to different numbers of attached oxygen atoms were obtained, which are represented by the formula [C₆₀F_2nO_m]^?, where n ranged from 0 to 30 and m from 0 to 5. The sublimed material in EC-NICI produced the same six series of ions with up to 48 fluorine atoms attached to C₆₀. The field desorption of the same sample produced similar results, but the signal-to-noise ratios of the spectra were low. Both samples, in the two different techniques examined, yielded C₆₀F₆₀ ions with only an even number of fluorine atoms attached. The present investigation, for the first time, provides direct experimental evidence for the existence of higher fluorinated C₆₀ up to C₆₀F₆₀ and multiple oxides of polyfluoro-C₆₀ with up to five oxygen atoms attached.     

Deconvolution of scanning transmission electron microscopy images of ionomers

Previously, we studied a variety of ionomer morphologies with scanning transmission electron microscopy (STEM). Other groups have found that deconvoluting STEM images dramatically improve the overall image quality and the detection of sub‐nanometer‐scale features. In this study, STEM images of nanometer‐scale ion‐rich aggregates were deconvolved via the Pixon method with a simulated electron probe. The image models are considerably sharper with significantly decreased noise levels, thus making the size and shape of the ionic aggregates easier to distinguish relative to those in the raw STEM images. Raw and deconvoluted images of Zn‐neutralized poly(styrene‐ran‐methacrylic acid) ionomers containing spherical ionic aggregates indicate that the electron density varies smoothly from the edge to the center of the aggregates. Deconvolution also clarifies the issue of aggregate overlap in the STEM images. Furthermore, line scans across deconvoluted STEM images suggest that the three‐dimensional density distribution of these nanoaggregates compares favorably with a radially symmetric Gaussian distribution as opposed to a uniformly dense sphere. The overall result of this work is that deconvolution of STEM images provide ways in which to better investigate the morphologies of ionomers. © 2003 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 41: 319–326, 2003