De novo refolding and aggregation of insulin in a nonaqueous environment: an inside out protein remake

While thermodynamic penalties associated with protein-water interactions are the key driving force of folding, perturbed hydration of destabilized protein molecules may trigger aggregation, which in vivo often causes cellular and histological damage. Here we show, that the denatured state of an alpha-helical protein, insulin, converts to a non-native beta-sheet-rich structure upon de novo "refolding" in an anhydrous environment. The beta-pleated conformer precipitates from solutions of DMSO-denatured insulin upon dilution with chloroform. DMSO destroys hydrogen bond network of the native protein acting as a strong acceptor of main chain hydrogen bonds. Upon the addition of chloroform, which is a weak hydrogen bond donor per se, competitive hydrogen bonds between DMSO and chloroform are formed. This leads to the release of unfolded insulin molecules. In the absence of water, the imminent saturation of polypeptide's dandling hydrogen bonds does not produce the native and predominantly alpha-helical state but a beta-sheet-rich structure, which is morphologically and spectrally distinct from insulin amyloid fibrils. Unlike insulin fibrils, the beta-sheet conformer is metastable and refolds spontaneously to the native form in an aqueous environment. This implies that "folding" in the absence of water results in inefficient burial of hydrophobic side-chains, and thermodynamic frustration at the water-protein interface.     

Equilateral triangles on a Jordan curve and a generalization of a theorem of Dold

Let be a Jordan curve in the plane. It is a simple topological riddle to determine if there is an equilateral triangle with vertices on γ. By reformulating this question in the paradigm of configuration spaces and test maps, we can solve this riddle using a Borsuk-Ulam type theorem obtained using equivariant methods.     

Synthetic studies directed toward dideoxy lomaiviticinone lead to unexpected 1,2-oxazepine and isoxazole formation

In the course of studies directed toward the synthesis of dideoxy lomaiviticinone, 3-(nitromethyl)cyclohexenones 2a (X = H) and 2b (X = I) were prepared. The corresponding enolates were reacted with naphthazarin (1) and unexpectedly afforded 1,2-oxazepine 3 and isoxazole 4, respectively. Rationale for their formation is proposed.     

Controlling the macrocycle size by the stoichiometry of the applied template ion

Reaction of 4-tert-butyl-2,6-diformylphenol with (1R,2R)- or (1S,2S)-1,2-diaminocyclohexane in the presence of 1 equivalent of Zn(2+) ions leads to selective formation of a chiral 2+2 macrocycle. Application of 0.5 equivalent of Zn(2+) ions under the same conditions leads to selective formation of a chiral 3+3 macrocycle, which forms a cavitand-shaped trinuclear double-decker complex with Zn(II).     

Thermochromic discotic 6-oxoverdazyls

6-Oxoverdazyls 1b[n], substituted with three 3,4,5-trialkoxyphenyl groups (n = 8 and 10), exhibit a columnar hexagonal phase (Col(h)) below 130 °C. They display reversible color change from red to green at the transition to the isotropic phase. XRD and magnetization data do not support dimerization of the radicals in the mesophase.     

The synthesis of opiorphin and studies on its binding ability toward Cu(II)

Opiorphin (OPI) is an endogenous pentapeptide isolated from human saliva. A characteristic feature of this peptide is the presence of an N-terminal Gln residue. The synthesis and binding abilities of opiorphin toward Cu(II) ions are described. The use of potentiometric and spectroscopic methods allows us to propose the binding mode of the formed complexes.     

Polymer Composites Based on Reactive Carboxylate-Alumoxanes

Summary: The possibility of applying basic aluminum carboxylates as the cross-linking monomers in radical polymerization processes as well as the initiators for ATRP of styrene and coordination ROP of heterocyclic monomers was examined. It was established, that aluminum carboxylates containing in their structure the acrylic and lauric acids derivatives show high activity in the copolymerization with vinyl monomers which results in the hybrid polymer networks formation. In the typical ATRP conditions, polymers grafted with styrene are obtained while basic aluminum 2-bromopropionate is used as the initiator. Hybrid composites i.e. core-shell nanospheres can be obtained in this way at low degree of polymerization. Nanoparticles of basic aluminum caroboxylates when reacted with triethylaluminum show high activity as initiators in the polymerization processes of ε-caprolactone, trimethylene carbonate as well as propylene and ethylene oxides. Cross-linked products in the form of a gel were formed as the result of ROP in such systems. However, linear polymers characterized by M_n above 10⁴ and PDI ≥ 1.9 were obtained after aluminum residuals removal.     

Dual field nonlinear dielectric spectroscopy in a glass forming EPON 828 epoxy resin

Results of the dual field nonlinear dielectric spectroscopy (NDS) studies in supercooled glass forming epoxy resin EPON 828 are presented. For the NDS, changes of dielectric permittivity induced by DC (rectangular) or AC (sine-wave) pulses of a strong electric field were probed by a weak radio frequency electric field. A clear stretched exponential (x < 1) decay after switching off the DC pulse and a single exponential decay (x = 1) after switching off the AC pulse were found. The same results are presented for preliminary studies in superpressed low molecular glass former di-isobutyl phthalate. This observation may be considered as an argument for the heterogeneous picture of supercooled glass forming materials. The temperature dependences of the stationary responses related to DC and AC strong electric field excitations are also shown. The sensitivity of the applied set up made it possible to detect NDS outputs even for electric fields E(strong) < 10 kV cm(-1), qualitatively weaker than in similar 'nonlinear, dielectric' experimental studies on glass forming materials carried out so far.