Protein Protection by Antioxidants: Development of a Convenient Assay and Structure‐Activity Relationships of Natural Polyphenols

In this work, a convenient test of antioxidant activity was developed, with BChE‐contaminated HSA as the target of AAPH‐induced oxidation and its esterase activity as the marker of protein integrity or degradation. The method is relatively simple, of low cost, and convenient to use. Its application to natural polyphenols showed that quercetin ( 1 ), verbascoside ( 2 ), chlorogenic acid ( 3 ), caffeic acid ( 4 ), 1,3,6,7‐tetrahydroxyxanthone ( 5 ), and mangiferin ( 6 ), are good antioxidants (IC₅₀<9 μM ). 1,5‐Dihydroxy‐3‐methoxyxanthone ( 7 ), flemichin D ( 8 ), and cordigone ( 9 ) showed modest activities (ca. 50 μM <IC₅₀<350 μM ), whereas danthrone ( 10 ) was inactive. Complementary experiments with two of the more active antioxidants, namely quercetin ( 1 ) and chlorogenic acid ( 3 ) showed that both antioxidants were better radical scavengers than chain‐breaking antioxidants. The relative adiabatic oxidation potential (ΔH_ox), the relative H‐bond dissociation energy (ΔH_abs), and the first oxidation potential measured by cyclic voltammetry were found to be related to the radical‐scavenging activity of these antioxidants.     

Facile Synthesis of Diastereoisomerically and Optically Pure 2‐Substituted Hexahydro‐1H‐pyrrolizin‐3‐ones

We report a short synthetic route that provides optically active 2‐substituted hexahydro‐1H‐pyrrolizin‐3‐ones in four steps from commercially available Boc (tert‐but(oxy)carbonyl))‐protected proline. Diastereoisomers (−)‐ 11 and (−)‐ 12 were assembled from the proline‐derived aldehyde (−)‐ 8 and ylide 9 via a Wittig reaction and subsequent catalytic hydrogenation (Scheme 3). Cleavage of the Boc protecting group under acidic conditions, followed by intramolecular cyclization, afforded the desired hexahydro‐1H‐pyrrolizinones (−)‐ 1 and (+)‐ 13 . Applying the same protocol to ylide 19 afforded hexahydro‐1H‐pyrrolizinones (−)‐ 25 and (−)‐ 26 (Scheme 5). The absolute configuration of the target compounds was determined by a combination of NMR studies (Figs. 1 and 2) and X‐ray crystallographic analysis (Fig. 3).     

N‐Arylated 3,5‐Dihydro‐4H‐dinaphtho[2,1‐c:1′,2′‐e]azepines: Axially Chiral Donors with High Helical Twisting Powers for Nonplanar Push–Pull Chromophores

Axially chiral, N‐arylated 3,5‐dihydro‐4H‐dinaphtho[2,1‐c:1′,2′‐e]azepines have been prepared by short synthetic protocols from enantiopure 1,1′‐bi(2,2′‐naphthol) (BINOL) and anilines. Alkynes substituted with two N‐phenyldinaphthazepine donors readily undergo a formal [2+2] cycloaddition, followed by retro‐electrocyclization, with tetracyanoethene (TCNE) to yield donor‐substituted 1,1,4,4‐tetracyanobuta‐1,3‐dienes (TCBDs) featuring intense intramolecular charge‐transfer (CT) interactions. A dicyanovinyl derivative substituted with one N‐phenyldinaphthazepine donor was obtained by a “one‐pot” oxidation/Knoevenagel condensation from the corresponding propargylic alcohol. Comparative electrochemical, X‐ray crystallographic, and UV/Vis studies show that the electron‐donor qualities of N‐phenyldinaphthazepine are similar to those of N,N‐dimethylanilino residues. The circular dichroism (CD) spectrum of a push–pull chromophore incorporating the chiral donor moiety features Cotton effects of exceptional intensity. With their elongated shape and the rigidity of the chiral N‐aryldinaphthazepine donors, these chromophores are effective inducers of twist distortion in nematic liquid crystals (LCs). Thus, a series of the dinaphthazepine derivatives was used as dopants in the nematic LC E7 (Merck) and high helical twisting powers (β) of the order of hundreds of μm^?1 were measured. Theoretical calculations were employed to elucidate the relation between the structure of the dopants and their helical twisting power. For the derivatives with two dinaphthazepine moieties, a strong dependence of the β‐values on the structure and conformation of the linker between them was found.     

Air‐Stable {(C5H5)Co} Catalysts for [2+2+2] Cycloadditions

Cobalt cyclopentadienyl complexes incorporating a fumarate and a CO ligand (see picture) efficiently catalyze inter‐ and intramolecular [2+2+2] cycloadditions of alkynes, nitriles, and/or alkenes to give benzenes, pyridines, or 1,3‐cyclohexadienes. Unlike catalysts such as [CpCo(CO)₂] or [CpCo(C₂H₄)₂] (Cp=C₅H₅), they are air‐stable, easy to handle, compatible with microwave conditions, and do not necessarily require irradiation to be active.

     

Contrast or assimilation: choosing camps in simple or realistic modeling

The contrast effect is a psychological phenomenon in which people exaggerate their differences. When making social comparisons, people cope with the discomforts associated with negative comparisons by criticizing others and splitting into smaller groups of similar others or by assimilation, depending on whether they perceive themselves as the member of a majority or minority group, respectively. This contrast or assimilation phenomena can explain the exaggeration of differences among computational simulation scholars. Those exaggerations are discussed in this paper as well as some realistic reasons for differences. Recognition of our status as minority group members and the virtues of assimilation and mutual support are advocated.

Synthesis and characteristics of a nonaggregating tris(tetrathiafulvaleno)dodecadehydro[18]annulene

A new tris(tetrathiafulvaleno)dodecadehydro[18]annulene with six peripheral n-hexyl substituents was prepared by oxidative Glaser-Hay cyclization of a corresponding diethynylated tetrathiafulvalene (TTF) precursor. The electronic properties of the neutral and oxidized species were studied by both UV/Vis absorption spectroscopy and electrochemistry. From these studies, it transpires that the strongly violet-colored macrocycle does not aggregate in solution to any significant degree, which was confirmed by (1)H NMR spectroscopy. This reluctance towards aggregation contrasts that observed for related TTF-annulenes containing other peripheral substitutents. Oxidation of the TTF-annulene occurs in two three-electron steps as inferred from both the peak amplitudes and the spectroelectrochemical study. We find that the tris(TTF)-fused dehydro[18]annulene is more difficult to oxidize (by +0.20 V) than the silyl-protected diethynylated mono-TTF precursor. In contrast, the first vertical ionization energy calculated at the B3 LYP/6-311+G(2d,p) level for the parent tris(TTF)-fused dehydro[18]annulene devoid of peripheral hexyl substituents is in fact lower (by 0.44 eV). Moreover, the surface morphology of 1 d drop-cast on a mica substrate was investigated by atomic force microscopy (AFM). Crystalline domains with slightly different orientations were observed. The thickness of individual layers seen in the crystalline domains and the thickness of a monolayer obtained from a very dilute solution were determined to 1.8-1.9 nm. This thickness corresponds to the diameter of the macrocycle and the layers seen in the film are apparently formed when the molecules stack in the horizontal direction relative to the substrate.     

Why are ionic liquids liquid? A simple explanation based on lattice and solvation energies

We have developed a simple and quantitative explanation for the relatively low melting temperatures of ionic liquids (ILs). The basic concept was to assess the Gibbs free energy of fusion (Delta(fus)G) for the process IL(s) --> IL(l), which relates to the melting point of the IL. This was done using a suitable Born-Fajans-Haber cycle that was closed by the lattice (i.e., IL(s) --> IL(g)) Gibbs energy and the solvation (i.e., IL(g) --> IL(l)) Gibbs energies of the constituent ions in the molten salt. As part of this project we synthesized and determined accurate melting points (by DSC) and dielectric constants (by dielectric spectroscopy) for 14 ionic liquids based on four common anions and nine common cations. Lattice free energies (Delta(latt)G) were estimated using a combination of Volume Based Thermodynamics (VBT) and quantum chemical calculations. Free energies of solvation (Delta(solv)G) of each ion in the bulk molten salt were calculated using the COSMO solvation model and the experimental dielectric constants. Under standard ambient conditions (298.15 K and 10(5) Pa) Delta(fus)G degrees was found to be negative for all the ILs studied, as expected for liquid samples. Thus, these ILs are liquid under standard ambient conditions because the liquid state is thermodynamically favorable, due to the large size and conformational flexibility of the ions involved, which leads to small lattice enthalpies and large entropy changes that favor melting. This model can be used to predict the melting temperatures and dielectric constants of ILs with good accuracy. A comparison of the predicted vs experimental melting points for nine of the ILs (excluding those where no melting transition was observed and two outliers that were not well described by the model) gave a standard error of the estimate (s(est)) of 8 degrees C. A similar comparison for dielectric constant predictions gave s(est) as 2.5 units. Thus, from very little experimental and computational data it is possible to predict fundamental properties such as melting points and dielectric constants of ionic liquids.     

Photoinduced processes in dipyrrolyl-perfluoro-cyclopentenes

The photobehavior of five photochromic dipyrrolyl-perfluoro-cyclopentenes was studied by steady state and time-resolved absorption spectroscopy. The quantum yields of the UV-photoinduced ring-closing reaction (coloration) and the visible-stimulated cycloreversion reaction (bleaching) were measured. Kinetic and thermodynamic parameters of thermal bleaching were also determined. Nanosecond time-resolved experiments showed formation of a transient, which was not a precursor of the reaction photoproduct. This transient was tentatively assigned to a radical cation formed by direct photoionization through a short-lived triplet state. The nature of the transient species was supported by photoinduced electron transfer to electron acceptors.     

Cobalt-mediated cyclic and linear 2:1 cooligomerization of alkynes with alkenes: a DFT study

The mechanism of the cobalt-mediated [2 + 2 + 2] cycloaddition of two alkynes to one alkene to give CpCo-complexed 1,3-cyclohexadienes (cyclic oligomerization) has been studied by means of DFT computations. In contrast to the mechanism of alkyne cyclotrimerization, in which final alkyne inclusion into the common cobaltacyclopentadiene features a direct "collapse" pathway to the complexed arene, alkene incorporation proceeds via insertion into a Co-C sigma-bond rather than inter- or intramolecular [4 + 2] cycloaddition. The resulting seven-membered metallacycle 7 is a key intermediate which leads to either CpCo-complexed cyclohexadiene 5 or hexatriene 13. The latter transformation, particularly favorable for ethene, accounts, in part, for the linear oligomerization observed occasionally in these reactions. With aromatic double bonds, a C-H activation mechanism by the cobaltacyclopentadiene seems more advantageous in hexatriene product formation. Detailed investigations of high- and low-spin potential energy surfaces are presented. The reactivity of triplet cobalt species was found kinetically disfavored over that of their singlet counterparts. Moreover, it could not account for the formation of CpCo-complexed hexatrienes. However, triplet cobalt complexes cannot be ruled out since all unsaturated species appearing in this study were found to exhibit triplet ground states. Consequently, a reaction pathway that involves a mixing of both spin-state energy surfaces is also described (two-state reactivity). Support for such a pathway comes from the location of several low-lying minimum-energy crossing points (MECPs) of the two surfaces.