Designed Topology and Site‐Selective Metal Composition in Tetranuclear [MM′⋅⋅⋅M′M] Linear Complexes

The ligand 1,3‐bis[3‐oxo‐3‐(2‐hydroxyphenyl)propionyl]benzene (H₄L), designed to align transition metals into tetranuclear linear molecules, reacts with M^II salts (M=Ni, Co, Cu) to yield complexes with the expected [MM???MM] topology. The novel complexes [Co₄L₂(py)₆] ( 2 ; py=pyridine) and [Na(py)₂][Cu₄L₂(py)₄](ClO₄) ( 3 ) have been crystallographically characterised. The metal sites in complexes 2 and 3 , together with previously characterised [Ni₄L₂(py)₆] ( 1 ), favour different coordination geometries. These have been exploited for the deliberate synthesis of the heterometallic complex [Cu₂Ni₂L₂(py)₆] ( 4 ). Complexes 1 , 2 , 3 and 4 exhibit antiferromagnetic interactions between pairs of metals within each cluster, leading to S=0 spin ground states, except for the latter cluster, which features two quasi‐independent S=1/2 moieties within the molecule. Complex 4 gathers the structural and physical conditions, thus allowing it to be considered as prototype of a two‐qbit quantum gate.     

A Simple and Versatile Re‐Catalyzed Meyer–Schuster Rearrangement of Propargylic Alcohols to α,β‐Unsaturated Carbonyl Compounds

Rhenium does the job! A readily available rhenium complex efficiently catalyzed the direct Meyer–Schuster‐like rearrangement of different alkyl‐ and aryl‐substituted propargylic secondary and tertiary alcohols to the corresponding α,β‐unsaturated compounds, which were produced with virtually complete E stereoselectivity. The reaction proceeded under neutral conditions and no racemization of potentially enolizable stereocenters was observed.

     

Dihydroxyacetone Phosphate Aldolase Catalyzed Synthesis of Structurally Diverse Polyhydroxylated Pyrrolidine Derivatives and Evaluation of their Glycosidase Inhibitory Properties

The chemoenzymatic synthesis of a collection of pyrrolidine‐type iminosugars generated by the aldol addition of dihydroxyacetone phosphate (DHAP) to C‐α‐substituted N‐Cbz‐2‐aminoaldehydes derivatives, catalyzed by DHAP aldolases is reported. L ‐Fuculose‐1‐phosphate aldolase (FucA) and L ‐rhamnulose‐1‐phosphate aldolase (RhuA) from E. coli were used as biocatalysts to generate configurational diversity on the iminosugars. Alkyl linear substitutions at C‐α were well tolerated by FucA catalyst (i.e., 40–70 % conversions to aldol adduct), whereas no product was observed with C‐α‐alkyl branched substitutions, except for dimethyl and benzyl substitutions (20 %). RhuA was the most versatile biocatalyst: C‐α‐alkyl linear groups gave the highest conversions to aldol adducts (60–99 %), while the C‐α‐alkyl branched ones gave moderate to good conversions (50–80 %), with the exception of dimethyl and benzyl substituents (20 %). FucA was the most stereoselective biocatalyst (90–100 % anti (3R,4R) adduct). RhuA was highly stereoselective with (S)‐N‐Cbz‐2‐aminoaldehydes (90–100 % syn (i.e., 3R,4S) adduct), whereas those with R configuration gave mixtures of anti/syn adducts. For iPr and iBu substituents, RhuA furnished the anti adduct (i.e., FucA stereochemistry) with high stereoselectivity. Molecular models of aldol products with iPr and iBu substituents and as complexes with the RhuA active site suggest that the anti adducts could be kinetically preferred, while the syn adducts would be the equilibrium products. The polyhydroxylated pyrrolidines generated were tested as inhibitors against seven glycosidases. Among them, good inhibitors of α‐L ‐fucosidase (IC₅₀=1–20 μM ), moderate of α‐L ‐rhamnosidase (IC₅₀=7–150 μM ), and weak of α‐D ‐mannosidase (IC₅₀=80–400 μM ) were identified. The apparent inhibition constant values (K_i) were calculated for the most relevant inhibitors and computational docking studies were performed to understand both their binding capacity and the mode of interaction with the glycosidases.     

Adenine versus guanine quartets in aqueous solution: dispersion-corrected DFT study on the differences in π-stacking and hydrogen-bonding behavior

We have investigated the performance of the dispersion-corrected density functionals (BLYP-D, BP86-D and PBE-D) and the widely used B3LYP functional for describing the hydrogen bonds and the stacking interactions in DNA base dimers. For the gas-phase situation, the bonding energies have been compared to the best ab initio results available in the literature. All dispersion-corrected functionals reproduce well the ab initio results, whereas B3LYP fails completely for the stacked systems. The use of the proper functional leads us to find minima for the adenine quartets, which are energetically and structurally very different from the C_4h structures, and might explain why adenine has to be sandwiched between guanine quartets to form planar adenine quartets.     

Further Insight into the Photostability of the Pyrene Fluorophore in Halogenated Solvents

Pyrene fluorophores of pyrene‐functionalized CdSe quantum dots (QD@Py), as well as alkylpyrene and pyrene itself (Py), undergo fast degradation in aerated chloroform under ultraviolet‐A (UV‐A, 316<λ<400 nm) illumination. Steady‐state fluorescence studies of irradiated chloroform solutions of QD@Py show formation of new bands, red‐shifted compared to that of the pyrene moiety. Similar behaviour is observed for pyrene and the alkylpyrene system. Column chromatography of the pyrene photolysate in chloroform allowed us to isolate photoproducts arising from pyrene degradation, and to obtain information on the structure of the photoproducts responsible for the emission bands. The most predominant photoproducts were those originating from the reaction of pyrene with dichloromethyl radicals. The phototransformation of QD@Py and the alkylpyrene involves mainly detachment of the alkyl chain from the aromatic ring, induced also by dichloromethyl radicals, and oxidation of the alkyl chain at the benzylic position was detected as well. By contrast, these pyrene systems show a high photostability in aerated dichloromethane. Transient absorption measurements showed formation of both pyrene triplet and pyrene radical cation for all pyrene systems in these halogenated solvents. The yield of pyrene radical cations for Py is higher than for QD@Py and the alkylpyrene. In addition, pyrene radical cations were longer‐lived in dichloromethane than in chloroform. The reason for the pyrene photostability in dichloromethane is the different reactivity of chloromethyl and dichloromethyl radicals towards pyrene and oxygen. These studies show that the use of dichloromethane can be a suitable alternative to chloroform when the good solubility properties of these halogenated solvents are needed to dissolve pyrene when this chromophore is used as a fluorescent probe.     

1,2-Oxopalladation versus pi-allyl palladium route. A regioconvergent approach to a key intermediate for cyclopentanoids synthesis. New insights into the Pd(II)-catalyzed lactonization reaction

Regioconvergent synthesis of the key lactone 1 from an equimolar mixture of the two olefins 4 and 5 was achieved by unique Pd(II) chemistry. The synthetic versatility of lactone 1 has been demonstrated in the synthesis of iridoids and of the endo-Corey lactone 2, which is a key intermediate for the F(2)-isoprostane synthesis. Upon exposure of the sodium salts of 4 and 5 to a catalytic amount of Pd(OAc)(2) under oxygen, in the presence of AcOH, an isomeric lactone 12 was obtained in addition to the title compound 1. The Pd(II) lactonization was optimized by fine-tuning all the factors participating in the catalytic cycle: solvent, oxidant, co-oxidant, and Pd(II) source. The Hosokawa's heterobimetallic couple emerged as the catalyst of choice. With a Cu(II)-Pd(II) couple, the redox process was transferred to copper, and the formal oxidation state of palladium remained constant during the reaction. By virtue of this new methodology, lactone 1 was obtained in a rewarding 60% yield, along with isomeric lactone 12 in 30% yield. A detailed mechanistic study was carried out in order to elucidate the formation of lactones 1 and 12. Lactone 1 was formed from either olefin 8 or olefin 10; on the other hand, lactone 12 was formed exclusively from olefin 10. An intramolecular 1,2-acyloxypalladiation was invoked for the transformation of 8 into 1, whereas the pi-allyl complexes 13 and 11 were involved in the transformation of olefin 10 into 12 and 1, respectively.     

A solid-phase synthetic route to unnatural amino acids with diverse side-chain substitutions

Reacting imine derivatives of resin-bound amino acids with alpha,omega-dihaloalkanes provides highly versatile intermediates to racemic alpha,alpha-disubstituted amino acids with a wide variety of side-chain functionality. Two strategies were developed to convert the intermediate omega-chloro or omega-bromo derivatives to the desired products. Together, they allow the creation of amino acids with diverse functionalities (omega-chlorides, nitriles, azides, acetates, thioacetates, thioethers, secondary and tertiary aliphatic amines, and anilines) placed at varying chain lengths (2-5) from the alpha-center of the amino acid.     

(Eta3-phenylallyl)(phosphanyloxazoline)palladium complexes: X-ray crystallographic studies,NMR investigations,and Ab initio/DFT calculations

All possible (eta(3)-allyl)palladium complexes (1-4) of the ligand (4S)-[2-(2'-diphenylphosphanyl)phenyl]-4,5-dihydro-4-(2-propyl)-oxazole (L 1) and eta(3)-allyl ligands with one to three phenyl substituents at the terminal allylic centers were synthesized and characterized by X-ray crystal structure analysis and, with respect to allylic isomers, by NMR investigations. Equilibrium geometries, electronic structures, and relative energies of isomeric complexes were computed by restricted Hartree-Fock (RHF) and density functional theory (DFT) calculations; experimentally determined isomer ratios could be reproduced. The results allowed important conclusions to be drawn regarding the mechanism of Pd-catalyzed asymmetric allylic substitutions.     

Measurement of the sign and the magnitude of heteronuclear coupling constants from spin-state-edited J-cross-polarization NMR experiments

New spin-state-selective (S3) NMR pulse sequences exclusively applying cross-polarization schemes to achieve optimum homonuclear and heteronuclear 1H-X coherence transfer are reported for the simple and accurate measurement of the magnitude and sign of heteronuclear coupling constants for samples at natural abundance. The proposed spin-edited HCP-TOCSY experiments are based on clean heteronuclear S3 excitation, generated by simultaneous co-addition of two independent in-phase and anti-phase components created during the mixing heteronuclear J-cross-polarization (HCP) step, which is finally transferred to other protons by a conventional homonuclear TOCSY mechanism. Selective 1D and non-selective 2D approaches for the easy determination of long-range proton-carbon and proton-nitrogen coupling constants on any protonated and non-protonated heteronuclei are presented and discussed for several organic molecules.     

Physicochemical aspects of the liposome-wool interaction in wool dyeing

Despite the promising application of liposomes in wool dyeing, little is known about the mechanism of liposome interactions with the wool fiber and dyestuffs. The kinetics of wool dyeing by two dyes, Acid Green 27 (hydrophobic) and Acid Green 25 (hydrophilic), were compared in three experimental protocols: (1) without liposomes, (2) in the presence of phosphatidylcholine (PC) liposomes, and (3) with wool previously treated with PC liposomes. Physicochemical interactions of liposomes with wool fibers were studied under experimental dyeing conditions with particular interest in the liposome affinity to the fiber surface and changes in the lipid composition of the wool fibers. The results obtained indicate that the presence of liposomes favors the retention of these two dyes in the dyeing bath, this effect being more pronounced in case of the hydrophobic dye. Furthermore, the liposome treatment is accompanied by substantial absorption of PC by wool fibers with simultaneous partial solubilization of their polar lipids (more evident at higher temperatures). This may result in structural modification of the cell membrane complex of wool fibers, which could account for a high level of the dye exhaustion observed at the end of the liposome dyeing process.