Photocontrolled Release of Chemicals from Nano‐ and Microparticle Containers

A benzoin‐derived diol linker was synthesized and used to generate biocompatible polyesters that can be fully decomposed on demand upon UV irradiation. Extensive structural optimization of the linker unit was performed to enable the defined encapsulation of diverse organic compounds in the polymeric structures and allow for a well‐controllable polymer cleavage process. Selective tracking of the release kinetics of encapsulated model compounds from the polymeric nano‐ and microparticle containers was performed by confocal laser scanning microscopy in a proof‐of‐principle study. The physicochemical properties of the incorporated and released model compounds ranged from fully hydrophilic to fully hydrophobic. The demonstrated biocompatibility of the utilized polyesters and degradation products enables their use in advanced applications, for example, for the smart packaging of UV‐sensitive pharmaceuticals, nutritional components, or even in the area of spatially selective self‐healing processes.     

Discovering novel targets for autoantibodies in dilated cardiomyopathy

There is increasing evidence that a large proportion of dilated cardiomyopathy (DCM) cases are mediated by autoimmune processes. Since DCM is a fatal disorder with rapid aggravation and is the leading cause of heart transplantation, further insights into disease pathogenesis are needed. Recent studies have separated the pathogenic capacity of autoantibodies and initial clinical trials removing such autoantibodies via immunoadsorption have been promising. In order to elucidate the full autoantibody repertoire involved in DCM, we applied an autoantibody screening test using ventricular and atrial proteomes as autoantigenic sources and subsequently tested the autoantibody-binding patterns of sera from dogs with spontaneous DCM. With this method, we detected five potentially DCM-related autoantigens which were identified by MS as being: myosin heavy chain cardiac muscle alpha isoform, alpha cardiac actin, mitochondrial aconitate hydratase, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and brain glycogen phosphorylase (GPBB). The recovery of two known DCM autoantigens (myosin heavy chain and alpha cardiac actin) and the discovery of three novel autoantigens (mitochondrial aconitate hydratase, GADPH, and GPBB) underscore the efficacy of this experimental method and the significance of the spontaneous canine DCM model.     

Mechanistic and kinetic insights into the thermally induced rearrangement of alpha-pinene

The thermal rearrangement of alpha-pinene (1) is interesting from mechanistic as well as kinetic point of view. Carrier gas pyrolyses with 1 and its acyclic isomers ocimene (2) and alloocimene (3) were performed to investigate the thermal network of these hydrocarbons. Kinetic analysis of the major reaction steps allows for a deeper insight in the reaction mechanism. Thus it was possible to explain the racemization of 1, the formation of racemic limonene (4), and the absence of the primary pyrolysis product 2 in the reaction mixture resulting from thermal rearrangement of 1. Results supported the conclusion that the reactions starting with 1 involve biradical transition states.     

Effect of the guest size and shape on its binding dynamics with sodium cholate aggregates

The binding dynamics of the guests acenaphthene, phenanthrene, fluorene, and acenaphthenol with sodium cholate aggregates were studied using laser flash photolysis and fluorescence. The location of the guests in the bile salt aggregate is determined by the guest's hydrophobicity, where acenaphthene, phenanthrene, and fluorene bind to the primary aggregates, while acenaphthenol binds to the secondary bile salt aggregates. The residence time of the guests in the primary aggregates and the access of ionic species from the aqueous phase to the guest in the aggregate depend on the size and the shape of the guest. These results show that bile salt aggregates are adaptable supramolecular host systems.     

Mechanistic insights into stereoselective catalysis-the effects of counterions in a CuII-bissulfoximine-catalyzed Diels-Alder reaction

The initial steps of an enantioselective Diels-Alder reaction catalyzed by a CuII-bissulfoximine complex were followed by EXAFS (EXAFS=extended X-ray absorption fine structure), EPR (EPR=electron paramagnetic resonance) spectroscopy (CW-EPR, FID-detected EPR, pulse ENDOR, HYSCORE; CW=continuous wave; ENDOR=electron nuclear double resonance; HYSCORE=hyperfine sublevel correlation; FID=free induction decay), and UV-visible spectroscopy. The complexes formed between the parent CuX2 (X=Cl-, Br-, TfO-, SbF6-) salts, the chiral bissulfoximine ligand (S,S)-1, and N-(1-oxoprop-2-en-1-yl)oxazolidin-2-one (2) as the substrate in CH2Cl2 were investigated in frozen and fluid solution. In all cases, penta- or hexacoordinated CuII centers were established. The complexes with counterions indicating high stereoselectivity (TfO- and SbF6-) reveal one unique species in which substrate 2 binds to pseudoequatorial positions (via O atoms), shifting the counterions to axial locations. On the other hand, those lacking stereoselectivity (X=Cl- and Br-) form two species in which the parent halogen anions remain at equatorial positions preventing the formation of geometries compatible with those found for X=TfO- and SbF6-.     

Glycine- and sarcosine-based models of vanadate-dependent haloperoxidases in sulfoxygenation reactions

Reaction of R-styreneoxide with glycine-tert-butylester yielded amino alcohols of the general formula NR1R2R3, where R1 = CH2COOtBu and R2 = R3 = 2-phenyl-2-hydroxyethyl (H2LA); R2 = 2-phenyl-2-hydroxyethyl and R3 = 1-phenyl-2-hydroxyethyl (H2LB); R2 = H and R3 = 2-phenyl-2-hydroxyethyl (HLC); and R2 = H and R3 = 1-phenyl-2-hydroxyethyl (HLD). The corresponding reaction with sarcosine-tert-butylester and subsequent hydrolysis provided the zwitterion +NH(CH3){CH2CHPh(OH)}(CH2CO2-), HLE* (asterisk refers to unprotected carboxylate). Reaction of these ligands with VO(OiPr)3 in CH2Cl2 gave the oxovanadium(V) complexes [VOL(OiPr)2] and [VOL2(OiPr)] (for LC and LD) or, when reacted in the presence of MeOH, [VOL'(OMe)], where L' represents the methyl ester of LA, LB, and LE. The crystal and molecular structures of R-HLC, S-HLD, R,S-HLE* x H2O, and lambda-[VO(R,S-LB')OMe] have been determined. The complex [VOLB'(OMe)] contains vanadium in a distorted trigonal-bipyramidal array (tau = 0.72), the oxo group in the equatorial plane, and methoxide and N in the apical positions, and thus, it structurally models the active center of vanadate-dependent haloperoxidases. The structure and the bonding parameters, including a particularly long d(V-N) of 2.562 A, are backed up by DFT calculations. The isolated oxovanadium(V) complexes and the in situ systems L + VO(OiPr)3 catalyze the oxidation, by cumylhydroperoxide HO2R', of prochiral sulfides (MeSPh, MeSp-Tol, PhSBn) to chiral sulfoxides plus some sulfone. The best results with respect to enantioselectivity (enantiomeric excess (ee) = 38%) were obtained with the system VO(OiPr)3/LA, and the best selectivity with respect to sulfoxide (100%) was obtained with [VOLA(OiPr)]. The reaction with the hexacoordinated [VO(OMe)(HOMe)LD*] was very slow. Oxidation of PhSBn is faster than that of MeSPh and MeSpTol. Turn-over numbers are up to 60 mol of sulfoxide mol-1 of catalyst h-1 (-20 degrees C). The unspectacular ee apparently is a consequence of flexibility of the active catalyst in solution, as shown by the 51V NMR of the catalysts [VOL(OR)] and the oxo-peroxo intermediates [VOL(O2R')]. As shown by DFT calculations, the peroxo ligand coordinates in the tilted end-on fashion in the axial or equatorial position (energy difference = 17.6 kJ/mol).     

Supramolecular photochirogenesis with biomolecules. Mechanistic studies on the enantiodifferentiation for the photocyclodimerization of 2-anthracenecarboxylate mediated by bovine serum albumin

Photophysics and photochemistry of 2-anthracenecarboxylate (AC) bound to bovine serum albumin (BSA) were investigated in detail for the first time by electronic absorption, circular dichroism (CD), steady-state and time-resolved fluorescence, fluorescence quenching, and product analysis studies. Through the spectroscopic investigations, it was revealed that the four independent binding pockets of BSA, which are known to accommodate 1, 3, 2, and 3 AC molecules in the order of decreasing affinity, are distinctly different in hydrophobicity, chiral environment, and accessibility. Interestingly, AC bound to site 1 gave highly structured fluorescence with dual lifetimes of 4.8 and 2.1 ns in an intensity ratio of 3:2, which may be assigned to the existence of two positional or orientational isomers within the very hydrophobic site 1. In contrast, the lifetime of AC in site 2 was much longer (13.3 ns), and ACs in sites 3 and 4 have broader fluorescence spectra with lifetimes that were practically indistinguishable from that in bulk water (15.8 ns). Although each of sites 2-4 simultaneously binds multiple AC molecules, no CD exciton coupling or static fluorescence quenching was detected, indicating that ACs bound to each site are not in close proximity to each other. Quenching studies with nitromethane further confirmed the significant difference in accessibility among the binding sites; thus, ACs bound to sites 1 and 2 are highly protected from the attack of the quencher, affording 32 and 10 times smaller rate constants than that for free AC in water. Product studies in the presence and absence of nitromethane more clearly revealed the photochirogenic performance of each binding site. Although the addition of nitromethane did not greatly alter the product distribution, the enantiomeric excesses (ee's) of chiral cycloadducts 2 and 3 were critically manipulated by selectively retarding the photoreaction occurring at the more accessible binding sites. Thus, the highest ee of 38% was obtained for 2 in the presence of 18 mM nitromethane, while the highest ee of 58% was attained for 3 in the absence of nitromethane, both at [AC]/[BSA]=3.6.