Andreas Herrmann

Alteration of the aminophospholipid translocase activity during in vivo and artificial aging of human erythrocytes

Human erythrocytes were separated into three density groups representing different age groups. Phospholipid outside-inside translocation rates and equilibrium distribution were determined in each group with spin-labeled phosphatidylserine (PS*), phosphatidylethanolamine (PE*), and phosphatidylcholine (PC*), at 37 degrees C and 4 degrees C. At both temperatures, the initial velocity of aminolipid translocation was reduced in the more dense (older) cells. The equilibrium distribution was not significantly modified for PS*, but a larger fraction of PE* remained on the outer monolayer of the more dense cells. PC* transmembrane diffusion was identical in the three fractions. Cytosolic ATP, which is required for aminophospholipid translocation, was not responsible for the variability of the density separated cells since ATP enrichment did not cancel the differences between top and bottom fractions, although it equalized the ATP concentration of the various fractions. Variations in the level of intracellular Ca2+ could also be excluded. Thus, the enzyme aminophospholipid translocase seemed to be directly altered in aged cells, possibly due to oxidation caused by lipid peroxidation products. Experiments with malonyldialdehyde or H2O2 treated cells confirmed this interpretation and suggest that defects in endogenous lipid asymmetry observed in aged human erythrocytes may be due to altered activity of the translocase.

Preparation of enantiomerically pure C76 with a general electrochemical method for the removal of Di(alkoxycarbonyl)methano bridges from methanofullerenes: The retro-bingel reaction

Serendipitously discovered during electrochemical investigations on the stability of anion 1, a preparatively useful electrochemical procedure, the retro-Bingel reaction, has been identified as a method for removing di(alkoxycarbonyl)methano bridges from methanofullerenes. This procedure was applied to prepare the first samples of enantiomerically pure D2-C76 with unambiguous optical purity.

Electric-field triggered controlled release of bioactive volatiles from imine-based liquid crystalline phases.

Application of an electric field to liquid crystalline film forming imines with negative dielectric anisotropy, such as N-(4-methoxybenzylidene)-4-butylaniline (MBBA, 1), results in the expulsion of compounds that do not participate in the formation of the liquid crystalline phase. Furthermore, amines and aromatic aldehydes undergo component exchange with the imine by generating constitutional dynamic libraries. The strength of the electric field and the duration of its application to the liquid crystalline film influence the release rate of the expelled compounds and, at the same time, modulate the equilibration of the dynamic libraries. The controlled release of volatile organic molecules with different chemical functionalities from the film was quantified by dynamic headspace analysis. In all cases, higher headspace concentrations were detected in the presence of an electric field. These results point to the possibility of using imine-based liquid crystalline films to build devices for the controlled release of a broad variety of bioactive volatiles as a direct response to an external electric signal.

Dynamic Mixtures: Challenges and Opportunities for the Amplification and Sensing of Scents

Nature generates compounds as complicated mixtures, but surprisingly little is known about the synergies or inhibitory effects of compound mixtures, which is likely to become an important research area in life sciences in the near future. Some recently developed concepts in dynamic combinatorial/covalent chemistry (DCC) have been applied to amplify (increase the intensity and long-lastingness of perception) and sense (selectively detect and discriminate) individual bioactive volatile molecules in compound mixtures. This Concept article focuses on the potential of DCC to impact and modulate the biological and chemical properties of mixtures of bioactive volatile compounds to gain a more fundamental understanding of the properties of compound mixtures in molecular recognition.

Light induced controlled release of fragrances by Norrish type II photofragmentation of alkyl phenyl ketones.

The use of alkyl phenyl ketones as delivery systems for the controlled release of fragrances was investigated by photoirradiation of undegassed solutions with a xenon lamp as well as natural sunlight. A large variety of precursor compounds was prepared efficiently in a few reaction steps from commercially available starting materials. The Norrish type II photofragmentation was found to be the predominant reaction pathway to yield the desired perfumery alkenes and acetophenones in polar and apolar solution. Systematic GC-MS analysis of the irradiated solutions allowed identification of a series of side products that are due to the presence of oxygen. A detailed analysis of the product distribution after irradiation was carried out for a series of 4-alkoxy-1-phenylbutanone derivatives. Besides the expected acetophenones, vinyl ethers and phenylcyclobutanols, the formation of alkyl formates, alcohols and 4-oxo-4-phenylbutanoates was observed. The product distribution as influenced by solvent polarity, precursor concentration and substituent effects was investigated. The utility of alkyl phenyl ketones as precursors for the light induced controlled release of fragrances under natural daylight conditions was also demonstrated.

Dynamic headspace analysis of the light-induced controlled release of perfumery aldehydes and ketones from α-keto esters in bodycare and household applications

The controlled release of citronellal and menthone from α-keto esters was tested in different household and bodycare applications by photochemical irradiation of these esters with artificial light sources or natural sunlight. Quantitative dynamic headspace analyses carried out with different application bases, such as all-purpose cleaners and hair conditioners, as well as investigations on different supports, such as glass surfaces, hair or cotton, clearly showed that a sufficient amount of perfume was released in all cases, thus allowing a very broad use of this principle as an efficient delivery system for the controlled release of perfumery chemicals. In addition, the quantitative dynamic headspace analyses carried out in these studies help to elucidate the kinetics of perfume release tested in the different applications for a large variety of compounds. Copyright

Synthesis of hydroxypropyl cellulose derivatives modified with amphiphilic diblock copolymer side-chains for the slow release of volatile molecules

Hydroxypropyl cellulose (HPC) was used as carrier material to prepare comb-like grafted block copolymers having an amphiphilic core–shell structure. The hydroxyl groups of HPC were partially protected with trimethylsilyl groups and the free OH groups used to initiate the ring opening polymerisation (ROP) of L-lactide. The end-chain of the grafted hydrophobic poly(L-lactide) (PLLA) chain was then functionalised with 2-bromopropionyl bromide which was used to polymerise the tert-butyl acrylate (tBA) monomer by atom transfer radical polymerisation (ATRP). The hydrophobic PtBA block was then hydrolysed to a hydrophilic poly(acrylic acid) (PAA) block. The resulting amphiphilic grafted copolymer HPC-g-(PLLA-b-PAA) was dissolved in an ethanol/water mixture (9u2006:u20061), such as a typical Eau de Toilette (EdT) formulation. Atomic force microscopy (AFM) and size measurements confirmed the presence of core–shell structures in solution. A significant swelling of HPC-g-(PLLA-b-PAA) in the presence of a volatile bioactive molecule, methyl 2,2-dimethyl-6-methylene-1-cyclohexanecarboxylate (Romascone®), was observed by dynamic light scattering (DLS). Furthermore, the presence of HPC-g-(PLLA-b-PAA) significantly decreased the evaporation rate of Romascone®, thus serving as an efficient fragrance delivery system in formulations with high ethanol content.

Achiral and Chiral Higher Adducts of C70 by Bingel Cyclopropanation

Five optically active isomeric C70 bis-adducts with (R)-configured chiral malonate addends were prepared by Bingel cyclopropanation (Schemeu20051) and their circular dichroism (CD) spectra investigated in comparison to those of the corresponding five bis-adducts with (S)-configured addends (Fig.u20052). Pairs of diastereoisomers, in which the inherently chiral addition patterns on the fullerene surface have an enantiomeric relationship, display mirror-image shaped CD spectra that are nearly identical to those of the corresponding pairs of enantiomers (Fig.u20053, b and c). This result demonstrates that the Cotton effects arising from the chiral malonate addends are negligible as compared to the chiroptical contribution of the chirally functionalized fullerene chromophore. A series of four stereoisomeric tetrakis-adducts (Fig.u20054) was prepared by Bingel cyclopropanation starting from four stereoisomeric bis-adducts. A comparison of the CD spectra of both series of compounds showed that the magnitude of the Cotton effects does not decrease with increasing degree of functionalization (Fig.u20055). Bingel cyclopropanations of C70 in Me2SO are dramatically faster than in apolar solvents such as CCl4, and the reaction of bis-adducts (±)-13 and 15 with large excesses of diethyl 2-bromomalonate and DBU generated, via the intermediacy of defined tetrakis-adducts (±)-16 and 17, respectively, a series of higher adducts including hexakis-, heptakis-, and octakis-adducts (Tableu20051). A high regioselectivity was observed up to the stage of the hexakis-adducts, whereas this selectivity became much reduced at higher stages of addition. The regioselectivity of the nucleophilic cyclopropanations of C70 correlates with the coefficients of the LUMO (lowest unoccupied molecular orbital) and LUMO+1 at the positions of preferential attack calculated by restricted Hartree-Fock – self-consistent field (RHF-SCF) methods (Figs.u20059u2009–u200911). Based on predictions from molecular-orbital calculations (Fig.u200511) and the analysis of experimental 13C-NMR data (Fig.u20057,u2009a), the structure of a unique hexakis-adduct ((±)-22, Fig.u200512), prepared from (±)-13, was assigned. The C2-symmetrical compound contains four 6−6-closed methanofullerene sub-structures in its polar regions (at the bonds C(1)−C(2), C(31)−C(32), C(54)−C(55), and C(59)−C(60)), and two 6−5-open methanofullerene sub-structures parallel to the equator (at C(22)−C(23) and C(26)−C(27)). The 6−5-open sub-structures are formed by malonate additions to near-equatorial 6−5 bonds with enhanced LUMO coefficients, followed by valence isomerization (Fig.u200512).

Influence of the backbone structure on the release of bioactive volatiles from maleic acid-based polymer conjugates.

Poly(maleic acid monoester)-based β-mercapto ketones were synthesized and investigated as potential delivery systems for the controlled release of bioactive, volatile, α,β-unsaturated enones (such as damascones and damascenones) by retro 1,4-addition. The bioconjugates were prepared in a one-pot synthesis using 2-mercaptoethanol as a linker. The thiol group of 2-mercaptoethanol adds to the double bond of the enone to form a β-mercapto ketone, which was then grafted via nucleophilic ring-opening of the remaining alcohol function onto a series of alternating copolymers of maleic anhydride and 1-octadecene, ethylene, isobutylene, and methyl vinyl ether. The influence of copolymer backbones on the release of δ-damascone was investigated in buffered aqueous solution as a function of pH and time. In the presence of a cationic surfactant, the polymer conjugates were transferred from an aqueous medium to a cotton surface. The deposition and the release of δ-damascone from the cotton surface as a function of the polymer backbone structure were measured by fluorescence spectroscopy and dynamic headspace analysis, respectively. All polymer conjugates were found to deliver higher amounts of the volatile into the headspace than the reference consisting of unmodified δ-damascone. Polymers with a hydrophobic backbone were generally efficiently deposited on the cotton surface, but released δ-damascone only moderately in solution. Conjugates with a more hydrophilic backbone release the active compound more efficiently in water, but are deposited to a lower extent onto the target surface. A good balance of the hydrophobicity and hydrophilicity of the polymer backbone is the key factor to maximize the deposition of the conjugates on the target surface and to optimize the release of the bioactive volatiles.

Controlled release of encapsulated bioactive volatiles by rupture of the capsule wall through the light-induced generation of a gas.

The encapsulation of photolabile 2-oxoacetates in core-shell microcapsules allows the light-induced, controlled release of bioactive compounds. On irradiation with UVA light these compounds degrade to generate an overpressure of gas inside the capsules, which expands or breaks the capsule wall. Headspace measurements confirmed the light-induced formation of CO and CO2 and the successful release of the bioactive compound, while optical microscopy demonstrated the formation of gas bubbles, the cleavage of the capsule wall, and the leakage of the oil phase out of the capsule. The efficiency of the delivery system depends on the structure of the 2-oxoacetate, the quantity used with respect to the thickness of the capsule wall, and the intensity of the irradiating UVA light.