The natural drug, paclitaxel (taxol), is highly effectiveas a tumor chemotherapeuticwith a low probability of inducing chemoresistance,but shows severe toxic side effectsat the therapeutic dose. How can this toxicitybe overcome? Here we report the synthesisof cyclodextrin dimers connected at thesecondary face by amide-bonded aliphatic spacers. The spacer length of one of the dimers referred to asdiβCD(2N-A4C5A4) or dimer 7cmatches the distance between the twobenzoic acid residues of paclitaxel. We investigated the physical inclusion of taxol into this dimer using the TNS-label competition method. Affinity constants with the dimer in comparison to free β-cyclodextrin are found to be of the order of 107 l/mole.When included into the cyclodextrin dimer, the drug shows a considerable time delay of incorporation into human tumor cell cultures (OAT SCLC cells) or a total exclusion from the cells. This is the prerequisite to avoid intoxication of other organs of a patient. Possibilities are discussed to detoxify chemotherapeutics and to target their inclusioncomplexes specifically to tumors using specific biological signals. 相似文献
Hydroxide-loaded anion exchangers have been successfully employed to shift the equilibrium of a one-pot, two-step, two-enzyme cascade reaction affording enantiopure epoxides starting from prochiral α-chloroketones. The α-chloroketones were asymmetrically reduced employing an alcohol dehydrogenase and then transformed further to the corresponding epoxides employing halohydrin dehalogenases. Each epoxide enantiomer could be obtained with up to 93% conversion in enantiomerically pure form (>99% ee). In contrast to previous studies the amount of hydride donor (2-propanol) could be reduced due to favoured halohydrin formation in the reduction of α-chloroketones. 相似文献
Determination of the speciation of arsenic in groundwaters, using cathodic stripping voltammetry (CSV), is severely hampered by high levels of iron and manganese. Experiments showed that the interference is eliminated by addition of EDTA, making it possible to determine the arsenic speciation on-site by CSV. This work presents the CSV method to determine As(III) in high-iron or -manganese groundwaters in the field with only minor sample treatment. The method was field-tested in West-Bengal (India) on a series of groundwater samples. Total arsenic was subsequently determined after acidification to pH 1 by anodic stripping voltammetry (ASV). Comparative measurements by ICP-MS as reference method for total As, and by HPLC for its speciation, were used to corroborate the field data in stored samples. Most of the arsenic (78 ± 0.02%) was found to occur as inorganic As(III) in the freshly collected waters, in accordance with previous studies. The data shows that the modified on-site CSV method for As(III) is a good measure of water contamination with As. The EDTA was also found to be effective in stabilising the arsenic speciation for longterm sample storage at room temperature. Without sample preservation, in water exposed to air and sunlight, the As(III) was found to become oxidised to As(V), and Fe(II) oxidised to Fe(III), removing the As(V) by adsorption on precipitating Fe(III)-hydroxides within a few hours. 相似文献
Controlled presentation of biomolecules on synthetic substrates is an important aspect for biomaterials development. If the immobilization of multiple biomolecules is required, highly efficient orthogonal surface chemistries are needed to ensure the precision of the immobilization. In this communication, chemical vapor deposition (CVD) copolymerization is used to fabricate polymer coatings with controlled ratio of alkyne and pentafluorophenyl ester (Pfp‐ester) groups. Cyclic argine‐glycine‐aspartic acid (cRGD) adhesion peptide and epidermal growth factor (EGF) are immobilized through alkyne–azide cycloaddtion (“click” chemistry) and active ester–amine reaction, respectively. Cell studies with human umbilical vein endothelial cells (HUVEC) and A431 cell lines demonstrate the biological activity of the coimmobilized biomolecules. 相似文献
Summary: The reaction of hydrazine with ethyl glycolate results in 1,2‐bisglycoylhydrazine, a monomer that was used for the lipase‐catalyzed synthesis of biodegradable poly(ester hydrazide)s. The polymers derived from the hydrazide‐containing monomer and vinyl‐activated adipic, suberic, and sebacic acid, respectively, showed low melting temperatures of 136 to 141 °C and are thermally stable up to 300 °C. The aliphatic poly(ester hydrazide)s (PEHs) are highly crystalline, as proven by polarization microscopy and atomic force microscopy. Further, the PEHs represent the first described biodegradable poly(hydrazide)s. They degrade in the presence of lipase at 37 °C within a few weeks.
The antimicrobial activity of poly(alkyloxazoline) telechelics with one quaternary N,N-dimethyldodecylammonium (DDA) end group was found to be greatly controlled by the non-bioactive distal end group, the so-called satellite group. In systematic investigations, the nature of the latter groups was varied to explore the mechanism of the satellite effect. To this end, poly(2-alkyl-1,3-oxazoline)s (alkyl = ethyl, methyl) with a DDA-group at the terminating end and varying alkyl, aminoalkyl, and polyphenyloxazoline block satellite groups, have been synthesized. Poly(oxazoline) derivatives with polydispersity indices of 1.06-1.20 and molecular weights from 2,200 to 12,800 g . mol(-1) could be obtained. The macromolecular structures have been confirmed by NMR spectroscopy and ESI-MS measurements. The polymers were investigated with regard to their antibacterial efficiency towards the Gram-positive bacterium Staphylococcus aureus and the Gram-negative bacterium Escherichia coli. It was found that the introduction of alkyl chain satellites of 4-10 carbon atoms in length afforded antimicrobial activity of the polymers against both microbes that was about 2-3 times higher than that of the well-known structurally comparable low molecular weight biocide, dodecyltrimethylammonium chloride (DTAC). Based on the antimicrobial effects of the investigated polymers, a mechanism for the satellite effect was proposed. 相似文献
We demonstrate spatially controlled photoreactions within bicompartmental microparticles and microfibers. Selective photoreactions are achieved by anisotropic incorporation of photocrosslinkable poly(vinyl cinnamate) in one compartment of either colloids or microfibers. Prior to photoreaction, bicompartmental particles, and fibers were prepared by EHD co‐jetting of two compositionally distinct polymer solutions. Physical and chemical anisotropy was confirmed by confocal laser scanning microscopy, Fourier‐transformed infrared spectroscopy, and scanning electron microscopy. The data indicate adjustment of polymer concentrations of the jetting solutions to be the determining factors for particle and fiber structures. Subsequent exposure of poly(vinyl cinnamate)‐based particles and fibers to UV light at 254 nm resulted in spatially controlled crosslinking. Treatment of the crosslinked bicompartmental colloids with chloroform produced half‐moon shaped objects. These hemishells exhibited a distinct porous morphology with pore sizes in the range of 70 nm. Based on this novel synthetic approach, Janus‐type particles and fibers can be prepared by EHD co‐jetting and can be selectively photocrosslinked without the need for masks or selective laser writing.
Chemical vapor deposition (CVD) co‐polymerization was used to fabricate polymer coatings, which comprise of reactive surface composition gradients. Two functionalized derivatives of [2.2]paracyclophane were fed into a two‐source CVD system at a 180 ° angle, then copolymerized and deposited as a polymer gradient. Infrared and X‐ray photoelectron spectroscopy (XPS) confirmed the compositional changes within the bulk polymer and at the surface. By manipulating process parameters, gradients of tailored compositional slope can be deposited on a wide range of substrates. We also were able to selectively immobilize fluorescence‐labeled ligands onto the reactive polymer gradients, making CVD‐based gradient surfaces a flexible platform for fabricating biomolecular substrates.
A contact-active antimicrobial coating is described that is only degraded in the presence of cellulase, which is an extracellular enzyme of numerous microbial strains. Antimicrobial DDA was grafted to a cellulose backbone via a polymeric spacer. The antimicrobial activity of the coatings, their biodegradability and their self-polishing potential were investigated. It was found that all coatings were antimicrobially active against Staphylococcus aureus. Coatings with high DS and long polymeric spacers degraded in water, while coatings with low DS and short spacers were not hydrolyzed even in the presence of cellulase. One coating was found to be selectively degradable by cellulase and recovered most of its antimicrobial activity after overloading and subsequent treatment with cellulase. 相似文献
