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Pavel Anzenbacher

Publications and source records attributed to Pavel Anzenbacher.

At least 19 recordsLinked to original sources
PubMed2006

True blue: blue-emitting aluminum(III) quinolinolate complexes.

Blue-emitting heteroleptic aluminum(III) bis(2-methyl-8-quinolinolate)phenolate complexes were synthesized. A tunable, blue-to-green emission is achieved by attaching electron-withdrawing modulators to the emisssive quinaldinate ligand. The electronic nature of modulator substituents attached to the position of the highest HOMO (highest occupied molecular orbital) density is used to modulate ligand HOMO levels to achieve effective emission tuning to obtain blue-emitting materials. Optical and electrochemical properties of the resulting complexes were investigated and compared to the results of density functional theory (DFT/B3LYP/6-31G*) studies. The resulting materials may find application as organic light-emitting device materials.

Journal Article↗
PubMed2006

Structural analysis of cytochromes P450 shows differences in flexibility of heme 2- and 4-vinyls.

Structural analysis of the orientations of heme vinyl side chains was carried out using the published crystallographic data for different cytochromes P450. Torsional angles (tau, C(alpha)C(beta)-C(a)C(b)) show different distributions for the vinyls in positions 2 and 4. Whereas the orientation of 2-vinyls is rather restricted (tau between -120 degrees and -180 degrees ), the 4-vinyls have a much higher mobility over almost the entire conformational space. On the basis of the empirical correlation recently reported for peroxidases (M.P. Marzocchi, G. Smulevich, Relationship between heme vinyl conformation and the protein matrix in peroxidases, J. Raman Spectrosc. 34 (2003), 725-736), an attempt has been made to compare the observed vinyl orientations with the experimental frequencies of the vinyl stretching vibrational modes. The data for P450 proteins do not exactly match the peroxidase-derived function, although a qualitatively similar relationship is likely to exist. Differences between P450 forms suggest a variability in heme-region flexibility and in communication with the rest of enzyme.

Bacterial Proteins↗
PubMed2006

What common structural features and variations of mammalian P450s are known to date?

Sufficient structural information on mammalian cytochromes P450 has now been published (including seventeen X-ray structures of these enzymes by June 2006) to allow characteristic features of these enzymes to be identified, including: (i) the presence of a common fold, typical of all P450s, (ii) similarities in the positioning of the heme cofactor, (iii) the spatial arrangement of certain structural elements, and (iv) the access/egress paths for substrates and products, (v) probably common orientation in the membrane, (vi) characteristic properties of the active sites with networks of water molecules, (vii) mode of interaction with redox partners and (viii) a certain degree of flexibility of the structure and active site determining the ease with which the enzyme may bind the substrates. As well as facilitating the identification of common features, comparison of the available structures allows differences among the structures to be identified, including variations in: (i) preferred access/egress paths to/from the active site, (ii) the active site volume and (iii) flexible regions. The availability of crystal structures provides opportunities for molecular dynamic simulations, providing data that are apparently complementary to experimental findings but also allow the dynamic behavior of access/egress paths and other dynamic features of the enzymes to be explored.

Amino Acid Sequence↗
PubMed2006

Molecular-wire behavior of OLED materials: exciton dynamics in multichromophoric Alq3-oligofluorene-Pt(II)porphyrin triads.

Donor-bridge-acceptor triads consisting of the Alq3 complex, oligofluorene bridge, and PtII tetraphenylporphyrin (PtTPP) were synthesized. The triads were designed to study the energy level/distance-dependence in energy transfer both in a solution and in solid state. The materials show effective singlet transfer from the Alq3-fluorene fluorophore to the porphyrin, while the triplet energy transfer, owing to the shorter delocalization of triplet excitons, appears to take place via a triplet energy cascade. Using femtosecond transient spectroscopy, the rate of the singlet-singlet energy transfer was determined. The exponential dependence of the donor-acceptor distance and the respective energy transfer rates of 7.1 x 1010 to 1.0 x 109 s-1 with the attenuation factor â of 0.21 +/- 0.02 A-1 suggest that the energy transfer proceeds via a mixed incohererent wire/superexchange mechanism. In the OLEDs fabricated using the Alq3-oligofluorene-PtTPP triads with better triplet level alignment, the order of a magnitude increase in efficacy appears to be due to facile triplet energy transfer. The devices, where the triplet-triplet energy transfer is of paramount importance, showed high color purity emission (CIE X,Y: 0.706, 0.277), which is almost identical to the emission from thin films. Most importantly, we believe that the design principles demonstrated above are general and may be used to prepare OLED materials with enhanced quantum efficacy at lowered operational potentials, being crucial for improved lifespan of OLEDs.

Journal Article↗
PubMed2006

Synthesis, structure, anion binding, and sensing by calix[4]pyrrole isomers.

The synthesis, structure, and anion binding properties of chromogenic octamethylcalix[4]pyrroles (OMCPs) and their N-confused octamethylcalix[4]pyrrole isomers (NC-OMCPs) containing an inverted pyrrole ring connected via alpha'- and beta-positions are described. X-ray diffraction analyses proved the structures of two synthesized isomeric pairs of OMCPs and NC-OMCPs. The addition of anions to solutions of chromogenic OMCPs and NC-OMCPs resulted in different colors suggesting different anion-binding behaviors. The chromogenic NC-OMCPs showed significantly stronger anion-induced color changes compared to the corresponding chromogenic OMCP, and the absorption spectroscopy titrations indicated that chromogenic OMCPs and NC-OMCPs also possess different anion binding selectivity. Detailed NMR studies revealed that this rather unusual feature stems from a different anion-binding mode in OMCPs and NC-OMCPs, one where the beta-pyrrole C-H of the inverted pyrrole moiety participates in the hydrogen-bonded anion-NC-OMCP complex. Preliminary colorimetric microassays using synthesized chromogenic calixpyrroles embedded in partially hydrophilic polyurethane matrices allow for observation of analyte-specific changes in color when the anions are administered in the form of their aqueous solutions and in the presence of weakly competing anions.

Journal Article↗
PubMed2006

Effective manipulation of the electronic effects and its influence on the emission of 5-substituted tris(8-quinolinolate) aluminum(III) complexes.

The unique electron-transport and emissive properties of tris(8-quinolinolate) aluminum(III) (Alq(3)) have resulted in extensive use of this material for small molecular organic light-emitting diode (OLED) fabrication. So far, efforts to prepare stable and easy-to-process red/green/blue (RGB)-emitting Alq(3) derivatives have met with only a limited success. In this paper, we describe how the electronic nature of various substituents, projected via an arylethynyl or aryl spacer to the position of the highest HOMO density (C5), may be used for effective emission tuning to obtain blue-, green-, and red-emitting materials. The synthetic strategy consists of four different pathways for the attachment of electron-donating and electron-withdrawing aryl or arylethynyl substituents to the 5-position of the quinolinolate ring. Successful tuning of the emission color covering the whole visible spectrum (lambda=450-800 nm) was achieved. In addition, the photophysical properties of the luminophores were found to correlate with the Hammett constant of the respective substituents, providing a powerful strategy with which to predict the optical properties of new materials. We also demonstrate that the electronic nature of the substituent affects the emission properties of the resulting complex through effective modification of the HOMO levels of the quinolinolate ligand.

Aluminum↗
PubMed2006

1,3-indane-based chromogenic calixpyrroles with push-pull chromophores: synthesis and anion sensing.

[structure: see text]. Knoevenagel condensation of 2-formyl-octamethylcalix[4]pyrrole with selected 1,3-indanedione derivatives yields calix[4]pyrrole anion sensors with push-pull chromophores displaying strong intramolecular charge transfer. The push-pull feature results in augmented signal output as well as in dramatic changes in anion selectivity exemplified by a 50-fold increase in acetate vs chloride selectivity compared to the parent calix[4]pyrrole.

Journal Article↗
PubMed2006

In vivo effects of antiviral acyclic nucleoside phosphonate 9-[2-(phosphonomethoxy)ethyl]adenine (adefovir) on cytochrome P450 system of rat liver microsomes.

Interference of antiviral agent adefovir, i.e. 9-[2-(phosphonomethoxy)ethyl]adenine (PMEA) with microsomal drug metabolizing system was investigated in rats. The content of total liver cytochrome P450 (CYP) was lowered while that of its denaturated form, P420, was elevated in animals intraperitoneally treated with PMEA (25 mg/kg). Similar effect was observed after treatment with a prodrug of adevofir, adefovir dipivoxil (bisPOM-PMEA). The CYP2E1-dependent formation of 4-nitrocatechol from p-nitrophenol was diminished, though the specific activity of p-nitrophenol hydroxylase remained unchanged. PMEA had no influence on expression of CYP2E1 protein and mRNA and mRNAs of other P450 isoenzymes (1A1, 1A2, 2C11, 3A1, 3A2, and 4A1). It may be concluded that repeated systemic administration of higher doses of PMEA results in a partial degradation of rat CYP protein to inactive P420.

Adenine↗
PubMed2006

Quantitative structure-activity relationships (QSARs) within cytochromes P450 2B (CYP2B) subfamily enzymes: the importance of lipophilicity for binding and metabolism.

The results of qualitative structure-activity relationship (QSAR) analysis are reported for several series of compounds which act as substrates for mammalian CYP2B subfamily enzymes, together with a homologous series of aliphatic primary amines which are known to inhibit CYP2B enzymes. It is found that the compound lipophilicity in the form of the log P value (where P is the octanol/water partition coefficient) is related, either linearly or quadratically, to equilibrium constants of inhibition (Ki), binding (Ks) or metabolism (Km) depending on the series of compounds in question. In some instances, the difference between frontier orbital energy levels (deltaE) also features in several of the log P expressions with biological activity. Also present in a small number of correlations are parameters which are likely to be related to logP: namely, Rm, which is the partitioning factor derived from thin layer chromatography (TLC) retention times, and also the compound molecular weight (Mr). All of these three parameters ((log P, Rm and Mr) are thought to be related to the compound's ability to desolvate the P450 active site when they bind to the enzyme. Although the linear relationships between lipophilicity and CYP2B-related activity point to a major role for desolvation of the enzyme binding site in the overall interaction, it is noted that there may be an optimal log P value displayed by preferred substrates as shown by parabolic relationships with this lipophilic parameter. In addition, there is a remarkable similarity in the coefficients for the log P term of any QSAR expression, which suggests that the hydrophobicity of CYP2B active sites may be broadly equivalent between the various mammalian species.

Animals↗
PubMed2006

Experimental approaches to studies on drug metabolism and drug interactions in man: interaction of acyclic nucleoside phosphonates with human liver cytochromes P450 and flavin-containing monooxygenase 3.

OBJECTIVES: To determine a possible influence of acyclic nucleoside phosphonates on FMO3 and CYP activity at molecular level in vitro. METHODS: Inhibition of individual CYP and FMO3 activities in the reconstituted system and in artificial membranes (bactosomes) was studied. RESULTS: Activity of FMO3 was inhibited by PMPA and bisPOC-PMPA even at low levels of these drugs (below 100 microM). In reconstituted system with CYP2C9, no inhibition of CYP2C9 activity was observed. On the other hand, experiments based on membrane coexpressed system showed a modest extent of inhibition (for PMEA, PMPA, bisPOM-PMEA and bisPOC-PMPA the level of inhibition was 77.8%; 74.1%; 64.2% and 68.6%, respectively at 400 microM). CONCLUSIONS: PMPA and bisPOC-PMPA are able to inhibit FMO3 activity at relatively low levels (10-100 microM) indicating a relatively specific interaction. Activity of CYP2C9 was affected when using the membranes coexpressed with NADPHcytochrome P450 reductase. This is probably due to more natural conditions for maintaining the CYP activity in bacterial membranes. As the inhibitor concentration in the systemic circulation does not exceed 2 microM, the probability of a significant in vivo effect of adefovir, tenofovir and the respective prodrugs on the microsomal system of cytochromes P450 and FMO3 is relatively low.

Adenine↗
PubMed2005

Simple electrooptical sensors for inorganic anions.

[reaction: see text] Electrooptical sensors consisting of a conjugated chromophore undergoing a change in color and a redox-active moiety such as quinone fused to the chromophore were synthesized. Strong changes in colorimetric and electrochemical properties were observed in the presence of inorganic anions. A unique anion-specific response was observed for fluoride, pyrophosphate, and acetate. DFT (B3LYP/6-31G) calculations performed for both "on/off" states of a sensor-fluoride model are in good agreement with the observed electrochemical and spectroscopic data.

Journal Article↗
PubMed2005

Interaction of porphyrins with a dendrimer template: self-aggregation controlled by pH.

The interaction between self-aggregated porphyrins such as 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin (TPPS) and 5,10,15,20-tetrakis(4-phosphonatophenyl)porphyrin (TPPP), and a generation 5 (G5) PAMAM dendrimer template is governed by minute differences of porphyrin acido-basic properties. While at neutral pH both monomeric TPPS and TPPP form complexes with G5, decreasing pH did not lead to porphyrin ring protonation (pK(a) approximately 5) but rather to the preferential formation of H-aggregates (probably H-dimers), most likely due to protonation of the G5. Upon further acidification of the solution, this face-to-face orientation of the porphyrin units is being converted to edge-to-edge aligned J-aggregates with a tightly defined structure. This process starts by protonation of the porphyrin ring at pH below 2.3 and 2.8 for TPPS and TPPP, respectively. The AFM imaging of porphyrin/G5 nanostructures obtained at pH 0.7 shows the formation of long nanorods of TPPS with partially aggregated G5 and small aggregates of TPPP connected to individual G5 molecules.

Journal Article↗
PubMed2005

Active sites of two orthologous cytochromes P450 2E1: differences revealed by spectroscopic methods.

Cytochromes P450 2E1 of human and minipig origin were examined by absorption spectroscopy under high hydrostatic pressure and by resonance Raman spectroscopy. Human enzyme tends to denature to the P420 form more easily than the minipig form; moreover, the apparent compressibility of the heme active site (as judged from a redshift of the absorption maximum with pressure) is greater than that of the minipig counterpart. Relative compactness of the minipig enzyme is also seen in the Raman spectra, where the presence of planar heme conformation was inferred from band positions characteristic of the low-spin heme with high degree of symmetry. In this respect, the CYP2E1 seems to be another example of P450 conformational heterogeneity as shown, e.g., by Davydov et al. for CYP3A4 [Biochem. Biophys. Res. Commun. 312 (2003) 121-130]. The results indicate that the flexibility of the CYP active site is likely one of its basic structural characteristics.

Animals↗
PubMed2005

Expression of cytochrome P450 genes in CD34+ hematopoietic stem and progenitor cells.

Expression of major cytochrome P450 forms (P450) was followed in preparation of purified hematopoietic CD34+ stem and progenitor cells. Levels of transcripts as well as mature proteins were traced by quantitative real-time polymerase chain reaction and by Northern and Western blotting. P450 1B1 and P450 2E1 proteins and respective mRNAs were found in all cases. On the other hand, no expression of P450 3A4, P450 3A7, and P450 2C9 was found. The results showed that expression of various P450 enzymes starts at different stages of cell differentiation. Both P450 forms found are known to be connected with cancer cells and with activation of procarcinogens (P450 1B1, polycyclic aromatic hydrocarbons; P450 2E1, nitrosamines, and solvents). Hence, cells at the early stage of differentiation already may be influenced by interaction with xenobiotics. This fact should also be taken into consideration when hematopoietic cell transplant therapy is applied.

Antigens, CD34↗
PubMed2005

Sensing of antipyretic carboxylates by simple chromogenic calix[4]pyrroles.

We present a simple, two- or three-step method for the synthesis of chromogenic octamethylcalix[4]pyrrole-based (OMCP) sensors for anions. Electrophilic aromatic substitution allows for converting the pyrrole moieties of OMCP into a dye. The formation of a sensor-anion complex results in partial charge transfer and a dramatic change in color. The absorption (UV-vis) and NMR titration experiments show that the chromogenic OMCPs sense anions administered as aqueous solutions, even at high ionic strength ( approximately 0.1 M NaCl), while displaying selectivity for pyrophosphate and carboxylate anions. The experiments with polyurethane sensor films show a strong response for aqueous carboxylates, such as antipyretics naproxen approximately ibuprofen > salicylate, without being biased by bicarbonate or carboxy termini of blood plasma proteins.

Analgesics, Non-Narcotic↗
PubMed2005

Minipig cytochrome P450 2E1: comparison with human enzyme.

Cytochrome P450 2E1 was isolated from minipig liver microsomes. The protein has been cloned and the respective cDNA sequenced (GenBank Accession Number AY581116). Minipig CYP2E1 is two residues shorter than its human ortholog. The only difference between pig and minipig sequence is the presence of aspartic acid residue in position 346 contrary to valine in the pig enzyme. Minipig CYP2E1 was shown to be able to convert two prototypical substrates of human CYP2E1, chlorzoxazone and p-nitrophenol, to the respective metabolites. The experiments performed with both the liver microsomal fraction and reconstituted systems with human or minipig CYP2E1 confirmed the similarity of both enzymes. Inhibition with diethyldithiocarbamate gave comparable Ki values for minipig as well as for the human CYP2E1. The results indicate that the systems containing minipig CYP2E1 may be used to model the respective CYP2E1-catalyzed reactions of drug metabolism in humans.

Animals↗
PubMed2005

Comparison of "high throughput" micromethods for determination of cytochrome P450 activities with classical methods using HPLC for product identification.

Enzyme activities of the CYP enzymes (CYP3A4, CYP2C9 and CYP2A6) were determined using classical substrates (testosterone, diclofenac and coumarin, respectively) as well as with luminogenic or fluorogenic substrates in micromethod arrangement. The luciferin-based luminogenic substrates for CYP3A4 and CYP2C9 as well as coumarin in micromethod for assay of CYP2A6 activity gave results well comparable with the classical methods with determination of reaction products by the HPLC.

Aryl Hydrocarbon Hydroxylases↗