: The unpolarized absorption and circular dichroism spectra of the fundamental vibrational transitions of the chiral molecule, 4-methyl-2-oxetanone, are calculated ab initio. Harmonic force fields are obtained using Density Functional Theory (DFT), MP2, and SCF methodologies and a 5S4P2D/3S2P (TZ2P) basis set. DFT calculations use the Local Spin Density Approximation (LSDA), BLYP, and Becke3LYP (B3LYP) density functionals. Mid-IR spectra predicted using LSDA, BLYP, and B3LYP force fields are of significantly different quality, the B3LYP force field yielding spectra in clearly superior, and overall excellent, agreement with experiment. The MP2 force field yields spectra in slightly worse agreement with experiment than the B3LYP force field. The SCF force field yields spectra in poor agreement with experiment.The basis set dependence of B3LYP force fields is also explored: the 6-31G* and TZ2P basis sets give very similar results while the 3-21G basis set yields spectra in substantially worse agreements with experiment. jg

Ab initio calculation of vibrational absorption and circular dichroism spectra using density functional force fields

Epik is a computer program for predicting pKa values for drug-like molecules. Epik can use this capability in combination with technology for tautomerization to adjust the protonation state of small drug-like molecules to automatically generate one or more of the most probable forms for use in further molecular modeling studies. Many medicinal chemicals can exchange protons with their environment, resulting in various ionization and tautomeric states, collectively known as protonation states. The protonation state of a drug can affect its solubility and membrane permeability. In modeling, the protonation state of a ligand will also affect which conformations are predicted for the molecule, as well as predictions for binding modes and ligand affinities based upon protein–ligand interactions. Despite the importance of the protonation state, many databases of candidate molecules used in drug development do not store reliable information on the most probable protonation states. Epik is sufficiently rapid and accurate to process large databases of drug-like molecules to provide this information. Several new technologies are employed. Extensions to the well-established Hammett and Taft approaches are used for pKa prediction, namely, mesomer standardization, charge cancellation, and charge spreading to make the predicted results reflect the nature of the molecule itself rather just for the particular Lewis structure used on input. In addition, a new iterative technology for generating, ranking and culling the generated protonation states is employed.

Epik: a software program for pK a prediction and protonation state generation for drug-like molecules

Modern synthetic methods have revolutionized polymer chemistry through the development of new and powerful strategies for the controlled synthesis of complex polymer architectures. 1-5 Many of these developments were spawned by new classes of transition metal catalysts for the synthesis of new polyolefin microstructures, 5 the design of highly efficient families of “living” polymerization strategies for the synthesis of block, graft, and star polymers, 6-12 controlled methods for the synthesis of dendritic macromolecules, 3,13,14

Organocatalytic ring-opening polymerization.

Vibrational Energy Distribution Analysis (VEDA): Scopes and limitations

Epidemiological evidence suggests that flavonoids may play an important role in the decreased risk of chronic diseases associated with a diet rich in plant-derived foods. Flavonoids are also common constituents of plants used in traditional medicine to treat a wide range of diseases. The purpose of this article is to summarize the distribution and biological activities of one of the most common flavonoids: luteolin. This flavonoid and its glycosides are widely distributed in the plant kingdom; they are present in many plant families and have been identified in Bryophyta, Pteridophyta, Pinophyta and Magnoliophyta. Dietary sources of luteolin include, for instance, carrots, peppers, celery, olive oil, peppermint, thyme, rosemary and oregano. Preclinical studies have shown that this flavone possesses a variety of pharmacological activities, including antioxidant, anti-inflammatory, antimicrobial and anticancer activities. The ability of luteolin to inhibit angiogenesis, to induce apoptosis, to prevent carcinogenesis in animal models, to reduce tumor growth in vivo and to sensitize tumor cells to the cytotoxic effects of some anticancer drugs suggests that this flavonoid has cancer chemopreventive and chemotherapeutic potential. Modulation of ROS levels, inhibition of topoisomerases I and II, reduction of NF-kappaB and AP-1 activity, stabilization of p53, and inhibition of PI3K, STAT3, IGF1R and HER2 are possible mechanisms involved in the biological activities of luteolin.

Distribution and biological activities of the flavonoid luteolin.

Clear and cloudy apple juices from Idared and Champion varieties were studied for their radical-scavenging effects. The polyphenolic content and composition of the juices before and after thiolysis were determined by high-performance liquid chromatography with diode array detection. Cloudy juices, especially that prepared from Champion variety, had a higher content of procyanidins than clear juices. Radical-scavenging activity was measured by electron paramagnetic resonance (EPR) spectroscopy using the stable 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical. All juices showed long-lasting radical-scavenging activity, and EPR spectra were recorded over time to follow the reaction kinetics. Scavenging of DPPH showed pseudo-first-order kinetics, which might be expected in the presence of polymerised antioxidants that prevent closer contact between the DPPH radical and hydroxyl groups. The content of polymeric procyanidins showed a linear dependence on the rate constant, suggesting that these compounds are mainly responsible for time-extended radical-scavenging activity. The antioxidant properties of apple juices were much better reproduced by EPR spectroscopy than by UV–visible measurements. The former method is especially sensitive to the concentration of polymerised or bound procyanidins, whilst the latter method requires transparent (clear) samples. Apple juices, especially cloudy ones, are a rich source of natural antioxidants that may be used in the pharmaceutical or food industry. Copyright © 2006 Society of Chemical Industry

Comparative study of polyphenolic content and antiradical activity of cloudy and clear apple juices

NMR spectroscopy in pharmacy.

For almost a decade, quantitative NMR spectroscopy (qNMR) has been established as valuable tool in drug analysis. In all disciplines, i.e. drug identification, impurity profiling and assay, qNMR can be utilized. Separation techniques such as high performance liquid chromatography, gas chromatography, super fluid chromatography and capillary electrophoresis techniques, govern the purity evaluation of drugs. However, these techniques are not always able to solve the analytical problems often resulting in insufficient methods. Nevertheless such methods find their way into international pharmacopoeias. Thus, the aim of the book is to describe the possibilities of qNMR in pharmaceutical analysis. Beside the introduction to the physical fundamentals and techniques the principles of the application in drug analysis are described: quality evaluation of drugs, polymer characterization, natural products and corresponding reference compounds, metabolism, and solid phase NMR spectroscopy for the characterization drug substances, e.g. the water content, polymorphism, and drug formulations, e.g. tablets, powders. This part is accompanied by more special chapters dealing with representative examples. They give more detailed information by means of concrete examples. This work: combines theory, techniques, and concrete applications - all of which closely resemble the laboratory experience; considers international pharmacopoeias, addressing the concern for licensing; and, features the work of academics and researchers, appealing to a broad readership.

NMR spectroscopy in pharmaceutical analysis

13C CP/MAS NMR spectra were recorded to characterize the solid-state conformation of flavonoids: galangin, kaempferol, quercetin, myricetin, chrysin, apigenin, luteolin, acacetin, hesperetin and naringenin. Correct assignment of the signals in solution-state spectra (using APT, HSQC and HMBC) and solid-state spectra (using dipolar dephased and short contact sequences) for the above flavonoids is reported. The locked conformation of OH and OCH3 groups in solids results in an increased shielding of carbon adjacent to C—OH or C—OCH3 hydrogens, enabling conclusions as to the orientations of these groups to be drawn. The C-5—OH hydroxyl (and C-3—OH) points towards the carbonyl group oxygen, forming intramolecular hydrogen bonds. Considerations of C2′ and C6′ carbon shielding suggest that ring B is not coplanar with the benzopyran fragment in kaempferol, acacetin and myricetin. Copyright © 2001 John Wiley & Sons, Ltd.

Iwona Wawer

Papers

Comparative study of polyphenolic content and antiradical activity of cloudy and clear apple juices

NMR spectroscopy in pharmacy.

NMR spectroscopy in pharmaceutical analysis

13C CP/MAS NMR studies of flavonoids

Influence of apple purée preparation and storage on polyphenol contents and antioxidant activity