Modulating charge-transfer interactions in topologically different porphyrin-C60 dyads

Control over the interchromophore separation, their angular relationship, and the spatial overlap of their electronic clouds in several ZnP-C(60) dyads (ZnP=zinc porphyrin) is used to modulate the rates of intramolecular electron transfer. For the first time, a detailed analysis of the charge transfer absorption and emission spectra, time-dependent spectroscopic measurements, and molecular dynamics simulations prove quantitatively that the same two moieties can produce widely different electron-transfer regimes. This investigation also shows that the combination of ZnP and C(60) consistently produces charge recombination in the inverted Marcus region, with reorganization energies that are remarkably low, regardless of the solvent polarity. The time constants of electron transfer range from the mus to the ps regime, the electronic couplings from a few tens to several hundreds of cm(-1), and the reorganization energies remain below 0.54 eV and can be as low as 0.16 eV.     

The trigonal–bipyramidal triiodo­thallium(III) complex [TlI3{(CH3)2SO}2]

The title compound, bis(dimethyl sulfoxide)triiodo­thallium(III), [TlI₃(C₂H₆OS)₂], was crystallized from equimolar amounts of Tl^II and I₂ in a dimethyl sulfoxide (DMSO) solution. After the initial redox reaction, the thallium(III)–iodo complex forms and precipitates as a DMSO solvate. In the crystal structure, Tl is surrounded by three iodide ligands in the equatorial plane and two O‐coordinated DMSO mol­ecules in the axial positions, forming a slightly distorted trigonal bipyramid. The complex lies on a twofold rotation axis, making the DMSO mol­ecules and two of the I atoms crystallographically equivalent.     

Investigation of the pharmacokinetics of celecoxib by liquid chromatography-mass spectrometry

A new method for the quantification of celecoxib in human plasma based on reversed-phase high-performance liquid chromatography (HPLC) coupled to atmospheric pressure chemical ionization (APCI) mass spectrometry (MS) after liquid-liquid extraction is presented. The method is rapid, sensitive and highly selective. The retention time of celecoxib was 2.3 min. The limit of quantification was 5 microg/L. Rofecoxib was used as internal standard. After validation, the method was used to study the pharmacokinetic profile of celecoxib following administration of a single oral dose (200 mg) in 12 healthy volunteers. Since celecoxib should be metabolized primarily by cytochrome 2C9 (CYP2C9), a poor metabolizer (PM) for this cytochrome P450 enzyme was included in the study. Pharmacokinetic characteristics (mean +/- SD) of extensive metabolizers (EM) were t(max) 2.9+/-1.2h, c(max) 842+/-280 microg/L, AUC(infinity) 6246+/-2147 microg h/L and t(1/2) 7.8+/-2.7h. The area under the curve (AUC(infinity)) for the PM was 12561 microg h/L. However, we found no noticeable increase in half life in the PM (11.5 h) after a single dose of celecoxib.     

Tuning single nucleotide discrimination in polymerase chain reactions (PCRs): synthesis of primer probes bearing polar 4'-C-modifications and their application in allele-specific PCR

There are many methods available for the detection of nucleotide variations in genetic material. Most of these methods are applied after amplification of the target genome sequence by the polymerase chain reaction (PCR). Many efforts are currently underway to develop techniques that can detect single nucleotide variations in genes either by means of, or without the need for, PCR. Allele-specific PCR (asPCR), which reports nucleotide variations based on either the presence or absence of a PCR-amplified DNA product, has the potential to combine target amplification and analysis in one single step. The principle of asPCR is based on the formation of matched or mismatched primer-target complexes by using allele-specific primer probes. PCR amplification by a DNA polymerase from matched 3'-primer termini proceeds, whereas a mismatch should obviate amplification. Given the recent advancements in real-time PCR, this technique should, in principle, allow single nucleotide variations to be detected online. However, this method is hampered by low selectivity, which necessitates tedious and costly manipulations. Recently, we reported that the selectivity of asPCR can be significantly increased through the employment of chemically modified primer probes. Here we report further significant advances in this area. We describe the synthesis of various primer probes that bear polar 4'-C-modified nucleotide residues at their 3' termini, and their evaluation in real-time asPCR. We found that primer probes bearing a 4'-C-methoxymethylene modification have superior properties in the discrimination of single nucleotide variations by PCR.     

Electron Impact Induced Fragmentation of Aromatic Alkoxyimines II [5]. Formation and Transformation of Heterocyclic Radical Cations in the Gas Phasea

 The molecular ion 1 of N-(n-propoxy)benzaldimine I rearranges by an 1,5-H-shift to the δ-distonic ion 2 which subsequently cyclizes to the α-distonic ion 3. Homolytic cleavage of the N–O bond in 3 results in the δ-distonic ion 4 which expels CH₂O leading to the β-distonic ion 5. Ion 5 is also formed from the molecular ions of tetrahydrooxazines II and III and from M^+• of phenylazetidine IVa. In a subsequent step, ion 5 cyclizes to the N-protonated 3,4-dihydroisoquinolinium ion 6. The syntheses of II–IV and their derivatives are described.     

Structurally and chemically heterogeneous nanofibrous nonwovens via electrospinning

Homogeneous nonwovens composed of polymer nanofibers of a given diameter are characterized by structural parameters such as the average pore sizes and internal surfaces as well as by transport properties, which are strongly correlated to the fiber diameter at a given porosity. Such nonwovens are used among others for filter applications, protective clothing or as scaffolds for tissue engineering. A frequent requirement is that, to be able to prepare nonwovens optimised for the specific application, one has to find ways to disrupt this strong correlation allowing independent modification of pore diameter, transport properties and internal surface or to induce local chemical and structural heterogeneities within the nonwoven. The route explored in this paper is based on the electrospinning of heterogeneous nonwovens composed of nanofibers with two different average diameters (by a ratio of up to 10 and more) on the one hand and/or different chemical nature on the other hand. Spinning parameters have been optimised to achieve this goal. In addition, nonwovens composed of fibers with circular cross-section and with ribbon-like cross-section have been prepared.     

Simple diffuse reflectance UV-vis spectroscopic determination of organic pigments (fringelites) in fossils

To screen for organic pigments, like fringelites or porphyrins, in sediments and fossil specimen, a simple diffuse reflectance UV-vis spectroscopic determination was developed. In contrast to common inorganic pigments, like Fe₂O₃, these pigments exhibit well-structured characteristic absorption peaks which allow their recognition. This method was then used to identify fringelite H in a non-crinoidSolenopora species from the Jurassic. Reflectance FTIR spectroscopy proved not to be useful for this purpose.     

Effect of proline and glycine residues on dynamics and barriers of loop formation in polypeptide chains

Glycine and proline residues are frequently found in turn and loop structures of proteins and are believed to play an important role during chain compaction early in folding. We investigated their effect on the dynamics of intrachain loop formation in various unstructured polypeptide chains. Loop formation is significantly slower around trans prolyl peptide bonds and faster around glycine residues compared to any other amino acid. However, short loops are formed fastest around cis prolyl bonds with a time constant of 6 ns for end-to-end contact formation in a four-residue loop. Formation of short loops encounters activation energies in the range of 15 to 30 kJ/mol. The altered dynamics around glycine and trans prolyl bonds can be mainly ascribed to their effects on the activation energy. The fast dynamics around cis prolyl bonds, in contrast, originate in a higher Arrhenius pre-exponential factor, which compensates for an increased activation energy for loop formation compared to trans isomers. All-atom simulations of proline-containing peptides indicate that the conformational space for cis prolyl isomers is largely restricted compared to trans isomers. This leads to decreased average end-to-end distances and to a smaller loss in conformational entropy upon loop formation in cis isomers. The results further show that glycine and proline residues only influence formation of short loops containing between 2 and 10 residues, which is the typical loop size in native proteins. Formation of larger loops is not affected by the presence of a single glycine or proline residue.     

Computer-Assisted Solution of Chemical Problems—The Historical Development and the Present State of the Art of a New Discipline of Chemistry

The topic of this article is the development and the present state of the art of computer chemistry, the computer-assisted solution of chemical problems. Initially the problems in computer chemistry were confined to structure elucidation on the basis of spectroscopic data, then programs for synthesis design based on libraries of reaction data for relatively narrow classes of target compounds were developed, and now computer programs for the solution of a great variety of chemical problems are available or are under development. Previously it was an achievement when any solution of a chemical problem could be generated by computer assistance. Today, the main task is the efficient, transparent, and non-arbitrary selection of meaningful results from the immense set of potential solutions—that also may contain innovative proposals. Chemistry has two aspects, constitutional chemistry and stereochemistry, which are interrelated, but still require different approaches. As a result, about twenty years ago, an algebraic model of the logical structure of chemistry was presented that consisted of two parts: the constitution-oriented algebra of be- and r-matrices, and the theory of the stereochemistry of the chemical identity group. New chemical definitions, concepts, and perspectives are characteristic of this logic-oriented model, as well as the direct mathematical representation of chemical processes. This model enables the implementation of formal reaction generators that can produce conceivable solutions to chemical problems—including unprecedented solutions—without detailed empirical chemical information. New formal selection procedures for computer-generated chemical information are also possible through the above model. It is expedient to combine these with interactive methods of selection. In this review, the Munich project is presented and discussed in detail. It encompasses the further development and implementation of the mathematical model of the logical structure of chemistry as well as the experimental verification of the computer-generated results. The article concludes with a review of new reactions, reagents, and reaction mechanisms that have been found with the PC-programs IGOR and RAIN.     

Antimalarial activity of n(6)-substituted adenosine derivatives (part 2)

We have investigated the in vitro antimalarial activity of a new series of adenosine derivatives. The results show that N(6)-(1-naphthylmethyl)-5'-deoxy-5'-(amido)adenosines as well as N(6)-(4-phenylbenzyl)-5'-deoxy-5'-(amido)adenosines display significant activity against the malaria-causing parasites, with the sterically demanding bisubstituted species reported being active in most cases in the low-micromolar range. The novel compounds with unusual substitution pattern were obtained applying an efficient convergent polymer-assisted solution-phase (cPASP) synthesis protocol. Thus, we were able to prepare a series of substituted derivatives in parallel that would have been difficult to synthesize by standard techniques. The scope and limitations of the synthetic methodology are discussed.