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Partovi-Azar P.,Institute of Chemistry and Biochemistry | Kaghazchi P.,Institute of Chemistry and Biochemistry
Journal of Computational Chemistry | Year: 2016

We report on real-time time-dependent density functional theory calculations on direction-dependent electron and hole transfer processes in molecular systems. As a model system, we focus on α-sulfur. It is shown that time scale of the electron transfer process from a negatively charged S8 molecule to a neighboring neutral monomer is comparable to that of a strong infrared-active molecular vibrations of the dimer with one negatively charged monomer. This results in a strong coupling between the electrons and the nuclei motion which eventually leads to S8 ring opening before the electron transfer process is completed. The open-ring structure is found to be stable. The similar infrared-active peak in the case of hole transfer, however, is shown to be very weak and hence no significant scattering by the nuclei is possible. The presented approach to study the charge transfer processes in sulfur has direct applications in the increasingly growing research field of charge transport in molecular systems. © 2017 Wiley Periodicals, Inc.


Gschwind S.,ETH Zurich | Aja Montes M.D.L.,Institute of Chemistry and Biochemistry | Gunther D.,ETH Zurich
Analytical and Bioanalytical Chemistry | Year: 2015

In 2011, the European Commission introduced new regulations on how nanomaterials are defined. Since then, researchers have emphasized that more complete characterization of nanoparticles (NPs) includes not just mass and size determinations, but also the determination of the particle number concentrations. In this study, two different sample introduction approaches for the analysis of NP suspensions with inductively coupled plasma mass spectrometry (ICP-MS) were investigated: pneumatic nebulization (sp-ICP-MS) and microdroplet generation (MDG-ICP-MS). These approaches were compared for the determination of particle number concentrations (PNCs) of gold and silver NP suspensions diluted in either ultra-pure water or citrate solution. For accurate sp-ICP-MS analysis, it is crucial to know the transport efficiency of nebulized sample into the plasma. Here, transport efficiencies, measured by the waste collection method, were 11–14 % for Ag suspensions and 9–11 % for Au. In contrast, the droplet transport efficiency of MDG-ICP-MS was 100 %. Analysis by sp-ICP-MS yielded a lower particle number concentration than expected (only 20–40 % of the expected value), whereas MDG-ICP-MS had NP recoveries up to 80 %. This study indicates that NP reference materials are of major importance for particle number determination and detailed results on particle number concentrations for different suspensions with respect to storage time are discussed. © 2015 Springer-Verlag Berlin Heidelberg


Numata J.,Institute of Chemistry and Biochemistry | Juneja A.,Institute of Chemistry and Biochemistry | Juneja A.,Karolinska Institutet | Diestler D.J.,Institute of Chemistry and Biochemistry | And 2 more authors.
Journal of Physical Chemistry B | Year: 2012

Experiments show that a ligand-receptor complex formed by binding a bivalent ligand (D) in which the two ligating units are joined covalently by a flexible polymeric spacer (S) can be orders of magnitude more stable than the corresponding complex formed with monomeric ligands. Although molecular models rationalizing this "enhancement effect" have been proffered, they ignore spacer-receptor (S-R) interactions, which can substantially influence the relative stability of complexes. Here, the results of a computational study designed to assess the impact of S-R interactions in the prototypic bivalent complex are presented and compared to results of experiments. The S-R interactions mimicking general features of biological systems are modeled by contoured R surfaces with hills (or depressions) at the binding sites. In the fictitious limit of vanishing S-R interactions, the enhancement is pronounced, as observed in experiments. For strictly repulsive S-R interactions (hard R surface), the enhancement vanishes, or even reverses. This is particularly the case if the R surface is convex (i.e., rising between the binding sites), while the enhancement is only moderately reduced if the R surface is concave. Alternatively, a weak S-R attraction close to the R surface can increase the enhancement. It is concluded that large enhancement should be observed only if both features are present: a concave R surface plus a weak S-R attraction. The latter occurs for spacer material such as polyethylene glycol (PEG), which is weakly hydrophobic and thus attracted by protein surfaces. It is shown that the enhancement of bivalent binding can be characterized by a single key parameter, which may also provide guidelines for the design of multivalent complexes with large enhancement effect. © 2012 American Chemical Society.


PubMed | University of Vienna, University of Veterinary Medicine Vienna, Institute of Chemistry and Biochemistry, Max Planck Institute for Chemical Ecology and Medical University of Vienna
Type: Journal Article | Journal: Nature | Year: 2016

Organisms use endogenous clocks to anticipate regular environmental cycles, such as days and tides. Natural variants resulting in differently timed behaviour or physiology, known as chronotypes in humans, have not been well characterized at the molecular level. We sequenced the genome of Clunio marinus, a marine midge whose reproduction is timed by circadian and circalunar clocks. Midges from different locations show strain-specific genetic timing adaptations. We examined genetic variation in five C. marinus strains from different locations and mapped quantitative trait loci for circalunar and circadian chronotypes. The region most strongly associated with circadian chronotypes generates strain-specific differences in the abundance of calcium/calmodulin-dependent kinase II.1 (CaMKII.1) splice variants. As equivalent variants were shown to alter CaMKII activity in Drosophila melanogaster, and C. marinus (Cma)-CaMKII.1 increases the transcriptional activity of the dimer of the circadian proteins Cma-CLOCK and Cma-CYCLE, we suggest that modulation of alternative splicing is a mechanism for natural adaptation in circadian timing.


Schlieben P.,Free University of Berlin | Meyer A.,Free University of Berlin | Weise C.,Institute of Chemistry and Biochemistry | Bondzio A.,Free University of Berlin | And 3 more authors.
Veterinary Journal | Year: 2012

Cutaneous mast cell tumours (MCTs) are the most common skin tumours in dogs. However, the molecular differences between benign tumours with a good prognosis and highly malignant, invasive and metastatic tumours with short survival times are for the most part unclear. In the present study the proteome of low-grade MCTs with a good prognosis was compared with that of poor-prognosis high-grade tumours independent of their mutational status of exon 11 of the KIT gene.Using two-dimensional difference gel electrophoresis and mass spectrometry, 13 proteins with a significant differential expression between the two groups were identified. Four stress response proteins (HSPA9, PDIA3, TCP1A and TCP1E) were significantly up-regulated in high-grade tumours, while proteins mainly associated with cell motility and metastasis had either increased (WDR1, ACTR3, ANXA6) or decreased (ANXA2, ACTB) expression levels. High-grade tumours also had a paradox down-regulation of transferrin, a protein that is usually up-regulated in neoplastic cells. The histologically observable dedifferentiation of high-grade tumours was reflected by decreased tryptase protein expression levels. Results of quantitative real-time RT-PCR analysis indicated that the differences in protein expression levels of most proteins were regulated at the transcript level. Based on these findings, it is hypothesized that high-grade MCT cells have a higher resistance to cellular stress and thus are able to better cope with the adverse environment in highly proliferating tumours independent of increased KIT signalling. It is noteworthy that some of the proteins identified have been proposed as therapeutic targets for human oncology and it will be interesting to evaluate their therapeutic and diagnostic potential for canine MCTs. © 2012 Elsevier Ltd.


Klopfleisch R.,Free University of Berlin | Klose P.,Free University of Berlin | Weise C.,Institute of Chemistry and Biochemistry | Bondzio A.,Free University of Berlin | And 3 more authors.
Journal of Proteome Research | Year: 2010

Mammary tumors are a major health threat to women and female dogs. In both, metastasis of the primary tumor to distant organs is the most common cause of tumor-related death. Nevertheless, the molecular mechanisms of tumor metastasis are far from being understood, and it is still unknown why some human and canine carcinomas metastasize and others do not. Using 2D-DIGE and MALDI-TOF-MS we identified 21 proteins with significant changes (fold change >1.5; p < 0.05) in protein expression between metastasizing (n = 6) and nonmetastasizing (n = 6) canine mammary carcinomas. Quantitative RT-PCR was used to identify transcriptional or post-transcriptional regulation of protein expression. Up-regulated proteins in metastatic carcinomas included proliferating cell nuclear antigen, ferritin light chain, bomapin, tropomyosin 3, thioredoxin-containing domain C5, adenosin, ornithine aminotransferase, coronin 1A, RAN-binding protein 1,3-phosphoglycerate dehydrogenase, and eukaryotic translation elongation factor 1. Down-regulated proteins in metastatic carcinomas included calretinin, myosin, light chain 2, peroxiredoxin 6, maspin, ibrinogen beta chain, vinculin, isocitrate dehydrogenase 1, tropomyosin 1, annexin A5, and Rho GTPase activating protein 1. Interestingly, 19 of these 21 proteins have been described with a malignancy-associated expression in human breast cancer and other human cancer types before. Further investigations are now necessary to test whether these markers are of prognostic value for canine mammary carcinomas and whether their expression is directly involved in canine mammary carcinogenesis or represent solely a secondary reactive phenotype. © 2010 American Chemical Society.


Klose P.,Free University of Berlin | Weise C.,Institute of Chemistry and Biochemistry | Bondzio A.,Free University of Berlin | Multhaup G.,Institute of Chemistry and Biochemistry | And 3 more authors.
Journal of Proteome Research | Year: 2011

The molecular mechanisms of the development of canine mammary tumors are still incompletely understood. In the present study we hypothesized that there is a malignant progression from normal gland to malignant carcinomas that is associated with a linear change in protein expression. To this end, the proteome of canine normal mammary gland, adenomas, nonmetastatic carcinomas, and metastatic carcinomas was compared. Application of 2D-DIGE and MALDI-TOF-MS identified 48 proteins with significant changes (fold change >|1.5|; p < 0.05) in expression levels at the different stages of malignant progression. Forty-two of these followed three major stepwise but not linear expression patterns. Thirteen proteins showed the adenoma pattern characterized by a change in protein expression levels during progression from normal gland to adenomas which persisted on the same level at the subsequent stages of malignancy. Nine proteins followed the carcinoma pattern with an up- or down-regulation between adenomas and carcinomas. The majority of 20 proteins followed the metastasis pattern with a significant change of protein expression levels between nonmetastatic and metastatic carcinomas. The present study therefore shows that differences in malignancy are associated with a stepwise but not linear change in protein expression levels, which does not finally confirm or disapprove the existence of a malignant progression in canine mammary tumors. In addition, the acquisition of metastatic potential seems to be associated with the strongest changes in protein expression levels. © 2011 American Chemical Society.


Achazi A.J.,Institute of Chemistry and Biochemistry | von Krbek L.K.S.,Institute of Chemistry and Biochemistry | Schalley C.A.,Institute of Chemistry and Biochemistry | Paulus B.,Institute of Chemistry and Biochemistry
Journal of Computational Chemistry | Year: 2015

The Gibbs energies of association ΔGsolT between primary alkyl ammonium ions and crown ethers in solution are measured and calculated. Measurements are performed by isothermal titration calorimetry and revealed a strong solvent-dependent ion pair effect. Calculations are performed with density functional theory including Grimme's dispersion correction D3(BJ). The translational, rotational, and vibrational contributions to the Gibbs energy of association ΔGsolT are taken into account by a rigid-rotor-harmonic-oscillator approximation with a free-rotor approximation for low lying vibrational modes. Solvation effects δGseT are taken into account by applying the continuum solvation model COSMO-RS. Our study aims at finding a suitable theoretical method for the evaluation of the host guest interaction in crown/ammonium complexes as well as the observed ion pair effects. A good agreement of theory and experiment is only achieved, when solvation and the effects of the counterions are explicitly taken into account. © 2015 Wiley Periodicals, Inc.


Numata J.,Institute of Chemistry and Biochemistry | Knapp E.-W.,Institute of Chemistry and Biochemistry
Journal of Chemical Theory and Computation | Year: 2012

The mutual information (MI) expansion is applied to two molecular systems to probe algorithms that serve to estimate conformational entropy differences more precisely. The individual terms of the MI expansion are evaluated with a histogram method. Internal coordinates are used to avoid spurious correlations, which would require higher order terms in the MI expansion. Two approaches are applied that compensate for systematic errors that occur with a histogram method: (1) Simulation data are balanced by using the same number of coordinate sets (frames) for both conformer domains considered for the entropy difference computation. Balancing puts fluctuations of the histogram bin contents on the same level for both conformer domains, allowing efficient error cancellation. (2) Bias correction compensates for systematic deviations due to a finite number of frames per bin. Applying both corrections improves the precision of entropy differences drastically. Estimates of entropy differences are compared to thermodynamic benchmarks of a simple polymer model and trialanine, where excellent agreement was found. For trialanine, the average error for the estimated conformational entropy difference is only 0.3 J/(mol K), which is 100 times smaller than without applying the two corrections. Guidelines are provided for efficiently estimating conformational entropies. The program ENTROPICAL, used for the computations, is made available, which can be used for molecular dynamics or Monte Carlo simulation data on macromolecules like oligopeptides, polymers, proteins, and ligands. © 2012 American Chemical Society.


PubMed | Institute of Chemistry and Biochemistry
Type: Journal Article | Journal: Journal of chemical theory and computation | Year: 2015

The mutual information (MI) expansion is applied to two molecular systems to probe algorithms that serve to estimate conformational entropy differences more precisely. The individual terms of the MI expansion are evaluated with a histogram method. Internal coordinates are used to avoid spurious correlations, which would require higher order terms in the MI expansion. Two approaches are applied that compensate for systematic errors that occur with a histogram method: (1) Simulation data are balanced by using the same number of coordinate sets (frames) for both conformer domains considered for the entropy difference computation. Balancing puts fluctuations of the histogram bin contents on the same level for both conformer domains, allowing efficient error cancellation. (2) Bias correction compensates for systematic deviations due to a finite number of frames per bin. Applying both corrections improves the precision of entropy differences drastically. Estimates of entropy differences are compared to thermodynamic benchmarks of a simple polymer model and trialanine, where excellent agreement was found. For trialanine, the average error for the estimated conformational entropy difference is only 0.3 J/(mol K), which is 100 times smaller than without applying the two corrections. Guidelines are provided for efficiently estimating conformational entropies. The program ENTROPICAL, used for the computations, is made available, which can be used for molecular dynamics or Monte Carlo simulation data on macromolecules like oligopeptides, polymers, proteins, and ligands.

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