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ABSTRACT: Circular dichroism (CD) spectroscopy is widely used to characterize the structures of DNA G-quadruplexes. CD bands at 200-300 nm have been empirically related to G-quadruplexes having parallel or antiparallel sugar-phosphate backbones. We propose that a more fundamental interpretation of the origin of the CD bands is in the stacking interactions of neighboring G-quartets, which can have the same or opposing polarities of hydrogen bond acceptors and donors. From an empirical summation of CD spectra of the d(G)5 G-quadruplex and of the thrombin binding aptamer that have neighboring G-quartets with the same and opposite polarities, respectively, the spectra of aptamers selected by the Ff gene 5 protein (g5p) appear to arise from a combination of the two types of polarities of neighboring G-quartets. The aptamer CD spectra resemble the spectrum of d(G3T4G3), in which two adjacent quartets have the same and two have opposite polarities. Quantum-chemical spectral calculations were performed using a matrix method, based on guanine chromophores oriented as in d(G3T4G3). The calculations show that the two types of G-quartet stacks have CD spectra with features resembling experimental spectra of the corresponding types of G-quadruplexes.
Chirality 04/2008; 20(3-4):431-40. · 2.35 Impact Factor
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ABSTRACT: The CD spectra of the pyrrole-imidazole alkaloids, (-)-dibromophakellin and (-)-dibromophakellstatin, have been calculated employing the quantum-chemical time-dependent density functional theory. Comparison of calculated and measured spectra showed that this well-established method is also a useful tool to elucidate the absolute stereochemistry of this class of compounds. The computational results have further been used to analyze the spectra measured in methanol and to explain the remarkable red shift of one CD band when trifluoroethanol is used as a solvent instead of methanol.
Chirality 08/2007; 19(7):542-9. · 2.35 Impact Factor
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Anja Krick,
Stefan Kehraus,
Clarissa Gerhäuser,
Karin Klimo,
Martin Nieger,
Armin Maier,
Heinz-Herbert Fiebig,
Iuliana Atodiresei,
Gerhard Raabe, Jörg Fleischhauer,
Gabriele M König
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ABSTRACT: Investigation of the fungal strain Monodictys putredinis isolated from the inner tissue of a marine green alga led to the isolation of four new monomeric xanthones and a benzophenone. All structures were elucidated by extensive spectroscopic measurements. The relative configuration of compound 1 was determined by X-ray crystal structure analysis, while for 2 and 3 configurations were confirmed by NOE experiments. Absolute configurations for compounds 1-3 were deduced by comparing experimental circular dichroism spectroscopic data with those calculated employing quantum-chemical time-dependent density functional theory (TDDFT). The compounds were examined for their cancer chemopreventive potential. Xanthone 2 was shown to inhibit cytochrome P450 1A activity with an IC50 value of 3.0 microM. Compounds 2 and 3 displayed moderate activity as inducers of NAD(P)H:quinone reductase (QR) in cultured mouse Hepa 1c1c7 cells, with CD values (concentration required to double the specific activity of QR) of 12.0 and 12.8 microM, respectively. Compound 3 showed weak inhibition of aromatase activity.
Journal of Natural Products 04/2007; 70(3):353-60. · 3.13 Impact Factor
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Simon F Seibert,
Ekaterina Eguereva,
Anja Krick,
Stefan Kehraus,
Elena Voloshina,
Gerhard Raabe, Jörg Fleischhauer,
Eckhard Leistner,
Michael Wiese,
Heino Prinz,
Kirill Alexandrov,
Petra Janning,
Herbert Waldmann,
Gabriele M König
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ABSTRACT: Chemical investigation of the marine fungus Ascochyta salicorniae led to the isolation of two new epimeric compounds, ascolactones A (1) and B (2), in addition to the structurally-related polyketides hyalopyrone (3), ascochitine (4), ascochital (5) and ascosalipyrone (6). The absolute configurations of the epimeric compounds 1 and 2 were assigned as (1R,9R) and (1S,9R), respectively, through simulation of the chiroptical properties using quantum-chemical CD calculations, and chiral GC-MS subsequent to oxidative cleavage (Baeyer-Villiger oxidation) of the side chain. In silico screening using the PASS software identified some of the A. salicorniae compounds (1-6) as potential inhibitors of protein phosphatases. Compound was found to inhibit the enzymatic activity of MPtpB with an IC(50) value of 11.5 microM.
Organic & Biomolecular Chemistry 07/2006; 4(11):2233-40. · 3.70 Impact Factor
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ABSTRACT: Two stereoisomers of ascolactone (A, B), natural products with two asymmetric carbon atoms, are isolated from the marine-derived fungus Ascochyta salicorniae. Although these compounds show virtually opposite CD spectra and [alpha]D, 1H- and 13C-NMR data exclude the presence of enantiomers and suggest ascolactone A and B to be epimeric lactones. By comparing the experimental CD spectra with those calculated employing time-dependent density functional theory (TDDFT), we elucidate the configuration at one of the asymmetric carbon atoms.
Chirality 07/2006; 18(6):413-8. · 2.35 Impact Factor
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Annalen der Chemie und Pharmacie 11/2004; 2004(23):4856 - 4863. · 3.10 Impact Factor
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ABSTRACT: The chiroptical properties of calliactine (2) have been studied experimentally as well as by quantum chemical calculations based on density functional theory (DFT). According to the DFT calculations, the four energetically lowest conformers of the title compound lie within a range of 1.1 kcal/mol and are separated from other conformers by an energy gap of nearly 9 kcal/mol. Based on their geometries, the excitation energies and rotational strengths have been calculated using time-dependent DFT (TDDFT) and the dipole velocity formalism. The circular dichroism (CD) spectrum of calliactine has been obtained as a Boltzmann-weighted superposition of the spectra of each of the four structures. By comparison of the calculated and experimental CD spectra, the absolute configuration of calliactine has been elucidated as S. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004
International Journal of Quantum Chemistry 08/2004; 100(6):1104 - 1113. · 1.36 Impact Factor
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ABSTRACT: Circular dichroism spectra of two beta-peptides, i.e. peptides composed of beta-amino acids, calculated using ensembles of configurations obtained by molecular dynamics simulation are presented. The calculations were based on 200 ns simulations of a beta-heptapeptide in methanol at 298 K and 340 K and a 50 ns simulation of a beta-hexapeptide in methanol at 340 K. In the simulations the peptides sampled both folded (helical) and unfolded structures. Trajectory structures with common backbone conformations were identified and grouped into clusters. The CD spectra were calculated for individual structures, based on peptide-group dipole transition moments obtained from semi-empirical molecular orbital theory and using the so-called matrix method. The single-structure spectra were then averaged over entire trajectories and over clusters of structures. Although certain features of the experimental CD spectra of the beta-peptides are reproduced by the trajectory-average spectra, there exist clear differences between the two sets of spectra in both wavelength and peak intensities. The analysis of individual contributions to the average spectra shows that, in general, the interpretation of a CD signal in terms of a single structure is not possible. Moreover, there is a large variation in the CD spectra calculated for a set of individual structures that belong to the same cluster, even when a structurally tight clustering criterion is used. This indicates that the CD spectra of these peptides are very sensitive to small local structural differences.
European Biophysics Journal 01/2004; 32(8):661-70. · 2.14 Impact Factor
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ABSTRACT: Circular dichroism spectra of two -peptides, i.e. peptides composed of -amino acids, calculated using ensembles of configurations obtained by molecular dynamics simulation are presented. The calculations were based on 200ns simulations of a -heptapeptide in methanol at 298K and 340K and a 50ns simulation of a -hexapeptide in methanol at 340K. In the simulations the peptides sampled both folded (helical) and unfolded structures. Trajectory structures with common backbone conformations were identified and grouped into clusters. The CD spectra were calculated for individual structures, based on peptide-group dipole transition moments obtained from semi-empirical molecular orbital theory and using the so-called matrix method. The single-structure spectra were then averaged over entire trajectories and over clusters of structures. Although certain features of the experimental CD spectra of the -peptides are reproduced by the trajectory-average spectra, there exist clear differences between the two sets of spectra in both wavelength and peak intensities. The analysis of individual contributions to the average spectra shows that, in general, the interpretation of a CD signal in terms of a single structure is not possible. Moreover, there is a large variation in the CD spectra calculated for a set of individual structures that belong to the same cluster, even when a structurally tight clustering criterion is used. This indicates that the CD spectra of these peptides are very sensitive to small local structural differences.
European Biophysics Journal 11/2003; 32(8):661-670. · 2.14 Impact Factor
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ABSTRACT: Chiral bis-porphyrins are currently the subject of intense interest as chiral receptors and as probes in the determination of structure and stereochemistry. To provide an improved framework for interpreting the circular dichroism (CD) spectra of bis-porphyrins, we have calculated the CD spectra of chiral bis-porphyrins from three classes: I, where porphyrins can adopt a relatively wide range of orientations relative to each other; II, porphyrins have a fixed relative orientation; III, porphyrins undergo pi-stacking. The calculations primarily utilized the classical polarizability theory of DeVoe, but were supplemented by the quantum mechanical matrix method. Class I was represented by three isomers of the diester of 5alpha-cholestane-3,17-diol with 5-(4'-carboxyphenyl)-10,15,20-triphenylporphin (2-alphabeta, 2-betaalpha, 2-betabeta). Careful analysis of the torsional degrees of freedom led to two to four minimum-energy conformers for each isomer, in each of which the phenyl-porphyrin bonds had torsional angles near 90 degrees. Libration about these bonds is relatively unrestricted over a range of +/-45 degrees. CD spectra in the Soret region were calculated as Boltzmann-weighted averages over the low-energy conformers for each isomer. Three models were used: the effective transition moment model, in which only one of the degenerate Soret components is considered, along the 5-15 direction; the circular oscillator model, in which both Soret components are given equal weight; and the hybrid model, in which the 10-20 oscillator is given half the weight of the 5-15 oscillator, to mimic the effect of extensive librational averaging about the 5-15 direction. All three models predict Soret exciton couplets with signs in agreement with experiment. Quantitatively, the best results are given by the hybrid and circular oscillator models. These results validate the widely used effective transition moment model for qualitative assignments of bis-porphyrin chirality and thus permit application of the exciton chirality model. However, for quantitative studies, the circular oscillator or hybrid models should be used. The simplified effective transition moment and hybrid models are justified by the librational averaging in the class I bis-porphyrins and should only be used with such systems. Two class II bis-porphyrins were also studied by DeVoe method calculations in the circular oscillator model, which yielded good agreement with experiment. Class III bis-porphyrins were represented by 2-alphaalpha, for which the calculations gave qualitative agreement. However, limitations in the conformational analysis with the close contacts and dynamic effects in these pi-stacked systems preclude quantitative results.
Journal of the American Chemical Society 07/2003; 125(25):7613-28. · 9.91 Impact Factor
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ABSTRACT: The absolute configuration of rubroflavin has been determined by comparison of its measured and calculated CD spectra. For this purpose the structures of 30 plausible isomers of the title compound have been optimized with density functional theory (DFT/BP86) using a triple-zeta valence basis set. The absolute (S) configuration at the S(O)CH3 group has been assumed in these calculations. One quinoid isomer, which is separated from all other structures by an energy gap of about 4 kcal/mol, was found to be the most stable species and to dominate the CD spectrum. The structure of this isomer has been reoptimized under the influence of a solvent using an electrostatic model (COSMO). Based on the geometries of the most stable isomer obtained in the presence and absence of the solvent the excitation energies and oscillator as well as rotational strengths have then been calculated using time-dependent DFT (TDDFT/TZVP/BP86). Comparison of the measured CD spectrum with that calculated for the energetically lowest isomer shows that especially the long wavelength parts of the spectra agree fairly well as far as the wavelengths and the signs of the Cotton effects are concerned while the correspondence between calculated and measured intensities is less satisfying. The agreement between the measured and calculated spectrum is better if the geometry optimized under the influence of the solvent is used. A detailed analysis of the spectra led us to the conclusion that the absolute configuration of rubroflavin is (S). These results support earlier assignments based on semiempirical and ab initio studies on a thermal decomposition product of rubroflavin. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem 93: 265–270, 2003
International Journal of Quantum Chemistry 03/2003; 93(4):265 - 270. · 1.36 Impact Factor
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ABSTRACT: The absolute configuration of rubroflavin has been determined indirectly by comparison of the measured and the calculated CD spectrum of its thermal decomposition product 3-methanesulfinyl-5-methylmercaptophenol. Performing geometry optimizations at the HF/6-31+G* level we found fifteen local minima for the (R)-isomer of 3-methanesulfinyl-5-methylmercaptophenol. The CD spectrum of the compound was then obtained as a superposition of the Boltzmann-weighted spectra for each structure calculated with the non-empirical CIS method. The corresponding Boltzmann factors have been calculated employing the relative energies of these minima determined at the ZPE + MP2/6-31+G*//HF/6-31+G* level of ab initio theory. Comparing the signs of the observed and calculated longest wave length Cotton effect we assign an absolute configuration to the thermolysis product. Since additional calculations revealed that the tricoordinate sulfur atom in rubroflavin and in its decomposition product is configurationally stable under the conditions of thermolysis we conclude that the absolute configuation at the corresponding sulfur atom of rubroflavin is the same.
Enantiomer A Journal of Stereochemistry 02/2002; 7(2-3):77-83.
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ABSTRACT: The orange pigment rubroflavin (1) from the dried fruit bodies of Calvatia rubro-flava (Lycoperdaceae) owes its high optical rotation to a methanesulfinyl group directly attached to a 1,4-benzoquinone semicarbazone chromophore. Rubroflavin is present in fresh fungi in its leuco form 4, which is easily oxidized to 1. Thermal fragmentation of 1 yields (−)-3-methanesulfinyl-5-(methylthio)phenol (6), whose configuration was assigned as (S) by quantum mechanical calculations. This result is supported by CD comparison of 6 with (S)-4-(methanesulfinyl)toluene, and the synthesis of (S)-1 from esters of deoxyrubroflavin (8) by stereoselective sulfoxidation. In the same manner, optically active (S,S)-oxyrubroflavin (2) and (S)-craniformin (3) were obtained. NMR measurements in different solvents indicate that 1 and the related 1,4-benzoquinone semicarbazones are in equilibrium with their azophenol tautomers.
Annalen der Chemie und Pharmacie 07/2001; 2001(16):3097 - 3104. · 3.10 Impact Factor
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Journal of Computational Chemistry. 01/2001; 22:1273-1278.
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ABSTRACT: Transition moment directions of chromophores are critical for predicting CD and absorption spectra of biological macromolecules. Single-crystal polarized reflection spectra of a primary amide (propionamide, PrN) and a secondary amide (N-acetylglycine, NAG) were recently analyzed, yielding transition moment directions for the first (NV1) and second (NV2) ππ* transitions (Clark, L. J. Am. Chem. Soc. 1995, 117, 7974). In terms of the angle θ, measured from the CO bond with the C−N bond at positive θ, the directions for the NV1 transitions are −37° for PrN and −55° for NAG. INDO/S MO calculations on the isolated molecules give NV1 transition moment directions of −25° and −36° for PrN and NAG, respectively. When the mixing of excited states due to the crystal field and the exciton effect are considered, the calculated angles are −35° and −42°, respectively. For the NV2 transitions, the angles (experiment for crystal, theory for free molecule, theory for molecule in crystal) are 46, 59, 49° for PrN and 61, 53, 55° for NAG. The present results are compared with recent ab initio results. It is proposed that the best results may be obtained by combining ab initio transition moment directions for the isolated molecule with the gas-to-crystal shift calculated by the present semiempirical method. Simplified charge models have been developed that give results for crystals of NAG essentially equivalent to those obtained with the detailed charge model. The method used in the prediction of the CD and absorption spectra of polypeptides for calculating the mixing of excited states under the influence of a static field was tested on crystals of NAG with satisfactory results. Calculations for an amide group in the middle of a 21-peptide α-helix give θ = −42° for the NV1 transition.
10/1999;
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ABSTRACT: The present study (see ref 1) delineates the scope and limitations of porphyrin chromophores for structural studies by the exciton coupled circular dichroic (CD) method. A distance dependency of the porphyrin coupling was investigated in the range between 10 and 50 Å. Over short interchromophoric distances, significant changes in the conformational distribution introduced by the bulky porphyrin chromophores were observed. Over longer distances, the porphyrins showed ca. 10-fold sensitivity increase over commonly used chromophores, and an effective direction for the interacting porphyrin transition moments was assigned by comparison. Porphyrins at the termini of dimeric steroids and brevetoxin B exhibited exciton coupling over interchromophoric distances up to 50 Å. These results represent the porphyrins as promising reporter chromophores for extending the exciton coupled CD method to structural studies of biopolymers.
06/1996;
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ABSTRACT: Ab initio calculations of the (methylsulfonyl)methyl anion (1), the ((trifluoromethyl)sulfonyl)methyl anion (1T), the (fluorosulfonyl)methyl anion (1F), and the (methylsulfonyl)isopropyl anion (1D) at the HF/6-31+G*//HF/6-31+G* level revealed a significant effect of fluorine substitution upon the structure and energy of α-sulfonyl carbanions. The Cα−S bond in 1T and 1F is shorter and the pyramidalization of the anionic carbon atom is less than in 1. In the anions 1T and 1F the Cα−S bond is shortened and the S−CF3(F) and the S−O bonds are lengthened as compared to the sulfones 3T and 3F. For all anions the staggered conformation (1, 1T, 1F, 1D) is energetically more stable than the eclipsed conformation (2, 2T, 2F, 2D). At the MP2/6-31+G*//HF/6-31+G* level the energy difference between the staggered and the eclipsed conformation is much larger for the fluorinated anions 1T and 1F than for 1 and 1D. The rotational barriers about the Cα−S bond of the fluorinated species 1T and 1F are in accordance with related experimental results significantly higher than the barriers of the non-fluorinated species 1 and 1D. A Fourier series analysis of the rotational potential curves shows the dominance of a positive V2 term (conjugative overlap effects) which is much higher for 1T and 1F than for 1 and 1D. Negative hyperconjugation (nC−σ*SR) is an important mechanism which determines the conformation of the anions and particularly of the fluorinated anions. In the dimethyl anion 1D, which has a strongly pyramidalized anionic carbon atom, the V3 term (steric and torsional effects) also contributes significantly to the rotational barrier. The configurational stability of chiral α-sulfonyl carbanions thus depends on the height of the Cα−S rotational barrier which is determined by nC−σ*SR interaction and the steric contribution of the substituents. The calculations suggest that S-(trifluoromethyl) substitution of other S-stabilized carbanions should lead also to derivatives of a higher configurational stability.
05/1996;
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Seibert,
Simon,
Ekaterina Eguereva,
Anja Krick,
Stefan Kehraus,
Elena Voloshina,
Gerhard Raabe, Jörg Fleischhauer,
Eckhard Leistner,
Michael Wiese,
Heino Prinz,
Kirill Alexandrov,
Petra Janning,
Herbert Waldmann,
Konig,
Gabriele
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ABSTRACT: Chemical investigation of the marine fungus Ascochyta salicorniae led to the isolation of two new epimeric compounds, ascolactones A ( 1) and B ( 2), in addition to the structurally-related polyketides hyalopyrone ( 3), ascochitine ( 4), ascochital ( 5) and ascosalipyrone ( 6). The absolute configurations of the epimeric compounds 1 and 2 were assigned as (1R,9R) and (1S,9R), respectively, through simulation of the chiroptical properties using quantum-chemical CD calculations, and chiral GC–MS subsequent to oxidative cleavage (Baeyer–Villiger oxidation) of the side chain.In silico screening using the PASS software identified some of the A. salicorniae compounds ( 1– 6) as potential inhibitors of protein phosphatases. Compound 4 was found to inhibit the enzymatic activity of MPtpB with an IC50 value of 11.5 µM.
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ABSTRACT: An enantiomerically pure dinuclear triple-stranded titanium(IV) helicate is formed from a dicatechol diimine ligand with an (R,R)-1,2-diaminocyclohexane spacer and its stereochemical features are elucidated by experimental and theoretical methods.
Mendeleev Communications 14(6):250-253. · 0.90 Impact Factor
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ABSTRACT: Theoretical calculations of CD spectra have generally assumed a single conformation, or a small number of conformers with Boltzmann averaging. Solvent effects on both the conformation and the CD have been neglected. In this work, we have calculated the CD spectrum of cyclo(l-Tyr-l-Tyr) in aqueous solution, taking dynamics and solvation into account. Starting geometries with χ1 ≈ 300° or 60° for both Tyr side chains were derived from mndo / mopac, followed by energy minimization using gromos. After addition of 368 water molecules, the system was simulated for 1000 ps at 300 K using gromos. In addition to the starting conformer, two other conformers were observed during each simulation. However, each trajectory gave a distinct set of conformers. Rotational strengths were calculated for the cyclic dipeptide at each ps along the trajectories, using the matrix method. The CD spectra calculated from these rotational strengths were averaged over the trajectories. Agreement is very good for the strong negative band near 200 nm, while for the lower energy bands (near 230 and 280 nm), the signs are correct, but the magnitudes are too low. The spectrum calculated from a Boltzmann-weighted average over the in vacuomndo / mopac conformers was in poor agreement with experiment. Although the solvent did not significantly affect the rotational strength calculated for a given conformer, it is essential to include the solvent in the MD simulations because it affects the relative energies of the conformers and promotes transitions among them.
Biophysical Chemistry.
