@article{BelasriTopalHeydenreichetal.2020, author = {Belasri, Khadija and Topal, Leila and Heydenreich, Matthias and Koch, Andreas and Kleinpeter, Erich and Fulop, Ferenc and Szatmari, Istvan}, title = {Synthesis and conformational analysis of naphthoxazine-fused phenanthrene derivatives}, series = {Molecules}, volume = {25}, journal = {Molecules}, number = {11}, publisher = {MDPI}, address = {Basel}, issn = {1420-3049}, doi = {10.3390/molecules25112524}, pages = {15}, year = {2020}, abstract = {The synthesis of new phenanthr[9,10-e][1,3]oxazines was achieved by the direct coupling of 9-phenanthrol with cyclic imines in the modified aza-Friedel-Crafts reaction followed by the ring closure of the resulting bifunctional aminophenanthrols with formaldehyde. Aminophenanthrol-type Mannich bases were synthesised and transformed to phenanthr[9,10-e][1,3]oxazines via [4 + 2] cycloaddition. Detailed NMR structural analyses of the new polyheterocycles as well as conformational studies including Density Functional Theory (DFT) modelling were performed. The relative stability of ortho-quinone methides (o-QMs) was calculated, the geometries obtained were compared with the experimentally determined NMR structures, and thereby, the regioselectivity of the reactions has been assigned.}, language = {en} } @phdthesis{Vranic2019, author = {Vranic, Marija}, title = {3D Structure of the biomarker hepcidin-25 in its native state}, doi = {10.25932/publishup-45929}, url = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-459295}, school = {Universit{\"a}t Potsdam}, pages = {xii, 135}, year = {2019}, abstract = {Hepcidin-25 (Hep-25) plays a crucial role in the control of iron homeostasis. Since the dysfunction of the hepcidin pathway leads to multiple diseases as a result of iron imbalance, hepcidin represents a potential target for the diagnosis and treatment of disorders of iron metabolism. Despite intense research in the last decade targeted at developing a selective immunoassay for iron disorder diagnosis and treatment and better understanding the ferroportin-hepcidin interaction, questions remain. The key to resolving these underlying questions is acquiring exact knowledge of the 3D structure of native Hep-25. Since it was determined that the N-terminus, which is responsible for the bioactivity of Hep-25, contains a small Cu(II)-binding site known as the ATCUN motif, it was assumed that the Hep-25-Cu(II) complex is the native, bioactive form of the hepcidin. This structure has thus far not been elucidated in detail. Owing to the lack of structural information on metal-bound Hep-25, little is known about its possible biological role in iron metabolism. Therefore, this work is focused on structurally characterizing the metal-bound Hep-25 by NMR spectroscopy and molecular dynamics simulations. For the present work, a protocol was developed to prepare and purify properly folded Hep-25 in high quantities. In order to overcome the low solubility of Hep-25 at neutral pH, we introduced the C-terminal DEDEDE solubility tag. The metal binding was investigated through a series of NMR spectroscopic experiments to identify the most affected amino acids that mediate metal coordination. Based on the obtained NMR data, a structural calculation was performed in order to generate a model structure of the Hep-25-Ni(II) complex. The DEDEDE tag was excluded from the structural calculation due to a lack of NMR restraints. The dynamic nature and fast exchange of some of the amide protons with solvent reduced the overall number of NMR restraints needed for a high-quality structure. The NMR data revealed that the 20 Cterminal Hep-25 amino acids experienced no significant conformational changes, compared to published results, as a result of a pH change from pH 3 to pH 7 and metal binding. A 3D model of the Hep-25-Ni(II) complex was constructed from NMR data recorded for the hexapeptideNi(II) complex and Hep-25-DEDEDE-Ni(II) complex in combination with the fixed conformation of 19 C-terminal amino acids. The NMR data of the Hep-25-DEDEDE-Ni(II) complex indicates that the ATCUN motif moves independently from the rest of the structure. The 3D model structure of the metal-bound Hep-25 allows for future works to elucidate hepcidin's interaction with its receptor ferroportin and should serve as a starting point for the development of antibodies with improved selectivity.}, language = {en} } @article{KochStamboliyskaMikhovaetal.2019, author = {Koch, Andreas and Stamboliyska, Bistra and Mikhova, Bozhana and Breznica-Selmani, Pranvera and Mladenovska, Kristina and Popovski, Emil}, title = {Calculations of C-13 NMR chemical shifts and F-C coupling constants of ciprofloxacin}, series = {Magnetic resonance in chemistry}, volume = {57}, journal = {Magnetic resonance in chemistry}, number = {4}, publisher = {Wiley}, address = {Hoboken}, issn = {0749-1581}, doi = {10.1002/mrc.4827}, pages = {75 -- 84}, year = {2019}, abstract = {Ciprofloxacin is a widely used fluoroquinolone antibiotic. In this work, a comprehensive evaluation of MP2 and DFT with different functionals and basis sets was carried out to select the most suitable level of theory for the study of the NMR properties of ciprofloxacin. Their relative predictive capabilities were evaluated comparing the theoretically predicted and experimental spectral data. Our computational results indicated that in contrast to the solid state, the molecule of ciprofloxacin does not exist as a zwitterion in gaseous state. The results of the calculations of the chemical shifts most close to the experimental were obtained with B3LYP/aug-cc-pVDZ. The F-C coupling constants were calculated systematically with different DFT methods and several basis sets. In general, the calculations of the coupling constants with the BHandH computational method including the applied in this work 6-311++G**, EPRII, and EPRIII basis sets showed a good reproducibility of the experimental values of the coupling constants.}, language = {en} } @article{PazHeydenreichSchmidtetal.2018, author = {Paz, Cristian and Heydenreich, Matthias and Schmidt, Bernd and Vadra, Nahir and Baggio, Ricardo}, title = {Three new dihydro-beta-agarofuran sesquiterpenes from the seeds of Maytenus boaria}, series = {Acta Crystallographica Section C}, volume = {74}, journal = {Acta Crystallographica Section C}, publisher = {International Union of Crystallography}, address = {Chester}, issn = {2053-2296}, doi = {10.1107/S2053229618005429}, pages = {564 -- 570}, year = {2018}, abstract = {As part of a project studying the secondary metabolites extracted from the Chilean flora, we report herein three new beta-agarofuran sesquiterpenes, namely (1S,4S,5S,6R,7R,8R,9R,10S)-6-acetoxy-4,9-dihydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b] oxepine-5,10-diylbis(furan-3-carboxylate), C27H32O11, (II), (1S,4S,5S,6R,7R,9S,10S)-6-acetoxy-9-hydroxy-2,2,5a, 9-tetramethyloctahydro-2H-3,9a-methanobenzo[ b] oxepine-5,10-diyl bis(furan-3-carboxylate), C27H32O10, (III), and (1S,4S,5S,6R,7R,9S,10S)-6-acetoxy-10-(benzoyloxy)-9-hydroxy-2,2,5a,9-tetramethyloctahydro-2H-3,9a-methanobenzo[b]oxepin-5-yl furan-3-carboxylate, C29H34O9, (IV), obtained from the seeds of Maytenus boaria and closely associated with a recently published relative [Paz et al. (2017). Acta Cryst. C73, 451-457]. In the (isomorphic) structures of (II) and (III), the central decalin system is esterified with an acetate group at site 1 and furoate groups at sites 6 and 9, and differ at site 8, with an OH group in (II) and no substituent in (III). This position is also unsubstituted in (IV), with site 6 being occupied by a benzoate group. The chirality of the skeletons is described as 1S, 4S, 5S, 6R, 7R, 8R, 9R, 10S in (II) and 1S, 4S, 5S, 6R, 7R, 9S, 10S in (III) and (IV), matching the chirality suggested by NMR studies. This difference in the chirality sequence among the title structures (in spite of the fact that the three skeletons are absolutely isostructural) is due to the differences in the environment of site 8, i.e. OH in (II) and H in (III) and (IV). This diversity in substitution, in turn, is responsible for the differences in the hydrogen-bonding schemes, which is discussed.}, language = {en} } @article{ShainyanMoskalikHeydenreichetal.2014, author = {Shainyan, Bagrat A. and Moskalik, Mikhail Yu and Heydenreich, Matthias and Kleinpeter, Erich}, title = {Conformational equilibrium and dynamic behavior of bis-N-triflyl substituted 3,8-diazabicyclo[3.2.1]octane}, series = {Magnetic resonance in chemistry}, volume = {52}, journal = {Magnetic resonance in chemistry}, number = {8}, publisher = {Wiley-Blackwell}, address = {Hoboken}, issn = {0749-1581}, doi = {10.1002/mrc.4086}, pages = {448 -- 452}, year = {2014}, abstract = {Restricted rotation about the N-S partial double bonds in a bis-N-triflyl substituted 3,8-diazabicyclo[3.2.1]octane derivative 1 has been frozen at low temperature (Delta G* = 11.6 kcal mol(-1)), and the existence of all four rotamers about the two N-S bonds, 3-in, 8-in, 3-in, 8-out, 3-out, 8-in, and 3-out, 8-out, respectively, proved experimentally by NMR spectroscopy and theoretically by DFT and MP2 calculations. Copyright (C) 2014 John Wiley \& Sons, Ltd.}, language = {en} } @article{PihlajaSinkkonenStajeretal.2011, author = {Pihlaja, Kalevi and Sinkkonen, Jari and Stajer, Geza and Koch, Andreas and Kleinpeter, Erich}, title = {1-Oxo-1,3-dithiolanes - synthesis and stereochemistry}, series = {Magnetic resonance in chemistry}, volume = {49}, journal = {Magnetic resonance in chemistry}, number = {7}, publisher = {Wiley-Blackwell}, address = {Malden}, issn = {0749-1581}, doi = {10.1002/mrc.2764}, pages = {443 -- 449}, year = {2011}, abstract = {1-Oxo-1,3-dithiolane (4) and its cis- and trans-2-methyl (5,6), -4-methyl (7,8) and -5-methyl (9,10) derivatives were prepared by oxidizing the corresponding 1,3-dithiolanes (1-3) with NaIO(4) in water. The oxides were purified and their isomers separated using thin layer chromatography. The structural characterization was carried out with (1)H and (13)C NMR spectroscopy and molecular modelling. The sulfoxides 4-6 and 8-10 attain two S(1) type envelopes (sometimes slightly distorted) the S=O(ax) envelope greatly dominating. Cis-4-methyl-1-oxo-1,3-dithiolane is a special case exhibiting both two closely related S=O(ax) (30 and 27\%) as well as S=O(eq) (21 and 22\%) forms [S(1) and C(4) envelopes, respectively]. The relative energies of these conformations, the values of (1)H-(1)H coupling constants and (1)H and (13)C chemical shifts were estimated by computational methods and they support well the conclusions based on the experimental data.}, language = {en} } @article{KleinpeterLaemmermannKuehn2011, author = {Kleinpeter, Erich and Laemmermann, Anica and K{\"u}hn, Heiner}, title = {Synthesis and NMR spectra of the syn and anti isomers of substituted cyclobutanes-evidence for steric and spatial hyperconjugative interactions}, series = {Tetrahedron}, volume = {67}, journal = {Tetrahedron}, number = {14}, publisher = {Elsevier}, address = {Oxford}, issn = {0040-4020}, doi = {10.1016/j.tet.2011.02.012}, pages = {2596 -- 2604}, year = {2011}, abstract = {The syn and anti isomers of cis,cis-tricyclo[5.3.0.0(2.6)]dec-3-ene derivatives have been synthesized and their (1)H and (13)C NMR spectra unequivocally analyzed. Both their structures and their (1)H and (13)C NMR chemical shifts were calculated by DFT, the latter two calculations employing the GIAO perturbation method. Additionally, calculated NMR shielding values were partitioned into Lewis and non-Lewis contributions from the bonds and lone pairs involved in the molecules by accompanying NBO and NCS analyses. The differences between the syn and anti isomers were evaluated with respect to steric and spatial hyperconjugation interactions.}, language = {en} } @article{KramerKleinpeter2011, author = {Kramer, Markus and Kleinpeter, Erich}, title = {A conformational study of N-acetyl glucosamine derivatives utilizing residual dipolar couplings}, series = {Journal of magnetic resonance}, volume = {212}, journal = {Journal of magnetic resonance}, number = {1}, publisher = {Elsevier}, address = {San Diego}, issn = {1090-7807}, doi = {10.1016/j.jmr.2011.06.029}, pages = {174 -- 185}, year = {2011}, abstract = {The conformational analyses of six non-rigid N-acetyl glucosamine (NAG) derivatives employing residual dipolar couplings (RDCs) and NOEs together with molecular dynamics (MD) simulations are presented. Due to internal dynamics we had to consider different conformer ratios existing in solution. The good quality of the correlation between theoretically and experimentally obtained RDCs show the correctness of the calculated conformers even if the ratios derived from the MD simulations do not exactly meet the experimental data. If possible, the results were compared to former published data and commented.}, language = {en} } @article{CsuetoertoekiSzatmariKochetal.2011, author = {Csuetoertoeki, Renata and Szatmari, Istvan and Koch, Andreas and Heydenreich, Matthias and Kleinpeter, Erich and Fueloep, Ferenc}, title = {Synthesis and conformational analysis of new naphth[1,2-e][1,3]oxazino[3,4-c]quinazoline derivatives}, series = {Tetrahedron}, volume = {67}, journal = {Tetrahedron}, number = {44}, publisher = {Elsevier}, address = {Oxford}, issn = {0040-4020}, doi = {10.1016/j.tet.2011.08.074}, pages = {8564 -- 8571}, year = {2011}, abstract = {A new highly functionalized aminonaphthol derivative, 1-(amino(2-aminophenyl)methyl)-2-naphthol (4), was synthesized by the reaction of 2-naphthol, 2-nitrobenzaldehyde and tert-butyl carbamate or benzyl carbamate, followed by reduction and/or removal of the protecting group. The aminonaphthol derivative thus obtained was converted in ring-closure reactions with formaldehyde. benzaldehyde and/or phosgene to the corresponding naphth[1,2-e][1,3]oxazino[3,4-c]quinazoline derivatives. The conformational analysis of some derivatives by NMR spectroscopy and accompanying molecular modelling are also reported.}, language = {en} }