Structure Determination by Joint Effort of X-ray Powder Diffraction and Quantum Calculations: Crystal Structure and Short Hydrogen Bonding in Pentadecafluorooctanoic Acid Hydrate

A precise X-ray crystal structure determination of systems that exist in a polycrystalline form often poses a challenge due to several factors that limit the resolution of the diffraction measurement. The location of atoms is usually determined at significantly lower precision than the unit cell parameters, rendering the complete characterization of the structure difficult. This is particularly pronounced when precise location of hydrogen atoms is required, for instance in ionizable biomolecules or in hydrogen bonds. In such cases periodic quantum (DFT) calculations may crucially assist structure determination, because they can reliably predict the location of atoms, provided that the unit cell parameters, the space group and tentative atomic positions are known. In this work we present DFT-assisted structure determination of pentadecafluorooctanoic acid hydrate, a benchmark system featuring short hydrogen bonds (RO...O ≈ 2.5 Å) between acid and water molecules. While Rietveld refinement based solely on powder diffraction data cannot reliably resolve the location of crystal water molecules and even less so the position of hydrogen atoms in the network of hydrogen bonds, periodic DFT optimization yields several minimum energy structures suitable for further refinement. Due to the low experimental resolution and similarity, comparison between model and experimental powder diffraction pattern can barely distinguish between certain structure candidates provided by DFT calculations, but it can rule out those featuring larger misfits. The proposed structure solution is delivered from a tandem application of structure determination from powder diffraction data and DFT optimization, the former providing the unit cell parameters and estimated atomic positions that are finely tuned by DFT. The present strategy can in principle be generalized to other examples of structure determination at relatively low resolution, such as is often the case with biological macromolecules. This work is licensed under a Creative Commons Attribution 4.0 International License

Conformational Analysis of the D Ring of Lysergic Acid Amides and its Bioactive Conformation

1H, 13Cnuclear magnetic resonance data on simple lysergic acid amides and ergopeptines indieate eonsiderable flexibility of the D ring. The actual conformation depends upon the existence (or absence) of intramolecular hydrogen bonding between N6 and the central amide N20-H group. The results are in agreement with molecular mechanics calculations. The proposal for the bioactive conformation is based on the comparison of key geometric parameters of the possible ergolene conformers with ones derived for the conformationally restricted dopamine congeners

Smolni kit in premaz za žare

In the graves excavated in 1971 in the courtyard of the Slovenian Academy of Sciences (Ljubljana) two urns were found one of which was mended with a resinous material and the other was peinted black. The infrared spectra of both materials are identical and very similar to the spectra published by Sanderman (1) and Sauter (2) of the so called grave resins. W. Sanderman (1) produced infrared spectroscopic and other evidence that the resinous material found in prehistoric graves from the north of Europe is in fact pitch obtained from birch bark. This material seems to be used since neolithic times and up to the very recent past as putty, peint, and for waterproofing of wooden and bark vessels. Sanderman has compared the infrared spectra of the prehistoric material with laboratory made birch bark pitch, but did not consider any other resinuous materials nor pitch from wood tar nor bark pitches from other tree species. Since birch population in this country is not large and, moreover, birch wood was so far not found amongst the remnants of wood used for incinerations, we were wondering whether the pitch from the urns found in Ljubljana originates from birch bark or from any sort of wood. The question appeared interesting because if pitch was indeed made of bark then it was made on purpose and not obtained as a byproduct of burning wood for heating purposes or in making charcoal. Therefore we have prepared pitch from bark of several tree species (birch, beech, poplar, oak, elm) as well as from beech wood, and recorded the infrared spectra. The spectra of a pitch coating formed on an aluminium vessel used for cooking on an open fire was also recorded. In general, the spectra of the bark pitches differ significantly from the wood tar pitch. The differences between the bark pitches are not so well pronounced, but still sufficient to show that the spectrum of birch bark pitch is definitely most similar to the pitch from the urns. Minor differences are possibly due to differences in the conditions of the distillation and, particularly, to ageing. NMR spectra of the pitch from urns, birch bark pitch, and beech wood pitch were also investigated. The spectra of the first two materials are very similar between them, but differ strikingly from the latter. Thus it has been prooved that the pitch from the urns has been made of tree bark, most probably birch bark, and not from wood. The implication of these results are discussed. Some details of the chemical procedures are given and the spectral characteristics are discussed

Conformational Analysis of the D Ring of Lysergic Acid Amides and its Bioactive Conformation

1H, 13Cnuclear magnetic resonance data on simple lysergic acid amides and ergopeptines indieate eonsiderable flexibility of the D ring. The actual conformation depends upon the existence (or absence) of intramolecular hydrogen bonding between N6 and the central amide N20-H group. The results are in agreement with molecular mechanics calculations. The proposal for the bioactive conformation is based on the comparison of key geometric parameters of the possible ergolene conformers with ones derived for the conformationally restricted dopamine congeners

Solution Conformation of the Immunomodulator Muramyl Dipeptide: Restrained Molecular Dynamics Based on Nuclear Magnetic Resonance Data and Semiempirical MO Study

Conformational analysis of IV-acetyl-muramyl-L-alanyl-isoglutamine (MAG) was preformed by molecular dynamics. Initial geometries were generated by random setting of dihedral angles. In order to narrow the vast conformational space of MAG, experimental NOE connectivities and connectivities based on hydrogen bonds1 were included in the potential energy function. The energy differences between seven structures with the lowest total energy are surprisingly small. The rank order of energy minimized structures yielded by the semiempirical MO method AMI is not the same as predicted by molecular mechanics, but the differences in energies are very small. The S-shaped conformation suggested by NMR analysis1 seems to be possible according to the energy criterion

The Molecular Electrostatic Potential as a Determinant of Receptor-Drug Recognition

The validity of the concept of the molecular electrostatic . potential and its applicability in rationalizing drug-receptor interactions are discussed on hand of examples covering the qualitative aspects. The computational methods are briefly reviewed with respect to economy and quality of results

Evidence of Polaron Excitations in Low Temperature Raman Spectra of Oxalic Acid Dihydrate

Low temperature Raman spectra of oxalic acid dihydrate (8K - 300 K) both for polycrystalline and single crystal phase show strong variation with temperature in the interval from 1200 to 2000 cm-1. Previous low temperature diffraction studies all confirmed the stability of the crystal P21/n phase with no indications of any phase transition, reporting the existence of a strong hydrogen bond between the oxalic acid and a water molecule. A new group of Raman bands in the 1200 – 1300 cm-1 interval below 90 K is observed, caused by possible loss of the centre of inversion. This in turn could originate either due to disorder in hydroxyl proton positions, or due to proton transfer from carboxylic group to water molecule. The hypothesis of proton transfer is further supported by the emergence of new bands centered at 1600 cm-1 and 1813 cm-1, which can be explained with vibrations of H3O+ ions. The broad band at 1600 cm-1 looses intensity, while the band at 1813 cm-1 gains intensity on cooling. The agreement between quantum calculations of vibrational spectra and experimentally observed Raman bands of hydronium ions in oxalic acid sesquihydrate crystal corroborate this hypothesis

Povezanost kliničkih parametara i prisustva Aggregatibacter actinomycetemcomitans i Porphyromonas gingivalis kod pacijenata sa progresivnim parodontalnim lezijama

Background/Aim. Periodontitis is a chronic inflammatory disease of periodontal tissues with consequential is bone loss as a result of host immunological reactions caused by periopathogens. The aim of the study was to investigate if there is a correlation between clinical parameters and the presence of two most aggressive periopathogens (Aggregatibacter actinomycetemcomitans - Aa and Porphyromonas gingivalis - Pg) in patients with progressive periodontal lesions. Methods. A total of 34 systemic healthy people, 23 to 70 years old, were included in the study. The patients were clinically and radiologically examined, and after that, the representative pocket with greatest pocket depth was chosen and the sample was collected from that place. The measured clinic parameters were: gingival index, index of gingival bleeding, pocket depth and plaque indices. The multiplex Polymerase Chain Reaction (PCR) method was used for detection of periopathogens. After obtaining results, appropriate statistical tests were used to correlate the clinical and microbiological results. Results. Aa and Pg were detected in the same percentage of samples. Aa and Pg were detected in 35.29% samples alone, and in 29.41% both were detected. The values of measured clinical parameters did not show a statistical significance between the groups. In analysis of correlations among clinical parameters inside the groups, a statistical significance was found only between gingival and plaque index in the group with Aa. Conclusion. Clinical course of periodontitis in the developed stage does not differ in relation to the presence of different periopathogens as the major inductors of immunologically guided destructive processes.Uvod/Cilj. Parodontopatija je hronično inflamatorno oboljenje parodontalnih tkiva koje za krajnji ishod ima gubitak potpornog koštanog tkiva zuba usled imunoloških reakcija izazvanih parodontopatogenim bakterijama. Cilj studije bio je korelisanje kliničkih parametara i prisustva dve najagresivnije parodontopatogene bakterije (Aggregatibacter actinomycetemcomitans - A.a. i Porphyromonas gingivalis - P.g.) kod bolesnika sa progresivnim parodontalnim lezijama. Metode. U studiju su bila uključena 34 sistemski zdrava ispitanika, starost 23-70 godina. Ispitanici su klinički i radiološki pregledani i uzorak je uziman iz reprezentativnog parodontalnog džepa sa najvećom dubinom sondiranja. Od kliničkih parametara mereni su gingivalni indeks, indeks krvarenja gingive, dubina parodontalnog džepa i indeks plaka. Prisustvo parodontopatogena dokazivano je multipleks metodom PCR (Polymerase Chain Reaction), a rezultati su korelisani sa kliničkim parametrima primenom odgovarajućih statističkih testova. Rezultati. Ista procentualna zastupljenost oba mikroorganizma dokazana je u uzorcima, naime i A.a. i P.g. bili su prisutni u po 35,39% uzoraka, a u 29,41% dokazana su oba mikroorganizma. Rezultati su korelisani po grupama formiranim u odnosu na prisustvo bakterija. Vrednosti merenih kliničkih parametara nisu se statistički značajno razlikovale u zavisnosti od prisustva parodontopatogena. Međusobne korelacije kliničkih parametara unutar grupe nisu pokazale statističku značajnost, osim korelacije gingivalnog i plak indeksa u grupi sa A.a. Zaključak. Klinički tok uznapredovale faze parodontopatije ne razlikuje se u odnosu na vrstu parodontalnih bakterija kao induktora imunološki posredovanih destruktivnih procesa