ROESY Experiments Research Articles

A Squaramide-Based Organocatalyst as a Novel Versatile Chiral Solvating Agent for Carboxylic Acids.

A squaramide-based organocatalyst for asymmetric Michael reactions has been tested as a chiral solvating agent (CSA) for 26 carboxylic acids and camphorsulfonic acid, encompassing amino acid derivatives, mandelic acid, as well as some of its analogs, propionic acids like profens (ketoprofen and ibuprofen), butanoic acids and others. In many cases remarkably high enantiodifferentiations at 1H, 13C and 19F nuclei were observed. The interaction likely involves a proton transfer from the acidic substrates to the tertiary amine sites of the organocatalyst, thus allowing for pre-solubilization of the organocatalyst (when a chloroform solution of the substrate is employed) or the simultaneous solubilization of both the catalyst and the substrate. DOSY experiments were employed to evaluate whether the catalyst-substrate ionic adduct was a tight one or not. ROESY experiments were employed to investigate the role of the squaramide unit in the adduct formation. A mechanism of interaction was proposed in accordance with the literature data.

Inclusion Complexes of Ethanamizuril with β- and Hydroxypropyl-β-Cyclodextrin in Aqueous Solution and in Solid State: A Comparison Study.

Ethanamizuril (EZL) is a new anticoccidial drug developed by our Shanghai Veterinary Research Institute. Since EZL is almost insoluble in water, we conducted a study to improve the solubility of EZL by forming inclusion complexes with β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD). In this study, we performed molecular docking and then systematically compared the interactions of EZL with β-CD and HP-β-CD in both aqueous solution and the solid state, aiming to elucidate the solubilization effect and mechanism of cyclodextrins (CDs). The interactions were also examined in the solid state using DSC, PXRD, and FT-IR. The interactions of EZL with CDs in an aqueous solution were investigated using PSA, UV-vis spectroscopy, MS, 1H NMR, and 2D ROESY. The results of phase solubility experiments revealed that both β-CD and HP-β-CD formed inclusion complexes with EZL in a 1:1 molar ratio. Among them, HP-β-CD exhibited higher Kf (stability constant) and CE (complexation efficiency) values as well as a stronger solubilization effect. Furthermore, the two cyclodextrins were found to interact with EZL in a similar manner. The results of our FT-IR and 2D ROESY experiments are in agreement with the theoretical results derived from molecular simulations. These results indicated that intermolecular hydrogen bonds existing between the C=O group on the triazine ring of EZL and the O-H group of CDs, as well as the hydrophobic interactions between the hydrogen on the benzene ring of EZL and the hydrogen of CDs, played crucial roles in the formation of EZL/CD inclusion complexes. The results of this study can lay the foundation for the future development of high-concentration drinking water delivery formulations for EZL.

Bis-[C(sp3)-chelating] Ti2 catalysts supported by arylene-1,4-diyl-2,3-X2 bridges for olefin copolymerisation: X substituents impose conformational cooperative effects.

The synthesis, spectroscopic characterisation and catalytic olefin polymerisation behaviour of a class of binuclear titanium bis(benzyl) complexes bearing bis-(pyridine-2-phenolate-6-methine)-[μ-(arylene-1,4-diyl-2,3-X2)] ligands [X2 = -C4H4- (1), F2 (2), H2 (3)], and mononuclear analogues, are described. These bimetallic catalyst frameworks are designed to exhibit a degree of conformational flexibility, which is regulated by steric effects and crucially permits tuning of intermetallic distances and geometry, yet their shape-persistent nature can also confer favourable entropic terms. Complexes 1-3 are characterised as two diastereomers [meso (RS) and rac (RR,SS)] in ratios of 1.32, 1.18 and 1.13 respectively, according to 1H NMR spectroscopy. In contrast to 3, [1H,1H]-ROESY experiments for 1 and 2 revealed that the X2 substituents can impose preferred conformations with syn orientations of Ti2 centres and benzyl groups, thus implying that the activated catalysts would present binding sites with the same direction of access. For ethylene-(1-octene) copolymerisation reactions, in conjunction with [Ph3C][B(C6F5)4], catalyst 1 displayed superior efficiencies and produced polymers with higher Mw values and enhanced comonomer incorporation ratios (up to 41%), when compared with the mononuclear 5m (22%). These results are indicative of enhanced comonomer enchainment and cooperative reactivity by the Ti2 sites.

Bioassay-guided isolation and characterisation of α-glucosidase inhibitors from Sanghuangporus baumii

Bioassay-guided fractionation of the isopropanol extract of the medicinal mushroom Sanghuangporus baumii led to the isolation and characterisation of a new acorane-type sesquiterpenoid bauminene (1) and seven known compounds 2–8. The planar structure of 1 was elucidated on the basis of extensive spectroscopic analysis, including 1D, 2D NMR and HR-ESI-MS. The relative configuration of 1 was determined by a combination of ROESY experiment, density functional theory calculation of 13C NMR, and DP4+ probability analysis, while the absolute configuration of 1 was established by comparative electronic circular dichroism (ECD) spectra analysis. In the in vitro bioassay, compounds 1–8 exhibited potent to moderate α-glucosidase inhibitory activity with IC50 values ranging from 6.8 ± 0.68 to 221.4 ± 6.57 µM. The presences of these bioactive constituents in the sclerotia of S. baumii may be related to the use of the fungus as ‘Sanghuang’ for the adjuvant treatment of DM.

Four previously undescribed diketopiperazines from marine fungus Aspergillus puniceus FAHY0085 and their effects on liver X receptor α

Four previously undescribed diketopiperazine-type alkaloids including one oxepin-containing diketopiperazine-type alkaloid, oxepinamide L (1), three 4-quinazolinone alkaloids, puniceloids E-G (10–12), together with 12 known analogues, protuboxepin D (2), oxepinamides D-G, J-K and I (3–9), puniceloids B-D (13–15) and protubonine B (16), were isolated from the culture of the marine-derived fungus Aspergillus puniceus FAHY0085. The structures of the previously undescribed compounds were comprehensively elucidated by detailed interpretation of their NMR and HRESIMS data. Their absolute configurations were unambiguously determined by ROESY experiments, Marfey's method, calculated ECD experiments and single-crystal X-ray diffraction analysis. Compounds (3–4, 6–8, 14–15) were evaluated for their cytotoxic activity against HepG2, MCF-7, SW1116 and HeLa cells and compound 6 and 14 showed moderate cytotoxic activity against HeLa cells with IC50 49.61 ± 2.91 and 28.38 ± 1.57 μM, respectively. Compounds (1–8, 11–15) were screened for their transcriptional activation of liver X receptor α and compound 11 with known compounds 13–15 showed significant transcriptional activation of liver X receptor α with EC50 values in the range 2–50 μM.

Isoselective Polymerization of rac-Lactide by Magnesium Initiators Bearing Achiral Di(2-pyridyl)methyl Substituted Aminophenolate Ligands.

Reactions of achiral di(2-pyridyl)methyl substituted aminophenols L1-6H (2-{N-R3-N-[di(2-pyridyl)methyl]aminomethyl}-4-R1-6-R2-C6H2OH: R1 = R2 = tBu, R3 = nBu (L1H), R3 = nhexyl (L2H), R3 = cyclohexyl (L3H); R1 = R2 = cumyl, R3 = nBu (L4H), R3 = nhexyl (L5H), R3 = cyclohexyl (L6H)) with {Mg[N(SiMe3)2]2}2 ([L1-6H]:[Mg] = 1:1) afforded a series of magnesium silylamido complexes 1-6. In the solid state, the magnesium center of 3, 4, and 6 is penta-coordinated by the tetradentate aminophenloate ligand and one silylamido ligand to form a seriously distorted square-pyramidal geometry as confirmed by X-ray crystallography diffraction analysis. VT 1H NMR and ROESY experiments further indicate that these magnesium complexes are also five-coordinated in solutions where the coordination of either of the two pyridyl pendants to the magnesium center is maintained. Complexes 1-6 are highly active toward the ring-opening polymerization of rac-lactide (rac-LA) at r.t. both in toluene and in tetrahydrofuran, capable of polymerizing 500 equiv of monomer to high conversions just within minutes. Among them, complex 3 exhibited the highest iso-stereoselectivity, affording moderately isotactic polylactide in toluene (Pm = 0.75). It is found that the isoselectivities and activities of these magnesium complexes toward the polymerization of rac-LA are closely associated with the substituents at the ortho-position of the phenoxide unit and on the skeleton nitrogen atom of the ligand. On the basis of NMR spectroscopic studies, the formation of isotactic PLAs with dominant stereoblock sequences was witnessed by using these magnesium complexes as initiators, and the inequivalent coordination of two pyridyl pendant arms in these magnesium complexes might be the source of exerting isoselective control.

A chiral pentanidium and pyridinyl-sulphonamide ion pair as an enantioselective organocatalyst for Steglich rearrangement.

Enantioselective ion pair catalysis has gained significant attention due to its ability to exert selectivity control in various reactions. Achiral counterions have been found to play crucial roles in modulating reactivity and selectivity. The modular nature of an ion pair catalyst allows rapid alterations of the achiral counterion to achieve optimal outcomes, without the need to modify the more onerous chiral component. In this study, we report the successful development of a stable chiral pentanidium pyridinyl-sulphonamide ion pair as a nucleophilic organocatalyst for asymmetric Steglich rearrangement. The ion pair catalyst demonstrated excellent performance, leading to enantioenriched products with up to 99% ee through simple alterations of the achiral anions. We conducted extensive ROESY experiments and concluded that the reactivity and enantioselectivity were correlated to the formation of a tight ion pair in solution. Further computational analyses provided greater clarity to the structure of the ion pair catalyst in solution. Our findings reveal the critical roles of NMR experiments and computational analyses in the design and optimisation of ion pair catalysts.

Synthesis of New 3-Morpholyl-Substituted 4-Aryl-2-Arylimino-2,3-Dihydrothiazole Derivatives and Their Anti-Inflammatory and Analgesic Activity

New 4-aryl-3-(morpholin-4-yl)-2-arylimino-2,3-dihydrothiazole derivatives 1.1-1.16 were obtained using the Hantzsch reaction by condensation of N-(morpholin-4-yl)-N'-arylthioureas with the corresponding α bromoacetophenones in alcohols. Synthesized hydrobromides 1.1-1.8 were formed as crystalline precipitates during the boiling of the reaction mixture. Bases 1.9-1.16 were obtained by neutralizing the corresponding hydrobromides with NH4OH solution. It has been proposed a possible mechanism of the reaction that is based on the study of the structure of the synthesized compounds. The structures of the synthesized compounds were confirmed by 1H NMR spectroscopy with its special techniques (NOESY and ROESY experiments). It has been shown the formation of the isomer 4-(4'-chlorophenyl)-3-(morpholin-4-yl)-2-(4'-chlorophenylamino)-2.3-dihydrothiazole on the basis of compound 1.14. Pharmacological screening of synthesized derivatives of 4-aryl-2-arylimino-2,3-dihydrothiazole compounds revealed the analgesic effect in the model of visceral pain caused by the introduction of acetic acid to white mice. The anti-inflammatory effect of the synthesized compounds was evaluated in vivo by reducing limb edema in rats with carrageenan-induced inflammation. Thus, the synthesized compounds have analgesic and anti-inflammatory activity.

Scalarane Sesterterpenoids Isolated from the Marine Sponge Hyrtios erectus and their Cytotoxicity.

Eighteen scalarane sesterterpenoids (1–18), including eight new derivatives (1–8), were isolated from the sponge Hyrtios erectus (family Thorectidae), the extract of which showed cytotoxicity against the HeLa and MCF-7 cell lines. Of the new derivatives, six compounds (1–6) were found to contain a γ-hydroxybutenolide moiety capable of reversible stereoinversion at the hydroxylated carbon center. Under the influence of other adjacent functional groups, each derivative exhibited a different stereochemical behavior, which was fully deduced by ROESY experiments. All the isolated compounds were examined for their cytotoxicity by MTS assay using staurosporine as a positive control (IC50 0.18 and 0.13 μΜ against HeLa and MCF-7 cells, respectively), and they were found to show weak growth inhibitory activities against HeLa and MCF-7 cells, with a minimal IC50 value of 20.0 μΜ. The compounds containing a γ-hydroxybutenolide moiety (1–3, 10, 12) showed cytotoxicity, with IC50 values ranging from 24.3 to 29.9 μΜ, and the most potent derivative was heteronemin (16). Although the cytotoxicities of isolated compounds were insufficient to discuss the structure–activity relationship, this research could contribute to expanding the structural diversity of scalaranes and understanding the stereochemical behavior of γ-hydroxybutenolides.

Combined in-silico and in-vitro experiments support acid-base equilibrium as a tool to estimate the localization depth of 4-nitrophenol within a phospholipid bilayer

The interaction and location of 4-nitrophenol (PNP) in biomembranes are relevant in the bioaccumulation and potentiation of the intensive toxic effects of this persistent organic pollutant. In this work, in-silico analyses predicted that, in a fluid phospholipid bilayer, the minimum energy of the protonated (PNPH) and deprotonated (PNP−) species is located within the glycerol and choline region, respectively. This was experimentally confirmed by acid-base equilibrium experiments and theory, allowing the estimation of the mean location of PNP within a bilayer region with a dielectric constant D = 50.6 compatible with the phosphate/choline moiety of egg-yolk phosphatidylcholine unilamellar (EPC) vesicles. The comparison with the D = 43.2 value obtained in Triton X-100 micelles allow predicting a mean surface potential of ψ = 25.37 mV for the EPC-water interface. Changes in the chemical shifts and longitudinal relaxation times of EPC hydrogens by 1H NMR confirm the deeper location of the PNPH within the glycerol region and at the choline region (PNP−) at higher pH. Intermolecular PNP−EPC dipolar interactions within the choline region was also demonstrated at pH 10.2 using ROESY experiments. Additional information was obtained trough 31P NMR, that detected an increase in the anisotropy at the membrane interface after insertion of PNP which probably act as a bridge between choline moieties rigidizing the crystalline structure at that spot. Concluding, here we provide experimental support to the “pH-piston hypothesis” proposed some decades ago in the pharmaceutical field, and that reinforce the importance of the environmental conditions (e.g. pH) to modulate the bioavailability of this highly toxic pollutant.

Characterization of Heparin's Conformational Ensemble by Molecular Dynamics Simulations and Nuclear Magnetic Resonance Spectroscopy.

Heparin is a highly charged, polysulfated polysaccharide and serves as an anticoagulant. Heparin binds to multiple proteins throughout the body, suggesting a large range of potential therapeutic applications. Although its function has been characterized in multiple physiological contexts, heparin's solution conformational dynamics and structure-function relationships are not fully understood. Molecular dynamics (MD) simulations facilitate the analysis of a molecule's underlying conformational ensemble, which then provides important information necessary for understanding structure-function relationships. However, for MD simulations to afford meaningful results, they must both provide adequate sampling and accurately represent the energy properties of a molecule. The aim of this study is to compare heparin's conformational ensemble using two well-developed force fields for carbohydrates, known as GLYCAM06 and CHARMM36, using replica exchange molecular dynamics (REMD) simulations, and to validate these results with NMR experiments. The anticoagulant sequence, an ultra-low-molecular-weight heparin, known as Arixtra (fondaparinux, sodium), was simulated with both parameter sets. The results suggest that GLYCAM06 matches experimental nuclear magnetic resonance three-bond J-coupling values measured for Arixtra better than CHARMM36. In addition, NOESY and ROESY experiments suggest that Arixtra is very flexible in the sub-millisecond time scale and does not adopt a unique structure at 25 C. Moreover, GLYCAM06 affords a much more dynamic conformational ensemble for Arixtra than CHARMM36.

β-cyclodextrin complex formation and protonation equilibria of morphine and other opioid compounds of therapeutic interest

The inclusion complex formation of morphine and its 18 opioid derivatives with β-cyclodextrin has been studied using nuclear magnetic resonance spectroscopy. Initially, the protonation equilibria and the acid-base properties of dibasic opioid compounds have been fully characterized. Apparent protonation constants and the relative concentration of the microspecies in cyclodextrin excess were also determined. The 1:1 complex stoichiometry was confirmed by the continuous variation method of Job using UV-VIS spectroscopy. The stability constants of the different protonation forms were determined by 1H NMR titrations. The highest stability was observed in highly alkaline solutions where the amino group is in its unprotonated, neutral state. The structures of the complexes were investigated by two-dimensional ROESY experiments. Based on the stability constants and ROESY experiments, morphine derivatives with longer side chain on the nitrogen atom such as nalbuphine and naltrexone show stronger complexation. The protonation state of the phenolate group, positioned outside the CD cavity, has only a slight influence on the complex stability.

Spirostanol Sapogenins and Saponins from Convallaria majalis L. Structural Characterization by 2D NMR, Theoretical GIAO DFT Calculations and Molecular Modeling.

Two new spirostanol sapogenins (5β-spirost-25(27)-en-1β,2β,3β,5β-tetrol 3 and its 25,27-dihydro derivative, (25S)-spirostan-1β,2β,3β,5β-tetrol 4) and four new saponins were isolated from the roots and rhizomes of Convallaria majalis L. together with known sapogenins (isolated from Liliaceae): 5β-spirost-25(27)-en-1β,3β-diol 1, (25S)-spirostan-1β,3β-diol 2, 5β-spirost-25(27)-en-1β,3β,4β,5β-tetrol 5, (25S)-spirostan-1β,3β,4β,5β-tetrol 6, 5β-spirost-25(27)-en-1β,2β,3β,4β,5β-pentol 7 and (25S)-spirostan-1β,2β,3β,4β,5β-pentol 8. New steroidal saponins were found to be pentahydroxy 5-O-glycosides; 5β-spirost-25(27)-en-1β,2β,3β,4β,5β-pentol 5-O-β-galactopyranoside 9, 5β-spirost-25(27)-en-1β,2β,3β,4β,5β-pentol 5-O-β-arabinonoside 11, 5β-(25S)-spirostan-1β,2β,3β,4β,5β-pentol 5-O-galactoside 10 and 5β-(25S)-spirostan-1β,2β,3β,4β,5β-pentol 5-O-arabinoside 12 were isolated for the first time. The structures of those compounds were determined by NMR spectroscopy, including 2D COSY, HMBC, HSQC, NOESY, ROESY experiments, theoretical calculations of shielding constants by GIAO DFT, and mass spectrometry (FAB/LSI HR MS). An attempt was made to test biological activity, particularly as potential chemotherapeutic agents, using in silico methods. A set of 12 compounds was docked to the PDB structures of HER2 receptor and tubulin. The results indicated that diols have a higher affinity to the analyzed targets than tetrols and pentols. Two compounds (25S)-spirosten-1β,3β-diol 1 and 5β-spirost-25(27)-en-1β,2β,3β,4β,5β-pentol 5-O-galactoside 9 were selected for further evaluation of biological activity.

Hybrid Peptides Based on α-Aminoxy Acids as Antimicrobial and Anticancer Foldamers.

α-Aminoxy peptides represent an interesting group of peptidomimetics with high proteolytic stability and the ability to fold into specific, predictable secondary structures. Here, we present a series of hybrid peptides consisting of α-aminoxy acids and α-amino acids with cationic and aromatic, hydrophobic side chains in an alternating manner synthesized using an efficient protocol that combines solution- and solid-phase synthesis. 2D ROESY experiments with a representative hexamer suggested the presence of a 7/8 helical conformation in solution. Biological evaluation revealed a significant impact of the peptide chain length and the N-terminal cap on the antimicrobial and anticancer properties of this series of hybrid peptides. The Fmoc-capped peptide 6e displayed the most potent antimicrobial activity against a panel of Gram-negative and Gram-positive bacterial strains (e. g. against E. Coli: MIC=8 mg/L; S. aureus: MIC=4 mg/L).

Highly oxygenated angucycline from Streptomyces sp. KCB15JA014.

LC/MS-based chemical screening of culture extract led to a new highly oxygenated angucycline derivative, grecocycline D (1), from Streptomyces sp. KCB15JA014, isolated from a soil sample of Oedolgae in Jeju Island, Korea. The planar structure was determined on the basis of spectroscopic analysis, including 1D and 2D NMR techniques as well as HRESIMS and comparison with data from the literature. A relative and absolute configuration of 1 was assigned by ROESY experiment and electronic circular dichroism calculation. Compound 1 showed weak inhibitory activity against indoleamine 2,3-dioxygenase.

Correlating Solution- and Solid-State Structures of Conformationally Flexible Resorcinarenes: Significance of a Sulfonyl Group in Intramolecular Self-Inclusion.

The synthesis of tetramethoxyresorcinarene podands bearing p‐toluene arms connected by ‐SO3‐ (1) and ‐CH2O‐ (2) linkers is presented herein. In the solid state, the resorcinarene podand 1 forms an intramolecular self‐inclusion complex with the pendant p‐toluene group of a podand arm, whereas the resorcinarene podand 2 does not show self‐inclusion. The conformations of the flexible resorcinarene podands in solution were investigated by variable‐temperature experiments using 1D and 2D NMR spectroscopic techniques as well as by computational methods, including a conformational search and subsequent DFT optimisation of representative structures. The 1H NMR spectra of 1 and 2 at room temperature show a single set of proton signals that are in agreement with C 4v symmetry. At low temperatures, the molecules exist as a mixture of boat conformations featuring slow exchange on the NMR timescale. Energy barriers (ΔG ≠ 298) of 55.5 and 52.0 kJ mol−1 were calculated for the boat‐to‐boat exchange of 1 and 2, respectively. The results of the ROESY experiments performed at 193 K and computational modelling suggest that in solution the resorcinarene podand 1 adopts a similar conformation to that present in its crystal structure, whereas podand 2 populates a more versatile range of conformations in solution.

Structurally diverse lanostane triterpenoids from medicinal and edible mushroom Ganoderma resinaceum Boud.

Ganoderma resinaceum is a multi-purpose herbal medicine that is homologous to functional food that has long been used for enhancing health and treating chronic hepatopathy in Traditional Chinese Medicine. In a search program to discover the key bioactive composition of G. resinaceum, sixteen new lanostane-type triterpenoids (1-16), and twenty known analogues (17-36) were isolated from the fruiting bodies of G. resinaceum. Spectroscopic analyses and X-ray crystallography were used to determine the new structures. Furthermore, the spectroscopic properties of 15β-hydroxy-4,4,14α- trimethyl-3,7,11,20-tetraoxo-5α-pregn-8-ene (15) and 15α-hydroxy-4,4,14α-trimethyl- 3,7,11,20-tetraoxo-5α-pregn-8-ene (34) indicated a potential structural misassignment of their analogues, lucidone E and lucidone H, reported previously. To probe this hypothesis, ROESY experiments and single-crystal X-ray diffraction analysis were conducted. These results undoubtedly reassigned the structure of lucidone E and lucidone H. Biological evaluation of the selected compounds disclosed that compounds 3, 4, 7/21, 11, 12, 13/14, 17, 18, 24/25, 27, 30, 31, and 35 had significant hepatoprotective activities, due to their remarkable in vitro inhibitory activities against the increase of ALT and AST levels in HepG2 cells induced by H2O2.

Separation of terbutaline enantiomers in capillary electrophoresis with neutral cyclodextrin-type chiral selectors and investigation of the structure of selector-selectand complexes using nuclear magnetic resonance spectroscopy.

The major goal of this study was to determine the affinity pattern of the terbutaline (TB) enantiomers toward α-, β-, γ-, and heptakis(2,3-di-O-acetyl)-β-cyclodextrins and using NMR spectroscopy for the understanding of the fine mechanisms of interaction between the cyclodextrins (CD) and TB enantiomers. It was shown once again that CE in combination with NMR spectroscopy represents a sensitive tool to study the affinity patterns and structure of CD complexes with chiral guests. Opposite affinity patterns of TB enantiomers toward native α- and β-CDs were associated with significant differences between the structure of the related complexes in solution. In particular, the complex between TB enantiomers and α-CD was of the external type, whereas an inclusion complex was formed between TB enantiomers and β-CD. One of the possible structures of the complex between TB and heptakis(2,3-di-O-acetyl)-β-CD (HDA-β-CD) was quite similar to that of TB and β-CD, although the chiral recognition pattern and enantioselectivity of TB complexation with these two CDs were very different.

The Problem of Dynamic Process Manifestation in Identification of Organic Compounds by NMR Spectroscopy

The number, shape and position of NMR spectral lines depend on dynamic processes, and this creates certain difficulties in identification of pharmaceutical substances by NMR spectroscopy. The aim of the paper was to study instances of manifestation of intramolecular dynamic processes that affect identification of organic compounds by NMR, and to illustrate the potential of the methods used for their reduction, as well as associated problems.Materials and methods: 1H and 13C spectra of the following pharmaceutical substances: «buserelin acetate», «valsartan», «goserelin acetate», «iopromide», «clopidogrel hydrogensulfate», «omeprazole», «proroxan», «risperidone», «triptorelin acetate», and «enalapril maleate» were used to demonstrate negative effects of dynamic processes. The spatial structures of conformers were established by 1H-1H ROESY experiments. The quantum-chemical calculation of geometric and thermodynamic characteristics of different conformers was carried out by the PM3 method, and electronic characteristics—by the AM1 method with the help of the HyperChem software.Results: the authors analysed intramolecular dynamic processes which are most commonly encountered in expert work: pyramidal inversion of nitrogen in a heterocyclic compound (risperidone, proroxan, clopidogrel), rotation of molecular fragments around the amide bond (valsartan, iopromide, enalapril), prototropic rearrangements (buserelin, goserelin, omeprazole, triptorelin). The change in exchange rates was explained from the perspective of the change in the system of intra- and intermolecular nonvalent interactions.Conclusions: the use of traditional methods for increasing the rate of dynamic processes (increasing the temperature and changing the solvent) does not always eliminate the negative effects of intramolecular transformations. Methods of smoothing the spectral manifestations of dynamic processes have limited application due to strong intramolecular nonvalent interactions which prevent the conversion of the dynamic process rate into fast exchange. Experts and manufacturers should take into account the manifestation of dynamic processes during identification of pharmaceutical substances by NMR spectroscopy.

Unusual bridged angucyclinones and potent anticancer compounds from Streptomyces bulli GJA1.

Two new unique angucyclinones (1 and 2) with unprecedented ether bridges connecting carbons 5 and 7 were isolated from the cultures of Streptomyces bulli GJA1, an endophyte of Gardenia jasminoides, together with two known ones (3 and 4). The MS2-based molecular networking system facilitated the isolation of compounds with target functionalities. The stereochemistry of 1 was completely established by ROESY and ECD experiments. Compound 3 showed antivirulence activities by inhibiting the peptide toxin (PSMs) production and the biofilm formation of MRSA. Compounds 3 and 4 showed very potent anti-proliferative effects against OV1 and ES2 ovarian cancer cells.