In October 2003, 20 years ago, the open-source and open-content database NMRshiftDB was announced. Since then, the database, renamed as nmrshiftdb2 later, has been continuously available and is one of the longer-running projects in the field of open data in chemistry. After 20 years, we evaluate the success of the project and present lessons learnt for similar projects.

BACKGROUND: Natural deep eutectic solvents (NADES) have emerged as interesting extractants to develop botanical ingredients. They are nontoxic and biodegradable, nonflammable, easy to prepare, and able to solubilize a wide range of molecules. However, NADES extracts remain difficult to analyze because the metabolites of interest stay highly diluted in the nonvolatile viscous NADES matrix.
OBJECTIVE: This study presents a robust analytical workflow for the chemical profiling of NADES extracts. It is applied to Hypericum perforatum aerial parts extracted with the neutral mixture fructose/glycerol/water (3/1/1, w/w/w), and compared to the chemical profiling of a classical dry methanol extract.
METHODS: Exploiting polarity differences between metabolites, the H. perforatum NADES extract was partitioned in a liquid-liquid solvent system to trap the hydrophilic NADES constituents in the lower phase. The upper phase, containing a diversity of secondary metabolites from H. perforatum, was fractionated by centrifugal partition chromatography. All fractions were chemically investigated using a 13 C NMR dereplication method which involves hierarchical clustering analysis of the whole NMR dataset, a natural metabolite database for metabolite identification, and 2D NMR analyses for validation. Liquid chromatography-mass spectrometry (LC-MS) analyses were also performed to complete the identification process.
RESULTS: A range of 21 metabolites were unambiguously identified, including glycosylated flavonols, lactones, catechins, phenolic acids, lipids, and simple sugars, and 15 additional minor extract constituents were annotated by LC-MS based on exact mass measurements.
CONCLUSIONS: The proposed identification process is rapid and nondestructive and provides good prospects to deeply characterize botanical extracts obtained in nonvolatile and viscous NADES systems.

Gastric metastases from primary renal cell carcinoma (RCC) are rare and poorly documented in the existing literature. This case report presents the clinical course of a 65-year-old male with multi-metastatic clear cell RCC (ccRCC) who was incidentally found to have stomach metastases during follow-up magnetic resonance imaging (MRI). Gastric metastases from ccRCC are typically associated with other metastatic sites. They often emerge at an advanced stage of the disease, indicating a poor prognosis. It is therefore important to consider gastric metastases as a potential site of involvement in RCC patients. MRI revealed three gastric mucosal lesions exhibiting hypervascularity, a characteristic feature of ccRCC. Histological analysis confirmed the presence of malignant cells compatible with RCC.

Values of S 2 CH and S 2 NH order parameters derived from NMR relaxation measurements on proteins cannot be used straightforwardly to determine protein structure because they cannot be related to a single protein structure, but are defined in terms of an average over a conformational ensemble. Molecular dynamics simulation can generate a conformational ensemble and thus can be used to restrain S 2 CH and S 2 NH order parameters towards experimentally derived target values S 2 CH (exp) and S 2 NH (exp). Application of S 2 CH and S 2 NH order-parameter restraining MD simulation to bond vectors in 63 side chains of the protein hen egg white lysozyme using 51 S 2 CH (exp) target values and 28 S 2 NH (exp) target values shows that a conformational ensemble compatible with the experimentally derived data can be obtained by using this technique. It is observed that S 2 CH order-parameter restraining of C-H bonds in methyl groups is less reliable than S 2 NH order-parameter restraining because of the possibly less valid assumptions and approximations used to derive experimental S 2 CH (exp) values from NMR relaxation measurements and the necessity to adopt the assumption of uniform rotational motion of methyl C-H bonds around their symmetry axis and of the independence of these motions from each other. The restrained simulations demonstrate that side chains on the protein surface are highly dynamic. Any hydrogen bonds they form and that appear in any of four different crystal structures, are fluctuating with short lifetimes in solution.

A methodology for the qualitative analysis of a mixture of compounds obtained during the synthesis of difluprednate is described herein for the first time. For this scope a multi-technique analytical approach was developed, combining Liquid Chromatography/Mass Spectrometry (LC/MS), Nuclear Magnetic Resonance (NMR) and computational chemistry. Separation of isomers is frequently required for the identification of impurities in active pharmaceutical ingredients (APIs) to assess the impact they may exhibit on public health. During the final step of the difluprednate synthesis apart from the desired product, various by-products may be obtained. Structural analysis of the products using LC/MS and NMR indicated that the steroid difluprednate was obtained along with its acetyl/butyryl regional isomers, whereas the results were further supported by semi-empirical calculations of the MS-derived data. Following the proposed approach, we managed to elucidate the structures of the challenging 11-acetate, 17-butyrate from the 17-acetate, 21-butyrate, 6α,9α-difluoro prednisolone isomers. The approach utilized may be of general applicability for the analysis of impurities in active pharmaceutical ingredients obtained during chemical synthesis.

Over the past decade intrinsically disordered proteins (IDPs) have emerged as a biologically important class of proteins, many of which are of therapeutic relevance. Here, we investigated the interactions between a model IDP system, tau K18, and nine literature compounds that have been reported as having an effect on tau in order to identify a robust IDP-ligand system for the optimization of a range of biophysical methods. We used NMR, surface plasmon resonance (SPR) and microscale thermophoresis (MST) methods to investigate the binding of these compounds to tau K18; only one showed unambiguous interaction with tau K18. Several near neighbors of this compound were synthesized and their interactions with tau K18 characterized using additional NMR methods, including 1D ligand-observed NMR, diffusion-ordered spectroscopy (DOSY) and 19F NMR. This study demonstrates that it is possible to detect and characterize IDP-ligand interactions using biophysical methods. However, care must be taken to account for possible artefacts, particularly the impact of compound solubility and where the protein has to be immobilized.

The purpose of this report is to describe a case of a unilateral congenital absence of the lacrimal gland in a 7-year-old girl with ocular symptoms, no tear production and a conjunctival tumour at the supero-external angle of the right eye. The visual acuity was 20/20 in both the eyes. The right eye showed mucous secretion, corneal erosions and filaments. Anamnesis, physical examination and clinical tests ruled out systemic diseases associated with congenital alacrima, as well as rheumatic, immunological and infectious diseases. Nuclear magnetic resonance, with various fat suppression techniques, demonstrated the absence of the right lacrimal gland and the presence of a tumour compatible with lipoma. This case, to our knowledge, is the first report of unilateral absence of the lacrimal gland combined with lipoma.

The authors report the case of a 41-year-old man known as a polydrug addict and found dead at home. The initial toxicological screening was inconclusive for a toxic death. However, 7 small bags of unknown powders and crystals, supposed to be NPS, were found near the body and sent to the laboratory 3 weeks later. This article focuses on the interest of nuclear magnetic resonance (NMR) spectroscopy to solve this fatal case. The 7 items were identified by 1H NMR and their purities were measured by the quantitative NMR (qNMR) method using maleic acid as internal standard. The compounds were 4-chloro-α-pyrrolidinopentiophenone, dibutylone, 4-chloroethcathinone, 4-α-pyrrolidinohexuiphenone, 3,4-methylenedioxy-N-benzylcathinone, 3-methoxy-phencyclidine and α-pyrrolidinopropiophenone, with purities in the range 51-89%. In the biological specimens of the victim, only 3-methoxy-phencyclidine (3-MeO-PCP) was identified in cardiac blood, peripheral blood and urine at 743, 489 and 16,700 ng/mL. Hair (6 cm) concentration of the drug was 15,600 pg/mg. The other NPS were not detected. The peripheral blood concentration was higher than the values reported in previous intoxicated and fatal cases. The toxicological significance of the measured concentration in hair was difficult to establish because this is only the second case describing a test result for 3-MeO-PCP.

To better apply nuclear magnetic resonance (NMR) to evaluate the petrophysical characterization of high-rank coal, six anthracite samples from the Baijiao coal reservoir were measured by NMR. The porosity, T 2 cutoff value, permeability and pore type were analysed using the transverse relaxation time (T 2) spectrum before and after centrifugation. The results show that the T 2 spectrum of water-saturated anthracite can be divided into a discontinuous and continuous trimodal distribution. According to the connectivity among pores, three T 2 spectrum peaks were identified at the relaxation times of 0.01-1.7 ms, 1.7-65 ms and greater than 65 ms, which correspond to the micropores (less than 100 nm), mesopores (100-1000 nm) and macropores (greater than 1000 nm), respectively. Based on the T 2 cutoff value, we divided the T 2 spectrum into two parts: bound fluid and free fluid. By comparing two classic permeability models, we proposed a permeability model to calculate the permeability of anthracite. This result demonstrates that NMR has great significance to the exploration of coal reservoirs and to the understanding of the development of coalbed methane.

BACKGROUND: The paper presents the results of the use of phytotherapy in a 33-year-old woman who, after finishing the oncological treatment of diffuse astrocytoma, had tumour progression.
METHODS: Phytotherapy was introduced after the tumour had progressed. It consisted of 4 types of herbal medicine which the subject was taking in form of tea once a day at regular intervals. The patient started phytotherapy along with temozolomide, which was the only oncological treatment she was under after the tumour had progressed. Following the finished chemotherapy, the patient continued the treatment with herbal medicine only. She regularly took phytotherapy without interruption and to the fullest extent for 30 months, and the results of treatment were monitored by periodic scanning using nuclear magnetic resonance technique.
RESULTS: The control scanning that was conducted after the end of combined treatment with temozolomide and phytotherapy showed tumour regression. The patient continued with phytotherapy after finishing chemotherapy and, during the following 24 months, it was the sole treatment option. In that period, the regression of the tumour continued, until a control examination 30 months after the introduction of phytotherapy showed no clinical and radiological signs of tumour.
CONCLUSIONS: The results presented in this research paper clearly indicate the potential of phytotherapy in the treatment of some types of brain tumours. A complete regression of tumour following the treatment with nothing but herbal medicine offers support for such claim. Future research should demonstrate the effectiveness of phytotherapy, as a supplementary form of brain tumour treatment, and the results of this research should be compared with the existing information on the effectiveness of the protocols currently used in the treatment of these types of tumour.