Isolation and characterization of synthesis intermediates and side products in hexahydrocannabiphorol.

After the Swiss ban of hexahydrocannabinol (HHC) in March 2023, other semisynthetic dibenzopyran cannabinoids emerged on the Swiss gray market. Hexahydrocannabiphorol (HHCP) was the most prominent of them due to its potent cannabimimetic effects, as anecdotal reports from recreational users suggest. In October 2023, a class wide ban of dibenzopyran cannabinoids was introduced in Switzerland to prevent new similar substances from entering the drug market.

Fluorescence lifetime imaging and phasor analysis of intracellular porphyrinic photosensitizers applied with different polymeric formulations.

The fluorescence lifetime of a porphyrinic photosensitizer (PS) is an important parameter to assess the aggregation state of the PS even in complex biological environments. Aggregation-induced quenching of the PS can significantly reduce the yield of singlet oxygen generation and thus its efficiency as a medical drug in photodynamic therapy (PDT) of diseased tissues. Hydrophobicity and the tendency to form aggregates pose challenges on the development of efficient PSs and often require carrier systems.

Intracellular Fate of the Photosensitizer Chlorin e4 with Different Carriers and Induced Metabolic Changes Studied by H NMR Spectroscopy.

Porphyrinic photosensitizers (PSs) and their nano-sized polymer-based carrier systems are required to exhibit low dark toxicity, avoid side effects, and ensure high in vivo tolerability. Yet, little is known about the intracellular fate of PSs during the dark incubation period and how it is affected by nanoparticles. In a systematic study, high-resolution magic angle spinning NMR spectroscopy combined with statistical analyses was used to study the metabolic profile of cultured HeLa cells treated with different concentrations of PS chlorin e4 (Ce4) alone or encapsulated in carrier systems.

Liposomal aggregates sustain the release of rapamycin and protect cartilage from friction.

Liposomes show promise as biolubricants for damaged cartilage, but their small size results in low joint and cartilage retention. We developed a zinc ion-based liposomal drug delivery system for local osteoarthritis therapy, focusing on sustained release and tribological protection from phospholipid lubrication properties. Our strategy involved inducing aggregation of negatively charged liposomes with zinc ions to extend rapamycin (RAPA) release and improve cartilage lubrication.

Comparing PVP and Polymeric Micellar Formulations of a PEGylated Photosensitizing Phthalocyanine by NMR and Optical Techniques.

Phthalocyanines are ideal candidates as photosensitizers for photodynamic therapy (PDT) of cancer due to their favorable chemical and photophysical properties. However, their tendency to form aggregates in water reduces PDT efficacy and poses challenges in obtaining efficient forms of phthalocyanines for therapeutic applications. In the current work, polyvinylpyrrolidone (PVP) and micellar formulations were compared for encapsulating and monomerizing a water-soluble zinc phthalocyanine bearing four non-peripheral triethylene glycol chains ().

H HR-MAS NMR Based Metabolic Profiling of Lung Cancer Cells with Induced and De-Induced Cisplatin Resistance to Reveal Metabolic Resistance Adaptations.

Cisplatin (cisPt) is an important drug that is used against various cancers, including advanced lung cancer. However, drug resistance is still a major ongoing problem and its investigation is of paramount interest. Here, a high-resolution magic angle spinning (HR-MAS) NMR study is presented deciphering the metabolic profile of non-small cell lung cancer (NSCLC) cells and metabolic adaptations at different levels of induced cisPt-resistance, as well as in their de-induced counterparts (cells cultivated in absence of cisPt).

Probing the Interactions of Porphyrins with Macromolecules Using NMR Spectroscopy Techniques.

Porphyrinic compounds are widespread in nature and play key roles in biological processes such as oxygen transport in blood, enzymatic redox reactions or photosynthesis. In addition, both naturally derived as well as synthetic porphyrinic compounds are extensively explored for biomedical and technical applications such as photodynamic therapy (PDT) or photovoltaic systems, respectively. Their unique electronic structures and photophysical properties make this class of compounds so interesting for the multiple functions encountered.

Interactions of Cationic Diruthenium Trithiolato Complexes with Phospholipid Membranes Studied by NMR Spectroscopy.

To apprehend the possible mechanisms involved in the cellular uptake and the membrane interactions of cytotoxic dinuclear -cymene trithiolato ruthenium(II) complexes, the interactions of the complexes [(η--MeCHPr)Ru(R)(R)] (R = R = SCH--Pr:; R = SCH--OMe, R = SCH--OH:; R = SCHCH--OMe, R = SCH--OH:) with 1,2-dioleoyl-glycero-3-phosphocholine (DOPC) vesicles and 1,2-dihexanoyl--glycero-3-phosphocholine (DHPC) micelles were studied using nuclear magnetic resonance (NMR) spectroscopy. H NMR, nuclear Overhauser effect (NOE), diffusion ordered spectroscopy (DOSY), and and relaxation data provided information on interactions between the complexes and the model membranes and on the submolecular localization of the complexes at the membrane interface. The results suggest that (a) the interaction takes place without new covalent adduct formation, (b) the cationic diruthenium complexes interact with DOPC head groups most likely involving electrostatic interactions while remaining structurally unchanged, (c) the changes indicating interactions are more pronounced for the most lipophilic complex , and (d) the diruthenium complexes remain at the exterior vesicle surface and are unlikely inserted between the phospholipid chains.

Metabolomic Profiling of Wildtype and Transgenic Strains by H HR-MAS NMR Spectroscopy.

, a causative agent of persistent diarrhea in humans, domestic animals, and cattle, is usually treated with nitro compounds. Consequently, enzymes involved in anaerobic nitro reduction have been investigated in detail as potential targets. Their role within the normal metabolic context is, however, not understood.

Evaluation of polyvinylpyrrolidone and block copolymer micelle encapsulation of serine chlorin e6 and chlorin e4 on their reactivity towards albumin and transferrin and their cell uptake.

Encapsulation of porphyrinic photosensitizers (PSs) into polymeric carriers plays an important role in enhancing their efficiency as drugs in photodynamic therapy (PDT). Porphyrin aggregation and low solubility as well as the preservation of the advantageous photophysical properties pose a challenge on the design of efficient PS-carrier systems. Block copolymer micelles (BCMs) and polyvinylpyrrolidone (PVP) are promising drug delivery vehicles for physical entrapment of PSs.

Carbon source regulates polysaccharide capsule biosynthesis in .

The exopolysaccharide capsule of is an important virulence factor, but the mechanisms that regulate capsule thickness are not fully understood. Here, we investigated the effects of various exogenously supplied carbohydrates on capsule production and gene expression in several pneumococcal serotypes. Microscopy analyses indicated a near absence of the capsular polysaccharide (CPS) when was grown on fructose.

H HR-MAS NMR-Based Metabolomics of Cancer Cells in Response to Treatment with the Diruthenium Trithiolato Complex [(-MeCHPr)Ru(SCH--Bu)] (DiRu-1).

The trithiolato bridged diruthenium complex DiRu-1 [(p-MeCHPr)Ru(SCH-p-Bu)] is highly cytotoxic against various cancer cell lines, but its exact mode of action remains unknown. The present H HR-MAS NMR-based metabolomic study was performed on ovarian cancer cell line A2780, on its cis-Pt resistant variant A2780cisR, and on the cell line HEK-293 treated with 0.03 µM and 0.

Metabolic profiling of listeria rhombencephalitis in small ruminants by H high-resolution magic angle spinning NMR spectroscopy.

Listeria rhombencephalitis is caused by infection with Listeria monocytogenes and is associated with a high mortality rate in humans and ruminants. Little is known about the metabolic changes associated with neurolisteriosis in particular and infectious central nervous system (CNS) diseases in general. The purpose of our study was to investigate the metabolic changes associated with listeria rhombencephalitis in small ruminants (goats and sheep) as a model for inflammatory CNS disease by H high-resolution magic angle spinning nuclear magnetic resonance ( H HR-MAS NMR) spectroscopy of brain biopsies obtained from the brainstem and thalamus.

Longitudinal investigation of the metabolome of 3D aggregating brain cell cultures at different maturation stages by H HR-MAS NMR.

The aim of the present study was to establish the developmental profile of metabolic changes of 3D aggregating brain cell cultures by H high-resolution magic angle spinning (HR-MAS) NMR spectroscopy. The histotypic 3D brain aggregate, containing all brain cell types, is an excellent model for mechanistic studies including OMICS analysis; however, their metabolic profile has not been yet fully investigated. Chemometric analysis revealed a clear separation of samples from the different maturation time points.

H HR-MAS NMR spectroscopy to study the metabolome of the protozoan parasite Giardia lamblia.

Knowledge of the metabolic profile and exchange processes in the protozoan parasite Giardia lamblia is of importance for a better understanding of the biochemical processes and for the development of drugs to control diseases caused by G. lamblia. In the current paper, H High Resolution Magic Angle Spinning (HR-MAS) NMR spectroscopy was directly applied to G.

How Does the Encapsulation of Porphyrinic Photosensitizers into Polymer Matrices Affect Their Self-Association and Dynamic Properties?

Photodynamic therapy (PDT) with porphyrinic photosensitizers largely relies on efficient drug formulations to prevent porphyrin aggregation and to enhance water solubility and stability in physiologic environments. In this study, we compare two polymeric carrier systems, polyvinylpyrrolidone (PVP) and block copolymer micelles (BCMs) formed by the poloxamer Kolliphor P188 (KP), for their encapsulation efficiencies of porphyrin (xPP) and chlorin e6 (xCE) derivatives. Monomerization, loading efficiency, and dynamic properties were examined by H NMR spectroscopy chemical shift titration, DOSY, and T relaxation time measurements.

Metabolic profiling of apples from different production systems before and after controlled atmosphere (CA) storage studied by H high resolution-magic angle spinning (HR-MAS) NMR.

Determination of metabolic alterations in apples induced by such processes as different crop protection strategies or storage, are of interest to assess correlations with fruit quality or fruit disorders. Preliminary results proposed the metabolic discrimination of apples from organic (BIO), integrated (IP) and low-input (LI) production. To determine contributions of temporal metabolic developments and to define the type of metabolic changes during storage, H high resolution-magic angle spinning (HR-MAS) NMR spectroscopy of apple pulp was performed before and after two time points of controlled atmosphere storage.

Metabolic Profiling of Cells in Response to Drug Treatment using H High-resolution Magic Angle Spinning (HR-MAS) NMR Spectroscopy.

High-resolution magic angle spinning (HR-MAS) is an NMR technique that provides access to well resolved liquid-like 1H NMR spectra of semi-solid samples. Therefore, 1H HR-MAS NMR spectroscopy has become an important tool for the direct analysis of biological samples such as tissues and cells in a mostly non-destructive way. Here, we focus on the application of HR-MAS NMR combined with multivariate statistical methods used for metabolic profiling of cells and in particular for the study of cellular metabolic responses to drug exposure.

Insights into the formation of carlactone from in-depth analysis of the CCD8-catalyzed reactions.

Strigolactones are a new class of phytohormones synthesized from carotenoids via carlactone. The complex structure of carlactone is not easily deducible from its precursor, a cis-configured β-carotene cleavage product, and is thus formed via a poorly understood series of reactions and molecular rearrangements, all catalyzed by only one enzyme, the carotenoid cleavage dioxygenase 8 (CCD8). Moreover, the reactions leading to carlactone are expected to form a second, yet unidentified product.

Hepatitis C virus infection triggers a tumor-like glutamine metabolism.

Unlabelled: Chronic infection with hepatitis C virus (HCV) is one of the main causes of hepatocellular carcinoma. However, the molecular mechanisms linking the infection to cancer development remain poorly understood. Here we used HCV-infected cells and liver biopsies to study how HCV modulates the glutaminolysis pathway, which is known to play an important role in cellular energetics, stress defense, and neoplastic transformation.

Direct determination of phosphate sugars in biological material by (1)H high-resolution magic-angle-spinning NMR spectroscopy.

The study aim was to unambiguously assign nucleotide sugars, mainly UDP-X that are known to be important in glycosylation processes as sugar donors, and glucose-phosphates that are important intermediate metabolites for storage and transfer of energy directly in spectra of intact cells, as well as in skeletal muscle biopsies by (1)H high-resolution magic-angle-spinning (HR-MAS) NMR. The results demonstrate that sugar phosphates can be determined quickly and non-destructively in cells and biopsies by HR-MAS, which may prove valuable considering the importance of phosphate sugars in cell metabolism for nucleic acid synthesis. As proof of principle, an example of phosphate-sugar reaction and degradation kinetics after unfreezing the sample is shown for a cardiac muscle, suggesting the possibility to follow by HR-MAS NMR some metabolic pathways.

Interactions of Polyvinylpyrrolidone with Chlorin e6-Based Photosensitizers Studied by NMR and Electronic Absorption Spectroscopy.

Polyvinylpyrrolidone (PVP) can act as potential drug delivery vehicle for porphyrin-based photosensitizers in photodynamic therapy (PDT) to enhance their stability and prevent porphyrin self-association. In the present study the interactions of PVP (MW 10 kDa) were probed with five different derivatives of chlorin e6 (CE6) bearing either one of the amino acids serine, lysine, tyrosine or arginine, or monoamino-hexanoic acid as substituent. All derivatives of CE6 (xCE) formed aggregates of a similar structure in aqueous buffer in the millimolar range.