Monthly Archives: September 2023

Generation of Cannabigerolic Acid Derivatives and Their Precursors by Using the Promiscuity of the Aromatic Prenyltransferase NphB

Posted on by
Generation of Cannabigerolic Acid Derivatives and Their Precursors by Using the Promiscuity of the Aromatic Prenyltransferase NphB

The conversion of novel olivetolic acid derivatives with the highly promiscuous prenyltransferase NphB is analyzed as a tool for the creation of synthetic cannabinoid libraries. By using in silico and in vitro experiments CBGA derivatives were synthesized and characterized as products of enzyme catalysis.


Abstract

NphB is an aromatic prenyltransferase with high promiscuity for phenolics including flavonoids, isoflavonoids, and plant polyketides. It has been demonstrated that cannabigerolic acid is successfully formed by the reaction catalysed by NphB using geranyl diphosphate and olivetolic acid as substrates. In this study, the substrate specificity of NphB was further determined by using olivetolic acid derivatives as potential substrates for the formation of new synthetic cannabinoids. The derivatives differ in the hydrocarbon chain attached to C6 of the core structure. We performed in silico experiments, including docking of olivetolic acid derivatives, to identify differences in their binding modes. Substrate acceptance was predicted. Based on these results, a library of olivetolic acid derivatives was constructed and synthesized by using different organic synthetic routes. Conversion was monitored in in vitro assays with purified NphB versions. For the substrates leading to a high conversion olivetolic acid-C8, olivetolic acid-C2 and 2-benzyl-4,6-dihydroxybenzoic acid, the products were further elucidated and identified as cannbigerolic acid derivatives. Therefore, these substrates show potential to be adapted in cannabinoid biosynthesis.

Attachment of Hydrogen Molecules to Atomic Ions (Na+, Cl−): Examination of an Adiabatic Separation of the H2 Rotational Motion

Posted on by
Attachment of Hydrogen Molecules to Atomic Ions (Na+, Cl−): Examination of an Adiabatic Separation of the H2 Rotational Motion

In this computational work it is shown that hydrogen clusters doped with ions, formed by molecules in the first excited rotational state (ortho-H2), are more stable and tend to have larger coordination numbers than clusters composed by molecules in the ground rotational state (para-H2).


Abstract

Interactions between molecular hydrogen and ions are of interest in cluster science, astrochemistry and hydrogen storage. In dynamical simulations, H2 molecules are usually modelled as point particles, an approximation that can fail for anisotropic interactions. Here, we apply an adiabatic separation of the H2 rotational motion to build effective pseudoatom-ion potentials and in turn study the properties of (H2) n Na+/Cl− clusters. These interaction potentials are based on high-level ab initio calculations and Improved Lennard-Jones parametrizations, while the subsequent dynamics has been performed by quantum Monte Carlo calculations. By comparisons with simulations explicitly describing the molecular rotations, it is concluded that the present adiabatic model is very adequate. Interestingly, we find differences in the cluster stabilities and coordination shells depending on the spin isomer considered (para- or ortho-H2), especially for the anionic clusters.

Ligand and Linkage Isomers of Bis(ethylthiocarbamato) Copper Complexes with Cyclic C6H8 Backbone Substituents: Synthesis, Characterization, and Antiproliferation Activity

Posted on by
Ligand and Linkage Isomers of Bis(ethylthiocarbamato) Copper Complexes with Cyclic C6H8 Backbone Substituents: Synthesis, Characterization, and Antiproliferation Activity

Four isomeric copper(II) complexes based on a pair of ligand isomers that each yield a pair of linkage isomers have been synthesized and characterized. The effect of isomerism on the electronic structure and antiproliferation activity of the complexes is described.


Abstract

A series of isomeric bis(alkylthiocarbamate) copper complexes have been synthesized, characterized, and evaluated for antiproliferation activity. The complexes were derived from ligand isomers with 3-methylpentyl (H2L2) and cyclohexyl (H2L3) backbone substituents, which each yield a pair of linkage isomers. The thermodynamic products CuL2a/3a have two imino N and two S donors resulting in three five-member chelate rings (555 isomers). The kinetic isomers CuL2b/3b have one imino and one hydrazino N donor and two S donors resulting in four-, six-, and five-member rings (465 isomers). The 555 isomers have more accessible CuII/I potentials (E1/2=−811/−768 mV vs. ferrocenium/ferrocene) and lower energy charge transfer bands than their 465 counterparts (E1/2=−923/-854 mV). Antiproliferation activities were evaluated against the lung adenocarcinoma cell line (A549) and nonmalignant lung fibroblast cell line (IMR-90) using the MTT assay. CuL2a was potent (A549EC50=0.080 μM) and selective (IMR-90EC50/A549EC50=25) for A549. Its linkage isomer CuL2b had equivalent A549 activity, but lower selectivity (IMR-90EC50/A549EC50=12.5). The isomers CuL3a and CuL3b were less potent with A549EC50 values of 1.9 and 0.19 M and less selective with IMR-90EC50/A549EC50 ratios of 2.3 and 2.65, respectively. There was no correlation between reduction potential and A549 antiproliferation activity/selectivity.

Challenges and Recommendations in Assessing Potential Endocrine‐Disrupting Properties of Metals in Aquatic Organisms

Posted on by

Abstract

New tools and refined frameworks for identifying and regulating endocrine-disrupting chemicals (EDCs) are being developed as our scientific understanding of how they work advances. Although focus has largely been on organic chemicals, the potential for metals to act as EDCs in aquatic systems is receiving increasing attention. Metal interactions with the endocrine system are complicated because some metals are essential to physiological systems, including the endocrine system, and nonessential metals can have similar physiochemical attributes that allow substitution into or interference with these systems. Consequently, elevated metal exposure could potentially cause endocrine disruption (ED) but can also cause indirect effects on the endocrine system via multiple pathways or elicit physiologically appropriate compensatory endocrine-mediated responses (endocrine modulation). These latter two effects can be confused with, but are clearly not, ED. In the present study, we provide several case studies that exemplify the challenges encountered in evaluating the endocrine-disrupting (ED) potential of metals, followed by recommendations on how to meet them. Given that metals have multiple modes of action (MOAs), we recommend that assessments use metal-specific adverse outcome pathway networks to ensure that accurate causal links are made between MOAs and effects on the endocrine system. We recommend more focus on establishing molecular initiating events for chronic metal toxicity because these are poorly understood and would reduce uncertainty regarding the potential for metals to be EDCs. Finally, more generalized MOAs such as oxidative stress could be involved in metal interactions with the endocrine system, and we suggest it may be experimentally efficient to evaluate these MOAs when ED is inferred. These experiments, however, must provide explicit linkage to the ED endpoints of interest. Environ Toxicol Chem 2023;00:1–16. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.

Investigation of Anticholinesterase Activity of Chemically Characterised Hieracium s. str. Methanol Extracts and Their Selected Metabolites

Posted on by

The composition and anticholinesterase activity of the dried MeOH extracts of Hieracium scheppigianum and H. naegelianum underground parts (rhizomes and roots), as well as the anticholinesterase activity of the dried, previously chemically characterised MeOH extracts of the flowering aerial parts of these two and 26 other Hieracium species in the strict sense (s. str.), were investigated. Furthermore, the anticholinesterase activity of 12 selected secondary metabolites of these extracts was evaluated. Using semi-preparative LC-MS, five caffeoylquinic acids and the sesquiterpene lactone crepiside E were isolated from H. scheppigianum underground parts extract. All these compounds were also identified in the underground parts extract of H. naegelianum. Quantitative LC-MS analysis showed that the analysed underground parts extracts were rich in both caffeoylquinic acids (139.77 and 156.62 mg/g of extract, respectively) and crepiside E (126.88 and 116.58 mg/g). In the Ellman method, the tested extracts showed an interesting anti-AChE and/or anti-BChE activity (IC50=0.56-1.58 mg/mL), which can be explained, at least partially, by the presence of some of their constituents. Among the metabolites tested, the best activity was revealed for the flavonoids apigenin, luteolin and diosmetin, and the sesquiterpene lactone 8-epiixerisamine A (IC50=68.09-299.37 μM).

Laser‐Induced Carbon Nanofiber‐Based Redox Cycling System

Posted on by
Laser-Induced Carbon Nanofiber-Based Redox Cycling System

Laser-induced carbon nanofibers are used to create porous freestanding electrode systems for redox cycling. Either by closely spacing the interdigitated electrodes carbonized directly onto the nanofibrous network, or by fabricating an additional nanofibers layer onto the electrodes, amplification via redox cycling was achieved in these new approaches, facilitating a flow-through electroanalytical device with favorable sensitivity.


Abstract

Redox cycling is a powerful amplification strategy for reversible redox species within miniaturized electrochemical sensors. Herein, we generate three-dimensional (3D) porous carbon nanofiber electrodes by CO2 laser-writing on electrospun polyimide (PI) nanofiber mats, referred to as laser-induced carbon nanofibers (LCNFs). The technique allowed the fabrication of interdigitated electrode (IDE) arrays with finger width and gap distance of ~400 μm and ~40 μm, respectively, offering approximately 3.5 times amplification efficiency (AF) and 95 % collection efficiency (CE). Such dimensions could not be achieved with IDEs fabricated on conventional PI film because the devices were short-circuited. Stacked electrodes were also constructed as an alternative to the IDE design. Here, nanofiber mats as thin as ~20 μm were fabricated and used as vertical insulation between two LCNF band electrodes. While redox cycling efficiency was similar, the IDE design is more favorable considering the lower complexity and better signal reproducibility. Our strategy thus paves the way for creating flexible 3D porous electrodes with redox cycling ability that can be integrated into microfluidics and lab-on-a-chip systems. In particular, the devices offer inherent flow-through features in miniaturized analytical devices where separation and sensitive detection could be further realized.

Quantitative and Non‐Quantitative Assessments of Enzymatic Electrosynthesis: A Case Study of Parameter Requirements

Posted on by
Quantitative and Non-Quantitative Assessments of Enzymatic Electrosynthesis: A Case Study of Parameter Requirements

Compare, contrast, scrutinize and decide: Various process options can be used to bring enzyme processes to industrial application; these include electroenzymatic processes. To evaluate the processes quantitatively, appropriate performance indicators must be determined. In addition, there are non-quantitative variables that need to be considered. This article shows how laboratory processes can be evaluated and how options for action can be identified.


Abstract

The integration of enzymatic and electrochemical reactions offers a unique opportunity to optimize production processes. Recently, an increasing number of laboratory-scale enzymatic electrosyntheses have shown impressive performance indicators, leading to scientific interest in technical implementation. However, important process parameters are missing in most of the relevant literature. On one hand, this is due to the large variety of relevant performance indicators. On the other hand, enzyme technologists and electrochemists use different parameters to describe a process. In this article, we review the most important performance indicators in electroenzymatic processes and suggest that in order to allow quantitative comparison, these indicators should be reported in all respective publications. In addition to quantitative parameters, non-quantitative assessments often need to be included in a final evaluation. Examples of such parameters are sustainability, contribution to the UN Sustainable Development Goals or interactions with the overall process. We demonstrate the evaluation of processes using hydrogen peroxide-dependent peroxygenases. The strength of the proposed evaluation system lies in its ability to identify weaknesses in a process at an early stage of development. Finally, it can be concluded that all evaluated enzymatic electrosynthesis do not yet meet typical industrial requirements for an enzyme-based process.

Data‐Driven Analysis of Amine‐Based Sorbents for CO2 Removal from the Atmosphere

Posted on by
Data-Driven Analysis of Amine-Based Sorbents for CO2 Removal from the Atmosphere

CO2 sorbents are considered key components of the direct air capture (DAC) process. Various types of amines are widely applied for CO2 capture from the atmosphere. Their activities and efficiencies depend on various factors including their support material, operating conditions, and environment. Statistical data analysis is done to provide more insights into the performance of these amines for DAC.


Abstract

Available data on amine-based sorbents used for the direct air capture (DAC) process were gathered and analyzed to identify the correlations between various aspects of these sorbents and the operating conditions they are used in. It is demonstrated that a moderately high temperature (∼ 50 °C) can help with higher CO2 capture capacity. The effect of sorbent preparation method on its activity and stability was studied. Also, the influence of amine groups and support choice on amine efficiency and CO2 capture capacity was discussed. The DAC process conditions proved to play a major role in determining the optimal sorbent. An outlook for characteristics to be sought for in future DAC sorbents for CO2 removal is proposed.

Unlocking High‐Performance Supercapacitor Behavior and Sustained Chemical Stability of 2D Metallic CrSe2 by Optimal Electrolyte Selection

Posted on by
Unlocking High-Performance Supercapacitor Behavior and Sustained Chemical Stability of 2D Metallic CrSe2 by Optimal Electrolyte Selection

Supercapacitor: 2D metallic conductor CrSe2 synthesized at scale as crystalline powder remains stable in acidic conditions and outperforms high surface area carbon in supercapacitor applications


Abstract

Supercapacitors are energy storage devices with the ability to rapidly charge and discharge, making them a valuable complement to battery systems. To maximize their fast-charging capabilities, identifying materials and methods to enhance their energy density is crucial. In this work, we carried out a comprehensive study of an emerging 2D dichalcogenide, CrSe2, as a supercapacitor material. We demonstrate that CrSe2 can be obtained at ambient temperature through deintercalation of a relevant KCrSe2 precursor using a 0.5 M solution of I2 in acetonitrile. Although CrSe2 decomposed in 1 M KOH, it was found to be chemically stable in common electrolytes such as H2SO4, Li2SO4, and Na2SO4. Despite low surface area CrSe2 reached a specific capacitance of 27 F g−1 in 1 M H2SO4 and, thus consistently outperformed high surface carbon black. Computational studies suggested that the metallic conductivity of CrSe2 was likely the primary factor contributing to the superior performance of this 2D chalcogenide over high surface carbon analogues.

The increased Diels–Alder reactivity of umpolung tropone: analysis of individual atoms and bonds using QTAIM and IQA along complete IRC paths

Posted on by
The increased Diels–Alder reactivity of umpolung tropone: analysis of individual atoms and bonds using QTAIM and IQA along complete IRC paths

The IQA@IRC protocol enables us to see, in a much deeper detail, how the energy of each atom or group is varying along the IRC. It acts like a magnifying glass, allowing us to see things that are unreachable from the standard IRC analysis.


Abstract

A fruitful debate took place recently in literature, discussing the enhanced Diels–Alder reactivity of tropone derivatives for which the carbonyl polarity was reversed by means of umpolung. Karas et al. sustained that the umpolung increases the antiaromatic character of the ring, affecting the highest occupied molecular orbital (HOMO)/least unoccupied molecular orbital (LUMO) energies, speeding up the reaction. Tiekink et al. challenged this interpretation by sustaining that the asynchronicity of the reaction mechanisms, rather than orbital energy perturbation, was the main responsible for the smaller reaction barriers. We shed light on this dispute by computing full interaction quantum atom (IQA) and quantum theory of atoms in molecules (QTAIM) analyses over complete intrinsic reaction coordinate (IRC) paths for the Diels–Alder reaction of tropone and its umpolung derivatives, using the same systems studied by Karas et al. and Tiekink et al. Our results confirm that the asynchronicity is indeed very high for those reactions with smaller reaction barriers and offer an atom-by-atom and bond-by-bond analysis of the entire IRC pathways. Even though asynchronicity and lower reactions barriers seem to be related, antiaromaticity and lower barriers are related as well, but discussing both these interpretations does not necessarily require arguments on HOMO/LUMO energies to be invoked.