Saturated Cannabinoids: Update on Synthesis Strategies and Biological Studies of These Emerging Cannabinoid Analogs.

Natural and non-natural hexahydrocannabinols (HHC) were first described in 1940 by Adam and in late 2021 arose on the drug market in the United States and in some European countries. A background on the discovery, synthesis, and pharmacology studies of hydrogenated and saturated cannabinoids is described. This is harmonized with a summary and comparison of the cannabinoid receptor affinities of various classical, hybrid, and non-classical saturated cannabinoids. A discussion of structure-activity relationships with the four different pharmacophores found in the cannabinoid scaffold is added to this review. According to laboratory studies in vitro, and in several animal species in vivo, HHC is reported to have broadly similar effects to Δ9-tetrahydrocannabinol (Δ9-THC), the main psychoactive substance in cannabis, as demonstrated both in vitro and in several animal species in vivo. However, the effects of HHC treatment have not been studied in humans, and thus a biological profile has not been established.

Variations on a demonic theme: Szilard's other engines.

Szilard's now-famous single-molecule engine was only the first of three constructions he introduced in 1929 to resolve several challenges arising from Maxwell's demon paradox. Given that it has been thoroughly analyzed, we analyze Szilard's remaining two demon models. We show that the second one, though a markedly different implementation employing a population of distinct molecular species and semipermeable membranes, is informationally and thermodynamically equivalent to an ideal gas of the single-molecule engines. One concludes that (i) it reduces to a chaotic dynamical system-called the Szilard Map, a composite of three piecewise linear maps and associated thermodynamic transformations that implement measurement, control, and erasure; (ii) its transitory functioning as an engine that converts disorganized heat energy to work is governed by the Kolmogorov-Sinai entropy rate; (iii) the demon's minimum necessary "intelligence" for optimal functioning is given by the engine's statistical complexity; and (iv) its functioning saturates thermodynamic bounds and so it is a minimal, optimal implementation. We show that Szilard's third construction is rather different and addresses the fundamental issue raised by the first two: the link between entropy production and the measurement task required to implement either of his engines. The analysis gives insight into designing and implementing novel nanoscale information engines by investigating the relationships between the demon's memory, the nature of the "working fluid," and the thermodynamic costs of erasure and measurement.

The 10-nm chromatin fiber and its relationship to interphase chromosome organization.

A chromosome is a single long DNA molecule assembled along its length with nucleosomes and proteins. During interphase, a mammalian chromosome exists as a highly organized supramolecular globule in the nucleus. Here, we discuss new insights into how genomic DNA is packaged and organized within interphase chromosomes. Our emphasis is on the structural principles that underlie chromosome organization, with a particular focus on the intrinsic contributions of the 10-nm chromatin fiber, but not the regular 30-nm fiber. We hypothesize that the hierarchical globular organization of an interphase chromosome is fundamentally established by the self-interacting properties of a 10-nm zig-zag array of nucleosomes, while histone post-translational modifications, histone variants, and chromatin-associated proteins serve to mold generic chromatin domains into specific structural and functional entities.

HPLC Method for Better Separation of THC Isomers to Ensure Safety and Compliance in the Hemp Market.

The 2018 Farm Bill dictates that delta-9-tetrahydrocannabinol (Δ9-THC) concentrations must not exceed 0.3% in hemp and hemp-derived products in order to be "compliant." This narrow margin of error necessitates very precise testing methods throughout every facet of the hemp industry. Though gas chromatography has become the industry's gold standard, many hemp laboratories still use high-performance liquid chromatography (HPLC) to quantify cannabinoids, and thus there exists a need for HPLC methods that can separate delta-8-tetrahydrocannabinol (Δ8-THC) and Δ9-THC-a notoriously difficult task. This article details one such method, while simultaneously acknowledging the inevitable limits of using HPLC to separate cannabinoids. The method was also used to test Δ8-THC samples that were marketed as compliant, and it was found that all of the samples contained well over 0.3% Δ9-THC. The use of refined testing methodologies is crucial for hemp companies to ensure compliance, prevent adverse health effects, and provide consumers with accurate cannabinoid profiles of the products that they purchase.

Ultrasonic or Microwave Modified Continuous Flow Chemistry for the Synthesis of Tetrahydrocannabinol: Observing Effects of Various Solvents and Acids.

Synthesizing tetrahydrocannabinol is a lengthy process with minimal yields and little applicability on an industrial scale. To close the gap between bench chemistry and industry process chemistry, this paper introduces a small-scale flow chemistry method that utilizes a microwave or ultrasonic medium to produce major tetrahydrocannabinol isomers. This process produces excellent yields and minimal side products, which leads to more efficient large-scale production of the desired cannabinoids.

Thermodynamic uncertainty theorem.

Thermodynamic uncertainty relations (TURs) express a fundamental lower bound on the precision (inverse scaled variance) of any thermodynamic charge-e.g., work or heat-by functionals of the average entropy production. Relying on purely variational arguments, we significantly extend TUR inequalities by incorporating and analyzing the impact of higher statistical cumulants of the entropy production itself within the general framework of time-symmetrically-controlled computation. We derive an exact expression for the charge that achieves the minimum scaled variance, for which the TUR bound tightens to an equality that we name the thermodynamic uncertainty theorem (TUT). Importantly, both the minimum scaled variance charge and the TUT are functionals of the stochastic entropy production, thus retaining the impact of its higher moments. In particular, our results show that, beyond the average, the entropy production distribution's higher moments have a significant effect on any charge's precision. This is made explicit via a thorough numerical analysis of "swap" and "reset" computations that quantitatively compares the TUT against previous generalized TURs.

Psychoactive Isoxazoles, Muscimol, and Isoxazole Derivatives from the Amanita (Agaricomycetes) Species: Review of New Trends in Synthesis, Dosage, and Biological Properties.

Herbal products found in nature can serve as great systems of study for drug design. The Amanita muscaria mushroom is native to many parts of the Northern Hemisphere and has a very distinctive appearance with its red cap and white spotted warts. The mushroom comprises several pharmacologically active alkaloids, including muscazone, muscarine, ibotenic acid, and muscimol, the latter two compounds being potent GABA agonists. Muscimol has served as a backbone in the design of GABA agonists devoid of effects on the GABA-metabolizing enzyme, GABA transaminase, and GABA uptake systems. In this sense, several analogs of muscimol have been synthesized and studied including THIP, THPO, iso-THIP, iso-THAZ and 4-PIOL which all interact with the GABA receptors much differently. The growing pharmacological and toxicological interest based on many conflicting opinions on the use of the neuroprotective role of muscimol analogs against some neurodegenerative diseases, its potent role in the treatment of cerebral ischemia and other socially significant health conditions provided the basis for this review.

Photoresponse of Natural van der Waals Heterostructures.

Van der Waals heterostructures consisting of two-dimensional materials offer a platform to obtain materials by design and are very attractive owing to unique electronic states. Research on 2D van der Waals heterostructures (vdWH) has so far been focused on fabricating individually stacked atomically thin unary or binary crystals. Such systems include graphene, hexagonal boron nitride, and members of the transition metal dichalcogenide family. Here we present our experimental study of the optoelectronic properties of a naturally occurring vdWH, known as franckeite, which is a complex layered crystal composed of lead, tin, antimony, iron, and sulfur. We present here that thin film franckeite (60 nm < d < 100 nm) behaves as a narrow band gap semiconductor demonstrating a wide-band photoresponse. We have observed the band-edge transition at ∼1500 nm (∼830 meV) and high external quantum efficiency (EQE ≈ 3%) at room temperature. Laser-power-resolved and temperature-resolved photocurrent measurements reveal that the photocarrier generation and recombination are dominated by continuously distributed trap states within the band gap. To understand wavelength-resolved photocurrent, we also calculated the optical absorption properties via density functional theory. Finally, we have shown that the device has a fast photoresponse with a rise time as fast as ∼1 ms. Our study provides a fundamental understanding of the optoelectronic behavior in a complex naturally occurring vdWH, and may pave an avenue toward developing nanoscale optoelectronic devices with tailored properties.