Advanced Structure Analysis Reveals a Transient Portimine B Hydrate.

Portimine B was isolated from an extract derived from the dinoflagellate Vulcanodinium rugosum, a known producer of the closely related portimine A. Initial molecular characterization studies of portimine B suggested an open tetrahydrofuranyl ring isomer, contrary to the intact ring moiety found in portimine A. In 2023, the Baran lab synthesized both portimines A and B suggesting that both macrocyclic analogs contained the intact tetrahydrofuranyl ring. In this note, we utilize newly acquired NMR data, the i-HMBC NMR experiment, and advanced density functional theory calculations to define the structural divergence, originating from the presence of a transient hydrate.

Wheldone Revisited: Structure Revision Via DFT-GIAO Chemical Shift Calculations, 1,1-HD-ADEQUATE NMR Spectroscopy, and X-ray Crystallography Studies.

Wheldone is a fungal metabolite isolated from the coculture of Aspergillus fischeri and Xylaria flabelliformis, displaying cytotoxic activity against breast, melanoma, and ovarian cancer cell lines. Initially, its structure was characterized as an unusual 5-methyl-bicyclo[5.4.0]undeca-3,5-diene scaffold with a 2-hydroxy-1-propanone side chain and a 3-(2-(1-hydroxyethyl)-2-methyl-2,5-dihydrofuran-3-yl)acrylic acid moiety. Upon further examination, minor inconsistencies in the data suggested the need for the structure to be revisited. Thus, the structure of wheldone has been revised using an orthogonal experimental-computational approach, which combines 1,1-HD-ADEQUATE NMR experiments, DFT-GIAO chemical shift calculations, and single-crystal X-ray diffraction (SCXRD) analysis of a semisynthetic p-bromobenzylamide derivative, formed via a Steglich-type reaction. The summation of these data now permits the unequivocal assignment of both the structure and absolute configuration of the natural product.

Janus helices: From fully attractive to hard helices.

The phase diagram of hard helices differs from its hard rods counterpart by the presence of chiral "screw" phases stemming from the characteristic helical shape, in addition to the conventional liquid crystal phases also found for rod-like particles. Using extensive Monte Carlo and Molecular Dynamics simulations, we study the effect of the addition of a short-range attractive tail representing solvent-induced interactions to a fraction of the sites forming the hard helices, ranging from a single-site attraction to fully attractive helices for a specific helical shape. Different temperature regimes exist for different fractions of the attractive sites, as assessed in terms of the relative Boyle temperatures, that are found to be rather insensitive to the specific shape of the helical particle. The temperature range probed by the present study is well above the corresponding Boyle temperatures, with the phase behaviour still mainly entropically dominated and with the existence and location of the various liquid crystal phases only marginally affected. The pressure in the equation of state is found to decrease upon increasing the fraction of attractive beads and/or on lowering the temperature at fixed volume fraction, as expected on physical grounds. All screw phases are found to be stable within the considered range of temperatures with the smectic phase becoming more stable on lowering the temperature. By contrast, the location of the transition lines do not display a simple dependence on the fraction of attractive beads in the considered range of temperatures.

Cannabicitran: Its unexpected racemic nature and potential origins.

Cannabicitran is a cannabinoid found in levels up to ~10% in commercial "purified" cannabidiol (CBD) extracts. The structure of this natural product was first reported more than 50 years ago. However, few studies have investigated cannabicitran or its origin despite the rapidly increasing interest in the use of cannabinoids for the treatment of a wide range of physiological conditions. Following on a recent detailed NMR and computational characterization of cannabicitran, our group initiated ECD and TDDFT studies aimed at unequivocally determining the absolute configuration of cannabicitran present in Cannabis sativa extracts. To our surprise, we discovered the natural product was racemic, raising questions around its presumed enzymatic origin. Herein, we report the isolation and absolute configuration of (-)-cannabicitran and (+)-cannabicitran. Several possible scenarios for production of the racemate in the plant and/or during extract processing are discussed.

Quantitative nuclear magnetic resonance of chloride by an accurate internal standard approach.

Chloride is the most common counterion used to improve aqueous solubility and enhance stability of small molecule active pharmaceutical ingredients. While several analytical techniques, such as titration, HPLC with charged aerosol detection, and ion chromatography, are currently utilized to assay the level of chloride, they have notable limitations, and these instruments may not be readily available. Here, we present a generally applicable 35 Cl solution NMR method to assay the level of chloride in pharmaceutical compounds. The method uses KClO4 as an internal standard for improved accuracy in comparison with external standard methods, and it was found to be robust, linear over three orders of magnitude, precise (<3% RSD), and accurate (<0.5% absolute error).

DELTA50: A Highly Accurate Database of Experimental 1H and 13C NMR Chemical Shifts Applied to DFT Benchmarking.

Density functional theory (DFT) benchmark studies of 1H and 13C NMR chemical shifts often yield differing conclusions, likely due to non-optimal test molecules and non-standardized data acquisition. To address this issue, we carefully selected and measured 1H and 13C NMR chemical shifts for 50 structurally diverse small organic molecules containing atoms from only the first two rows of the periodic table. Our NMR dataset, DELTA50, was used to calculate linear scaling factors and to evaluate the accuracy of 73 density functionals, 40 basis sets, 3 solvent models, and 3 gauge-referencing schemes. The best performing DFT methodologies for 1H and 13C NMR chemical shift predictions were WP04/6-311++G(2d,p) and ωB97X-D/def2-SVP, respectively, when combined with the polarizable continuum solvent model (PCM) and gauge-independent atomic orbital (GIAO) method. Geometries should be optimized at the B3LYP-D3/6-311G(d,p) level including the PCM solvent model for the best accuracy. Predictions of 20 organic compounds and natural products from a separate probe set had root-mean-square deviations (RMSD) of 0.07 to 0.19 for 1H and 0.5 to 2.9 for 13C. Maximum deviations were less than 0.5 and 6.5 ppm for 1H and 13C, respectively.

Calculated and experimental 1 H and 13 C NMR assignments for cannabicitran.

Cannabicitran is an important cannabinoid natural product produced by Cannabis sativa and is often found at surprisingly high levels (up to ~10%) in "purified" commercial cannabidiol (CBD) extract preparations. Despite the prevalence of this molecule in CBD oil and other cannabinoid-related products, and the rapidly expanding interest in cannabinoids for treatment of a wide range of physiological conditions, only unassigned 1 H NMR data and partial unambiguous 13 C assignments have been published. Herein, we report the complete 1 H and 13 C NMR assignments of cannabicitran and comparatively evaluate the performance of several density functional theory (DFT) methods with varying levels of theory for the calculation of NMR chemical shifts.

Crystal nucleation in colloidal rod suspensions: The effect of depletant size.

In order to better control the assembly of nanorods, knowledge of the pathways by which they form ordered structures is desirable. In this paper, we characterize crystal nucleation in suspensions of spherocylindrical rods with aspect ratio L/D = 2.3 in the presence of both small and large polymer depletants. Using a combination of Langevin dynamics and Monte Carlo simulations, together with biased sampling techniques, we show that the preferred pathway always involves the formation of monolayer assemblies irrespective of the volume fraction of the initial isotropic phase and the diameter of the depletants. This includes the previously neglected case of nucleation from the colloidal liquid phase and shows that the presence of depletion attraction can alter nucleation pathways even when the initial phase is dense.

Insights into the introduction history and population genetic dynamics of the Argentine black-and-white tegu (Salvator merianae) in Florida.

Invasive species are a major threat to global biodiversity. The US state of Florida is especially susceptible to the spread of exotic reptiles due to its subtropical climate, disturbed habitats, and robust pet trade. The Argentine black-and-white tegu (Salvator merianae) is a large, omnivorous lizard currently established in two different regions of Southern Florida. These two populations pose potential threats to sensitive ground nesting species such as gopher tortoises, American crocodiles, and migratory birds. At present, the introduction histories of these populations and the degree to which they are connected by gene flow are largely unknown. To address these issues, we genotyped S. merianae from Hillsborough and Miami-Dade Counties at ten microsatellite loci to assess intrapopulation genetic diversity, the degree of gene flow between populations, and compare the plausibilities of several potential introduction scenarios. Our results indicate that both populations have low genetic diversity [mean number of effective alleles across loci in both populations = 2.09 and are highly differentiated from each other (GST = 0.170; G″ST = 0.545)]. In addition, our results suggest that these populations underwent a bottleneck event prior to their divergence. We discuss what our results suggest about the histories of Florida's invasive tegu populations, as well as how they inform ongoing management strategies.

Insights into the Introduction History and Population Genetic Dynamics of the Nile Monitor (Varanus niloticus) in Florida.

Invasive species are widely recognized as important drivers of the ongoing biodiversity crisis. The US state of Florida is especially susceptible to the proliferation of invasive reptiles, and nonnative lizards currently outnumber native lizard species. At present, there are 3 documented breeding populations of the Nile monitor (Varanus niloticus) in different regions of Southern Florida, and these populations are considered potential dangers to threatened, fossorial endemics, such as burrowing owls, American crocodiles, and gopher tortoises. Nevertheless, at present, both the introduction histories of these populations and the degree to which they are connected by gene flow are not known. To address these issues, we genotyped V. niloticus from Cape Coral, Homestead Air Reserve Base, and West Palm Beach at 17 microsatellite loci and conducted a variety of analyses to assess both intrapopulation genetic diversity, the degree of gene flow between populations, and the most likely introduction scenario. The results of our analyses demonstrate that all 3 populations have limited genetic diversity (mean number of effective alleles across loci in all 3 populations ~ 2.00) and are highly differentiated from one another (G ST = 0.268; G″ST = 0.628). Our results also suggest that these populations resulted from independent introduction events that occurred within the past few decades. Consequently, we advise that wildlife managers focus management efforts on containment of existing populations and intensification of monitoring efforts on potential migration corridors.

Interfacial and bulk nanostructure of liquid polymer nanocomposites.

Liquid polymer nanocomposites (l-PNCs) have been prepared using silica nanoparticles with diameters of 15 nm (l-PNC-15) and 24 nm (l-PNC-24), and Jeffamine M-2070, an amine-terminated ethylene oxide/propylene oxide (PEO/PPO, ratio 31/10) copolymer. Jeffamine M-2070 was used as the host liquid in which the particles were suspended and was also grafted onto the particle surface to prevent aggregation. The grafting density of Jeffamine M-2070 on the particle surfaces was ∼0.75 chains nm(-2). When the total polymer content (surface layer + host) was greater than ∼30 wt %, the PNC was a liquid, while at lower polymer volume fractions the PNC was solid. In this work, the bulk and surface structures of l-PNCs with ∼70 wt % polymer and 30% silica are characterized and compared. Small-angle neutron scattering (SANS) was used to probe the bulk structure of the l-PNCs and revealed that the particles are well-dispersed with minor clustering in l-PNC-15 and substantial clustering in l-PNC-24. This is attributed to stronger van der Waals attractions between particles due to the larger particle size in l-PNC-24. Corresponding effects were revealed using tapping mode atomic force microscopy (TM-AFM) at the l-PNC-air interface; clustering was minimal on the surface of l-PNC-15 but significant for l-PNC-24 droplets. In regions of the l-PNC where the particles were well-dispersed, the spacing between particles is consistent with their volume fractions. This is the first time that the distribution of polymer and particles within l-PNCs has been imaged in situ.

Comparing the cost-effectiveness of drones, camera trapping and passive acoustic recorders in detecting changes in koala occupancy.

Quantifying the cost-effectiveness of alternative sampling methods is crucial for efficient biodiversity monitoring and detection of population trends. In this study, we compared the cost-effectiveness of three novel sampling methods for detecting changes in koala (Phascolarctos cinereus) occupancy: thermal drones, passive acoustic recorders and camera trapping. Specifically, we fitted single-season occupancy-detection models to data recorded from 46 sites in eight bioregions of New South Wales, Australia, between 2018 and 2022. We explored the effect of weather variables on daily detection probability for each method and, using these estimates, calculated the statistical power to detect 30%, 50% and 80% declines in koala occupancy. We calculated power for different combinations of sites (1-200) and repeat surveys (2-40) and developed a cost model that found the cheapest survey design that achieved 80% power to detect change. On average, detectability of koalas was highest with one 24-h period of acoustic surveys (0.32, 95% CI's: 0.26, 0.39) compared to a 25-ha flight of drone surveys (0.28, 95% 0.15, 0.48) or a 24-h period of camera trapping consisting of six cameras (0.019, 95% CI's: 0.014, 0.025). We found a negative quadratic relationship between detection probability and air temperature for all three methods. Our power and cost analysis suggested that 148 sites surveyed with acoustic recorders deployed for 14 days would be the cheapest method to sufficiently detect a 30% decline in occupancy with 80% power. We recommend passive acoustic recorders as the most efficient sampling method for monitoring koala occupancy compared to cameras or drones. Further comparative studies are needed to compare the relative effectiveness of these methods and others when the monitoring objective is to detect change in koala abundance over time.

The thermodynamic origins of chiral twist in monolayer assemblies of rod-like colloids.

The propagation of chirality across scales is a common but poorly understood phenomenon in soft matter. Here, using computer simulations, we study twisted monolayer assemblies formed by both chiral and achiral rod-like particles in the presence of non-adsorbing polymer and characterise the thermodynamic driving forces responsible for the twisting. We observe assemblies with both like and inverted chirality relative to the rods and show that the preferred twist is already determined during the initial stage of the self-assembly. Depending on the geometry of the constituent rods, the chiral twist is regulated by either the entropy gain of the polymer, or of the rods, or both. This can include important contributions from changes in both the surface area and volume of the monolayer and from rod fluctuations perpendicular to the monolayer. These findings can deepen our understanding of why chirality propagates and of how to control it.

Structural revision of a Wnt/ß-catenin modulator and confirmation of cannabielsoin constitution and configuration.

In this report, we revise the structure for a previously reported synthetic product proposed to be the 1R,2S-cannabidiol epoxide and reassign it as cannabielsoin using anisotropic NMR and synthetic chemistry methods. These results provide a direct link to the first known biological target and function of cannabielsoin.

Over 13,000 elements from a single bonebed help elucidate disarticulation and transport of an Edmontosaurus thanatocoenosis.

Over twenty years of work on the Hanson Ranch (HR) Bonebed in the Lance Formation of eastern Wyoming has yielded over 13,000 individual elements primarily of the hadrosaurid dinosaur Edmontosaurus annectens. The fossil bones are found normally-graded within a fine-grained (claystone to siltstone) bed that varies from one to two meters in thickness. Almost all specimens exhibit exquisite preservation (i.e., little to no abrasion, weathering, and breakage), but they are disarticulated which, combined with our sedimentological observations, suggests that the bones were remobilized and buried after a period of initial decay and disarticulation of Edmontosaurus carcasses. Because of the large number of recovered fossil elements, we have been able to gain deeper insight into Edmontosaurus biostratigraphy including disarticulation and transport of skeletal elements. The most common postcranial elements in the bonebed are pubes, ischia, scapulae, ribs, and limb bones. By contrast, vertebrae, ilia, and chevrons are rare. The most common craniomandibular bones include dentaries, nasals, quadrates, and jugals, whereas the premaxillae, predentaries, and braincase bones are underrepresented. Thus, overall, chondrocranial and axial elements, as well as distal elements of the limbs, are distinctly underrepresented. We hypothesize that following decay and disarticulation, hydraulic winnowing removed the articulated sections (e.g., vertebral columns) and the small, distal-most elements before, or at the same time, the remaining bones were swept up in a subaqueous debris flow that generated the deposit. Comparison of the HR Bonebed with other widely dispersed Upper Cretaceous hadrosaurid-dominated bonebeds reveals many shared attributes, which suggests similar processes at work in the formation of these bonebeds across space and time. This in turn reflects similar behavior by populations of these species around the world resulting in similar modes of death, becoming interred in similar depositional settings.

Combining genetic and distributional approaches to sourcing introduced species: a case study on the Nile monitor (Varanus niloticus) in Florida.

Three separate breeding populations of the Nile monitor (Varanus niloticus) have been identified in Florida, USA, located in Cape Coral, West Palm Beach and Homestead Air Reserve Base. This large, predatory lizard could have negative effects on Florida's native wildlife. Here, we infer the source of the introduced populations using genetic and statistical approaches, as well as estimate the potential non-native distribution of V. niloticus in North America. We collected genetic data from 25 Florida individuals as well as utilized genetic datasets from reference individuals spanning the full native distribution throughout sub-Saharan Africa. Using occurrence data from the inferred source population and the full species range, we built ecological niche models (ENMs) and projected them onto North America to determine regions with suitable climate. Our results indicated that the introduced populations resulted from three separate introduction events, and all originated from the southern coastal region of West Africa. The ENM built from the West African source population predicted only the southernmost portions of North America to be suitable. Conversely, the model derived from the full species' range predicted suitable climates across a large portion of the United States. This information can be used to focus management and eradication efforts.