An SN1-Approach to Cross-Coupling: Deoxygenative Arylation Facilitated by the ß-Silicon Effect.

We report a dual metal-catalyzed method for the cross-coupling of unprotected alcohols by exploiting the ß-Si effect. This deoxygenative Suzuki-Miyaura reaction tolerates a range of primary, secondary, and tertiary alcohol substrates along with diverse functional groups and heterocycles. Mechanistic experiments including KIE, VTNA, and Eyring analyses suggest the existence of a carbocation intermediate on the reaction pathway, consistent with a rare SN1 pathway for the activation of an electrophile in cross-coupling reactions. A novel bis-imidazolium N-heterocyclic carbene (NHC) ligand was found to be optimal for reactivity, and nickel(0)-, nickel(I)- and nickel(II)- complexes of this ligand were isolated and characterized. In contrast to more well-established shorter chain ligands, these long-chain NHCs are found to have characteristically large bite angles, which may be critical for enabling the deoxygenative arylation of aliphatic alcohols.

Thalamic atrophy and dysconnectivity are associated with cognitive impairment in a multi-center, clinical routine, real-word study of people with relapsing-remitting multiple sclerosis.

BACKGROUND: Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient. OBJECTIVE: To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting. METHODS: This was an international, multi-center (11 centers), longitudinal, retrospective, real-word study of people with relapsing-remitting MS (pwRRMS). Brain MRI exams acquired at baseline and follow-up were collected. Cognitive status was evaluated using the Symbol Digit Modalities Test (SDMT). Thalamic volume (TV) measurement was performed on T2-FLAIR, as well as on T1-WI, when available. Thalamic dysconnectivity, T2-lesion volume (T2-LV), and volumes of gray matter (GM), whole brain (WB) and lateral ventricles (LVV) were also assessed. RESULTS: 332 pwMS were followed for an average of 2.8 years. At baseline, T2-LV, LVV, TV and thalamic dysconnectivity on T2-FLAIR (p < 0.016), and WB, GM and TV volumes on T1-WI (p < 0.039) were significantly worse in 90 (27.1 %) CI vs. 242 (62.9 %) non-CI pwRRMS. Greater SDMT decline over the follow-up was associated with lower baseline TV on T2-FLAIR (standardized ß = 0.203, p = 0.002) and greater thalamic dysconnectivity (standardized ß = -0.14, p = 0.028) in a linear regression model. CONCLUSIONS: PwRRMS with thalamic atrophy and worse thalamic dysconnectivity present more frequently with CI and experience greater CW over mid-term follow-up in a real-world setting.

Alcohols as Substrates in Transition-Metal-Catalyzed Arylation, Alkylation, and Related Reactions.

Alcohols are abundant and attractive feedstock molecules for organic synthesis. Many methods for their functionalization require them to first be converted into a more activated derivative, while recent years have seen a vast increase in the number of complexity-building transformations that directly harness unprotected alcohols. This Review discusses how transition metal catalysis can be used toward this goal. These transformations are broadly classified into three categories. Deoxygenative functionalizations, representing derivatization of the C-O bond, enable the alcohol to act as a leaving group toward the formation of new C-C bonds. Etherifications, characterized by derivatization of the O-H bond, represent classical reactivity that has been modernized to include mild reaction conditions, diverse reaction partners, and high selectivities. Lastly, chain functionalization reactions are described, wherein the alcohol group acts as a mediator in formal C-H functionalization reactions of the alkyl backbone. Each of these three classes of transformation will be discussed in context of intermolecular arylation, alkylation, and related reactions, illustrating how catalysis can enable alcohols to be directly harnessed for organic synthesis.

Controlling Reactivity and Selectivity in the Mizoroki-Heck Reaction: High Throughput Evaluation of 1,5-Diaza-3,7-diphosphacyclooctane Ligands.

We report a high throughput evaluation of the Mizoroki-Heck reaction of diverse olefin coupling partners. Comparison of different ligands revealed the 1,5-diaza-3,7-diphosphacyclooctane (P2N2) scaffold to be more broadly applicable than common "gold standard" ligands, demonstrating that this family of readily accessible diphosphines has unrecognized potential in organic synthesis. In particular, two structurally related P2N2 ligands were identified to enable the regiodivergent arylation of styrenes. By simply altering the phosphorus substituent from a phenyl to tert-butyl group, both the linear and branched Mizoroki-Heck products can be obtained in high regioisomeric ratios. Experimental and computational mechanistic studies were performed to further probe the origin of selectivity, which suggests that both ligands coordinate to the metal in a similar manner but that rigid positioning of the phosphorus substituent forces contact with the incoming olefin in a π-π interaction (for P-Ph ligands) or with steric clash (for P-tBu ligands), dictating the regiocontrol.

A large-scale experiment finds no consistent evidence of change in mortality or commercial productivity in silverlip pearl oysters (Pinctada maxima) exposed to a seismic source survey.

High-intensity, impulsive sounds are used to locate oil and gas reserves during seismic exploration of the seafloor. The impacts of this noise pollution on the health and mortality of marine invertebrates are not well known, including the silverlip pearl oyster (Pinctada maxima), which comprises one of the world's last remaining significant wildstock pearl oyster fisheries, in northwestern Australia. We exposed ≈11,000 P. maxima to a four-day experimental seismic survey, plus one vessel-control day. After exposure, survival rates were monitored throughout a full two-year production cycle, and the number and quality of pearls produced at harvest were assessed. Oysters from two groups, on one sampling day, exhibited reduced survival and pearl productivity compared to controls, but 14 other groups receiving similar or higher exposure levels did not. We therefore found no conclusive evidence of an impact of the seismic source survey on oyster mortality or pearl production.

Utility of body and otolith morphometry to discriminate cryptic juveniles of two sympatric red snappers (Perciformes: Lutjanidae).

The sympatric red snappers, Lutjanus erythropterus and Lutjanus malabaricus, are highly valued by commercial and recreational fishers along the tropical northern coasts of Australia and throughout their distribution. Studies on the life history and ecology of these congeners are confounded by difficulties in distinguishing the cryptic juveniles of each species (i.e., < 200 mm total length). This study aimed to validate a robust and cost-effective method to discriminate these juveniles using body and/or otolith morphometric data in a multivariate analysis. Juvenile samples were collected from the northwest (n = 71) and northeast (n = 19) coasts of Australia, and species identification was confirmed using DNA barcoding. The most parsimonious multivariate models achieved accurate species prediction rates of 98.8%, which consisted of just three body variables (dorsal fin length, the distance from the snout to the anterior edge of the eye, and either jaw length or distance from the snout to the preoperculum). The high level of discrimination for these cryptic juveniles highlights the robustness of this morphometric approach. The slightly lower rate of discrimination using otolith morphology (84.9%) was associated with greater regional variation in L. malabaricus between the northwest and northeast coasts. Slight variations in otolith shape are typically used to determine stock structure, which highlights the potential need to collect samples over a broader area of a species geographic range when using an otolith morphometric discrimination model. The method outlined in this study could be applied to distinguish other cryptic congeneric fish species, including from archived otolith collections. Moreover, this method has the potential to be utilized in assessing species compositions using body measurements from in situ stereo-video.

Reductive Cleavage of C(sp2)-CF3 Bonds in Trifluoromethylpyridines.

A reductive detrifluoromethylation protocol has been developed making use of an earth-abundant alkoxide base and silicon hydride species. A variety of pyridine and quinoline substrates bearing alkyl, aryl, and amino functional groups are reduced in moderate to high yields. The reaction is chemoselective for C(sp2)-CF3 groups located at the 2-position on the pyridine ring, leaving trifluoromethyl groups located elsewhere on the molecule intact. Preliminary mechanistic studies demonstrate that the combination of silane and base generates a strongly reducing system that may transfer an electron to electron-deficient π systems.

SMART Drumlines Ineffective in Catching White Sharks in the High Energy Capes Region of Western Australia: Acoustic Detections Confirm That Sharks Are Not Always Amenable to Capture.

The management of human-shark interactions can benefit from the implementation of effective shark hazard mitigation measures. A Shark-Management-Alert-in-Real-Time (SMART) drumline trial in the Capes region of Western Australia was instigated after several serious incidents involving surfers and white sharks (Carcharodon carcharias). The project aimed to determine whether white sharks (target species), which were relocated after capture, remained offshore using satellite and acoustic tagging. Over a 27-month period, 352 fish were caught, 55% of which comprised tiger sharks (Galeocerdo cuvier). Ninety-one percent of animals were released alive in good condition. Only two white sharks were caught; both were relocated ≥ 1 km offshore before release and moved immediately further offshore after capture, remaining predominately in offshore waters for the duration of their 54-day and 186-day tag deployments. Our results confirm that desirable animal welfare outcomes can be achieved using SMART drumlines when response times are minimised. The low target catches and the detection of 24 other tagged white sharks within the study area supported the decision to cease the trial. Our results reiterate there is no simple remedy for dealing with the complexities of shark hazards and reinforce the importance of trialing mitigation measures under local conditions.

Hyporthodus griseofasciatus (Perciformes: Epinephelidae), a new species of deep-water grouper from the west coast of Australia.

A new species of deep-water epinephelid fish is described from the west coast of Australia based on 14 specimens, 99-595 mm standard length. Hyporthodus griseofasciatus sp. nov. is endemic to Western Australia from Barrow Island to Two Peoples Bay in depths of 76-470 m. It has a series of eight grey bands alternating with eight brown bands along the body and the soft dorsal, soft anal and caudal fin margins are pale cream to white. It is distinguished from its nearest congener, H. ergastularius, by the presence of a star-like pattern of radiating lines on the head versus an overall brownish colour in the latter as well as significant differences in the quantitative analyses of 25 morphological characters. The two species have allopatric distributions on either side of the Australian continent. H. griseofasciatus is distinguished from H. octofasciatus by several grey bands being distinctly narrower than other grey bands (vs. all grey bands subequal in the latter) and the presence of broad white margins on the dorsal, caudal and anal fins (vs. narrow or absent in the latter). Some scale counts appear to also differ. Analyses of mitochondrial cytochrome oxidase subunit 1 sequences revealed reciprocally monophyletic clades with fixed differences and genetic distances typical of recently diverged species of fishes.

Reductive 1,2-Arylation of Isatins.

We report an intermolecular Ni-catalyzed reductive coupling of aryl iodides and isatins to form 3-hydroxyoxindoles. In contrast to common metal-mediated methods, sec-butanol is used as a mild stoichiometric reductant resulting in benign waste products. This formal 1,2-addition reaction is facilitated by a 1,5-diaza-3,7-diphosphacyclooctane (P2N2) ligand. Two Ni(0)-P2N2 species are prepared and found to be catalytically active, supporting a mechanistic hypothesis that this reaction proceeds by a modified carbonyl-Heck-type pathway.

Fine Particle Fraction: The Good and the Bad.

Fine particle fraction (FPF) is defined in general terms as the fraction or percentage of the drug mass contained in an aerosol cloud that may be small enough to enter the lungs and exert a clinical effect. An aerodynamic diameter of 5 µm represents the approximate border between "fine" and "coarse" particles, but there is no universally agreed upon definition of FPF in terms of an aerodynamic particle size range. FPF alone does not adequately describe a heterodisperse aerodynamic particle size distribution, and it needs to be combined with another measure or measures indicating the width of the distribution. When determined using techniques specified in United States and European Pharmacopeias, FPF is measured by cascade impactors that have straight-sided ninety degree inlets through which air is drawn at a constant rate. It is not the purpose of in vitro tests to predict in vivo behavior, and FPF is primarily a measure of aerosol quality. Despite this, FPF broadly predicts the amount of drug from an inhaler device depositing in the lungs, but it systematically overestimates whole lung deposition and may not correctly predict the relative lung depositions for two inhalers of different types. The relationship between FPF and both drug pharmacokinetics and clinical response is incompletely understood at the present time, and more studies are needed to investigate these relationships. Modifications to impactor technologies, including inlets that mimic the human extrathoracic airways and the use of realistic breathing patterns, would be expected to improve the predictive power of in vitro tests for drug delivery in vivo.

Effects of human footprint and biophysical factors on the body-size structure of fished marine species.

Marine fisheries in coastal ecosystems in many areas of the world have historically removed large-bodied individuals, potentially impairing ecosystem functioning and the long-term sustainability of fish populations. Reporting on size-based indicators that link to food-web structure can contribute to ecosystem-based management, but the application of these indicators over large (cross-ecosystem) geographical scales has been limited to either fisheries-dependent catch data or diver-based methods restricted to shallow waters (<20 m) that can misrepresent the abundance of large-bodied fished species. We obtained data on the body-size structure of 82 recreationally or commercially targeted marine demersal teleosts from 2904 deployments of baited remote underwater stereo-video (stereo-BRUV). Sampling was at up to 50 m depth and covered approximately 10,000 km of the continental shelf of Australia. Seascape relief, water depth, and human gravity (i.e., a proxy of human impacts) were the strongest predictors of the probability of occurrence of large fishes and the abundance of fishes above the minimum legal size of capture. No-take marine reserves had a positive effect on the abundance of fishes above legal size, although the effect varied across species groups. In contrast, sublegal fishes were best predicted by gradients in sea surface temperature (mean and variance). In areas of low human impact, large fishes were about three times more likely to be encountered and fishes of legal size were approximately five times more abundant. For conspicuous species groups with contrasting habitat, environmental, and biogeographic affinities, abundance of legal-size fishes typically declined as human impact increased. Our large-scale quantitative analyses highlight the combined importance of seascape complexity, regions with low human footprint, and no-take marine reserves in protecting large-bodied fishes across a broad range of species and ecosystem configurations.

Las pesquerías marinas de los ecosistemas costeros en muchas áreas del mundo históricamente han removido a individuos de gran tamaño, potencialmente perjudicando el funcionamiento ambiental y la sostenibilidad a largo plazo de las poblaciones de peces. Los reportes sobre los indicadores basados en el tamaño que se vinculan con la estructura de la red alimenticia pueden contribuir al manejo basado en el ecosistema, aunque la aplicación de estos indicadores a grandes (inter-ecosistemas) escalas geográficas ha estado limitada a datos de captura dependientes de las pesquerías o métodos basados en el buceo restringidos a aguas someras (<20 m), lo cual puede representar erróneamente la abundancia de peces de gran tamaño capturados para la pesca. Obtuvimos los datos de la estructura del tamaño corporal de 82 teleósteos marinos demersales focalizados por razones recreativas o comerciales tomados de 2,904 despliegues de video estéreo subacuático remoto con cebo (stereo-BRUV, en inglés). El muestreo se realizó hasta los 50 metros de profundidad y abarcó aproximadamente 10,000 km del talud continental de Australia. El relieve marino, la profundidad del agua y la gravedad humana (es decir, un indicador de los impactos humanos) fueron los pronosticadores más sólidos de la probabilidad de incidencia de los peces de gran tamaño y de la abundancia de peces por encima del tamaño legal mínimo de captura. Las reservas marinas de protección total tienen un efecto positivo sobre la abundancia de los peces que están por encima del tamaño legal, aunque el efecto varió según el grupo de especies. Como contraste, los peces de tamaño sublegal fueron pronosticados de mejor manera usando gradientes de la temperatura de la superficie marina (media y varianza). En las áreas con un impacto humano reducido, los peces de gran tamaño corporal tenían hasta tres veces mayor probabilidad de aparecer y los peces de tamaño legal eran aproximadamente cinco veces más abundantes. Para los grupos de especies conspicuas con afinidades contrastantes de hábitat, ambiente y biogeografía, la abundancia de peces de tamaño legal normalmente declinó conforme aumentó el impacto humano. Nuestros análisis cuantitativos a gran escala resaltan la importancia conjunta que tienen la complejidad marina, las regiones con una huella humana reducida y las reservas marinas de protección total para la protección de los peces de gran tamaño corporal en una extensa gama de especies y configuraciones ecosistémicas. Efectos de la Huella Humana y los Factores Biofísicos sobre la Estructura del Tamaño Corporal de Especies Marinas Capturadas para la Pesca.

Complementary evidence for small-scale spatial assemblages of the exploited grass emperor (Lethrinus laticaudis) in the Shark Bay World Heritage Area, Western Australia.

Understanding the connectivity of exploited fish populations is critical to their management under both rapid and long-term environmental change. Patterns of connectivity are unknown for most fishes in the Shark Bay World Heritage Area (Western Australia), a large, shallow embayment in the eastern Indian Ocean, vulnerable to marine heatwaves. The composition of oxygen (δ18O) and carbon (δ13C) stable isotopes in whole otoliths of the recreationally-important reef fish Lethrinus laticaudis did not differ between Shark Bay's two large inner gulfs, separated by the Peron Peninsula. However, significant differences were found between pairs of locations with different salinities over a spatial scale of ∼60 km within each gulf. Misclassification of samples was greatest between locations mostly in different gulfs, but with similar salinities (15-41%), and rare between adjacent locations in the same gulf with different salinities (0-5%). This is influenced by the strong correlation (ρ = 0.93) between δ18O in otoliths and the salinity gradient of the two gulfs, and further supported by a lack of correlation in the similarities of isotope compositions and distances between locations (ρ = 0.16). Fish samples from each of the different locations were composed of multiple year-classes, yet the otolith chemistry distinguished them at a minimum distance of 16 km apart, indicating that small-scale connectivity of L. laticaudis is likely during the majority of their life cycle. Physical barriers to movement of post-settlement individuals (land masses, expansive seagrass and sand) between the small, isolated reefs of Shark Bay may reduce large scale connectivity, which instead would occur mostly by egg and larval dispersal. The probable scale of connectivity of post-settlement L. laticaudis indicates that this major recreational fishing target species may be vulnerable to localised over-exploitation and negative environmental effects on population sources and sinks within this shallow embayment. Maintaining sustainable spawning biomass at scales relevant to the extent of connectivity for such a species in a World Heritage Area is an important management consideration.

Catalytic Aldehyde and Alcohol Arylation Reactions Facilitated by a 1,5-Diaza-3,7-diphosphacyclooctane Ligand.

We report a catalytic method to access secondary alcohols by the coupling of aryl iodides. Either aldehydes or alcohols can be used as reaction partners, making the transformation reductive or redox-neutral, respectively. The reaction is mediated by a Ni catalyst and a 1,5-diaza-3,7-diphosphacyclooctane. This P2N2 ligand, which has previously been unrecognized in cross-coupling and related reactions, was found to avoid deleterious aryl halide reduction pathways that dominate with more traditional phosphines and NHCs. An interrupted carbonyl-Heck type mechanism is proposed to be operative, with a key 1,2-insertion step forging the new C-C bond and forming a nickel alkoxide that may be turned over by an alcohol reductant. The same catalyst was also found to enable synthesis of ketone products from either aldehydes or alcohols, demonstrating control over the oxidation state of both the starting materials and products.

Age, growth and reproductive life-history characteristics infer a high population productivity for the sustainably fished protogynous hermaphroditic yellowspotted rockcod (Epinephelus areolatus) in north-western Australia.

The yellowspotted rockcod, Epinephelus areolatus, is a small-sized grouper that is widely distributed throughout the Indo-Pacific, where it forms a valuable component of the harvest derived from multispecies fisheries along continental and insular shelves. Samples of E. areolatus were collected from 2012 to 2018 from commercial catches and research surveys in the Kimberley, Pilbara and Gascoyne regions of north-western Australia to improve the understanding of the life history, inherent vulnerability and stock status of this species. Histological analysis of gonads (n = 1889) determined that E. areolatus was a monandric protogynous hermaphrodite. Non-functional spermatogenic crypts were dispersed within the ovaries of 23% of mature functioning females; nonetheless, these crypts were not observed during the immature female phase. The length and age at which 50% of females matured were 266 mm total length (LT ) and 2.7 years, respectively. The spawning period was protracted over 10-12 months of the year with biannual peaks at the start of spring and autumn (i.e., September and March) when the photoperiod was at its mid-range (i.e., 12.1 h). Estimates of the lengths and ages at which 50% of E. areolatus change sex from female to male were very similar (i.e., <5% difference) between the Kimberley and Pilbara regions, i.e., L 50 sc of 364 and 349 mm LT and A 50 sc of 7.9 and 7.3 years, respectively. A maximum age of 19 years was observed in all three regions, but there was significant regional variation in growth. These variations in growth were not correlated with latitude; instead a parabolic relationship was evident, where the smallest mean length-at-age and fastest growth rates (k) occurred in the mid-latitudes of the Pilbara region. In the Kimberley and Pilbara regions, individuals were not fully selected by commercial fish traps until 5-6 years of age, hence, several years after reaching maturity. These life-history characteristics infer a high population productivity, which underpins the sustainable harvest of this species, despite comprising the largest catches of all epinephelids in the multispecies tropical fisheries across north-western Australia.

Does the benthic biota or fish assemblage within a large targeted fisheries closure differ to surrounding areas after 12 years of protection in tropical northwestern Australia?

A large (~2450 km2) offshore (~75 km) targeted fisheries closure (TFC) area was implemented on the North West Shelf of Australia (NWS) in 1998 as part of a suite of management controls to address overfishing concerns, and in the process to potentially mitigate any impacts of trawling to benthic habitats. Twelve years later, the benthic biota and fish assemblages in the TFC were assessed using stereo-video and compared with adjacent areas that have been consistently fished with a range of commercial fishing methods. The remote nature of the region has meant that these areas would be inaccessible to recreational fishers. After 12 years of protection there were significant differences between the TFC and comparable fished areas in both the composition and the height of biogenic structures, however the magnitude of these differences were subtle, except for branching soft corals, which were significantly taller in the TFC area. Despite the relatively young age of the TFC, significant differences in the fish abundance and biomass compositions were driven by the slower growing, longer lived and inherently less productive fishery target species. The abundance of Lutjanus sebae (red emperor) and Epinephelus multinotatus (Rankin cod), and the associated biomass of L. sebae and Pristipomoides multidens (goldband snapper) were all greater within the TFC. However, neither the abundance or biomass of the relatively shorter lived and more productive fishery species (e.g. the bluespotted emperor Lethrinus punctulatus and the brownstripe snapper Lutjanus vitta) were greater within the TFC. Growth rates of benthic biota across the NWS are unknown, however the limited detectable differences in benthic biota between the TFC and fished areas, suggests that either recovery of the benthic biota is slow and may not yet be at a threshold for detection and/or alternatively that current fishing activities are not causing adverse impacts to biogenic structures. These large, offshore targeted fishery closures provide a useful reference point to examine the natural variability, growth and recovery of benthic biota and fish assemblages after the cessation of fishing.

A large-scale experiment finds no evidence that a seismic survey impacts a demersal fish fauna.

Seismic surveys are used to locate oil and gas reserves below the seabed and can be a major source of noise in marine environments. Their effects on commercial fisheries are a subject of debate, with experimental studies often producing results that are difficult to interpret. We overcame these issues in a large-scale experiment that quantified the impacts of exposure to a commercial seismic source on an assemblage of tropical demersal fishes targeted by commercial fisheries on the North West Shelf of Western Australia. We show that there were no short-term (days) or long-term (months) effects of exposure on the composition, abundance, size structure, behavior, or movement of this fauna. These multiple lines of evidence suggest that seismic surveys have little impact on demersal fishes in this environment.