Synthesis of the Key Intermediate of SM-406 (Xevinapant) and Its Analogues.

Efficient methods for the synthesis of three dipeptide mimetics with diazabicycloalkanone amino acid scaffolds were developed. Among them, compound 3, which contains a 1,5-diazabicyclo[6,3,0]dodecanone amino acid core structure, was used as the key intermediate of a clinical staged IAP inhibitor SM-406 (Xevinapant). Compared with the reported methods for the synthesis of compound 3 and its derivatives, our method is more efficient and more suitable for large scale preparation.

Halogen Radicals Contribute to the Halogenation and Degradation of Chemical Additives Used in Hydraulic Fracturing.

In hydraulic fracturing fluids, the oxidant persulfate is used to generate sulfate radical to break down polymer-based gels. However, sulfate radical may be scavenged by high concentrations of halides in hydraulic fracturing fluids, producing halogen radicals (e.g., Cl•, Cl2•-, Br•, Br2•-, and BrCl•-). In this study, we investigated how halogen radicals alter the mechanisms and kinetics of the degradation of organic chemicals in hydraulic fracturing fluids. Using a radical scavenger (i.e., isopropanol), we determined that halogenated products of additives such as cinnamaldehyde (i.e., α-chlorocinnamaldehyde and α-bromocinnamaldehyde) and citrate (i.e., trihalomethanes) were generated via a pathway involving halogen radicals. We next investigated the impact of halogen radicals on cinnamaldehyde degradation rates. The conversion of sulfate radicals to halogen radicals may result in selective degradation of organic compounds. Surprisingly, we found that the addition of halides to convert sulfate radicals to halogen radicals did not result in selective degradation of cinnamaldehyde over other compounds (i.e., benzoate and guar), which may challenge the application of radical selectivity experiments to more complex molecules. Overall, we find that halogen radicals, known to react in advanced oxidative treatment and sunlight photochemistry, also contribute to the unintended degradation and halogenation of additives in hydraulic fracturing fluids.

Erratum: Multimode Kapitza-Dirac Interferometry with Trapped Cold Atoms [Phys. Rev. Lett. 113, 023003 (2014)].

This corrects the article DOI: 10.1103/PhysRevLett.113.023003.

Multimode Kapitza-Dirac interferometry with trapped cold atoms.

We design a multimode interferometer with cold atoms confined in a harmonic trap. A first Kapitza-Dirac pulse creates several spatially addressable modes which are coherently recombined by the harmonic potential and mixed again by a second Kapitza-Dirac pulse. A phase shift among the mode is estimated by fitting the density profile or by measuring the number of atoms in each output mode. The expected sensitivity is rigorously calculated with the Fisher information and the Cramér-Rao lower bound. For the measurement of the gravitational acceleration g we predict, with typical parameters of a compact setup, a temperature independent sensitivity which can exceed, by several orders of magnitude, the sensitivity of current atomic interferometers.

Repeated pulses of volcanism drove the end-Permian terrestrial crisis in northwest China.

The Permo-Triassic mass extinction was linked to catastrophic environmental changes and large igneous province (LIP) volcanism. In addition to the widespread marine losses, the Permo-Triassic event was the most severe terrestrial ecological crisis in Earth's history and the only known mass extinction among insects, but the cause of extinction on land remains unclear. In this study, high-resolution Hg concentration records and multiple-archive S-isotope analyses of sediments from the Junggar Basin (China) provide evidence of repeated pulses of volcanic-S (acid rain) and increased Hg loading culminating in a crisis of terrestrial biota in the Junggar Basin coeval with the interval of LIP emplacement. Minor S-isotope analyses are, however, inconsistent with total ozone layer collapse. Our data suggest that LIP volcanism repeatedly stressed end-Permian terrestrial environments in the ~300 kyr preceding the marine extinction locally via S-driven acidification and deposition of Hg, and globally via pulsed addition of CO2.

An enormous sulfur isotope excursion indicates marine anoxia during the end-Triassic mass extinction.

The role of ocean anoxia as a cause of the end-Triassic marine mass extinction is widely debated. Here, we present carbonate-associated sulfate δ34S data from sections spanning the Late Triassic-Early Jurassic transition, which document synchronous large positive excursions on a global scale occurring in ~50 thousand years. Biogeochemical modeling demonstrates that this S isotope perturbation is best explained by a fivefold increase in global pyrite burial, consistent with large-scale development of marine anoxia on the Panthalassa margin and northwest European shelf. This pyrite burial event coincides with the loss of Triassic taxa seen in the studied sections. Modeling results also indicate that the pre-event ocean sulfate concentration was low (<1 millimolar), a common feature of many Phanerozoic deoxygenation events. We propose that sulfate scarcity preconditions oceans for the development of anoxia during rapid warming events by increasing the benthic methane flux and the resulting bottom-water oxygen demand.

Possible links between extreme oxygen perturbations and the Cambrian radiation of animals.

The role of oxygen as a driver for early animal evolution is widely debated. During the Cambrian explosion, episodic radiations of major animal phyla occurred coincident with repeated carbon isotope fluctuations. However, the driver of these isotope fluctuations and potential links to environmental oxygenation are unclear. Here, we report high-resolution carbon and sulphur isotope data for marine carbonates from the southeastern Siberian Platform that document the canonical explosive phase of the Cambrian radiation from ~524 to ~514 Myr ago. These analyses demonstrate a strong positive covariation between carbonate δ13C and carbonate-associated sulphate δ34S through five isotope cycles. Biogeochemical modelling suggests that this isotopic coupling reflects periodic oscillations in atmospheric O2 and the extent of shallow ocean oxygenation. Episodic maxima in the biodiversity of animal phyla directly coincided with these extreme oxygen perturbations. Conversely, the subsequent Botoman-Toyonian animal extinction events (~514 to ~512 Myr ago) coincided with decoupled isotope records that suggest a shrinking marine sulphate reservoir and expanded shallow marine anoxia. We suggest that fluctuations in oxygen availability in the shallow marine realm exerted a primary control on the timing and tempo of biodiversity radiations at a crucial phase in the early history of animal life.

Coupling of ocean redox and animal evolution during the Ediacaran-Cambrian transition.

The late Ediacaran to early Cambrian interval witnessed extraordinary radiations of metazoan life. The role of the physical environment in this biological revolution, such as changes to oxygen levels and nutrient availability, has been the focus of longstanding debate. Seemingly contradictory data from geochemical redox proxies help to fuel this controversy. As an essential nutrient, nitrogen can help to resolve this impasse by establishing linkages between nutrient supply, ocean redox, and biological changes. Here we present a comprehensive N-isotope dataset from the Yangtze Basin that reveals remarkable coupling between δ15N, δ13C, and evolutionary events from circa 551 to 515 Ma. The results indicate that increased fixed nitrogen supply may have facilitated episodic animal radiations by reinforcing ocean oxygenation, and restricting anoxia to near, or even at the sediment-water interface. Conversely, sporadic ocean anoxic events interrupted ocean oxygenation, and may have led to extinctions of the Ediacaran biota and small shelly animals.

Publisher Correction: Coupling of ocean redox and animal evolution during the Ediacaran-Cambrian transition.

The original version of this Article incorrectly gave the second address in the list of affiliations as "State Key Laboratory of Palaeobiology and Stratigraphy & Center for Excellence in Life and Paleoenvironment, Nanjing Institute of Geology and Palaeontology, Chinese Academy of Sciences, 210008 Nanjing, China", instead of the correct 'State Key Laboratory for Mineral Deposits Research, School of Earth Sciences and Engineering, Nanjing University, Nanjing 210023, China". This has been corrected in both the PDF and HTML versions of the Article.