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Preparation of cyclohexene isotopologues and stereoisotopomers from benzene 期刊论文
NATURE, 2020, 581 (7808) : 288-+
作者:  Shimazaki, Yuya;  Schwartz, Ido;  Watanabe, Kenji;  Taniguchi, Takashi;  Kroner, Martin;  Imamoglu, Atac
收藏  |  浏览/下载:12/0  |  提交时间:2020/07/03

The hydrogen isotopes deuterium (D) and tritium (T) have become essential tools in chemistry, biology and medicine(1). Beyond their widespread use in spectroscopy, mass spectrometry and mechanistic and pharmacokinetic studies, there has been considerable interest in incorporating deuterium into drug molecules(1). Deutetrabenazine, a deuterated drug that is promising for the treatment of Huntington'  s disease(2), was recently approved by the United States'  Food and Drug Administration. The deuterium kinetic isotope effect, which compares the rate of a chemical reaction for a compound with that for its deuterated counterpart, can be substantial(1,3,4). The strategic replacement of hydrogen with deuterium can affect both the rate of metabolism and the distribution of metabolites for a compound(5), improving the efficacy and safety of a drug. The pharmacokinetics of a deuterated compound depends on the location(s) of deuterium. Although methods are available for deuterium incorporation at both early and late stages of the synthesis of a drug(6,7), these processes are often unselective and the stereoisotopic purity can be difficult to measure(7,8). Here we describe the preparation of stereoselectively deuterated building blocks for pharmaceutical research. As a proof of concept, we demonstrate a four-step conversion of benzene to cyclohexene with varying degrees of deuterium incorporation, via binding to a tungsten complex. Using different combinations of deuterated and proteated acid and hydride reagents, the deuterated positions on the cyclohexene ring can be controlled precisely. In total, 52 unique stereoisotopomers of cyclohexene are available, in the form of ten different isotopologues. This concept can be extended to prepare discrete stereoisotopomers of functionalized cyclohexenes. Such systematic methods for the preparation of pharmacologically active compounds as discrete stereoisotopomers could improve the pharmacological and toxicological properties of drugs and provide mechanistic information related to their distribution and metabolism in the body.


Cyclohexene isotopologues and stereoisotopomers with varying degrees of deuteration are formed by binding a tungsten complex to benzene, which facilitates the selective incorporation of deuterium into any position on the ring.


  
Quantum entanglement between an atom and a molecule 期刊论文
NATURE, 2020, 581 (7808) : 273-+
作者:  Trisos, Christopher H.;  Merow, Cory;  Pigot, Alex L.
收藏  |  浏览/下载:30/0  |  提交时间:2020/07/03

Conventional information processors convert information between different physical carriers for processing, storage and transmission. It seems plausible that quantum information will also be held by different physical carriers in applications such as tests of fundamental physics, quantum enhanced sensors and quantum information processing. Quantum controlled molecules, in particular, could transduce quantum information across a wide range of quantum bit (qubit) frequencies-from a few kilohertz for transitions within the same rotational manifold(1), a few gigahertz for hyperfine transitions, a few terahertz for rotational transitions, to hundreds of terahertz for fundamental and overtone vibrational and electronic transitions-possibly all within the same molecule. Here we demonstrate entanglement between the rotational states of a (CaH+)-Ca-40 molecular ion and the internal states of a Ca-40(+) atomic ion(2). We extend methods used in quantum logic spectroscopy(1,3) for pure-state initialization, laser manipulation and state readout of the molecular ion. The quantum coherence of the Coulomb coupled motion between the atomic and molecular ions enables subsequent entangling manipulations. The qubit addressed in the molecule has a frequency of either 13.4 kilohertz(1) or 855 gigahertz(3), highlighting the versatility of molecular qubits. Our work demonstrates how molecules can transduce quantum information between qubits with different frequencies to enable hybrid quantum systems. We anticipate that our method of quantum control and measurement of molecules will find applications in quantum information science, quantum sensors, fundamental and applied physics, and controlled quantum chemistry.


Quantum entanglement is realized between rotational levels of a molecular ion with energy differences spanning several orders of magnitude and long-lived internal states of a single atomic ion.


  
What can you do to make your lab greener? 期刊论文
NATURE, 2020, 581 (7807) : 228-229
作者:  Dance, Amber;  Mundell, Carole
收藏  |  浏览/下载:0/0  |  提交时间:2020/07/03
Julian Perry Robinson (1941-2020) Obituary 期刊论文
NATURE, 2020, 581 (7809) : 378-378
作者:  Silver, Andrew;  Cyranoski, David
收藏  |  浏览/下载:9/0  |  提交时间:2020/07/03

Chemist and lawyer who shaped international weapons conventions.


Chemist and lawyer who shaped international weapons conventions.


  
Elixirs for times of plague and bullion shortage 期刊论文
NATURE, 2020, 580 (7805) : 584-585
作者:  Grant, Monica
收藏  |  浏览/下载:0/0  |  提交时间:2020/07/03

Spectacular alchemical scrolls record ideas of flux in times of massive upheaval - medical, social, economic and political. By Jennifer Rampling.


Spectacular alchemical scrolls record ideas of flux in times of massive upheaval - medical, social, economic and political.


  
Automated synthesis on a hub-and-spoke system 期刊论文
NATURE, 2020, 579 (7799) : 346-348
作者:  Bae-Jump, Victoria L.;  Levine, Douglas A.
收藏  |  浏览/下载:7/0  |  提交时间:2020/07/03

A non-linear platform for flow chemistry.


Organic compounds can be synthesized in a continuous flow of solutions, but the need to balance mass flow across multiple reactors complicates the development of such systems. A new platform for flow chemistry addresses this issue.


  
Elixirs for times of plague and bullion shortage 期刊论文
NATURE, 2020, 580 (7805) : 592-593
作者:  Gibney, Elizabeth
收藏  |  浏览/下载:5/0  |  提交时间:2020/07/03

The addition of a methyl group to a drug molecule can greatly alter the drug'  s pharmacological properties. A catalyst has been developed that enables this '  magic methyl effect'  to be rapidly explored for drug discovery.


Late-stage functionalization of complex organic molecules.


  
Collisional cooling of ultracold molecules 期刊论文
NATURE, 2020, 580 (7802) : 197-+
作者:  Wang, Qinyang;  Wang, Yupeng;  Ding, Jingjin;  Wang, Chunhong;  Zhou, Xuehan;  Gao, Wenqing;  Huang, Huanwei;  Shao, Feng;  Liu, Zhibo
收藏  |  浏览/下载:11/0  |  提交时间:2020/07/03

Since the original work on Bose-Einstein condensation(1,2), the use of quantum degenerate gases of atoms has enabled the quantum emulation of important systems in condensed matter and nuclear physics, as well as the study of many-body states that have no analogue in other fields of physics(3). Ultracold molecules in the micro- and nanokelvin regimes are expected to bring powerful capabilities to quantum emulation(4) and quantum computing(5), owing to their rich internal degrees of freedom compared to atoms, and to facilitate precision measurement and the study of quantum chemistry(6). Quantum gases of ultracold atoms can be created using collision-based cooling schemes such as evaporative cooling, but thermalization and collisional cooling have not yet been realized for ultracold molecules. Other techniques, such as the use of supersonic jets and cryogenic buffer gases, have reached temperatures limited to above 10 millikelvin(7,8). Here we show cooling of NaLi molecules to micro- and nanokelvin temperatures through collisions with ultracold Na atoms, with both molecules and atoms prepared in their stretched hyperfine spin states. We find a lower bound on the ratio of elastic to inelastic molecule-atom collisions that is greater than 50-large enough to support sustained collisional cooling. By employing two stages of evaporation, we increase the phase-space density of the molecules by a factor of 20, achieving temperatures as low as 220 nanokelvin. The favourable collisional properties of the Na-NaLi system could enable the creation of deeply quantum degenerate dipolar molecules and raises the possibility of using stretched spin states in the cooling of other molecules.


NaLi molecules are cooled to micro- and nanokelvin temperatures through collisions with ultracold Na atoms by using molecules and atoms in stretched hyperfine spin states and applying two evaporation stages.


  
Nightside condensation of iron in an ultrahot giant exoplanet 期刊论文
NATURE, 2020, 580 (7805) : 597-+
作者:  Lu, Zhihao;  Zou, Jianling;  Li, Shuang;  Topper, Michael J.;  Tao, Yong;  Zhang, Hao;  Jiao, Xi;  Xie, Wenbing;  Kong, Xiangqian;  Vaz, Michelle;  Li, Huili;  Cai, Yi;  Xia, Limin;  Huang, Peng;  Rodgers, Kristen;  Lee, Beverly;  Riemer, Joanne B.;  Day, Chi-Ping;  Yen, Ray-Whay Chiu;  Cui, Ying;  Wang, Yujiao;  Wang, Yanni;  Zhang, Weiqiang;  Easwaran, Hariharan;  Hulbert, Alicia;  Kim, KiBem;  Juergens, Rosalyn A.;  Yang, Stephen C.;  Battafarano, Richard J.;  Bush, Errol L.;  Broderick, Stephen R.;  Cattaneo, Stephen M.;  Brahmer, Julie R.;  Rudin, Charles M.;  Wrangle, John;  Mei, Yuping;  Kim, Young J.;  Zhang, Bin;  Wang, Ken Kang-Hsin;  Forde, Patrick M.;  Margolick, Joseph B.;  Nelkin, Barry D.;  Zahnow, Cynthia A.;  Pardoll, Drew M.;  Housseau, Franck;  Baylin, Stephen B.;  Shen, Lin;  Brock, Malcolm V.
收藏  |  浏览/下载:58/0  |  提交时间:2020/07/03

Ultrahot giant exoplanets receive thousands of times Earth'  s insolation(1,2). Their high-temperature atmospheres (greater than 2,000 kelvin) are ideal laboratories for studying extreme planetary climates and chemistry(3-5). Daysides are predicted to be cloud-free, dominated by atomic species(6) and much hotter than nightsides(5,7,8). Atoms are expected to recombine into molecules over the nightside(9), resulting in different day and night chemistries. Although metallic elements and a large temperature contrast have been observed(10-14), no chemical gradient has been measured across the surface of such an exoplanet. Different atmospheric chemistry between the day-to-night ('  evening'  ) and night-to-day ('  morning'  ) terminators could, however, be revealed as an asymmetric absorption signature during transit(4,7,15). Here we report the detection of an asymmetric atmospheric signature in the ultrahot exoplanet WASP-76b. We spectrally and temporally resolve this signature using a combination of high-dispersion spectroscopy with a large photon-collecting area. The absorption signal, attributed to neutral iron, is blueshifted by -11 +/- 0.7 kilometres per second on the trailing limb, which can be explained by a combination of planetary rotation and wind blowing from the hot dayside(16). In contrast, no signal arises from the nightside close to the morning terminator, showing that atomic iron is not absorbing starlight there. We conclude that iron must therefore condense during its journey across the nightside.


Absorption lines of iron in the dayside atmosphere of an ultrahot giant exoplanet disappear after travelling across the nightside, showing that the iron has condensed during its travel.


  
Automated radial synthesis of organic molecules 期刊论文
NATURE, 2020, 579 (7799) : 379-+
作者:  van den Brink, Susanne C.;  Alemany, Anna;  van Batenburg, Vincent;  Moris, Naomi;  Blotenburg, Marloes;  Vivie, Judith;  Baillie-Johnson, Peter;  Nichols, Jennifer;  Sonnen, Katharina F.;  Martinez Arias, Alfonso;  van Oudenaarden, Alexander
收藏  |  浏览/下载:16/0  |  提交时间:2020/07/03

An automated synthesis instrument comprising a series of continuous flow modules that are radially arranged around a central switching station can achieve both linear and convergent syntheses.


Automated synthesis platforms accelerate and simplify the preparation of molecules by removing the physical barriers to organic synthesis. This provides unrestricted access to biopolymers and small molecules via reproducible and directly comparable chemical processes. Current automated multistep syntheses rely on either iterative(1-4) or linear processes(5-9), and require compromises in terms of versatility and the use of equipment. Here we report an approach towards the automated synthesis of small molecules, based on a series of continuous flow modules that are radially arranged around a central switching station. Using this approach, concise volumes can be exposed to any reaction conditions required for a desired transformation. Sequential, non-simultaneous reactions can be combined to perform multistep processes, enabling the use of variable flow rates, reuse of reactors under different conditions, and the storage of intermediates. This fully automated instrument is capable of both linear and convergent syntheses and does not require manual reconfiguration between different processes. The capabilities of this approach are demonstrated by performing optimizations and multistep syntheses of targets, varying concentrations via inline dilutions, exploring several strategies for the multistep synthesis of the anticonvulsant drug rufinamide(10), synthesizing eighteen compounds of two derivative libraries that are prepared using different reaction pathways and chemistries, and using the same reagents to perform metallaphotoredox carbon-nitrogen cross-couplings(11) in a photochemical module-all without instrument reconfiguration.