The TRENDS High-Contrast Imaging Survey. VI. Discovery of a Mass, Age, and Metallicity Benchmark Brown Dwarf

The mass and age of substellar objects are degenerate parameters leaving the evolutionary state of brown dwarfs ambiguous without additional information. Theoretical models are normally used to help distinguish between old, massive brown dwarfs and young, low mass brown dwarfs but these models have yet to be properly calibrated. We have carried out an infrared high-contrast imaging program with the goal of detecting substellar objects as companions to nearby stars to help break degeneracies in inferred physical properties such as mass, age, and composition. Rather than using imaging observations alone, our targets are pre-selected based on the existence of dynamical accelerations informed from years of stellar radial velocity (RV) measurements. In this paper, we present the discovery of a rare benchmark brown dwarf orbiting the nearby ($d=18.69\pm0.19$ pc), solar-type (G9V) star HD 4747 ([Fe/H]=$-0.22\pm0.04$) with a projected separation of only $\rho=11.3\pm0.2$ AU ($\theta \approx$ 0.6"). Precise Doppler measurements taken over 18 years reveal the companion's orbit and allow us to place strong constraints on its mass using dynamics ($m \sin(i) = 55.3\pm1.9M_J$). Relative photometry ($\Delta K_s=9.05\pm0.14$, $M_{K_s}=13.00\pm0.14$, $K_s - L' = 1.34\pm0.46$) indicates that HD 4747 B is most-likely a late-type L-dwarf and, if near the L/T transition, an intriguing source for studying cloud physics, variability, and polarization. We estimate a model-dependent mass of $m=72^{+3}_{-13}M_J$ for an age of $3.3^{+2.3}_{-1.9}$ Gyr based on gyrochronology. Combining astrometric measurements with RV data, we calculate the companion dynamical mass ($m=60.2\pm3.3M_J$) and orbit ($e=0.740\pm0.002$) directly. As a new mass, age, and metallicity benchmark, HD 4747 B will serve as a laboratory for precision astrophysics to test theoretical models that describe the emergent radiation of brown dwarfs.Comment: Accepted to Ap

Enzyme-like Acyl Transfer Catalysis in a Bifunctional Organic Cage

Amide-based organic cage cavities are, in principle, ideal enzyme active site mimics. Yet, cage-promoted organocatalysis has remained elusive, in large part due to synthetic accessibility of robust and functional scaffolds. Herein, we report the acyl transfer catalysis properties of robust, hexaamide cages in organic solvent. Cage structural variation reveals that esterification catalysis with an acyl anhydride acyl carrier occurs only in bifunctional cages featuring internal pyridine motifs and two crucial antipodal carboxylic acid groups. H NMR data and X-ray crystallography show that the acyl carrier is rapidly activated inside the cavity as a covalent mixed-anhydride intermediate with an internal hydrogen bond. Michaelis-Menten (saturation) kinetics suggest weak binding ( = 0.16 M) of the alcohol pronucleophile close to the internal anhydride. Finally, activation and delivery of the alcohol to the internal anhydride by the second carboxylic acid group forms ester product and releases the cage catalyst. Eyring analysis indicates a strong enthalpic stabilization of the transition state (5.5 kcal/mol) corresponding to a rate acceleration of 10 over background acylation, and an ordered, associative rate-determining attack by the alcohol, supported by DFT calculations. We conclude that internal bifunctional organocatalysis specific to the cage structural design is responsible for the enhancement over the background reaction. These results pave the way for organic-phase enzyme mimicry in self-assembled cavities with the potential for cavity elaboration to enact selective acylations

Computational Modeling of Supramolecular Metallo-organic Cages-Challenges and Opportunities

[Image: see text] Self-assembled metallo-organic cages have emerged as promising biomimetic platforms that can encapsulate whole substrates akin to an enzyme active site. Extensive experimental work has enabled access to a variety of structures, with a few notable examples showing catalytic behavior. However, computational investigations of metallo-organic cages are scarce, not least due to the challenges associated with their modeling and the lack of accurate and efficient protocols to evaluate these systems. In this review, we discuss key molecular principles governing the design of functional metallo-organic cages, from the assembly of building blocks through binding and catalysis. For each of these processes, computational protocols will be reviewed, considering their inherent strengths and weaknesses. We will demonstrate that while each approach may have its own specific pitfalls, they can be a powerful tool for rationalizing experimental observables and to guide synthetic efforts. To illustrate this point, we present several examples where modeling has helped to elucidate fundamental principles behind molecular recognition and reactivity. We highlight the importance of combining computational and experimental efforts to speed up supramolecular catalyst design while reducing time and resources

Origins of High-Activity Cage-Catalyzed Michael Addition

Cage catalysis continues to create significant interest, yet catalyst function remains poorly understood. Herein, we report mechanistic insights into coordination-cage-catalyzed Michael addition using kinetic and computational methods. The study has been enabled by the detection of identifiable catalyst intermediates, which allow the evolution of different cage species to be monitored and modeled alongside reactants and products. The investigations show that the overall acceleration results from two distinct effects. First, the cage reaction shows a thousand-fold increase in the rate constant for the turnover-limiting C–C bond-forming step compared to a reference state. Computational modeling and experimental analysis of activation parameters indicate that this stems from a significant reduction in entropy, suggesting substrate coencapsulation. Second, the cage markedly acidifies the bound pronucleophile, shifting this equilibrium by up to 6 orders of magnitude. The combination of these two factors results in accelerations up to 109 relative to bulk-phase reference reactions. We also show that the catalyst can fundamentally alter the reaction mechanism, leading to intermediates and products that are not observable outside of the cage. Collectively, the results show that cage catalysis can proceed with very high activity and unique selectivity by harnessing a series of individually weak noncovalent interactions

P53 IMMUNOHISTOCHEMISTRY AS A SURROGATE FOR TP53 MUTATIONAL ANALYSIS IN ENDOMETRIAL CANCER BIOPSIES

Meeting abstract from 17th Biennial Meeting of the International Gynecologic Cancer Society Kyoto, Japan September 14-16, 201

Zirconium-based metal–organic frameworks as acriflavine cargos in the battle against coronaviruses : a theoretical and experimental approach

[Image: see text] In this study, we present a complementary approach for obtaining an effective drug, based on acriflavine (ACF) and zirconium-based metal–organic frameworks (MOFs), against SARS-CoV-2. The experimental results showed that acriflavine inhibits the interaction between viral receptor-binding domain (RBD) of spike protein and angiotensin converting enzyme-2 (ACE2) host receptor driving viral cell entry. The prepared ACF@MOF composites exhibited low (MOF-808 and UiO-66) and high (UiO-67 and NU-1000) ACF loadings. The drug release profiles from prepared composites showed different release kinetics depending on the local pore environment. The long-term ACF release with the effective antiviral ACF concentration was observed for all studied ACF@MOF composites. The density functional theory (DFT) calculations allowed us to determine that π–π stacking together with electrostatic interaction plays an important role in acriflavine adsorption and release from ACF@MOF composites. The molecular docking results have shown that acriflavine interacts with several possible binding sites within the RBD and binding site at the RBD/ACE2 interface. The cytotoxicity and ecotoxicity results have confirmed that the prepared ACF@MOF composites may be considered potentially safe for living organisms. The complementary experimental and theoretical results presented in this study have confirmed that the ACF@MOF composites may be considered a potential candidate for the COVID-19 treatment, which makes them good candidates for clinical trials

Exoplanet phase curves: observations and theory

Phase curves are the best technique to probe the three dimensional structure of exoplanets' atmospheres. In this chapter we first review current exoplanets phase curve observations and the particular challenges they face. We then describe the different physical mechanisms shaping the atmospheric phase curves of highly irradiated tidally locked exoplanets. Finally, we discuss the potential for future missions to further advance our understanding of these new worlds.Comment: Fig.5 has been updated. Table 1 and corresponding figures have been updated with new values for WASP-103b and WASP-18b. Contains a table sumarizing phase curve observation