Synthesis of a Sterically Encumbered Pincer Au(III)−OH Complex

We report the synthesis and crystallographic characterization of a novel Au(III)−OH complex featuring a N^N^N-pincer ligand. Reactivity studies towards oxygen atom transfer (OAT), a type of reactivity previously reported for a Au(III)−OH complex, indicate that this complex provides both a sterically encumbered Au atom and a sterically poorly accessible OH group leading to no reactivity with a series of phosphines. The steric encumbrance sets this example apart from the known examples of Au(III)−OH (pincer) complexes, which commonly feature planar ligands that provide little control over steric accessibility of the Au and O atoms in these complexes. Implications for the mechanism of OAT from Au−OH complexes are briefly discussed

CCDC 2053430: Experimental Crystal Structure Determination

Related Article: Silène Engbers, Evgeniya A. Trifonova, Kristopher M. Hess, Folkert Vries, Johannes E. M. N. Klein|2021|Eur.J.Inorg.Chem.|2021|3561|doi:10.1002/ejic.20210030

Gold(III) Catalyzed Overman Rearrangements: Controlling Steric Interactions using Pincer-Type Ligands

Spatial control of reactivity is intrinsically difficult in gold catalysis due to the linear coordination mode of Au(I) and the commonly flat ligands employed for Au(III) complexes. Our recent report of a novel and sterically encumbered (NNN)diiPrAu−OH complex (Eur. J. Inorg. Chem. 2021, 3561–3564.) suggested that the (NNN) ligand framework is capable of sterically interacting with substrates through its conveniently oriented aryl groups. We have now examined these steric properties in more detail by varying the ortho-substituent of the aryl group in (NNN)xAu−Cl complexes. With just small modifications we were able to vary the buried volume around the Cl atom and correlate this to yields obtained in a Au-catalyzed Overman rearrangement. Computationally we further elucidate that the stark difference in yields obtained originates from a shift in binding mode of the substrate to the Au catalyst in the rate limiting step of the reaction. We thus conclude that delicate spatial control can be exercised in gold catalysis and propose the (NNN) ligand framework to be an attractive platform for the efficient design of Au(III) complexes for stereoselective catalysis

CCDC 2053431: Experimental Crystal Structure Determination

Related Article: Silène Engbers, Evgeniya A. Trifonova, Kristopher M. Hess, Folkert Vries, Johannes E. M. N. Klein|2021|Eur.J.Inorg.Chem.|2021|3561|doi:10.1002/ejic.20210030

Influence of C-5 substituted cytosine and related nucleoside analogs on the formation of benzo[a]pyrene diol epoxide-dG adducts at CG base pairs of DNA

Endogenous 5-methylcytosine ((Me)C) residues are found at all CG dinucleotides of the p53 tumor suppressor gene, including the mutational ‘hotspots’ for smoking induced lung cancer. (Me)C enhances the reactivity of its base paired guanine towards carcinogenic diolepoxide metabolites of polycyclic aromatic hydrocarbons (PAH) present in cigarette smoke. In the present study, the structural basis for these effects was investigated using a series of unnatural nucleoside analogs and a representative PAH diolepoxide, benzo[a]pyrene diolepoxide (BPDE). Synthetic DNA duplexes derived from a frequently mutated region of the p53 gene (5′-CCCGGCACCC GC[(15)N(3),(13)C(1)-G]TCCGCG-3′, + strand) were prepared containing [(15)N(3), (13)C(1)]-guanine opposite unsubstituted cytosine, (Me)C, abasic site, or unnatural nucleobase analogs. Following BPDE treatment and hydrolysis of the modified DNA to 2′-deoxynucleosides, N(2)-BPDE-dG adducts formed at the [(15)N(3), (13)C(1)]-labeled guanine and elsewhere in the sequence were quantified by mass spectrometry. We found that C-5 alkylcytosines and related structural analogs specifically enhance the reactivity of the base paired guanine towards BPDE and modify the diastereomeric composition of N(2)-BPDE-dG adducts. Fluorescence and molecular docking studies revealed that 5-alkylcytosines and unnatural nucleobase analogs with extended aromatic systems facilitate the formation of intercalative BPDE–DNA complexes, placing BPDE in a favorable orientation for nucleophilic attack by the N(2) position of guanine

Federated learning for predicting clinical outcomes in patients with COVID-19

Federated learning (FL) is a method used for training artificial intelligence models with data from multiple sources while maintaining data anonymity, thus removing many barriers to data sharing. Here we used data from 20 institutes across the globe to train a FL model, called EXAM (electronic medical record (EMR) chest X-ray AI model), that predicts the future oxygen requirements of symptomatic patients with COVID-19 using inputs of vital signs, laboratory data and chest X-rays. EXAM achieved an average area under the curve (AUC) >0.92 for predicting outcomes at 24 and 72 h from the time of initial presentation to the emergency room, and it provided 16% improvement in average AUC measured across all participating sites and an average increase in generalizability of 38% when compared with models trained at a single site using that site's data. For prediction of mechanical ventilation treatment or death at 24 h at the largest independent test site, EXAM achieved a sensitivity of 0.950 and specificity of 0.882. In this study, FL facilitated rapid data science collaboration without data exchange and generated a model that generalized across heterogeneous, unharmonized datasets for prediction of clinical outcomes in patients with COVID-19, setting the stage for the broader use of FL in healthcare

Firefly: The Case for a Holistic Understanding of the Global Structure and Dynamics of the Sun and the Heliosphere

This white paper is on the HMCS Firefly mission concept study. Firefly focuses on the global structure and dynamics of the Sun's interior, the generation of solar magnetic fields, the deciphering of the solar cycle, the conditions leading to the explosive activity, and the structure and dynamics of the corona as it drives the heliosphere