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Abstract We describe a bundle for UCSF ChimeraX called SEQCROW that provides advanced structure editing capabilities and quantum chemistry utilities designed for complex organic and organometallic compounds. SEQCROW includes graphical presets and bond editing tools that facilitate the generation of publication‐quality molecular structure figures while also allowing users to build molecular structures quickly and efficiently by mapping new ligands onto existing organometallic complexes as well as adding rings and substituents. Other capabilities include the ability to visualize vibrational modes and simulated IR spectra, to compute and visualize molecular descriptors including percent buried volume, ligand cone angles, and Sterimol parameters, to process thermochemical corrections from quantum mechanical computations, to generate input files for ORCA, Psi4, and Gaussian, and to run and manage computational jobs. 

Abstract There is an urgent need for new antibiotics to mitigate the existential threat posed by antibiotic resistance. Within the ketolide class, solithromycin has emerged as one of the most promising candidates for further development. Crystallographic studies of bacterial ribosomes and ribosomal subunits complexed with solithromycin have shed light on the nature of molecular interactions (π‐stacking and H‐bonding) between from the biaryl side‐chain of the drug and key residues in the 50S ribosomal subunit. We have designed and synthesized a library of solithromycin analogs to study their structure‐activity relationships (SAR) in tandem with new computational studies. The biological activity of each analog was evaluated in terms of ribosomal affinity (K_ddetermined by fluorescence polarization), as well as minimum inhibitory concentration assays (MICs). Density functional theory (DFT) studies of a simple binding site model identify key H‐bonding interactions that modulate the potency of solithromycin analogs. 

Abstract As the tools of computational quantum chemistry have continued to mature, larger and more complex molecular systems have become amenable to computational study. However, studies of these complex systems often require the execution of enormous numbers of computations, which can be a tedious and error‐prone process if done manually. We have developed a suite of free, open‐source tools to facilitate the automation of quantum chemistry workflows. These tools are collected under the organization QChASM (Quantum Chemistry Automation and Structure Manipulation) and include functionality for building and manipulating complex molecular structures and performing routine tasks (AaronTools), a toolkit for automating TS optimizations and predictions of the outcomes of selective homogeneous catalytic reactions, and a plug‐in for UCSF ChimeraX that provides a graphical interface for building complex molecular structures and representing output from quantum chemistry computations. These tools are described below, with a focus on the recent Python implementation of AaronTools. This article is categorized under:Structure and Mechanism > Reaction Mechanisms and CatalysisSoftware > Quantum Chemistry 

Abstract The design of catalysts for asymmetric propargylations remains a challenging task, with only a handful of methods providing access to enantioenriched homopropargylic alcohols. In this work, guided by previously reported computational predictions, a set of atropisomeric bipyridineN,N’‐dioxides was tested as Lewis base catalysts for the asymmetric propargylation of aldehydes with trichloroallenylsilane. The catalysts are easily prepared in four simple steps starting from readily available methyl ketones. Aryl‐substituted derivatives proved to be highly active and showed a high level of enantiocontrol even at 1 mol% loading. The reaction scope includes a wide range of aromatic, heteroaromatic, and unsaturated aldehydes. New computations confirm that the key stereodetermining transition state structures for the synthesized catalysts are similar to those previously reported for the model structure. magnified image 

Automated transition state (TS) structure computations for a recently reported Pd-catalysed conjugated addition of arylboronic acids to 2-substituted chromones (D. Baek, H. Ryu, J. Y. Ryu, J. Lee, B. M. Stoltz and S. Hong, Chem. Sci. , 2020, 11 , 4602–4607) reveal unexpected conformations of the key stereodifferentiating benzyl group on the pyridine-dihydroisoquinoline (PyDHIQ) ligand. Detailed analysis shows that stereoselectivity is determined primarily by favourable non-covalent contacts between this benzyl group and the substrates, combined with torsional strain in the primary TS structure leading to the minor stereoisomer. This finding should inform further use and analysis of PyDHIQ and related ligands in other stereoselective transformations. 

Chiral phosphoric acids (CPAs) have emerged as powerful organocatalysts for asymmetric reactions, and applications of computational quantum chemistry have revealed important insights into the activity and selectivity of these catalysts. In this tutorial review, we provide an overview of computational tools at the disposal of computational organic chemists and demonstrate their application to a wide array of CPA catalysed reactions. Predictive models of the stereochemical outcome of these reactions are discussed along with specific examples of representative reactions and an outlook on remaining challenges in this area.