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Article
Open AccessUnequivocal identification of two-bond heteronuclear correlations in natural products at nanomole scale by i-HMBC
HMBC is an essential NMR experiment for determining multiple bond heteronuclear correlations in small to medium-sized organic molecules, including natural products, yet its major limitation is the inability to...
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Article
The merger of decatungstate and copper catalysis to enable aliphatic C(sp3)–H trifluoromethylation
The introduction of a trifluoromethyl (CF3) group can dramatically improve a compound’s biological properties. Despite the well-established importance of trifluoromethylated compounds, general methods for the tri...
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Article
The PMI Predictor app to enable green-by-design chemical synthesis
The development of sustainable processes for the synthesis of new clinical candidates is a priority for every pharmaceutical company. The ultimate efficiency of a molecule’s synthesis results from a combinatio...
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Article
Open AccessComplex macrocycle exploration: parallel, heuristic, and constraint-based conformer generation using ForceGen
ForceGen is a template-free, non-stochastic approach for 2D to 3D structure generation and conformational elaboration for small molecules, including both non-macrocycles and macrocycles. For conformational sea...
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Article
Mechanistic Study of the Gas-Phase In-Source Hofmann Elimination of Doubly Quaternized Cinchona-Alkaloid Based Phase-Transfer Catalysts by (+)-Electrospray Ionization/Tandem Mass Spectrometry
An unusual in-source fragmentation pattern observed for 14 doubly quaternized cinchona alkaloid-based phase-transfer catalysts (PTC) was studied using (+)-ESI high resolution mass spectrometry. Loss of the sub...
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Article
The evolution of drug design at Merck Research Laboratories
On October 5, 1981, Fortune magazine published a cover article entitled the “Next Industrial Revolution: Designing Drugs by Computer at Merck”. With a 40+ year investment, we have been in the drug design busin...
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Article
Structural and dynamic variations in DNA hexamers containing T-T and F-F single and tandem internal mispairs
Molecular dynamics simulations of double-helical DNA oligomers have been performed to investigate differences in the structure, dynamics, and hydration of F-F and T-T mispairs. Hexamers containing F-F pairs we...
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Article
A Semiempirical Transition State Structure for the First Step in the Alkaline Hydrolysis of Cocaine. Comparison between the Transition State Structure, the Phosphonate Monoester Transition State Analog, and a Newly Designed Thiophosphonate Transition State Analog
Semiempirical molecular orbital calculations have been performed for the first step in the alkaline hydrolysis of the neutral benzoylester of cocaine. Successes, failures, and limitations of these calculations...
