Acoustic Droplet Ejection Enabled Automated Reaction Scouting

Miniaturization and acceleration of synthetic chemistry are critically important for rapid property optimization in pharmaceutical, agrochemical, and materials research and development. However, in most laboratories organic synthesis is still performed on a slow, sequential, and material-consuming scale and not validated for multiple substrate combinations. Herein, we introduce fast and touchless acoustic droplet ejection (ADE) technology into small-molecule chemistry to transfer building blocks by nL droplets and to scout a newly designed isoquinoline synthesis. With each compound in a discrete well, 384 random derivatives were synthesized in an automated fashion, and their quality was monitored by SFC-MS and TLC-UV-MS analysis. We exemplify a pipeline of fast and efficient nmol scouting to mmol- and mol-scale synthesis for the discovery of a useful novel reaction with great scope

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Beyond Scientific Visualization: Mapping Information

The term "scientific visualization" conjures up mental images of molecules reacting or velocity vectors whizzing around. Yet, visualization is migrating beyond the scientific domain because it maps not only numerical, but all data into visual representations. This panel compares several visualization methodologies and how they have employed advanced computer graphics to map abstract information into meaningful animations and interactive software. Panelists demonstrate how they have organized abstract data or concepts using spatial, quantitative, dynamic, and symbolic techniques to visually communicate maximum information. Examples from linguistics, humanities, education, statistics, engineering, and science are presented

Beyond Scientific Visualization: Mapping Information

The term "scientific visualization" conjures up mental images of molecules reacting or velocity vectors whizzing around. Yet, visualization is migrating beyond the scientific domain because it maps not only numerical, but all data into visual representations. This panel compares several visualization methodologies and how they have employed advanced computer graphics to map abstract information into meaningful animations and interactive software. Panelists demonstrate how they have organized abstract data or concepts using spatial, quantitative, dynamic, and symbolic techniques to visually communicate maximum information. Examples from linguistics, humanities, education, statistics, engineering, and science are presented

Automated and Accelerated Synthesis of Indole Derivatives on a Nano-Scale

Automated, miniaturized and accelerated synthesis for efficient property optimization is a formidable challenge for chemistry in the 21st century as it helps to reduce resources and waste and can deliver products in shorter time frames. Here, we used for the first-time acoustic droplet ejection (ADE) technology and fast quality control to screen efficiency of synthetic reactions on a nanomole scale in an automated and miniaturized fashion. The interrupted Fischer indole combined with Ugi-type reactions yielded several attractive drug-like scaffolds. In 384-well plates, a diverse set of interrupted Fischer indole intermediates were produced and reacted to the tricyclic hydantoin backbone by a 2-step sequence. Similarly, preformed Fischer indole intermediates were used to produce divers sets of Ugi products and the efficiency was compared to the in-situ method. Multiple reactions were resynthesized on a preparative millimole scale, showing scalability from nano to mg and thus synthetic utility. An unprecedented large number of building was used for fast scope and limitation studies (68 isocyanides, 72 carboxylic acids). Miniaturization and analysis of the generated big synthesis data enabled deeper exploration of the chemical space and permitted gain of knowledge that was previously impractical or impossible, such as the rapid survey of reactions, building block and functional group compatibility

Rapid approach to complex boronic acids

The compatibility of free boronic acid building blocks in multicomponent reactions to readily create large libraries of diverse and complex small molecules was investigated. Traditionally, boronic acid synthesis is sequential, synthetically demanding, and time-consuming, which leads to high target synthesis times and low coverage of the boronic acid chemical space. We have performed the synthesis of large libraries of boronic acid derivatives based on multiple chemistries and building blocks using acoustic dispensing technology. The synthesis was performed on a nanomole scale with high synthesis success rates. The discovery of a protease inhibitor underscores the usefulness of the approach. Our acoustic dispensing-enabled chemistry paves the way to highly accelerated synthesis and miniaturized reaction scouting, allowing access to unprecedented boronic acid libraries