MISER chromatography (multiple injections in a single experimental run): the chromatogram is the graph

Rise of the Robots

“…A deep understanding of an instrument and its relationship with chemistry is never more needed than when pushing to expand the limits of automation technology. This can be from developing protocols to ensure overlapped injections do not lead to compound carryover, to the impressive development from Merck in New Jersey, of MISER‐MS analysis …”

Implementation of Hadamard encoding for rapid multisample analysis in liquid chromatography

“…Welch et al. developed multiple injections in a single experimental run chromatography, where in analogy to the FIA technique, rapid sequential analysis of samples is carried out in a single run using HPLC or HPLC–MS . This approach has successfully been applied several times as a screening platform in liquid chromatography and GC .…”

Rapid Catalyst Identification for the Synthesis of the Pyrimidinone Core of HIV Integrase Inhibitors

“…However, many synthetic problems arise for which rationally designed platforms are not available, and cannot be designed owing to a lack of precedent or understanding. Finally, after reaction incubation, we envisioned using MISER chromatography [12,13] for sample analysis, as this method enables an entire 96-well plate to be evaluated in about 1 hour, and produces a convenient graphical output that facilitates hit identification.We were interested in applying this platform to the synthesis of 2-substituted-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid (pyrimidinone) derivatives of type 2 (Scheme 1), an important class of compounds with welldocumented biological activity. [1][2][3][4][5][6][7][8] Herein, we describe a broad-based, microscale additivescreening platform that was designed to minimize complexity and cost/time bottlenecks in the discovery of new ways to improve the performance for a wide variety of reactions.…”

“…The additives that were chosen are displayed in Figure S1 of the Supporting Information. Finally, after reaction incubation, we envisioned using MISER chromatography [12,13] for sample analysis, as this method enables an entire 96-well plate to be evaluated in about 1 hour, and produces a convenient graphical output that facilitates hit identification. To minimize reagent cost, we utilized very small 250 mL HPLCvial inserts (microvials) [11] as reaction vials, thus permitting reaction screening at approximately 20 mL of solvent (ca.…”

“…[12,13] Thus, with this platform and workflow in hand, 475 different reactions were evaluated with just 370 mg of material in a single day. The additive screening was carried out by dosing the substrate 1 a (2.5 mmol) and internal standard (0.25 mmol biphenyl) in 20 mL of five different solvents (o-xylene, 1,4dioxane, methanol, NMP and DMF) to five of the 250 mL additives plates containing 20-50 % of the pre-dosed additives.…”