A high throughput screening method for the nano-crystallization of salts of organic cations

Abstract

96 nano-crystallization trials can be done with just (sub)-milligram amounts of an organic salt to directly yield single crystal structures.

Chemistry at High Dilution: Dinuclear 99 mTc Complexes

“…For growing X‐ray quality crystals, we screened systematically the crystallization conditions by altering the anions in the solutions. According to the nano‐crystallization method, we got the nitrate salt of 3 − (Re 2 ), with all three ‐NEt 2 groups being protonated (Figure ) . When the same reaction was now done with 1 + ( 99m Tc) and 2‐diethylaminoethanethiol (1 m m ) in water at room temperature, and with a 99m Tc‐concentration of about 100 n m , one main radioactive species was observed as a single peak on HPLC ( R t =18.4 min, γ‐channel, Figures S3 and S4).…”

“…Note: The three ‐NEt 2 groups are protonated, two [NO 3 ] − anions are not shown. Crystals were grown using nano‐crystallization screening experiments . Ellipsoids are drawn on the 30 % level.…”

“…According to the nano-crystallization method, we got the nitrate salt of 3 À À (Re 2 ), with all three -NEt 2 groups being protonated ( Figure 2). [8] When the same reactionw as now done with 1 + + ( 99m Tc )a nd 2diethylaminoethanethiol (1 mm)i nw ater at room temperature, Figure 1. Reactionof1 + + (Re) and 1 + + ( 99m Tc )w ith 2-mercapto-ethanol yields the dinuclear heterometallic (Re/ 99m Tc )complex 2 À À (top).…”

“…Crystals were grown using nano-crystallization screening experiments. [8] (19), Re1-S1-Re2 86.27 (5),R e1-S2-Re2 86.32 (6), Re1-S3-Re2 86.31 (6). and with a 99m Tc-concentration of about 100 nm,o ne main radioactive species was observed as as ingle peak on HPLC (R t = 18.4 min, g-channel, Figures S3 and S4).…”

Bestimmung der absoluten Konfiguration pharmazeutischer Wirkstoffe durch Röntgenpulverdiffraktometrie

“…Ein zweites Problem ist die begrenzte Substanzmenge, die in einer frühen Forschungsphase zur Verfügung steht (typischerweise nur wenige Milligramm), was die Durchführung von Kristallzüchtungsexperimenten weiter erschwert. [5] Wirv erfolgen daher einen anderen Ansatz und bestimmen die absolute Konfiguration pharmazeutischer Wirkstoffe durch Rçntgenpulverdiffraktometrie.I mR çntgenpulverdiagramm kann zwar nicht zwischen Enantiomeren unterschieden werden, jedoch problemlos zwischen Diastereomeren. Da heute die meisten Pharma-Wirkstoffe saure oder basische Gruppen enthalten, [6] Mit beiden Verfahren erhielten wir mikrokristalline Pulver von fünf Salzen: R1a, R1b, S1b, 2c und 3c (füre xperimentelle Details,s iehe die Hintergrundinformationen).…”