Chirality in Liquid Crystals DOI: 10.1002/anie.200603692 A General Method for Measurement of Enantiomeric Excess by Using Electrooptics in Ferroelectric Liquid Crystals** David M. Walba,* Lior Eshdat, Eva Korblova, Renfan Shao, and Noel A. Clark Dedicated to Professor SvenT. Lagerwall on the occasion of his 70th birthday The strongest applications of combinatorial technology to catalyst discovery exploit very large libraries. For example, RNA libraries of approximately 10 14 distinct members have beenscreenedtoproducecatalystsfororganicreactionssuch astheDiels–Alderreaction. [1] Applicationofthistechnology toasymmetriccatalystdevelopment, [2] however,isblockedby lack of an effective high-throughput screen. Although con- siderable effort aimed at development of high-throughput methodsformeasurementofenantiomericexcess(ee)values isunderwayworldwide, [3] massivelyparallelselectionsuchas that demonstrated for RNA catalyst discovery is not avail- able,evenconceptually. Liquid crystals (LCs) have been used for sensitive and convenient detection of ee values for some time. [4] Recently, technology for creating ferroelectric liquid crystal (FLC) on silicon video microdisplays comprised of greater than 10 5 individually switched electrooptic (EO) pixels (  25-fL pixel volume) on small semiconductor substrates has been developed to high-volume commercialization. [5] AsthisFLC EO depends upon enantioenrichment of at least one of the FLC components, [6] a project has been initiated, aimed at exploringitsuseasthebasisofamethodanddeviceforhigh- throughput measurement of enantiomeric excess, the “ee- microdisplay.” This approach involves fabrication of devices similar to video microdisplays, but in which the LC in each pixel is differentwhilethedrivingsignalisthesame.Thisobviatesthe needforexpensivesemiconductorsubstrates,asarerequired forvideomicrodisplays.TheEOsignalfromeachpixelwould berelatabletothe ee valueoftheLCtherein,whichwouldbe composedofanachiralLChostdopedwithasmallamountof chiralanalyte. Therearemanypotentiallyusefulchiralsignalsavailable with doped smectic LCs. Initial experiments were directed towards use of the EO response time in a smectic C phase (SmC) doped with a chiral analyte, forming a chiral smectic C phase (SmC*) as a measure of the ee values. [7,8] It has already been demonstrated that chiral EO in the SmC* is a verysensitivechiralitydetector. [9] However,itwasfoundthat for SmC hosts doped with a chiral analyte, dielectric responses, [10] electric-field-driven deracemization, [11] and alignment issues not directly associated with molecular chiralityofthedopantcomplicatequantitativemeasurement of ee valuesbyusingFLCEO. Therefore,developmentofamethodutilizingtheelectro- cliniceffect [12] inchirallydopedSmAhosts [13] wasundertaken. In the electroclinic effect, application of an electric field paralleltothelayersofaSmA*LCinducesatiltintheoptic axis in the plane that is normal to the applied field. Enantiomers show equal magnitude but opposite signs for thisopticaxisrotation,whichislinearwiththefieldforsmall induced tilts. Herein, the basic feasibility of this approach is demonstratedbyusingthechiraldrugs(S)-naproxen(1)and (S,S)-pseudoephedrine (2) as test analytes. No covalent chemistry is required for the measurement, which should be quitegenerallyapplicabletochiralorganics. Thus, an achiral SmA host composed of three phenyl- pyrimidine smectic mesogens was formulated (see the Sup- porting Information). In these initial experiments, the chiral drug naproxen, commercially available as both the unichiral S enantiomer(1)andastheracemate,waschosenasamodel analyte. A good, linear calibration curve [14] could, in fact, be obtainedbyusingthephenylpyrimidineSmAhostdopedwith naproxen. However, the expected strong dependence of the electrocliniceffectontemperaturesclosetotheSmA*–SmC* transition, [11,13] combinedwiththefactthatthevariousanalyte samples possessed slightly different transition temperatures, precludeduseofthismethodformeasurementof ee valuesat a single absolute temperature. This effectively negates the utilityofthemethodforhigh-throughputscreening. This problem was solved through the use of the racemic deVries SmA [15] host 3 (phase sequence with transition [*] Prof. D.M. Walba, Dr. L. Eshdat, Dr. E. Korblova Department of Chemistry and Biochemistry University of Colorado 215 UCB Boulder, CO 80309-0215 (USA) Fax: (+ 1)303-492-5894 E-mail: walba@colorado.edu R. Shao, Prof. N. A. Clark Department of Physics University of Colorado 390 UCB, Boulder, CO 80309-0390 (USA) [**] We thank the Liquid Crystal Materials Research Center (NSF MRSEC award no. DMR-0213918) for financial support of this work. Supporting information for this article is available on the WWW under http://www.angewandte.org or from the author. Angewandte Chemie 1473 Angew. Chem. Int. Ed. 2007, 46, 1473–1475 # 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim