title: Application of Hadamard spectroscopy to automated structure verification in high-throughput NMR.
abstract: Combined verification using 1-D proton and HSQC has been proved to be quite successful; the acquisition time of HSQC spectra, however, can be limiting in its high-throughput applications. The replacement with Hadamard HSQC can significantly enhance the throughput. We hereby propose a protocol to optimize the grouping of the predicted carbon chemical shifts from the proposed structure and the associated Hadamard frequencies and bandwidths. The resulting Hadamard HSQC spectra compare favorably with their Fourier-transformed counterparts, and have demonstrated to perform equivalently in terms of combined verification, but with several fold enhancement in throughput, as illustrated for 21 commercial available molecules and 16 prototypical drug compounds. Further improvement of the verification accuracy can be achieved by the cross validation from Hadamard TOCSY, which can be acquired without much sacrifice in throughput.
authors.affiliation: Pfizer Global Research & Development, 700 Chesterfield Parkway, St. Louis, MO 63017, USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Ruan
authors.forename: Shengtian
authors.initials: S
authors.lastname: Yang
authors.forename: Karey A
authors.initials: KA
authors.lastname: Van Sant
authors.forename: John J
authors.initials: JJ
authors.lastname: Likos
mesh_terms: D002626:Chemistry, Pharmaceutical; D003198:Computer Simulation; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D015394:Molecular Structure