Two-photon circular dichroism (TPCD) has recently emerged as a powerful tool for structural and conformational characterization of chiral systems. TPCD was first measured in 1995, but it was not until the invention of the double-L scan technique that a reliable and more versatile method for measuring this property was developed. Since then, we have performed the theoretical-experimental characterization of a series of chiral asymmetric catalysts and compounds with helical chirality using TPCD.   Recently, we embarked on the conformational study of an axially chiral ligand, AFX-155, in THF solution using this novel technique. Due to large size of AXF-155, theoretical calculation of its TPCD spectrum proved to be impossible for current computational methods. In order to overcome this limitation we employed a fragment-recombination approach (FRA), where molecular fragmentation is carried out in such a way that the sum of the TPCD spectra of the fragments is equal to that of the entire molecule. Three fragments where obtained from applying FRA to AXF-155; two AXF-155 halves (AXF-169') and the center (C-AXF-155).   FRA-TPCD enabled us to prove the presence of two dominant conformers, Trans-R-Intra(NHB)//Trans-R-Extra(HB) and Trans-R-Intra(NHB)//Trans-R-Extra(NHB) in THF solution. This study shows that FRA can be used for the analysis of the TPCD spectra of large chiral molecules, thus opening the door for potential applications in the conformational study and characterization of large biological systems, such as peptides, polypeptides and proteins.

Conformational study of an axially-chiral ligand in solution using two-photon circular dichroism and the fragment-recombination approach

247th National Meeting (2014)

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