Determination of the Absolute Configuration of Flexible Molecules by ab Initio ORD Calculations:  A Case Study with Cytoxazones and Isocytoxazones

Abstract

Ab initio calculations of the optical rotatory power of the natural cytokine modulator cytoxazone 1 and its trans-diastereomer 2, as well as the structural isomers cis-3 and trans-4 isocytoxazones, have been performed at four different wavelengths (589, 546, 435, and 405 nm) by Density Functional Theory. The calculation of ORD curves provides a reliable method for the assignment of absolute configuration of these conformationally flexible molecules. The absolute configurations of isocytoxazones has been established as (+)-(4R,5S)-cis-3 and (+)-(4S,5S)-trans-4.

Absolute configurations of DNA lesions determined by comparisons of experimental ECD and ORD spectra with DFT calculations

“…Following a protocol first introduced by Polavarapu (94), Giorgio et al (37) systematically used the prediction of ORD curves and their comparison with experimental data for assignment of absolute configurations. With the ORD curves calculated near to but not at the frequency of the resonance, this approach provided a reliable method for the assignment of absolute configuration of both rigid and conformationally flexible molecules (37, 53, 95–97). Thus, the assignment of absolute configurations by comparison of predicted and observed ORD curves has been satisfactory, although the exact match between experiment and theory is a function of the computational methodologies used (see, for example (90)).…”

“…The ORD curves were calculated near to but not at the frequency of the resonance, following a protocol first introduced by Polavarapu (94). The calculation of ORD curves provides a more reliable method for the assignment of absolute configuration of the rigid and conformationally flexible molecules than single-wavelength [α] D values (37, 95). In addition, the B3LYP density functional and three different basis sets, namely 3-21G**, MidiX and DGDZVP were used for (+)-chlorofluoroiodomethane (96).…”

Determination of the absolute configurations of flexible molecules: Synthesis and theoretical simulation of electronic circular dichroism/optical rotation of some pyrrolo[2,3‐b]indoline alkaloids—A case study

“…Despite this fact, the ab initio prediction of OR for the purpose of the assignment of AC became possible only very recently. Also recently, it has been shown 62,66 that calculations of [a] at different wavelength rather than at a single frequency could be in general a better approach for determining the AC. For such approach, even a use of small basis set can provide reliable results.…”

“…12 The technique of time-dependent density functional theory (TDDFT) in conjunction with the B3LYP hybrid functional turned out to be the best choice (Some recent examples of assignment of absolute configuration by the TDDFT calculation of [a] D are reported in Refs. [63][64][65][66] to get correct reproduction of OR values and of ECD spectra with reasonable computational efforts. Some researchers 30 state that the use in CD and OR calculations of large basis sets containing diffuse functions is mandatory to obtain reliable results.…”

Device-Compatible Chiroptical Surfaces through Self-Assembly of Enantiopure Allenes

“…1,2 These spectroscopies present remarkable high sensitivity to conformational changes and supramolecular interactions. As a consequence they are routinely used not only for absolute configuration determination [3][4][5] and conformational assignments, 6,7 but also for the characterization of molecular assemblies where at least one of the components is chiral. 8,9 Moreover, a guest molecule may be identified by the characteristic chiroptical responses when forming a complex with a chiral host, a task far from trivial for non-chiral techniques.…”