¹H and ¹³C NMR and Molecular Dynamics Study of Chiral Recognition of Camphor Enantiomers by α-Cyclodextrin

Abstract

1H and (13)C NMR spectra of the complexes of camphor enantiomers with alpha-cyclodextrin in D(2)O manifest splittings due to chiral recognition. The complexes were found to be of 1:2 guest-to-host stoichiometry. Free energies of the complex formation obtained from (1)H NMR titration data are equal to -7.95 +/- 0.09 kcal mol(-)(1) for the complex with (1S,4S)- and -7.61 +/- 0.06 kcal mol(-)(1) for that with (1R,4R)-enantiomer. Thus, the free energy difference between the complexes is equal to 0.34 +/- 0.11 kcal mol(-)(1), with the complex involving the (1S,4S)-camphor more stable. A strong positive cooperativity of the guests binding has been found. In agreement with experimental results, molecular dynamics simulations yielded greater stability of the complex with (1S,4S)-camphor. However, they reproduced only qualitatively the experimental trend since the corresponding difference in average energies obtained from molecular dynamic simulations carried out in a water solution is equal to 5 kcal/mol with the CVFF force field.

Enantioselective detection of chiral phosphorescent analytes in cyclodextrin complexes

“…3 also reveals that the phosphorescence intensities of the two CQ enantiomers in the ␣-CD inclusion complex are very different. In other words, the formation of diastereoisomeric complexes of CQ with ␣-CD (in agreement with the literature [17][18][19]25]), does allow chiral discrimination by means of RTP, without the need to involve a separation technique. The same was not found for the 1:1 CQ-CD complexes; Bortolus et al [18] reported that for ␤-CD no difference in RTP could be observed between the two isomers.…”

“…Fig. 3 shows that above a [␣-CD]/[CQ] ratio of 10, a plateau was reached for the RTP enhancement for both enantiomers, indicating that the 2:1 complex formation is practically complete, in full agreement with the association constants reported in the literature [17,18]. Furthermore, in a 20 mM ␣-CD solution, the signal varied roughly linearly with the CQ concentration over the range 0.5-2.0 mM CQ (not shown).…”

“…Tran and Fendler [16] reported how CDs can be used to discriminate between (+)-and (−)-␣-(1)-naphtylethylamine based on differences in fluorescence lifetimes. Studies using NMR spectra [17] as well as papers dealing with spectroscopic and photophysical investigations [18,19] also show the possibility of chiral discrimination by CDs for bicyclic compounds such as camphorquinone (CQ), the compound concerned with in the present paper. CQ is a chiral bicyclic 2,3-dione (see Fig.…”

Molecular Modeling of the Chiral Recognition of Propranolol Enantiomers by a β-Cyclodextrin

“…The calculated results are in agreement with experimental observation in predicting the correct elution order in propranolol separation. Molecular dynamics simulations indicate that average energy difference between the complexes, which is frequently used as a measure of chiral recognition, [22][23][24][25] depends on the length of the simulation time. We found that only in case of much longer MD simulations, more than 10 times for the general MD time scale, noticeable chiral separation was observed.…”

“…In most molecular dynamics studies of CD complexes, calculations were carried out for quite short simulation time (< 5 ns). [22][23] 12 ns MD simulations in water was considered by Dodziuk et al, however, these systems have not reached complete equilibrium states particularly for the chiral recognition process. 24 Therefore, we have extended the MD simulations with the implicit solvent for considerably longer times, about 100 ns, and analyzed how the calculated average energy differences between the enantiomeric complexes depend on the length of the simulation.…”