Correlation between 13C NMR chemical shifts and antiradical activity of flavonoids

Abstract

The 13 C NMR chemical shifts of a range of flavonoids are predicted by the Mnova NMRPredict soft- ware and related to their radical scavenging activity (RSA). 13 C NMR chemical shifts of C atoms bearing phenolic OH groups associated with radical attack tend to decrease with increasing antiradical activity. For a data set of 27 flavo- noids, fair correlation (r =- 0.881) was found between the antiradical activity and minimal value of the 13 CN MR chemical shift (NMRmin), and it was similar to the corre- lation (r =- 0.850) obtained with the minimal O-H bond dissociation enthalpy (BDEmin) calculated by the PM7 method. For a particular flavonoid molecule, 13 CN MR chemical shifts of C atoms bearing phenolic OH groups correlate nicely with the corresponding O-H BDEs (e.g., for robinetin r = 0.953). For the complete data set, there is a similar correlation between NMRmin and BDEmin values (r = 0.944). As a rule, NMRmin is related to nuclei bearing a3 0 ,4 0 -dihydroxy moiety in the B ring or 3-OH phenolic group in the C ring, i.e., to the preferred sites of radical attack. Thus, the 13 C NMR chemical shifts of C atoms bearing phenolic OH groups are in accordance with the O- H BDEs, i.e., describe the H atom donor ability of phenolic OH groups. The statistical significance of the relationship between the minimal 13 C NMR chemical shift and RSA was verified by comparison with correlations between RSA and each of 1,140 Dragon molecular descriptors, where the highest correlation coefficient of 0.812 was obtained.