Vibrational and electronic optical activity of the chiral disulphide group: Implications for disulphide bridge conformation

Abstract

Using dihydrogendisulphide (H(2)S(2)), dimethyl- ((CH(3))(2)S(2)), and diethyldisulphide ((CH(3)CH(2))(2)S(2))as model molecules, theoretical ECD, VCD, and ROA spectra of nonplanar disulphides were calculated by DFT methods. Most of the calculated electronic and vibrational chiroptical features suffer an equivocal relation between calculatedsigns of ECD, VCD, or ROA and the sense of disulphide nonplanarity as noted earlier for low-lying ECD bands. This is a consequence of local C(2) symmetry of a disulphide group causing most electronic and vibrational transitions to occur as pairs falling to alternative A, B symmetry species, which become degenerate and switch their succession (and consequently the observed chiroptical sign pattern) at the energetically most favorable perpendicular conformation. According to present calculations, the key to resolving this ambiguity may involve the S-S stretching vibrational mode at approximately 500 cm(-1). The relation of signs of the relevant VCD and ROA features to sense of disulphide chirality seems simpler and less ambiguous. The right-handed arrangement of the S-S group (0 < chi(S-S) < 180 degrees) results in mostly negative VCD signals. Although relation to ROA still suffers some ambiguity, it gets clearer along the series H(2)S(2)-(CH(3))(2)S(2)-(CH(3)CH(2))(2)S(2). ROA is also attractive for the analysis of disulphide-containing peptides and proteins, because applying it to aqueous solutions is not problematic.

Raman Optical Activity of Amide and Disulfide Groups in Peptides and Model Systems

“…We have also identified features in ROA spectra which are associated with the S-S and C-S stretching vibrations. These allow us to infer the sense of disulfide twist in the particular compounds when signs of ROA features are compared to ROA calculations on simple model disulfides [5] and verified by a comparison with spectra of disulfidebridged cyclodextrins [6]. The ROA signals in the S-S and C-S stretching vibration regions are observable also with neurohypophyseal hormones and their sign can be used to deduce the sense of disulfide twist.…”

Disulfide chromophore and its optical activity

“…In accord with the above suggested presence of two conformations of different handedness, we can expect a couplet of ROA bands and tentatively assign it to particular conformations. 16 In that case, the smaller negative ROA feature at 490 cm 21 would correspond to a conformation with v SÀ ÀS angle 21208, whereas the positive feature at 570 cm 21 should correspond to 11008. It is somewhat surprising that in the spectra of III and IV, it is much easier to identify Raman bands corresponding to SÀ ÀS stretching (Fig.…”

“…16 We added several supplementary results to further enlighten the optical rotatory strength data in situations where the angle v SÀ ÀS approaches 908. The calculations used Gaussian program, DFT B3LYP functional, 6-31111G** basis set, and the COSMO continuum solvent model.…”

“…We report experimental ECD, Raman, and ROA data together with analysis and basic comparison of experimental results with our previous calculations on simple models. 16 More detailed theoretical calculations will be the subject of a subsequent paper.…”

“…28,29 The theoretical description of the possibility to study disulfide bridge conformation using vibrational optical activity (VOA) in combination with ECD was presented in Ref. 16. We applied DFT calculations of electronic and vibrational optical activity to nonplanar conformations of the simple models dihydrogendisulfide, dimethyldisulfide, and diethyldisulfide.…”