This work provides a systematic comparison of vibrational CD (VCD) and electronic CD (ECD) methods for spectral prediction of secondary structure. The VCD and ECD data are simplified to a small set of spectral parameters using the principal component method of factor analysis (PC/FA). Regression fits of these parameters are made to the X-ray-determined fractional components (FC) of secondary structure. Predictive capability is determined by computing structures for proteins sequentially left out of the regression. All possible combinations of PC/FA spectral parameters (coefficients) were used to form a full set of restricted multiple regressions with the FC values, both independently for each spectral data set as well as for the two VCD sets and all the data grouped together. The complete search over all possible combinations of spectral parameters for different types of spectral data is a new feature of this study, and the focus on prediction is the strength of this approach. The PC/FA method was found to be stable in detail to expansion of the training set. Coupling amide I1 to amide I' parameters reduced the standard deviations of the VCD regression relationships, and combining VCD and ECD data led to the best fits. Prediction results had a minimum error when dependent on relatively few spectral coefficients. Such a limited dependence on spectral variation is the key finding of this work, which has ramifications for previous studies as well as suggests future directions for spectral analysis of structure. The best ECD prediction for helix and sheet uses only one parameter, the coefficient of the first subspectrum. With VCD, the best predictions sample coefficients of both the amide I' and I1 bands, but error is optimized using only a few coefficients. In this respect, ECD is more accurate than VCD for a-helix, and the combined VCD (amide I'+II) predicts the P-sheet component better than does ECD. Combining VCD and ECD data sets yields exceptionally good predictions by utilizing the strengths of each. However, the residual error, its distribution, and, most importantly, the lack of dependence of the method on many of the significant components derived from the spectra leads to the conclusion that the heterogeneity of protein structure is a fundamental limitation to the use of such spectral analysis methods. The underutilization of these data for prediction of secondary structure suggests spectral data could predict a more detailed descriptor.

The infrared (IR) and vibrational circular dichroism (VCD) spectra of S-2,2'-dimethyl-biphenyl-6,6'-dicarboxylic acid, S-1, in CDCl(3) solution are concentration-dependent, showing that oligomerization occurs with increasing concentration. DFT calculations support the conclusion that the oligomer formed is the cyclic tetramer (S-1)(4), in which S-1 monomers are linked by hydrogen(H)-bonded (COOH)(2) moieties. Due to the existence of two inequivalent tautomeric conformations of each (COOH)(2) moiety, six inequivalent conformations of (S-1)(4) are possible. B3LYP/6-31G* DFT calculations predict that the conformation "aaab", possessing three equivalent (COOH)(2) conformations, a, and one tautomeric conformation, b, has the lowest free energy. B3LYP/6-31G* IR and VCD spectra vary substantially with conformation. The B3LYP/6-31G* IR and VCD spectra of the C=O stretch modes of "aaab" are in excellent agreement with the experimental spectra, while those of all other conformations exhibit poor agreement, confirming the prediction that the "aaab" conformation is the predominant conformation. Comparison of the calculated IR and VCD spectra of the six conformations to the experimental spectra in the range 1100-1600 cm(-1) further supports this conclusion. The study is the first to use VCD spectroscopy to determine the structure of a supramolecular species.

Nine geranylated flavanones isolated from the fruits of Paulownia tomentosa (4-12) and two from the roots of Morus alba (13 and 14) were examined for cytotoxicity to selected human cancer cell lines and normal human fibroblasts. Cytotoxicity was determined in vitro using a calcein AM cytotoxicity assay. Cytotoxicity for the THP-1 monocytic leukemia cell line was tested using erythrosin B cell staining. The geranylated compounds tested were compared with the known simple flavanone standards taxifolin (1), naringenin (2), and hesperetin (3) and with the standard anticancer drugs olomoucine II, diaziquone, and oxaliplatin and the antineoplastic compound camptothecin, and showed different levels of cytotoxicity. The effects of structural changes on cytotoxic activity, including geranyl substitution of the flavanone skeleton and the oxidation pattern of ring B of the flavanones, are discussed.

The conformation of the milk protein alpha-lactalbumin has been studied using vibrational circular dichroism (VCD) and compared to parallel studies on lysozyme. These proteins have been shown by Acharya et al. [(1989) J. Mol. Biol. 208, 99-127] to have very similar three-dimensional crystal structures. However, their VCD spectra in D2O solution are quite different. The VCD of lysozyme in D2O more resembles that of alpha-lactalbumin in 33% propanol/D2O, under which conditions alpha-lactalbumin has conformationally transformed to a structure with increased helical fraction. These results can be seen to be consistent with UVCD and resolution-enhanced FTIR spectra of alpha-lactalbumin and lysozyme in both D2O and H2O environments. The solvent sensitivity of the alpha-lactalbumin spectra and hence of its conformation contrasted with the lack of such sensitivity for lysozyme suggest that the alpha-lactalbumin crystal structure represents a conformation different from that which is dominant in aqueous solution.

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