Prasad L. Polavarapu

Comprehensive Chiroptical Spectroscopy: Applications in Stereochemical Analysis of Synthetic Compounds, Natural Products, and Biomolecules

This book provides an introduction to the important methods of chiroptical spectroscopy in general, and circular dichroism (CD) in particular, which are increasingly important in all areas of chemistry, biochemistry, and structural biology. The book can be used as a text for undergraduate and graduate students and as a reference for researchers in academia and industry. Experimental methods and instrumentation are described with topics ranging from the most widely used methods (electronic and vibrational CD) to frontier areas such as nonlinear spectroscopy and photoelectron CD, as well as the theory of chiroptical methods and techniques for simulating chiroptical properties. Applications of chiroptical spectroscopy to problems in organic stereochemistry, inorganic stereochemistry, and biochemistry and structural biology are also discussed, and each chapter is written by one or more leading authorities with extensive experience in the field.

Experimental and ab initio theoretical vibrational Raman optical activity of alanine

The vibrational Raman optical activity (ROA) spectra of l-alanine in water, 1 N NaOH and 1 N HCl between 720 and 1500 cm−1 measured in backscattering are reported. Unlike the associated vibrational circular dichroism (VCD), the main ROA features are relatively insensitive to pH changes. Ab initio Raman and ROA intensities were evaluated using 6-31G and 6-31G* basis sets and found to agree remarkably well with the experimental parameters in the lower-frequency region.

A Single Chiroptical Spectroscopic Method May Not Be Able To Establish the Absolute Configurations of Diastereomers: Dimethylesters of Hibiscus and Garcinia Acids

Electronic circular dichroism (ECD), optical rotatory dispersion (ORD), and vibrational circular dichroism (VCD) spectra of hibiscus acid dimethyl ester have been measured and analyzed in combination with quantum chemical calculations of corresponding spectra. These results, along with those reported previously for garcinia acid dimethyl ester, reveal that none of these three (ECD, ORD, or VCD) spectroscopic methods, in isolation, can unequivocally establish the absolute configurations of diastereomers. This deficiency is eliminated when a combined spectral analysis of either ECD and VCD or ORD and VCD methods is used. It is also found that the ambiguities in the assignment of absolute configurations of diastereomers may also be overcome when unpolarized vibrational absorption is included in the spectral analysis.

Fourier Transform Infrared Spectroscopy as a Powerful Tool for the Study of Carbohydrates in Aqueous Solutions

FT-IR spectral investigations on carbohydrates were undertaken in aqueous media in order to facilitate the assignments of vibrational bands. For pure anomeric forms of glucose, FT-IR spectra obtained as a function of time revealed many changes in spectral content, providing new information about anomer characteristic bands in aqueous media. It was also found that fructose, which is known to undergo complex mutarotation, exhibits two types of spectral changes, whereas glucose, which undergoes simple mutarotation, shows a single type of spectral change. Thus FT-IR spectral investigations in aqueous carbohydrates should be able to distinguish between simple and complex mutarotation cases. As a vibrational spectroscopic technique, the importance of FT-IR spectroscopy is further emphasized by showing that Raman spectroscopy is not sensitive enough to reveal the structural changes of carbohydrates in aqueous media.

Similarity in dissymmetry factor spectra: a quantitative measure of comparison between experimental and predicted vibrational circular dichroism.

To quantitatively determine the agreement between experimental and calculated vibrational circular dichroism (VCD) spectra, a new approach, based on the similarity of dissymmetry factor spectra has been developed and implemented. This method, which places emphasis on robust regions both in the experimental and in the calculated spectra, has been tested with six chiral compounds of known absolute configurations, namely, (R)-(+)-3-chloro-1-butyne, (3R)-(+)-methylcyclopentanone, (3R)-(+)-methylcyclohexanone, (1S)-(-)-α-pinene, (1R)-(+)-camphor, and (S)-(+)-epichlorohydrin. The criterion of maximum overlap among experimental and calculated dissymmetry factor spectra is shown to have definite advantages over those using maximum overlap among VCD or absorption spectra individually. The new method provides a better assessment of the comparison between experimental observations and quantum chemical VCD predictions and improves the confidence in the assignment of absolute configurations.

A comparison of ab initio optical rotations obtained with static and dynamic methods

Abstract Optical rotations of several chiral molecules have been calculated with both static and dynamic methods and these predictions are compared to the experimental optical rotations. The optical rotation signs predicted by the static method are the same as those predicted by the dynamic method with London orbitals, except for one molecule. The optical rotations predicted by these two methods compare favorably with the experimental observations. Nevertheless, the ability to calculate wavelength-dependent and gauge-origin-independent optical rotations makes the use of the dynamic method with London orbitals more attractive.

Evidence for covalent binding between copper ions and cyclodextrin cavity: a vibrational circular dichroism study

Vibrational absorption and circular dichroism (VCD) spectra were obtained for parent cyclodextrins, hydroxyl deuterated alpha-cyclodextrin, cyclodextrin-copper complexes, and for the cyclodextrin inclusion complexes with Methyl Orange, methyloxirane, 1-propanol, and substituted cyclohexanones, in the solution phase. Changes in the VCD spectra, reflecting perturbations of cyclodextrin cavity, were found in the case of an inclusion complex with Methyl Orange, but for the remaining inclusion complexes measurable changes in VCD were not found. Significant changes observed in the VCD spectra of cyclodextrin-copper complexes suggest that the covalent binding of copper ions to the hydroxyl groups of cyclodextrin is involved.

Ab initio and experimental vibrational Raman optical activity in (+)-(R)-methylthiirane

Experimental and theoretical vibrational Raman optical activity (ROA) spectra of (+)-(R)-methylthiirane are presented. The vibrational origin of the observed bands is discussed and the predictive capabilities of the theoretical calculations are evaluated in relation to the experimental observations. The ROA spectral sign patterns predicted with the 6-31G* basis set are in good agreement with those in the experimental spectra. For most of the vibrations the predicted magnitudes of the normalized ROA quantities are larger than those experimentally observed.

Vibrational spectra of epoxypropane

Vibrational band assignments for epoxypropane were derived from experimental vibrational spectral data and ab initio calculations with a 6‐31G basis. Using the ab initio normal coordinates and bond moment theory, vibrational circular dichroism (VCD) parameters for (S)‐epoxypropane were calculated and compared to experimental VCD observations.

Atropisomeric Dihydroanthracenones as Inhibitors of Multiresistant Staphylococcus aureus

Two bisdihydroanthracenone atropodiastereomeric pairs, including homodimeric flavomannin A (1) and the previously unreported flavomannin B (2), two new unsymmetrical dimers (3 and 4), and two new mixed dihydroanthracenone/anthraquinone dimers (5 and 6) were isolated from Talaromyces wortmannii , an endophyte of Aloe vera . The structures of 2-6 were elucidated by extensive NMR and mass spectrometric analyses. The axial chirality of the biaryls was determined using TDDFT ECD and VCD calculations, the combination of which however did not allow the assignment of the central chirality elements of 1. The compounds exhibited antibacterial activity against Staphylococcus aureus , including (multi)drug-resistant clinical isolates. Reporter gene analyses indicated induction of the SOS response for some of the derivatives, suggesting interference with DNA structure or metabolism. Fluorescence microscopy demonstrated defective segregation of the bacterial chromosome and DNA degradation. Notably, the compounds showed no cytotoxic activity, encouraging their further evaluation as potential starting points for antibacterial drug development.