Steric analysis of glycerophospholipids by circular dichroism. Stereospecifity of phospholipase D catalyzed transesterification.

The circular dichroism spectra of natural glycerophospholipids and synthetic 1-$\text{sn}$-phosphatidic acid were recorded. 3-$\text{sn}$-phosphatidic acid derivatives were found to show a positive Cotton effect, while 1-$\text{sn}$-phosphatidic acid revealed a negative Cotton effect. The results are interpreted in terms of the carboxyl sector rule. By this method phospholipase D was shown to produce stereospecifically 3-$\text{sn}$-phosphatidyl-1-$\text{sn}$-glycerol when incubated with egg yolk lecithin and exess of glycerol.     

Circular dichroism of the nucleic acid monomers.

Circular dichroism spectra of the nucleic acid monomers have been measured in aqueous solution and extended into the vacuum ultraviolet region to about 166 nm. Measurements were made on ribo and deoxyribo derivatives of adenine, guanine, hypoxanthine, cytosine, thymine, and uracil derivatives both with and without the 5′-phosphate (with the exception of ribosyl thymine 5′-phosphate). Absorption spectra of the deoxyribonucleotides measured to about 175 nm are also presented. The results demonstrate that both the circular dichroism and absorption spectra observed below 200 nm are no more complicated than the spectra normally recorded above 200 nm. In most cases, the circular dichroism spectra of the various derivatives of a given base are similar, indicating that the conformations are similar. On the other hand, the differences among the circular dichroism spectra of the various derivatives of a given base are sufficient to identify a particular derivative. The average circular dichroism for the deoxyribonucleotides is compared with the circular dichroism of native E. coli DNA. The comparison reveals that the circular dichroism of DNA below 200 nm is due principally to the interaction between the bases rather than the intrinsic circular dichroism of the monomers. The monomer transitions are discussed in relationship to the absorption and circular dichroism spectra presented.     

Optical Rotatory Dispersion and Circular Dichroism of Amino Acid Hydantoins

Optical rotatory dispersion (ORD) and circular dichroism (CD) of 17 amino acid hydantoins were measured between 190 and 600 nm. Most of hydantoins exhibited the negative Cotton effect which showed the trough between 238 and 245 nm. The negative trough of CD was also observed between 212 and 236 nm. The Cotton effect of hydantoins was attributable to n→π^* transition of carbonyl group at C-4 of hydantoin ring.     

Circular dichroism of metallothioneins. A structural approach.

A comprehensive study on circular dichroism of metallothioneins containing Zn, Cd and Cu was carried out. The contributions of the metals, the sulphur and the polypeptide chain to the observed Cotton effects was shown. From the pH dependency of the extrinsic Cotton effects which are due to the metal-thiolate chromophore the stability of the metal clusters was found to decrease in the order Cu greater than Cd greater than Zn. The pH values corresponding to the dissociation of half of the bound metal ions are 0.44 for Cu-thionein, 3.05 for Cd-thionein and 4.6 for Zn-thionein. The extrinsic Cotton effects of Cd, Zn-thioneins of varying Cd to Zn ratio could be simulated using the difference circular dichroic spectra of Cd-thionein (bands at 227, 242.5 and 262 nm), Zn-thionein (bands at 225 and 244 nm) and the circular dichroic spectrum of cysteine-thionein (band at 200 nm, shoulder at 225 nm). Since during the dissociation of the metals the circular dichroic spectra exhibited changes only in amplitude and not in shape we can conclude that the dissociation of the metal ions involves the complete sequential degradation of metal clusters. In the near-ultraviolet region the metal-free proteins show only Cotton effects attributable to a disulphide chromophore. Thus Cotton bands are observed for cystine-thionein at 282.5 and 260 nm. From the intrinsic circular dichroism of Cd- and Zn-thionein (negative Cotton effect at 200 nm, shoulder at 225 nm) it follows that the protein conformation consists of less than 5% helical or pleated sheet structure and therefore has to be classified as unordered structure or "fixed" random coil     

A circular dichroism study of modified nucleosides

The conformation of 5-methoxycarbonylmethyluridine and 5-methoxycarbonylmethyl-2-thiouridine was studied by means of circular dichroism in various solvents. In order to calculate the accurate spectral parameters of the Cotton effects, the circular dichroism spectra were resolved into component Gaussian functions which simultaneously fit the adsorption spectra. On the basis of circular dichroism and proton magnetic resonance spectra, these nucleosides were found to occur in the β-configuration with the ³E-gg-anti conformation preferred. Due to the fact that the long-wavelength Cotton effect of mcm⁵s²U is not masked by the Cotton effects of the other nucleic acid monomers, the molecular parameters of this band may be useful for the conformational analysis of tRNA segments.     

Circular dichroism studies on alpha- and beta-ketosides of 5-acetamido-3,5-dideoxy-D-glycero-D-galacto- nonulopyranosonic acid (N-acetylneuraminic acid) and of some of its derivatives.

The circular dichroism spectra of a number of N-acetylneuraminic acid derivatives in aqueous solution were studied. For all compounds, the Cotton effects were found to be in the spectral range of the acetamido and carboxyl chromophores. The c.d. curves of the methy, ethyl, and allyl alpha-D-ketosides are characterized by a broad, positive band centered at lambda similar to 195 nm with a slight skew towards the higher wavelengths and weak bands between lambda 225 and 255 nm, whereas the methyl beta-D-ketoside and the corresponding methyl ester show only an intense positive band with a broad shoulder in the same spectral range. 5-Acetamido-3,5-dideoxy-D-glycero-beta-D-galacto-nonulopyranose, its methyl beta-D-ketoside, and 5-acetamido-3,5-dideoxy-D-glycero-D-galacto-nonulopyranosonamide containing only the acetamido chromophore showed one single positive Cotton effect centered at lambda similar to 192 nm. The c.d. spectrum of 5-acetamido-3,5-dideoxy-D-glycero-D-galacto-nonulopyranosonic acid confirms the beta-D configuration of the free acid in aqueous solution, whereas the shape of the c.d. curve of O-(N-acetyl-alpha-D-neuraminopyranosyl)-(2yields3)-O-beta-D-galactopyranosyl-(1 yields 4)-D-glucopyranose resembles that of the methyl, ethyl, and allyl alpha-D-ketosides 2-4.     

Circular dichroism of axially chiral methaqualone, 3-Aryl-2-mercapto- and 3-aryl-2-alkylthio-4(3H)-quinazolinones: conformational dependence of CD and assignment of absolute configuration

Rotational strengths calculated on the basis of quantum-mechanically obtained minimum energy geometries were used to determine the absolute configurations of axially chiral 3-aryl-4(3H)-quinazolinones from the sign of the observed Cotton effects (CEs). For the spectral data, CNDO/S calculations were used; for the geometries, ab initio (RHF/6-31G) and semiempirical (AM1) theories were used. Oscillator and rotational strengths of all excited states down to 200 nm were compared to experimental absorption and circular dichroism (CD) data. It was found that the sign of the ¹L_b Cotton effects obtained for the enantiomers of methaqualone and derivatives of 3-aryl-2-alkylthio-4(3H)-quinazolinones can be correlated unambiguously with the absolute configuration. Furthermore, the sign of the Cotton effect of the π-π* transition of the thiocarbonyl chromophore of 3-aryl-2-mercapto-4(3H)-quinazolinones is suitable for a successful stereochemical correlation. Chirality 10:253–261, 1998. © 1998 Wiley-Liss, Inc.     

Rotatory dispersion and circular dichroism of low-molecular-weight poly- -benzyl-L-glutamate

Rotatory dispersion and circular dichroism of low-molecular-weight poly-γ-benzyl-L -glutamate, which was prepared from the N-carboxyanhydride by n-hexylamine initiation at [A]/[I] 3, 4, and 8, have been measured in ethylene dichloride and dioxane at different concentrations. The rotatory properties of the polypeptides are all characterized by a trough at 233 mμ of a negative Cotton effect or by a negative circular dichroic band at 223 mμ. With increasing A/I value or concentration, dextrorotation increases and the negative dichroic band becomes deeper. Both the trough magnitude and the negative ellipticity are linearly dependent on the content of β-structure, and the rotatory parameters for the pure β-structure are estimated by extrapolation of the linear relations. Circular dichroism and infrared spectra of the polypeptides have also been measured in trifluoroethanol, and the effect of solvents on the polypeptide conformation is discussed.     

Circular dichroism spectroscopy of 2-aminotetralins

The circular dichroism (CD) spectra of a series of oxygenated 2-(dipropylamino)tetralin derivatives are reported. On the basis of known absolute configurations and conformational preferences of the compounds, the validity of published correlations between the sign of the ¹L_b Cotton effect and the three-dimensional structure was examined. Contrary to predictions, substitution in position 6 or 7 of the tetralin moiety did not change the sign of the ¹L_b Cotton effect. An unexpected sign inversion was, however, observed in some of the compounds containing methyl substituents in the nonaromatic ring. The occurrence of this inversion was not correlated with a change in conformational behaviour and varied depending on the position and nature of the aromatic substituent. No correlations were obvious between the sign of the ¹L_b Cotton effect and the absolute configuration and conformational preferences of the compounds. Therefore, at present, CD spectroscopy does not appear to be useful in assignments of the absolute configurations of 2-(dipropylamino)tetralin derivatives. © 1995 Wiley-Liss, Inc.     

Better than CD: Eugénie Cotton (1881-1967)

Aimé Cotton is known for his invention of circular dichroism spectroscopy. In 1913, he married Eugénie Feytis, a scientist who studied physics with Marie Curie. Following the Second World War, Eugénie Cotton was determined to advance the rights and standing of women, sure in the belief that doing so was necessary not only because it was just but also because a world with women in the forefront would be more secure and less susceptible to the catastrophe worldwide military conflict. She was a cofounder of the Women's International Democratic Federation and served as its first president. In 1951, she was awarded the Stalin Peace Prize, and in 1961, the gold medal from the World Peace Council. The extraordinary life of Eugénie Cotton is reconstructed in a new biography by Loukia Efthymiou, Eugénie Cotton (1881-1967) (Éditions Universitaires Européennes, 2019) that is reviewed here. Among the contributions of Eugénie Cotton of particular interest to the Chirality readership is the biography she wrote of her husband, Aimé Cotton, l'optique et magneto-optique (Éditions Seghers, 1967), the most complete source of information on the founder of the science of circular dichroism. This biography is also discussed here, thereby building two reviews of books, one new and one old, one about Eugénie Cotton and one by her, into a single essay.     

Conformational studies of proteins with aromatic side-chain effects

We present here a brief analysis of ultraviolet isotropic absorption and related circular dichroism of the n–π* and π–π* transitions for the peptide (amide) chromophore in the 185–240 mμ region. Investigations by ultraviolet absorption and circular dichroism techniques on natural amino acids with aromatic chromophores in their side chains are also reported. By taking into account both the peptide and aromatic transitions we discuss the conformational studies of proteins with aromatic side-chain effects. Our attention is largely focused on the optical rotatory dispersion and circular dichroism spectra of these proteins in the near ultraviolet region, where characteristic aromatic side-chain bands occur. The 185–240 mμ region is also discussed when evidence exists of overlapping Cotton effects of aromatic and peptide groups.     

Absolute Configurations of Four Resorcylic Acid Lactones,Paecilomycins J − M,by CD/TDDFT Calculations

The absolute configurations of four resorcylic acid lactones (RALs), paecilomycins J ? M ( 1 ? 3 and 5 ), were assigned by Time‐Dependent Density‐Functional Theory (TDDFT) calculations of their electronic circular dichroism (CD) spectra. The previously reported structure 4 for paecilomycin M was found to be incorrect and should be changed to structure 5 . Analysis of structure‐spectrum relationship for this group of RALs suggested that V′‐shape conformations give type I CD spectra (two negative Cotton effects around 300 and 260 nm, a positive Cotton effect around 220 nm) while V‐shape conformations yield type II spectra (signs of three Cotton effects were opposite to those in type I). Chirality 26:44–50, 2013. © 2013 Wiley Periodicals, Inc.     

The effect of temperature and salt concentration on the circular dichroism exhibited by unionized derivatives of L-alanine in aqueous solution

The circular dichroism of Ac–Ala–NHMe, cyclo(–Ala–Ala–), Ac–Ala–OMe, Ac–Ala–Ala–OMe, and Ac–Ala–Ala–Ala–OMe has been measured in water and in aqueous salt solutions as a function of temperature. Only cyclo(–Ala–Ala–) exhibits circular dichroism which is independent of temperature. Each of the linear derivatives of L -alanine exhibits a positive circular dichroism in the range 208–218 nm at 15°C in water. Heating reduces the intensity of the positive circular dichroism, and only Ac–Ala–OMe retains positive circular dichroism at 75°C in water. Isothermal addition of salts produces changes in the circular dichroism of linear derivatives of L -alanine which resemble those seen on heating. The relative effectiveness of the salts tested, at a concentration of 4M, is LiCl ? KCl = NaCl < MgCl₂ ? CaCl₂ ? NaClO₄. The circular dichroism of cyclo(–Ala–Ala–) is also affected by the salts. Extrapolation of the results obtained with Ac–Ala–OMe, Ac–Ala–Ala–OMe, and Ac–Ala–Ala–Ala–OMe to a long polypeptide with a –CH₂R side chain in the L -configuration leads to the conclusion that this polypeptide should exhibit a temperature-dependent salt-sensitive positive circular dichroism between 208 and 218 nm when it exists as a statstical coil.     

Mass Spectra of Volatile Sulfur Compounds in Foods

The absolute configurations of twelve α-aryl and α,β-diarylalkylamines were studied as N-acyl derivatives by circular dichroism (CD) measurements and by gas chromatography (GC).

The signs of Cotton effects for the S-configuration around 260 nm were positive and those around 210 nm were negative, although some exceptions were found due to the substituents on the benzene nuclei. In contrast, the GC behavior was considered less sensitive to the substituents on the benzene nuclei, and the elution orders were an R-before S-configuration consistently on a chiral OA-300 column. The absolute configurations of some amines were estimated in this study. GC as well as CD measurements could be a promising method for the assignment of the absolute configuration.     

Molecular biology of copper. A circular dichroism study on copper complexes of thionein and penicillamine.

Chicken liver Cd, Zn-thionein (metallothionein) was isolated from Cd-pretreated chickens weighing 1 500 g. The native Cd, Zn-thionein contained 9 g-atoms of metals per 12 000 g of protein. Upon the addition of Cu(CH3CN)4ClO4, all Cd2 and Zn2 were successfully replaced. 15 g-atoms of Cu from the acetonitrile perchlorate complex were bound to the protein. Due to the absence of aromatic amino acid residues, thionein has unique ultraviolet and circular dichroism properties. The shoulder of the ultraviolet spectrum at 250 nm (A250 X A280(-1) = 23.9) was shifted to 275 nm (A250 X A280(-1) = 1.6). No significant absorption was detected in the visible region. Th conformational changes of the protein moiety were much more visible in the circular dichroism spectra. The titration with Cu(CH3CH)2 caused the appearence of three new Cotton effects: 257.5 nm (+), 350 nm (+) and 301 nm (-). The negative Cotton effect at 239 nm of the original metallothionein was completely levelled off. The binding strength of copper with thionein is extraordinarily high: it survives proton treatment up to pH 1.9. Displacement of the Cd2 by Cu employing Cd-thionein which was formed at pH 2.2 resulted in the same circular dichroism properties as observed for Cu-thionein. D-Penicillamine proved a suitable model for the metal-free thionein, since redox reactions and polymerization of the sterically hindered thiol residue are known to be slow. The correlation of the circular dichroism properties of either copper complex using thionein or D-penicillamine was surprisingly high. Circular dichroism measurements of Cu(I)-D-penicillamine revealed Cotton effects at 255 nm (+), 280 nm (+) and 355 nm (-). Upon examining the red-violet mixed Cu(-i)-cu(II)-D-penicillamine complex, Cotton bands in the visible region at 425 nm (-) and 495 nm (+) were seen. In many blue copper enzymes, the copper is assumed to be in the neighborhood of both cysteine and aromatic amino acid residues, which are known to play an important role in the electron transfer. This is not the case in the Cu-thionein, which would explain many different properties of this copper protein. It is very attractive to conclude that the sterically hindered SH-group of D-penicillamine reacts with excess copper in a specific way, similar to the Cu-thionein. This phenomenon could explain the considerable success of D-penicillamine in the treatment of Wilson's disease.     

Circular dichroism of bilirubin-amine association complexes: insights into bilirubin-albumin binding

Bichromophoric (4Z, 15Z)-bilirubin-IX alpha, the yellow-orange cytotoxic pigment of jaundice, adopts either of two intramolecularly hydrogen-bonded enantiomeric conformations that are in dynamic equilibrium in solution. The addition of optically active amines induces the pigment solutions to exhibit intense bisignate circular dichroism in the region of the bilirubin long wavelength uv-visible absorption band. The most intense circular dichroism Cotton effects, (delta epsilon) approximately equal to 130, are induced by beta-arylamines and are comparable to those exhibited by bilirubin complexes with serum albumin and other proteins. Like serum albumin and other proteins, the optically active base acts as a chiral complexation agent to induce an asymmetric transformation of bilirubin, whose induced bisignate circular dichroism Cotton effect is characteristic of exciton splitting of the component pyrromethenone chromophores. The amines thus serve as chiral templates for molecular recognition, and the complementary action of the amine complexation sites provides insight into the binding forces important in protein-bilirubin heteroassociation.     

Circular dichroism studies on α- and β-ketosides of 5-acetamido-3,5-dideoxy- -glycero- -galacto-nonulopyranosonic acid (N-acetylneuraminic acid) and of some of its derivatives

The circular dichroism spectra of a number of N-acetylneuraminic acid derivatives in aqueous solution were studied. For all compounds, the Cotton effects were found to be in the spectral range of the acetamido and carboxyl chromophores. The c.d. curves of the methyl, ethyl, and allyl α- -ketosides are characterized by a broad, positive band centered at λ ≈ 195 nm with a slight skew towards the higher wavelengths and weak bands between λ 225 and 255 nm, whereas the methyl β- -ketoside and the corresponding methyl ester show only an intense positive band with a broad shoulder in the same spectral range. 5-Acetamido-3,5-dideoxy- -glycero-β- -galacto-nonulopyranose, its methyl β- -ketoside, and 5-acetamido-3,5-dideoxy- -glycero- -galacto-nonulopyranosonamide containing only the acetamido chromophore showed one single positive Cotton effect centered at λ ≈ 192 nm. The c.d. spectrum of 5-acetamido-3,5-dideoxy- -glycero- -galacto-nonulopyranosonic acid confirms the β- configuration of the free acid in aqueous solution, whereas the shape of the c.d. curve of O-(N-acetyl-α- -neuraminopyranosyl)-(2→3)-O-β- -galactopyranosyl-(1→4)- -glucopyranose resembles that of the methyl, ethyl, and allyl α- -ketosides 2-4.     

Induced circular dichroism of DNA-dye complexes

The binding of methylene blue, proflavine, and ethidium bromide with DNA has been studied by spectrophotometric titration. Methylene blue and proflavine or methylene blue and ethidium bromide were simultaneously titrated by DNA. The results indicate that all of these dyes compete for the same bindine sites. The binding properties are discussed in terms of symmetry. The optical properties of the dye–DNA complexes have been studied as a function of DNA/dye ratio. The induced circular dichriosm due to dye–dye interaction was measured at low dye/DNA ratios for cases involving both the same dye and different dyes. A positive Cotton effect for DNA–proflavine complex may be induced at 465 mμ by eithr proflavine or ethidium bromide, whereas a netgative Cotton effect at 465 mμ may be induced by methylene blue. The limiting circular dichroism, with no dye–dye interaction, and the induced circular dichroism spectra are discussed in terms of symmetry rules.     

Random copolymers of alpha-benzyl-L-aspartate with ortho- and para-nitrobenzyl-L-aspartates. Intrinsic and extrinsic dichroic bands and the left-to-right-handed alpha-helical transition.

Copolymers of benzylaspartate with the corresponding para-nitro and ortho-nitro derivatives are known to undergo, at increasing nitro content, a transition from a left-handed α-helical conformation to a right-handed α-helical conformation. The circular dichroism associated with the n, π* transition of the amide group, as well as the extrinsic bands associated with the nitrobenzyl chromophore, have been studied for these copolymers as a function of the nitro content. The circular dichroism associated with the 330-nm extrinsic band is shown to present an abrupt change, which parallels the change in the 222-nm band characteristic of the left- to right-handed helix transition. The intensity of the 222-nm CD band seems unaffected by the interaction with the side-band chromophore. The circular dichroism associated with the 330-nm band is much stronger in the right-handed conformation and is unaffected by increasing interactions between side chains. Interpretation in the light of the possible mechanism for optical activity of helical molecules seems to indicate that the 330-nm extrinsic effect is essentially due to the Condon, Altar, and Eyring (CAE) mechanism and μ-m perturbation (in Schellmann terminology) on the side-chain chromophore n, π* transition.     

Synthesis,Molecular Structure,and Chiroptical Properties of Dibenzylidene Derivatives of Bicyclo[3.3.1]nonane and Brexane

Synthesis of several enantiomerically pure unsaturated bicyclo[3.3.1]nonane and related brexane (tricyclo[4.3.0.0^3,7]nonane) derivatives bearing exocyclic benzylidene substituents from readily available (+)‐(1S,5S)‐bicyclo[3.3.1]nonane‐2,6‐dione was accomplished. Molecular geometry and chiroptical properties of compounds with enone and styrene chromophores were studied by X‐ray diffraction analysis, molecular modeling, and circular dichroism (CD) spectroscopy. Difunctional 3,7‐dibenzylidenebicyclo[3.3.1]nonanes, such as 2 and 7 , 8 , 9 , exhibited intense CD couplets, arising from the exciton coupling between the two unsaturated chromophores. The observed negative sign of the exciton couplets is congruent with the negative twist (negative chirality) defined by the two interacting transition dipoles. The sign of the Cotton effect corresponding to the π→π* transitions in the CD spectra of monoenone 4 and tricyclic brexane acetate 11 was correlated with the intrinsic dissymmetry (helicity) of the styrene chromophore. Chirality 27:728–737, 2015. © 2015 Wiley Periodicals, Inc.