Sign Of Cotton Effect Research Articles

Mitomycin antitumor compounds: Part 1. CD studies on their molecular structure

The UV-Vis and circular dichroism (CD) spectra of several mitomycin antitumor compounds and some of their derivatives were analyzed in order to attribute the proper assignment to their electronic transitions. The lowest energy π→π* transition was found to depend on the effect of the auxochromic group in the aromatic ring, whereas the three n→π* transitions, present at around 240, 400 and 560 nm, are related to the C(9)O of the carbamoyl group and to the C(8)O and the C(5)O of the quinone, respectively. The chirality of the C(9) is responsible for the sign of the Cotton effect (CE) at around 240 nm, whereas the substituents of the chromophore for mitosane derivatives and the conformation of the carbamoyloxymethyl group at C(9) determine the CE sign of the 1A→ 1L b transition. When the aziridine ring was opened and mitosenes derivatives were obtained, CD spectra did not differ significantly among the compounds and the bands associated to the different transitions had similar Cotton effect. Our findings suggest that the differences in the CD spectra, observed between mitosanes and mitosenes, are probably related to the more rigid molecular structure of the mitosene derivatives and the different conformations in solution of the C(9) side chain.

Chirality inversion in the bilirubin molecular exciton.

The bichromophoric pigment bilirubin acts as a molecular exciton in its UV-visible and circular dichroism (CD) spectroscopy. In both polar and nonpolar solvents, an optically active analog, (beta R,beta 'R)-dimethylmesobilirubin-XIII alpha (1), exhibits intense bisignate CD Cotton effects in the region of its long wavelength UV-vis absorption near 400 nm: Delta epsilon(434)(max) + 337, Delta epsilon(389)(max) - 186 (CHCl(3)), and Delta epsilon(431)(max) + 285, Delta epsilon(386)(max) - 177 (CH(3)OH). However, introduction of an amine into a CHCl(3) solution of 1 causes the Cotton effect signs to become inverted, e.g., after addition of NH(3), Delta epsilon(433)(max) - 345, Delta epsilon(389)(max) + 243, and after addition of ethylene diamine, Delta epsilon(435)(max) - 420, Delta epsilon(390)(max) + 299. The sign inversions imply inversion of molecular chirality of the bilirubin and the phenomenon appears to be general for amines, including alpha,omega-diamines. 1,8-Diaminooctane was found to be more effective than longer or shorter chain analogs in producing CD sign inversion.

Asymmetric transformation of N-nitrosamines by inclusion crystallization with optically active hosts.

Several N-nitrosopiperidines with chirality solely due to a hindered rotation about the N-N bond were resolved to enantiomers by inclusion crystallization with optically active diols (TADDOLs). The absolute configuration of the guest nitrosamines was deduced from the X-ray crystal structures of the inclusion complexes. The enclathrated nitrosamines were liberated by a competitive complexation of the host diols with piperazine. The optical activity of the resolved nitrosamines is manifested by their CD spectra. A simple chirality rule was proposed for a rationalization of the observed Cotton effect sign corresponding to the n-pi* electronic transition. The optically active nitrosamines are configurationally labile compounds and gradually racemize in solution but they are indefinitely stable in the solid state. The first-order kinetics of the racemization in solution allowed us to assign the N-N rotation barriers by simple polarimetric measurements.

Conformational properties and chiroptical spectra of lactams and thiolactams with 2-azabicyclo[2.2.1]heptane, 2- and 3-azabicyclo[3.2.1]octane skeletons

The CD spectra of several bicyclic lactams and thiolactams were measured in different solvents. The concentration dependence of the spectra observed in hydrocarbon solvents was attributed to shifts in the equilibrium between monomer and hydrogen-bonded dimer forms. The CD of some compounds is characterized by unusually strong Cotton effects resulting from non-planarity of the amide bonds due to internal strain of the bicyclic skeletons. The X-ray crystallographic structures of 2a, c, 3b, d and 4a, b showed different degrees of distortion of the amide or thioamide moieties from planarity, which causes inherent chirality of the chromophores and profoundly affects the Cotton effect sign and magnitude. This distortion also restricts application of the sector rules for prediction of the n–π * CD sign, since they can be used only for compounds with planar chromophores.

1,8-Naphthalimides as Stereochemical Probes for Chiral Amines: A Study of Electronic Transitions and Exciton Coupling.

The absorption and magnetic circular dichroism (MCD) spectra of 1,8-naphthalimide are analyzed in terms of the number of contributing electronic transitions and their polarization. The experimental results are supported by semiempirical INDO/S calculations. It is demonstrated that the strongly allowed, pi --> pi naphthalene transition of the 1,8-naphthalimide chromophore located at 231 nm is perfectly suited for absolute configuration assignments of amine derivatives on the basis of the bichromophoric exciton coupling. Both degenerate (bis-1,8-naphthalimide) and nondegenerate (1,8-naphthalimide-phthalimide, 1,8-naphthalimide-phenyl, or 1,8-naphthalimide-benzoate) couplings were studied. In the latter case, the sign of the exciton Cotton effect was opposite to the sign of the degenerate exciton Cotton effect for the same absolute configuration. An extension of the application of the exciton coupling to the 264 nm pi --> pi transition of 1,9-anthraimide is also shown.

Solving challenging bioorganic problems by exciton coupled CD

Abstract

Autoassembling of the cage structures

Enantiomeric dilactones ((1R,4R)-(+)-1 and (1S,4S)-(-)-1) of αα′-dihydroxy-αα′-di-tert-butylglutaric acid have been prepared. The Cotton effect sign of the n→π*-transition of the lactone chromophore in enantiomers1 is determined by the contribution of the uncompensated bonds of the δ-dilactone ring, but not by that of the γ-monolactone ring of1. The correlation of the Cotton effect sign of the n→π*-transition with the chirality of the cage structure and the absolute configuration for the series of 1,4-dialkyldilactones of type1 has been suggested. The contribution of the pseudo-a-oriented amide group to, the Cotton effect sign of the lactone n→π*-transition (the effect of the third chiral sphere) in diastereomeric lactonamides2a,b predominates over that of the nonplanar bonds of the heterocycle (over the effect of the second chiral sphere).

Chirality Assignment of Amines and Amino Alcohols Based on Circular Dichroism Induced by Helix Formation of a Stereoregular Poly((4-carboxyphenyl)acetylene) through Acid−Base Complexation

An optically inactive polyacetylene, poly((4-carboxyphenyl)acetylene) (poly-1), exhibits an induced circular dichroism (ICD) in the UV−visible region upon complexation with chiral amines and amino alcohols in DMSO and in the film, the sign of which reflects the stereochemistry including bulkiness, type (primary, secondary, or tertiary), and absolute configuration of the amines. Therefore, the polyacetylene can be used as a novel probe for determining the chirality of amines. Most primary amines and amino alcohols of the same configuration gave the same sign for the induced Cotton effect; however, secondary and/or tertiary amines used in the present study tended to show Cotton effect signs opposite to those of the primary amines and amino alcohols of the same configuration. The magnitude of the ICD likely increases with an increase in the bulkiness of the chiral amines. The complexation dynamics during the formation of the helical structure of poly-1 with chiral amines were investigated on the basis of the spin−spin relaxation behavior and 1H NMR, CD, and optical rotatory dispersion (ORD) titrations. The complex formation of poly-1 with chiral amines such as 1-(1-naphthyl)ethylamine and 2-amino-1-propanol exhibits a positive nonlinear effect between the enantiomeric excess of the chiral amines and amino alcohols and the observed ellipticity of the Cotton effects. The excess enantiomer bound to poly-1 may induce an excess of a single-handed helix (right- or left-handed helix), which may result in a more intense ICD than that expected from the ee of the amine. Moreover, it was found that the coexistence of achiral amines such as 1-aminoethanol also induced an excess of one helical sense of poly-1.

Stereochemistry and chiroptical spectra of 3-azabicyclo[3.1.0]hexan-2-ones and thiones

Several optically active substituted 3-azabicyclo[3.1.0]hexan-2-ones and their thiocarbonyl analogues have been synthesized, and their circular dichroism spectra studied. The crystal structure of thiolactam 1a showed that the bicyclic skeleton of the title compounds assumes a sofa-like geometry. It is postulated that the cyclopropyl moiety and amide or thioamide group constitute an inherently chiral chromophore, helicity of which determines the Cotton effect sign corresponding to the n-π ∗ electronic transition. The weak π-π ∗ Cotton effect of thiolactams shows opposite sign to that observed for the lowest energy excitation.

Synthesis, stereochemistry, and chiroptical spectra of cyclopropyl lactones and thionolactones

Several optically active substituted 3-oxabicyclo[3.1.0]hexan-2-ones and their thiocarbonyl analogues were synthesized, and their circular dichroism spectra are reported. It was found that the n-π ∗ Cotton effect sign is determined by the helicity of an inherently chiral chromophore formed by the lactone or thiolactone group and the cyclopropyl moiety. The π-π ∗ Cotton effect of thiocarbonyl compounds shows opposite sign to that observed for the lowest energy transition. The crystal structures of two compounds were solved to establish their molecular geometries.

A difference CD method for determining absolute stereochemistry of acyclic 1,2,4-triols

A general method based on difference circular dichroic (DIF CD) spectroscopy for assigning the absolute configuration of 1,2,4-triol is presented. Four possible stereoisomers of 6-heptene-1,2,4-triol were prepared and served as models to develop the procedure. The sign of the DIF CD Cotton effect is correlated to the absolute configuration of the C2 position.

Stereospecificity of Trans-Dihydrodiol Oxidation by Dimeric and Monomeric Dihydrodiol Dehydrogenases from Mammalian Tissues1

The stereochemical course in the enzymatic oxidation of trans-dihydrodiols of benzene and naphthalene by dimeric dihydrodiol dehydrogenase of monkey kidney was compared with that by monomeric dihydrodiol dehydrogenase of rat liver. The monkey kidney and rat liver enzymes each oxidized about half of the racemic dihydrodiol of benzene added to the reaction mixture, but almost all the substrate was disappeared in the reaction mixture containing both enzymes. The CD spectra of the unreacted dihydrodiols of benzene and naphthalene in reaction mixtures containing the rat liver enzyme showed the negative sign of Cotton effect, while those in reaction mixtures containing the monkey kidney enzyme gave the positive sign of Cotton effect. Thus, the monkey kidney dimeric enzyme selectively oxidized (-)-[1R,2R]-dihydrodiols of aromatic hydrocarbons, in contrast to the stereo-specificity of the rat liver enzyme for the (+)-[1S,2S]-isomers. The (+)-[1S,2S]- and (-)-[1R,2R]-dihydrodiols of benzene were separately prepared from the racemic form by using the two enzymes, and were used as substrates to determine the stereospecificity of dihydrodiol dehydrogenases from other mammalian tissues. The dimeric enzymes from pig liver and rabbit lens also exhibited specificity for the (-)-isomer, which was opposite to that of the monomeric enzymes from human and mouse liver, although aldehyde reductase and aldose reductase oxidized both (+)- and (-)-isomers.

Stereochemistry and chiroptical properties of 1,3-dialkylaziridinones (α-lactams). Chiral rules for the nonplanar amide chromophore

Structural features, configurational stability, and chiroptical properties of the nonplanar amide group in α-lactams were investigated by means of ab initio (6-31 + G*) molecular orbital calculations on (1R)-aziridinone 1, (1R)-1-methylaziridinone 2, (1R,3R)-3-methylaziridinone 3, (1R,3R)-1,3-dimethylaziridinone 4a, its cis diastereomer (1S,3R)-1,3-dimethylaziridinone 4b, and (1R,3R)-3-tert-butyl-1-methylaziridinone 5, and by experimental CD spectra of 1-tert-butyl- and 1-(1′-adamantyl)-substituted 3(R)-3-tert-butylaziridinones 6 and 7. The nitrogen inversion barriers of 4a and 4b are 2.8 and 1.6 kcal mol−1, respectively. The lowest excited singlet state of all of the aziridinones is a valence state (the nO–πCO* transition); the second is a Rydberg state (the nN–3s transition). The signs of the first and second Cotton effects in the CD spectra of the compounds 6 and 7 coincide with the calculated ones for 1 and 2 and the trans isomers 3, 4a, and 5. According to the calculated and experimental data for aziridinones 1–7 as well as to the well-known data for other nonplanar amides, the sign of the first Cotton effects is determined by the intrinsic chirality of the nonplanar amide chromophore and obeys a spiral rule. For cases where the chromophore has the conformation around the N—C(O) bond, which is close to the antiperiplanar, a reverse octant rule is proposed.

Absolute Configuration of 1,4-Dialkyl-2,5-dioxabicyclo[2.2.1]heptane-3,6-dione Enantiomers

The correlation of the Cotton effect sign of the n → π* transition with the cage structure chirality and the absolute configuration of 1,4-dialkyl-2,5-dioxabicyclo[2.2.1]heptane-3,6-diones has been established.

Conformational dependence of the circular dichroism of N-nitrosopyrrolidines

Several suhstituted N-nitrosopyrrolidines were prepared and their chiroptical spectra studied. The circular dichroism of monocyclic compounds depends on substituents, solvents, and temperature changes. Some of these N-nitrosamines exhibit bisignate CD curves in the region of n-π * transition. On the contrary, conformationally restrictcd bi- and tricyclic compounds show monosignate Cotton effects, the magnitudes of which are almost solvent independent. Bisignate CD curves result from two half-chair conformers of the pyrrolidine ring being in equilibrium and contributing with the opposite CD signs. The Cotton effect signs can be predicted with our «lowered symmetry» sector rule developcd earlier

Chiroptical properties of C2-symmetric N-haloaziridines. Chiral rules for the N-haloaziridine chromophore

N-Chloro(a) and N-bromo (b) derivatives of C 2 -symmetricaziridines (2S,3S)-1-halogen-2,3-dimethylaziridines 1a,b and (2S,3S)-1-halogen-2,3-bis(alkoxycarbonyl)aziridines 2a,b and 3a,b were obtained. Haloaziridines 1a,b are an example of the «pure» N-haloaziridine chromophore which has the first Cotton effect (CE) in the region of 260-300 nm. A quadrant rule which connects the first CE sign with the stereochemical environment of the chromophore is offered. Haloaziridinecarboxylic esters are a specific case of the N-haloaziridine chromophore. The second CE sign at 220-230 nm in the CD spectra of these compounds obeys a reverse quadrant rule

Molecular geometry and circular dichroism spectra of bicyclo[2.2.1]heptane-2,3-dicarboxylic anhydrides and imides

Several tricyclic anhydrides and imides derived from optically active bicyclo[2.2.1]heptane-2,3-dicarboxylic acids were synthesized, and their circular dichroism spectra are reported. On the basis of MNDO calcultions it was estalished that despite rigidity of the norbornane system the five-membered rings of succinic anhydride and imide moieties are slightly twisted. The chromophores are flexible and can be more or less skewed depending on solvent polarity. The chromophore nonplanarity significantly influences magnitude and sign of the first Cotton effect associated with the lowest energy n-π * electronic transition. The sign of the second n-π * Cotton effect is governed by vicinal effect of substituents

Optically active 2-cymantrenyloxazolines: synthesis and regioselective metallation

Three optically active oxazolines with a cymantrenyl substituent at position 2 of the heterocycle have been prepared. Metallation of these compounds withn-BuLi proceeds only at the two diastereotopic α- and α'-positions of the Cp-ring to an equal extent. The dependence of the sign of Cotton effect in the region of 300–350 nm upon the absolute configuration of chiral centers remote from the Cp-ring has been demonstrated.

Chiroptical properties of the non-planar nitrosamine chromophore in N-nitrosaziridines

The sign of the long-wavelength Cotton effect in the circular dichroism (CD) spectra of N-nitrosaziridines, possessing a non-planar nitrosamine chromophore, is determined by the intrinsic chirality of the chromophore, as in the cases of N-acylaziridines and gauche-cyclopropylketones.

Nucleosides and Nucleotides. 108. Synthesis and Optical Properties of Syn-Fixed Carbon-Bridged Pyrimidine Cyclonuclesides.

6, 1'-Propanouridine (10), a carbon-bridged cyclouridine fixed in the syn-conformation, was synthesized from D-fructose. Two additional carbon-units were introduced at the 1'-position of 1'-hydroxymethyl-O2, 2'-anhydrouridine 13 and inversion of the 2' hydroxyl group was achieved by sequential oxidation-reduction reactions. Finally, the spiro-carbon bridge was constructed by radical cyclization of the 1'-iodopropyl derivative of 5-chlorouridine. Dehydrochlorination followed by deprotection gave the desired 10. The circular dichroism (CD) spectrum of 10 showed a negative Cotton effect ([θ]=-6100) at the main absorption region, whereas 5'-O-tert-butyldimethylsilyl-2', 3'-O-isopropylidene-6, 1'-propanouridine (30) showed almost no Cotton band at the same absorption region. These results suggest that the critical region in which the CD Cotton effect changes from negative to positive is present in the syn region where 10 is located. Correlation of the magnitude and the direction of the sign of the CD Cotton effect and the torsion angle (χ) is also discussed.