Sign Of Cotton Effect Research Articles

Controlling Chirogenic Effects in Porphyrin Based Supramolecular Systems: Theoretical Analysis Versus Experimental Observations.

Electronic circular dichroism (ECD) spectroscopy is a widely employed method for studying chiral analysis, requiring the presence of a chromophore close to a chiral centre. Porphyrinoids are found to be one of the best chromophoric systems serving for this purpose and enabling the application of ECD spectroscopy for chirality determination across diverse classes of organic compounds. Consequently, it is crucial to understand the induction mechanisms of ECD in the porphyrin-based complexes. The present study explores systematically the influence of secondary chromophores, bonded to an achiral zinc porphyrin or to chiral guest molecules, on the B-region of ECD spectra using the time-dependent density functional theory (TD-DFT) calculations. The study analyses the impact of change in both the conformation of achiral porphyrin (host) and change in position and conformation of chiral organic molecule (guest) on the B-band of ECD spectra (energy, intensity, sign of Cotton effect). Finally, conclusions made on model complexes are applied to published experimental data, contributing to a deeper understanding of various factors influencing ECD spectra in chiral systems. In addition, a computer program aimed to help rationalise ECD spectra by visualizing corresponding orbital energies, rotatory strengths, electric and magnetic transition moments, and angles between them, is presented.

Photoinvertible Chiral Liquid Crystal that Affords Helicity‐Controlled Aromatic Conjugated Polymers

AbstractPhotoinvertible chiral compounds are synthesized by linking a photoresponsive bisbenzothienylethene moiety with an axially chiral binaphthyl moiety and used as chiral dopants to prepare a photoinvertible chiral nematic liquid crystal (N*‐LC) field. Subsequently, electrochemical polymerizations of ethylenedioxythiophene (EDOT) in the N*‐LC field to synthesize helical poly(ethylenedioxythiophene)s (H‐PEDOTs) are achieved. The H‐PEDOTs show not only spiral morphologies resembling the fingerprinted texture of N*‐LC in polarizing optical microscope but also bisignate Cotton effects in circular dichroism spectra, indicating the formation of a helically π‐stacked structure in terms of the main chains of H‐PEDOT. In addition, the signs of the bisignate Cotton effect are strictly determined by the helicity of the N*‐LC. The present N*‐LC is the first reaction field exhibiting photoinvertible chirality with extremely high fatigue resistance and serves as an asymmetric medium for electrochemical polymerization, leading to dynamic helicity control of conjugated polymers.

Absolute Configuration Assignment to Chiral Natural Products by Biphenyl Chiroptical Probes: The Case of the Phytotoxins Colletochlorin A and Agropyrenol

The application of flexible biphenyls as chiroptical probes for the absolute configuration assignment to chiral natural products is described. The method is straightforward and reliable and can be applied to conformationally mobile and ECD silent compounds, not treatable by computational analysis of chiroptical data. By this approach, the (6′R) absolute configuration of the phytotoxin colletochlorin A (1) was confirmed, while the absolute configuration of the phytotoxin agropyrenol (2), previously assigned by the NMR Mosher method, was revised and assigned as (3′S,4′S). Moreover, with the biphenyl method the configurational assignment can be obtained simply by the sign of a diagnostic Cotton effect at 250 nm in the ECD spectrum, thus allowing application without the need of advanced knowledge of chiroptical spectroscopy and computational protocols.

Decoding the ECD Spectra of Poly(phenylacetylene)s: Structural Significance.

The role of the main dihedral angles in the electronic circular dichroism (ECD) spectra of poly(phenylacetylene)s (PPAs) was estimated by using time-dependent density functional theory (TD-DFT) for oligo(phenylacetylene)s (n = 12). These studies reveal that in cis–transoidal arrangements, the first Cotton effect is dominated by excitations involving molecular orbitals (MOs) mainly related to the polyene backbone. Hence, for this scaffold, the ± sign of the first Cotton effect reflects the P/M helical sense of the internal helix of the polymer. However, in cis–cisoidal arrangements, contribution of MOs in the polyene and the aryl rings of the PPA backbone produce the first Cotton effect band. As a result, two different ECD signatures with three or four alternating Cotton effects can be produced depending on the sign of the ω1 and ω3 dihedral angles which determine the helical sense of the polyene (ω1) and the relative orientation of the aryl ring toward the polyene (ω3), respectively. Thus, on the one hand, if ω1 and ω3 rotate in opposite directions, a CD with three alternating Cotton effects is observed, where the sign of first Cotton correlates with the P/M helical sense of the polyene. On the other hand, if ω1 and ω3 rotate in the same direction, a CD signature with four alternating Cotton effects is produced where the information relative to the P/M helical sense of the polyene is contained in the second Cotton effect.

L-Stercobilin-HCl and d-Urobilin-HCl. Analysis of Their Chiroptical and Conformational Properties by VCD, ECD, and CPL Experiments and MD and DFT Calculations.

Vibrational circular dichroism (CD) and IR spectra of dichloromethane solutions of l-stercobilin and d-urobilin hydrochlorides have been recorded in the mid-IR region. The spectra are best interpreted by combining molecular dynamics calculations and density functional theory (DFT) calculations within the quantum mechanics/molecular mechanics ONIOM-type framework, and the combined predicted results are better and more informative than the more standard analysis provided by DFT calculations. The same approach also sheds light on the Cotton effect sign inversion of room temperature versus low-temperature electronic CD spectra of the same compounds in methanol-glycerol solution. Finally, circularly polarized luminescence spectra for l-stercobilin in chloroform solution provide information on the excited-state geometry of this molecule.

Diagnostic absolute configuration determination of clavulanate potassium: A comprehensive investigation of chiroptical spectroscopies and theoretical calculations

Clavulanate potassium (CP) is a classic β-lactamase inhibitor, which is extensively used as a combination drug in antibiotics therapy. As a chiral drug, CP is the only effective stereoisomer revealing prominent activities. To determine the chirality of CP efficiently, we provide an accurate and convenient method based on the comprehensive investigation of circular dichroism spectra and theoretical calculations. The results demonstrate two distinguishable cotton effects in electronic circular dichroism (ECD) and a sequence of cotton effect signs at specific wavenumbers in vibrational circular dichroism (VCD) can be regarded as diagnostic characteristics for the determination of absolute configuration. Additionally, the corresponding spectroscopic appearance of CP was elucidated with the help of theoretical analysis of molecular orbitals, natural bond orbitals and molecular electrostatic potential. The explicit absolute configuration determination of CP facilitates the thorough understanding in the stereochemistry of clavulanate potassium and its derivatives.

Solvation of 2-(hydroxymethyl)-2,5,7,8-tetramethyl-chroman-6-ol revealed by circular dichroism: a case of chromane helicity rule breaking.

The primary goal of this work is to clarify why 2-(hydroxymethyl)-2,5,7,8-tetramethyl-chroman-6-ol {(S)-TMChM} deviates from the chromane helicity rule under solvent change. The rule, applicable to determining the absolute configuration of molecules containing the chromane chromophore, binds the sign of the 1Lb Cotton effect (CE) with the helicity of the dihydropyran ring. In case of TMChM, however, this CE exhibits extreme solvent dependence: it is negative in non-coordinating solvents and positive in coordinating ones, irrespective of the helicity of the heterocyclic ring. TD-DFT calculations using PCM and hybrid solvation models were performed to explain origin of this phenomenon. It turned out that the 1Lb CE sign directly depends on the position of the phenolic OH group at carbon atom C6 (OHC6). In the absence of interactions with solvents (as in CCl4 or nC6H14) or when a solvent plays proton donor role (as in CHCl3), the OHC6 lies in the phenyl plane and the 1Lb CE sign follows the P/M helicity rule. In contrast, in proton acceptor solvents, like DMSO, CH3OH or CH3CN, the OHC6 group is deflected from the phenyl plane, and the 1Lb CE sign of individual (S)-TMChM conformers depends on the sector in which the OHC6 is located. Thus, in solution, the 1Lb CE sign is an average over different orientations of the OHC6 group and can be positive (as in DMSO and CH3OH) or negative (as in CH3CN) which means that it does not follow the chromane helicity rule. The impact of OHC6 on the 1Lb CE sign and thus the conclusions for the stereochemistry of chromans are demonstrated here for the first time. Additionally, a comparison of experimental and simulated ECD spectra, supported by VCD data, allowed to determine the geometry of intermolecular clusters formed in different solvents.

Circular dichroism spectroscopy and DFT calculations in determining absolute configuration and E/Z isomers of conjugated oximes.

The primary purpose of this work was to demonstrate the suitability of circular dichroism (CD) spectroscopy in stereochemical studies of α,β-unsaturated oximes, with particular emphasis on determination of E and Z geometry of the oxime double bond. As models for this study, O-phenyl and O-triphenylmethyl (trityl) oximes of 4-hydroxy-2-methylcyclopent-2-en-1-one were selected. These model compounds differ in both absolute configuration at C4 carbon atom and E-Z configuration of the oxime double bond. The basic dichroic technique applied was electronic circular dichroism (ECD) assisted by quantum-chemical calculations and vibrational circular dichroism (VCD) for selected cases. Such an approach enabled effective implementation of both goals. Thus, we were able to associate the signs of Cotton effects in the range of 190-240nm with the absolute configuration at C4 and within 240-300nm with the E- or Z-geometry of the oxime double bond. Within this work, optical activity of the protecting trityl group was also studied towards formation of the propeller-shaped conformations by using the same combined CD/DFT methodology. As shown, the helical structure of the trityl group has a considerable influence on the ECD spectra. However, the MPM and PMP conformers of the trityl group are in fact almost equally populated in the conformational equilibrium, making it impossible to distinguish them. On the other hand, rotamers of the hydroxyl group at C4 show a decisive impact on the VCD spectra in both phenoxy and trityl oximes.

Synthesis and Comprehensive Structural and Chiroptical Characterization of Enones Derived from (-)-α-Santonin by Experiment and Theory.

The aim of the present work is to explain the causes of the observed deviations from sector and helicity rules to determine the absolute configuration of optically active α,β-unsaturated ketones by means of electronic circular dichroism (ECD). To this end, a series of model compounds with a common decahydronaphthalene skeleton representing both cisoid and transoid enones were synthesized. In the framework of this work, detailed dichroic studies supported by single crystal X-ray analysis were performed where possible. To assist the achievement of the desired objectives the conformational flexibility of the selected cis-enones through the dependence of solvent and temperature on the ECD spectra were examined. All experimental studies were supplemented by detailed DFT calculations. A notable result of the study is assessing the applicability of the enone sector and helicity rules in dichroic studies and potential restrictions. To this end, a number of factors that could determine the signs of the individual Cotton effects has been considered. Among these nonminimum structure effects, i.e., twisting of the enone chromophore and nonplanarity of the enone double bond can be mentioned.

Molecular geometry and optical activity of helically chiral N-nitrosamines derived from 1,2,3,4-tetrahydro- and 1,2,3,4,7,8,9,10-octahydro-1,10-phenanthroline

X-ray crystallographic analysis of the title N-nitrosamines revealed that they assume helical conformations in the solid state. Nitrosamines 1b and 2b were resolved by inclusion crystallization with optically active diols (TADDOLs). The absolute configuration of the guest molecules in the complexes 1b·3b and 2b·3b was assigned as M. The optical activity of the resolved compounds is manifested by their solid state CD spectra, which showed relatively strong Cotton effects in the region of the nitrosamine n–π∗ transition. Theoretical calculations of the electronic and CD spectra performed by classic ab initio methods predicted the correct Cotton effect signs of 1b and 2b.

Dimolybdenum Tetracarboxylates as Auxiliary Chromophores in Chiroptical Studies ofvic-Diols

The aim of the present work was to check the suitability of dimolybdenum carboxylates, other than commonly used [Mo2(OAc)4], as auxiliary chromophores for determining the absolute configuration of optically active vic-diols by means of electronic circular dichroism (ECD). To this end, a set of dimolybdenum tetracarboxylates was synthesized, and subsequently, the two most promising compounds were selected, namely dimolybdenum tetrakis(μ-pivalate) and tetrakis(μ-isovalerate). The selection was based on their solubility in commonly used solvents, their stability in solution, their tolerance to air exposure, as well as their utility for dichroic studies. The stability of the obtained in situ chiral complexes was verified by measuring the dependence of ECD, UV-vis, and NMR spectra on time, temperature, and concentration. We have shown that the ECD spectra of diverse vic-diols with these complexes are suitable for configurational assignment based on the correlation between signs of Cotton effects (CEs) arising in the spectra and the stereostructure of the ligand. Furthermore, to aid in the interpretation of experimental results, a separate set of DFT calculations has been incorporated to provide additional insight into the structure of the chiral complexes involved. In contrast to the earlier assumptions, experiments showed that the chelating mode of ligation is preferred for the studied complexes.

Chiral isothiocyanates – An approach to determination of the absolute configuration using circular dichroism measurement

Chiral alkyl 2-isothiocyanates have been obtained from enantiopure, aliphatic amines. ECD measurements allowed us to correlate an absolute configuration at C-2 with a sign of the Cotton effect (CE) observed for n–π* transition at the longer-wavelength range of the spectrum. Chirooptical data calculated for all enantiomers were consistent with the measured CE values and indicated that the weak absorption band at 240nm could give an important information concerning the stereochemistry of simple, chiral isothiocyanates. Optically active esters of 2-isothiocyanatocarboxylic acids, prepared from α-amino acids, showed two absorption bands located over 195nm. The more intensive band near 200nm and the weak absorption located at 250nm were related to n–π* transitions in NCS group. TD DFT calculations carried out for methyl esters of 2-isothiocyanatocarboxylic acids showed the correlation between signs of CE determined for both absorption bands, and the absolute configuration on C-2.

Spontaneous generation of chirality and chiroptical spectra of N-nitroso-2,4-diaryl-3-azabicyclo[3.3.1]nonanes

The crystal structures of several bicyclic N-nitrosamines indicate that they crystallize in the chiral (Sohncke) space group P212121 as conglomerates. This allows the resolution of these compounds by manual picking of the enantiomorphous crystals. The optical activity of the single crystals was confirmed by their CD spectra taken in KBr disks. The absolute configurations of the title nitrosamines were assigned by crystallographic measurements and by a comparison of their CD spectra with those of a reference compound resolved by classical methods. The observed Cotton effect signs, corresponding to the n–π∗ transition, were correlated with the helicity of the inherently chiral nitrosamine chromophore.

Chirality sensing of chiral pyrrolidines and piperazines with a liquid crystalline dynamic helical poly(phenylacetylene) bearing ethyl phosphonate pendant groups

AbstractStereoregular cis‐transoidal poly(phenylacetylene) bearing a phosphonic acid monoethyl ester as the pendant group (poly‐1‐H) was found to form a preferred‐handed helix upon complexation with various optically active pyrrolidines and piperazines in dilute dimethyl sulfoxide and water, and the complexes exhibited characteristic induced circular dichroisms (ICDs) in the UV‐vis region of the polymer backbone. The Cotton effect signs in water reflect the absolute configuration of the pyrrolidines. The sodium salt of poly‐1‐H (poly‐1‐Na) and poly‐1‐H in the presence of optically active amines formed lyotropic nematic and cholesteric liquid crystalline phases in concentrated water solutions, respectively, indicating the rigid‐rod characteristic of the polymer main chain regardless of the lack of a single‐handed helix, as evidenced by the long persistence length of about 18 nm before and after the preferred‐handed helicity induction in the polymer. X‐ray diffraction of the oriented films of the nematic and cholesteric liquid crystalline polymers exhibited almost the same diffraction pattern, suggesting that both polymers have the same helical structure; dynamically racemic and one‐handed helices, respectively. On the basis of the X‐ray analysis, a possible helical structure of poly‐1 is proposed. © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 1383–1390, 2010

Vortex‐induced chiral bifurcation in aggregating insulin

Chiral symmetry breaking occurs during vortex-assisted crystallization of several simple compounds leading to a stochastically determined emergence of an enantiomeric excess of one chiral isomer. This article summarizes recent developments in studies of a similar phenomenon observed in agitated solutions of aggregating insulin, when a phase transition-precipitation of insoluble amyloid fibrils from solutions of the native protein-is coupled to a conformational transition of the native alpha-helical structure into aggregated beta-sheets. In contrast to the previously known cases of chiral bifurcation, the substrate is built of L-amino acids and, therefore, chirally biased. However, under certain conditions, insulin forms fibrils with superstructural chiral features that are independent of the left-handedness of amino acid residues, as revealed by the sign of extrinsic Cotton effect induced in amyloid-bound achiral dye-thioflavin T. The inherent chiral bias of the protein results in a diastereomeric relationship between the two optical isomers of amyloid superstructures and the fact that relative probability of formation of either isomer is temperature dependent. As the formation of amyloid fibrils in vivo is associated with several degenerative disorders such as Alzheimer's disease, this newly observed phenomenon may have important implications in the context of structural basis of biological activity of misfolded proteins.

Generation of chirality in 4,4′-azopyridine by co-crystallization with optically active dicarboxylic acids

The co-crystals of anti-4,4′-azopyridine apy with optically active 9,10-dihydro-9,10-ethanoanthracene-11,12-dicarboxylic acid 1 and trans-1,2-cyclohexanedicarboxylic acid 2 were prepared and their solid state CD spectra were measured. The positive Cotton effect sign, corresponding to the lowest energy n–π ∗ transition, was correlated with the M helicity of the twisted Ar–N N chromophore. The absolute sense of the twist of the guest apy molecule was deduced from the X-ray structures of the ( S,S)- 1· apy and ( S,S)- 2· apy complexes.

Toluene Dioxygenase‐Catalyzed Synthesis of cis‐Dihydrodiol Metabolites from 2‐Substituted Naphthalene Substrates: Assignments of Absolute Configurations and Conformations from Circular Dichroism and Optical Rotation Measurements

cis-Dihydrodiol metabolites have been isolated from naphthalene and six 2-substituted naphthalene substrates. Their structures and absolute configurations have been determined by a combination of calculated (TDDFT) and experimentally based circular dichroism (CD) and optical rotation (OR) methods. The "inverse" styrene helicity rule is shown to be incorrect for the interpretation of the CD spectra of cis-dihydrodiols. A striking conclusion is that CD spectra correlate directly with the helicity of the styrene chromophore: that is, the sign of the long-wavelength Cotton effect is identical with the sign of styrene torsion angle, whereas the OR sign is dependent on the absolute configuration of the allylic carbon atom. The results demonstrate that a predictive model previously used for the determination of preferred regio- and stereoselectivity associated with TDO-catalyzed cis-dihydroxylation of substituted benzene substrates can now be successfully extended to substituted naphthalene substrates.

Enantiomeric Resolution ofN,N′-Dimethyldithiodianthranilide through Diastereomeric Silver(I) Complex. Circular Dichroism Spectra, Racemization Barrier, and Molecular Self-Assembly

Planar chiral N,N'-dimethyldithiodianthranilide (2b) was resolved to enantiomers through a diasteromeric complex with easily accessible silver(I) (1S)-camphorosulfonate (3). The (-)-2b enantiomer was assigned the R absolute configuration from the X-ray crystal structure of the silver complex. The compound is configurationally stable and its racemization occurs through boat-to-boat ring inversion (DeltaG(double dagger) = 36.5 +/- 0.2 kcal mol(-1) at 438 K). The analysis of the CD spectrum of the title compound showed that the n-pi* Cotton effect sign is determined by the helicity of the skewed thiobenzamide chromophore. The molecules of 2b are unable to achieve efficient crystal packing by themselves and easily form inclusion complexes with toluene or pentafluorophenol.

Helix-Sense-Controlled Polymerization of Optically Active Phenyl Isocyanides

A series of optically active phenyl isocyanides bearing various chiral functional groups, such as l-alanine, l-alaninol, l-phenylalanine, and l-lactic acid residues, with a long n-decyl chain as the pendants were prepared, and these were polymerized with an achiral nickel catalyst (NiCl2) in various organic solvents at different temperatures. The chiroptical properties and structures of the resulting helical polyisocyanides investigated by circular dichroism (CD) and IR spectroscopy revealed that the Cotton effect signs and intensities of the polyisocyanides, which correspond to their helical senses (right- or left-handed helix) and the excess of one helical sense, respectively, were significantly dependent on the pendant structures of the polymers and the polymerization conditions, such as the solvent polarity and temperature. The effect of the alkyl chain length of l-alanine-bound phenyl isocyanides on the helix-sense-controlled polymerization was also investigated.

Synthesis and chiroptical properties of a helical poly(phenylacetylene) bearing optically active pyrene pendants

A novel poly(phenylacetylene) derivative bearing optically active pyrene moieties as the pendant groups (poly-(R)-1) was prepared by the polymerization of the corresponding monomer (R)-1 in the presence of a rhodium catalyst, and its chiroptical property was investigated. Poly-(R)-1 exhibited an induced circular dichroism (ICD) in the polymer backbone region due to the predominantly one-handed helical conformation. The ICD pattern dramatically changed and was accompanied by inversion of the Cotton effect sign in response to a change in the temperature and solvent, indicating that poly-(R)-1 underwent a helix-helix transition in response to the external stimuli.