Vibronically resolved electronic circular dichroism spectra of (R)-(+)-3-methylcyclopentanone: a theoretical study

The vibrationally resolved electronic circular dichroism (ECD) spectra of the two dominant conformers of (R)-(+)-3-methylcyclopentanone in gas phase are computed by density functional response theory, with a full account of Franck-Condon and Herzberg-Teller vibrational contributions at the harmonic level. Proper inclusion of the latter contributions was made possible by the recent implementation of effective-scaling computations of vibrational overlaps and of analytical gradients of time dependent DFT. The Coulomb-attenuated Becke three parameters Lee-Yang-Parr (CAM-B3LYP) functional reproduces both the position and the intensity of the experimental peaks, providing a remarkable improvement over the spectra obtained with the popular hybrid B3LYP functional, and allowing a confident assignment of the CD fine vibrational structure. Franck-Condon and Herzberg-Teller contributions are discussed in detail. The computed decrease of the CD intensity in the gas phase upon increase of the temperature of the sample follows the trend observed experimentally in different solvents.     

Chromatographic resolution, solution and crystal phase conformations, and absolute configuration of tert-butyl(dimethylamino)phenylphosphine-borane complex

The enantiomers of tert-butyl(dimethylamino)phenylphosphine-borane complex 2 have been separated by HPLC using cellulose tris-p-methylbenzoate as chiral stationary phase. The borane protection could be removed without racemization and the P-configuration of the free aminophosphine 1 has shown to be stable in solution. Infrared (IR) and vibrational circular dichroism (VCD) spectra have been measured in CD2Cl2 solution for both enantiomers. B3LYP/6-31+G(d) DFT calculations allowed a prediction that complex (S)-2 exists as three conformers in equilibrium and computed population-weighted IR and VCD spectra. Predicted and experimental IR and VCD spectra compared very well and indicate that enantiomer (+)-2 has the S absolute configuration. This assignment has been confirmed by an X-ray diffraction study on a single crystal of (+)-2. The crystal structure of enantiomerically pure 2 appears to be very close to the most stable computed conformer which proved to be predominant in solution.     

Circular dichroism spectra and absolute configuration of some aryl methyl sulfoxides

The absorption and circular dichroism (CD) spectra of three aryl sulfoxides, i.e. (-)-(S)-1-naphthyl methyl sulfoxide, (S)-1, (-)-(S)-1-(2-methyl)naphthyl methyl sulfoxide, (S)-2 and (-)-(S)-9-phenanthryl methyl sulfoxide, (S)-3, have been interpreted by means of the coupled oscillator model formulated by DeVoe. Theoretical spectra have been calculated starting from input geometries provided by molecular mechanics (MMX) calculations and by employing standard spectroscopic parameters to describe the allowed transitions of the aromatic and the sulfoxide chromophores. The satisfactory agreement between the predicted and experimental spectra allows us to confirm the configurational assignment of these compounds as (-)/(S). The analysis of CD spectra, affording the right assignment of the absolute configuration (AC) of the alkyl aryl sulfoxides, then offers a practical alternative to the more complex vibrational circular dichroism spectroscopy and ab initio optical rotation calculation techniques that have been used very recently to assign the AC of (-)-2 and (-)-3.     

Theoretical UV circular dichroism of aliphatic cyclic dipeptides

Four cyclic dipeptides (piperazine-2,5-diones), cyclo(L-Pro-Gly), cyclo(L-Pro-L-Leu), cyclo(L-Ala-L-Ala), and cyclo(L-Pro-L-Ala), were modeled from crystal structure data. Conformations resulting from energy minimization using molecular mechanics were compared with traditional ab initio and density functional theory geometric optimizations for each dipeptide. In all computational cases, the gas phase was assumed. The pi-pi transition feature of the UV circular dichroic (CD) spectra was predicted for each peptide structure via the classical dipole interaction model. The dipole interaction model predicted CD spectra that qualitatively agreed with experiment when MP2 or DFT geometries were used. By coupling MP2 or DFT geometric optimizations with the classical physics method of the dipole interaction model, significantly better CD spectra were calculated than those using geometries obtained by molecular mechanics. Thus, one can couple quantum mechanical geometries with a classical physics model for calculation of circular dichroism.     

Determination of the absolute configurations of natural products via density functional theory calculations of vibrational circular dichroism, electronic circular dichroism, and optical rotation: the iridoids plumericin and isoplumericin

The absolute configurations (ACs) of the iridoid natural products, plumericin (1) and isoplumericin (2), have been re-investigated using vibrational circular dichroism (VCD) spectroscopy, electronic circular dichroism (ECD) spectroscopy, and optical rotatory dispersion (ORD). Comparison of DFT calculations of the VCD spectra of 1 and 2 to the experimental VCD spectra of the natural products, (+)-1 and (+)-2, leads unambiguously to the AC (1R,5S,8S,9S,10S)-(+) for both 1 and 2. In contrast, comparison of time-dependent DFT (TDDFT) calculations of the ECD spectra of 1 and 2 to the experimental spectra of (+)-1 and (+)-2 does not permit definitive assignment of their ACs. On the other hand, TDDFT calculations of the ORD of (1R,5S,8S,9S,10S)-1 and -2 over the range of 365-589 nm are in excellent agreement with the experimental data of (+)-1 and (+)-2, confirming the ACs derived from the VCD spectra. Thus, the ACs initially proposed by Albers-Sch?nberg and Schmid are shown to be correct, and the opposite ACs recently derived from the ECD spectra of 1 and 2 by Els?sser et al. are shown to be incorrect. As a result, the ACs of other iridoid natural products obtained by chemical correlation with 1 and 2 are not in need of revision.     

Density functional calculations on electronic circular dichroism spectra of chiral transition metal complexes

Time-dependent density functional theory (TD-DFT) has for the first time been applied to the computation of circular dichroism (CD) spectra of transition metal complexes, and a detailed comparison with experimental spectra has been made. Absorption spectra are also reported. Various Co(III) complexes as well as [Rh(en)(3)](3+) are studied in this work. The resulting simulated CD spectra are generally in good agreement with experimental spectra after corrections for systematic errors in a few of the lowest excitation energies are applied. This allows for an interpretation and assignment of the spectra for the whole experimentally accessible energy range (UV/vis). Solvent effects on the excitations are estimated via inclusion of a continuum solvent model. This significantly improves the computed excitation energies for charge-transfer bands for complexes of charge +3, but has only a small effect on those for neutral or singly charged complexes. The energies of the weak d-to-d transitions of the Co complexes are systematically overestimated due to deficiencies of the density functionals. These errors are much smaller for the 4d metal complex. Taking these systematic errors and the effect of a solvent into consideration, TD-DFT computations are demonstrated to be a reliable tool in order to assist with the assignment and interpretation of CD spectra of chiral transition metal complexes.     

Absolute configuration in 4-alkyl- and 4-aryl-3,4-dihydro-2(1H)-pyrimidones: a combined theoretical and experimental investigation

Structural features (orientation of the carboxyl group, ring puckering), electronic absorption, and circular dichroism spectra of 4-alkyl- and 4-aryl-dihydropyrimidones 1-5 are calculated by semiempirical (AM1, INDO/S), ab initio (HF/6-31G, CIS/6-31G, RPA/6-31G), and density functional theory (B3LYP/6-31G) methods. These calculations allow an assignment of the absolute configuration by comparison of simulated and experimental CD spectra. Although the ab initio methods greatly overestimate electronic transition energies, the general appearance of the experimental CD spectra is quite nicely reproduced by these calculations. Thus, comparison of experimental with calculated CD spectra is a reliable tool for the assignment of the absolute configuration. For 4-methyl derivatives 1, the first enantiopure DHPM examples with no additional aromatic substituent, the stereochemistry at C4 provided by the theoretical results is confirmed by X-ray structure determination of the diastereomeric salt 6. Additional support is the consistent HPLC elution order found for all investigated DHPMs on a cellulose-derived chiral stationary phase.     

Enantiomer resolution of intrinsically chiral C21-alkylated N-confused porphyrin complexes

The resolution of stereoisomers of C21‐alkylated nickel(II) complexes of N‐confused porphyrin (NCP) was performed by means of chiral‐phase HPLC with an effectiveness of above 90 % molar ratio for each isomer. The reverse signs of the Cotton effects in the circular dichroism (CD) spectra of the separated fractions are indicative of the pair of enantiomers. The application of low‐temperature 2D NMR methods to the separated diastereomers of the system comprising a chiral 2‐(S)‐methylbutyl substituent, in connection with the CD spectra and relative HPLC migration rates, allowed the assignment of the absolute configuration of the chiral C21‐substituted complexes of NCP. The assignment was confirmed by time‐dependent DFT (TDDFT) calculations of CD spectra for the C21‐methylated nickel(II) complex. The system remains chiral after removal of the metal ion from the macrocyclic crevice, despite the fact that this demetalation is connected with a change of the C21 hybridization from pyramidal to trigonal. The retention of chirality was established by means of CD spectra and confirmed by TDDFT calculations for a C21‐methylated NCP free base. Stereoisomers were also separated for three covalently linked bis(NCP) systems with bridges involving one or two C21 carbon atoms. The occurrence of a pair of enantiomers was established for nonsymmetrical dimers comprising only one stereogenic center. In the case of the 21,21′‐(o‐xylene)‐linked dimer, three stereoisomers, that is, a pair of enantiomers and an optically inactive meso‐form, were separated and analyzed by CD and ¹H NMR spectroscopy. The stereoisomers of a diastereoselectively formed nonsymmetrical chloroplatinum(II)‐linked dimer, consisting of heterochiral C21‐alkylated NCP nickel(II) subunits, after separation displayed a strong optical activity, which can be ascribed to the rigid helical structure of the complex.     

Vibrational circular dichroism spectroscopy of chiral pheromones: frontalin (1,5-dimethyl-6,8-dioxabicyclo[3.2.1]octane)

Ab initio density functional theory (DFT) is used to predict the vibrational absorption and circular dichroism spectra of the insect pheromone 1,5-dimethyl-6,8-dioxabicyclo[3.2.1]octane: frontalin. Excellent agreement with experimental spectra is obtained for the structure in which the six-membered ring is in a chair conformation and the seven-membered ring is in a boat conformation. Vibrational circular dichroism (VCD) intensities, predicted on the basis of the previously determined absolute configuration, are in excellent agreement with experiment. We conclude that VCD spectroscopy, in combination with ab initio DFT, is now an efficient tool for determining the absolute configuration and/or conformation of chiral organic molecules, including pheromones.     

秋水仙碱立体异构体电子结构及圆二色谱性质的理论研究

采用量子化学密度泛函理论(DFT)在B3LYP/6-311++G二水平上对秋水仙碱四个立体异构体分子几何构型进行了优化,在优化的基础上进行了振动圆二色谱(VCD),紫外-可见光谱(UV-Vis)和电子圆二色谱(ECD)研究.为模拟真实条件,以水为溶剂,计算其对分子电子结构和光谱性质的影响.研究结果表明:秋水仙碱四个立体...     

Enantioselective HPLC combined with spectroscopic methods: A valid strategy to determine the absolute configuration of potential β-secretase inhibitors

A direct HPLC enantioseparation of three representative compounds of a new family of potential non-peptide β-secretase inhibitors was performed on the immobilized Chiralpak IA chiral stationary phase. Semipreparative amounts of enantiopure forms were collected and submitted to stereochemical characterization. The absolute configuration was assigned by a multi-step methodology based on the combination of Mosher's method with circular dichroism (CD) spectroscopy. The results from the NMR/CD study fully correlated the configurational assignment obtained by a second approach involving single crystal X-ray diffraction.     

Circular dichroism of quinoid pigments from Far Eastern representatives of the family Boraginaceae

The electronic absorption and circular dichroism (CD) spectra of ten natural and modified quinoid pigments are described. An assignment has been made of the dichroic absorption in the 250–600 nm region of the CD spectra of the pigments investigated. It has been shown that in the solution of stereochemical questions for such compounds the most informative region of the CD spectrum is the 250–350 nm interval.Pacific Ocean Institute of Bioorganic Chemistry, Far Eastern Scientific Center, Academy of Sciences of the USSR, Vladivostok. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 568–573, September–October, 1983.     

Reversible plasmonic circular dichroism of Au nanorod and DNA assemblies

Reversible plasmonic circular dichroism (CD) responses are realized for the first time based on temperature-dependent assembly and disassembly of Au nanorod (Au NR) and DNA hybrids. Compared with the conventional UV-vis absorption spectra, the changes in both intensity and line shape of plasmonic CD signals are much more pronounced, leading to a preliminary detection limit of DNA as low as 75 nM. The mechanism and influence factors of reversible plasmonic CD responses are explored.     

Calculation of circular dichroism spectra of michellamines A and C, based on a complete conformational analysis

The first quantum chemical calculation of the circular dichroism (CD) spectra of michellamines has been achieved, based on a complete quantum chemical conformational analysis. Michellamines are dimeric naphthylisoquinoline alkaloids and thus naturally occurring quateraryls, with a large molecular size and flexibility and equipped with stereogenic centers and axes.     

Chiroptical properties of 12,15-dichloro[3.0]orthometacyclophane—correlations between molecular structure and circular dichroism spectra of a biphenylophane

The valence excited electronic states and the circular dichroism (CD) spectra of the recently synthesized 12,15-dichloro[3.0]orthometacyclophane 1 are discussed by means of quantum chemical calculations which combine density functional theory with the single-excitation configuration interaction approach (DFT/SCI). The X-ray structure of this highly strained biphenylophane is presented. In order to investigate the influence of the cyclophane-type distortions on the CD spectrum of 1, the CD spectra of three model geometries (2a–2c) are also calculated. It appears that the CD spectrum of the biphenylophane 1 differs substantially from that of the corresponding unstrained biphenyl 2c. Furthermore, it is found that the pyramidalization of the bridging atoms of the cyclophane ring is an important factor for the red shift of the first band with respect to that of an unstrained benzene chromophore.     

Calculation of the circular dichroism spectra of carbon monoxy- and deoxy myoglobin: interpretation of a time-resolved circular dichroism experiment

A calculation of the circular dichroism (CD) spectra of carbon monoxy- and deoxy myoglobin is carried out in relation with a time-resolved CD experiment. The calculation is based on the polarizability theory and the parameters are adjusted to fit the experimental absorption and CD spectra. By performing the calculation for intermediate configurations of the protein, we are able to propose an explanation of the CD structure observed on a sub-100 ps time scale. The role of the proximal histidine is, in particular, clearly demonstrated in the first step of the myoglobin relaxation from its liganded to it deliganded form.     

Absolute configurations of N,N-dialkyl alpha-amino acids and beta-amino alcohols from exciton-coupled circular dichroism spectra of Cu(II) complexes

[formula: see text] A circular dichroism technique has been applied to the absolute configurational assignment of acyclic alpha-amino acids and beta-amino alcohols with single stereogenic centers via a one-step derivitization procedure requiring microgram quantities of material. Metal ions fix the geometrical relationship of two chromophores, affording CD spectra that agree with theory on the basis of the expected conformation of the ligands in the metal complexes.     

Saludimerines A and B, novel-type dimeric alkaloids with stereogenic centers and configurationally semistable biaryl axes

The first biarylic bis-morphinanedienone alkaloids, saludimerines A (3a) and B (3b), isolated from a tree of Croton flavens (Euphorbiaceae) are described. These naturally occurring dimers of the known alkaloid salutaridine are joined together via a rotationally hindered biaryl axis, giving rise to atropo-diastereomers that are configurationally stable at room temperature but slowly interconvert in methanolic solution within several days. Their structures were established by spectroscopic methods and by partial synthesis, which was achieved by a highly atropo-diastereoselective biomimetic oxidative coupling of the monomeric precursor, salutaridine. Their axial configurations were elucidated by circular dichroism (CD) investigations, which succeeded despite the fact that the two atropo-diastereomers exhibit near-identical CD spectra. This remarkable phenomenon was rationalized by quantum chemical CD calculations. The configurational assignment of saludimerines A (3a) as P-axial and B (3b) as M was corroborated by atropisomer-specific NOE interactions between protons of the one molecular half with nuclei in the other.     

Determining the absolute configuration of two marine compounds using vibrational chiroptical spectroscopy

Chiroptical techniques are increasingly employed for assigning the absolute configuration of chiral molecules through comparison of experimental spectra with theoretical predictions. For assignment of natural products, electronic chiroptical spectroscopies such as electronic circular dichroism (ECD) are routinely applied. However, the sensitivity of electronic spectral parameters to experimental conditions and the theoretical methods employed can lead to incorrect assignments. Vibrational chiroptical methods (vibrational circular dichroism, VCD, and Raman optical activity, ROA) provide more reliable assignments, although they, in particular ROA, have been little explored for assignments of natural products. In this study, the ECD, VCD, and ROA chiroptical spectroscopies are evaluated for the assignment of the absolute configuration of a highly flexible natural compound with two stereocenters and an asymmetrically substituted double bond, the marine antibiotic Synoxazolidinone A (SynOxA), recently isolated from the sub-Arctic ascidian Synoicum pulmonaria. Conformationally averaged nuclear magnetic resonance (NMR), ECD, Raman, ROA, infrared (IR) and VCD spectral parameters are computed for the eight possible stereoisomers of SynOxA and compared to experimental results. In contrast to previously reported results, the stereochemical assignment of SynOxA based on ECD spectral bands is found to be unreliable. On the other hand, ROA spectra allow for a reliable determination of the configuration at the double bond and the ring stereocenter. However, ROA is not able to resolve the chlorine-substituted stereogenic center on the guanidinium side chain of SynOxA. Application of the third chiroptical method, VCD, indicates unique spectral features for all eight SynOxA isomers in the theoretical spectra. Although the experimental VCD is weak and restricted by the limited amount of sample, it allows for a tentative assignment of the elusive chlorine-substituted stereocenter. VCD chiroptical analysis of a SynOxA derivative with three stereocenters, SynOxC, results in the same absolute configuration as for SynOxA. Despite the experimental challenges, the results convincingly prove that the assignment of absolute configuration based on vibrational chiroptical methods is more reliable than for ECD.     

Magnetic circular dichroism study of directly fused porphyrins.

The magnetic circular dichroism (MCD) spectra of doubly and triply linked fused bisporphyrins (2MD and 2MT, M = Ni, Zn, Cu, Pd, and H2) and triply linked higher oligomers (3ZnT and 4ZnT) have been measured, and their Q-bands assigned based on the results of INDO/s calculations. In contrast to the Faraday A term observed for the Q(0,0) band of Ni(II) tetraphenylporphyrin, a single positive Faraday B term was observed for the lowest energy transition of the fused systems. The calculations indicated that the molecular orbitals (MOs) of the directly fused porphyrins consist of linear combinations of the constituent monomeric MOs, and that the effect of lowering the symmetry is always larger on the lowest unoccupied molecular orbital (LUMO) than on the highest occupied molecular orbital (HOMO). On the basis of Michl's perimeter model, these features can be correlated with the observed positive MCD signs in the near infrared region. A weak absorption band at 600-700 nm for the fused dimers can be assigned to a short-axis polarized Q transition.