1,721,015 research outputs found
Application of Electronic Circular Dichroism in Configurational and Conformational Analysis of Organic Compounds
No full textThis tutorial review is addressed to readers with a background in basic organic chemistry and spectroscopy, but without a specific knowledge of electronic circular dichroism. It describes the fundamental principles, instrumentation, data analysis, and different approaches for interpretation of ECD. The discussion focuses on the application of ECD, also in combination with other methods, in structural analysis of organic compounds, including host–guest complexes, and will emphasize the importance of the interplay between configurational and conformational factors. The tutorial also covers modern supramolecular aspects of ECD and recent developments in computational methods
CD-sensitive Zn-porphyrin tweezer host-guest complex; Part 1. OPLS computational approach for predicting preferred interporphyrin helicity
No full textThis article describes a computational study on dimeric zinc porphyrin tweezer complexes with primary/secondary amines and secondary alcohols that validates the use of Optimized Potential for Liquid Simulations (OPLS-2005) as the lead computational choice for assisting the tweezer methodology in the absolute configurational assignment of organic compounds. A supramolecular, microscale approach known as the tweezer method has been widely applied in the past decade for determining the absolute configuration of chiral substrates that are difficult to study by other readily available methods. The method relies on a host/guest complexation mechanism between a porphyrin tweezer moiety and a substrate, after its conversion into a bidentate conjugate. The formation of 1:1 complexes is a stereodifferentiating process: upon complexation, the originally achiral tweezer adopts a preferential interporphyrin helicity, dictated by the absolute configuration of the chiral substrate. By correctly predicting the sign of the interporphyrin helicity in the complex, OPLS-2005 provides a correlation between the observed circular dichroism (CD) signal and the absolute configuration of the substrate. It also offers a great degree of insight into the structural factors responsible for chiral recognition and the amplitude of exciton couplets. Moreover, the preferential binding sites between the Zn-tweezer and secondary amine conjugates were revealed by using the new computational approach
Magnesium Tetraarylporphyrin Tweezer: a CD-Sensitive Host for Absolute Configurational Assignment of alpha-Chiral Carboxylic Acids
No full textA protocol to determine the absolute configuration of α-chiral carboxylic acids based on a modified circular dichroic (CD) exciton chirality method has been developed. The protocol relies on a host-guest complexation mechanism: the chiral substrates are derivatized to give bifunctional amide conjugates ("guests") that form complexes with a dimeric magnesium porphyrin host, Mg-T (T stands for "tweezer") that acts as a "receptor". The two porphyrins in the complex adopt a preferred helicity dictated by the substituents at the chiral center in accordance with their steric sizes (assigned on the basis of conformational energy A-values) and, consequently, with the absolute configuration of the substrates under investigation. This chiroptical method, verified with a variety of chiral substrates, has been demonstrated to be reliable and generally applicable, including natural products with complex structures. Molecular modeling, NMR, and FTIR experiments of selected host-guest complexes revealed the mode of ligation of the substrates to the magnesium porphyrin species and led to clarification of the structure of the complex. When oxygen functionalities were directly attached to the chiral center, the signs of the CD couplets were opposite to those predicted on the basis of steric size. NMR and molecular modeling experiments indicated that this apparent inconsistency was due to conformational characteristics of the guest molecules. The stereochemical analysis is shown to be a sensitive technique, not only for the determination of absolute configurations of substrates but also for elucidation of their solution conformations
Absolute Configurational Determination of an All-trans-Retinal Dimer Isolated From Photoreceptor Outer Segments
No full textAn all-trans-retinal (ATR) dimer (1) isolated from photoreceptor outer segments was found to have a stereogenic center at C13' flanked by tetraene (295 nm) and hexaenal (438 nm) chromophores. Analytical chiral HPLC (Chiralcel OD) revealed that the isolated retinoid had formed in 13% enantiomeric excess. Using a combination of 1H-1H NOESY constraints, molecular modeling, and CD exciton coupling analysis, it was determined that the favored enantiomer was 13V(R). Three low-energy conformers of the 13V(S) model were found with MMFF/DFT and were used to calculate the CD spectrum of the ATR dimer (DeVoe method). The Boltzmann weighted spectrum was found to exhibit a positive exciton couplet, in excellent agreement with the experimental spectrum for the first eluted enantiomer. This further suggested that despite the large energy difference between the two interacting chromophores, the dominant source of optical activity in the CD spectrum is the nondegenerate exciton mechanism
Fluorescence Detected Exciton Coupled Circular Dichroism: Development of New Fluorescent Reporter Groups for Structural Studies
No full textIn collaboration with Jasco Corporation we have recently developed an FDCD (fluorescence detected circular dichroic) instrument J-465, which eliminates the photoselection artifacts and efficiently collects the emitted light from the sample solution based on the ideal ellipsoidal mirror principle. Using the J-465 we have investigated a variety of fluorophores with/without polarization for
exciton-coupled FDCD stereochemical analysis. The following three cases extend the FDCD methodology to new challenging areas beyond the limits of conventional CD: (1) substrates containing C=C double bonds, (2) molecules with sterically hindered hydroxyls, and (3) substrates bearing remote stereogenic centers. The pico- to nano-level FDCD analysis described in this paper leads to promising opportunities for the stereochemical analysis of a wide range of natural products with minuscule amounts of sample available
Probing molecular chirality by CD-sensitive dimeric metalloporphyrin hosts
No full textThis feature article reviews dimeric metalloporphyrin hosts employed as chirality probes in chiral recognition processes involving synthetic compounds and natural products. Upon formation of a chiral host–guest supramolecular complex between an achiral bis-metalloporphyrin derivative and a chiral non-racemic guest, a CD response occurs in the porphyrin spectral region, which is diagnostic of the guest’s absolute configuration. Several bis-porphyrin hosts used in the stereochemical investigation of organic compounds are described and the scope of their application as chirality probes critically assessed. The review encompasses the description of structural features of the host–guest complexes, the nature of the chirality transfer mechanism and the practical application in solving stereochemical problems. In particular, with reference to the method based on bis-porphyrin tweezers, we describe recent advances based on the use of molecular modeling, which have broadened the applicability of the tweezer methodology and allowed extraction of deeper structural information contained in the experimental CD data
Theoretical Analysis of the Porphyrin-Porphyrin Exciton Intercation in Circular Dichroism Spectra of Dimeric Tetraarylporphyrins
No full textChiral bis-porphyrins are currently the subject of intense interest as chiral receptors and as probes in the determination of structure and stereochemistry. To provide an improved framework for interpreting the circular dichroism (CD) spectra of bis-porphyrins, we have calculated the CD spectra of chiral bis-porphyrins from three classes: I, where porphyrins can adopt a relatively wide range of orientations relative to each other; II, porphyrins have a fixed relative orientation; III, porphyrins undergo π-stacking. The calculations primarily utilized the classical polarizability theory of DeVoe, but were supplemented by the quantum mechanical matrix method. Class I was represented by three isomers of the diester of 5α-cholestane-3,17-diol with 5-(4′-carboxyphenyl)-10,15,20-triphenylporphin (2-αβ, 2-βα, 2-ββ). Careful analysis of the torsional degrees of freedom led to two to four minimum-energy conformers for each isomer, in each of which the phenyl - porphyrin bonds had torsional angles near 90°. Libration about these bonds is relatively unrestricted over a range of ±45°. CD spectra in the Soret region were calculated as Boltzmann-weighted averages over the low-energy conformers for each isomer. Three models were used: the effective transition moment model, in which only one of the degenerate Soret components is considered, along the 5-15 direction; the circular oscillator model, in which both Soret components are given equal weight; and the hybrid model, in which the 10-20 oscillator is given half the weight of the 5-15 oscillator, to mimic the effect of extensive librational averaging about the 5-15 direction. All three models predict Soret exciton couplets with signs in agreement with experiment. Quantitatively, the best results are given by the hybrid and circular oscillator models. These results validate the widely used effective transition moment model for qualitative assignments of bis-porphyrin chirality and thus permit application of the exciton chirality model. However, for quantitative studies, the circular oscillator or hybrid models should be used. The simplified effective transition moment and hybrid models are justified by the librational averaging in the class I bis-porphyrins and should only be used with such systems. Two class II bis-porphyrins were also studied by DeVoe method calculations in the circular oscillator model, which yielded good agreement with experiment. Class III bis-porphyrins were represented by 2-αα, for which the calculations gave qualitative agreement. However, limitations in the conformational analysis with the close contacts and dynamic effects in these π-stacked systems preclude quantitative results
Development of a Universal Ellipsoidal Mirror Device for Fluorescence Detected Circular Dichroism (FDCD) - Elimination of Polarization Artifacts
No full textWe have developed an ellipsoidal mirror fluorescence detected circular dichroism (FDCD) device with enhanced detection sensitivity that eliminates the polarization artifact; this is applicable to samples with strongly polarized fluorescence. The device, JASCO FDCD465, has an ellipsoidal mirror structure with a framework consisting of three mirrors (one elliptical and two plane mirrors) that maximally collects light in the FDCD. All assemblies on the device including the ellipsoidal mirror, cylindrical cell, and photomultiplier tube (PMT) are aligned on the chamber-fitting sample mount as an attachment compatible with a standard CD spectropolarimeter. The new FDCD465 device eliminates the polarization artifact caused by anisotropic distribution of the emitted light. It represents a convenient, reliable, and sensitive FDCD attachment to the JASCO J-800 CD spectrometer series that can be used under both isotropic and photoselected conditions
Absolute configurations of Inuloxins B and C, plant phytotoxins with potential application as bioherbicides by computational analysis of chiroptical properties
No full textSolution and Biologically Relevant Conformations of Enantiomeric 11-cis-Locked Cyclopropyl Retinals
No full textTo gain information on the conformation of the 11-cis-retinylidene chromophore bound to bovine opsin, the enantiomeric pair (2a and 2b) of 11-cis-locked bicyclo[5.1.0]octyl retinal (retCPr) 2 was prepared and its conformation was investigated by NMR, geometry optimization, and CD calculations. This compound is also of interest since it contains a unique moiety in which a chiral cyclopropyl group is flanked by triene and enal chromophores, and hence would clarify the little-known chiroptical contribution of a cyclopropyl ring linked to polyene systems. NMR revealed that the seven-membered ring of retCPr adopts a twist chair conformation. The NMR-derived structure constraints were then used for optimizing the geometry of 2 with molecular mechanics and ab initio methods. This revealed that enantiomer 2a with a 11β, 12β-cyclopropyl group exists as two populations of diastereomers depending on the twist around the 6-s bond; however, the sense of twist around the 12-s is positive in both rotamers. The theoretical Boltzmann-weighted CD obtained with the π-SCF-C-DV MO method and experimental spectra were consistent, thus suggesting that the conjugative effect of the cyclopropyl moiety is minimal. It was found that only the β-cyclopropyl enantiomer 2a, but not the α-enantiomer 2b, binds to opsin. This observation, together with earlier retinal analogues incorporation results, led to the conclusion that the chromophore sinks into the N-terminal of the opsin receptor from the side of the 4-methylene and 15-aldehyde, and that the binding cleft accommodates 11-cis-retinal with a slightly positive twist around C12/C13. A reinterpretation of the previously published negative CD couplet of 11,12-dihydrorhodopsin also leads to a chromophoric C12/C13 twist conformation with the 13-Me in front as in 1b. Such a conformation for the chromophore accounts for both the observed biostereoselectivity of retCPr 2a and the observed negative couplet of 11,12-dihydro-Rh7
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