Marcin Kwit

Density Functional Theory Calculations of the Optical Rotation and Electronic Circular Dichroism: The Absolute Configuration of the Highly Flexible trans-Isocytoxazone Revised

Ab initio calculations of the optical rotation (OR) and electronic circular dichroism (ECD) for a series of trans-diastereomers of the natural cytokine modulator cytoxazone 1-4 have been performed by density functional theory (DFT). The calculation of OR and ECD curves provides, after critical assessment, a reliable method for the assignment of absolute configuration of these conformationally flexible molecules. The effects of the level of theory used for calculations, changes of conformer equilibrium, and the solvent influence on the geometry and values of calculated OR data are discussed, leading to the conclusion that the most frequently used B3LYP/6-31G(d) method is not adequate for prediction of the absolute configuration of this type of highly flexible molecules. The absolute configurations of levorotatory trans-isocytoxazone 2 and analogues 1, 3, and 4 have been established as (-)-(4S,5S)-trans-1-4; i.e., it is in opposition to the previously published configuration (-)-(4R,5R)-trans-2.

Circular Dichroism of 9,10‐Dihydrophenanthrene Derivatives Reveals both the Absolute Configuration and Conformation: A Novel Approach to Mislow's Helicity Rule

The absolute configuration and the conformation of 9,10-trans-disubstituted 9,10-dihydrophenanthrenes, known chiral metabolites of phenanthrene-9,10-oxide, have been determined by circular dichroism. The absolute configuration assignment is based on the sign of the long-wavelength Cotton effect (A-band), which is conformation invariant and originates from benzylic chirality. This provides a new interpretation of the Mislow biphenyl-helicity rule for the case of the 9,10-dihydrophenanthrene chromophore. The sign of the B-band Cotton effect reflects the conformation of the biphenyl chromophore in 9,10-dihydrophenanthrenes. It is shown that the origin of chiroptical properties of 9,10-dihydrophenanthrenes is closely related to those of 5,6-trans-disubstituted 1,3-cyclohexadienes.

Unexpected narcissistic self-sorting at molecular and supramolecular levels in racemic chiral calixsalens

The [3 + 3] cyclocondensation of 2-hydroxyisophthalaldehyde derivatives with racemic trans-1,2-diaminocyclohexane results in formation of triangular vase-like hexaimines called calixsalens. Calixsalen formation is highly stereoselective, yielding racemic mixtures that contain homochiral products with absolute configuration of either all-R or all-S at their stereogenic centres. Calixsalens form tail-to-tail dimers that are assembled into higher-order structures in the solid state. The formation of these dimers is accomplished by enantioselective self-recognition of chiral calixsalen units driven by non-covalent interactions only.

Induced homohelicity of diphenimide bis-propellers

Helicity correlation in switchable diphenimide bis-propellers results in their preferential homohelical, rather than heterohelical structures.

Synthesis, conformation and chiroptical properties of diaryl esters of tartaric acid.

Previously unknown diaryl esters of l-tartaric acid have been synthesized. Their conformations have been studied by DFT calculations, NMR and circular dichroism spectroscopy in solution, as well as by X-ray diffraction in the crystalline state. The four-carbon tartrate chain of diaryl esters was found to be extended in all cases, with a higher degree of nonplanarity in the crystals. Dinaphthyl tartrates show unusually strong exciton Cotton effects (A = -228 for di-1-naphthyl l-tartrate) due to the coupling of allowed 1B(b) transitions in naphthyl chromophores, despite the acyclic structure and significant distance (over 10 A) between the two chromophores.

The Use of Benzamide Derivatives of Secondary Amines for Stereochemical Studies by Circular Dichroism

The benzamide chromophore is widely used as a Cottonogenic derivative of primary amines for stereochemical studies by circular dichroism. The assignments based on the exciton chirality method are reliable since the benzamide group has well-defined geometry and conformation. A recent report (J.D. Chisholm, J. Golik, B. Krishnan, J.A. Matson, D.L. Van Vranken, J. Am. Chem. Soc. 1999, 121: 3801-3802) claimed a caveat in the application of the exciton chirality method to benzamides derived from secondary amines. By the use of benzoyl derivatives of amino alcohols (1-4) and diamines (5, 6) of known absolute configuration we demonstrate that the 250-210 nm range exciton Cotton effects due to secondary and tertiary benzamides are generally of opposite sign. The origin of such disparity is traced to different conformational equilibria of the amide C-N bond in secondary and tertiary benzamides, as shown by semiempirical molecular modelling and NMR data. This feature can be useful in the determination of absolute configuration by analysis of the CD spectra due to exciton coupling of tertiary benzamides.

Fine tuning of molecular and supramolecular properties of simple trianglimines – the role of the functional group

Chiral, triangular poly-azamacrocycles (trianglimines) readily available from enantiomerically pure trans-1,2-diaminocyclohexane and various aromatic dialdehydes, differ in their nature and substitution pattern. The highly symmetrical macrocycle having two electron-donating groups attached to the aryl moieties is formed under thermodynamic control that fulfilled the so called entropy of symmetry rule. Conversely, from the 2-nitroterephthaldehyde a kinetic product of trivial C1 symmetry is solely obtained, whereas from 2-methoxyterepthaldehyde a mixture of C3- and C1-symmetrical macrocycles are formed. The factors that contribute to the mechanism of the macrocycle formation were determined on the basis of an experimental/theoretical approach. The non-symmetrical structure of the macrocycle resulted from a symmetrical intermediate that appeared during cyclocondensation. The chiroptical properties of the trianglimines were studied by means of experimental ECD and VCD methods supported by quantum-chemical calculations. The nitro-substituted trianglimine appeared to be a simple, low molecular weight supergelator forming in polar media of stable chiral organogels. The structure of the gel is affected by the nature and chirality of the dopant. The hexaimine macrocycles after reduction of the CN imine bonds formed trianglamines – useful chiral ligands in stereoselective synthesis. The Zn–trianglamine complexes were employed as catalysts for asymmetric hydrosilylation of prochiral ketones, providing products of enantiomeric excess up to 98%. This remains the best result obtained for Zn–diamine catalysed asymmetric hydrosilylation of ketones so far.

Vibrationally resolved circular dichroism spectra of a molecule with isotopically engendered chirality

We present a theoretical study of vibrationally resolved circular dichroism spectra, both in the adiabatic and non-adiabatic frameworks, with a full account of Franck-Condon and Herzberg-Teller vibrational contributions for the former. Model calculations have been performed on 2(R)-deuteriocyclopentanone, whose chirality is due solely to isotopic substitution. This molecule has two distinct, nearly isoenergetic, half-chair conformations in equilibrium, and its demanding nature in terms of computational accuracy makes it a perfect candidate for performing a detailed comparison between different vibronic models. Comparisons are made with experimental spectra, and we also consider temperature effects. In order to reproduce the experimental spectrum, it is necessary to consider the geometry relaxation occurring during the n→π* transition.

New Insight into Chiroptical Properties of 1,2-Diols Cyclic Sulfites.

The present work examines the relationship between the structure and chiroptical properties of cyclic sulfites utilizing the electronic circular dichroism (CD) and time-dependent density functional theory (TD-DFT). For some of the model compounds the study was additionally supported by the X-ray diffraction analysis. A comparison of the experimental and simulated CD spectra gave a reasonable interpretation of the Cotton effects observed in the 200-220 nm spectral range. The study revealed a high sensitivity of the CD spectra with regard to the configuration at the sulfur atom as well as the conformation of the ring bearing the sulfite chromophore. The results demonstrated that such a combined treatment enabled the determination of absolute configuration with a high degree of confidence.

From Single Molecule to Crystal: Mapping Out the Conformations of Tartaric Acids and Their Derivatives

Stereoisomers of one of the most important organic compounds, tartaric acid, optically active and meso as well as the ester or amide derivatives, can show diverse structures related to the rotation around the three carbon-carbon bonds. This study determines the controlling factors for conformational changes of these molecules in vacuo, in solution, and in the crystalline state using DFT calculations, spectroscopic measurements, and X-ray diffraction. All structural variations can be logically accounted for by the possibility of formation and breaking of hydrogen bonds between the hydroxy or amide donors and oxygen acceptors, among these the hydrogen bonds that close five-membered rings being the most stable. These findings are useful in designing molecular and crystal structures of highly polar, polyfunctional, chiral compounds.