Absolute configuration of seco-eudesmanolide inuloxin D from experimental and predicted chiroptical studies of its 4-O-acetyl derivative.

Sesquitepenoids inuloxins A-D, belonging to different subgroups, were isolated from Dittrichia viscosa and showed potential biocontrol of some parasitic plants as Pelipanche, Orobanche, and Cuscuta species. The absolute configurations of the first three inuloxins A-C were previously determined by using experimental and computational chiroptical spectroscopic methods. The absolute configuration of inuloxin D remains to be established. The bioactive inuloxin E, closely related to inuloxin D, was recently isolated from the same plant organic extract. The same relative configuration of inuloxin D was assigned to inuloxin E by comparison of their NMR spectroscopic data. The absolute configurations of inuloxin D and inuloxin E are suggested in this work by analysis of the experimental and predicted chiroptical properties of the 4-O-acetyl derivative of inuloxin D.

The enduring legacy of Koji Nakanishi's research on bioorganic chemistry and natural products. Part 1: Isolation, structure determination and mode of action.

In this brief review on Koji Nakanishi's remarkable career in natural products chemistry, we have highlighted a number of his accomplishments that illustrate the broad diversity of his interests. These include the isolation, structure determination, and biological mechanism of action of many natural products including the triterpenoid pristimerin; the diterpenoid ginkgolides; insect and crustacean molting hormones; phytoalexins; the toxic red tide principle brevetoxin; the vanadium tunicate pigments; philanthotoxin from killer wasps; antisickling agents; mitomycin DNA adducts; insect antifeedants; a mitotic hormone, the small molecule fish attractants from the sea anemone; new isolation and purification technologies; molecular chemistry of vision; age-related macular degeneration; and the development of the exciton circular dichroism (CD) chirality method for microscale determination of absolute configuration of natural products and chirality of other chiral molecules and supramolecular assembly.

Complexation of Chiral Zinc(II) Porphyrin Tweezer with Achiral Aliphatic Diamines Revisited: Molecular Dynamics, Electronic CD, and 1H NMR Analysis.

We have reported here the complexation and chiroptical behavior of the host-guest complexes using a new chiral Zn(II) bisporphyrin tweezer host and a series of achiral aliphatic diamine guests varying the chain length. (1R,2R)-Cyclohexanediamine covalently links two Zn(II) porphyrin moieties, which thereby produces a strong chiral field around the bisporphyrin tweezer framework. The chiral tweezer upon complexation with achiral guest exhibited large changes in the UV-vis spectra and CD exciton couplets due to a sudden change in the porphyrin disposition, which is controlled by the host-guest stoichiometry as well as the chain lengths of the diamine guest. Addition of smaller diamines (n: 2-5) to the host resulted in the formation of 1:1 sandwich and 1:2 open complexes, respectively, at the low and high guest concentration, which eventually display two-step inversions of the CD couplet. With longer diamines (n: 6-8), however, only 1:1 sandwich complexes are formed with retention of the CD sign. Similar observations were also reported by us recently using another chiral bisporphyrin tweezer having (1R,2R)-diphenylethylenediamine as the spacer. In an effort to obtain deeper insights into the sudden changes of interporphyrin disposition just by changing the length of the achiral diamines, we have extended a series of computational studies and correlated closely with the results obtained from the experiment. While the previously published study has relied on commonly applied Monte Carlo (MC) sampling of the potential energy surface in addition to being guided by porphyrin effective transition moment approximation, the present study uses a considerably more robust molecular modeling protocol, namely Molecular Dynamics (MD) simulations followed by full ab initio geometry optimization and TD-DFT CD prediction. The experimental data corroborate with the results obtained from the theoretical conformational analysis. The latter are also supported by experimental 1H NMR data empowered by the porphyrin ring-current effect. The NMR spectral patterns of pyrrolic protons of the free host and the 1:1 sandwich complexes appear very diagnostic and reflect the changes in the mutual porphyrin disposition on moving from the free host to the complexed ones with short and long diamines. Overall, the experimental NMR data underscore the sensitivity of pyrrolic protons chemical shifts to subtle alterations of the geometrical features, and as such, they come in agreement with the theoretically derived models.

A Helicene Nanoribbon with Greatly Amplified Chirality.

We report the synthesis and characterization of a chiral, shape-persistent, perylene-diimide-based nanoribbon. Specifically, the fusion of three perylene-diimide monomers with intervening naphthalene subunits resulted in a helical superstructure with two [6]helicene subcomponents. This π-helix-of-helicenes exhibits very intense electronic circular dichroism, including one of the largest Cotton effects ever observed in the visible range. It also displays more than an order of magnitude increase in circular dichroism for select wavelengths relative to its smaller homologue. These impressive chiroptical properties underscore the potential of this new nanoribbon architecture in the context of chiral electronic materials.

Pimarane diterpenes: Natural source, stereochemical configuration, and biological activity.

Plants and fungi are seemingly inexhaustible sources of interesting natural products with remarkable structural and biological diversity. One of the most important groups is the terpenes, ubiquitous natural products that are generated by 2 now well-established biosynthetic pathways: the older mevalonate and the more recently discovered 1-deoxyxylulose-5-phosphate. Among the diterpenes, the pimarane diterpenes are a very representative subgroup with several and interesting biological activities resulting from different functional group modifications. In this review, we outline the method of their structure determination, mainly spectroscopic results, their absolute configuration, and structure-activity relationships, were reported, as well as the mode of action for selected examples from plants, marine organisms, and fungi. The pimarane, isopimarane, and ent-pimarane diterpenes covered in this review have a wide range of biological activities including antimicrobial, antifungal, antiviral, phytotoxic, phytoalexin, cytotoxicity, and antispasmodic and relaxant effects.

Complexation of Chiral Zinc-Porphyrin Tweezer with Achiral Diamines: Induction and Two-Step Inversion of Interporphyrin Helicity Monitored by ECD.

We report here the synthesis of a new chiral Zn(II) bisporphyrin tweezer in which two achiral Zn(II) porphyrin moieties are covalently linked by (1R,2R)-diphenylethylenediamine, which produces a strong chiral field around the porphyrin moieties. The chiral tweezer exhibits not only intensity modulation in UV-vis and CD exciton couplets but also a dramatic change, namely, the inversion in the sign of the interporphyrin helicity upon binding of achiral diamines of varying lengths. The stoichiometry-controlled formation of a 1:1 sandwich complex followed by a 1:2 open complex was realized with smaller achiral diamines (n: 2-5) at their low and high concentration regions, respectively, leading to two-step inversion of chirality. With longer achiral diamines (n: 6-8), however, only 1:1 sandwich complexes are formed with no change of sign in the CD couplet. As compared to a 1:2 open complex, a 1:1 sandwich complex shows an enhanced CD response as two porphyrin units come closer in space. Structural insights of the host-guest complexes have been obtained spectroscopically along with molecular mechanics minimizations with the newly implemented OPLS-3 force field followed by geometry optimization using density functional theory of the most stable conformer. The amide bridge in the Zn(II) bisporphyrin has a low rotational barrier, which provides conformational flexibility to change interporphyrin helicity between 1:1 and 1:2 binding depending on the size of the achiral guests in order to minimize host-guest steric interactions.

Increased duplex stabilization in porphyrin-LNA zipper arrays with structure dependent exciton coupling.

Porphyrins were attached to LNA uridine building blocks via rigid 5-acetylene or more flexible propargyl-amide linkers and incorporated into DNA strands. The systems show a greatly increased thermodynamic stability when using as little as three porphyrins in a zipper arrangement. Thermodynamic analysis reveals clustering of the strands into more ordered duplexes with both greater negative ΔΔS and ΔΔH values, and less ordered duplexes with small positive ΔΔS differences, depending on the combination of linkers used. The exciton coupling between the porphyrins is dependent on the flanking DNA sequence in the single stranded form, and on the nature of the linker between the nucleobase and the porphyrin in the double stranded form; it is, however, also strongly influenced by intermolecular interactions. This system is suitable for the formation of stable helical chromophore arrays with sequence and structure dependent exciton coupling.

Effect of Different Z-Inducers on the Stabilization of Z Portion in BZ-DNA Sequence: Correlation Between Experimental and Simulation Data.

In this study we show the outstanding agreement between simulation and experimental data concerning the efficient stabilization effect by NaCl of Z conformation. We demonstrate by circular dichroism (CD) experiments that Na(+) not only is able to induce a B to Z form transition in a short (GC)3 alternated portion of a sequence having 17 basis, but also is the best stabilizer in comparison with other Z inducers used (spermine and NiCl2). This result was confirmed by free energy calculations.

Structural Studies on Porphyrin-PNA Conjugates in Parallel PNA:PNA Duplexes: Effect of Stacking Interactions on Helicity.

Parallel PNA:PNA duplexes were synthesized and conjugated with meso-tris(pyridyl)phenylporphyrin carboxylic acid at the N-terminus. The introduction of one porphyrin unit was shown to affect slightly the stability of the PNA:PNA parallel duplex, whereas the presence of two porphyrin units at the same end resulted in a dramatic increase of the melting temperature, accompanied by hysteresis between melting and cooling curves. The circular dichroism (CD) profile of the Soret band and fluorescence quenching strongly support the occurrence of a face-to-face interaction between the two porphyrin units. Introduction of a L-lysine residue at the C-terminal of one strand of the parallel duplex induced a left-handed helical structure in the PNA:PNA duplex if the latter contains only one or no porphyrin moiety. The left-handed helicity was revealed by nucleobase CD profile at 240-280 nm and by the induced-CD observed in the presence of the DiSC2 (5) cyanine dye at ~500-550 nm. Surprisingly, the presence of two porphyrin units led to the disappearance of the nucleobase CD signal and the absence of CD exciton coupling within the Soret band region. In addition, a dramatic decrease of induced CD of DiSC2 (5) was observed. These results are in agreement with a model where the porphyrin-porphyrin interactions cause partial loss of chirality of the PNA:PNA parallel duplex, forcing it to adopt a ladder-like conformation.

Application of electronic circular dichroism in the study of supramolecular systems.

Chiral supramolecular architectures constitute crucial structural and functional elements in living systems and have been long mimicked by chemists to synthesize new artificial systems endowed with desired properties and functions. Among several techniques to study noncovalent chiral assemblies or aggregates, electronic circular dichroism (ECD) plays a key role because many mechanisms responsible for the appearance of ECD bands occur through space, and therefore are intrinsically sensitive to intermolecular interactions, from short to long-range. The aim of this tutorial review is to emphasize the different kinds of information which can be obtained specifically when chiral supramolecular species are characterized by means of ECD spectroscopy. We will survey several typical applications of ECD in the context of supramolecular chemistry, ranging from the simple detection of chiral aggregates or complexes, to the definition of stoichiometric ratios between the partners, the derivation of thermodynamic and kinetic parameters such as binding and rate constants, and ultimately to the refinement of the most plausible structure of the supramolecular species.

Absolute stereochemistry of a 4 a-hydroxyriboflavin analogue of the key intermediate of the FAD-monooxygenase cycle.

The biological action of flavoenzymes, such as flavin adenine dinucleotide (FAD)-containing monooxygenase, involves the formation of oxygenated flavin derivatives, such as 4 a-hydroperoxyflavin and 4 a-hydroxyflavin, in which a new center of chirality is created at the 4 a position during the enzymatic reactions. So far, the absolute configuration of this center of chirality in natural 4 a-oxygenated flavins has remained unknown in spite of its key importance for the diverse functions of flavoenzymes. Herein, we report the 4 a-hydroxy adduct 3 of 3-benzyl-5-ethyl-10-(tetraacetyl-D-ribityl)flavinium (1), one of the key intermediates involved in the enantioselective organocatalytic oxidation of sulfides to sulfoxides. The 4 a-hydroxyflavin diastereomers (+)-3 and (-)-3, separated by HPLC, were characterized by electronic circular dichroism (CD) spectroscopy. Their absolute configurations at the 4 a position were, for the first time, determined by comparing experimental CD spectra with those calculated by means of time-dependent density functional theory (TDDFT) on DFT-optimized structures obtained after an extensive conformation analysis.

Absolute configurations of fungal and plant metabolites by chiroptical methods. ORD, ECD, and VCD studies on phyllostin, scytolide, and oxysporone.

The absolute configuration (AC) of the bioactive metabolites phyllostin (1) and scytolide (2), two hexahydro-1,4-benzodioxines produced by Phyllosticta cirsii, and oxysporone (3), a dihydrofuropyranone recently isolated from a strain of Diplodia africana, has been assigned by computational analysis of their optical rotatory dispersion (ORD), electronic circular dichroism (ECD), and vibrational circular dichroism (VCD) spectra. Computational prediction of ORD, ECD, and VCD allowed us to assign (3S,4aR,8S,8aR) AC to naturally occurring (-)-1, while (4aR,8S,8aR) AC was assigned to (-)-2 employing only ECD and VCD, because in this case ORD analysis turned out to be unsuitable for AC assignment. Theoretical prediction of both ORD and ECD spectra of 3 led to assignment of (4S,5R,6R) AC to (+)-3. In this case a satisfactory agreement between experimental and calculated VCD spectra was obtained only after taking into account solvent effects. This study shows that in the case of flexible and complex natural products only a concerted application of more than a single chiroptical technique permits unambiguous assignment of absolute configuration.