CPL of Mellein and Related Natural Compounds: Analysis of the ESIPT Phenomenon.

(R)-(-)-Mellein, (3R,4R)-4-hydroxymellein and (3R,4S)-4-hydroxymellein obtained from fungi, i. e. from Diplodia globulosa, were investigated as a class of natural products presenting ESIPT (excited state intramolecular proton transfer) phenomenon, through fluorescence and CPL (circularly polarized luminescence). The study was preceded by the assessment of the absolute configuration through ECD and VCD (electronic and vibrational circular dichroism) spectroscopies in addition to NMR spectra. It is found that ESIPT takes place in these systems very rapidly, and no dual fluorescence has been observed. The experimental study is backed up by TD-DFT calculations of ECD and CPL spectra, plus MD calculations to follow proton transfer in the excited state and careful analysis of the puckering dynamics of the lactone ring. Deprotonated forms of the three compounds were also investigated by the same chiroptical experimental and theoretical methods, showing how one can find in natural compounds not only biological activity but also biologically compatible sensing probes.

Organocatalytic hydrogen bond donor/Lewis base (HBD/LB) synthesis and chiroptical properties of thiabridged [5]helicenes.

Thiabridged [5]helicenes are obtained from thioaryl-N-phthalimido benzo[a]phenothiazines using a hydrogen bond donor/Lewis base organocatalytic approach. Resolution of [5]helicenes using either (1S)-(-)-camphanic acid as a chiral auxiliary or CSP-HPLC is reported. Thiabridged [5]helicenes show an exceptional configurational stability with racemization energy barriers higher than 40 kcal mol-1. Electronic circular dichroism and TD-DFT calculations permit the assignment of the absolute configuration, demonstrating that the sign of optical rotation is not easily related to the M or P structure. Separated enantiomers show circularly polarized luminescence with high dissymmetry ratio.

Mid-IR and CH stretching vibrational circular dichroism spectroscopy to distinguish various sources of chirality: The case of quinophaneoxazoline based ruthenium(II) complexes.

Five diastereomers of ruthenium(II) complexes based on quinolinophaneoxazoline ligands were investigated by vibrational circular dichroism (VCD) in the mid-IR and CH stretching regions. Diastereomers differ in three sources of chirality: the planar chirality of the quinolinophane moiety, the central chirality of an asymmetric carbon atom of the oxazoline ring, and the chirality of the ruthenium atom. VCD, allied to DFT calculations, has been found to be effective in disentangling the various forms of chirality. In particular, a VCD band is identified in the CH stretching region directly connected to the chirality of the metal. The analysis of the calculated VCD spectra is carried out by partitioning the complexes into fragments. The anharmonic analysis is also performed with a recently proposed reduced-dimensionality approach: such treatment is particularly important when examining spectroscopic regions highly perturbed by resonances, like the CH stretching region.

Chiral Teropyrenes: Synthesis, Structure, and Spectroscopic Studies.

We present the inaugural synthesis of a chiral teropyrene achieved through a four-fold alkyne benzannulation catalyzed by InCl3, resulting in good yields. The product underwent thorough characterization using FT-Raman and FT-IR spectroscopies, demonstrating a close agreement with calculated spectra. X-ray crystallographic analysis unveiled a notable twist in the molecule's backbone, with an end-to-end twist angle of 51°, consistent with computational predictions. Experimentally determined enantiomeric inversion barriers revealed a significant energy barrier of 23 kcal/mol, facilitating the isolation of enantiomers for analysis by circular dichroism (CD) and circularly polarized luminescence (CPL) spectroscopies. These findings mark significant strides in the synthesis and characterization of chiral teropyrenes, offering insights into their structural and spectroscopic properties.

Can Magnetic Dipole Transition Moment Be Engineered?

The development of chiral compounds with enhanced chiroptical properties is an important challenge to improve device applications. To that end, an optimization of the electric and magnetic dipole transition moments of the molecule is necessary. Nevertheless, the relationship between chemical structure and such quantum mechanical properties is not always clear. That is the case of magnetic dipole transition moment (m) for which no general trends for its optimization have been suggested. In this work we propose a general rationalization for improving the magnitude of m in different families of chiral compounds. Performing a clustering analysis of hundreds of transitions, we have been able to identify a single group in which |m| value is maximized along the helix axis. More interestingly, we have found an accurate linear relationship (up to R2 =0.994) between the maximum value of this parameter and the area of the inner cavity of the helix, thus resembling classical behavior of solenoids. This research provides a tool for the rationalized synthesis of compounds with improved chiroptical responses.

Stacked or Folded? Impact of Chelate Cooperativity on the Self-Assembly Pathway to Helical Nanotubes from Dinucleobase Monomers.

Self-assembled nanotubes exhibit impressive biological functions that have always inspired supramolecular scientists in their efforts to develop strategies to build such structures from small molecules through a bottom-up approach. One of these strategies employs molecules endowed with self-recognizing motifs at the edges, which can undergo either cyclization-stacking or folding-polymerization processes that lead to tubular architectures. Which of these self-assembly pathways is ultimately selected by these molecules is, however, often difficult to predict and even to evaluate experimentally. We show here a unique example of two structurally related molecules substituted with complementary nucleobases at the edges (i.e., G:C and A:U) for which the supramolecular pathway taken is determined by chelate cooperativity, that is, by their propensity to assemble in specific cyclic structures through Watson-Crick pairing. Because of chelate cooperativities that differ in several orders of magnitude, these molecules exhibit distinct supramolecular scenarios prior to their polymerization that generate self-assembled nanotubes with different internal monomer arrangements, either stacked or coiled, which lead at the same time to opposite helicities and chiroptical properties.

Circularly polarized luminescence of natural products lycorine and narciclasine: role of excited-state intramolecular proton-transfer and test of pH sensitivity.

Circularly polarized luminescence (CPL) is increasingly gaining interest not only for its applicative potentialities but also for providing an understanding of the excited state properties of chiral molecules. However, applications of CPL are mainly in the field of materials science: special organic molecules and polymers, metal (lanthanide) complexes, and organic dyes are actively and intensely studied. So far natural compounds have not been investigated much. We fill the gap here by measuring circular dichroism (CD) and CPL of lycorine and narciclasine, the most abundant known alkaloid and isocarbostyril from Amaryllidaceae, which exhibit a large spectrum of biological activities and are promising anticancer compounds. Dual fluorescence detection in narciclasine led us to unveil an occurring excited-state intramolecular proton transfer (ESIPT) process, this mechanism well accounts for the Stokes shift and CPL spectra observed in narciclasine. The same molecule is interesting also as a pH chiroptical switch. Both in absorption and emission, lycorine and narciclasine are also studied computationally via density functional theory (DFT) calculations further shedding light on their properties.

Insights into the Structures of Bilirubin and Biliverdin from Vibrational and Electronic Circular Dichroism: History and Perspectives.

In this work we review research activities on a few of the most relevant structural aspects of bilirubin (BR) and biliverdin (BV). Special attention is paid to the exocyclic C=C bonds being in mostly Z rather than E configurations, and to the overall conformation being essentially different for BR and BV due to the presence or absence of the double C=C bond at C-10. In both cases, racemic mixtures of each compound of either M or P configuration are present in achiral solutions; however, imbalance between the two configurations may be easily achieved. In particular, results based on chiroptical spectroscopies, both electronic and vibrational circular dichroism (ECD and VCD) methods, are presented for chirally derivatized BR and BV molecules. Finally, we review deracemization experiments monitored with ECD data from our lab for BR in the presence of serum albumin and anesthetic compounds.

(BO)2 -Doped Tetrathia[7]helicene: A Configurationally Stable Blue Emitter.

Helicenes combine two central themes in chemistry: extended π-conjugation and chirality. Hetero-atom doping preserves both characteristics and allows modulation of the electronic structure of a helicene. Herein, we report the (BO)2 -doped tetrathia[7]helicene 1, which was prepared from 2-methoxy-3,3'-bithiophene in four steps. 1 is formally derived by substituting two (Mes)B-O moieties in place of (H)C=C(H) fragments in two benzene rings of the parent tetrathia[7]helicene. X-ray crystallography revealed a dihedral angle of 50.26(9)° between the two terminal thiophene rings. The (P)-/(M)-1 enantiomers were separated by chiral HPLC and are configurationally stable at room temperature. The experimentally determined enantiomerization barrier of 27.4±0.1 kcal mol-1 is lower than that of tetrathia[7]helicene (39.4±0.1 kcal mol-1 ). The circular dichroism spectra of (P)- and (M)-1 show a perfect mirror-image relationship. 1 is a blue emitter (λem =411 nm) with a photoluminescence quantum efficiency of ΦPL =6 % (cf. tetrathia[7]helicene: λem ≈405 nm, ΦPL =5 %).

Chiral Single-Molecule Potentiometers Based on Stapled ortho- Oligo(phenylene)ethynylenes.

We report on the chemical design of chiral molecular junctions with stress-dependent conductance, whose helicity is maintained during the stretching of a single molecule junction due to the stapling of both ends of the inner helix. In the reported compounds, different conductive pathways are observed, with clearly different conductance values and plateau-length distributions, attributed to different conformations of the helical structures. The large chiro-optical responses and the potential use of these molecules as unimolecular spin filters have been theoretically proved using state-of-the-art Density Functional Theory (DFT) calculations, including a fully ab-initio estimation of the CISS-originating spin polarization which is done, for the first time, for a realistic molecular system.

Anharmonic Aspects in Vibrational Circular Dichroism Spectra from 900 to 9000 cm-1 for Methyloxirane and Methylthiirane.

Vibrational circular dichroism (VCD) spectra and the corresponding IR spectra of the chiral isomers of methyloxirane and of methylthiirane have been reinvestigated, both experimentally and theoretically, with particular attention to accounting for anharmonic corrections, as calculated by the GVPT2 approach. De novo recorded VCD spectra in the near IR (NIR) range regarding CH-stretching overtone transitions, together with the corresponding NIR absorption spectra, were also considered and accounted for, both with the GVPT2 and with the local mode approaches. Comparison of the two methods has permitted us to better describe the nature of active "anharmonic" modes in the two molecules and the role of mechanical and electrical anharmonicity in determining the intensities of VCD and IR/NIR data. Finally, two nonstandard IR/NIR regions have been investigated: the first one about ≈2000 cm-1, involving mostly two-quanta bending mode transitions, the second one between 7000 and 7500 cm-1 involving three-quanta transitions containing CH-stretching overtones and HCC/HCH bending modes.

Resolution of a Configurationally Stable Hetero[4]helicene.

We have developed an efficient chemical resolution of racemic hydroxy substituted dithia-aza[4]helicenes (DTA[4]H) 1(OH) using enantiopure acids as resolving agents. The better diastereomeric separation was achieved on esters prepared with (1S)-(-)-camphanic acid. Subsequent simple manipulations produced highly optically pure (≥ 99% enantiomeric excess) (P) and (M)-1(OH) in good yields. The role of the position where the chiral auxiliary is inserted (cape- vs. bay-zone) and the structure of the enantiopure acid used on successful resolution are discussed.

Synthesis and Stereochemical Characterization of a Novel Chiral α-Tetrazole Binaphthylazepine Organocatalyst.

A novel α-tetrazole-substituted 1,1'-binaphthylazepine chiral catalyst has been synthesized and its absolute configuration has been determined by DFT computational analysis of the vibrational circular dichroism (VCD) spectrum of its precursor. The VCD analysis, carried out through the model averaging method, allowed to assign the absolute configuration of a benzylic stereocenter in the presence of a chiral binaphthyl moiety. The 1,1'-binaphthylazepine tetrazole and the nitrile its immediate synthetic precursor, have been preliminarily tested as chiral organocatalysts in the asymmetric intramolecular oxa-Michael cyclization of 2-hydroxy chalcones for the synthesis of chiral flavanones obtaining low enantioselectivity.

Biliverdin chiral derivatives as chiroptical switches for pH and metal cation sensing.

A series of six optically active derivatives of the bile pigment biliverdin, namely (ßS,ß'S)-dimethylmesobiliverdin-XIIIα, cyclic esters of linear diols [HO(CH2)nOH] where n = 1-6, have been investigated by vibrational circular dichroism (VCD) and density functional theory (DFT) calculations. The results were correlated with the length (n) of the diester belt, the verdin helicity and an M ⇄ P conformational equilibrium - as previously shown by electronic circular dichroism (ECD). Furthermore, ECD spectra have been found to be quite sensitive to solvent nature and pH. TD-DFT calculations of the protonated/deprotonated verdins with n = 1 and 2 diester belts respectively have allowed one, moreover, to explain the spectroscopic data in terms of a change in the M ⇄ P equilibrium. Finally, the set of investigated compounds, together with other chirally functionalized "non-belted" biliverdin analogs, has also been found to be sensitive to the presence of metal ions, with which the verdins chelate. On the basis of ECD and VCD data, we propose that the spectroscopic changes observed are consistent with self-association (dimerization) of the verdin molecules promoted by the metal cations, as bolstered by DFT calculations, and for which a dimerization constant of 73 000 M-1 is evaluated. We envision the use of current chiroptical spectroscopies in connection with chiral biliverdin derivatives as natural sensors or probes of the micro-environmental conditions, such as pH or the presence of metal ions.

Toward Fully Unsupervised Anharmonic Computations Complementing Experiment for Robust and Reliable Assignment and Interpretation of IR and VCD Spectra from Mid-IR to NIR: The Case of 2,3-Butanediol and trans-1,2-Cyclohexanediol.

The infrared (IR) and vibrational circular dichroism (VCD) spectra of 2,3-butanediol and trans-1,2-cyclohexanediol from 900 to 7500 cm-1 (including mid-IR, fundamental CH and OH stretchings, and near-infrared regions) have been investigated by a combined experimental and computational strategy. The computational approach is rooted in density functional theory (DFT) computations of harmonic and leading anharmonic mechanical, electrical, and magnetic contributions, followed by a generalized second-order perturbative (GVPT2) evaluation of frequencies and intensities for all the above regions without introducing any ad hoc scaling factor. After proper characterization of large-amplitude motions, all resonances plaguing frequencies and intensities are taken into proper account. Comparison of experimental and simulated spectra allows unbiased assignment and interpretation of the most interesting features. The reliability of the GVPT2 approach for OH stretching fundamentals and overtones is confirmed by the remarkable agreement with a local mode model purposely tailored for the latter two regions. Together with the specific interest of the studied molecules, our results confirm that an unbiased assignment and interpretation of vibrational spectra for flexible medium-size molecules can be achieved by means of a nearly unsupervised reliable, robust, and user-friendly DFT/GVPT2 model.

Testing the vibrational exciton and the local mode models on the instructive cases of dicarvone, dipinocarvone, and dimenthol vibrational circular dichroism spectra.

The vibrational circular dichroism (VCD) spectra of dicarvone (1), dipinocarvone (2), and dimenthol (3) have been recorded in the range 900-3200 cm-1 , encompassing the mid-infrared (mid-IR), the CO stretching, and the CH-stretching regions. For compound 3 also, the fundamental and the first overtone OH stretching regions have been investigated by IR/NIR absorption and VCD. Density functional theory (DFT) calculations allow one to interpret the IR and VCD spectra and to confirm the configuration/conformational studies previously conducted by X-ray diffraction. The most intense VCD signals are associated with the vibrational normal modes involving symmetry-related groups close to the CC bond connecting covalently the two molecular units. The vibrational exciton (VCDEC) model is fruitfully tested on the VCD data of compounds 1 and 2 for the spectroscopic regions at ~1700 cm-1 , and the local mode model is tested on compound 3 at ~3500 and ~6500 cm-1 . For compounds 1 and 2 also, ECD spectra are reported, and the exciton mechanism is tested also there, and connections to the VCDEC model are examined.

Characterization of tetrakis(thiadiazole)porphyrazine metal complexes by magnetic circular dichroism and magnetic circularly polarized luminescence.

The magnetic circular dichroism (MCD) spectra of metal complexes of tetrakis(thiadiazole)porphyrazines ([TTDPzM] with M = 2HI , ZnII , MgII (H2 O), and CdII ) have been recorded in dimethyl formamide solution. Together with the UV-Vis spectra, the MCD spectra provide useful information about the structure and electronic properties of the complexes. The experimental UV-Vis and MCD spectra compare pretty well with DFT calculations of two sorts, based either on the sum-over-states (SOS) approach or on the complex polarization propagator approach. They further corroborate the findings and interpretation of MCD spectra of porphyrazines based on the model of Michl for peripheral molecular orbitals. Magnetic circularly polarized luminescence (MCPL) spectra, quite uncommon in the literature, have been recorded for [TTDPzM] (M = 2HI , ZnII , MgII (H2 O)).

Optically active Ag(i): o-OPE helicates using a single homochiral sulfoxide as chiral inducer.

In this work we describe the ability of a simple enantiopure sulfoxide group to promote folding of oligo ortho-phenylene ethynylenes (o-OPEs) with one helical sense. A family of foldamers with up to seven triple bonds was synthesized and fully characterized. Moreover, changes in structure and chiroptical properties caused by Ag(i) coordination have been studied by NMR, UV, VCD and ECD measurements. Quantum mechanical DFT calculations support experimental results.

Ferrocenes with simple chiral substituents: an in-depth theoretical and experimental VCD and ECD study.

Circular dichroism spectra in the IR range (VCD = vibrational circular dichroism) and in the UV range (ECD = electronic circular dichroism) have been recorded for both enantiomers of simple mono-substituted ferrocenes containing chiral pendants: 1-acetoxyethylferrocene, 1, 1-methoxyethylferrocene, 2, and 1-hydroxyethylferrocene, 3; the related disubstituted 1,1'-bis(1-hydroxyethyl)ferrocene, 4, was also considered. These two types of spectra, with the support of DFT calculations, concur to unequivocally confirm the absolute configuration for 1-4. In particular, our computational results point out the clear advantage of using an anharmonic oscillator model for the interpretation of VCD spectra of chiral ferrocenes. Interesting conformational properties are either confirmed or established by the technique, like the eclipsed conformation of the two cyclopentadienyl rings and an intra-molecular interaction involving the OH for 3. For 4, NMR, VCD and IR spectra are compatible with dimer formation and in this case a distorted conformation is predicted. Of utmost importance for the absolute configuration assignment in mono-substituted ferrocenes, we were able to identify a diagnostic VCD band at 950 cm-1 and a (low intensity) ECD band that clearly indicate the absolute configuration of the whole series.

Assignment Through Chiroptical Methods of The Absolute Configuration of Fungal Dihydropyranpyran-4-5-Diones Phytotoxins, Potential Herbicides for Buffelgrass (Cenchrus ciliaris) Biocontrol.

Radicinin and cochliotoxin (1 and 2) two phytotoxic pyranpyran-4,5-diones were isolated together with their close metabolites 3-epi-radicinin, radicinol, and its 3-epimer (3-5), from the culture filtrates of Cochliobolus australiensis, a fungus proposed as mycoherbcide for biocontrol of buffelgrass, a very noxious and dangerous weed. The absolute configuration of cochliotoxin was determined by chiroptical Optical Rotatory Dispersion (ORD), Electronic Circular Dichroism (ECD), and Vibrational Circular Dichroism (VCD)) and computational methods. The same methods were used to confirm that of radicinin, radicinol and their 3-epimers, previously determined with chemical, spectroscopic and ECD methods.