Helicene Appended Benzothiadiazoles as Chiral Emitters.

A homologous series of 4,7-bis(aryl) substituted benzothiadiazole (BTD) compounds, containing the helicenic derivatives bis([4]helicene), bis([5]helicene) and bis([6]helicene), have been prepared upon a double Suzuki coupling between 3,6-bis(pinacolyl-borane)-BTD and the corresponding bromo-aryl precursors. The single crystal X-ray structure of the bis([4]helicene) compound shows the existence of both helicities (M) and (P) on the same molecule. All the compounds of the series are highly emissive in solution, with quantum yields of the emission ranging from 50 to 91 %. The enantiopure compounds (M,M) and (P,P) for the BTD-bis([6]helicene) have been prepared from the corresponding enantiopure 2-bromo-[6]helicene precursors. Their chiroptical properties have been investigated in correlation with density functional theory (DFT) calculations, which allowed to confidently assign the absolute configuration of the helicene arms and to characterize the different electronic transitions, including the low energy charge transfer excitation from helicenes to BTD. The enantiomerically pure fluorophores (M,M)- and (P,P)-BTD-bis([6]helicene), which exist in solution as two main conformers, according to the DFT calculations, show CPL activity in solution, with glum factors of ≈1.7×10-3 at λem=525 nm, and also in the solid state, with glum factors of ≈1.2×10-3 in spite of the strong decrease of the quantum efficiency.

Chiral Spiro-Tetrathiafulvalenes: Synthesis, Chiroptical Properties, Conformational Issues and Charge Transfer Complexes.

Within this work we have investigated spiro-based tetrathiafulvalenes (TTFs) obtained as mixtures of stereoisomers from racemic spiro[5.5]undeca-1,8-dien-3-one. Compared to previously described spiro-TTFs, enantiomeric and diastereoisomeric forms have been here separated by chiral HPLC and fully characterized both experimentally and theoretically. The two types of spiro-based chiral derivatives contain either one (2) or three (1) chiral centres out of each one is spiro-type. Experimental CD, supported by TD-DFT calculations, shows differences in the optical activity between the 1 and 2 and their intermediates. The low optical activity of 2 and 3 (spiro alone chirality) was attributed to the presence of two conformers in the solution (ax and eq) of opposite Cotton effect whereas in the case of 1 and 5 (spiro and stereogenic centres) the spiro chirality seems to be responsible of the Cotton effect in the high energy region whereas the R and S chirality in the low energy region. Racemic and enantiopure forms have been successfully used for the synthesis of charge transfer complexes with tetracyanoquinodimethane (TCNQ) based acceptors.

A Cyclotriveratrylene Solvent-Dependent Chiral Switch.

Chiral molecular switches are attracting attention as they could pave the way to chiral molecular machines. Herein, we report on the design and synthesis of a single molecule chiral switch based on a cyclotriveratrylene scaffold, in which the chirality inversion is controlled by the solvent. Hemicryptophanes are built around a C3 cyclotriveratrylene chiral unit, with either M or P handedness, connected to another tripod and usually displaying an "out" configuration. Here, we demonstrate that solvents are able to control the "in" and "out" configurations of the CTV unit, creating a chiral molecular switch from (M/P)"in" to (P/M)"out" handedness. The full characterization of the "in" and "out" configurations and of the chirality switch were made possible by combining NMR, HPLC, ECD, DFT and molecular dynamics. Interestingly, bulky aromatic solvents such as 2-t-butylphenol favor the "in" configuration while polar aprotic solvents such as acetone favor the "out" configuration. This chiral switch was found to be fully reversible allowing the system to oscillate between two different M and P configurations several times upon the action of solvents stimuli.

Conformational, Structural, and Chiroptical Properties of an Overcrowded Triply Fused Carbo[7]helicene.

Recently, the synthesis of the racemate of an overcrowded triply fused carbo[7]helicene of formula C66H36 with three carbo[7]helicenes fused within a central six-membered ring was described. This molecule was found to embed an extremely contorted central six-membered ring and two negative curvatures. We report herein the resolution of the corresponding enantiomers and their conformational, structural, photophysical, and chiroptical properties. The racemization of the triply fused carbo[7]helicene was determined to proceed at a rate of krac = 8.06 × 10-4 s-1 at 175 °C in ortho-dichlorobenzene, corresponding to a barrier to enantiomerization ΔGenant‡ = 140.4 kJ·mol-1, a value significantly lower than for pristine carbo[7]helicene. Interestingly, the crystalline structures of the racemic and enantiopure materials show some differences regarding the molecular geometry, with an increased negative curvature in the latter cases. This unusual curved delocalized π-conjugated system afforded notably green fluorescence at room temperature and far-red phosphorescence at low temperature. Finally, electronic circular dichroism and circularly polarized luminescence responses of the enantiopure compounds have been measured and showed very close absorption and emission dissymmetry factors, gabs and glum, respectively, of ca. 2.6 × 10-3, indicating a similar chiral rigid geometry for both ground and excited states.

Chiroptical activity of benzannulated N-heterocyclic carbene rhenium(I) tricarbonyl halide complexes: towards efficient circularly polarized luminescence emitters.

The design of enantiomerically pure circularly polarized luminescent (CPL) emitters would enormously benefit from the accurate and in-depth interpretation of the chiroptical properties by means of jointly (chiroptical) photophysical measurements and state-of-the-art theoretical investigation. Herein, computed and experimental (chiro-)optical properties of a series of eight enantiopure phosphorescent rhenium(I) tricarbonyl complexes are systematically compared in terms of electronic circular dichroism (ECD) and CPL. The compounds have general formula fac-[ReX(CO)3(N^CNHC)], where N^CNHC is a pyridyl benzannulated N-heterocyclic carbene deriving from a (substituted) 2-(pyridin-2-yl)imidazo[1,5-a]pyridin-2-ium proligand and X = Cl, Br and I, and display structured red phosphorescence with long-lived (τ = 7.0-19.1 µs) excited-state lifetime and dissymmetry factors |gLum| up to 4 × 10-3. The mixing of the character of the lowest-lying emitting triplet excited state is finely modulated between ligand centred (3LC), metal-to-ligand charge transfer (3MLCT) and halogen-to-ligand charge transfer (3XLCT) by the nature of the ancillary halogen and the chromophoric N^CNHC ligand. The study unravels the effect exerted by the nature of the excited state onto the ECD and CPL activity and will help to pave the way to construct efficient CPL emitters by chemical design.

Hybrid Peptide-Alkoxyamine Drugs: A Strategy for the Development of a New Family of Antiplasmodial Drugs.

The emergence and spread of drug-resistant Plasmodium falciparum parasites shed a serious concern on the worldwide control of malaria, the most important tropical disease in terms of mortality and morbidity. This situation has led us to consider the use of peptide-alkoxyamine derivatives as new antiplasmodial prodrugs that could potentially be efficient in the fight against resistant malaria parasites. Indeed, the peptide tag of the prodrug has been designed to be hydrolysed by parasite digestive proteases to afford highly labile alkoxyamines drugs, which spontaneously and instantaneously homolyse into two free radicals, one of which is expected to be active against P. falciparum. Since the parasite enzymes should trigger the production of the active drug in the parasite's food vacuoles, our approach is summarized as "to dig its grave with its fork". However, despite promising sub-micromolar IC50 values in the classical chemosensitivity assay, more in-depth tests evidenced that the anti-parasite activity of these compounds could be due to their cytostatic activity rather than a truly anti-parasitic profile, demonstrating that the antiplasmodial activity cannot be based only on measuring antiproliferative activity. It is therefore imperative to distinguish, with appropriate tests, a genuinely parasiticidal activity from a cytostatic activity.

Reactivity and Steric Parameters from 2D to 3D Bulky Pyridines: Increasing Steric Demand at Nitrogen with Chiral Azatriptycenes.

Sterically hindered pyridines embedded in a three-dimensional triptycene framework have been synthesized, and their resolution by chiral HPLC enabled access to unprecedented enantiopure pyridines exceeding the known steric limits. The design principles for new axially chiral pyridine derivatives are then described. To rationalize their associations with Lewis acids and transition metals, a comprehensive determination of the steric and electronic parameters for this new class of pyridines was performed. This led to the general parameterization of the steric parameters (percent buried volume %VBur, Tolman cone angle θ, and He8_steric descriptor) for a large set of two- and three-dimensional pyridine derivatives. These parameters are shown to describe quantitatively their interactions with carbon- and boron-centered Lewis acids and were used to predict the ΔG° of association with the prototypical B(C6F5)3 Lewis acid widely used in frustrated Lewis pair catalysis. This first parameterization of pyridine sterics is a fundamental basis for the future development of predictive reactivity models and for guiding new applications of bulky and chiral pyridines in organocatalysis, frustrated Lewis pairs, and transition-metal catalysis.

Phosphetene-Based Polyaromatics: Structure-Property Relationships and Chiroptical Tuning.

We describe the synthesis of π-extended phosphetene rings (4-member P-rings) flanked with PAH systems of various topologies. These compounds are fully characterized including X-ray diffraction. The impact of both the polyaromatic platform and the P-ring on the structure, and the optical and redox properties are investigated both experimentally and theoretically. Although neither the P centre nor the 4-membered ring significantly takes part in the HOMO or LUMO orbitals, both structural features have an important modulating role in distorting the symmetry of the orbitals, leading to chiroptical properties. The stereogenic P-atom is used as a remote chiral perturbator to induce circularly polarized luminescence of the polyaromatic system. The dissymmetry factor is highly dependent on the polyaromatic topology, as supported by theoretical calculations.

Chiral Truxene-Based Self-Assembled Cages: Triple Interlocking and Supramolecular Chirogenesis.

Incorporating chiral elements in host-guest systems currently attracts much attention because of the major impact such structures may have in a wide range of applications, from pharmaceuticals to materials science and beyond. Moreover, the development of multi-responsive and -functional systems is highly desirable since they offer numerous benefits. In this context, we describe herein the construction of a metal-driven self-assembled cage that associates a chiral truxene-based ligand and a bis-ruthenium complex. The maximum separation between both facing chiral units in the assembly is fixed by the intermetallic distance within the lateral bis-ruthenium complex (8.4 Å). The resulting chiral cavity was shown to encapsulate polyaromatic guest molecules, but also to afford a chiral triply interlocked [2]catenane structure. The formation of the latter occurs at high concentration, while its disassembly could be achieved by the addition of a planar achiral molecule. Interestingly the planar achiral molecule exhibits induced circular dichroism signature when trapped within the chiral cavity, thus demonstrating the ability of the cage to induce supramolecular chirogenesis.

Subtle Stereochemical Effects Influence Binding and Purification Abilities of an FeII4L4 Cage.

A tetrahedral FeII4L4 cage assembled from the coordination of triangular chiral, face-capping ligands to iron(II). This cage exists as two diastereomers in solution, which differ in the stereochemistry of their metal vertices, but share the same point chirality of the ligand. The equilibrium between these cage diastereomers was subtly perturbed by guest binding. This perturbation from equilibrium correlated with the size and shape fit of the guest within the host; insight as to the interplay between stereochemistry and fit was provided by atomistic well-tempered metadynamics simulations. The understanding thus gained as to the stereochemical impact on guest binding enabled the design of a straightforward process for the resolution of the enantiomers of a racemic guest.

Modulation of Chiroptical and Photophysical Properties in Helicenic Rhenium(I) Systems: The Use of an N-(Aza[6]helicenyl)-NHC Ligand.

The photophysical and chiroptical properties of a novel, chiral helicene-NHC-Re(I) complex bearing an N-(aza[6]helicenyl)-benzimidazolylidene ligand are described, showing its ability to emit yellow circularly polarized luminescence. A comparative analysis of this new system with other helicene-Re(I) complexes reported to date illustrates the impact of structural modifications on the emissive and absorptive properties.

Weakly Self-Assembled [6]Helicenes: Circularly Polarized Light and Spin Filtering Properties.

Self-assembling features, chiroptical activity, and spin filtering properties are reported for 2,15- and 4,13-disubstituted [6]helicenes decorated in their periphery with 3,4,5-tris(dodecyloxy)-N-(4-ethynylphenyl)benzamide moieties. The weak non-covalent interaction between these units conditions the corresponding circularly polarized luminescence and spin polarization. The self-assembly is overall weak for these [6]helicene derivatives that, despite the formation of H-bonding interactions between the amide groups present in the peripheral moieties, shows very similar chiroptical properties both in the monomeric or aggregated states. This effect could be explained by considering the steric effect that these groups could generate in the growing of the corresponding aggregate formed. Importantly, the self-assembling features also condition chiral induced spin selectivity (CISS effect), with experimental spin polarization (SP) values found between 35-40 % for both systems, as measured by magnetic-conducting atomic force microscopy (AFM) technique.

Chiral Atropisomeric-NHC Catechodithiolate Ruthenium Complexes for Z-Selective Asymmetric Ring-Opening Cross Metathesis of Exo-Norbornenes.

A set of 16 chiral ruthenium complexes containing atropisomerically stable N-Heterocyclic Carbene (NHC) ligands was synthesized from prochiral NHC precursors. After a rapid screening in asymmetric ring-opening-cross metathesis (AROCM), the most effective chiral atrop BIAN-NHC Ru-catalyst (up to 97 : 3 er) was then converted to a Z-selective catechodithiolate complex. The latter proved to be highly efficient in Z-selective AROCM of exo-norbornenes affording valuable trans-cyclopentanes with excellent Z-selectivity (>98 %) and high enantioselectivity (up to 96.5 : 3.5 er).

Synthesis and Chiroptical Properties of a Chiral Isotopologue of syn-Cryptophane-B.

We report the synthesis and absolute configuration (AC) of a chiral isotopologue of syn-cryptophane-B. Low chiral signatures were measured by polarimetry and electronic circular dichroism, whereas most significant chiroptical effects were observed by vibrational circular dichroism (VCD) and Raman optical activity (ROA). The comparison of experimental VCD and ROA spectra with those predicted by DFT calculations allows the determination of the AC of the two enantiomers as (-)589-MP-syn-2 and (+)589-PM-syn-2.

Magneto-Chiral Dichroism in a One-Dimensional Assembly of Helical Dysprosium(III) Single-Molecule Magnets.

Here we report magneto-chiral dichroism (MChD) detected through visible and near-infrared light absorption of a chiral dysprosium(III) coordination polymer. The two enantiomers of [DyIII(H6(py)2)(hfac)3]n [H6(py)2 = 2,15-bis(4-pyridyl)ethynylcarbo[6]helicene; hfac- = 1,1,1,5,5,5-hexafluoroacetylacetonate], where the chirality is provided by a functionalized helicene ligand, were structurally, spectroscopically, and magnetically investigated. Magnetic measurements reveal a slow relaxation of the magnetization, with differences between enantiopure and racemic systems rationalized on the basis of theoretical calculations. When the enantiopure complexes are irradiated with unpolarized light in a magnetic field, they exhibit multiple MChD signals associated with the f-f electronic transitions of DyIII, thus providing the coexistence of MChD-active absorptions and single-molecule-magnet (SMM) behavior. These findings clearly show the potential that rationally designed chiral SMMs have in enabling the optical readout of magnetic memory through MChD.

Porphyrin- and Bodipy-helicene conjugates: syntheses, separation of enantiomers and chiroptical properties.

The synthesis of several new compounds containing a chromophore and a helicenic moiety is reported. The preparation, characterisation and some physico-chemical studies are detailed. In particular, the two enantiomers of several chiral molecules of this type were separated by chiral HPLC (both analytically and in a preparative way) and their racemisation rates were determined for short-lived species. Electronic circular dichroism (ECD) and circular polarised luminescence (CPL) measurements were performed for the compounds with a very long racemisation half-life. Chiral porphyrins and Bodipys both gave ECD and CPL responses over a large area of the visible spectrum.

Synthesis, structural characterization, and chiroptical properties of planarly and axially chiral boranils.

2-Amino[2.2]paracyclophane reacts with salicylaldehyde or 2-hydroxyacetophenone to yield imines that then give access to a new series of boranils (8b-d) upon complexation with BF2 . These novel boron-containing compounds display both planar and axial chiralities and were examined experimentally and computationally. In particular, their photophysical and chiroptical properties were studied and compared to newly prepared, simpler boranils (9a-d) exhibiting axial chirality only. Less sophisticated chiral architectures were shown to demonstrate overall stronger circularly polarized luminescence (CPL) activity.

NMR and DFT Studies with a Doubly Labelled 15 N/6 Li S-Trifluoromethyl Sulfoximine Reveal Why a Directed ortho-Lithiation Requires an Excess of n-BuLi.

This work shows why it is imperious to use an excess of butyllithium for a directed ortho-lithiation of a trifluoromethyl sulfoximine. The analysis of mixtures of n-BuLi and sulfoximine 1 in THF-d8 using {1 H, 6 Li, 13 C, 15 N, 19 F} NMR experiments at low temperatures reveal that a first deprotonation occurs that leads to dimeric and tetrameric N-lithiated sulfoximine (93 : 7). Using an excess n-BuLi (5 equivalents), the second deprotonation on the ortho-position of the aromatic occurs. Six species were observed and characterized on the way. It includes three aggregates involving a sulfoximine: i) a [dilithiated sulfoximine/(n-BuLi)] dimer solvated by four molecules of THF (Agg2, 39 %); ii) a [dilithiated sulfoximine/(n-BuLi)3 ] tetramer solvated by six molecules of THF (Agg3, 39 %); iii) a [dilithiated sulfoximine/(n-BuOLi)3 ] tetramer solvated by four molecules of THF (Agg1, 22 %). A DFT study afforded optimized solvated structures for all these aggregates, fully consistent with the NMR data.

Perfluoroalkyl Selenoxides, Selenones and Selenoximines: General Preparation and Properties.

A selective access to perfluoroalkyl selenoxides, via Oxone® as oxidant or to selenones by using a Polyoxometalate-based Ionic Liquid (POM-IL) as a catalyst for the oxidation step is described. The reaction works with various perfluoralkyl chains and substituents with satisfactory to excellent yields. A two-step one-pot reaction from selenocyanates was performed to gain access to perfluoroalkyl selenoxides. The previously unknown perfluoroalkyl selenoximines family was also prepared with good yields. Having unlocked two strategies for the synthesis of fluoroalkylated SeIV and SeVI compounds, we then evaluated the Hansch-Leo lipophilicity parameters of these groups. Finally, asymmetric aryl perfluoroalkyl selenoximines were resolved to determine their absolute configurations.

Circularly Polarized Luminescence from Cyclic (Alkyl)(Amino) Carbene Derived Propellers.

Organic circularly polarized luminescence (CPL)-active molecular emitters featuring dynamic propeller-like luminophores were prepared in one step from cyclic(alkyl)(amino) carbenes (CAACs). These molecules exhibit through-space arene-arene π-delocalization and rapid intramolecular inter-system crossing (ISC) in line with their helical character.