Chirality determination in crystals.

This tutorial review article discusses chirality determination in the solid state, both in single crystals and in crystal assemblies, with an emphasis on X-ray diffraction. The main principles of using X-ray diffraction to reliably determine absolute structure are summarized, and the complexity which can be encountered in chiral structures-kryptoracemates, scalemates, and inversion twinning-is illustrated with examples from our laboratories and the literature. We then address the problem of the bulk crystallization and discuss different techniques to determine chirality in a large assembly of crystal structures, with a special prominence given to an X-ray natural circular dichroism mapping technique that we recently reported.

Magneto-chiral anisotropy: From fundamentals to perspectives.

The interplay between chirality and magnetic fields gives rise to a cross effect referred to as magneto-chiral anisotropy (MChA), which can manifest itself in different physical properties of chiral magnetized materials. The first experimental demonstration of MChA was by optical means with visible light. Further optical manifestations of MChA have been evidenced across most of the electromagnetic spectrum, from terahertz to X-rays. Moreover, exploiting the versatility of molecular chemistry toward chiral magnetic systems, many efforts have been made to identify the microscopic origins of optical MChA, necessary to advance the effect toward technological applications. In parallel, the replacement of light by electric current has allowed the observation of nonreciprocal electrical charge transport in both molecular and inorganic conductors as a result of electrical MChA (eMChA). MChA in other domains such as sound propagation, photochemistry, and electrochemistry are still in their infancy, with only a few experimental demonstrations, and offer wide perspectives for further studies with potentially large impact, like the understanding of the homochirality of life. After a general introduction to MChA, we give a complete review of all these phenomena, particularly during the last decade.

Rapid Discrimination of Crystal Handedness by X-ray Natural Circular Dichroism (XNCD) Mapping.

An original method for determining the handedness of individual non-centrosymmetric crystals in a mixture using a tightly-focused, circularly polarized X-ray beam is presented. The X-ray natural circular dichroism (XNCD) spectra recorded at the metal K-edge on selected crystals of [Δ-M(en)3 ](NO3 )2 and [Λ-M(en)3 ](NO3 )2 (M=CoII , NiII ) show extrema at the metal pre-edge (7712 eV for Co, 8335 eV for Ni). A mapping of a collection of some 220 crystals was performed at the respective energies by using left and right circular polarizations. The difference in absorption for the two polarizations, being either negative or positive, directly yielded the handedness of the crystal volume probed by the beam. By using this technique, it was found that the addition of l-ascorbic acid during the synthesis of [Co(en)3 ](NO3 )2 resulted in an enantiomeric enrichment of the Λ-isomer of 67±13 %, whereas the Ni analogue was similarly, but conversely, enriched in the Δ-isomer (65±22 %).

The Origin of Magnetic Anisotropy and Single-Molecule Magnet Behavior in Chromium(II)-Based Extended Metal Atom Chains.

Chromium(II)-based extended metal atom chains have been the focus of considerable discussion regarding their symmetric versus unsymmetric structure and magnetism. We have now investigated four complexes of this class, namely, [Cr3(dpa)4X2] and [Cr5(tpda)4X2] with X = Cl- and SCN- [Hdpa = dipyridin-2-yl-amine; H2tpda = N2,N6-di(pyridin-2-yl)pyridine-2,6-diamine]. By dc/ac magnetic techniques and EPR spectroscopy, we found that all these complexes have easy-axis anisotropies of comparable magnitude in their S = 2 ground state (|D| = 1.5-1.8 cm-1) and behave as single-molecule magnets at low T. Ligand-field and DFT/CASSCF calculations were used to explain the similar magnetic properties of tri- versus pentachromium(II) strings, in spite of their different geometrical preferences and electronic structure. For both X ligands, the ground structure is unsymmetric in the pentachromium(II) species (i.e., with an alternation of long and short Cr-Cr distances) but is symmetric in their shorter congeners. Analysis of the electronic structure using quasi-restricted molecular orbitals (QROs) showed that the four unpaired electrons in Cr5 species are largely localized in four 3d-like QROs centered on the terminal, "isolated" Cr2+ ion. In Cr3 complexes, they occupy four nonbonding combinations of 3d-like orbitals centered only on the two terminal metals. In both cases, then, QRO eigenvalues closely mirror the 3d-level pattern of the terminal ions, whose coordination environment remains quite similar irrespective of chain length. We conclude that the extent of unpaired-electron delocalization has little impact on the magnetic anisotropy of these wire-like molecular species.

Resolution, structures, and vibrational circular dichroism of helicoidal trinickel and tricobalt paddlewheel complexes.

It has been recently shown that enantiomers of the helicoidal paddlewheel complex [Co3 (dpa)4 (CH3 CN)2 ]2+ (dpa = the anion of 2,2'-dipyridylamine) can be resolved using the chiral [As2 (tartrate)2 ]2- anion (AsT) and that these complexes demonstrate a strong chiroptical response in the ultraviolet-visible and X-ray energy regions. Here we report that the nickel congener, [Ni3 (dpa)4 (CH3 CN)2 ]2+ , can likewise be resolved using AsT. Depending on the stereochemistry of the enantiopure AsT anion, one or the other of the trinickel enantiomers crystallize from CH3 CN and diethyl ether in space group P421 2 as the (NBu4 )2 [Ni3 (dpa)4 (CH3 CN)2 ](AsT)2 ·[solvent] salt. After resolution, the AsT salts were converted into the PF6 - salts by anion exchange, with retention of the chirality of the trinickel complex. The enantiopure [Ni3 (dpa)4 (CH3 CN)2 ](PF6 )2 ·2CH3 CN and [Co3 (dpa)4 (CH3 CN)2 ](PF6 )2 ·CH3 CN·C4 H10 O compounds crystallize in space groups C2 and P21 , respectively. Both the Ni(II) and Co(II) complex cations are stable towards racemization in CH3 CN. Vibrational circular dichroism (VCD) data obtained in CD3 CN demonstrate the expected mirror image spectra for the enantiomers, the observed peaks arising from the dpa ligand. The VCD response is significant, with Δε values up to 6 Lmol-1 cm-1 and vibrational dissymmetry factors on the order of 10-3 . Density functional theory calculations well reproduce the experimental spectra, showing little difference between the peak position, sign, and intensity in the VCD for the cobalt and nickel complexes. These results suggest that VCD enhancement of these peaks is unlikely, and their remarkable intensity may be due to their rigid helicoidal structure.

Isomeric Column-Forming Esters and Imides with Varying Curvatures of the Aromatic Plane.

Dibenzo[a,j]coronene-tetracarboxylic alkyl esters and imides with either a centrosymmetric bis-peri substitution pattern or a polar bis-ortho substitution pattern form hexagonal columnar mesophases, which in the case of the imides persist at room temperature. The bis-peri isomers are obtained via a two-fold oxidative photocyclization; the bis-ortho isomers are accessed via a glyoxylic Perkin reaction of triphenylene and naphthalene building blocks. Steric congestion between the substituents and the adjacent benzo protrusion in the bis-ortho esters and imides leads to bending of the aromatic plane, which thus avoids twisting. These isomers surprisingly show a more pronounced liquid crystalline behaviour than their non-bent bis-peri homologs, accommodating non-planarity with columnar order by slipped stacking. Whereas both types of ester and the bis-peri imide show an optical behaviour typical for perylene chromophores, the strongly bent bis-ortho imide distinguishes itself notably from them by its absorption spectrum. The electron acceptor strength of the isomeric diimides is found to differ, the hexagonal (peri) diimide having a 0.20 eV lower LUMO energy than the pentagonal (ortho) isomer.

Columnar Liquid-Crystalline Dibenzopentacenodithiophenes by Photocyclization.

The twofold glyoxylic Perkin reaction of perylene-3,9-diglyoxylic acid with thiophene-diacetic acid followed by oxidative photocylization and reaction with α-branched primary alkylamines yields columnar liquid-crystalline diimides with two sulfur atoms in the condensed arene system. A broad temperature range of the hexagonal columnar mesophase is induced by racemic doubly branched alkyl chains. The HOMO and LUMO energy levels of these thiophene-derived diimides qualify them as electron donors with respect to perylene diimides.

Columnar liquid-crystalline dinaphthoperylenetetracarboxdiimides.

Although the double Friedel-Crafts acylation of arenes with ethyl chloroglyoxylate is hindered by the strongly deactivating effect of the first-entering glyoxylic substituent, the double reaction is successful with the reactive arene perylene under long reaction times and with concomitant ester hydrolysis. The reaction is regiospecific, giving the 3,9-regioisomer exclusively. This perylenylenediglyoxylic acid is condensed first with o-bromophenylacetic acid and then with α-branched alkylamines to yield the title compounds. Whilst the corresponding tetraalkyl esters only show monotropic mesophases, these diimides show enantiotropic columnar mesophases that can be maintained at room temperature if racemically branched alkyl chains of moderate size are used. A palladium-induced C-C bond migration during the build-up of the arene system leads to an isomeric side product of reduced symmetry that can be isolated by aggregation-controlled chromatographic separation. The HOMO and LUMO energies of the title compounds are considerably higher than those of established perylenetetracarboxdiimides.

Plank-shaped column-forming mesogens with substituents on one side only.

Prolonged glyoxylation of pyrenyl-1-glyoxylic acid ethyl ester leads to a mixture of isomers with polar pyrenylene-1,8-diglyoxylic acid as the main product, whereas the centrosymmetric 1,6-isomer is obtained in good yield from the corresponding dibromopyrene. Perkin condensations followed by Pd-catalyzed cyclizations lead to isomeric dinaphthopyrene-tetracarboxdiimides that self-assemble into columnar liquid crystals of hexagonal and rectangular symmetry, of which the rectangular mesophases have unusually elongated unit cells. The cisoid diimides with both alkylimide substituents on the same side of the oblong arene system show a much greater tendency to self-assemble into fluid stacks of disks than their centrosymmetric isomers. With racemically branched alkyl substituents, uniform vertical surface alignment of the columns in the high-temperature hexagonal mesophase is resilient to cycling through the lower-temperature rectangular and crystalline phases.

Electronic Structure of Ru2(II,II) Oxypyridinates: Synthetic, Structural, and Theoretical Insights into Axial Ligand Binding.

Reduction of (4,0)-Ru2(chp)4Cl (1) (chp = 6-chloro-2-oxypyridinate) with Zn or FeCl2 yields a series of axial ligand adducts of the Ru2(II,II) species Ru2(chp)4(L), with L = tetrahydrofuran (2), dimethyl sulfoxide (DMSO; 3), PPh3 (4), pyridine (5), or MeCN (6). Zn reduction in noncoordinating solvents such as toluene or CH2Cl2 leads to the dimeric species [Ru2(chp)4]2 (7) or [Ru2(chp)4]2(ZnCl2) (8), whereas addition of strongly σ-donating ligands such as CO causes cleavage of the Ru-Ru bond. Density functional theory (DFT) models of these complexes, the axially free species, and the axial adducts of several other potential ligands (H2O, NH3, CH2Cl2, S-bound DMSO, N2, and CO) indicate that these compounds can be divided into three distinct categories, based on their Ru-Ru bond length and electronic structure. Compounds 2, 3, 5, 6, 7, and 8, the hypothetical axially free species, and adducts of H2O and NH3 fit in Category 1 with a (δ*)(2)(π*)(2) ground state, as indicated by their electronic spectra, magnetic properties, and Ru-Ru bond distances. However, compound 4 and the CH2Cl2 adduct (Category 2) show a pseudo-Jahn-Teller distortion and spectroscopic signs of δ*/π* orbital mixing suggestive of a new electronic ground state intermediate between the (δ*)(2)(π*)(2) and (δ*)(1)(π*)(3) configurations. Category 3 consists of the hypothetical adducts of N2, S-bound DMSO, and CO, all of which are predicted to have a (δ*)(1)(π*)(3) configuration. Electronic spectra were recorded and assigned using time-dependent DFT, allowing assignment of a band in the 10,000-13,000 cm(-1) range as the δ → π* transition. The axial ligand's π-acid character heavily influences the δ*-π* gap, and thereby the ground-state electronic configuration, but not the axial ligand binding strength, which is dictated more by the σ-donor character of the ligands. Thus, this work greatly expands the number of axial ligand adducts known for Ru2(II,II) complexes supported by N,O-donor ligands and provides a predictive theoretical framework for their stability and electronic structures.

High rectification in organic diodes based on liquid crystalline phthalocyanines.

The optical and electrical properties of mesogenic metal-free and metalated phthalocyanines (PCs) with a moderately sized and regioregular alkyl periphery were investigated. In solution, the individualized molecules show fluorescence lifetimes of 4-6 ns in THF. When deposited as solid thin films the materials exhibit significantly shorter fluorescence lifetimes with bi-exponential decay (1.4-1.8 ns; 0.2-0.4 ns) that testify to the formation of aggregates viaπ-π intermolecular interactions. In diode structures, their pronounced columnar order outbalances the unfavorable planar alignment and leads to excellent rectification behavior. Field-dependent charge carrier mobilities are obtained from the J-V curves in the trap-limited space-charge-limited current regime and demonstrate that the metalated PCs display an improved electrical response with respect to the metal-free homologue. The excited-state lifetime characterization suggest that the π-π intermolecular interactions are stronger for the metal-free PC, confirming that the metallic centre plays an important role in the charge transport inside these materials.

An "intermediate spin" nickel hydride complex stemming from delocalized Ni2(µ-H)2 bonding.

The nickel hydride complex [Cp'Ni(µ-H)]2 (1, Cp' = 1,2,3,4-tetraisopropylcyclopentadienyl) is found to have a strikingly short Ni-Ni distance of 2.28638(3) Å. Variable temperature and field magnetic measurements indicate an unexpected triplet ground state for 1 with a large zero-field splitting of +90 K (63 cm(-1)). Electronic structure calculations (DFT and CASSCF/CASPT2) explain this ground state as arising from half occupation of two nearly degenerate Ni-Ni π* orbitals.

Oxidative stretching of metal-metal bonds to their limits.

Oxidation of quadruply bonded Cr2(dpa)4, Mo2(dpa)4, MoW(dpa)4, and W2(dpa)4 (dpa = 2,2'-dipyridylamido) with 2 equiv of silver(I) triflate or ferrocenium triflate results in the formation of the two-electron-oxidized products [Cr2(dpa)4](2+) (1), [Mo2(dpa)4](2+) (2), [MoW(dpa)4](2+) (3), and [W2(dpa)4](2+) (4). Additional two-electron oxidation and oxygen atom transfer by m-chloroperoxybenzoic acid results in the formation of the corresponding metal-oxo compounds [Mo2O(dpa)4](2+) (5), [WMoO(dpa)4](2+) (6), and [W2O(dpa)4](2+) (7), which feature an unusual linear M···M≡O structure. Crystallographic studies of the two-electron-oxidized products 2, 3, and 4, which have the appropriate number of orbitals and electrons to form metal-metal triple bonds, show bond distances much longer (by >0.5 Å) than those in established triply bonded compounds, but these compounds are nonetheless diamagnetic. In contrast, the Cr-Cr bond is completely severed in 1, and the resulting two isolated Cr(3+) magnetic centers couple antiferromagnetically with J/kB= -108(3) K [-75(2) cm(-1)], as determined by modeling of the temperature dependence of the magnetic susceptibility. Density functional theory (DFT) and multiconfigurational methods (CASSCF/CASPT2) provide support for "stretched" and weak metal-metal triple bonds in 2, 3, and 4. The metal-metal distances in the metal-oxo compounds 5, 6, and 7 are elongated beyond the single-bond covalent radii of the metal atoms. DFT and CASSCF/CASPT2 calculations suggest that the metal atoms have minimal interaction; the electronic structure of these complexes is used to rationalize their multielectron redox reactivity.

Size-tunable silicon nanoparticles synthesized in solution via a redox reaction.

A current challenge in silicon chemistry is to perform liquid-phase synthesis of silicon nanoparticles, which would permit the use of colloidal synthesis techniques to control size and shape. Herein we show how silicon nanoparticles were synthesized at ambient temperature and pressure in organic solvents through a redox reaction. Specifically, a hexacoordinated silicon complex, bis(N,N'-diisopropylbutylamidinato)dichlorosilane, was reduced by a silicon Zintl phase, sodium silicide (Na4Si4). The resulting silicon nanoparticles were crystalline with sizes tuned from a median particle diameter of 15 nm to 45 nm depending on the solvent. Photoluminescence measurements performed on colloidal suspensions of the 45 nm diameter silicon nanoparticles indicated a blue emission signal, attributed to the partial oxidation of the Si nanocrystals or to the presence of nitrogen impurities.

Induced circular dichroism from helicoidal nano substrates to porphyrins: the role of chiral self-assembly.

Because the combination of chiral and magnetic properties is becoming more and more attractive for magneto-chiral phenomena, we here aim at exploring the induction of chirality to achiral magnetic molecules as a strategy for the preparation of magneto-chiral objects. To this end, we have associated free base- and metallo-porphyrins with silica nano helices, using a variety of elaboration methods, and have studied them mainly by electronic natural circular dichroism (NCD) and magnetic circular dichroism (MCD) spectroscopies. While electrostatic or covalent surface grafting uniformly yielded very low induced CD (ICD) for the four assayed porphyrins, a moderate response was observed when the porphyrins were incorporated into the interior of the double-walled helices, likely due to the association of the molecules with the chirally-organized gemini surfactant. A generally stronger, but more variable, ICD was observed when the molecules were drop casted onto the helices immobilised on a quartz plate, likely due to the different capacities of the porphyrins to aggregate into chiral assemblies. Electronic spectroscopy, electron microscopy and IR spectroscopy were used to interpret the patterns of aggregation and their influence on ICD and MCD. No enhancement of MCD was observed as a result of association with the nanohelices except in the case of the free base, 5,10,15,20-tetra-(4-sulfonatophenyl)porphyrin (TPPS). This nanocomposite demonstrated a large ICD in the Soret region and a large MCD in the Q-region due to J-aggregation. However, no induced MChD was observed, possibly due to the spectral mismatch between the ICD and MCD peaks.

Deciphering the activation sequence of ferrociphenol anticancer drug candidates.

The complete oxidation sequence of a model for ferrociphenols, a new class of anticancer drug candidate, is reported. Cyclic voltammetry was used to monitor the formation of oxidation intermediates on different timescales, thereby allowing the electrochemical characterization of both the short-lived and stable species obtained from the successive electron-transfer and deprotonation steps. The electrochemical preparation of the ferrocenium intermediate enabled a stepwise voltammetric determination of the stable oxidation compounds obtained upon addition of a base as well as the electron stoichiometry observed for the overall oxidation process. A mechanism has been established from the electrochemical data, which involves a base-promoted intramolecular electron transfer between the phenol and the ferrocenium cation. The resulting species is further oxidized then deprotonated to yield a stable quinone methide. To further characterize the transient species successively formed during the two-electron oxidation of the ferrociphenol to its quinone methide, EPR was used to monitor the fate of the paramagnetic species generated upon addition of imidazole to the electrogenerated ferrocenium. The study revealed the passage from an iron-centered to a carbon-centered radical, which is then oxidized to yield the quinone methide, namely, the species that interacts with proteins and so forth under biological conditions.

Design of Binary Nb2O5-SiO2 Self-Standing Monoliths Bearing Hierarchical Porosity and Their Efficient Friedel-Crafts Alkylation/Acylation Catalytic Properties.

Alkylation of aromatic hydrocarbons is among the most industrially important reactions, employing acid catalysts such as AlCl3, H2SO4, HF, or H3PO4. However, these catalysts present severe drawbacks, such as low selectivity and high corrosiveness. Taking advantage of the intrinsic high acid strength and Lewis and Brønsted acidity of niobium oxide, we have designed the first series of Nb2O5-SiO2(HIPE) monolithic catalysts bearing multiscale porosity through the integration of a sol-gel process and the physical chemistry of complex fluids. The MUB-105 series offers efficient solvent-free heterogeneous catalysis toward Friedel-Crafts monoalkylation and -acylation reactions, where 100% conversion has been reached at 140 °C while cycling. Alkylation reactions employing the MUB-105(1) catalyst have a maximum turnover number (TON) of 104 and a turnover frequency (TOF) of 9 h-1, whereas for acylation, MUB-105(1) and MUB-105(2) yield maximum TON and TOF values of 107 and 11 h-1, respectively. Moreover, the catalysts are selective, producing equal amounts of ortho- and para-substituted alkylated products and greater than 90% of the para-substituted acylated product. The highest catalytic efficiencies are obtained for the MUB-105(1) catalyst, bearing the smallest Nb2O5 particle sizes, lowest Nb2O5 content, and the highest amorphous character. The catalysts presented here are in a monolithic self-standing state, offering easy handling, reusability, and separation from the final products.

Ferrocenyl chalcone difluoridoborates inhibit HIV-1 integrase and display low activity towards cancer and endothelial cells.

We report here the discovery of a potent series of HIV-1 integrase (IN) inhibitors based on the ferrocenyl chalcone difluoridoborate structure. Ten new compounds have been synthesized and were generally found to have similar inhibitory activities against the IN 3' processing and strand transfer (ST) processes. IC(50) values were found to be in the low micromolar range, and significantly lower than those found for the non-coordinated ferrocenyl chalcones and other ferrocene molecules. The ferrocenyl chalcone difluoridoborates furthermore exhibited low cytotoxicity against cancer cells and low morphological activity against epithelial cells.

A linear metal-metal bonded tri-iron single-molecule magnet.

The linear trinuclear complex cation [Fe3(DpyF)4]2+ was prepared as [Fe3(DpyF)4](BF4)2·2CH3CN. With large Fe-Fe distances of 2.78 Å, this complex demonstrates intramolecular ferromagnetic coupling between the anisotropic FeII centers (J/kB = +20.9(5) K) giving an ST = 6 ground state and exhibits single-molecule magnet properties.

Nature of bonding in complexes containing "supershort" metal-metal bonds. raman and theoretical study of M2(dmp)4 [M = Cr (natural abundance Cr, 50Cr, and 54Cr) and Mo; dmp = 2,6-dimethoxyphenyl].

We report an investigation of complexes of the type M(2)(dmp)(4) (M = Mo, Cr; dmp = 2,6-dimethoxyphenyl) using resonance Raman (RR) spectroscopy, Cr isotopic substitution, and density functional theory (DFT) calculations. Assignment of the Mo-Mo stretching vibration in the Mo(2) species is straightforward, as evidenced by a single resonance-enhanced band at 424 cm(-1), consistent with an essentially unmixed metal-metal stretch, and overtones of this vibration. On the other hand, the Cr(2) congener has no obvious metal-metal stretching mode near 650-700 cm(-1), where empirical predictions based on the Cr-Cr distance as well as DFT calculations suggest that this vibration should appear if unmixed. Instead, three bands are observed at 345, 363, and 387 cm(-1) that (a) have relative RR intensities that are sensitive to the Raman excitation frequency, (b) exhibit overtones and combinations in the RR spectra, and (c) shift in frequency upon isotopic substitution ((50)Cr and (54)Cr). DFT calculations are used to model the vibrational data for the Mo(2) and Cr(2) systems. Both the DFT results and empirical predictions are in good agreement with experimental observations in the Mo(2) complex, but both, while mutually consistent, differ radically from experiment in the Cr(2) complex. Our experimental and theoretical results, especially the Cr isotope shifts, clearly demonstrate that the potential energy of the Cr-Cr stretching coordinate is distributed among several normal modes having both Cr-Cr and Cr-ligand character. The general significance of these results in interpreting spectroscopic observations in terms of the nature of metal-metal multiple bonding is discussed.