Adsorption isotherms and retention behavior of 1,1'-bis(2-naphthol) on CHIRIS AD1 and CHIRIS AD2 columns

The separation of the atropoisomers of 1,1'-bis(2-naphthol) was studied on CHIRIS AD1 and CHIRIS AD2, two Pirkle-type chiral stationary phases. Satisfactory selectivity was found only on CHIRIS AD2. The ternary mobile phases comprised hexane, dichloromethane and methanol. The effects of their composition and of the temperature on the retention under analytical conditions and on the single-component and competitive isotherms were investigated. The retention of the R- and S-isomers on CHIRIS AD1 and CHIRIS AD2 is controlled by the enthalpic contribution to adsorption, but the effect of the mobile phase on the retention should be attributed mainly to the entropic contribution. The adsorption of the less retained R-isomer is controlled by the achiral interactions, which are the same as for the S-isomer. The single-component and competitive isotherms of the R- and S-isomers are adequately described by the sum of a Langmuir term for the achiral contribution to adsorption and a linear-term characterising the selective or chiral adsorption of the S-isomer in the concentration range experimentally available, i.e. within the solubility limit of 1,1'-bis(2-naphthol).     

Homochiral crystallization of helical coordination chains bridged by achiral ligands: can it be controlled by the ligand structure?

Homochiral/heterochiral crystallizations of helical chiral polymer chains bridged by achiral poly-pyridyl ligands dependent on the structures of the bridging ligands and independent on the solvent are described, implying a possible strategy to design achiral crystals of helical chains using chiral bridging ligands.     

Molecular Chirality Recognized by Achiral Compounds

Abstract

Three cases are described where chirality is recognized by achiral molecules, where chirality is induced into achiral compounds through interactions with chiral compounds, and lastly where induced chirality in the solid-state is utilized for an enantio-selective photoreaction. In the first instance, the thermodynamically and kinetically preferred diastereoisomer of an optically labile chromium complex depended on the nature of the achiral solvent. In the second case, for the first time 1,2-chloroethane was trapped and observed in a chiral near-eclipsed form and 1-chloropropane in the truly eclipsed form at room temperature in a 1:1 inclusion complex with an optically active host molecule. Finally, induced chirality in a prochiral compound in the solid-state was successfully employed in an enantio-selective photoreaction. In the two cases, solid-state CD provided valuable information.     

Spontaneous resolution of a 3D chiral polyoxometalate-based polythreaded framework consisting of an achiral ligand

Two enantiomerically 3D chiral POM-based architectures have been constructed based on the achiral ligand bbi, [V10O26](4-) polyoxoanion and mixed valence Cu(I/II) without a chiral auxiliary, and they represent the first examples of enantiomerically 3D POM-based compounds using achiral ligands.     

Optically active polymer film tuned by a chirally self-assembled molecular organogel

Chirally-oriented lipid aggregates were doped into a solid polymer film, which was readily prepared by casting and removing a solvent from anionic l-glutamide-derived organogels and polystyrene. When a cationic achiral dye was mixed into this system, the resultant polymer film showed tunable circular dichroism (CD) due to chiral complex formation with the achiral dye on the highly-ordered structures based on the l-glutamide lipid.     

Combination of spectroscopic and computational methods to get an understanding of supramolecular chemistry of drugs: from simple host systems to biomolecules

Circular dichroism (CD) spectra of non-covalent ligand : biomolecule couples contain information on the equilibrium geometries of the associated structures that can be retrieved upon comparison of the sign and intensity of the experimental CD bands with the quantum mechanically calculated rotational strengths of low energy supramolecular complexes, obtained from molecular modelling methods. For both chiral and achiral ligands this approach proved useful to reach a structure based rationale of ground and excited state properties of the non-covalent ligand : protein associates. In this Perspective we illustrate the potential of this method focusing on the main achievements of our recent spectroscopic, conformational and photochemical studies on drug-albumin complexes and collocate it in the frame of current methodologies of molecular modelling and spectroscopic investigation of ligand : biomolecule binding.     

Supramolecular chirogenesis in zinc porphyrins: interaction with bidentate ligands,formation of tweezer structures,and the origin of enhanced optical activity

The complexation behavior, binding properties, and spectral parameters of supramolecular chirality induction in the achiral host molecule, syn (face-to-face conformation) ethane-bridged bis(zinc porphyrin), upon interaction with chiral bidentate guests (diamines and amino alcohols) have been studied by means of UV-vis, CD, fluorescence, (1)H NMR, and ESI MS techniques. It was found that the guest structure plays a decisive role in the chirogenesis pathway. The majority of bidentate ligands (except those geometrically unsuitable) exhibit two major equilibria steps: the first guest ligation leading to formation of the 1:1 host-guest tweezer structure (K(1)) and the second guest molecule ligation (K(2)) forming the anti bis-ligated species (1:2). The second ligation is much weaker (K(1) > K(2)) due to the optimal geometry and stability of the 1:1 tweezer complex. The enhanced conformational stability of the tweezer complex ensures an efficient chirality transfer from the chiral guest to the achiral host, consequently inducing a remarkably high optical activity in the bis-porphyrin.     

Enantioselective supramolecular catalysis induced by remote chiral diols

A new method of creating libraries of chiral diphosphines is presented. Supramolecular coordination compounds based on Ti, Rh, achiral ditopic ligands, and chiral diols were synthesized by in situ mixing and used as catalysts in the asymmetric hydrogenation of (Z)-methyl 2-acetamido-3-phenylacrylate, giving ee's of up to 92%. The ditopic ligands contain a Schiff base that coordinates to the assembly metal Ti and a phosphine as a ligand for Rh. Chirality is introduced by coordination of the chiral diols to Ti. The controlling chiral center and the substrate are separated by as much as 13 ?.     

Optimization of catalyst enantioselectivity and activity using achiral and meso ligands

The optimization of asymmetric catalysts for enantioselective synthesis has conventionally revolved around the synthesis and screening of enantiopure ligands. In contrast, we have optimized an asymmetric reaction by modification of a series of achiral ligands. Thus, employing (S)-3,3'-diphenyl BINOL [(S)-Ph(2)-BINOL] and a series of achiral diimine and diamine activators in the asymmetric addition of alkyl groups to benzaldehyde, we have observed enantiomeric excesses between 96% (R) and 75% (S) of 1-phenyl-1-propanol. Some of the ligands examined have low-energy chiral conformations that can contribute to the chiral environment of the catalyst. These include achiral diimine ligands with meso backbones that adopt chiral conformations, achiral diimine ligands with backbones that become axially chiral on coordination to metal centers, achiral diamine ligands that form stereocenters on coordination to metal centers, and achiral diamine ligands with pendant groups that have axially chiral conformations. Additionally, we have structurally characterized (Ph(2)-BINOLate)Zn(diimine) and (Ph(2)-BINOLate)Zn(diamine) complexes and studied their solution behavior.     

Evaluation of complexes of DNA duplexes and novel benzoxazoles or benzimidazoles by electrospray ionization mass spectrometry

Electrospray ionization mass spectrometry is used to compare the metal ion binding and metal-mediated DNA binding of benzoxazole (1, 2, 3, 4) and benzimidazole (5) compounds and to elucidate the putative binding modes and stoichiometries. The observed metal versus non-metal-mediated DNA binding, as well as the specificity of DNA binding, is correlated with the biological activities of the analogs. The ESI-MS spectra for the antibacterial benzoxazole and benzimidazole analogs 4 and 5 demonstrated non-specific and non-metal-mediated binding to DNA, with the appearance of DNA complexes containing multiple ligands. The anticancer analog 2 demonstrates a clear preference for metal-mediated DNA interactions, with an apparent selectivity for Ni2+ -mediated binding over the more physiologically relevant Mg2+ or Zn2+ cations. Complexation between DNA and the biologically inactive analog 1 was not observed, either in the absence or presence of metal cations.     

Chirality induction in metal-induced achiral polythiophene aggregates assisted by optically active amines and polythiophene

A regioregular achiral polythiophene bearing oxazoline pendant groups formed a unique optically active metal-induced supramolecular aggregate upon complexation with chiral amines or in the presence of a chiral polythiophene in a good solvent for the polymers, thus showing an induced circular dichroism.     

Spontaneous resolution of chiral polyoxometalate-based compounds consisting of 3D chiral inorganic skeletons assembled from different helical units

Four enantiomerically pure 3D chiral POM-based compounds, [Ni(2)(bbi)(2)(H(2)O)(4)V(4)O(12)]2 H(2)O (1 a and 1 b) and [Co(bbi)(H(2)O)V(2)O(6)] (2 a and 2 b) (bbi=1,1'-(1,4-butanediyl)bisimidazole) based on the achiral ligand, different vanadate chains, and different metal centers have been synthesized by hydrothermal methods. Single-crystal X-ray diffraction analyses revealed that 1 a and 1 b, and 2 a and 2 b, respectively, are enantiomers. In 1 a and 1 b two kinds of vanadate chains with different screw axes link Ni cations to generate 3D chiral inorganic skeletons, which are connected by the achiral bbi ligands to form complicated 3D 3,4-connected chiral self-penetrating frameworks with (7(2)8)(7(2)8(2)9(2))(7(3)8(2)10) topology. They represent the first examples of chiral self-penetrating frameworks known for polyoxometalate (POM) systems. Contrary to 1 a and 1 b, in 2 a and 2 b the vanadate chains link Co(II) cations to generate 3D chiral inorganic skeletons, which are assembled from two kinds of heterometallic helical units of opposite chirality along the c axes. The chiral inorganic skeletons are connected by bbi to form 3D 3,4-connected chiral POM-based frameworks with (6(2)8)(2)(6(2)8(2)10(2)) topology. It is believed that the asymmetrical coordination modes of the metal cations in 1 a-2 b generate the initial chiral centers, and that the formation of the various helical units and the hydrogen bond interactions are responsible for preservation of the chirality and spontaneous resolution when the chirality is extended into the homochiral 3D-networks. This is the first known report of chiral POM-based compounds consisting of 3D chiral inorganic skeletons being obtained by spontaneous resolution upon crystallization in the absence of any chiral source, which may provide a rational strategy for synthesis of chiral POM-based compounds by using achiral ligands and POM helical units.     

A Supramolecular Chiral Auxiliary Approach: “Remote Control” of Stereochemistry at a Hierarchically Assembled Dimeric Helicate

Dimeric hierarchically‐assembled titanium(IV) helicates are in solvent‐dependent equilibrium with the corresponding monomers. Statistically formed mixtures of such complexes bearing chiral stereocontrolling ligands and achiral diene‐substituted ligands show high diastereoselectivity and reasonable enantioselectivity in the Diels–Alder reaction with maleimides if the reaction proceeds with the dimer but not with the monomer. Thus, solvent dependent switching between the monomer and dimer enables on/off switching of the enantioselectivity.     

Induced chirality upon crocetin binding to human serum albumin: origin and nature

Binding to human serum albumin (HSA) of the natural, achiral carotenoid crocetin, having hypocholesterolemic and antitumour effects, was investigated in detail by circular dichroism (CD) and absorption spectroscopy. It has been shown that in the visible absorption region the crocetin–HSA complex exhibits a well-defined induced circular dichroic spectrum with two major bands of opposite sign, proving excitonic interaction between carotenoids bound in a left-handed chiral arrangement on the albumin molecule. In the course of CD titration experiments, palmitic acid gradually decreased the exciton band intensities indicating that crocetin and palmitic acid have common binding sites on HSA. To investigate potential sources of the intermolecular excitonic interaction, molecular modeling studies were performed fitting crocetin molecules to the long-chain fatty acid binding sites of HSA, determined recently by X-ray crystallographic measurements. The results suggest that binding of crocetin to domain III of the albumin might be responsible for the observed intermolecular exciton coupling. Crocetin binding was accompanied by a significant red shift in the visible absorption spectrum which has showed no excitonic contribution but rather indicates the higher polarizability of the protein environment.     

The significance of induced circular dichroism

[reaction: see text] Achiral molecules or ions can display induced circular dichroism (ICD) within their absorption bands on association with chiral inducing molecules. The reverse process is equally important, although less appreciated: chiral inducing molecules, such as tartrates, can show significantly differing CD bands in different achiral environments. Therefore true ICD due to achiral molecules can only be demonstrated in the spectral region outside the absorption bands of the chiral inducing molecules. The case of tartrate-trisimidazoline helical assembly in aqueous solvent is discussed.     

The use of mixtures of ligands in the Ir-catalyzed asymmetric reductive amination of 6-methyl-2,3,4,9-tetrahydro-1<Emphasis Type="Italic">H</Emphasis>-carbazol-1-one

A comparative testing of complex catalysts with homo and hetero combinations of chiral and achiral monodentate phosphite- and phosphine-type ligands in the Ir-catalyzed asymmetric direct reductive amination of 2,3,4,9-tetrahydro-1H-сarbozol-1-ones was carried out. A positive effect of the use in the reaction of a mixture of chiral and achiral ligands was demonstrated. This approach makes feasible a one-pot synthesis of valuable biologically active compounds of (tetrahydro-1H-carbazol-1-yl)amine series.     

Photochemically reversible and thermally stable axially chiral diarylethene switches

A series of dithienylcyclopentenes containing axially chiral 1,1'-binaphthyl units were successfully synthesized by a Suzuki-Miyaura protocol. All these compounds exhibited photochemically reversible isomerization with thermal stability in both organic solvent and a liquid crystal (LC) host. When doping into an achiral LC host, some of them exhibited very high helical twisting powers. Reversible reflection wavelength tuning in the visible region and LC phase switching between nematic and cholesteric upon light irradiation were demonstrated.     

SYNTHESIS AND EVALUATION OF 2-DIAZO-3,3,3-TRIFLUOROPROPANOYL DERIVATIVES OF COLCHICINE AND PODOPHYLLOTOXIN AS PHOTOAFFINITY LABELS: REACTIVITY, PHOTOCHEMISTRY, AND TUBULIN BINDING

Derivatives of the tubulin polymerization inhibitors colchicine and podophyllotoxin bearing the photoreactive 2-diazo-3,3,3-trifluoropropanoyl (DTFP) group were synthesized for evaluation as potential photoaffinity labels of the tubulin binding site. All labels were assayed for their ability to inhibit tubulin polymerization, and N-DTFP-deacetylthiocolchicine was shown to competitively inhibit tubulin-colchicine binding with a Ki of 4-5 microM. The tubulin off-rate of this analog was similar to that of podophyllotoxin, rather than to the relatively irreversibly bound colchicine. Photochemical solvent insertion reactions of the labels were investigated. Radioactive samples of the two most active labels were prepared and used in initial protein-labeling experiments, during which the fractional occupancy of tubulin and extent of covalent incorporation were determined. A rearrangement of DTFP amides was encountered which is relevant to the utility of this moiety for use in synthesis of photoaffinity labels.     

Induced circular dichroism by complexation of gadolinium(III) porphyrinates with chiral amino acids and dipeptides: effects of axial β-diketonate ligands on chirality sensing and recognition

Synthetic gadolinium(III)porphyrins with various achiral β-diketonates as axial ligands in benzene solutions extracted chiral -amino acids and dipeptides from aqueous phases to give intense induced CD peaks in the Soret region via 1:1 supercomplexation. Their CD spectral shapes were dependent on the stereochemistry at the -positions of amino acids and of the C-terminal components of dipeptides: a reverse S-shape for the -form and an S-shape for the -form. When chiral 3-acetylcamphorate was introduced as an axial ligand, Gd(III)porphyrins showed CD spectral changes by supercomplexation with chiral alanylalanine; (+)-acetylcamphorate ligating Gd(III)porphyrin offered larger CD signal with the - or -form than the corresponding (−)-type Gd(III)porphyrin did, while the former afforded smaller CD peaks by supercomplexation with the - or -form than the latter Gd(III)porphyrin.     

Construction of C1-symmetric zirconium complexes by the design of new Salan ligands. Coordination chemistry and preliminary polymerisation catalysis studies

The first synthesis of achiral and chiral [ONNO']-type Salan ligands featuring two different phenol arms, and the diastereoselective formation of the corresponding octahedral C1-symmetric zirconium complexes is described; the activity and isospecificity induction of the [ONNO']Zr(bn)2 complexes in 1-hexene polymerisation reflected those of the parent symmetric compounds.