Chiral recognition phenomena probed by steady-state luminescence measurements: Stern-Volmer analysis of chiral discriminatory behavior

The chiral recognition phenomenon observed in enantioselective excited-state energy transfer processes currently requires the use of chiroptical spectroscopic techniques to probe the magnitude and sense of the discriminatory interactions. The use of chiroptical spectroscopic techniques limits the study of chiral recognition to those molecular species with strong absorption or emission dissymmetry factors. This study presents the theoretical and experimental methodology to determine the magnitude of chiral discriminatory interactions with unpolarized, steady-state luminescence measurements. Based on bimolecular luminescence quenching kinetics for a system containing chiral molecules, the Stern-Volmer equation is derived and contains a chiral discriminatory term for a system containing a chiral but racemic luminophore and an enantiomerically resolved quencher species. The utility of this methodology is confirmed by examining the enantioselective excited-state quenching between several Ln(dpa)(3)(3-) complexes (where Ln = Eu(3+), Tb(3+), or Dy(3+) and dpa = pyridine-2,6-dicarboxylate) acting as the energy donor and either racemic or enantiomerically resolved [Co(dach)(3)](3+) (where dach = trans-1R,2R (or 1S,2S)-diaminocyclohexane) acting as the energy acceptor in an aqueous solution. The results of this study confirm the utility of unpolarized, steady-state luminescence measurements as a probe of chiral discriminatory behavior.     

Enantiomeric separation of several cyclic imides on a macrocyclic antibiotic (vancomycin) chiral stationary phase under normal and reversed phase conditions

Several cyclic imidic compounds (barbiturates, piperidine-2,6-diones, and mephenytoin) are enantiomerically resolved via high-performance liquid chromatography (HPLC) on a macrocyclic antibiotic covalently bonded to a silica gel support. The Chirobiotic V chiral stationary phase (CSP) column contains the antibiotic vancomycin as the chiral selector. The results of the analysis show that the substituents at the chiral carbon position of the racemic drugs affect chiral resolution. In addition, ring size may also play a role when considering the formation of analyte-CSP inclusion complexes. Contrary to the piperidine-2,6-diones, the chromatographic parameters for the barbiturates are much the same under normal- or reversed-phase conditions. The details of these results are discussed. Chirality 10:358–361, 1998. © 1998 Wiley-Liss, Inc.     

Thioamide, urea and thiourea bridged rhenium(I) complexes as luminescent anion receptors

Thioamides, urea and thiourea derivatives of 2,6-pyridinedicarbonyl dichloride, isophthaloyl dichloride and terephthaloyl dichloride have been synthesized. These ligands have been incorporated in dinuclear rhenium(I) diimine tricarbonyl complexes and the anion recognition properties of these complexes have been studied by luminescence, UV-Vis and ¹H NMR spectroscopic methods. The complexes act as receptors for anions via hydrogen bonding and electrostatic interactions. The anion sensing properties of the complexes are compared to earlier amide-based dinuclear rhenium(I) tricarbonyl complexes.     

Origin of the regioselectivity in an intramolecular nucleophilic addition to arene chromium tricarbonyl complexes

The source of the regioselectivity in the intramolecular nucleophilic addition of nitrile-stabilized carbanions to arene chromium tricarbonyl complexes was investigated for seven different substitution patterns on the arenes. All of the arenes are 1,4-dioxygenated and the substitution varies in the oxygen substituent and in the substituents of the arene carbons (hydrogen and alkyl). The regioselectivity is correlated with the preferred conformations of the chromium tricarbonyl group which in turn was determined by solution and solid-state ¹³C NMR spectroscopy, ¹H NMR spectroscopy in solution as well as X-ray diffraction. In the four complexes analyzed by X-ray diffraction and the three complexes analyzed by solid-state ¹³C NMR spectroscopy, there was only one complex where it was found that the preferred conformation of the -Cr(CO)₃ is different in solution than it is in the solid-state.     

Axially chiral Ni(II) complexes of α‐amino acids: Separation of enantiomers and kinetics of racemization

Herein we present design, synthesis, chiral HPLC resolution, and kinetics of racemization of axially chiral Ni(II) complexes of glycine and di‐(benzyl)glycine Schiff bases. We found that while the ortho‐fluoro derivatives are configurationally unstable, the pure enantiomers of corresponding axially chiral ortho‐chloro‐containing complexes can be isolated by preparative HPLC and show exceptional configurational stability (t_1/2 from 4 to 216 centuries) at ambient conditions. Synthetic implications of this discovery for the development of new generation of axially chiral auxiliaries, useful for general asymmetric synthesis of α‐amino acids, are discussed.     

Optically active titanium complexes containing a tridentate linked amido-cyclopentadienyl ligand

Optically active titanium complexes Tieta5:eta1-C5R4SiMe2NC6H10 (OCH2Ph)-2Cl2 (R = H, Me), containing a cyclopentadienyl ligand linked to the chiral trans-2-benzyloxycyclohexylamido group, were synthesized and characterized in both enantiomerically pure forms. A single crystal X-ray structure analysis of (-)-(R, R)-Tieta5:eta1-C5H4SiMe2NC6H10(OCH2Ph)-2Cl2 shows a structure in which the benzyloxy group in the amido sidechain is not interacting with the titanium center. Upon activation with n-butyllithium, these complexes hydrogenate acetophenone N-benzylimine with low enantioselectivity.     

Gas-chromatographic separation of tri(hetero)halogenomethane enantiomers

Five-atomic tri(hetero)halogenomethanes represent the simplest class of non-isotopic small chiral molecules suitable for the study of fundamental aspects of chirality. The analytical gas-chromatographic separation of the enantiomers of bromochlorofluoromethane 1 and of chlorofluoroiodomethane 2 on the immobilized chiral stationary phase octakis(3-O-butanoyl-2,6-di-O-n-pentyl)-gamma-cyclodextrin 3, chemically linked to polydimethylsiloxane, is described. By temperature-dependent thermodynamic measurements very low isoenantioselective temperatures T(iso) are found and for optimum enantiomeric separations cryogenic temperatures are required. The ee values of enantiomerically enriched tri(hetero)halogenomethanes 1 and 2 are determined and relative configurations are correlated with the chromatographic elution order of 1 and 2 on 3.     

Inexpensive chemical method for preparation of enantiomerically pure phenylalanine

Here, we report the most inexpensive procedure for chemical synthesis of enantiomerically pure phenylalanine. As a source of chirality, we use the ultimately inexpensive chiral auxiliary, 1-(phenyl)ethylamine, incorporated into the specially designed ligands which form the corresponding intermediate Ni(II) complexes with racemic phenylalanine. Diastereomerically pure Ni(II) complexes, containing either (S)- or (R)-phenylalanine, were disassembled to produce enantiomerically pure target amino acid, along with recycling the chiral ligand. All reactions were conducted under operationally convenient conditions, featuring high yields and thus underscoring attractive cost structure of this method.     

New bis(azolylcarbonyl)pyridine chromium(III) complexes as initiators for ethylene polymerization

Reaction of 2,6-pyridinedicarbonyl dichloride with 3,5-dimethylpyrazole and 1H-indazole, respectively, yield the tridentate ligands 2,6-bis(3,5-dimethylpyrazol-1-ylcarbonyl)pyridine (1) and 2,6-bis(indazol-1-ylcarbonyl)pyridine (2). The molecular structure of the new compound (2) was determined by single-crystal X-ray diffraction. These ligands react with CrCl₃(THF)₃ in THF to form neutral complexes of general formula [CrCl₃{2,6-bis(azolylcarbonyl)pyridine-N,N,N}] (3, 4) which were isolated in high yield as air stable green solids and characterized by elemental analysis, magnetic moment, IR, and mass spectroscopies. Theoretical calculations predict that the thermodynamically preferred structure of the complexes is the fac configuration. After reaction with methylaluminoxane (MAO) the chromium(III) complexes are active for the polymerization of ethylene.     

CH...Metal(II) axial interaction in planar complexes (metal=Cu, Pd) and implications for possible environmental effects of alkyl groups at biological copper sites

Intramolecular M(II)...H-C interactions (M(II)=Cu(II), Pd(II)) involving a side chain alkyl group of planar d8 and d9 metal complexes of the N-alkyl (R) derivatives of N,N-bis(2-pyridylmethyl)amine with an N3Cl donor set were established by structural and spectroscopic methods. The methyl group from the branched alkyl group (R=2,2-dimethylpropyl and 2-methylbutyl) axially interacts with the metal ion with the M...C and M...H distances of 3.056(3)-3.352(9) and 2.317(1)-2.606(1) A, respectively, and the M-H-C angles of 122.4-162.3 degrees . The Cu(II) complexes showing the interaction have a higher redox potential as compared with those without it, and the (1)H NMR signals of the interacting methyl group in Pd(II) complexes shifted downfield relative to the ligand signals. Dependence of the downshift values on the dielectric constants of the solvents used indicated that the M(II)...H-C interaction is mainly electrostatic in nature and may be regarded as a weak hydrogen bond. Implications for possible environmental effects of the leucine alkyl group at the type 1 Cu site of fungal laccase are also discussed.     

Interaction of antimalarial drugs with hemin

Hemin (ferriprotoporphyrin IX) is shown to form complexes with the chloroquine class of antimalarial drugs. The Soret band of hemin becomes optically active upon the addition of chiral drugs. Results on the hemin-induced quenching of the fluorescence of chloroquine are consistent with the formation of a 2:1 hemin:drug complex with a formation constant of 1.4 x 10(7) at 298 K. Also a direct comparison of the drug-treated and drug-free parasites themselves, by the noninvasive photoacoustic spectroscopic method, reveals an in vivo interaction between endogenous hemin and the added drug.     

Chirality-dependent interactions between molecular propeller structures in solution. Chiral recognition and discrimination processes modulated by temperature and incremental changes in structural chirality

Time-resolved chiroptical luminescence (TR-CL) measurements are used to study chirality-dependent intermolecular interactions in dynamic excited-state quenching processes. The measurements are carried out on solution samples that contain a racemic mixture of chiral luminophore molecules (with enantiomeric structures denoted by LambdaL and DeltaL) and a small, optically resolved concentration of chiral quencher (CQ) molecules. The luminophores are excited with a pulse of linearly polarized laser radiation to produce an initially racemic excited-state population of LambdaL* and DeltaL* enantiomers, and TR-CL measurements are then used to monitor the differential decay kinetics of the LambdaL* and DeltaL* subpopulations. Observed differences between the LambdaL* and DeltaL* decay kinetics reflect differential rate processes and efficiencies for LambdaL*-CQ vs. DeltaL*-CQ quenching actions, and they are diagnostic of chiral discriminatory interactions between the luminophore and quencher molecules. Twelve different luminophore-quencher systems are examined, in both H(2)O and D(2)O solutions, and in each case the quenching kinetics are measured over the 273-308 K temperature range. In all of the systems examined here, quenching occurs via electronic energy-transfer processes in transient (LambdaL*-CQ) and (DeltaL*-CQ) encounter complexes, and the chiral discriminatory rate parameters reflect the relative stabilities and lifetimes of these complexes as well as their structures and internal (electronic and nuclear) dynamics. All of the luminophore and quencher molecules examined in this study have three-bladed propeller-like structures that are very similar in overall shape and size. However, they exhibit small differences in the structural details of their propeller blades, and it is found that these small differences in structure can produce both qualitative and very substantial quantitative differences in their chiral recognition and discrimination properties.     

Reversible unfolding of fructose 6-phosphate, 2-kinase:fructose 2,6-bisphosphatase.

Reversible unfolding of rat testis fructose 6-phosphate,2-kinase:fructose 2,6-bisphosphatase in guanidine hydrochloride was monitored by following enzyme activities as well as by fluorescence methodologies (intensity, emission maximum, polarization, and quenching), using both intrinsic (tryptophan) and extrinsic (5((2-(iodoacetyl)amino) ethyl)naphthalene-1-sulfonic acid) probes. The unfolding reaction is described minimally as a 4-state transition from folded dimer-->partially unfolded dimer-->monomer-->unfolded monomer. The partially unfolded dimer had a high phosphatase/kinase ratio due to preferential unfolding of the kinase domain. The renaturation reaction proceeded by very rapid conversion (less than 1 s) of unfolded monomer to dimer, devoid of any enzyme activity, followed by slow (over 60 min) formation of the active enzyme. The recovery rates of the kinase and the phosphatase were similar. Thus, the refolding appeared to be a reversal of the unfolding pathway involving different forms of the transient dimeric intermediates. Fluorescence quenching studies using iodide and acrylamide showed that the tryptophans, including Trp-15 in the N-terminal peptide, were only slightly accessible to iodide but were much more accessible to acrylamide. Fructose 6-phosphate, but not ATP or fructose 2,6-bisphosphate, diminished the iodide quenching, but all these ligands inhibited the acrylamide quenching by 25%. These results suggested that the N-terminal peptide (containing a tryptophan) was not exposed on the protein surface and may play an important role in shielding other tryptophans from solvent.     

Effect of Chromatographic Conditions on Enantioseparation of Bovine Serum Albumin Chiral Stationary Phase in HPLC and Thermodynamic Studies

Twelve chiral compounds were enantiomerically resolved on bovine serum albumin chiral stationary phase (BSA‐CSP) by high‐performance liquid chromatography (HPLC) in reversed‐phase modes. Chromatographic conditions such as mobile phase pH, the percentage of organic modifier, and concentration of analyte were optimized for separation of enantiomers. For N‐(2, 4‐dinitrophenyl)‐serine (DNP‐ser), the retention factors (k) greatly increase from 0.81 to 6.23 as the pH decreasing from 7.21 to 5.14, and the resolution factor (R_s) exhibited a similar increasing trend (from 0 to 1.34). More interestingly, the retention factors for N‐(2, 4‐dinitrophenyl)‐proline (DNP‐pro) decrease along with increasing 1‐propanol in mobile phase (3%, 5%, 7% and 9% by volume), whereas the resolution factor shows an upward trend (from 0.96 to 2.04). Moreover, chiral recognition mechanisms for chiral analytes were further investigated through thermodynamic methods. Chirality 25:487–492, 2013. © 2013 Wiley Periodicals, Inc.     

Photoprotection in the antenna complexes of photosystem II: role of individual xanthophylls in chlorophyll triplet quenching

In this work the photoprotective role of all xanthophylls in LHCII, Lhcb4, and Lhcb5 is investigated by laser-induced Triplet-minus-Singlet (TmS) spectroscopy. The comparison of native LHCII trimeric complexes with different carotenoid composition shows that the xanthophylls in sites V1 and N1 do not directly contribute to the chlorophyll triplet quenching. The largest part of the triplets is quenched by the lutein bound in site L1, which is located in close proximity to the chlorophylls responsible for the low energy state of the complex. The lutein in the L2 site is also active in triplet quenching, and it shows a longer triplet lifetime than the lutein in the L1 site. This lifetime difference depends on the occupancy of the N1 binding site, where neoxanthin acts as an oxygen barrier, limiting the access of O(2) to the inner domain of the Lhc complex, thereby strongly contributing to the photostability. The carotenoid triplet decay of monomeric Lhcb1, Lhcb4, and Lhcb5 is mono-exponential, with shorter lifetimes than observed for trimeric LHCII, suggesting that their inner domains are more accessible for O(2). As for trimeric LHCII, only the xanthophylls in sites L1 and L2 are active in triplet quenching. Although the chlorophyll to carotenoid triplet transfer is efficient (95%) in all complexes, it is not perfect, leaving 5% of the chlorophyll triplets unquenched. This effect appears to be intrinsically related to the molecular organization of the Lhcb proteins.     

Determination of the absolute configuration of bicyclo[3.3.1]nonane-2,7-dione by circular dichroism spectroscopy and chemical correlation.

A study of the enantiomers of bicyclo[3.3.1]nonane-2,7-dione, a chiral molecule containing two carbonyl chromophores, was performed. Enantiomers of this structure were obtained by HPLC resolution and the (+)-(1R,5S)-enantiomer by enantiospecific synthesis from(+)-(1S,5S)-bicyclo[3.3.1]nonane-2,6-dione. The title structure is an interesting molecule to demonstrate the validity of the octant rule. The location of the major chair-chair conformer into octants placing each chromophore into the origin of the octants led to the opposite configuration assignments. In order to prove unequivocally absolute configuration, enantiospecific synthesis of the title compound was carried out. The kinetic resolution of racemic bicyclo[3.3.1]nonane-2,6-dione using baker's yeast afforded (+)-(1S,5S)-2,6-dione. Employing a reaction sequence analogous to one developed earlier by us with racemic substrates led to carbonyl group shift giving enantiomerically pure (+)-(1R,5S)-bicyclo[3.3.1]nonane-2,7-dione. The absolute configuration of the investigated compound was established by combined use of the octant rule and chemical correlation.     

Reactions of agostic manganese complexes with molecular hydrogen

Reactions between manganese agostic species having (Mn---C---H) interactions and molecular hydrogen have been investigated. Treatment of the bridging agostic cyclooctenylmanganese tricarbonyl, 3, and butenylmanganese tricarbonyl, 5, with hydrogen in benzene results in the formation of the cyclohexadienylmanganese tricarbonyl compound 4. This suggests that the hydrogen molecule is highly reactive toward organometallic manganese complexes containing an agostic C---H bond. In these reactions (η²-H₂) bonded species are plausible intermediates but these are not detected by NMR. The results indicate that the suggested intermediates in the reactions may be useful as hydrogenation catalysts and as precursors to prepare new manganese compounds which may not be accessible by other pathways.     

Free radicals in U.V.-irradiated aqueous solutions of substituted amides: an e.s.r. and spin-trapping study.

The radicals produced by reactions of hydroxyl radicals with alkyl substituted ureas and amides in aqueous solutions have been investigated. Hydroxyl radicals were produced by U.V. photolysis of H2O2 and the short-lived amide and urea radicals were spin-trapped by t-nitrosobutane and identified by e.s.r. For all N-alkyl derivatives of urea and acetamide, and for N,N-dimethyl propionamide and N,N-diethyl formamide, only radicals centred on N-alkyl groups were detected. Radicals situated only on alkyl groups attached to the carbonyl carbon were observed for dimethyl acetamide, trimethyl acetamide and butyramide. However, for N,N-dimethyl butyramide, N, N-diethyl butyramide, N-methyl propionamide and N, N-diethyl propionamide, free radicals were formed which were localized on the alkyl group attached to the amide carbon as well as those attached to nitrogen. The hydrogen atom bound to the carbonyl carbon was abstracted in N-ethyl formamide. Acyl radicals formed by C-N scission due to direct U.V. photolysis of N, N-dimethyl butyramide and N,N-dimethyl propionamide were also detected.     

Stereochemistry of Female-Specific Normonoterpenes,Sex Pheromone Candidates from the Acarid Mite,Tyreophagus sp. (Astigmata: Acaridae)

Two normonoterpenes were detected from an unidentified Tyreophagus sp. as new female-specific components. Both planar structures were identified to be 2,6-dimethyl-5-heptenal (1) and 2,6-dimethyl-5-hepten-1-ol (2) by GC/MS co-chromatography with synthetic 1 and 2. The stereochemistry of 2 was determined to be R by a GC analysis with a chiral column, while that of 1 was presumed to be similar to 2 based on the biosynthetic aspects.     

Eta4-pyrone iron(0)carbonyl complexes as effective CO-releasing molecules (CO-RMs)

The CO-releasing properties of iron(0)tricarbonyl complexes bearing a 2-pyrone ligand have been evaluated. In this report, we demonstrate that the intrinsic stability of the (eta4-2-pyrone)Fe(CO)3 complex influences the extent and rate of CO release, which is affected by the presence of a halogen substituent on the 2-pyrone ring. The cell viability index has been highlighted for the active carbon monoxide-releasing molecules (CO-RMs), demonstrating that these complexes and related derivatives are a promising new class of compounds with potential therapeutic applications.