Circularly polarized luminescence of Eu(III) complexes with chiral 1,1′-bi-2-naphtol-derived bisphosphate ligands

The interest for lanthanide circularly polarized luminescence (CPL) has been quickly growing for 10 years. However, very few of these studies have involved correlation between the dissymmetry factor (g_lum) and the chemical modifications in a series of chiral ligands. Four polymeric compounds of Eu(III) were prepared by using a series of binaphtyl derivatives for which the size of the π system as well as the number of stereogenic elements (i.e., the binaphtyl moiety) are modulated. The resulting {[Eu(hfac)₃((S)/(R)-L^x)]}_n (x = 1 and 3) and {[Eu(hfac)₃((S,S,S)/(R,R,R)-L^x)]}_n (x = 2 and 4) have been characterized by powder X-ray diffraction by comparison with the X-ray structures on single crystal of the Dy(III) analogs. In solution, the structure of the complexes is deeply modified and becomes monomeric. The nature of the ligand induces change in the shape of the CPL spectra in CH₂Cl₂ solution. Furthermore, a large |g_lum| = 0.12 of the magnetic-dipole transition for the [Eu(hfac)₃((S,S,S)/(R,R,R)-L²)] complex involving the ligand with three stereogenic elements and an extended ?? system has been measured. This report also shows CPL measurements in solid state for the series of {[Eu(hfac)₃((S)/(R)-L^x)]}_n (x = 1 and 3) and {[Eu(hfac)₃((S,S,S)/(R,R,R)-L^x)]}_n (x = 2 and 4) polymers.     

Remarkable chiral and luminescent properties of novel Yb(III) and Eu(III) complexes containing BINAPO ligand

Lanthanide complexes are of great importance for their prospective applications in wide range of science and technology. Chiral lanthanide complexes can constitute stereo-discriminating probes in biological media, owing to the luminescent properties of the rare-earth ions. Sensitized emission with narrow bandwidth, having fast radiation rate and high emission quantum efficiency are the main perspective for synthesizing the complexes. Attention has been given on remarkable chirality with high dissymmetry factors (g = Δε_ext/ε_max) of the complexes. For this purpose, beta-diketonato ligands with chiral BINAPO (1,1′-binapthyl phosphine oxide) ligand were chosen to achieve the goal. The complexes [Ln(TFN)₃(S-BINAPO)](TFN = 4,4,4-trifluoro-1(2-napthyl)-1,3-butanedione), [Ln(HFT)₃(S-BINAPO)] (HFT = 4,4,5,5,6,6,6-heptafluoro-1-(2-thienyl)-1,3-hexanedione) and [Ln(HFA)₃(S-BINAPO)](hfa = hexafluoroacetylacetonate) (where Ln = Yb, Eu) were synthesized. The complex, [Eu(TFN)₃(S-BINAPO)] gives strong red emission at 615 nm with narrow emission band (<10 nm) when excited by 465 nm light with quantum efficiency 86%. The dissymmetry factors (g = Δε_ext/ε_max) corresponding to the ⁷F₁ → ⁵D₀ transition at 590 nm is 0.091 for [Eu(TFN)₃(S-BINAPO)] and for [Yb(hfa)₃(S-BINAPO)](hfa = hexafluoroacetylacetonate) corresponding to the ²F_7/2 → ²F_5/2 transitions is 0.12, are among the largest values for both Eu and Yb complexes to date, respectively. The Eu complexes, [Eu(HFT)₃(S-BINAPO)] and [Eu(TFN)₃(S-BINAPO)] are found to be spontaneously emissive, showing bright red emission, when placed in sunlight or even in the laboratory when light is switched on.     

Synthesis and Chiral Recognition of Nickel(II) Macrocyclic Complex with (R)‐Naphthylethyleneamine Pendant Groups and its Self‐Assembled Framework

A novel nickel(II) hexaaza macrocyclic complex, [Ni(L^R,R)](ClO₄)₂ ( 1 ), containing chiral pendant groups was synthesized by an efficient one‐pot template condensation and characterized (L^R,R═1,8‐di((R)‐α‐methylnaphthyl)‐1,3,6,8,10,13‐hexaazacyclotetradecane). The crystal structure of compound 1 was determined by single‐crystal X‐ray analysis. The complex was found to have a square‐planar coordination environment for the nickel(II) ion. Open framework [Ni(L^R,R)]₃[C₆H₃(COO)₃]₂ ( 2 ) was constructed from the self‐assembly of compound 1 with deprotonated 1,3,5‐benzenetricarboxylic acid, BTC^3?. Chiral discrimination of rac‐1,1′‐bi‐2‐naphthol and rac‐2,2,2‐trifluoro‐1‐(9‐anthryl)ethanol was performed to determine the chiral recognition ability of the chiral complex ( 1 ) and its self‐assembled framework ( 2 ). Binaphthol showed a good chiral discrimination on the framework ( 2 ). The optimum experimental conditions for the chiral discrimination were examined by changing the weight ratio between the macrocyclic complex 1 or self‐assembled framework 2 and racemates. The detailed synthetic procedures, spectroscopic data including single‐crystal X‐ray analysis, and the results of the chiral recognition for the compounds are described. Chirality, 25:54‐58, 2013 © 2012 Wiley Periodicals, Inc.     

The determination of enantiomer composition of 1‐((3‐chlorophenyl)‐(phenyl)methyl) amine and 1‐((3‐chlorophenyl)(phenyl)‐methyl) urea (Galodif) by NMR spectroscopy,chiral HPLC,and polarimetry

For the first time, a method for enantiomer resolution of the anticonvulsant Galodif (1‐((3‐chlorophenyl)(phenyl)methyl) urea) by chiral HPLC was developed, whereas the enantiomeric composition of 1‐((3‐chlorophenyl)(phenyl)methyl) amine—precursor in Galodif synthesis—cannot be resolved by this method. However, starting 1‐((3‐chlorophenyl)(phenyl)methyl) amine quantitatively forms diastereomeric N‐((3‐chlorophenyl)(phenyl)methyl)‐1‐camphorsulfonamides in reaction with chiral (1R)‐(+)‐ or (1S)‐(?)‐camphor‐10‐sulfonyl chlorides. The diastereomeric ratio of obtained camphorsulfonamides can be easily determined by NMR ¹H and ¹³C spectroscopy. The DFT calculations of specific rotation of Galodif enantiomers showed good agreement with experimental data. The absolute configuration of enantiomers was proposed for the first time.     

Heteroleptic phthalocyaninato-[2,3,9,10,16,17,23,24-octakis(octyloxy)phthalocyaninato] rare earth(III) triple-deckers: synthesis and spectroscopic characterization

The homo-dinuclear heteroleptic phthalocyaninato-[2,3,9,10,16,17,23,24-octakis(octyloxy)phthalocyaninato] rare earth(III) triple-decker complexes (Pc)M[Pc(OC₈H₁₇)₈]M[Pc(OC₈H₁₇)₈] (M=Pr, Nd, Sm, Eu, Tb, Dy, Y, Ho, Er, Tm) (1a–10a) and (Pc)M[Pc(OC₈H₁₇)₈]M(Pc) (M=Nd, Sm, Eu, Tb, Dy, Y, Ho, Er, Tm) (2b–10b) were obtained by condensation of bis(phthalocyaninato) rare earths M[Pc(OC₈H₁₇)₈]₂ (M=Pr, Nd, Sm, Eu, Tb, Dy, Y, Ho, Er, Tm), Li₂(Pc) and M(acac)₃·nH₂O (M=Pr, Nd, Sm, Eu, Tb, Dy, Y, Ho, Er, Tm). These novel compounds were characterized by ¹H NMR, mass, electronic absorption (UV–Vis), and IR spectroscopic methods.     

Synthesis,Crystal Structure,and Biological Activities of Two Chiral Mononuclear Mn(III) Complexes

Two new chiral mononuclear Mn^(III) complexes, [Mn L ^{( R )}Cl (C₂H₅OH)]?C₂H₅OH ( 1 ) and [Mn L ^{( S )} (CH₃OH)₂]Cl?CH₃OH ( 2 ), {H₂ L = (R,R)‐or (S,S)‐N,N’‐bis‐(2‐hydroxy‐1‐naphthalidehydene)‐cyclohexanediamine} were synthesized and characterized by various physicochemical techniques. Bond valence sum (BVS) calculations and the Jahn‐Teller effect indicate that the Mn centers are in a +3 oxidation state. The statuses of the two complexes in the solution were confirmed as a pair of enantiomers by electrospray ionization, mass spectrometry (ESI‐MS) spectrum. The binding ability of the complexes with calf thymus CT‐DNA was investigated by spectroscopic and viscosity measurements. Both of the complexes could interact with CT‐DNA via an intercalative mode with the order of 1 ( R ‐enantiomer) > 2 ( S ‐enantiomer). Under the physiological conditions, the two compounds exhibit efficient DNA cleavage activities without any external agent, which also follows the order of R ‐enantiomer > S ‐enantiomer. Interestingly, the concentration‐dependent DNA cleavage experiments indicate an optimal concentration of 17.5 μM. In addition, the interaction of the compounds with bovine serum albumin (BSA) was also investigated, which indicated that the complexes could quench the intrinsic fluorescence of BSA by a static quenching mechanism. Chirality 27:142‐150, 2015. © 2014 Wiley Periodicals, Inc.     

Bis(phosphine)-Pd(II) and -Pt(II) complexes containing chiral tetrazole-thiolato rings: Synthesis, structures, and reactivity toward some electrophiles

Bis(azido)bis(phosphine)-Pd(II) and -Pt(II) complexes, [M(N₃)₂L₂] {L = PMe₃, PEt₃, PMe₂Ph, dppe = 1,2-bis(diphenylphosphino)ethane}, underwent 1,3-dipolar cycloaddition with organic chiral isothiocyanates (R^∗-NCS: R^∗ = (S)-(+)-1-phenylethyl, (R)-(−)-1-phenylethyl, (±)-1-phenylethyl, (S)-(+)-1-indanyl) to give the corresponding tetrazole-thiolato Pd(II) and Pt(II) complexes, trans-[M{S[CN₄(R^∗)]}₂L₂] or [M{S[CN₄(R^∗)]}₂(dppe)]. Spectroscopic (IR and NMR) and X-ray structural analyses of the products showed that the absolute configuration of the starting organic isothiocyanates is retained throughout the reaction. Further treatments of the isolated tetrazole-thiolato complexes with electrophiles such as HCl or benzoyl chloride produced heterocyclic compounds containing a tetrazole thione or a tetrazolyl sulfide group. In addition, organic tetrazole thiones, [S = {CN₄H(R^∗)}] containing a chiral moiety, were prepared from NaN₃ and R^∗-NCS in the presence of water.     

Synthesis of enantiopure planar chiral bis‐(para)‐pseudo‐meta‐type [2.2]paracyclophanes

A new type of planar chiral (R_p)‐ and (S_p)‐4,7,12,15‐tetrasubstituted [2.2]paracyclophanes was prepared from racemic 4,7,12,15‐tetrabromo[2.2]paracyclophane as the starting substrate. Regioselective lithiation and transformations afforded racemic bis‐(para)‐pseudo‐meta‐type [2.2]paracyclophane (4,15‐dibromo‐7,12‐dihydroxy[2.2]paracyclophane). Its optical resolution was performed by the diastereomer method using a chiral camphanoyl group as the chiral auxiliary. The diastereoisomers were readily isolated by simple silica gel column chromatography, and the successive hydrolysis afforded (R_p)‐ and (S_p)‐bis‐(para)‐pseudo‐meta‐type [2.2]paracyclophanes ((R_p)‐ and (S_p)‐4,15‐dibromo‐7,12‐dihydroxy[2.2]paracyclophanes). They can be used as pseudo‐meta‐substituted chiral building blocks.     

Synthesis and photoluminescent properties of series ternary lanthanide (Eu(III), Sm(III), Nd(III), Er(III), Yb(III)) complexes containing 4,4,4-trifluoro-1-(2-naphthyl)-1,3-butanedionate and carbazole-functionalized ligand

A series of new ternary lanthanide complexes Ln(TFNB)₃L (where Ln = Eu, Sm, Nd, Er, Yb, TFNB = 4,4,4-trifluoro-1-(2-naphthyl)-1,3-butanedionate, L = 1-(4-carbazolylphenyl)-2-pyridinyl benzimidazole) have been synthesised. The photoluminescence properties and TGA of them are described in detail. The trifluorinated ligand TFNB displays excellent antenna effect to sensitize the Ln(III) ions to emit characteristic spectra. The carbazole-containing ligand L is testified to be an outstanding synergistic ligand. The luminescence properties investigated and the quantum efficiency measured in dichloromethane solution of Eu(TFNB)₃L and Sm(TFNB)₃L show that the carbazole moiety is good at absorbing energy to sensitize the metal-centered emitting states and can make the complexes more rigid, provide efficient shielding of the Ln(III) core towards external quenching compared with the reference complexes of Eu(TFNB)₃(Pybm) and Sm(TFNB)₃(Pybm) (Pybm = 2-(2-pyridine)-benzimidazole) which have no carbazole unit. The quantum efficiency of Eu(TFNB)₃L in air-equilibrated CH₂Cl₂ solution is calculated to be 14.8% by using air-equilibrated aqueous [Ru(bpy)₃]²⁺·2Cl⁻ solution as reference sample (Φ_std = 2.8%).     

New complexes of La(III), Ce(III), Pr(III), Nd(III), Sm(III), Eu(III) and Gd(III) ions with morin

New solid complex compounds of La(III), Ce(III), Pr(III), Nd(III), Sm(III), Eu(III) and Gd(III) ions with morin were synthesized. The molecular formula of the complexes is Ln(C₁₅H₉O₇)₃ · nH₂O, where Ln is the cation of lanthanide and n = 6 for La(III), Sm(III), Gd(III) or n = 8 for Ce(III), Pr(III), Nd(III) and Eu(III). Thermogravimetric studies and the values of dehydration enthalpy indicate that water occurring in the compounds is not present in the inner coordination sphere of the complex. The structure of the complexes was determined on the basis of UV-visible, IR, MS, ¹H NMR and ¹³C NMR analyses. It was found that in binding the lanthanide ions the following groups of morin take part: 3OH and 4CO in the case of complexes of La, Pr, Nd, Sm and Eu, or 5OH and 4CO in the case of complexes of Ce and Gd. The complexes are five- and six-membered chelate compounds.     

Type 1 copper site synthetic model complexes with increased redox potentials

Reactions of NaSCPh₃ with (R₃tacn)Cu(OTf)₂ (R is Me, iPr; tacn is 1,4,7-triazacyclononane; OTf is CF₃SO₃ ⁻) yield blue complexes identified as ((R₃tacn)CuSCPh₃)(OTf) on the basis of UV–vis, resonance Raman, and electron paramagnetic resonance (EPR) spectroscopy and electrospray ionization mass spectrometry. These complexes exhibit spectroscopic properties typical of type 1 copper sites in proteins, including diagnostic Sπ → Cu(d_{x² - y²} ) (d_{{x^{2} - y^{2} }} ) ligand-to-metal charge transfer transitions at approximately 610–630 nm and small A _|| values in EPR spectra of less than 100 × 10⁻⁴ cm⁻¹. Cyclic voltammetry experiments revealed redox potentials for the complexes similar to those of several low-potential type 1 copper proteins (e.g., azurin, stellacyanin) and approximately 0.5 V higher than those of previously reported model compounds. Thus, the new complexes mimic key aspects of both the structure and the function of type 1 copper sites.     

Purification of glutathione S‐transferase enzyme from quail liver tissue and inhibition effects of (3aR,4S,7R,7aS)‐2‐(4‐((E)‐3‐(aryl)acryloyl)phenyl)‐3a,4,7,7a‐tetrahydro‐1H‐4,7‐methanoisoindole‐1,3(2H)‐dione derivatives on the enzyme activity

The use of quail meat and eggs has made this animal important in recent years, with its low cost and high yields. Glutathione S‐transferases (GST, E.C.2.5.1.18) are an important enzyme family, which play a critical role in detoxification system. In our study, GST was purified from quail liver tissue with 47.88‐fold purification and 12.33% recovery by glutathione agarose affinity chromatography. The purity of enzyme was checked by SDS‐PAGE method and showed a single band. In addition, inhibition effects of (3aR,4S,7R,7aS)‐2‐(4‐((E)‐3‐(aryl)acryloyl)phenyl)‐3a,4,7,7a‐tetrahydro‐1H‐4,7methanoisoindole‐1,3(2H)‐dion derivatives ( 1a–g ) were investigated on the enzyme activity. The inhibition parameters (IC₅₀ and K_i values) were calculated for these compounds. IC₅₀ values of these derivatives ( 1a–e ) were found as 23.00, 15.75, 115.50, 10.00, and 28.75 μM, respectively. K_i values of these derivatives ( 1a–e ) were calculated in the range of 3.04 ± 0.50 to 131.50 ± 32.50 μM. However, for f and g compounds, the inhibition effects on the enzyme were not found.     

Enantioselective cleavage of supercoiled plasmid DNA catalyzed by chiral macrocyclic lanthanide(III) complexes

The enantiomers of the Sm (III), Eu (III) and Yb (III) complexes [LnL(NO₃)₂](NO₃) of a chiral hexaazamacrocycle were tested as catalysts for the hydrolytic cleavage of supercoiled plasmid DNA. The catalytic activity was remarkably enantioselective; while the [LnL^SSSS(NO₃)₂](NO₃) enantiomers promoted the cleavage of plasmid pBR322 from the supercoiled form (SC) to the nicked form (NC), the [LnL^RRRR(NO₃)₂](NO₃) enantiomers were inactive. Kinetics of plasmid DNA hydrolysis was also investigated by agarose electrophoresis and it indicated typical single-exponential cleavage reaction. The hydrolytic mechanism of DNA cleavage was confirmed by the successful ligation of hydrolysis product by T4 ligase. The NMR study of the solutions of the complexes in various buffers indicated that the complexes exist as monomeric cationic complexes [LnL(H₂O)₃]^3 + in slightly acidic solutions and as dimeric cationic complexes [Ln₂L₂(μ-OH)₂(H₂O)₂]^4 + in slightly basic 8 mM solutions, with the latter form being a possible catalyst for hydrolysis of phosphodiester bonds.     

Experimental and Calculated CPL Spectra and Related Spectroscopic Data of Camphor and Other Simple Chiral Bicyclic Ketones

UV, circular dichroism (CD), fluorescence and circularly polarized luminescence (CPL) spectra were recorded for a set of four related [2.2.1] bicyclic compounds ((1S,4S)‐and (1R,4R)‐1,7,7‐trimethylbicyclo[2.2.1]heptan‐2‐one, namely (1S)‐ and (1R)‐camphor ( 1 ), (1S,4R)‐4,7,7‐trimethylbicyclo[2.2.1]hept‐5‐en‐2‐one, (1S)‐dehydro‐epicamphor ( 2 ), (1S,4S)‐1,7,7‐trimethylbicyclo[2.2.1]heptane‐2,5‐dione, (1S)‐5‐oxocamphor ( 3 ), (1S,4R)‐ and (1R,4S)‐1,7,7‐trimethylbicyclo[2.2.1]heptane‐2,3‐dione, (1S)‐ and (1R)‐camphorquinone ( 4 )) and a set of three related [2.2.2] bicyclic compounds (1S,4S)‐bicyclo[2.2.2]octan‐2,5‐dione (saturated diketone ( 5 )), (1R,4R)‐bicyclo[2.2.2]oct‐7‐en‐2,5‐dione (unsaturated diketone ( 6 )), ((1S,4S)‐bicyclo[2.2.2]oct‐7‐en‐5(S)‐ol‐2‐one (which we refer to as unsaturated hydroxy‐ketone ( 7 )). For the latter three compounds also mid‐IR vibrational circular dichroism (VCD) spectra were recorded and are presented. Time‐Dependent Density Functional (TD‐DFT) calculations provide a satisfactory interpretation of both absorption and emission chiroptical spectra and permit insight into ground and excited state electronic properties. We discuss the applicability of the octant rule or of other approximated models to rationalize the observed sign of the CPL. Chirality 25:589–599, 2013. © 2013 Wiley Periodicals, Inc.     

Novel biosynthesis of (R)-ethyl-3-hydroxyglutarate with (R)-enantioselective hydrolysis of racemic ethyl 4-cyano-3-hydroxybutyate by Rhodococcus erythropolis

(R)-ethyl-3-hydroxyglutarate with highly optical purity (≥99%) can be used as a novel precursor for synthesis of chiral side chain of rosuvastatin. In this study, a novel synthesis route of (R)-ethyl-3-hydroxyglutarate by whole microorganism cells from racemic ethyl 4-cyano-3-hydroxybutyate was created. A strain ZJB-0910 capable of transforming racemic β-hydroxy aliphatic nitrile was isolated by employing a screening method based on a colorimetric reaction of Co²⁺ ion with ammonia, and identified as Rhodococcus erythropolis based on its morphology, physiological tests, Biolog, and the 16S rDNA sequence. After cultivation in a sterilized medium with composition of 20 g glucose, 5 g yeast extract, 0.5 g KH₂PO₄, 0.5 g K₂HPO₄, 0.2 g MgSO₄·7H₂O per liter at 30°C and 150 rpm for 48 h, the whole cells of R. erythropolis ZJB-0910 were prepared as a catalyst in (R)-enantioselective hydrolysis of racemic ethyl 4-cyano-3-hydroxybutyate for synthesis of (R)-ethyl-3-hydroxyglutarate, without bearing hydrolase activity for the ester bond of ethyl 4-cyano-3-hydroxybutyate. Under the optimized biotransformation conditions of pH 7.5, 30°C, and 20 mM substrate concentration, (R)-ethyl-3-hydroxyglutarate with 46.2% yield (ee > 99%) was afforded, and its chemical structure was determined by ESI-MS, NMR, and IR. The apparent Michaelis constant K _m and maximum rate V _max for this biocatalytic reaction were 0.01 M and 85.6 μmol min⁻¹ g⁻¹, respectively.     

Enantioselective Degradation of (2RS, 3RS)‐Paclobutrazol in Rat Liver Microsomes

Paclobutrazol, with two stereogenic centers, but gives only (2R, 3R) and (2S, 3S)‐enantiomers because of steric‐hindrance effects, is an important plant growth regulator in agriculture and horticulture. Enantioselective degradation of paclobutrazol was investigated in rat liver microsomes in vitro. The degradation kinetics and the enantiomer fraction were determined using a Lux Cellulose‐1 chiral column on a reverse‐phase liquid chromatography–tandem mass spectrometry system. The t_1/2 of (2R, 3R)‐paclobutrazol is 18.60 min, while the t_1/2 of (2S, 3S)‐paclobutrazol is 10.93 min. Such consequences clearly indicated that the degradation of paclobutrazol in rat liver microsomes was stereoselective and the degradation rate of (2S, 3S)‐paclobutrazol was much faster than (2R, 3R)‐paclobutrazol. In addition, significant differences between the two enantiomers were also observed in enzyme kinetic parameters. The V_max of (2S, 3S)‐paclobutrazol was more than 2‐fold of (2R, 3R)‐paclobutrazol and the Cl_int of (2S, 3S)‐paclobutrazol was higher than that of (2R, 3R)‐paclobutrazol after incubation in rat liver microsomes. These results may have potential implications for better environmental and ecological risk assessment for paclobutrazol. Chirality 27:344–348, 2015. © 2015 Wiley Periodicals, Inc.     

DNA Binding,Antioxidant Activity,and DNA Damage Protection of Chiral Macrocyclic Mn(III) Salen Complexes

We are reporting the synthesis, characterization, and calf thymus DNA binding studies of novel chiral macrocyclic Mn(III) salen complexes S‐1 , R‐1 , S‐2 , and R‐2 . These chiral complexes showed ability to bind with DNA, where complex S‐1 exhibits the highest DNA binding constant 1.20 × 10⁶ M^?1. All the compounds were screened for superoxide and hydroxyl radical scavenging activities; among them, complex S‐1 exhibited significant activity with IC₅₀ 1.36 and 2.37 μM, respectively. Further, comet assay was used to evaluate the DNA damage protection in white blood cells against the reactive oxygen species wherein complex S‐1 was found effective in protecting the hydroxyl radicals mediated plasmid and white blood cells DNA damage. Chirality 24:1063–1073, 2012.© 2012 Wiley Periodicals, Inc.     

Enhanced diastereoselective synthesis of t‐Butyl 6‐cyano‐(3R,5R)‐dihydroxyhexanoate by using aldo‐keto reductase and glucose dehydrogenase co‐producing engineered Escherichia coli

t‐Butyl 6‐cyano‐(3R,5R)‐dihydroxyhexanoate ((3R,5R)‐ 2 ) is a key chiral diol precursor of atorvastatin calcium (Lipitor®). We have constructed a Kluyveromyces lactis aldo‐keto reductase mutant KlAKR‐Y295W/W296L (KlAKRm) by rational design in previous research, which displayed high activity and excellent diastereoselectivity (de_p > 99.5%) toward t‐butyl 6‐cyano‐(5R)‐hydroxy‐3‐oxohexanoate ((5R)‐ 1 ). To realize in situ cofactor regeneration, a robust KlAKRm and Exiguobacterium sibiricum glucose dehydrogenase (EsGDH) co‐producer E. coli BL 21(DE3) pETDuet‐esgdh (MCS1)/pET‐28b (+)‐klakrm was constructed in this work. Under the optimized conditions, AKR and GDH activities of E. coli BL 21(DE3) pETDuet‐esgdh (MCS1)/pET‐28b (+)‐klakrm peaked at 249.9 U/g DCW (dry cellular weight) and 29100 U/g DCW, respectively. It completely converted (5R)‐ 1 at substrate loading size of up to 60.0 g/L (5R)‐ 1 in the absence of exogenous NADH, which was one‐fifth higher than that of the separately prepared KlAKRm and EsGDH under the same conditions. In this manner, a biocatalytic process for (3R,5R)‐ 2 with productivity of 243.2 kg/m³ d was developed. Compared with the combination of separate expressed KlAKRm with EsGDH, co‐expression of KlAKRm and EsGDH has the advantages of alleviating cell cultivation burden and elevating substrate load. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:1235–1242, 2017     

Circularly polarized chlorophyll luminescence reflects the macro-organization of grana in pea chloroplasts

Circular polarization of luminescence (CPL; Steinberg IZ (1978) Annu Rev Biophys Bioeng 7: 113–137) was applied to study pea chloroplasts in different structural states. The structural changes of chloroplasts were induced by variation of osmotic pressure, concentration of magnesium-ions or photoinhibition. Both large CPL and psi-type circular dichroism (psi, polymerization and salt induced) signals appeared in the presence of granal macrostructure and were sensitive to structural changes of the grana. The relation was studied between the amount of CPL expressed as an emission anisotropy factor g _em and amplitudes of the red psi-type CD bands. The positive psi-type CD band was not directly correlated with g _em possibly due to a large contribution of circular intensity differential scattering to the measured CD spectra. However, a linear correlation between the amplitude of the negative psi-type CD band and g _em was found. The CPL signal of pea chloroplasts was attributed to a psi-type origin, which is observed in macroaggregates with densely packed chromophores with a long-range chiral order, and directly depends on the level of macroorganization. With the use of CPL-based microscopy, the long-range packing of LHC II particles can be studied in individual chloroplasts in future. In addition, the CPL method in general allows the study of the macro-organization of grana in green leaves, where conventional light-transmission methods fail. This revised version was published online in June 2006 with corrections to the Cover Date.     

No carrier added synthesis of O-(2'-[18F]fluoroethyl)-L-tyrosine via a novel type of chiral enantiomerically pure precursor, NiII complex of a (S)-tyrosine Schiff base

O-(2′-[¹⁸F]fluoroethyl)-l-tyrosine ([¹⁸F]FET) has gained much attention as a promising amino acid radiotracer for tumor imaging with positron emission tomography (PET) due to favorable imaging characteristics and relatively long half-life of ¹⁸F (110 min) allowing remote-site application. Here we present a novel type of chiral enantiomerically pure labeling precursor for [¹⁸F]FET, based on NiII complex of a Schiff’s base of (S)-[N-2-(N′-benzylprolyl)amino]benzophenone (BPB) with alkylated (S)-tyrosine, Ni-(S)-BPB-(S)-Tyr-OCH2CH2X (X = OTs (3a), OMs (3b) and OTf (3c)). A series of compounds 3a–c was synthesized in three steps from commercially available reagents. Non-radioactive FET as a reference was prepared from 3a in a form of (S)-isomer and (R,S) racemic mixture. Radiosynthesis comprised two steps: (1) n.c.a. nucleophilic fluorination of 3a–c (4.5–5.0 mg) in the presence of either Kryptofix 2.2.2.or tetrabutylammonium carbonate (TBAC) in MeCN at 80 °C for 5 min, followed by (2) removal of protective groups by treating with 0.5 M HCl (120 °C, 5 min). The major advantages of this procedure are retention of enantiomeric purity during the ¹⁸F-introduction step and easy simultaneous deprotection of amino and carboxy moieties in 3a–c. Radiochemically pure [¹⁸F]FET was isolated by semi-preparative HPLC (C18 μ-Bondapak, Waters) eluent aq 0.01 M CH₃COONH₄, pH 4/C₂H₅OH 90/10 (v/v). Overall synthesis time operated by Anatech RB 86 laboratory robot was 55 min. In a series of compounds 3a–c, tosyl derivative 3a provided highest radiochemical yield (40–45%, corrected for radioactive decay). Enantiomeric purity was 94–95% and 96–97%, correspondingly, for Kryptofix and TBAC assisted fluorinations. The suggested procedure involved minimal number of synthesis steps and suits perfectly for automation in the modern synthesis modules for PET radiopharmaceuticals. Preliminary biodistribution study in experimental model of turpentine-induced aseptic abscess and Glioma35 rat’s tumor (homografts) in Wistar rats has demonstrated the enhanced uptake of radiotracer in the tumor area with minimal accumulation in the inflamed tissues.