Polymer‐Supported Optically Active fac(S)‐Tris(thiotato)rhodium(III) Complex for Sulfur‐Bridging Reaction With Precious Metal Ions

The optically active mixed‐ligand fac(S)‐tris(thiolato)rhodium(III) complexes, Δ_L‐fac(S)‐[Rh(aet)₂(L‐cys‐N,S)]^? (aet = 2‐aminoethanethiolate, L‐cys = L‐cysteinate) ( 1 ) and Δ_LL‐fac(S)‐[Rh(aet)(L‐cys‐N,S)₂]^2? were newly prepared by the equatorial preference of the carboxyl group in the coordinated L‐cys ligand. The amide formation reaction of 1 with 1,10‐diaminodecane and polyallylamine gave the diamine‐bridged dinuclear Rh(III) complex and the single‐chain polymer‐supported Rh(III) complex with retention of the Δ_L configuration of 1 , respectively. These Rh(III) complexes reacted with Co(III) or Co(II) to give the linear‐type trinuclear structure with the S‐bridged Co(III) center and the two Δ‐Rh(III) terminal moieties. The polymer‐supported Rh(III) complex was applied not only to the CD spectropolarimetric detection and determination of a trace of precious metal ions such as Au(III), Pt(II), and Pd(II) but also to concentration and extraction of these metal ions into the solid polymer phase. Chirality 28:85–91, 2016. © 2015 Wiley Periodicals, Inc.     

Stereodynamics of Nitrogen Chiral Centers in aza‐β3‐Cyclodipeptides

The present work is devoted to the synthesis, conformational analysis, and stereodynamic study of aza‐β³‐cyclodipeptides. This pseudopeptidic ring shows E/Z hydrazide bond isomerism, eight‐membered ring conformation, and chirotopic nitrogen atoms, all of which are elements that are prone to modulate the ring shape. The (E,E) twist boat conformation observed in the solid state by X‐ray diffraction is also the ground conformation in solution, and emerges as the lowest in energy when using quantum chemical calculations. The relative configuration associated with ring chirality and with the two nitrogen chiral centers is governed by steric crowding and adopts the (P)S_NS_N/(M)R_NR_N combination which projects side chains in equatorial position. The nitrogen pyramidal inversion (NPI) at the two chiral centers is correlated with the ring reversal. The process is significantly hindered as was shown by VT‐NMR experiments run in C₂D₂Cl₄, which did not make it possible to determine the barrier to inversion. Finally, these findings make it conceivable to resolve enantiomers of aza‐β³‐cyclodipeptides by modulating the backbone decoration appropriately. Chirality 25:341–349, 2013. © 2013 Wiley Periodicals, Inc.     

Asymmetric Allylation of α‐Ketoester‐Derived N‐Benzoylhydrazones Promoted by Chiral Sulfoxides/N‐Oxides Lewis Bases: Highly Enantioselective Synthesis of Quaternary α‐Substituted α‐Allyl‐α‐Amino Acids

Chiral sulfoxides/N‐oxides (R)‐ 1 and (R,R)‐ 2 are effective chiral promoters in the enantioselective allylation of α‐keto ester N‐benzoylhydrazone derivatives 3a , 3b , 3c , 3d , 3e , 3f , 3g to generate the corresponding N‐benzoylhydrazine derivatives 4a , 4b , 4c , 4d , 4e , 4f , 4g , with enantiomeric excesses as high as 98%. Representative hydrazine derivatives 4a , 4b were subsequently treated with SmI₂, and the resulting amino esters 5a , 5b with LiOH to obtain quaternary α‐substituted α‐allyl α‐amino acids 6a , 6b , whose absolute configuration was assigned as (S), with fundament on chemical correlation and electronic circular dichroism (ECD) data. Chirality 25:529–540, 2013. © 2013 Wiley Periodicals, Inc.     

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 impact of β‐azido(or 1‐piperidinyl)methylamino acids in position 2 or 3 on biological activity and conformation of dermorphin analogues

The synthesis of new dermorphin analogues is described. The (R)‐alanine or phenylalanine residues of natural dermorphin were substituted by the corresponding α‐methyl‐β‐azidoalanine or α‐benzyl‐β‐azido(1‐piperidinyl)alanine residues. The potency and selectivity of the new analogues were evaluated by a competitive receptor binding assay in rat brain using [³H]DAMGO (a μ ligand) and [³H]DELT (a δ ligand). The most active analogue in this series, Tyr‐(R)‐Ala‐(R)‐α‐benzyl‐β‐azidoAla‐Gly‐Tyr‐Pro‐Ser‐NH₂ and its epimer were analysed by ¹H and ¹³C NMR spectroscopy and restrained molecular dynamics simulations. The dominant conformation of the investigated peptides depended on the absolute configuration around C^α in the α‐benzyl‐β‐azidoAla residue in position 3. The (R) configuration led to the formation of a type I β‐turn, whilst switching to the (S) configuration gave rise to an inverse β‐turn of type I′, followed by the formation of a very short β‐sheet. The selectivity of Tyr‐(R)‐Ala‐(R) and (S)‐α‐benzyl‐β‐azidoAla‐Gly‐Tyr‐Pro‐Ser‐NH₂ was shown to be very similar; nevertheless, the two analogues exhibited different conformational preferences. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.     

Circularly polarized luminescence of Sm (III) and Eu (III) complexes with chiral ligand (R/S)‐BINAPO

Luminescent lanthanide (III) ions have been exploited for circularly polarized luminescence (CPL) for decades. However, very few of these studies have involved chiral samarium (III) complexes. Complexes are prepared by mixing axial chiral ligands (R/S))‐2,2’‐bis(diphenylphosphoryl)‐1,1′‐binaphthyl (BINAPO) with europium and samarium Tris (trifluoromethane sulfonate) (Eu (OTf)₃ and Sm (OTf)₃). Luminescence‐based titration shows that the complex formed is Ln((R/S)‐BINAPO)₂(OTf)₃, where Ln = Eu or Sm. The CPL spectra are reported for Eu((R/S)‐BINAPO)₂(OTf)₃ and Sm((R/S)‐BINAPO)₂(OTf)₃. The sign of the dissymmetry factors, g_em, was dependent upon the chirality of the BINAPO ligand, and the magnitudes were relatively large. Of all of the complexes in this study, Sm((S)‐BINAPO)₂(OTf)₃ has the largest g_em = 0.272, which is one of the largest recorded for a chiral Sm³⁺ complex. A theoretical three‐dimensional structural model of the complex that is consistent with the experimental observations is developed and refined. This report also shows that (R/S)‐BINAPO are the only reported ligands where g_em (Sm³⁺) > g_em (Eu³⁺).     

Antibacterial,antifungal and in vitro antileukaemia activity of metal complexes with thiosemicarbazones

1‐phenyl‐3‐methyl‐4‐benzoyl‐5‐pyrazolone 4‐ethyl‐thiosemicarbazone (HL) and its copper(II), vanadium(V) and nickel(II) complexes: [Cu(L)(Cl)]·C₂H₅OH·( 1 ), [Cu(L)₂]·H₂O ( 2 ), [Cu(L)(Br)]·H₂O·CH₃OH ( 3 ), [Cu(L)(NO₃)]·2C₂H₅OH ( 4 ), [VO₂(L)]·2H₂O ( 5 ), [Ni(L)₂]·H₂O ( 6 ), were synthesized and characterized. The ligand has been characterized by elemental analyses, IR, ¹H NMR and ¹³C NMR spectroscopy. The tridentate nature of the ligand is evident from the IR spectra. The copper(II), vanadium(V) and nickel(II) complexes have been characterized by different physico‐chemical techniques such as molar conductivity, magnetic susceptibility measurements and electronic, infrared and electron paramagnetic resonance spectral studies. The structures of the ligand and its copper(II) ( 2 , 4 ), and vanadium(V) ( 5 ) complexes have been determined by single‐crystal X‐ray diffraction. The composition of the coordination polyhedron of the central atom in 2 , 4 and 5 is different. The tetrahedral coordination geometry of Cu was found in complex 2 while in complex 4 , it is square planar, in complex 5 the coordination polyhedron of the central ion is distorted square pyramid. The in vitro antibacterial activity of the complexes against Escherichia coli, Salmonella abony, Staphylococcus aureus, Bacillus cereus and the antifungal activity against Candida albicans strains was higher for the metal complexes than for free ligand. The effect of the free ligand and its metal complexes on the proliferation of HL‐60 cells was tested.     

Supramolecular chirality transfer in a stereodynamic catalysts

We present rhodium catalysts that contain stereodynamic axially chiral biphenol‐derived phosphinite ligands modified with non‐stereoselective amides for non‐covalent interactions. A chirality transfer was achieved with (R)‐ or (S)‐acetylphenylalanine methyl amide, and the interaction mechanism was investigated by NMR measurements. These interactions at the non‐stereoselective interaction sites and the formation of supramolecular complexes result in an enrichment of either the (R_ax)‐ or (S_ax) enantiomer of the tropos catalysts, which in turn provide the (R)‐ or (S)‐acetylphenylalanine methyl ester in the hydrogenation of (Z)‐methyl‐α‐acetamidocinnamate.     

Mutual inversion of flurbiprofen enantiomers in various rat and mouse strains

Flurbiprofen (F) is a nonsteroidal anti‐inflammatory drug (NSAID) used therapeutically as the racemate of (R)‐enantiomer and (S)‐enantiomer. The inversion of RF to SF and vice versa was investigated in C57Bl/6 and SJL mice and Dark Agouti and Lewis rats. The enzyme α‐methylacyl‐CoA racemase (AMACR) is involved in the chiral inversion pathway that converts members of the 2‐arylpropionic acid NSAIDs from the R‐enantiomer to the S‐enantiomer. We studied C57Bl/6 mice deficient in AMACR postulating that they should show reduced inversion of RF to SF. In line with the data of others in mice, (R)‐inversion to (S)‐inversion was relatively high in both the C57Bl/6 and SJL mice (fraction inverted, F_I = 37.7% and 24.7%, respectively). In contrast, in AMACR deficient mice, there was no measurable peak for SF after administration of RF. The results in both rat strains (Dark Agouti and Lewis rats, F_I = 1.4% and 4.1%, respectively) confirm the low chiral inversion of the enantiomers of flurbiprofen in the rat, as observed by other authors in the Sprague‐Dawley strain (<5%). From the present results, we conclude that for the study of flurbiprofen enantiomers, the rat is more suitable than the mouse as a model for the human in which (R)‐inversion to (S)‐inversion is negligible.     

Asymmetric Autocatalysis Induced by Chiral Crystals of Achiral Tetraphenylethylenes

The achiral hydrocarbon tetraphenylethylene crystallizes in enantiomorphous forms (chiral space group: P2₁) to afford right- and left-handed hemihedral crystals, which can be recognized by solid-state circular dichroism spectroscopic analysis. Chiral organic crystals of tetraphenylethylene mediated enantioselective addition of diisopropylzinc to pyrimidine-5-carbaldehyde to give, in conjunction with asymmetric autocatalysis with amplification of chirality, almost enantiomerically pure (S)- and (R)-5-pyrimidyl alkanols whose absolute configurations were controlled efficiently by the crystalline chirality of the tetraphenylethylene substrate. Tetrakis(p-chlorophenyl)ethylene and tetrakis(p-bromophenyl)ethylene also show chirality in the crystalline state, which can also act as a chiral substrate and induce enantioselectivity of diisopropylzinc addition to pyrimidine-5-carbaldehyde in asymmetric autocatalysis to give enantiomerically enriched 5-pyrimidyl alkanols with the absolute configuration correlated with that of the chiral crystals. Highly enantioselective synthesis has been achieved using chiral crystals composed of achiral hydrocarbons, tetraphenylethylenes, as chiral inducers. This chemical system enables significant amplification of the amount of chirality using spontaneously formed chiral crystals of achiral organic compounds as the seed for the chirality of asymmetric autocatalysis.     

Double Asymmetric Induction During the Addition of (RP)‐Menthyl Phenyl Phosphine Oxide to Chiral Aldimines

P,C‐Stereogenic α‐amino phosphine oxides were prepared from the addition of (R_P)‐menthyl phenyl phosphine oxide to chiral aldimines under neat condition at 80 °C in up to 91:9 dr_C and 99% yields. The diastereoselectivity was mainly induced by chiral phosphorus that showed matched or mismatched induction with (S)‐ or (R)‐aldimines, respectively. Chirality 28:132–135, 2016. © 2015 Wiley Periodicals, Inc.     

Conformations of peptides containing a chiral cyclic α, α‐disubstituted α‐amino acid within the sequence of Aib residues

A single chiral cyclic α,α‐disubstituted amino acid, (3S,4S)‐1‐amino‐(3,4‐dimethoxy)cyclopentanecarboxylic acid [(S,S)‐Ac₅c^dOM], was placed at the N‐terminal or C‐terminal positions of achiral α‐aminoisobutyric acid (Aib) peptide segments. The IR and ¹H NMR spectra indicated that the dominant conformations of two peptides Cbz‐[(S,S)‐Ac₅c^dOM]‐(Aib)₄‐OEt ( 1) and Cbz‐(Aib)₄‐[(S,S)‐Ac₅c^dOM]‐OMe (2) in solution were helical structures. X‐ray crystallographic analysis of 1 and 2 revealed that a left‐handed (M) 3₁₀‐helical structure was present in 1 and that a right‐handed (P) 3₁₀‐helical structure was present in 2 in their crystalline states. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Synthesis and X‐ray diffraction study of a chiral bis‐phosphahelicene palladium (II) complex

As a complement to our previous studies on the development of a class of chiral phosphahelicenes, this article discloses the synthesis, spectroscopic, and structural characterizations of a new phosphahelicene transition metal complex. It demonstrates the ability of these hindered chiral ligands to coordinate Pd (II) in trans‐complexes Cl₂Pd(L*)₂. In the solid state, the complex adopts a C2‐symmetric arrangement with two ligands facing each other on the same face of the coordination plane. X‐Ray data highlight bending of the Pd (II) unit from the expected planar coordination geometry that might be due to a significant π‐π stacking effect between the central rings of two helical units.     

Enantiopure 4‐oxazolin‐2‐ones and 4‐methylene‐2‐oxazolidinones as chiral building blocks in a divergent asymmetric synthesis of heterocycles

Enantiopure 3‐((R)‐ and 3‐((S)‐1‐phenylethyl)‐4‐oxazoline‐2‐ones were evaluated as chiral building blocks for the divergent construction of heterocycles with stereogenic quaternary centers. The N‐(R)‐ or N‐(S)‐1‐phenylethyl group of these compounds proved to be an efficient chiral auxiliary for the asymmetric induction of the 4‐ and 5‐positions of the 4‐oxazolin‐2‐one ring through thermal and MW‐promoted nucleophilic conjugated addition to Michael acceptors and alkyl halides. The resulting adducts were transformed via a cascade process into fused six‐membered carbo‐ and heterocycles. The structure of the reaction products depended on the electrophiles and reaction conditions used. Alternative isomeric 4‐methylene‐2‐oxazolidinones served as chiral precursors for a versatile and divergent approach to highly substituted cyclic carbamates. DFT quantum calculations showed that the formation of bicyclic pyranyl compounds was generated by a diastereoselective concerted hetero‐Diels‐Alder cycloaddition.     

Resolution of Enantiomers of Novel C2‐Symmetric Aminobisphosphinic Acids via Diastereomeric Salt Formation With Quinine

C₂‐symmetric N,N‐bis(phosphinomethyl)amines were prepared by the thermal reaction of aromatic aldehydes with ammonia and hypophosphorus acid as previously described. Both enantiomers of C₂‐symmetric N,N‐bis(phosphinomethyl)amine were obtained in a high enantiomeric purity through the diastereomeric salt formation with (–)‐quinine, and subsequent fractional crystallization. X‐ray crystallographic analysis of one of the diastereomeric salts clearly revealed that (–)‐quinine could be an efficient resolving agent for obtaining the single enantiomer (R,R)‐N,N‐bis(phosphinomethyl)amine. Chirality 27:71–74, 2015. © 2014 Wiley Periodicals, Inc.     

Synthesis,Structure, and Biological Activities of a New μ‐Oxamido‐Bridged Dicopper(II) Complex: The Influence of Hydrophobicity of Bridging Ligand on DNA Binding and Cytotoxic Activities

A new μ‐oxamido‐bridged dicopper(II) complex, [Cu₂(papo)(H₂O)‐ (phen)]Cl·CH₃OH·H₂O, where H₃papo and phen represent N‐(2‐hydroxyphenyl)‐N'‐(3‐aminopropyl)oxamide and 1,10‐phenanthroline, respectively, has been synthesized and characterized by elemental analysis, molar conductivity measurement, infrared and electronic spectra studies, and single‐crystal X‐ray diffraction. The complex crystallizes in the triclinic space group P‐1. Each copper(II) ion is located in a slightly distorted square‐pyramidal environment. The Cu···Cu distance through the oxamide bridge is 5.1848(7) Å. The three‐dimensional supramolecular structure is built‐up by hydrogen bonds and π–π stacking interactions. The dicopper(II) complex exhibits cytotoxic activity against the SMMC‐7721 and A549 cell lines. The reactivity toward herring sperm DNA and protein bovine serum albumin (BSA) reveals that the dicopper(II) complex can interact with the DNA by the intercalation mode, and effectively quench the intrinsic fluorescence of BSA via a static mechanism. The influence of hydrophobicity of the bridging ligand on DNA‐binding properties and in vitro cytotoxic activities of this kind of dicopper(II) complexes was investigated.     

Synthesis and structural investigations of Ni(II)- and Pd(II)-coordinated α-diimines with chlorinated backbones

Novel square planar Pd(II) α-diimines [PdX₂{ArNC(Cl)}₂], where Ar = C₆H₅, (2,6-Me₂C₆H₃), (2,6-ⁱPr₂C₆H₃) and X = Cl or Br, and the octahedral Ni(II) complex [NiBr₂{(C₆H₅)NC(Cl)}₂(THF)₂] have been prepared and characterised by spectroscopic methods. For two of the Pd(II) complexes and the Ni(II) complex the crystal structures were determined by X-ray crystallography. A further insight into the geometry and electronic structure of [PdBr₂{(2,6-Me₂C₆H₃)NC(Cl)}₂] was gained using density functional theoretical calculations (DFT). This compound resembles structurally and electronically typical olefin polymerisation pre-catalysts supported by α-diimines incorporating methyl- and 1,8-naphtalenyl substituents at the ligand backbone. The chlorine-substituted backbone of the free ligand [2,6-Me₂C₆H₃NC(Cl)]₂ can be employed in further alkylation reactions to generate new multifunctional ligand prototypes with potential uses as ansa-metallocene/diimines building blocks for catalytic applications of heterobimetallic complexes.     

Asymmetric epoxidation of cinnamyl alcohol with optically active titanium complexes

A family of titanium(IV) alkoxo compounds [{Ti(O‐i‐Pr)₂(OR)₂}₂] 1–4 prepared by alcohol exchange of Ti(O‐i‐Pr)₄ and a chiral higher‐boiling alcohol [ROH = 1,2:3,4‐di‐O‐isopropylidene‐α‐d ‐galactopyranose, 1,2:5,6‐di‐O‐isopropylidene‐α‐d ‐glucofuranose, (1R,2S,5R)‐(?)‐menthol, (1S‐endo)‐(?)‐borneol, (1S,2R,5S)‐(+)‐menthol, and (+)‐borneol] has been tested to evaluate their catalytic activity and stereoselectivity in the asymmetric epoxidation of cinnamyl alcohol. © 2005 Wiley‐Liss, Inc. Chirality     

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.     

Synthesis, structure, and catalytic activity of chiral silver(I) and copper(II) complexes with biaryl-based nitrogen-containing ligands

A series of chiral Ag(I) and Cu(II) complexes have been prepared from the reaction between AgX (X = NO₃, PF₆, OTf) or CuX₂ (X = Cl, ClO₄) and chiral biaryl-based N-ligands. The rigidity of the ligand plays an important role in the Ag(I) complex formation. For example, treatment of chiral N₃-ligands 1-3 with half equiv of AgX (X = NO₃, PF₆, OTf) gives the chiral bis-ligated four-coordinated Ag(I) complexes, while ligand 4 affords the two-coordinated Ag(I) complexes. Reaction of AgX with 1 equiv of chiral N₄-ligands 5, 7, 8 and 10 gives the chiral, binuclear double helicate Ag(I) complexes, while chiral mono-nuclear single helicate Ag(I) complexes are obtained with N₄-ligands 6 and 9. Treatment of either N₃-ligand 1 or N₄-ligand 9 or 10 with 1 equiv of CuX₂ (X = Cl, ClO₄) gives the mono-ligated Cu(II) complexes. All the complexes have been characterized by various spectroscopic techniques, and elemental analyses. Seventeen of them have further been confirmed by X-ray diffraction analyses. The Cu(II) complexes do not show catalytic activity for allylation reaction, in contrast to Ag(I) complexes, but they do exhibit catalytic activity for Henry reaction (nitroaldol reaction) that Ag(I) complexes do not.