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.     

In Vitro Cytotoxic Activities,DNA‐, and BSA‐Binding Studies of a New Dinuclear Copper(II) Complex with N‐[3‐(Dimethylamino)propyl]‐N′‐(2‐carboxylatophenyl)‐ Oxamide as Ligand

A new dinuclear copper(II) complex bridged by N‐[3‐(dimethylamino)propyl]‐N′‐ (2‐carbo‐xylatophenyl)oxamide (H₃dmapob), and endcapped with 2,2′‐diamino‐4,4′‐bithiazole (dabt), namely [Cu₂(dmapob)(dabt)(CH₃OH)(pic)]·(DMF)_0.75·(CH₃OH)_0.25 has been synthesized and characterized by elemental analysis, molar conductivity measurement, infrared and electronic spectra studies, and single‐crystal X‐ray diffraction. In the crystal structure, both copper(II) ions have square–pyramidal coordination geometries. The Cu···Cu separation through the oxamido bridge is 5.176(9) Å. A two‐dimensional supramolecular framework is formed through hydrogen bonds and π–π stacking interactions. The reactivities toward herring sperm DNA and bovine serum albumin (BSA) show that the complex can interact with the DNA via intercalation mode and bind to the BSA responsible for quenching of tryptophan fluorescence by the static quenching mechanism. The in vitro anticancer activities suggest that the copper(II) complex is active against the selected tumor cell lines. The influence of different bridging ligands in dinuclear complexes on the DNA‐ and BSA‐binding properties as well as anticancer activities is preliminarily discussed.     

A stereodynamic phosphoramidite ligand derived from 3,3′‐functionalized ortho‐biphenol and its rhodium(I) complex

Stereodynamic ligands and complexes bearing functional groups to attach chiral or achiral binding sites and auxiliaries are highly attractive due to the interesting opportunities for controlling the stereochemical outcome of enantioselective transformations. In this study we report the preparation of a 3,3′‐functionalized biphenol (BIPOL) phosphoramidite ligand (P_Am) bearing 3,5‐dichlorobenzoyl (3,5‐DCB) amide binding sites for noncovalent interactions. Upon coordination to [Rh(COD)₂]BF₄ this substitution pattern directs one of the 3,5‐DCB binding sites in close proximity of the metal center resulting in liberation of both COD ligands and the formation of a [Rh(P_Am)₂]BF₄ complex. Coordination of the amide carbonyl unit was found to be reversible, since the complex acted as an active catalyst in the hydrogenation of dehydroamino acid derivatives. X‐ray crystallographic investigation revealed that the second 3,5‐DCB unit is capable of forming noncovalent π–π interactions connecting both phosphoramidite ligands.     

Synthesis and structure of a new trinuclear nickel(II) complex bridged by N‐[3‐(Dimethylamino)propyl]‐N′‐(2‐hydroxyphenyl)oxamido: in vitro anticancer activities,and reactivities toward DNA and protein

A new trinickel(II) complex bridged by N‐[3‐(dimethylamino)propyl]‐ N ′‐(2‐hydroxylphenyl)oxamido (H₃pdmapo), namely [Ni₃(pdmapo)₂(H₂O)₂]?4CH₃OH, was synthesized and characterized by X‐ray single‐crystal diffraction and other methods. In the molecule, two symmetric cis‐ pdmapo^3? mononickel(II) complexes as a “complex ligand” using the carbonyl oxygen atoms coordinate to the center nickel(II) ion situated on an inversion point. The Ni···Ni distance through the oxamido bridge is 5.2624(4) Å. The center nickel(II) ion and the lateral ones have octahedral and square‐planar coordination geometries, respectively. In the crystal, a three‐dimensional supramolecular network dominated by hydrogen bonds is observed. The reactivity toward DNA/protein bovine serum albumin (BSA) revealed that the complex could interact with herring sperm DNA (HS‐DNA) through the intercalation mode and quench the intrinsic fluorescence of BSA via a static mechanism. The in vitro anticancer activities suggested that the complex is active against the selected tumor cell lines.     

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.     

Chirality in Distorted Square Planar Pd(O,N)2 Compounds

Salicylidenimine palladium(II) complexes trans‐Pd(O,N)₂ adopt step and bowl arrangements. A stereochemical analysis subdivides 52 compounds into 41 step and 11 bowl types. Step complexes with chiral N‐substituents and all the bowl complexes induce chiral distortions in the square planar system, resulting in Δ/Λ configuration of the Pd(O,N)₂ unit. In complexes 1 , 2 , 3 , 4 , 5 , 6 with enantiomerically pure N‐substituents ligand chirality entails a specific square chirality and only one diastereomer assembles in the lattice. Dimeric Pd(O,N)₂ complexes with bridging N‐substituents in trans‐arrangement are inherently chiral. For dimers 7 , 8 , 9 , 10 , 11 different chirality patterns for the Pd(O,N)₂ square are observed. The crystals contain racemates of enantiomers. In complex 12 two independent molecules form a tight pair. The (R_C) configuration of the ligand induces the same Δ chirality in the Pd(O,N)₂ units of both molecules with varying square chirality due to the different crystallographic location of the independent molecules. In complexes 13 and 14 atrop isomerism induces specific configurations in the Pd(O,N)₂ bowl systems. The square chirality is largest for complex 15 [(Diop)Rh(PPh₃)Cl)], a catalyst for enantioselective hydrogenation. In the lattice of 15 two diastereomers with the same (R_C,R_C) configuration in the ligand Diop but opposite Δ and Λ square configurations co‐crystallize, a rare phenomenon in stereochemistry. Chirality 25:663–667, 2013. © 2013 Wiley Periodicals, Inc.     

Synthesis and Crystal Structure of Binuclear Copper(II) Complex Bridged by N‐(2‐Hydroxyphenyl)‐N′‐[3‐(diethylamino)propyl]oxamide: In Vitro Anticancer Activity and Reactivity Toward DNA and Protein

A new oxamido‐bridged bicopper(II) complex, [Cu₂(pdpox)(bpy)(CH₃OH)](ClO₄), where H₃pdpox and bpy stand for N‐(2‐hydroxyphenyl)‐N′‐[3‐(diethylamino)propyl]oxamide and 2,2′‐bipyridine, respectively, has been synthesized and characterized by elemental analyses, molar conductivity measurements, infrared and electronic spectra studies, and X‐ray single crystal diffraction. In the crystal structure, the pdpox^3? ligand bridges two copper(II) ions as cisoid conformation. The inner copper(II) ion has a {N₃O} square‐planar coordination geometry, while the exo‐ one is in a {N₂O₃} square‐pyramidal environment. There are two sets of interpenetrating two‐dimensional hydrogen bonding networks parallel to the planes (2 1 0) and (), respectively, to form a three‐dimensional supramolecular structure. The bicopper(II) complex exhibits cytotoxic activity against the SMMC7721 and A549 cell lines. The reactivity toward herring sperm DNA and bovine serum albumin revealed that the bicopper(II) complex can interact with the DNA by intercalation mode, and the complex binds to protein BSA responsible for quenching of tryptophan fluorescence by static quenching mechanism. © 2013 Wiley Periodicals, Inc. J BiochemMol Toxicol 27:412‐424, 2013; View this article online at wileyonlinelibrary.com . DOI 10.1002/jbt.21504     

Structural Features and Asymmetric Environment of i‐Pr‐SPRIX Ligand

Novel chiral diisopropyl spiro bis(isoxazoline) ligands, anti‐i‐Pr‐SPRIX and syn‐i‐Pr‐SPRIX, were designed and synthesized. Their catalytic utility, X‐ray crystallographic analyses, and complexation studies demonstrated the structural features of tetraisopropyl spiro bis(isoxazoline) ligand, i‐Pr‐SPRIX, which is a prominent ligand in various enantioselective Pd catalytic processes: All i‐Pr groups work in collaboration to create an effective asymmetric environment. Chirality 27:532–537, 2015. © 2015 Wiley Periodicals, Inc.     

Synthesis and Structure of a Ternary Copper(II) Complex with Mixed Ligands of Diethylenetriamine and Picrate: DNA/Protein‐Binding Property and In Vitro Anticancer Activity Studies

Based on the importance of the design and synthesis of transition metal complexes with noncovalent DNA/protein‐binding abilities in the field of metallo pharmaceuticals, a new mononuclear ternary copper(II) complex with mixed ligands of diethylenetriamine (dien) and picrate anion (pic), identified as [Cu(dien)(pic)](pic), was synthesized and characterized by elemental analysis, molar conductivity measurement, infrared spectrum, electronic spectral studies, and single‐crystal X‐ray diffractometry. The structure analysis reveals that the copper(II) complex crystallizes in the monoclinic space group P2₁/c, and the copper(II) ion has a distorted square pyramidal coordination geometry. A two‐dimensional supramolecular structure is formed through hydrogen bonds. The DNA/bovine serum albumin (BSA)‐binding properties of the complex are explored, indicating that the complex can interact with herring sperm DNA via intercalation mode and bind to BSA responsible for quenching of tryptophan fluorescence by static quenching mechanism. The in vitro anticancer activity shows that the copper(II) complex is active against the selected tumor cell lines.     

Taniaphos and Walphos ligands: Oxidative electrochemistry and complexation. Synthesis, characterization, oxidative electrochemistry and X-ray structures of [(Taniaphos/Walphos)MCl2] (M = Pd or Pt)

The oxidative electrochemistry of chiral, bidentate ferrocenylphosphines, five Taniaphos and seven Walphos ligands, was studied in methylene chloride. In general, two waves of varying reversibility were observed. Complexes of the general type [(phosphine)MCl₂] (phosphine = Taniaphos or Walphos; M = Pd or Pt) were prepared and characterized by NMR. Upon coordination, the oxidative electrochemistry of the ligands was greatly simplified. The X-ray structures of a Taniaphos platinum complex as well as a palladium and a platinum complex with a Walphos ligand were determined.     

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⁺).     

Enantioselective liquid‐liquid extraction of 3‐chloro‐phenylglycine enantiomers using (S,S)‐DIOP as extractant

(S,S)‐DIOP, a common catalyst used in asymmetric reaction, was adopted as chiral extractant to separate 3‐chloro‐phenylglycine enantiomers in liquid‐liquid extraction. The factors affecting extraction efficiency were studied, including metal precursors, organic solvents, extraction temperature, chiral extractant concentration, and pH of aqueous phase. (S,S)‐DIOP‐Pd exhibited good ability to recognize 3‐chloro‐phenylglycine enantiomers, and the operational enantioselectivity (α) is 1.836. The highest performance factor (pf) was obtained under the condition of extraction temperature of 9.1°C, (S,S)‐DIOP‐Pd concentration of 1.7 mmol/L, and pH of aqueous phase of 7.0. In addition, the possible recognition mechanism of (S,S)‐DIOP‐Pd towards 3‐chloro‐phenylglycine enantiomers was discussed.     

Chiral Amine Enantiomeric Excess Determination Using Self‐Assembled Octahedral Fe(II)‐Imine Complexes

A receptor assembly composed of iron(II) triflate and pyridine‐2,6‐dicarbaldehyde was used to determine the enantiomeric excess (ee) of alpha‐chiral primary amines using circular dichroism spectroscopy. The alpha chiral amines condense with the dialdehyde to form a diimine, which forms a 2:1 octahedral complex with iron(II). The ee values of unknown concentrations of alpha‐chiral amines were determined by constructing calibration curves for each amine and then measuring the ellipticity at 600 nm. This improves our previously reported assay for ee determination of chiral primary amines by further increasing the wavelength at which CD is measured and reducing the absolute error of the assay. Chirality 27:294–298, 2015. 2015 Wiley Periodicals, Inc.     

Synthesis,characterization and luminescent properties of europium complexes with 2,4,6‐tris‐(2‐pyridyl)‐s‐triazine as highly efficient sensitizers

Using 2,4,6‐tris‐(2‐pyridyl)‐s‐triazine (TPTZ) as a neutral ligand, and p‐hydroxybenzoic acid, terephthalic acid and nitrate as anion ligands, five novel europium complexes have been synthesized. These complexes were characterized using elemental analysis, rare earth coordination titrations, UV/vis absorption spectroscopy and infrared spectroscopy. Luminescence spectra, luminescence lifetime and quantum efficiency were investigated and the mechanism discussed in depth. The results show that the complexes have excellent emission intensities, long emission lifetimes and high quantum efficiencies. The superior luminescent properties of the complexes may be because the triplet energy level of the ligands matches well with the lowest excitation state energy level of Eu³⁺. Moreover, changing the ratio of the ligands and metal ions leads to different luminescent properties. Among the complexes, Eu₂(TPTZ)₂(C₈H₄O₄)(NO₃)₄(C₂H₅OH)·H₂O shows the strongest luminescence intensity, longest emission lifetime and highest quantum efficiency. Copyright © 2015 John Wiley & Sons, Ltd.     

Synthesis of alternating metallocopolymers by chiral recognition

We report the synthesis of chiral enantiopure polytopic bridging ligands, which may lead to the formation of metallosupramolecular polymers with zinc (II) as metal linker. We show that chiral C₂‐symmetric bisoxazoline ligands are useful moieties to efficiently generate heterochiral complexes and thus polymeric entities. The corresponding metallopolymers were further characterized by powder X‐ray diffraction (PXRD) to obtain information on the level of crystallinity of our different metallopolymers.     

Axially chiral N‐(o‐aryl)‐4‐hydroxy‐2‐oxazolidinone derivatives from diastereoselective reduction of N‐(o‐aryl)‐2,4‐oxazolidinediones: Thermally interconvertible atropisomers via ring‐chain‐ring tautomerization

The reduction of the axially chiral N‐(o‐aryl)‐5,5‐dimethyl‐2,4‐oxazolidinediones by NaBH₄ yielded axially chiral N‐(o‐aryl)‐4‐hydroxy‐5,5‐dimethyl‐2‐oxazolidinone enantiomers having a chiral center at C‐4, with 100% diastereoselectivity as has been shown by their ¹H and ¹³C NMR spectra and by enantioselective HPLC analysis. The resolved enantiomeric isomers were found to interconvert thermally through an aldehyde intermediate formed upon ring cleavage via a latent ring‐chain‐ring tautomerization. It was found that the rate of enantiomerization depended on the size and the electronic effect of the ortho substituent present on the aryl ring bonded to the nitrogen of the heterocycle. Chirality 2010. © 2009 Wiley‐Liss, Inc.     

Synthesis,crystal structure and biological evaluation of spectroscopic characterization of Ni(II) and Co(II) complexes with N‐salicyloil‐N′‐maleoil‐hydrazine as anticholinergic and antidiabetic agents

[Ni(C₁₁H₉N₂O₅)₂(H₂O)₂]?3(C₃H₇NO) ( 1 ) and [Co(C₁₁H₉N₂O₅)₂(H₂O)₂]?3(C₃H₇NO) ( 2 ) are synthesized and characterized by elemental analysis, FT‐IR spectra, magnetic susceptibility, and thermal analysis. In addition, the crystal structure of Ni(II) complex is presented. Both complexes show distorted octahedral geometry. In 1 and 2, metal ions are coordinated by two oxygen atoms of salicylic residue and two nitrogen atoms of maleic amide residue from two ligands, and two oxygen atoms from two water molecules. In this paper, both compounds showed excellent inhibitory effects against human carbonic anhydrase (hCA) isoforms I, and II, α‐glycosidase, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE). Compounds 1 and 2 had Ki values of 18.36 ± 4.38 and 26.61 ± 7.54 nM against hCA I and 13.81 ± 3.02 and 29.56 ± 6.52 nM against hCA II, respectively. On the other hand, their Ki values were found to be 487.45 ± 54.18 and 453.81 ± 118.61 nM against AChE and 199.21 ± 50.35 and 409.41 ± 6.86 nM against BChE, respectively.     

Importance of the interaction protein–protein of the CaM–PDE1A and CaM–MLCK complexes in the development of new anti‐CaM drugs

Protein–protein interactions play central roles in physiological and pathological processes. The bases of the mechanisms of drug action are relevant to the discovery of new therapeutic targets. This work focuses on understanding the interactions in protein–protein–ligands complexes, using proteins calmodulin (CaM), human calcium/calmodulin‐dependent 3′,5′‐cyclic nucleotide phosphodiesterase 1A active human (PDE1A), and myosin light chain kinase (MLCK) and ligands αII–spectrin peptide (αII–spec), and two inhibitors of CaM (chlorpromazine (CPZ) and malbrancheamide (MBC)). The interaction was monitored with a fluorescent biosensor of CaM (hCaM M124C–mBBr). The results showed changes in the affinity of CPZ and MBC depending on the CaM–protein complex under analysis. For the Ca²⁺–CaM, Ca²⁺–CaM–PDE1A, and Ca²⁺–CaM–MLCK complexes, CPZ apparent dissociation constants (K_ds) were 1.11, 0.28, and 0.55 μM, respectively; and for MBC K_ds were 1.43, 1.10, and 0.61 μM, respectively. In competition experiments the addition of calmodulin binding peptide 1 (αII–spec) to Ca²⁺–hCaM M124C–mBBr quenched the fluorescence (K_d = 2.55 ± 1.75 pM) and the later addition of MBC (up to 16 μM) did not affect the fluorescent signal. Instead, the additions of αII–spec to a preformed Ca²⁺–hCaM M124C–mBBr–MBC complex modified the fluorescent signal. However, MBC was able to displace the PDE1A and MLCK from its complex with Ca²⁺–CaM. In addition, docking studies were performed for all complexes with both ligands showing an excellent correlation with experimental data. These experiments may help to explain why in vivo many CaM drugs target prefer only a subset of the Ca²⁺–CaM regulated proteins and adds to the understanding of molecular interactions between protein complexes and small ligands. Copyright © 2013 John Wiley & Sons, Ltd.     

Synthesis of dendrimer‐type chiral stationary phases based on the selector of (1S,2R)‐(+)‐2‐Amino‐1,2‐diphenylethanol derivate and their enantioseparation evaluation by HPLC

In our recent work, a series of dendritic chiral stationary phases (CSPs) were synthesized, in which the chiral selector was L‐2‐(p‐toluenesulfonamido)‐3‐phenylpropionyl chloride (selector I), and the CSP derived from three‐generation dendrimer showed the best separation ability. To further investigate the influence of the structures of dendrimer and chiral selector on enantioseparation ability, in this work, another series CSPs ( CSPs 1‐4 ) were prepared by immobilizing (1S,2R)‐1,2‐diphenyl‐2‐(3‐phenylureido)ethyl 4‐isocyanatophenylcarbamate (selector II) on one‐ to four‐generation dendrimers that were prepared in previous work. CSPs 1 and 4 demonstrated the equivalent enantioseparation ability. CSPs 2 and 3 showed the best and poorest enantioseparation ability respectively. Basically, these two series of CSPs exhibited the equivalent enantioseparation ability although the chiral selectors were different. Considering the enantioseparation ability of the CSP derived from aminated silica gel and selector II is much better than that of the one derived from aminated silica gel and selector I, it is believed that the dendrimer conformation essentially impacts enantioseparation. Chirality, 2010. © 2009 Wiley‐Liss, Inc.     

Chiral P-monodentate phosphoramidite and phosphite ligands for the enantioselective Pd-catalyzed allylic alkylation

The improved synthesis of the chiral phosphoramidite Ia, based on a biphenol backbone and bearing chiral bis(1-phenylethyl)amine group on the phosphorus atom, is described together with its Pd(II) complex. The chiral complex cis-PdCl₂L₂ (L = Ia) has been characterized by X-ray crystal structure analysis and spectroscopic data. The series of the chiral P-monodentate phosphoramidite and phosphite ligands was tested in Pd-catalyzed enantioselective allylic substitution of different substrates. In the palladium-catalyzed asymmetric allylic alkylation of 1,3-diphenylallyl acetate with dimethylmalonate, up to 79% ee was achieved with [Pd₂(dba)₃] × CHCl₃ as precatalyst.