Chiral Sensing of Various Amino Acids Using Induced Circularly Polarized Luminescence from Europium(III) Complexes of Phenanthroline Dicarboxylic Acid Derivatives

Circularly polarized luminescence (CPL) was observed from [Eu(dppda)₂]^? (dppda=4,7‐diphenyl‐1,10‐phenanthroline‐2,9‐dicarboxylic acid) and [Eu(pzpda)₂]^? (pzpda=pyrazino[2,3‐f][1,10]phenanthroline‐7,10‐dicarboxylic acid) in aqueous solutions containing various amino acids. The selectivity of these complexes towards amino acids enabled them to be used as chiral sensors and their behavior was compared with that of [Eu(pda)₂]^? (pda=1,10‐phenanthroline‐2,9‐dicarboxylic acid). As these Eu^III complexes have achiral D_2d structures under ordinary conditions, there were no CPL signals in the emission assigned to f–f transitions. However, when the solutions contained particular amino acids they exhibited detectable CPL signals with g_lum values of about 0.1 (g_lum=CPL/2 TL; TL=total luminescence). On examining 13 amino acids with these three Eu^III complexes, it was found that whether an amino acid induced a detectable CPL depended on the Eu^III complex ligands. For example, when ornithine was used as a chiral agent, only [Eu(dppda)₂]^? exhibited intense CPL in aqueous solutions of 10^?2 mol dm^?3. Steep amino acid concentration dependence suggested that CPL in [Eu(dppda)₂]^? and [Eu(pzpda)₂]^? was induced by the association of four or more amino acid molecules, whereas CPL in [Eu(pda)₂]^? was induced by association of two arginine molecules.     

Induced Circular‐Dichroism Chirality Probes for Selective Amino Acid Detection through Screening of a Dynamic Combinatorial Library of Lanthanide Complexes

A dynamic combinatorial library of lanthanide complexes was prepared to develop induced‐circular‐dichroism (CD) chirality probes. It totaled 168 combinations of coordinative N‐aromatic chromophores, trivalent lanthanide centers, and guest amino acids. Eu³⁺ and Tb³⁺ complexes prepared with quinolinecarboxylic acid were particularly effective as induced‐CD chirality probes for selective alanine detection, whereas a Yb³⁺ complex with terpyridine exhibited glutamine selectivity. The former two complexes highly preferred alanine to the corresponding amine, ester, amino alcohol, and carboxylic acid derivatives. As such, the present combinatorial screening of a dynamic lanthanide complex library has led to a new series of induced‐CD chirality probes for specific amino acids.     

Biocatalysis with Unnatural Amino Acids: Enzymology Meets Xenobiology

The goal of xenobiology is to design biological systems endowed with unusual biochemical functions, whereas enzymology concerns the study of enzymes, the workhorses of biocatalysis. Biocatalysis employs enzymes and organisms to perform useful biotransformations in synthetic chemistry and biotechnology. During the past few years, the effects of incorporating noncanonical amino acids (ncAAs) into enzymes with potential applications in biocatalysis have been increasingly investigated. In this Review, we provide an overview of the effects of new chemical functionalities that have been introduced into proteins to improve various facets of enzymatic catalysis. We also discuss future research avenues that will complement unnatural mutagenesis with standard protein engineering to produce novel and versatile biocatalysts with applications in synthetic organic chemistry and biotechnology.     

Photocatalytic Modification of Amino Acids,Peptides, and Proteins

In the last decade, visible-light photoredox catalysis has emerged as a powerful strategy to enable novel transformations in organic synthesis. Owing to mild reaction conditions (i.e., room temperature, use of visible light) and high functional-group tolerance, photoredox catalysis could represent an ideal strategy for chemoselective biomolecule modification. Indeed, a recent trend in photoredox catalysis is its application to the development of novel methodologies for amino acid modification. Herein, an up-to-date overview of photocatalytic methodologies for the modification of single amino acids, peptides, and proteins is provided. The advantages offered by photoredox catalysis and its suitability in the development of novel biocompatible methodologies are described. In addition, a brief consideration of the current limitations of photocatalytic approaches, as well as future challenges to be addressed, are discussed.     

Redox‐Driven Symmetry Change for Terbium(III) Bis(porphyrinato) Double‐Decker Complexes by the Azimuthal Rotation of the Porphyrin Macrocycles

Molecular structures for three oxidation forms (anion, radical, and cation) of terbium(III) bis(porphyrinato) double‐decker complexes have been systematically studied. We found that the redox state controls the azimuthal rotation angle (φ) between the two porphyrin macrocycles. For [Tb^III(tpp)₂]ⁿ (tpp: tetraphenylporphyrinato, n=?1, 0, and +1), φ decreases at each stage of the oxidation process. The decrease in φ is due to the higher steric repulsion between the phenyl rings on the porphyrin macrocycle and the β hydrogen atoms on the other porphyrin macrocycle, which results from the shorter interfacial distance between the two porphyrin macrocycles. Conversely, φ=45° for both [Tb^III(oep)₂]^?1 and [Tb^III(oep)₂]⁰ (oep: octaethylporphyrinato), but φ=36° for [Tb^III(oep)₂]⁺¹. Theoretical calculations suggest that the smaller azimuthal rotation angle of the cation form is due to the electronic interaction in the doubly oxidized ligand system.     

Lanthanide(III) Complexes of Tris(amide) PCTA Derivatives as Potential Bimodal Magnetic Resonance and Optical Imaging Agents

Lanthanide complexes of two tris(amide) derivatives of PCTA were synthesized and characterized. The relaxometric and luminescence properties of their lanthanide complexes were investigated as bimodal magnetic resonance (MR) and optical imaging agents. Luminescence studies show that one of the Tb^III complexes dimerizes in solution at low millimolar concentrations, whereas the other may have a higher than expected coordination number in solution. The corresponding Gd^III complexes display unusually high T₁ relaxivities and enhanced kinetic inertness compared to GdPCTA. These features suggest that these new chelates may be suitable for in vivo applications. The fast water‐exchange rates observed for these complexes make them unsuitable as paramagnetic chemical exchange saturation transfer (PARACEST) agents.     

Gas-Phase Structures of Potassium Tetrakis(hexafluoro- acetylacetonato) Lanthanide(III) Complexes [KLn(C5HF6O2)4] (Ln=La,Gd, Lu)

The molecular structures of potassium tetrakis(hexafluoroacetylacetonato)lanthanide(III) complexes [KLn(hfa)₄] (Ln=La, Gd, Lu; hfa=C₅HF₆O₂,) were studied by synchronous gas-phase electron diffraction/mass spectrometry (GED/MS) supported by quantum-chemical (DFT/PBE0) calculations. The compounds sublime congruently and the vapors contain a single molecular species: the heterobinuclear complex [KLn(hfa)₄]. All molecules are of C₁ symmetry with the lanthanide atom in the center of an LnO₈ coordination polyhedron, while the potassium atom is coordinated by three ligands with formation of three K−O and three K−F bonds. One hfa ligand is not bonded to the potassium atom. Topological analysis of the electron-density distributions confirmed the existence of ionic-type K−O and K−F bonding. The structures of the free [KLn(hfa)₄] molecules are compared with those of the related compounds [KDy(hfa)₄] and [KEr(hfa)₄] in their crystalline state. The complex nature of the chemical bonding is discussed on the basis of electron-density topology analyses.     

Synthesis,X‐ray Structure of Ferrocene Bearing Bis(Zn‐cyclen) Complexes and the Selective Electrochemical Sensing of TpT

The new ligand, [Fc(cyclen)₂] ( 5 ) (Fc=ferrocene, cyclen=1,4,7,10‐tetraazacyclododecane), and corresponding Zn^II complex receptor, [Fc{Zn(cyclen)(CH₃OH)}₂](ClO₄)₄ ( 1 ), consisting of a ferrocene moiety bearing one Zn^II‐cyclen complex on each cyclopentadienyl ring, have been designed and prepared through a multi‐step synthesis. Significant shifts in the ¹H NMR signals of the ferrocenyl group, cf. ferrocene and a previously reported [Fc{Zn(cyclen)}]²⁺ derivative, indicated that the two Zn^II‐cyclen units in 1 significantly affect the electronic properties of the cyclopentadienyl rings. The X‐ray crystal structure shows that the two positively charged Zn^II‐cyclen complexes are arranged in a trans like configuration, with respect to the ferrocene bridging unit, presumably to minimise electrostatic repulsion. Both 5 and 1 can be oxidized in 1:4 CH₂Cl₂/CH₃CN and Tris‐HCl aqueous buffer solution under conditions of cyclic voltammetry to give a well defined ferrocene‐centred (Fc^0/+) process. Importantly, 1 is a highly selective electrochemical sensor of thymidilyl(3′‐5′)thymidine (TpT) relative to other nucleobases and nucleotides in Tris‐HCl buffer solution (pH 7.4). The electrochemical selectivity, detected as a shift in reversible potential of the Fc^0/+ component, is postulated to result from a change in the configuration of bis(Zn^II‐cyclen) units from a trans to a cis state. This is caused by the strong 1:1 binding of the two deprotonated thymine groups in TpT to different Zn^II centres of receptor 1 . UV‐visible spectrophotometric titrations confirmed the 1:1 stoichiometry for the 1 :TpT adduct and allowed the determination of the apparent formation constant of 0.89±0.10×10⁶ M ^?1 at pH 7.4.     

含有络合功能基的非天然氨基酸的设计、合成及在生物活性肽中的应用

设计合成了一类侧链带有络合基团的非天然氨基酸, 即侧链带有N,N-二羧甲基氨甲基、N,N-二酰胺甲基氨甲基和N,N-二羟乙基氨甲基的苯丙氨酸衍生物, 并将这类非天然氨基酸用于促性腺激素释放激素(LHRH)类似物的固相合成. 高效液相色谱分析结果表明, 粗肽的纯度较好, 易于纯化; 用电喷雾质谱测定了多肽的分子量. 这些非天然氨基酸可作为其它肽类药物合成的构建单元.     

Electronic and ESR Spectra of Copper(II) Complexes with N,N-Dialkyl Amino Acids

Five N,N-dialkylamino acids were synthesised [4]: N,N-dimethylisoleucine (DMIL), N,N-dimethyl-alloisoleucine (DMAIL), N,N-dimethylvaline (DMV), N,N-diethyl-alanine (DEA), and N,N-diethylvaline (DEV), as well as their complexes with copper(II): Cu(DMIL)₂, Cu(DMAIL)₂, Cu(DMV)₂, Cu(DMIL)(DMV), Cu(DEA)₂, and Cu(DEV)₂. UV/VIS spectra of the complexes were recorded in CH₂Cl₂ solutions and the ESR spectra in CH₂Cl₂, CD₃OD, and D₂O solutions. By applying the analysis of variance, ESR spectra were shown to be influenced by the solvent and substituent differences, the former effect being related to the degree of covalency of the copper-ligand bonds. The effect of the ligand's spatial configuration (diastereoisomerism) upon the ESR spectrum of the complex was demonstrated and explained.     

Stable Anticancer Gold(III)–Porphyrin Complexes: Effects of Porphyrin Structure

In the design of physiologically stable anticancer gold(III) complexes, we have employed strongly chelating porphyrinato ligands to stabilize a gold(III) ion [Chem. Commun. 2003 , 1718; Coord. Chem. Rev. 2009 , 253, 1682]. In this work, a family of gold(III) tetraarylporphyrins with porphyrinato ligands containing different peripheral substituents on the meso‐aryl rings were prepared, and these complexes were used to study the structure–bioactivity relationship. The cytotoxic IC₅₀ values of [Au(Por)]⁺ (Por=porphyrinato ligand), which range from 0.033 to >100 μM , correlate with their lipophilicity and cellular uptake. Some of them induce apoptosis and display preferential cytotoxicity toward cancer cells than to normal noncancerous cells. A new gold(III)–porphyrin with saccharide conjugation [Au(4‐glucosyl‐TPP)]Cl ( 2 a ; H₂(4‐glucosyl‐TPP)=meso‐tetrakis(4‐β‐D ‐glucosylphenyl)porphyrin) exhibits significant cytostatic activity to cancer cells (IC₅₀=1.2–9.0 μM ) without causing cell death and is much less toxic to lung fibroblast cells (IC₅₀>100 μM ). The gold(III)–porphyrin complexes induce S‐phase cell‐cycle arrest of cancer cells as indicated by flow cytometric analysis, suggesting that the anticancer activity may be, in part, due to termination of DNA replication. The gold(III)–porphyrin complexes can bind to DNA in vitro with binding constants in the range of 4.9×10⁵ to 4.1×10⁶ dm³ mol^?1 as determined by absorption titration. Complexes 2 a and [Au(TMPyP)]Cl₅ ( 4 a ; [H₂TMPyP]⁴⁺=meso‐tetrakis(N‐methylpyridinium‐4‐yl)porphyrin) interact with DNA in a manner similar to the DNA intercalator ethidium bromide as revealed by gel mobility shift assays and viscosity measurements. Both of them also inhibited the topoisomerase I induced relaxation of supercoiled DNA. Complex 4 a , a gold(III) derivative of the known G‐quadruplex‐interactive porphyrin [H₂TMPyP]⁴⁺, can similarly inhibit the amplification of a DNA substrate containing G‐quadruplex structures in a polymerase chain reaction stop assay. In contrast to these reported complexes, complex 2 a and the parental gold(III)–porphyrin 1 a do not display a significant inhibitory effect (<10 %) on telomerase. Based on the results of protein expression analysis and computational docking experiments, the anti‐apoptotic bcl‐2 protein is a potential target for those gold(III)–porphyrin complexes with apoptosis‐inducing properties. Complex 2 a also displays prominent anti‐angiogenic properties in vitro. Taken together, the enhanced stabilization of the gold(III) ion and the ease of structural modification render porphyrins an attractive ligand system in the development of physiologically stable gold(III) complexes with anticancer and anti‐angiogenic activities.     

Water-Soluble Polynuclear Metallamacrocyclic Copper(II) and Lanthanide(III) Complexes Based on Amino Hydroxamic Acids

Data on the synthesis and structure of water-soluble polynuclear copper(II) and lanthanide(III) metallamacrocycles based on amino hydroxamic acids are presented. The structural features of the obtained 15-MC-5 metallacrown aqua complexes and their applicability as NMR contrast agents are considered. Additionally, the applicability as molecular precursors for the synthesis of nano-sized materials was demonstrated for Ce(III) compounds.     

Synthesis and Characterization of Phosphate-Catecholate Chelated Nd(III), Zr(IV), and Al(III) Complexes

Metal phosphates are important catalysts and materials in synthesis chemistry. Herein, we describe the synthesis and characterization of phosphate-catecholate chelated Nd(III), Zr(IV) and Al(III) chlorides ( 2 – 5 ). These species are achieved via ethyl chloride elimination reaction of oxophosphoranes with corresponding metal chlorides. The product 2 – 5 represent a new serial of monometallic and bimetallic phosphate-catecholate chelated metal complexes stabilized by both P−O and catecholate-O donors. These findings pave the way for future explorations of such species in catalysis.     

Two Series of Homodinuclear Lanthanide Complexes: Greatly Enhancing Energy Barriers through Tuning Terminal Solvent Ligands in Dy2 Single‐Molecule Magnets

The utilization of 2‐ethoxy‐6‐{[(2‐hydroxy‐3‐methoxybenzyl)imino]methyl}phenol (H₂L) as a chelating ligand, in combination with the employment of alcohols (EtOH and MeOH) as auxiliary ligands, in 4 f‐metal chemistry afforded two series of dinuclear lanthanide complexes of compositions [Ln₂L₂(NO₃)₂(EtOH)₂] (Ln=Sm ( 1 ), Eu ( 2 ), Gd ( 3 ), Tb ( 4 ), Dy ( 5 ), Ho ( 6 ), Er ( 7 )) and [Ln₂L₂(NO₃)₂(MeOH)₂] (Ln=Sm ( 8 ), Eu ( 9 ), Gd ( 10 ), Tb ( 11 ), Dy ( 12 ), Ho ( 13 ), Er ( 14 )). The structures of 1 – 14 were determined by single‐crystal X‐ray crystallography. Complexes 1 – 7 are isomorphous. The two lanthanide(III) ions in 1 – 7 are doubly bridged by two deprotonated aminophenoxide oxygen atoms of two μ₂:η⁰:η¹:η²:η¹:η¹:η⁰‐L²⁻ ligands. One nitrogen atom, two oxygen atoms of the NO₃⁻ anion, two methoxide oxygen atoms of two ligand sets, and one oxygen atom of the terminally coordinated EtOH molecule complete the distorted dodecahedron geometry of each lanthanide(III) ion. Compounds 8 – 14 are isomorphous and their structures are similar to those of 1 – 7 . The slight difference between 1 – 7 and 8 – 14 stems from purposefully replacing the EtOH ligands in 1 – 7 with MeOH in 8 – 14 . Direct‐current magnetic susceptibility studies in the 2–300 K range reveal weak antiferromagnetic interactions for 3 , 4 , 7 , 10 , 11 , and 14 , and ferromagnetic interactions at low temperature for 5 , 6 , 12 , and 13 . Complexes 5 and 12 exhibit single‐molecule magnet (SMM) behavior with energy barriers of 131.3 K for 5 and 198.8 K for 12 . The energy barrier is significantly enhanced by dexterously regulating the terminal ligands. To rationalize the observed difference in the magnetic behavior, complete‐active‐space self‐consistent field (CASSCF) calculations were performed on two Dy₂ complexes. Subtle variation in the angle between the magnetic axes and the vector connecting two dysprosium(III) ions results in a weaker influence on the tunneling gap of individual dysprosium(III) ions by the dipolar field in 12 . This work proposes an efficient strategy for synthesizing Dy₂ SMMs with high energy barriers.     

Spectrofluorimetric Study of the Complexes Between Calcein and Lanthanide(III) Ions

ABSTRACT

The equilibrium of calcein, an H6L type fluorescent ligand, with lanthanide(III) ions, Ln(III), was studied spectrofluorimetrically in aqueous solution at constant ionic strength =0.1 (KC1), pH 8.0 and 25.0±0.1°C. Application of the mole ratio and continuous variation methods reveals the formation of 1:1 complexes. The conditional stability constants (β') were calculated from the analysis of the observed fluorescence vs. [Ln(III)]/[calcein] mole ratio data by using an iterative non-linear least-squares computer program. The values obtained for β' are in the range 5.24×10⁶-5.77×10⁷ The thermodynamic stability constant (β) were estimated by calculating the sidereaction coefficients (α) fro lanthanides and calcein. The β values obtained were from 3.2×10¹² to 3.6×10¹³