The Synthesis of Novel Crown Ethers. Part IV. Coumarin Derivatives of [18]crown-6 and Cation Binding from Fluorescence Spectra

4-H, 4-methyl and 4-phenyl-1-benzopyran-2-one derivatives of [18]crown-6 derivatives were synthesised from 6,7- and 7,8-dihydroxy-1-benzopyran-2-one reacting with pentaethylene glycol ditosylate in K₂CO₃/DMF/water. The products were identified by elemental analysis, EI-GC-mass spectra and ₁H-NMR spectroscopy. The Na⁺ association constants of some coumarin derivatives were determined with an ion selective electrode in water. The Na⁺ , K⁺, Ba²⁺ and Sr²⁺ binding role of such compounds were particularly observed as remarkable alterations in acetonitrile. The 1 : 1 associations constants of K⁺ and Na⁺ with some coumarin-[18]crown-6 derivatives estimated by this way in acetonitrile exhibited the utility of complexing enhanced quenching fluorescence spectra for the ion binding power of the such macrocycles.     

Novel Methods of Synthesis of Dibenzo[3n]crown-n and Their Cation Binding Studied by Fluorescence Spectroscopy. Part V

The dibenzo[3n]crown-n were synthesised starting from bis[2-(o-hydroxyphenoxy)ethyl]ether obtained from bis[2-(o-formylphenoxy)ethyl]ether via Baeyer-Villiger oxidation in H₂O₂/CH₃COOH in a good yield. The cyclic condensation ofbis[2-(o-hydroxyphenoxy)ethyl]etherwith tri- and tetraethylene glycol bisdichlorides andthe bisditosylate of pentaethylene glycol in DMF/Me₂CO₃ afforded the large cyclic ethers of dibenzo[21]crown-7, dibenzo[24]crown-8 and dibenzo[27]crown-9. The structures were analysed with IR, ¹H NMR, ¹³C NMR and low-resolution mass spectroscopy methods. The Na⁺, K⁺, Rb⁺ and Cs⁺ cations' recognition of the molecules were conducted withsteady-state fluorescence spectroscopy. The 1:1 association constants, K_a, in acetonitrile were estimated. Dibenzo[21]crown-7 was the best both for K⁺ and Rb⁺ binding but showed too small an effect on Cs⁺. Dibenzo[24]crown-8 exhibited the binding power in the order of Rb⁺ > K⁺ > Na⁺ > Cs⁺. However, dibenzo[27]crown-9 displayed marked binding with only K⁺ but not with Rb⁺ or with Cs⁺ cations probably due to the heavy atom effect of fluorescence quenching.     

The Synthesis of Dibenzo[3n]crown-n by Novel Methods and their Cation Binding Studied by Fluorescence Spectroscopy. Part IV

The dibenzo[3n]crown-n were synthesised from1,2-bis(o-hydroxyphenoxy)ethane obtained from 1,2-bis(o-formylphenoxy)ethane via Bayer-Willigeroxidations with H₂O₂/CH₃COOH in good yields. The cyclic condensation of 1,2-bis(o-hydroxyphenoxy)ethanewith dichlorides, and ditosylates of polyethylene glycols in DMF/Me₂CO₃ gave the macrocyclesdibenzo[15]crown-5, dibenzo[18]crown-6, dibenzo[21]crown-7 anddibenzo[24]crown-8. The structures were identified using IR, mass, ¹H and ¹³C NMR spectroscopy. Therecognition of the molecules for the cations, Li⁺, Na⁺, K⁺, Rb⁺ and Zn²⁺were conducted quantitatively with steady state fluorescencespectroscopy. The 1:1 association constants in acetonitrileshowed a good relation of the appropriate size of the macrocyclic ether towards the fitting cationradii. Namely, dibenzo[15]crown-5 was the best for Li⁺ binding and more than 100 times better thanNa⁺ and K⁺. Dibenzo[21]crown-7 was excellent for Rb⁺ binding while K⁺ is 100 timesless preferred. The largest crown ether studied, dibenzo[24]crown-8, exhibited the order of binding power,Rb⁺ > K⁺ > Na⁺. Zn²⁺ displayed, however, a marked binding with only dibenzo[18]crown-6.p>     

Eu(fod)(3) binding on the (1)H-NMR spectra of some benzo[3n]crown-n and dibenzo[3n+2]crown-n

The complexing of Eu(fod)₃ with macrocyclic ethers, benzo[15]crown-5, benzo[12]crown-4, dibenzo[20]crown-6, dibenzo[23]crown-7 and dibenzo[26]crown-8 was observed on their ¹H-NMR spectra and the selective binding constants at 400 MHz and 305 K in CDCl₃ were reported. The Eu(fod)₃ interaction displayed the selective binding role of oxygen on macrocyclic, H₂COCH₂, backbones with o- or m-dioxyphenyl groups referring the ¹H chemical shifts. The estimated equilibrium constants, K_a of 1:1 ratio of interactions were in accordance with the Eu³⁺ ionic radii to bind the oxygen sites depending on the macrocyclic size and conformation of the ethers. The minimum lanthanide-macrocyclic ether distance displayed the maximum stability so that benzo[3n]crown-n (n=4, 5) group was found to bind the Eu(fod)₃ moderately whilst dibenzo[3n+2]crown-n (n=6-8) oligomer chemical shifts were induced largely since the such Eu³⁺ complexes are more stable with larger ethyleneoxy groups.     

The cation binding of benzo crown ethers in acetonitrile using fluorescence spectroscopy

The effects of Na⁺, K⁺ and Li⁺ cations on the fluorescence spectra of benzo[15]crown-5, benzo[18]crown-6 and dibenzo[18]crown-6 were investigated in acetonitrile. The alkali cation role observed was usually the complexation-enhanced quenching fluorescence effect (CEQF) in acetonitrile due to the increased fluorescence quenching rate of the complexed fluoroionophore. The association constants for 1 :1 stoichiometry InK _a have been obtained using the relationship 1/K _a[L ₀] = (1 –P)²/P. It was shown that the preferential interaction rule of compatibility of cationic radii and macrocyclic ring size is in excellent agreement with the association constants obtained by fluorescence spectroscopy. The order of InK _a found for benzo[15]crown-5 complexation was Li⁺ > Na⁺ > K⁺ and K⁺ > Na⁺ > Li⁺ for benzo[18]crown-6 in acetonitrile.Presented at the Sixth International Seminar on Inclusion Compounds, Istanbul, Turkey, 27–31 August, 1995.     

Cation complexing of crown ethers using fluorescence spectroscopy, part II

The complex formations of benzo[12]crown-4, benzo[15]crown-5 and benzo[18]crown-6 with perchlorate salts of Mg(2+), Li(+) and Na(+) were investigated using the steady state fluorescence emission spectroscopy in acetonitrile. The complexation enhanced quenched fluorescence spectra, (CEQFS) exhibited the ion complexation role of the macrocyclic ethers and equilibrium constant, K(e) of 1:1 stoichiometry were estimated. The K(e) were found in the order of Mg(+)>Na(+)>Li(+) for benzo[15]crown-5 whilst Na(+)>Mg(+)>Li(+) order was found with benzo[12]crown-4 at 298 K.     

The association constants of Na(+) with dibenzo[3n]crown-n in THF/water using ISE

The Na⁺ association constants, K₁₁ and β₁₂, of 1/1 and 1/2 stoichiometry of macrocycles of (1,2)dibenzo[15]crown-5, (1,3)dibenzo[18]crown-6, (1,4)dibenzo[21]crown-7, (2,3)dibenzo[21]crown-7, (2,4)dibenzo[24]-crown-8 and dicyclohexano[24]crown-8 were determined in THF/water, (50/50), mixtures. We used a Methrom Na⁺ ISE for the potentiometric measurements and applied the 1/(β_nm[A_o⁺])^n+m−1=(1−nP_c)(1−mP_c)/P_c equation where the P_c=P/[1+(m−1)P] and P is the mole fraction of the complexed cation, [A_n⁺L_m] for association constants with linear best fit. Results were in well agreement with the macrocyclic size and cation radii relationships. Measurements showed the role of aromatic groups of macrocyclics in THF/water (50/50) which allowed the macrocyclic molecules more selectively bind Na⁺ compared to the associations those obtained in water.     

Design and synthesis of a new coumarin-based ‘turn-on’ fluorescent probe selective for Cu

The novel coumarin-based ‘turn-on’ fluorescent probe (E)-3-(2,5-dimethoxybenzylideneamino)-7-hydroxy-2H-chromen-2-one (MGM) was designed, synthesized, and characterized. This compound shows high selectivity for Cu⁺², combined with a large fluorescence enhancement upon binding to Cu²⁺. Benesi-Hildebrand and Job plots demonstrate that the stoichiometry of the Cu²⁺ complex formed is 2:1. Preliminary studies employing epifluorescence microscopy demonstrated that Cu⁺² could be imaged in human neuroblastoma SH-SY5Y cells treated with MGM.     

The Synthesis and the Cationic Fluorescence Role of Glycols with Aromatic End Groups, Part III

Some novel bis-(substituted-phenoxy) ended glycols were synthesised usinghydroxy aromatics of vanillin, o-vanillin, iso-vanillin and 4-hydroxy coumarin which reacted with bis-dihalides of polyglycols in the presence ofDMSO/alkali carbonate. The novel podands, Ar-(CH₂CH₂O)_m-Ar,(m = 1–4), were identified with IR, ¹H-NMR, ¹³C-NMR and mass spectrometry. The various (formyl-methoxy)phenyl and 4-oxycoumarin derivatives of glycols were studied to estimate the cation binding selectivity of SCN^- salts ofLi⁺, Na⁺, K⁺ and Zn²⁺ cations in acetonitrile using steady statefluorescence spectroscopy. The relevant structures of podands have shown goodselectivity depending on the cation and the glycollength, although the chromophoreend groups have no specific contribution on binding.     

Estimation of Li+, K+ and Ca2+ Complexation with [12] crown-4, [15] crown-5 and [18] crown-6 Using a Na+ ISE in Dioxane-Water, Part IV*

 The (1:1) Na⁺ equilibrium constants, Ke1, of macrocyclic ethers of [12]crown-4, [12]crown-5 and [18]crown-6 were determined with a Na⁺ ISE in the presence of a second cation e.g. Li⁺, K⁺ and Ca²⁺ in dioxane/water (50/50). We estimated the (1:1) equilibrium constants, K e2 of the macrocyclic ethers with Li⁺, K⁺ and Ca²⁺ by this way. The binding selectivity of a macrocyclic ether between two cations was estimated in the same binary solvent mixture where the water hydration role is diminished. Results showed clearly the effect of macrocyclic size and cation radii in a solution. Received October 27, 1998. Revision March 22, 1999.     

Excellent Ag+ selective receptors: Syntheses and complexation properties of novel biscalix[4]arene with benzalazine groups

By reacting mono-substituted or 1,3-bi-substituted [2-(p-formylphenyloxy)ethyloxy]-p-tert-butylcalix[4]arene (3 or 4) with hydrazine hydrate in ‘1+2’ or ‘2+2’ condensation mode, novel benzalazine-bridging biscalix[4]arenes 5 and 7 were conveniently obtained in the yields of 76 and 81%, respectively. Condensation of compound 4 and salicylide hydrazone gave a novel calix[4]arene benzalazine derivative 6 in the yield of 85%. The structures and conformations of all new compounds were characterised by elemental analyses, ESI-MS, ¹H NMR and ¹H–¹H COSY techniques. Biscalix[4]arene 7 adopts a symmetrical cone conformation with tube cavity. The liquid–liquid extraction experiment showed that all new hosts possessed excellent complexation abilities towards soft metal cations. Compound 7 exhibited high complexation selectivity towards Ag⁺. The Ag⁺/Na⁺ and Ag⁺/Hg²⁺ extraction percentages of host 7 were as high as 73.1 and 54.9, respectively. The UV–vis spectra complexation experiments revealed that the complexation constant of receptor 7 with Ag⁺ was 1.9 × 10⁵ M^? 1 and the 1:1 stoichiometry of receptor 7–Ag⁺ complex was formed. The ¹H NMR spectra complexation experiments suggested that Ag⁺ was bound in a cavity composed of two benzalazine groups on bridging chains.     

Synthesis, NMR characterization and ion binding properties of 1,3-bridged p-tert-butyldihomooxacalix[4]crown-6 bearing pyridyl pendant groups

1,3-Di(2-pyridylmethoxy)-p-tert-butyldihomooxacalix[4]arene-crown-6 (2) was synthesized for the first time. 2 was isolated in a cone conformation in solution at room temperature, as established by NMR spectroscopy (¹H, ¹³C and NOESY). Complete assignment of both proton and carbon NMR spectra was achieved by a combination of COSY, HSQC and HMBC experiments. The binding properties of ligand 2 towards alkali, alkaline earth, transition and heavy metal cations have been assessed by phase transfer and proton NMR titration experiments. The results are compared to those obtained with other dihomooxacalix[4]arene-crowns-6 and closely-related calix[4]arene-crown derivatives. 2 shows a preference for the soft heavy metal cations (except for Cd²⁺), with a very strong affinity for Ag⁺. Some transition metal cations are also well extracted. 2 forms 1:1 complexes with K⁺, Ca²⁺ and Ag⁺, and ¹H NMR titrations indicate that they should be encapsulated into the cavity defined by the crown ether unit and by the two pyridyl pendant arms. A 1:2 (ML₂) complex is formed with Zn²⁺ and two species, probably 1:1 and 1:2 complexes, are obtained with Pb²⁺.     

Azocalixarenes. 6: Synthesis, complexation, extraction and thermal behaviour of four new azocalix[4]arenes

Four new azocalix[4]arenes {5,11,17,23-tetrakis[(2-hydroxy-5-tert-butylphenylazo)]-25,26,27,28-tetrahydroxycalix[4]arene (1), 5,11,17,23-tetrakis[(2-hydroxy-5-nitro phenylazo)]-25,26,27,28-tetrahydroxycalix[4]arene (2), 5,11,17,23-tetrakis[(2-amino-5-carboxylphenylazo)]-25,26,27,28-tetrahydroxycalix[4]arene (3) and 5,11,17,23-tetrakis[(1-amino-2-hydroxy-4-sulfonicacidnapthylazo)]-25,26,27,28-tetrahydroxycalix[4]arene (4)} have been synthesized from p-tert-butylphenol, p-nitrophenol, p-aminobenzoic acid and 1-amino-2-hydroxy-4-sulphonic acid by diazo coupling reaction with p-aminocalix[4]arene. The resulting ligands (1–4) were treated with three transition metal salts (e.g., CuCl₂·2H₂O, NiCl₂·6H₂O or CoCl₂·6H₂O). Cu(II), Ni(II) and Co(II) complexes of the azocalix[4]arene derivatives were obtained and characterized by UV-vis, IR, ¹H-NMR spectroscopic techniques and elemental analysis. All the complexes have a metal:ligand ratio of 2:1. The Cu(II) and Ni(II) complexes of azocalix[4]arenes are square-planar, while the Co(II) complexes of azocalix[4]arenes are octahedral with water molecules as axial ligands. The solvent extraction of various transition metal cations from the aqueous phase to the organic phase was carried out by using azocalix[4]arenes (1–4). It was found that, azocalix[4]arenes 1, 2 and 3 examined selectivity for transition metal cations such as Ag⁺, Hg⁺ and Hg²⁺. In addition, the thermal stability of metal:azocalix[4]arene complexes were also reported. Dedicated to Prof. Dr. Mustafa Yılmaz on the occasion of his 50th birthday     

Exploiting the deprotonation mechanism for the design of ratiometric and colorimetric Zn fluorescent chemosensor with a large red-shift in emission

The design, synthesis, and photophysical evaluation of a new naphthalimide-based fluorescent chemosensor, N-butyl-4-[di-(2-picolyl)amino]-5-(2-picolyl)amino-1,8-naphthalimide (1), were described for the detection of Zn²⁺ in aqueous acetonitrile solution at pH 7.0. Probe 1 showed absorption at 451 nm and a strong fluorescence emission at 537 nm (Φ_F=0.33). The capture of Zn²⁺ by the receptor resulted in the deprotonation of the secondary amine conjugated to 1,8-naphthalimide so that the electron-donating ability of the N atom would be greatly enhanced; thus probe 1 showed a 56 nm red-shift in absorption (507 nm) and fluorescence spectra (593 nm, Φ_F=0.14), respectively, from which one could sense Zn²⁺ ratiometrically and colorimetrically. The deprotonated complex, [(1-H)/Zn]⁺, was calculated at m/z 619.1800 and measured at m/z 618.9890. In contrast to these results, the emission of 1 was thoroughly quenched by Cu²⁺, Co²⁺, and Ni²⁺. The addition of other metal ions such as Li⁺, Na⁺, K⁺, Mg²⁺, Ca²⁺, Fe³⁺, Mn²⁺, Al³⁺, Cd²⁺, Hg²⁺, Ag⁺, and Pb²⁺ produced a nominal change in the optical properties of 1 due to their low affinity to probe 1. This means that probe 1 has a very high fluorescent imaging selectivity to Zn²⁺ among metal ions.     

铜转运蛋白C端金属结合域与Ag+及Hg2+的相互作用

铜转运蛋白(CTR1)不仅参与铜的细胞摄取,而且在其它重金属离子的摄取过程中也发挥重要作用. 本文采用紫外-可见(UV-Vis)光谱,核磁共振(NMR)和质谱(MS)的方法,研究了人源CTR1 (hCTR1)的C端金属结合域(C8)与Ag⁺和Hg²⁺的相互作用. 研究表明,Ag⁺和Hg²⁺都能与C8结合,但二者与C8的结合机制明显不同. 每个C8分子可以结合两个Ag⁺离子,但一个Hg²⁺却可以与两个C8形成桥联. 此外,Ag⁺离子与C8的配位是一个中等速度的交换过程,而Hg²⁺离子则为快速交换过程. C8的半胱氨酸残基是两种离子的重要结合位点,同时组氨酸残基也参与两种金属离子的配位,其中Ag⁺优先结合组氨酸,而Hg²⁺则对半胱氨酸的结合具有显著的优势. 虽然HCH基序对C8 与金属配位至关重要,一些远端的其它氨基酸也可以参与C8 与银离子的配位,这可能与CTR1 在摄取Ag⁺过程中的金属转移机制相关. 这些结果为理解hCTR1 蛋白摄取重金属离子的作用机制提供了必要的信息.     

Synthesis of crownophanes possessing three pyridine rings

Novel crownophanes with three pyridine moieties (pyridinocrownophanes 4 and 5) were prepared by means of intramolecular [2+2] photocycloaddition of vinylpyridine derivatives. In the liquid-liquid extraction of heavy metal cations, 4 and 5 exhibited high efficiency toward Ag⁺. Comparing the high extractability and complexing stability constant for Ag⁺ to those of the corresponding pyridinocrownophanes 2 and 3 and observing the ¹H NMR spectra in the presence of Ag⁺, the ethereal oxygen atoms and the three nitrogen atoms were found efficiently and cooperatively to act as ligating sites.     

Association constants of dibenzo[3n + 2]crown-n ethers using steady-state fluorescence spectroscopy

The steady-state fluorescence spectra of cation complexes of fluorophore macrocyclic ethers have been studied for the estimation of 1:1 association constants, and perchlorate salts of Li⁺, Na⁺, K⁺ Rb⁺ and Pb²⁺ complexing with dibenzo[23]crown-9, dibenzo[26]crown-10, and sym-dibenzo[26]crown-10, were investigated. The fluorescence emission maximum of the free and the various ligand/cation mixtures of complexed crown ethers were measured at room temperature in AN. The concentrations of chromophore crown ether were obtained from nonlinear calibration plots. The 1:1 stoichiometry of association constants (K_ass) were calculated using the equation, 1/K_ass [L_o] = (1 − nP)ⁿ(1 − m)^m/P with linear best fit of plots depending on 1/[L_o] where P = P_C/[1 + (m − 1)P_C] and P_C is the mole fraction of n/m ratio of the complexed ligand. The association constants of cations, K_ass, displayed the cation selectivities depending on the cation radii and the macrocyclic ether size, and Pb⁺ was found to give the strongest association with such crown ethers.     

Synthesis of crowned phenoxazine derivatives

Summary 16H-2,5,8,11,14-Pentaoxacyclopentadecano[2,3-a]phenoxazin-16-one, its 17-bromo analogue and 16-hydroxy-2,5,8,11,14-pentaoxacyclopentadecanophenoxazine were prepared by the reaction of 1,4-quinone of benzo[15]crown-5 or its dibromide with 2-aminophenol. Dehalogenation of the bromophenoxazinone was also investigated.

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Synthese von Kronen-Phenoxazin-Derivaten (Kurze Mitt.)

Zusammenfassung 16H-2,5,8,11,14-Pentaoxacyclopentadecano[2,3-a]phenoxazin-16-on, sein Brom-Analog und 16-Hydroxy-pentaoxacyclopentadecanophenoxazin wurden mittels der Reaktion des 1,4-Chinons von Benzo[15]krone-5 oder dessen Dibromid mit 2-Aminophenol hergestellt. Die Dehalogenierung von Bromphenoxazinon wurde ebenfalls untersucht.

     

An Efficient Way for the Recognition of Zinc Ion via the Fluorescence Enhancement

This study concentrates on the spectral and complexing properties of a tetraoxycalix[2]arene[2]triazine derivative bearing two bipyridines (Calix‐BIPY2) in a mixture of acetonitrile:chloroform (4:1, V:V). The results show that Calix‐BIPY2 has a highly selectivity and sensitivity towards Zn²⁺ over various competing cations (K⁺, Cu²⁺, Cd²⁺, Co²⁺, Fe²⁺, Hg²⁺, Ag⁺, Al³⁺ and Pb²⁺). The complexation of Zn²⁺ induces a remarkable fluorescence enhancement due to combination effects of the binding strength, electron spins state of metal ions, photoinduced charge transfer (PCT) and the rigidity of the complexing unit offered by calixarene‐based hosts.     

Novel Macrocycles. Part 6. Synthesis, Structures and Cation Binding from Optical Spectroscopy of 9,10-Anthraquinone-crown Ethers

The 9,10-anthraquinone-[12]crown-4, [15]crown-5 and [18]crown-6 derivatives were synthesized from 1,2-dihydroxy-9,10-anthraquinone and 1,8-dihydroxy-9,10-anthraquinone which were condensed with dihalides or ditosylates of polyethylene glycols in alkali carbonate/DMSO. The 9,10-anthraquinone derived polyoxacyclo-alkanes were characterized with IR, mass spectrometry, ¹H, ¹³C spectroscopy and elemental analysis. The cation binding properties were studied with UV-vis spectroscopy. The association constants found in acetonitrile were selectively dependent on the cation radius and macrocycle size as well as the molecular structures. The observed results from UV-vis studies, however, showed the stronger complexing role of 1,2-derived macrocycles compared to those of 1,8-derivatives. The theoretical conformational analysis and the energy optimisations of the 9,10-anthraquinone-macrocycles carried out with MM+ method explained the binding results.