Immunoaffinity for IgG antibodies of protein A labelled with 4,7-bis(chlorosulfophenyl)-1,10-phenanthroline-2,9-dicarboxylic acid

Summary Protein A was covalently labelled with 4,7-bis-(chlorosulfophenyl)-1,10-phenanthroline-2,9-dicarboxylic acid in several molar ratios. The binding affinity for IgG and the delayed fluorescence of the corresponding complexes with Eu(III) were determined for each labelled compound. The immunoaffinity decreased slowly with increase in ratio of the label. A better immunoaffinity/labelling ratio was obtained by coupling protein A to the chelate via bovine serum albumin. A suitable ratio of chelating agent to protein A for producing a universal marker to be used in time-resolved fluoroimmunoassays can be determined.     

Macrocyclic polyether- and polythioether-diesters and dithioesters from 1,10-phenanthroline-2,9-dicarboxylic acid

The synthesis of nine macrocyclic polyether- and polythioether-diesters 9–13 and dithioesters 14–17 derived from 1,10-phenanthroline-2,9-dicarboxylic acid are reported. The macrocycles were prepared under conditions of high dilution in the absence of metal templates in consistently good yields and their structures were confirmed by ¹H and ¹³C nmr spectroscopy. A macrocyclic phenanthroline-pyridine tetraester 18 is also recorded.     

Method of labeling antibodies with europium(III)-4,7-bis(chlorosulfophenyl)-1,10-phenanthroline-2,9-di-carboxylic acid chelate.

On the basis of Eu(III)-4,7-bis(chlorosulfophenyl)-1,10-phenanthroline-2,9-di-carboxylic acid chelate (BCPDA) that was synthesized and characterized for time-resolved fluoroimmunoassay (TRFIA), Donkey anti-hepatitis B surface (anti-HBs) was labeled with BCPDA-Eu3+. Coomassie Brilliant Blue was used to determine the protein concentration and radio immunoassay (RIA) for detecting the biological activity in the labeled protein. Optimal conditions for the protein labeling were obtained by monitoring the reaction. Results suggested that the protein could be labeled with BCPDA under relatively moderate conditions. As a practical application, a protein-BCPDA-Eu3+ chelate was obtained by using BCPDA-protein that reacted with EuCl3 under certain conditions. Some properties of BCPDA and protein-BCPDA-Eu3+, such as absorption spectrum, emission spectrum and fluorescence lifetime, were discussed. The detection limit and the linear working range of the established method were also investigated.     

4,7-(氯磺酸基苯基)-1,10-菲啰啉-2,9-二羧酸-铕标记甲胎蛋白抗体

在合成BCPDA基础上 ,对甲胎蛋白抗体与BCPDA连接及与铕离子螯合条件进行了研究。BCPDA与甲胎蛋白抗体反应后 ,分离纯化最佳淋洗液为pH 9.1的 0 .1mol/L碳酸盐缓冲溶液 ,BCPDA用量为甲胎蛋白抗体量 (mol)的 12 0～ 16 0倍 ;反应时间为 30min。讨论了Eu3 + BCPDA AFP抗体螯合物的荧光光谱 ,最佳温育时间为6 0min ,体系pH值为 7.8的Tris HCl溶液。当Eu3 + 浓度为 10 -6mol/L时 ,BCPDA的检出限为 4 .3× 10 -11mol/L。     

A ratiometric fluorescent chemosensor, 1,10-phenanthroline-4,7-dione, for anions in aqueous-organic media

A new fluorescent chemosensor, 1,10-phenanthroline-4,7-dione (1), which is capable of the ratiometric sensing of anions in aqueous MeCN, was developed. Chemosensor 1 recognized an anion via two NH groups in the molecule, and showed a much higher affinity for F⁻ than that of 4-quinolone, which binds to an anion at one NH group of the molecule. Upon binding to F⁻, the intensity of the emission band ascribed to the complex of 1-F⁻ was drastically enhanced, while the emission intensity of unbound 1 gradually decreased. The changes in these two emission bands enabled the successful ratiometric sensing.     

Synthesis of transition metal complexes containing a Schiff base ligand derived from 1,10-phenanthroline-2,9-dicarboxaldehyde and 2-aminobenzenethiol

The synthesis of a new Schiff base containing 1,10-phenanthroline-2,9-dicarboxaldehyde and 2-aminobenzenethiol subunits is described. The reaction of 1,10-phenanthroline-2,9-dicarboxaldehyde with 2-aminobenzenethiol leads to the isolation of 2,9-bis(2-benzothiazolinyl)-1,10-phenanthroline (I) which undergoes rearrangement when reacted with cobalt, nickel, copper or zinc ions to produce complexes of the tautomeric Schiff base 2,9-bis[2-(2-mercaptophenyl)-2-azaethene]-1,10-phenanthroline (L). The [Cu(L)ClO₄][ClO₄] and [M(L)X₂] complexes (where M = Co(II), Ni(II) and Zn(II) and X = Br) were characterized by physical and spectroscopic measurements which indicated that the ligand is acting probably as a tetradentate N₄ chelating agent.     

Efficient synthesis of 2,9-disubstituted 8-hydroxyadenine derivatives

An efficient and general method for the synthesis of 2,9-disubstituted 8-hydroxyadenines, which are expected to have various biological activities, was realized. 5-Amino-4-cyano-2-hydroxyimidazoles(1) were prepared from aminomalononitrile and isocyanates as key intermediates. The condensation of 1a with amidines, imidates, guanidine, urea and thioureas afforded 8-hydroxyadenines (2-6) possessing various substituents at the 2-position. Furthermore, selective alkylation of 2-amino- and 2-hydroxyadenines (4 and 6) successively proceeded to give the corresponding 2-alkylamino- and 2-alkoxyadenines (5 and 7), respectively. 2-Alkylthioadenines (15) were prepared by an analogous reaction of 1a with benzoyl isothiocyanate and subsequent S-alkylation. The imidazoles 1 are most useful intermediates for the synthesis of 8-hydroxyadenine derivatives.     

The disodium salt of 1,10-phenanthroline-4,7-diphenyl-p-disulfonic acid as an analytical reagent. Study of precipitation reactions

A spectrophotometric study is presented on the formation of colored complexes: disodium salt of 1,10-phenanthroline-4,7-diphenyl-p-disulfonic acid/metallic ions. In this paper, the relationship existing between the ionic radius of the cation and stoichiometries of the complex or complexes formed is found, giving the values of the apparent constants obtained for each of them. The optimum pH of the reaction is also established, as well as its spectrophotometric parameters.     

Unusual metal ion selectivities of the highly preorganized tetradentrate ligand 1,10-phenanthroline-2,9-dicarboxamide: a thermodynamic and fluorescence study

Some metal ion complexing properties of the ligand PDAM (1,10-phenanthroline-2,9-dicarboxamide) in aqueous solution are reported. Using UV-visible spectroscopy to follow the intense π-π* transitions of PDAM as a function of metal ion concentration, log K(1) values in 0.1 M NaClO(4) and at 25 °C are, for Cu(II), 3.56(5); Ni(II), 3.06(5); Zn(II), 3.77(5); Co(II), 3.8(1); Mg(II), 0.1(1); Ca(II), 1.94(4); and Ba(II), 0.7(1). For more strongly bound metal ions, competition reactions between PDAM and EDTA (ethylenedinitrilo-tetraacetic acid) or tetren (1,4,7,10,13-pentaazatridecane), monitored following the UV spectrum of PDAM, gave the following log K(1) values in 0.1 M NaClO(4) and at 25 °C: Cd(II), 7.1(1); Pb(II), 5.82(5); In(III), 9.4(1); and Bi(III), 9.4(1). The very low log K(1)(PDAM) values for small metal ions such as Cu(II) or Zn(II) are unprecedented for a phen-based ligand (phen = 1,10-phenanthroline), which is rationalized in terms of the low basicity of the N donors of the ligand (pK(a) = 0.6) and the fact that PDAM has a best-fit size corresponding to large metal ions of ionic radius ~1.0 ?. Large metal ions with ionic radius ≥1.0 ? show large increases in log K(1) relative to their phen complexes, which in turn produces unparalleled selectivities, such as a 3.5 log units greater log K(1)(PDAM) for Cd(II) than for Cu(II). PDAM shows strong fluorescence in aqueous solution, suggesting that its carboxamide groups do not produce a fluorescence-quenching photon-induced electron transfer (PET) effect. Only Ca(II) produces a weak CHEF (chelation enhanced fluorescence) effect with PDAM, while all other metal ions tested produce a decrease in fluorescence, a CHEQ (chelation enhanced quenching effect). The production of the CHEQ effect is rationalized in terms of the idea that coordination of metal ions to PDAM stabilizes a canonical form of the carboxamide groups that promotes a PET effect.     

The synthesis of certain 4-mono- and 4,7 dihydroxy-1,10-phenanthrolines

Aminocrotonates and cinnamates formed by the action of ethyl acetoacetate and ethyl benzoylacetate on substituted 8-aminoquinolines have been cyclized to 4-hydroxy and 4,7-dihydroxy-1,10-phenanthrolines.     

A rapid synthesis of asymmetric alkyl- and aryl-2,9-disubstitued 1,10-phenanthrolines

The finding that alkyl- and aryllithium reagents add almost instantly to the N-C2/C9 bond of 1,10-phenanthrolines led us to the development of a reaction scheme where the C2 and C9 positions of 1,10-phenanthroline can be functionalized by two different alkyl or aryl groups in a one-pot reaction. Furthermore, the total synthetic and work-up time needed for the entire transformation from unsubstituted 1,10-phenanthrolines into asymmetric 2,9-disubstituted 1,10-phenanthrolines was under 2 h and produced very high yields.     

Efficient synthesis of substituted dihydrotetraazapentacenes

We describe a versatile and very efficient synthesis of previously unknown substituted 5,14-dihydro-5,7,12,14-tetraazapentacenes (DHTAPs). A structural study by NMR spectroscopy showed that the conjugated pi-system of the pentacyclic skeleton rearranges depending on the electronic effect of the substituent(s).     

Efficient synthesis of orthogonally protected anti-2,3-diamino acids

An asymmetric synthesis of anti-2,3-diamino acids is reported. The enolates of N,N-dibenzylated β³-amino esters were treated with di-tert-butyl azodicarboxylate (DBAD) to afford their N′,N″-di-Boc-2-hydrazino derivatives with excellent anti diastereoisomeric ratio. Final Boc removal and reductive cleavage of the hydrazino bond led to the expected 2,3-diamino esters having only one free amino group. In comparison with other asymmetric C-2 amination procedures, this method does not need the use of expensive chiral reagents and/or chiral auxiliaries, while leads to products which can be orthogonally protected.     

Complexation behavior of trivalent actinides and lanthanides with 1,10-phenanthroline-2,9-dicarboxylic acid based ligands: insight from density functional theory

We have investigated the complexation behavior of preorganized 1,10-phenanthroline-2,9-dicarboxylic acid (PDA) based ligands with trivalent lanthanides and actinides using density functional theory with various GGA type exchange-correlation functionals and different basis sets. New ligands have been designed from PDA through functionalization with soft donor atoms such as sulfur, resulting in mono-thio-dicarboxylic acids (TCA/TCA1) and di-thio-dicarboxylic acid (THIO). It has been found that selectivity in terms of complexation energy of actinides over lanthanides is the maximum with TCA1 where the metal-ligand binding is through the O atoms. This unusual feature where a softer actinide metal ion is bonded strongly with hard donor oxygen atoms has been explained using the popular chemical concepts, viz., Pearson's Hard-Soft-Acid-Base (HSAB) principle and the frontier orbital theory of chemical reactivity as proposed by Fukui. Detailed analysis within the framework of the HSAB principle indicates that the presence of softer nitrogen atoms in the phenanthroline moiety (which also act as donors to the metal ion) has a profound influence in changing the soft nature of the actinide ion, which in turn binds with the hard oxygen atoms in a stronger way as compared to the valence isoelectronic lanthanide ion. Also, the trends in the variation of calculated values of the metal-ligand bond distances and the corresponding complex formation energies have been rationalized using the Fukui reactivity indices corresponding to the metal ions and the donor sites. All the calculations have also been done in the presence of solvent. The "intra-ligand synergistic effect" demonstrated here for PDA or TCA1 with soft and hard donor centers might be very important in designing new ligands for selective extraction of various metal ions in a competitive environment. However, for TCA and THIO ligands with only soft donor centers, "intra-ligand synergism" may not be very efficient although reports are available demonstrating soft-soft inter-ligand synergism. Nevertheless, in the case of TCA and THIO complexes, a shorter Am-S bond distance in conjunction with lower metal ion charge and a higher percentage of orbital interaction energy corroborate the presence of a higher degree of covalency in Am-S bonds, which in turn may be responsible for selectivity towards Am(3+).     

4,7-二苯基-1,10-菲啰啉的合成研究

以4-苯基-8-硝基喹啉为起始原料,经还原得到4-苯基-8-氨基喹啉,再以I2/KI为氧化剂,在乙酸和盐酸的存在下,用Skraup法合成了4,7-二苯基-1,10-菲啰啉.化合物结构经IR和1H NMR得到了证实.实验研究得到了最佳的合成条件为:n(3-氯苯丙酮)∶n(4-苯基-8-氨基喹啉)=1.5∶1,I2/KI用量为8%,反应温度120℃,反应时间2.5 h.产品收率可达82%.     

Synthesis of some 2,9-disubstituted-1,10-phenanthrolines

A series of symmetrically disubstituted compounds, with substituents linked to the ring through a carbon atom, has been prepared from 2,9-dimethyl-1,10-phenanthroline. Nmr data are also reported.     

Efficient one-pot synthesis of substituted pyrazoles

An efficient, one-pot synthesis of substituted pyrazoles from enones, hydrazides, and halides was developed. In comparison with the classical Knorr pyrazole synthesis, this methodology gave a different type of product (R³≥R⁵). A range of substituted pyrazoles were prepared in good to high yields with complete regioselectivity.     

First anionic 1,10-phenanthroline-2,9-dicarboxylate containing metal complex obtained from a novel 1:1 proton-transfer compound: synthesis,characterization, crystal structure,and solution studies

The new 1,10-phenanthroline containing 1:1 proton-transfer compound LH(2), [pyda.H(2)](2+)[phendc](2-), was synthesized from the reaction of 2,6-pyridinediamine, pyda, and 1,10-phenanthroline-2,9-dicarboxylic acid, phendc.H(2), and characterized by elemental analysis, ES-Ms, IR, (1)H, (13)C NMR, and UV/vis spectroscopies. Subsequently, the first example of [phendc](2)(-) containing anionic complex [pyda.H](2)[Co(phendc)(2)].10H(2)O, was prepared, using the above novel proton-transfer compound, and structurally characterized by single-crystal X-ray diffraction. The complex crystallizes in the space group P2(1)/n of the monoclinic system with four molecules in a unit cell of dimensions a = 11.877(3) A, b = 31.473(9) A, c = 12.915(4) A, and beta = 116.223(5) degrees. The structure has been refined to a final value for the crystallographic R factor of 0.0524 based on 9021 observed independent reflections. The complexation reactions of pyda, phendc.H(2), and LH(2) with H(+) as well as LH(2) with Co(II) in aqueous solution were investigated by potentiometric pH titrations, and the equilibrium constants for all major complexes formed are described. The results are presented in the form of distribution diagrams revealing the concentrations of individual complex species as a function of pH. The results revealed that, at a pH range of 5.2-6.2, the major complex species is [(pyda.H)](2)[Co(phendc)(2)], similar to the isolated crystalline complex.