Efficient synthesis and anion recognition of a colorimetric preorganized tripodal thiourea compound

A preorganized colorimetric tripodal thiourea receptor was synthesized in high yield utilizing a thiol-ene reaction as a primary step. The interaction of the receptor with dihydrogen phosphate, acetate, chloride, and fluoride anions was investigated using UV–vis. and ¹H NMR spectroscopic titration techniques. The binding stoichiometry of the receptor with dihydrogen phosphate and acetate was found to be 1:2, and 1:1 with chloride and fluoride. The binding constants for the receptor and dihydrogen phosphate, acetate, chloride, and fluoride were determined using HypNMR2008 and HypSpec.     

硫脲类阴离子受体的设计合成与阴离子识别

硫脲类化合物具有生物活性,是优良的氢键供体,与阴离子特别是含氧阴离子形成氢键配合物。本文设计合成了系列二苯基硫脲衍生物,通过取代基效应调控硫脲衍生物分子内电转移过程,阴离子与硫脲基团结合后,增强了分子内供体的给电子能力,进一步促进电荷转移过程,据此识别不同的阴离子。由于主体分子与阴离子间形成氢键的能力及阴离子碱性的差异,可达到选择性结合的目的。     

Amide-based tripodal receptors for selective anion recognition

The binding properties of ethylester derivative of p-tetraphenyl tetrahomodioxacalix[4]arenes (1) towards alkali, alkaline-earth, transition and heavy metal cations using UV-absorption spectrophotometry and ¹H-NMR spectroscopy are reported.     

Urea vs. thiourea in anion recognition

Neutral anion receptors (LH) form stable 1 : 1 H-bond [LH...X]- complexes with carboxylates, halides and phosphate (X-). Some of the [LH...X]- complexes, in presence of an excess of X-, release an HX fragment, with formation of [HX2]- and the deprotonated receptor L-. The tendency towards deprotonation increases with the acidity of the receptor and with the stability of the [HX2]- self-complex. Thus, the more acidic thiourea containing receptor deprotonates in the presence all the investigated anions except chloride, whereas the less acidic urea containing receptor undergoes deprotonation only in the presence of fluoride, due to the high stability of [HF2]-.     

DFT方法研究基于脲及硫脲衍生物的阴离子受体

采用密度泛函理论(DFT)模拟了两个基于脲和硫脲衍生物的受体分子对卤素阴离子的识别过程.结构优化表明基于脲衍生物的受体分子1最稳定构象为"反反"构象,分子内部形成稳定的C~α-H…O=C分子内氢键;而基于硫脲衍生物的受体分子2,不能形成分子内氢键,最稳定构象为"反顺"构象.受体1、2与卤素阴离子F~-、Cl~-可形成稳定的双氢键复合物,在此过程中,受体2经历了由"反顺"构象到"反反"构象的异构化过程.结构和能量分析表明,1、2受体分子与F~-离子间的氢键强度远大于其与Cl~-离子间的氢键;另一方面,受体2与阴离子间的氢键明显强于受体1,这是由于硫脲基N-H键具有更强的酸性.此外,对受体分子、氢键复合物及去质子化产物的吸收光谱计算结果表明,受体与F~-离子作用可产生明显的吸收光谱红移,而与Cl~-离子的作用对光谱影响较小.     

Molecular recognition of fluoride anion: benzene-based tripodal imidazolium receptor

A benzene-based tripodal imidazolium receptor utilizing the strong (C-H)(+)...X(-) hydrogen bonding interaction between imidazolium moieties and halide anions is extensively investigated both theoretically and experimentally. Ab initio calculations predict that this receptor has a very high affinity for fluoride ion (F(-)). The association constant and free energy gain of the N-butyl receptor 2 for F(-) in acetonitrile were measured to be 2.1 x 10(5) M(-1) and -7.25 kcal/mol, respectively, showing that the receptor has a high affinity for F(-) in highly polar organic solvents.     

A conformationally flexible, urea-based tripodal anion receptor: solid-state, solution, and theoretical studies

Tripodal tris(urea) cationic receptors 1 and 2 containing p-tolyl or octyl substituents, respectively, have been synthesized, and their association behavior with anionic guests has been studied via a variety of methods. The receptors are based around a hexasubstituted aryl core and contain both urea and pyridinium functionalities. For 1:1 complexes, anions reside within the central cavity of the host species, held by hydrogen bonds from both NH and CH donors. The following host-anion complexes have been characterized by X-ray crystallography: 1-(Br)3, 1-(PF6)3.2(CH3)2CO, and 1-(NO3)1.5(PF6)1.5. Each structure contains the receptor in a significantly different geometry, highlighting the anion-dependent conformational flexibility of 1. Solution 1H NMR spectroscopic titrations have shown the two host species to display significant affinity for both halides and hydrogen sulfate and strongly suggest the persistence of CH...X- interactions despite the presence of "stronger" NH donor groups. Variable-temperature 1H NMR studies on the more soluble octyl derivative 2 show that there is a distinct change in conformation associated with the formation of a 1:1 host/guest complex. Computations using density functional theory (with the B3LYP functional) have been employed to aid in understanding the geometry of the 1:1 host/chloride complexes of 1 and 2. These experiments suggest that the lowest energy conformation for 1-Cl is one in which the ureidopyridinium arms are orientated upward forming a cavity that is sealed by CH...pi interactions, effectively forming a unimolecular capsule, whereas for 2 a less symmetrical "2-up, 1-down" geometry is favored.     

Iminophosphorane-based synthesis of multinuclear ferrocenyl urea, thiourea and guanidine derivatives and exploration of their anion sensing properties

One-flask preparation of bisferrocenyl-substituted urea and thiourea and trisferrocenyl-substituted guanidine have been achieved from the iminophosphorane derived from ferrocenemethyl azide by using aza-Wittig reactions with carbon dioxide and carbon disulfide. Electrochemical studies indicate that there is no electronic communications between the peripheral ferrocene units and only one reversible redox wave is observed, which underwent a remarkable cathodic shift (ΔE_1/2=100-170 mV) in the presence of dihydrogenphosphate anion.     

Synthesis, structures and theoretical investigation of

The silylated derivative of thiophosphoric acid (S)P(SSiMe3)3 is used as a convenient starting compound for the synthesis of multinuclear Cu and Au cluster complexes. (S)P(SSiMe3)3 reacts with CuCI/PPh3 and [AuCClPPh3] to give the following compounds: [Cu4(P2S6)(PPh3)4] (1), [Cu6(P2S6)Cl2-(PPh3)6] (2) and [Au4(P2S6)(PPh3)4](3). According to X-ray structure determination, these compounds contain P2S6(4-) ions, in which S atoms act as ligands for Cu+ and Au+ ions. Although 1 and 3 have the same stoichiometry, bonding of the metal ions to the P2S6 skeleton displays small but remarkable differences. Au is twofold coordinated, whereas Cu shows a threefold coordination. Ab initio calculations have been carried out to rationalise these structural differences. The theoretical treatment of the corresponding Ag compound indicates the latter to be less stable.     

Recognition of carboxylate and dicarboxylates by azophenol–thiourea derivatives: a theoretical host–guest investigation

Geometries of azophenol–thiourea derivative complexes with acetate, oxalate, malonate, succinate, glutarate, adipate, pimelate, suberate and azelate were carried out using the integrated MO:MO method. The binding and complexation energies of these complexes were derived from the ONIOM(B3LYP/6-31G(d):AM1) calculations. The relative stabilities of the complexes of azophenol–thiourea derivatives with carboxylate guests are reported. The binding interactions of the azophenol–thiourea receptor 1, 2 and carboxylate guests are described as multipoints hydrogen bonding, where the amine and phenolic hydrogen atoms of receptors act as hydrogen bond donors in complex with acetate and all amine-hydrogen and phenolic hydrogen atoms act as hydrogen bond donors in complex with dicarboxylate guests. Thermodynamic properties of binding interactions between receptors 1, 2 and their preorganizations and complexations are also reported.     

A theoretical investigation on the structures,densities, detonation properties,and pyrolysis mechanism of the nitro derivatives of phenols

The nitro derivatives of phenols are optimized to obtain their molecular geometries and electronic structures at the DFT‐B3LYP/6‐31G* level. Detonation properties are evaluated using the modified Kamlet–Jacobs equations based on the calculated densities and heats of formation. It is found that there are good linear relationships between density, detonation velocity, detonation pressure, and the number of nitro and hydroxy groups. Thermal stability and pyrolysis mechanism of the title compounds are investigated by calculating the bond dissociation energies (BDEs) at the unrestricted B3LYP/6‐31G* level. The activation energies of H‐transfer reaction is smaller than the BDEs of all bonds and this illustrates that the pyrolysis of the title compounds may be started from breaking O? H bond followed by the isomerization reaction of H transfer. Moreover, the C? NO₂ bond with the smaller bond overlap population and the smaller BDE will also overlap may be before homolysis. According to the quantitative standard of energetics and stability as a high‐energy density compound, pentanitrophenol essentially satisfies this requirement. In addition, we have discussed the effect of the nitro and hydroxy groups on the static electronic structural parameters and the kinetic parameter. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

Structures of urea/thiourea 1,3-disubstituted thia[4]calixarenes and corresponding monofunctional receptors and their anion recognition properties

Two thiacalix[4]arenes in 1,3-alternate conformation functionalized by two (CH₂)₂NH(C=X)NHC₆H₄-NO₂-p groups (X = S,O) as well as two related monofunctional receptors MeO(CH₂)₂NH(C=X)NHC₆H₄-NO₂-p were prepared and characterized by X-ray crystal structures. The thioureido and ureido derivatives have E,Z and E,E conformations respectively both in monofunctional receptors and thiacalixarenes. The thiacalixarene attached thiourea groups are well separated from each other, but respective urea groups are much closer to each other and have mutual parallel orientation making the bisurea derivative a better preorganized receptor as compared to bisthiourea. Binding of Cl^?, F^?, H₂PO₄ ^? and AcO^? anions in chloroform and DMSO was studied by spectrophotometric and NMR titrations. In chloroform both bisurea and bisthiourea thiacalix[4]arenes bind anions 3–5 times stronger than corresponding monofunctional compounds in spite of better preorganization of the urea derivative. In DMSO simultaneous deprotonation of ureido NH groups of receptors and hydrogen bonding reactions are observed. Deprotonation by H₂PO₄ ^? is accompanied by a strong association between liberated H₃PO₄ and H₂PO₄ ^? (log K = 3.9). For hydrogen bonding associations the binding constants of H₂PO₄ ^? and AcO^? with bisurea thiacalixarene are up to two orders of magnitude larger than those with corresponding monofunctional receptor, but with bisthiourea thiacalixarene the effect is less than two-fold. Thus in this solvent in contrast to chloroform the preorganization is an important factor.     

Combined study of anion recognition by a carbazole-based neutral tripodal receptor in a competitive environment

Anion recognition studies have been carried out on a series of neutral synthetic receptors in which carbazole-2-carboxamide has been used as building block. Different ligands which include one to three carbazole units in their structure have been prepared. Binding experiments have been performed under competitive conditions in DMSO and DMSO-water solutions. The tripodal receptor offered a better host-guest association due to the synergistic effect of a well arranged set of hydrogen bonds. A selective response towards the biologically important pyrophosphate anion has been achieved. This selectivity is enhanced when studies are carried out with an increasing water content, which gets as high as 20% (v/v) in NMR experiments. The significance of this result lies in the use of a neutral receptor which exclusively interacts with the anionic guest through hydrogen bonding. The influence of multiple equilibria in the studied system has been analysed. Several techniques ((1)H NMR, (31)P NMR, mass spectrometry, diffusion-NMR, ITC, absorption and emission spectroscopy) have been employed to get a better understanding of the different processes taking place in solution for the evaluated receptors.     

亚胺型比色探针的制备及阴离子识别性能研究

合成了两种亚胺型阴离子识别受体:2-[(2-羟基-5-硝基亚苄基)氨基]4-硝基苯酚(R1)和2-[(蒽-9-亚甲基)氨基]-4-硝基苯酚(R2),其结构经核磁氢谱和红外表征.在紫外光谱实验中,受体R1和R2分别在乙腈和DMSO溶液中可以高选择性识别F-,AcC-和H2PO4-,同时观察到明显的颜色改变.实验结果表明,...     

Novel synthetic aromatic thiourea derivatives and investigations on their cytotoxic potential efficacy

Aromatic thiourea derivatives were synthesized by standard reactions from isothiocyanates in high yield. An efficient one-pot synthesis of primary amine with carbon disulfide involving the intermediate dithiocarbamate conversion using T₃P (propane phosphonic anhydride) to isothiocyanate is reported. Newly synthesized compounds showed excellent luminescence property. Cytotoxic investigation with different human cancer cell lines showed IC₅₀ values varying from of 17 to 40 μM for N-phenethyl-3,4-dihydroisoquinoline-2(1H)-carbothioamide (SCR172) among other molecules. Increase in Sub G1 population and increased depolarisation of mitochondria were evident in cells treated with SCR172, suggesting its role as a cancer therapeutic agent. This provides a lead structure for further synthetic modifications.     

缩氨基硫脲受体的合成及阴离子识别规律研究

设计合成了新型缩氨基硫脲受体分子,利用紫外-可见吸收光谱考察了其对F-,Cl-,Br-,I-,CH3COO-,HSO4-,H2PO4-和NO3-8种阴离子的识别作用。当加入F-,CH3COO-,H2PO4-时,溶液颜色立刻由无色转变为黄色,而加入其它阴离子则无变化,从而实现对这3种阴离子的裸眼检测。通过计算可知,两种受体分子对CH3COO-和H2PO4-的识别作用呈现出有规律的变化,即对同种阴离子:受体B1受体B2,且主客体间形成1∶1的配合物。质子溶剂效应实验证明了受体分子与阴离子之间以氢键作用方式相结合。     

A simple thiourea based colorimetric sensor for cyanide anion

A simple and easily synthesized colorimetric anion sensor, based on a thiourea moiety as a binding subunit on a 1,2-cyclohexane backbone and a p-nitrophenyl group as a signaling unit, has been synthesized in a one step procedure. The selective sensing of anions, particularly cyanide, has been investigated in DMSO by UV-vis titration, ¹H NMR titration techniques and through ‘naked eye’ observation experiments.     

Carbohydrate recognition of symmetrical tripodal receptor type tris(2-aminoethyl)amine derivatives

Carbohydrate recognition of some bioactive symmetrical tripodal receptor type tris(2-aminoethyl)amine (TAEA) derivatives was investigated. In calorimetric experiments, the highest binding constant (Ka) of compound C (C₃₅H₄₉N₅O₄S) with methyl α-d-mannopyranoside was Ka = 858 M^?1 with 1:1 stoichiometry. Formation of hydrogen bonds in binding between symmetrical tripodal receptor type compound C and sugars was suggested by the large negative values of ?H° (=?34 to ?511 kJ mol^?1). In a comparison of each set of α- and β-anomers of some monosaccharides (methyl α/β-d-galactopyranoside, methyl α/β-d-glucopyranoside, and methyl α/β-l-fucopyranoside), compound C showed that the binding constant of β-anomer was larger than that of the corresponding α-anomer, indicating higher β-anomer selectivity. The calculated energy-minimized structure of the complex of compound C with guest methyl α-d-mannopyranoside is also presented. The experimental results obtained from this work indicated that symmetrical tripodal receptor type TAEA derivative C has a lectin-like carbohydrate recognition property.     

Adsorptive stripping voltammetric determination of thiourea and thiourea derivatives

Adsorptive stripping voltammetry of thiourea, α-naphthylthiourea and diphenyl-thiourea is discussed. In perchlorate solution, these compounds are adsorbed at the hanging mercury drop electrode at positive potentials (or at open circuit) and can be stripped in a cathodic scan. Detection limits are 2.5 ng l^?1 for thiourea, 80 ng l^?1 for α-naphthylthiourea and 50 ng l^?4 for diphenylthiourea. The method is applicable in the determination of thiourea in cattle-feed and in the direct analysis of urine.