Multivalent macrocyclic hosts: histone surface recognition, guest binding, and delivery by cyclophane-based resorcinarene oligomers

As a new class of host for both specific proteins and hydrophobic molecular guests, cyclophane-based resorcinarene oligomers were designed on the basis of a molecular design that allows the assembly of four or 12 anionic resorcinarenes on a cyclophane skeleton. We prepared a cyclophane-based resorcinarene tetramer (4), constructed with a tetraaza[6.1.6.1]-paracyclophane skeleton and four resorcinarenes bearing heptacarboxylic acid residues that connect to the macrocycle through amide linkages. In addition, we prepared an extended analogical dodecamer (12), which was constructed with a pentakis(cyclophane) skeleton and 12 resorcinarenes. The cyclophane-based resorcinarene oligomers exhibited potent recognition capabilities toward histone, a small basic protein of eukaryotic chromatins. The binding constants (K) of cyclophane-based resorcinarene tetramer 4 and dodecamer 12 with histone were determined to be 1.3x107 and 8.4x107 M-1, respectively, by means of surface plasmon resonance measurements. The K values of 4 and 12 with histone were 31- and 200-fold larger than that of an untethered reference resorcinarene, reflecting the multivalency effects in resorcinarenes. In addition to that, cyclophane-based resorcinarene tetramer 4 and dodecamer 12 captured hydrophobic guests such as 6-p-toluidinonaphthalene-2-sulfonate, with respective binding constants of 2.4x103 and 2.5x104 M-1 in an aqueous HEPES buffer as evaluated by fluorescence spectroscopy. Furthermore, the resorcinarene oligomers were also found to act as guest carriers from the bulk aqueous phase to histone surfaces, as confirmed by fluorescence spectroscopy.     

Synthesis and cubic nonlinear optical behavior of phenyl and ferrocenyl-ended resorcinarene-based dendrimers

Dendrimers were synthesized with phenyl and ferrocenyl-ended groups joined by vinyl moieties. All the dendrons used for dendrimers synthesis had showed trans configuration. This configuration as well as the ‘cone’ conformation of the resorcinarenes was preserved in the dendrimers, as it was shown by ¹H NMR spectroscopy. The chemical structure and purity of the synthesized dendrimers were confirmed by ¹H and ¹³C NMR, FAB+, MALDI-TOF, electrospray mass spectra, and elemental analysis. Cubic nonlinear optical behavior of this first generation of resorcinarene dendrimers was studied. The χ⁽³⁾ values estimated from the THG Maker-fringe technique for the phenyl and ferrocenyl-ended resorcinarene dendrimers dispersed in thin solid films are of the order of 10⁻¹³ and 10⁻¹² esu, respectively.     

Synthesis and screening of bifunctional radiolabelled carborane-carbohydrate derivatives

A new bifunctional carborane ligand was prepared as a platform for the development of targeted molecular radioimaging and therapy agents. The carborane derivative was synthesized bearing a glucose substituent to increase the water solubility of the ligand and a benzoic acid group as a site for linking to amine containing targeting vectors. A convenient method to conjugate the ligand and the non-glycosylated analogue to amino groups was developed using simple active esters which were combined with a model amine generating two new N,N-diethyl(aminoethyl) benzamide derivatives. These were labelled with ¹²⁵I in good yield and the log P values measured for [¹²⁵I]-15 (log P = 0.82 ± 0.04) and [¹²⁵I]-16 (log P = 1.53 ± 0.01). The benzamides were also evaluated for their capacity to bind to B16F10 melanoma cells where the hydrophilic compound showed low binding while [¹²⁵I]-16 showed modest uptake (30.7 ± 2.2%) after 24 h.     

Silver-ion redox sensing based on colloid formation by gallate ester derivatives

Plasmon absorption of silver colloid, which was formed by reduction of silver ion with compounds bearing gallate ester groups in ethanol, was observed by absorption spectroscopy. The time-dependent absorption of silver colloid was found, which shows that the silver colloid is unstable and easy to aggregate. It seemed that a calixarene derivative bearing two gallate ester groups was the most suitable for determining silver ion. In order to prevent the silver colloid aggregation, poly(N-vinylpyrrolidone) (PVP) was added into the solution at a constant time after the preparation of sample solutions. In the calibration graph, the absorbance increased with increasing silver ion concentration, especially in the concentration range of 2.00 × 10⁻⁶ to 1.00 × 10⁻⁵ M. It is possible to determine silver ion concentrations using this method.     

Synthesis and structural characterization of metal complexes based on pyrazole/imidazolium chlorides

A series of imidzoalium salt, L · HCl, for the potentially bidentate pyrazole/N-heterocyclic carbene was synthesized. Reactions of a 2:1 mixture between L · HCl bearing bulky N-substitution and Ag₂O produced Ag(L)Cl, whereas a novel compound with unique stoichiometry AgL₂(AgCl)_0.5Cl was produced from L · HCl bearing N-methyl group under identical condition. Reactions of L · HCl with PdCl₂ produced zwitterionic Pd^IICl₃L · H. Selected structural determinations on L · HCl, Ag(L)Cl, AgL₂(AgCl)_0.5Cl, and Pd^IICl₃L · H revealed intriguing crystal chemistry in which the less-stable gauche rotamers were obtained exclusively. A preliminary application of the zwitterionic complexes, Pd^IICl₃L · H, in Heck coupling reaction of aryl bromide with n-butyl acrylate shows effective activity.     

Oligomerisation of ethylene to linear α-olefins by tetrahedral cobalt(II) precursors stabilised by benzo[b]thiophen-2-yl-substituted (imino)pyridine ligands

On activation by MAO, 2-(imino)pyridine cobalt dichlorides bearing a benzo[b]thiophen-2-yl substituent in the 6-position of the pyridine ring oligomerise ethylene to α-olefins with turn-over-frequencies as high as 1.5 × 10⁶ mol of C₂H₄ converted (mol of Co × h)⁻¹ and productivities as high as 3769 kg of oligomers (mol of Co × h × bar)⁻¹. Aldimine precursors are more active than ketimine analogues, yet ketimines give higher molecular weight oligomers.     

Ethylene polymerization promoted by dinuclear titanium p-tert-butylthiacalix[4]arene complexes

The dinuclear titanium p-tert-butylthiacalix[4]arene complexes 1 and 2 after activation with methylaluminoxane have been tested as homogeneous catalysts for the polymerization of ethylene. The results show that the catalytic activity of 1, although still poor, is higher than those of the related mononuclear titanium complexes bearing calix[4]arene as ligand. The molecular weight of the polyethylene produced are high (M_W up to 1.4 × 10⁶ Dalton) with broad molecular weight distribution. The polyethylenes have high melting point (133-142 °C) indicating a linear polymer microstructure which was confirmed by ¹³C NMR analysis.     

Anti to syn isomerization of oxacalix[4]arene bearing two methyl groups at the intra-annular distal positions

The thermal isomerization of anti to syn stereoisomers of oxacalix[4]arene bearing two methyl groups at the intra-annular distal positions was investigated by temperature-dependent NMR spectroscopy. The conversion followed a first-order kinetics, and very slowly proceeded at 473 K in nitrobenzene-d₅ with a half-life of 7.2 h. The free energy of activation (ΔG^≠ 139 kJ mol⁻¹) is much higher than those for the ring inversion of related calix[4]arene derivatives.     

Detection of cationic guest molecules by quenching of luminescence of a self-assembled host molecule consisting of terbium(III) and calix[4]arene-p-tetrasulfonates

By self-assembly in aqueous solution, calix- (CAS) and thiacalix[4]arene-p-tetrasulfonate (TCAS) formed luminescent complexes Tb^III·(CAS)₂ and Tb^III·TCAS, respectively, which were utilized as a host for cationic guests. Addition of 1-ethylpyridinium guest quenched luminescence of Tb^III·(CAS)₂ in accordance with the Stern-Volmer (SV) relation with a low detection limit (D.L.) of 5.94 × 10⁻⁸ M (S/N = 3, M ≡ mol dm⁻³). On the other hand, 1-ethylquinolinium quenched luminescence of Tb^III·TCAS most efficiently, affording a very low D.L. (6.71 × 10⁻¹⁰ M). The agreement of the SV coefficients obtained with luminescent intensity (K_SV,all = 6.74 × 10⁶ M⁻¹) and lifetime (K_SV,Tb = 6.50 × 10⁶ M⁻¹) implied that dynamic quenching of ⁵D₄ excited state of Tb^III was predominant in the quenching processes. The quenching rate was estimated to be k_q,Tb = 9.94 × 10⁹ M⁻¹ s⁻¹, which was as fast as diffusion-limited rate. Quenching of Tb^III·(CAS)₂ was also applied to detection of NAD⁺, with a D.L. of 2.78 × 10⁻⁷ M.     

Synthesis,characterization and ethylene oligomerization and polymerization of 2-(1H-2-benzimidazolyl)-6-(1-(arylimino)ethyl)pyridylchromium chlorides

A series of N^N^N tridentate chromium complexes (C1–C6) bearing 2-(1H-2-benzimidazolyl)-6-(1-(arylimino)ethyl)pyridine derivatives was synthesized and characterized by elemental and spectroscopic analysis along with single-crystal X-ray crystallography. X-ray crystallographic analyses reveal chromium complex C1 as a distorted six-coordinated octahedral geometry. On treatment with modified methylaluminoxane (MMAO), the chromium complexes exhibited high activities for ethylene oligomerization (up to 1.50 × 10⁶ g mol⁻¹ (Cr) h⁻¹) and polymerization (up to 2.06 × 10⁶ g mol⁻¹ (Cr) h⁻¹) at 10 atm ethylene pressure. Various reaction parameters were investigated in detail, and less steric hindrance and electron-withdrawing substituents of ligands enhance the catalytic activities of their chromium complexes.     

Synthesis, characterization and degradability of the novel aliphatic polyester bearing pendant N-isopropylamide functional groups

The synthesis, characterization, and degradability of the novel aliphatic polyester bearing pendant N-isopropylamide functional group are reported for the first time. 2-(N-Isopropyl-2-carbamoylethyl)cyclohexanone (CCH) was first synthesized by the Michael reaction of N-isopropylacrylamide with cyclohexanone and was subsequently converted into 6-(N-isopropyl-2-carbamoylethyl)-?-caprolactone (CCL) by the Baeyer-Villiger oxidation reaction using 3-chloroperoxybenzoic acid (mCPBA) as the oxidant. Finally, the novel functionalized poly(?-caprolactone) bearing the pendant N-isopropylamide functional groups, poly(6-(N-isopropyl-2-carbamoylethyl)-?-caprolactone-co-?-caprolactone)s (poly(CCL-co-CL)), were carried out successfully by bulk ring-opening polymerization of CCL and ?-CL initiated by Sn(Oct)₂. Poly(CCL-co-CL) were characterized by ¹H NMR, ¹³C NMR, SEC and DSC. The copolymer containing 9.1 mol% CCL formed flexible films and was used to study its degradability. A phosphate buffer (pH = 7.4) with temperature 37 °C was adopted to proceed the degrading study all through. Compared with poly(?-caprolactone), the hydrolytic degradation of poly(CCL-co-CL) was much faster, which is confirmed by the weight loss and change of intrinsic viscosity.     

Preparation and evaluation of solid-phase microextraction fibres based on functionalized latex nanoparticle coatings for trace analysis of inorganic anions

The use of a functionalized latex nanoparticle coating as a new sorbent phase for solid-phase microextraction (SPME) was examined. By means of electrostatic absorption onto ionized silanol groups, a fused-silica rod was coated with polymeric nanoparticles functionalized with quaternary ammonium groups. Optimum conditions for the preparation of the coated fibre are presented. The fibre was used for the extraction of a mixture of seven anions from water samples which are analysed by coupling the SPME fibre to an ion chromatographic system via a special interface. The results obtained proved the suitability of this novel coating as a new SPME fibre. A linear calibration for the target analytes was achieved over the concentration range from 5 μg L⁻¹ to 5 mg L⁻¹ (r² > 0.988), while limits of detection for these ions were all below 3.7 μg L⁻¹ (S/N = 3). The reproducibility of a single fibre (n = 4) under similar conditions was between 7 and 12%, while the fibre to fibre reproducibility (n = 5) was between 8.9 and 14%.     

Vinyl addition polymerization of norbornene catalyzed by β-iminoamine Ni(II) complexes/methylaluminoxane systems

Two nickel(II) complexes (A and B) bearing β-iminoamine ligands, [2-(ArNCH)-C₆H₄-NMe₂] (La, Ar = 2,6-i-Pr₂C₆H₃; Lb, Ar = 2,6-Me₂C₆H₃), were synthesized and characterized by elemental analyses and ¹H NMR. X-ray crystal structure of complex B reveals that the six-membered chelate ring adopts a envelope conformation, with nickel(II) atom deviating from the plane of backbone aromatic ring by 1.164 Å. In the presence of methylaluminoxane (MAO), both complexes showed moderate activities of 10⁵ g mol_Ni⁻¹ h⁻¹ for norbornene polymerization. β-iminoamine Ni(II)/MAO catalysts gave unimodal polymers (M_w, 3.16-8.02 × 10⁵ g/mol) with a relatively narrow MWD (M_w/M_n, 1.59-2.14), indicative of single-site catalyst behavior. The obtained polymers are vinyl-type polynorbornenes (PNBs), which are soluble in common solvents such as toluene, cyclohexane and dichlorobenzene.     

Synthesis of oligomers having a pendant dithienosilole unit and their applications to EL device materials

Oligomers bearing dithienosilole as a pendent were prepared by radical polymerization of the corresponding dithienosilole monomer using AIBN as an initiator. The resulting oligomers exhibited high solubility in common organic solvents and strong photofluorescences (Φ = 0.72-0.76) in THF which are a little higher than that of monomeric dithienosilole DTS(TMS)₂. Applications of the oligomers to EL devices as hole transporting materials were examined and the maximum electroluminance of 2140 cd/m² was obtained from a device composed of ITO/oligomer/Alq₃/Mg-Ag.     

Portable microfluidic system for determination of urinary creatinine

A simple, low cost and portable microfluidic system based on a two-point alkaline picrate kinetic reaction has been developed for the determination of urinary creatinine. The creatinine reacts with picric acid under alkaline conditions, forming an orange-red colour, which is monitored on PDMS microchip using a portable miniature fibre optic spectrometer at 510 nm. A linear range was displayed from 0 to 40 mg L⁻¹ creatinine (r² = 0.997) with a detection limit of 3.3 mg L⁻¹ (S/N = 3). On-chip absorbance signals are reproducible, with relative standard deviations (RSDs) of 7.1%, when evaluated with 20 mg L⁻¹ creatinine (n = 10). The standard curves in which the intra-run CVs (4.7-6.8%) and inter-run CVs (7.9%) obtained were performed on three different days and exhibited good reproducibility. The method was highly correlated with the conventional spectrophotometric method when real urine samples were evaluated (r² = 0.948; n = 15).     

Synthesis and photophysical behaviors of temperature/pH-sensitive polymeric materials. I. Vinyl monomer bearing 9-aminoacridine and polymers

A novel acrylic monomer bearing acridinyl group, acridine-9-N-acrylamide (Ac-9AA) was synthesized from 9-aminoacridine (9AA) and acryloyl chloride in the presence of triethylamine in dry dichloromethane (CCl₂) at room temperature. The synthesized Ac-9AA was identified by IR, MS and ¹H NMR spectra. Homopolymer of Ac-9AA was obtained using AIBN as a thermal initiator in THF under 65-70 °C and the average molecular weights (M_w) of poly(Ac-9AA) obtained was very low, being in the order of ca. 10³. Copolymer of Ac-9AA and acrylamide was synthesized with thermal initiator and poly(Ac-9AA-co-AM) was characterized by the method of IR, UV-vis and DSC. The photophysical behaviors of Ac-9AA and its polymers were explored by recording the fluorescence spectra in solution, solid and film. In addition, the pH and temperature dependence on fluorescence of the water-soluble poly(Ac-9AA-co-AM) were investigated in detail. The results showed that the relative fluorescence intensity of poly(Ac-9AA-co-AM) had an excellent linear response to temperature in the range of 0-60 °C. Moreover, the fluorescence intensity increased continuously from low pH to high pH while the excitation maxima at 388 nm and emission maxima at 400 nm had redshift after the addition of HCl or NaOH, which results from the fact that the predominance of tautomeric forms of Ac-9AA changed at different medium. This investigation may provide a convenient way to prepared multifunctional macromolecule biomaterial bearing aminoacridine to probe pH and temperature in biological system.     

Pentacene precursors for solution-processed OFETs

15-Acetoxy- and 15-hydroxy-6,13-dihydro-6,13-ethanopentacenes sublimed over 300 °C and no pentacene was formed below the temperature. The precursors bearing chlorinated epithiomethano bridges suffered complicated decomposition to give oligomeric pentacene derivatives. The precursor bearing an epithio-oxomethano bridge underwent smooth and clean conversion to pentacene by heat or light. An organic field-effect transistor fabricated by the spin-coating method of the precursor followed by light irradiation at 120 °C showed a good FET performance of μ=2.5×10⁻² cm² V⁻¹ s⁻¹ and on/off ratio=3.8×10⁴.     

Tris(2,2'-bipyridyl)ruthenium(II) electrochemiluminescence sensor based on carbon nanotube/organically modified silicate films

In this paper, a novel electrochemiluminescence (ECL) sensor was constructed to determine herring sperm (HS) double-stranded (ds) DNA. Tetramethoxysilane and dimethyldimethoxysilane were selected as co-precursors to form an organically modified silicate (ORMOSIL) film for the immobilization of multiwall carbon nanotubes (MWNTs) wrapped by poly(p-styrenesulfonate) (PSS), and then Tris(2,2′-bipyridyl)ruthenium(II) (Ru(bpy)₃²⁺) was successfully immobilized on a glassy carbon electrode via ion-association. PSS was employed to increase the conductivity of the ORMOSIL film and disperse the cut MWNTs, which were cut and shortened in a mixture of concentrated sulfuric and nitric acids, in the film. It was found that MWNTs could adsorb Ru(bpy)₃²⁺ and acted as conducting pathways to connect Ru(bpy)₃²⁺ sites to the electrode. MWNTs also played a key role as materials for the mechanical and thermal properties. The ECL performance of this modified electrode was evaluated in a flow injection analysis (FIA) system, and the detection limit (S/N = 3) for HS ds-DNA was 2.0 × 10⁻⁷ g mL⁻¹ with a linear range from 1.34 × 10⁻⁶ to 6.67 × 10⁻⁴ g mL⁻¹ (R² = 0.9876). In addition, the ECL sensor presented excellent characteristics in terms of stability, reproducibility and application life.     

Synthesis and properties of conducting organic/inorganic polyurethane hybrids

A series of polyurethane/polyaniline/silica organic/inorganic hybrids were synthesized via the conventional polyurethane (PU) prepolymer technique. Amine-endcapped polyaniline (PANI) with low molecular weight and higher solubility was firstly synthesized. This PANI oligomer was then used together with nano-silica bearing silanol groups as chain extenders to prepare the conducting polyurethane hybrids. The polyurethane hybrids were designated as PU-xPANI-ySiO₂ (x + y = 1). For comparison, the urethane-aniline block copolymer and the PU/silica hybrid were designated as PU-PANI and PU-SiO₂, respectively.The structures of PU-PANI, PU-SiO₂ and conducting polyurethane hybrids were confirmed by FT-IR, solid-state ¹³C, and ²⁹Si NMR spectra. In nano-silica containing organic/inorganic conducting polyurethane hybrids, UV-vis spectra revealed the maximum absorption bands similar to that of PU-PANI. X-ray diffraction patterns indicated that these samples are typical of semicrystalline/amorphous materials. SEM image of PU-0.5PANI-0.5SiO₂ showed that PANI was dispersed homogeneously and interconnected continuously in the insulating PU-silica matrix. TGA results of the polymer hybrids exhibited higher thermal stabilities and lower decomposition rates than that of PU-PANI both in nitrogen and air. Differential scanning calorimetry (DSC) studies indicated that the polyurethane hybrids had higher glass-transition temperatures (T_g) with the increase of PANI, but lower than that of PU-PANI. Stress-strain curves for all of the polyurethane hybrids showed the elastomeric behavior of typical polyurethanes. The surface resistivity values of all hybrids were about 10⁸ ∼ 10¹⁰ Ω/sq. and might meet the requirement of the anti-electrostatic materials.     

Mechanistic investigation of the thermal decomposition of Biphen(OPi-Pr)PtEt2: An entrance into C-C single bond activation?

Biphen(OPi-Pr) and (COD)PtCl₂ give Biphen(OPi-Pr)PtCl₂ which upon treating with ethyl Grignard forms Biphen(OPi-Pr)PtEt₂. The thermal decomposition of Biphen(OPi-Pr)PtEt₂ was investigated in the temperature range of 353-383 K. The clean and quantitative formation of the Pt(Ethene) adduct was observed. X-ray structures of a molecule in the solid state of all three reaction products and two further related complexes with phenyl fingers instead of i-Pr have been determined. For the complexes with i-Pr fingers a decisive deviation from a square plane is observed in contrast to the complexes with phenyl fingers. The P-Pt-P angle increases from about 95° in Biphen(OPi-Pr)PtCl₂ to about 120° in Biphen(OPi-Pr)Pt(Ethene), forcing the bridging C-C single bond of the biphenyl fragment as near as 4.17 Å to the Pt center. No through-space coupling between the bridging C atoms and the Pt center could be observed in ¹³C NMR spectroscopy. No bond lengthening of the bridging C-C single bond in the biphenyl fragment was observed in Biphen(OPi-Pr)Pt(Ethene) in comparison to the precursor complexes. The thermal decomposition of Biphen(OPi-Pr)PtEt₂ can be described by a first-order kinetic and the activation parameters were determined (temperature range: 353-383 K; ΔH^‡ = 173.8 ± 16.2 kJ/mol and ΔS^‡ = 104.7 ± 44.1 J/(mol K)). The reaction kinetics were also measured for perdeuterated ethyl groups yielding in a kinetic isotopic effect of 1.56 ± 0.14 which was almost temperature-independent. Selective deuteration at α and β position of the ethyl group, respectively, showed that β-H elimination takes place fast in comparison to the complete thermolysis. In the temperature range of 333-353 K only a scrambling of the deuterium atoms was found without further decomposition (temperature range: 333-353 K; Δ_scramH^‡ = 76.1 ± 15.2 kJ/mol, Δ_scramS^‡ = −80.7 ± 45.5 J/(mol K) for Biphen(OPi-Pr)PtEt₂-d⁶). The ethene is not lost during the scrambling process. The scrambling process is connected with a primary KIE decisively larger than 1.56. Biphen(OPi-Pr)Pt(Ethene) exchanges the coordinated ethene with ethene in solution as proven by labeling experiments. Both a dissociative and an associative mechanism could be shown to take place as ethene exchange reaction by means of VT¹H NMR spectroscopy via line shape analysis (temperature range: 333-373 K; Δ_assH^‡ = 26.9 ± 29.6 kJ/mol, Δ_assS^‡ = −148.0 ± 87.5 J/(mol K), Δ_dissH^‡ = 86.0 ± 6.5 kJ/mol, Δ_dissS^‡ = 5.4 ± 17.8 J/(mol K)). The Pt(0) complex formed during the dissociative loss of ethene activates several substrates among them: O₂, H₂, H₂SiPh₂ via Si-H activation, MeI presumably via forming a cationic methyl adduct and ethane via C-H activation but it was proven that the bridging C-C single bond of the biphenyl fragment is not even temporarily broken. The materials were characterized by means of ¹H NMR, ¹³C NMR, ³¹P NMR, ¹⁹⁵Pt NMR, EA, MS, IR, X-ray analysis and polarimetric measurement where necessary.