Highly diastereoselective chemoenzymatic synthesis of (2′R)- and (2′S)-2′-deoxy[2′-H]guanosines

In an effort to develop an efficient synthetic method of highly diastereoselective (2′R)- and (2′S)-2′-deoxy[2′-²H]guanosines, chemoenzymatic conversion was investigated. The synthesis of (2′R > 98% de)-2′-deoxy[2′-²H]guanosine was achieved by biological transdeoxyribosylation using (2′R > 98% de)-2′-deoxy[2′-²H]uridine, 2,6-diaminopurine, and Enterobacter aerogenes AJ-11125, followed by treatment with adenosine deaminase. (2′S > 98% de)-2′-Deoxy[2′-²H]guanosine was synthesized from (2′S > 98% de)-2′-deoxy[2′-²H]uridine and 2,6-diaminopurine using thymidine phosphorylase and purine nucleoside phosphorylase instead of E. aerogenes AJ-11125.     

Synergistic liquid-liquid extractive spectrophotometric determination of gold(III) using 1-(2′,4′-dinitro aminophenyl)-4,4,6-trimethyl-1,4-dihydropyrimidine-2-thiol

Synergistic liquid-liquid extractive spectrophotometric determination of gold(III) using 1-(2′,4′-dinitro aminophenyl)-4,4,6-trimethyl-1,4-dihydro pyrimidine-2-thiol [2′,4′-dinitro APTPT] has been described. Equal volumes (5 cm³) of the 2′,4′-dinitro APTPT (0.02 mol L⁻¹) in the presence of pyridine (0.5 mol L⁻¹) form an orange-red coloured ternary complex with gold(III) of molar ratio 1:1:1 at pH 1.8-2.4 with 5 min of shaking. The absorbance of coloured organic layer in 1,2-dichloroethane is measured spectrophotometrically at 445 nm against reagent blank. A pronounced synergism has been observed by the binary mixture of 2′,4′-dinitro APTPT and pyridine, which shows that the enhancement in the absorbance is observed in the presence of pyridine by the adduct formation in the organic phase. Beer's law was obeyed in the concentration range 2.5-20.0 μg mL⁻¹, with molar absorptivity and Sandell's sensitivity values of 8.7 × 10³ dm³ mol⁻¹ cm⁻¹ and 0.023 μg cm⁻² respectively. A repetition of the method was checked by finding relative standard deviation (R.S.D.) (n = 10) which was 0.17%. The composition of the gold(III)-2′,4′-dinitro APTPT-pyridine adduct was established by slope analysis, molar ratio and Job's method. The ternary complex was stable for more than 48 h. The influence of various factors such as pH, 2′,4′-dinitro APTPT concentration, solvent and pyridine on the degree of complexation has been established. A number of foreign ions tested for their interferences and use of suitable masking agents wherever necessary are tabulated, which show that selectivity of the method has been enhanced. The method is successfully employed for the determination of gold(III) in binary, synthetic mixtures and ayurvedic samples. The reliability of the method is assured by inter-comparison of experimental values, using an atomic absorption spectrometer.     

Syntheses and properties of complexes with bis(2,2′-bipyridyl)ruthenium(II) moieties coordinated to 4,4′:2′,2′′:4′′,4′′′-quaterpyridinium ligands

Eleven new complexes of the form cis-[Ru^II(bpy)₂(L^A)]⁴⁺ (bpy = 2,2′-bipyridyl; L^A = a pyridinium-substituted bpy derivative) have been prepared and isolated as their PF₆⁻ salts. Characterisation involved various techniques including ¹H NMR spectroscopy and MALDI mass spectrometry. The UV-Vis spectra show intense intraligand π → π^∗ absorptions and metal-to-ligand charge-transfer (MLCT) bands with two distinct maxima in the visible region. Small shifts in the MLCT bands correlate with the electron-withdrawing strength of the ligand L^A. Cyclic voltammograms show quasi-reversible or reversible Ru^III/II oxidation waves, and two or more ligand-based reductions with varying degrees of reversibility. The variations in the redox potentials correlate with changes in the structure of L^A, and also with the MLCT energies. Differential pulse voltammetry allows the first reduction process for two of the complex salts to be resolved into two peaks. Single-crystal X-ray structures have been solved for three of the new complex salts and also for a pro-ligand salt. Two carboxylate-functionalised compounds have been tested as photosensitizers on TiO₂-coated electrodes, but show only negligible efficiencies, in accord with expectations.     

2,2′,3,4-Tetrahydroxy-3′-sulpho-5′-nitroazobenzene for spectrophotometric determination of aluminium in pharmaceutical suspensions and granite

A selective and sensitive new spectrophotometric method has been developed for the determination of aluminium. 2,2′,3,4-Tetrahydroxy-3′-sulpho-5′-nitroazobenzene (tetrahydroxyazon SN) formed an orange chelate with aluminium at pH 4. Molar absorptivity of the complex in 1:2 is 5.46 × 10⁴ l mol⁻¹ cm⁻¹ at 479 nm. The method obeys Beer's law in the range of 0.005-1.079 μg ml⁻¹. The determination of aluminium is not interfered with by earth alkaline, alkaline elements, rare earth elements, halides, phosphates, sulphates, urea, ascorbic acid, Sn²⁺, Sr²⁺, Cr³⁺, Cd²⁺, Hg²⁺, or Mn²⁺. The proposed method is rapid and simple, and it has been successfully applied to the determination of aluminium in certified pharmaceutical suspension and granite.     

Synthesis and properties of 6,6′-dithienyl-4,4′-bipyrimidine and its hetero- and homo-leptic Ru(II) complexes

Hetero- and homo-leptic Ru(II) complexes of a new 4,4′-bipyrimidine ligand, th₂bpm (6,6′-di(2″-thienyl)-4,4′-bipyrimidine), have been synthesized and characterized. The parent ligand th₂bpm has electron rich thiophene units on the periphery of a bidentate ligand which is capable of binding to metal ions. The heteroleptic complex of th₂bpm [Ru(bpy)₂th₂bpm]²⁺ (bpy = 2,2′-bipyridine) exhibits a Ru-to-bpm metal-to-ligand charge transfer (MLCT) absorption centered at 547 nm and a Ru-to-bpy MLCT absorption centered at 438 nm. The assignment of the low energy absorption is supported by the relative ease of electrochemical reduction of the new complex as compared to [Ru(bpy)₃]²⁺. The homoleptic complex, [Ru(th₂bpm)₃]²⁺, exhibits a Ru-to-bpm MLCT absorption at slightly higher energy (544 nm). Both complexes are emissive at room temperature in fluid solution and 5 is one of the lowest energy emitters based on tris-bidentate Ru(II) complexes known (λ_max = 770 nm). The luminescence spectra is red-shifted compared to [Ru(bpy)₃]²⁺ and this effect is ascribed to the delocalization in the acceptor ligand.     

New active ruthenium(II) complexes based N3,N3′-bis(diphenylphosphino)-2,2′-bipyridine-3,3′-diamine and P,P′-diphenylphosphinous acid-P,P′-[2,2′-bipyridine]-3,3′-diyl ester ligands for transfer hydrogenation of aromatic ketones by propan-2-ol

The dimeric starting material [Ru(η⁶-p-cymene)(μ-Cl)Cl]₂ reacts with N3,N3′-bis(diphenylphosphino)-2,2′-bipyridine-3,3′-diamine, 1 and P,P′-diphenylphosphinous acid-P,P′-[2,2′-bipyridine]-3,3′-diyl ester, 2 ligands to afford bridged dinuclear complexes [C₁₀H₆N₂{NHPPh₂-Ru(η⁶-p-cymene)Cl₂}₂], 3 and [C₁₀H₆N₂{OPPh₂-Ru(η⁶-p-cymene)Cl₂}₂], 4 in quantitative yields. These bis(aminophosphine) and bis(phosphinite) based Ru(II) complexes serve as active catalyst precursors for the transfer hydrogenation of acetophenone derivatives in 2-propanol and especially 4 acts as a good catalyst, giving the corresponding alcohols in 99% yield in 20 min (TOF ? 280 h⁻¹).     

An experimental and DFT computational study of a novel zerovalent tetracarbonyl tungsten complex of 2-(2′-pyridyl)quinoxaline

Synthesis and characterization of the new complex W(CO)₄(2,2′-pq), (1), where 2,2′-pq = 2-(2′-pyridyl)quinoxaline, is presented. The non-symmetric ligand 2,2′-pq belongs to the general class of quinoxalines, which are natural products yielding a rich coordination chemistry. Complex (1) crystallizes in space group P2_1/n with α = 9.601(6) Å, b = 16.735(11) Å, c = 10.315(8) Å, Z = 4 and V = 1616.0(19) Å³. Although its structure resembles those of W(CO)₄(phen) and W(CO)₄(bpy), some distortions that stem from 2,2′-pq’s asymmetry are present. DFT calculations reveal a ground state consisting of HOMO, HOMO − 1 and HOMO − 2, mainly of metal and carbonyl character, while LUMO is diimine oriented. The bonding scheme of (1) is illustrated after its consideration as been consisted by two fragments, namely W(CO)₄ and 2,2′-pq, acting as a donor and acceptor of electron density, respectively. In that scheme, back-bonding interaction of the main core to 2,2′-pq is mainly related to the mixing of HOMO − 2 from W(CO)₄ moiety with LUMO from 2,2′-pq moiety. The performed TDDFT calculations, not only in the gas phase but also combined with the conductor like polarizable continuum model (CPCM), reveal that the lowest in energy highly solvatochromic transition of (1) can be ascribed as a HOMO − 2 → LUMO transition and it is better described as MLCT/LLCT, underlying the CO → diimine contribution. The solvatochromic behaviour of (1) is anticipated by DFT/CPCM calculations and is probed in detail by absorption and NMR spectroscopy. The correlation of the lowest-energy-band maximum to the dipole moment of the corresponding solvents provides overall good linear fits, while the correlation to the dielectric constant affords good linear patterns only after the segregation of the solvents into groups. The ¹H NMR data of 2,2′-pq and (1) reveal an increase of the solvent influence to the chemical shifts of the diimine ligand after its coordination to the metal and suggest two different types of solvent-effects for the complex and the ligand, respectively. The observed proton shifts of (1) are related with the results of the Mülliken population analysis in solvents of different polarity; the transition from CCl₄ to MeOH seems to signify a charge transfer from the axial COs and the central metal to the equatorial COs and the internal nuclei of 2,2′-pq.     

Soluble and thermally stable polyamides bearing 1,1′-thiobis(2-naphthoxy) groups

A new-type of sulfide containing diacid (1,1′-thiobis(2-naphthoxy acetic acid)) was synthesized from 2-naphthol in three steps. Reaction of 2-naphthol with sulfur dichloride afforded 1,1′-thiobis(2-naphthol) (TBN). 1,1′-Thiobis(2-naphthoxy acetic ester) (TBNAE) was successfully synthesized by refluxing the TBN with methylcholoroacetate in the presence of potassium carbonate. The related diacid was synthesized by basic solution reduction of TBNAE. The obtained diacid was fully characterized and used to prepare novel thermally stable poly(sulfide ether amide)s via polyphosphorylation reaction with different aromatic diamines. The properties of these new polyamides were investigated and compared with similar polyamides. These polyamides showed inherent viscosities in the range of 0.39-0.87 dL g⁻¹ in N,N-dimethylacetamide (DMAc) at 30 °C and at a concentration of 0.5 g dL⁻¹. All the polyamides were readily soluble in a variety of polar solvents such as DMAc and tetrahydrofuran (THF). These polyamides showed glass transition temperature (T_g) between 241-268 °C. Thermogravimetric analysis measurement revealed the decomposition temperature at 10% weight loss (T₁₀) ranging from 441- 479 °C in argon atmosphere.     

Simultaneous determination of Mn(II), Cu(II) and Fe(III) as 2-(5′-bromo-2′-pyridylazo)-5-diethylaminophenol complexes by adsorptive cathodic stripping voltammetry at a carbon paste electrode

A simple and precise square-wave adsorptive cathodic stripping voltammetry (SW-AdCSV) method has been described for simultaneous determination of Mn(II), Cu(II) and Fe(III) in water samples using a carbon paste electrode. In 0.1 mol L⁻¹ acetate buffer (pH 5) containing 50 μmol L⁻¹ of 2-(5′-bromo-2′-pyridylazo)-5-diethylaminophenol (5-Br-PADAP), Mn(II), Cu(II) and Fe(III) were simultaneously determined as metal-complexes with 5-Br-PADAP following preconcentration onto the carbon paste electrode by adsorptive accumulation at +1.0 V (vs. Ag/AgCl/3 M KCl). Insignificant interference from various cations (K⁺, Na⁺, Mg²⁺, Ca²⁺, Al³⁺, Bi³⁺, Sb³⁺, Se⁴⁺, Zn²⁺, Ni²⁺, Co²⁺, Cd²⁺, Pb²⁺, V⁵⁺, Ti⁴⁺ and NH₄⁺), anions (HCO₃⁻, Cl⁻, NO³⁻, SO₄²⁻ and PO₄³⁻) and ascorbic acid was noticed. Limits of detection of 0.066, 0.108 and 0.093 μg L⁻¹ and limits of quantitation of 0.22, 0.36 and 0.31 μg L⁻¹ Mn(II), Cu(II) and Fe(III), respectively, were achieved by the described method. The described stripping voltammetry method was successfully applied for simultaneous determination of Mn(II), Cu(II) and Fe(III) in ground, tap and bottled natural water samples.     

2,2′:6′,2″-Terpyridine[hydroxypropyl-β-cyclodextrin] 1:3 complex used as chelating agent for the determination of iron with a sensitive, selective and fast liquid chromatographic method

In the present work, 2,2′:6′,2″-Terpyridine (terpy), a substance with very poor aqueous solubility, was dissolved in water, after formation of its inclusion complex with hydroxypropyl-β-cyclodextrin (HPβCD), in a 1:3 stoichiometry. The obtained [terpy:(HPβCD)₃] supramolecule, with enhanced aqueous solubility, enables its usage as a reagent at RP-LC methods. It was found that, terpy after inclusion complexation retains unaffected the ability of binding to Fe²⁺. It was also observed that, the stable, reddish-purple [Fe(terpy)]²⁺ complex was formed quantitatively in a wide pH range (2-9). Subsequently, iron as active substance or impurity in a drug product, can be determined through UV-vis measurements of [Fe(terpy)₂]²⁺. Speed, sensitivity and selectivity are the most important features of the isocratic RP-LC method, developed to determine iron in pharmaceutical formulations. The duration of the chromatographic separation was less than 4.0 min. The method was linear, precise and accurate from 0.17 to 2.2 mg l⁻¹ of iron and the detection limit was found to be 5 μg l⁻¹. The absorbance at 318 and 552 nm allowed the quantitation of Fe (II) and Fe (III) after reduction, as well as of total Fe (II + III). Moreover, there were no interferences from Fe³⁺, Ni²⁺, Co²⁺ or Cu²⁺.     

Studies on photocrosslinkable copolymers of 4-methacryloyloxyphenyl-3′,4′-dimethoxystyryl ketone and methyl methacrylate

Copolymers with various contents of 4-methacryloyloxyphenyl-3′,4′-dimethoxystyryl ketone (MPDSK) and methyl methacrylate (MMA) were prepared in methyl ethyl ketone solution using benzoyl peroxide as a free radical initiator at 70 °C. Characterization of the resulting polymers was done by UV, FT-IR, ¹H NMR and ¹³C NMR spectroscopic techniques. The copolymer compositions were determined by ¹H NMR analysis. The monomer reactivity ratios were calculated using linearisation methods such as Finemann-Ross (r₁ = 0.4283 and r₂ = 0.3050), Kelen-Tudos (r₁ = 0.4264 and r₂ = 0.2606), and extended Kelen-Tudos (r₁ = 0.4022 and r₂ = 0.2704) methods as well as by a non-linear error-in-variables model (EVM) method using the computer program RREVM (r₁ = 0.4066 and r₂ = 0.2802). The molecular weights ( and ) and the polydispersity index of the copolymers were determined by gel permeation chromatography. The thermal stability of the copolymers increases with increase in concentration of MPDSK. Glass transition temperatures were determined by differential scanning calorimeter under nitrogen atmosphere. The photoreactivity of the copolymers having pendant chalcone moieties was studied in chloroform solution.     

Two-photon absorption chromophores with a tunable [2,2′]bithiophene core

Sonogashira coupling between 3,5,3′,5′-tetrabromo-[2,2′]bithiophene and various terminal alkynes provides two-photon absorption (TPA) chromophores 1-6, which possess electron donor (D) and/or acceptor (A) alkynyl substituents at 3(3′) and 5(5′) sites of the bithiophene core. The up-converted fluorescence emission excited at 800 nm (Ti:sapphire femtosecond laser, ∼100 fs pulses) was used to determine the two-photon absorption cross-sections (σ) of these compounds. The corresponding TPA cross-section (σ) values ranging from 132 to 1120 GM (10⁻⁵⁰ cm⁴ s photon⁻¹) can be fine-tuned by the substitutents. The quadrupolar-type (A-π-D-π-A) chromophore 5 exhibits the largest σ value (1120 GM) in CH₂Cl₂ upon 800 nm excitation.     

Synthesis of a new bidentate ferrocenyl N-heterocyclic carbene ligand precursor and the palladium (II) complex trans-[PdCl2(CfcC)], where (CfcC) = 1,1′-di-tert-butyl-3,3′-(1,1′-dimethyleneferrocenyl)-diimidazol-2-ylidene

A new ferrocenyl-N-heterocyclic carbene ligand precursor 1,1′-bis[(1-tert-butylimidazolium)-3-methyl]ferrocene dichloride has been synthesised and structurally characterised. The imidazolium salt was readily deprotonated in situ with KN(SiMe₃)₂ and reacted with [PdCl₂ (cod)] to afford the structurally characterised palladium (II) complex trans-[PdCl₂(C^∧fc^∧C)], where (cod) = 1,5-cyclooctadiene and (C^∧fc^∧C) = 1,1′-di-tert-butyl-3,3′-(1,1′-dimethyleneferrocenyl)-diimidazol-2-ylidene.     

Retention studies of 2′-2′-difluorodeoxycytidine and 2′-2′-difluorodeoxyuridine nucleosides and nucleotides on porous graphitic carbon: Development of a liquid chromatography–tandem mass spectrometry method

The development of a method for the separation of 2′-2′-difluorodeoxycytidine (gemcitabine, dFdC), 2′-2′-difluorodeoxyuridine (dFdU) and their mono-, di- and triphosphates using a porous graphitic carbon column (Hypercarb), without ion-pairing agent, is described. The retention of dFdC and dFdU could be controlled with an organic modifier (acetonitrile, CH₃CN) and the retention of the anionic nucleotides with an eluting ion (bicarbonate). Separation of all analytes was achieved using a 0–25 mM ammonium bicarbonate gradient in CH₃CN–H₂O (15:85, v/v). Under these conditions, however, very long re-equilibration times were required. Injection of an acidic solution (100 μL 10% formic acid in H₂O, v/v; 2.65 M) after running a gradient directly restored the separation capabilities of the column. Still, separation between the analytes slowly deteriorated over a period of months. These problems were solved by preconditioning the column with a pH buffered hydrogen peroxide (H₂O₂) solution (0.05% H₂O₂ in CH₃CN–H₂O (15:85, v/v), pH 4) before starting an analytical run. The oxidation of the stationary phase with H₂O₂ prevented its slow reduction, which most likely caused the decreasing retention times. The analytes were detected using tandem mass spectrometry.     

Ti-catalyzed reactions of 4,4′-bis(trimethylsilyl)bicyclohexyl-2,2′-diene with various electrophiles

Reductive disilylation (Li + Me₃SiCl − THF) of 1,3-cyclohexadiene led to 4,4′-bis(trimethylsilyl)bicyclohexyl-2,2′-diene (1). In the presence of TiCl₄ in dichloromethane, 1 reacted with some acyl chlorides, anhydrides, and aldehydes to give tricyclo[7.4.0.0^3,8]trideca-4,12-diene-2-yl derivatives.     

Synthesis of tricarbonyl rhenium and technetium complexes of a 5′-carboxamide 5-ethyl-2′-deoxyuridine for selective inhibition of herpes simplex virus thymidine kinase 1

Herpes simplex virus thymidine kinase type 1 (HSV1-TK) is frequently used as reporter protein in gene therapy. Our aim is to produce single photon emitting reporter probe based on technetium-99m. The synthesis of organometallic technetium and rhenium complexes of a 5′-carboxamide 5-ethyl-2′-deoxyuridine derivative able to selectively inhibit HSV1-TK is presented. The 5-ethyl-2′-deoxyuridine functionalized with a suitable tridentate chelating system at position 5′ was synthesized from commercial 2′-deoxyuridine in seven steps. The 5-ethyl-2′-deoxyuridine derivative was labeled with the fac-M(CO)₃-core (M = Tc, Re). The resulting rhenium complex was found to be a selective competitive inhibitor of HSV1-TK (K_i = 4.56 μM). Inhibition of the human cytosolic thymidine kinase (hTK1) previously reported with organometallic rhenium and technetium complexes of 5′-carboxamide thymidine derivative was not observed. The uptake of the technetium-99m complex in transfected cells expressing HSV1-TK has been evaluated to assess its possible use as reporter.     

Photoactive building blocks for coordination complexes: Gilding 2,2′:6′,2″-terpyridine

The alkyne unit of 4′-ethynyl-2,2′:6′,2″-terpyridine has been functionalized with Ph₃PAu, (2-tolyl)₃PAu or Au(dppe)Au units to produce compounds 1-3, respectively. These derivatives have been characterized by electrospray mass spectrometry, solution ¹H and ¹³C NMR, UV-Vis and emission spectroscopies, and single crystal X-ray diffraction. In the solid state, molecules of 1 or 2 pack with separated domains of tpy and R₃PAu units; the tpy units in 2 (but not 1) exhibit face-to-face π-stacking. Compound 3 crystallizes as 2(3)^.CHCl₃, and the folded conformation of the dppe backbone results in a short (2.9470(8) Å) aurophilic interaction. Folded molecule 3 captures CHCl₃, preventing intramolecular face-to-face π-interactions between the tpy units. In CH₂Cl₂ solution, 1-3 are emissive when excited between 230 and 300 nm, but over minutes when λ_ex = 230 nm, the emission bands decay as the compounds photodegrade.     

Novel oxorhenium complexes with 2-(2′-hydoxy-5′-methylphenyl)benzotriazolato ligand. X-ray studies,spectroscopic characterization and DFT calculations

The [ReOCl₂(hmpbta)(AsPh₃)] · MeCN, [ReOBr₂(hmpbta)(AsPh₃)] · MeCN, [ReOCl₂(hmpbta)(PPh₃)] · MeCN, [ReOBr₂(hmpbta)(PPh₃)] · MeCN, and [ReBr₂(hmpbta)(PPh₃)] · MeCN complexes have been prepared in the reactions of [ReOX₃(EPh₃)₂] (X = Cl, Br; E = P, As) with 2-(2’-hydoxy-5′-methylphenyl)benzotriazole in molar ratio 1:1. All the compounds were structurally and spectroscopically characterized. The electronic structure of [ReOCl₂(hmpbta)(AsPh₃)] has been calculated with the density functional theory (DFT) method. The TDDFT/PCM calculations have been employed to produce a hundred of singlet excited-states starting from the ground-state geometry optimized in the gas phase, and the UV–Vis spectrum of [ReOCl₂(hmpbta)(AsPh₃)] has been discussed on this basis. The paper reports also X-ray structure and DFT calculations for the disubstituted [ReOCl(hmpbta)₂] chelate.