Nucleophilic de-coordination and electrophilic regeneration of "hemilabile" pincer-type complexes: formation of anionic dialkyl, diaryl, and dihydride Pt(II) complexes bearing no stabilizing pi-acceptors

Novel anionic dialkyl, diaryl, and dihydride platinum(II) complexes based on the new "long-arm" hemilabile PCN-type ligand C6H4[CH2P(tBu)2](CH2)2N(CH3)2 with the general formula Li+[Pt(PCN)(R)2]- (R=Me (4), Ph (6) and H (9)) were prepared by reaction of [Pt(PCN)(R)] complexes (obtained from the corresponding chlorides) with an equivalent of RLi, as a result of the opening of the chelate ring. Alkylating agents based on other metals produce less stable products. These anionic d8 complexes are thermally stable although they bear no stabilizing pi acceptors. They were characterized by 1H, 31P[1H], 13C, and 7Li NMR spectroscopy; complex 9 was also characterized by single crystal X-ray crystallography, showing that the Li+ ion is coordinated to the nitrogen atom of the open amine arm and to the hydride ligand (trans to the P atom) of a neighboring molecule (H--Li=2.15 A), resulting in a dimeric structure. Complexes 4 and 9 exhibit high nucleophilic reactivity, upon which the pincer complex is regenerated. Reaction of 4 with water, methyl iodide, and iodobenzene resulted in the neutral complex [Pt(PCN)(CH3)] (3) and methane, ethane, or toluene, respectively. Labeling studies indicate that the reaction proceeds by direct electrophilic attack on the metal center, rather than attack on the alkyl ligand. The anionic dihydride complex 9 reacted with water and methyl iodide to yield [Pt(PCN)(H)] (8) and H2 or methane, respectively.     

Quantification of free and total salicylic acid in plants by solid-phase extraction and isocratic high-performance anion-exchange chromatography

Salicylic acid (SA) is an important signaling compound in plants and is involved in various defense responses. Here we report a new method for quantification of free and total soluble SA in Arabidopsis thaliana with 5-fluorosalicylic acid (5-FSA) as internal standard. The SA was isolated from leaf extracts by solid-phase extraction with phenyl-phase cartridges and selectively eluted as the cationic iron(III)-complex. Recoveries of SA and 5-FSA were equal and exceeded 90%. Free SA was subsequently released from the iron(III)-complex by addition of 2,2-bipyridyl and high-performance anion-exchange chromatography was performed on an NH₂ column. The SA appeared as last peak with a retention time of 15 min, baseline-separated from other substances. On-line detection was performed fluorimetrically for both SA and 5-FSA at an excitation wavelength of 300 nm and an emission wavelength of 410 nm, because both substances give similar fluorescence spectra. The detection limit for SA was 5 ng g^–1 FW for a sample size of 100 mg. Thus the main advantages of the method are highly selective sample preparation, increased sensitivity, reduced analysis time compared with reversed-phase HPLC, and use of a novel internal standard detectable under the same conditions as SA. The techniques described are applicable to other plant materials.     

Synthesis and pharmacological evaluation of new 16-methyl pregnane derivatives

The pharmacological activity of several new pregnane derivatives 15-19 were determined on gonadectomized male hamster flank organs, seminal vesicles and in vitro conversion of testosterone (T) to dihydrotestosterone (DHT) as 5alpha-reductase inhibitors. Steroids 15-19 decreased the diameter of the pigmented spot in the flank organs as compared to the T treated animals; in this model, steroids 16 and 19 showed a higher activity than the commercially available finasteride 3. Injection of T increased the weight of the seminal vesicles. Compounds 15-19 when injected together with T decreased the weight of the seminal vesicles thus showing an antiandrogenic effect. The trienone 19 exhibited a considerably higher activity than finasteride. Steroids 15-19 inhibited the in vitro metabolism of [3H]T to [3H]DHT in seminal vesicles homogenates of gonadectomized male hamsters. Compounds 18 and 19 showed a much higher antiandrogenic effect than finasteride. This enhancement of the biological activity could probably be attributed to the coplanarity of the steroidal skeleton as previously observed by our group. The high antiandrogenic activity of the epoxy compound 16 is probably the result of the ring opening of the oxiran ring with the nucleophilic part of the enzyme 5alpha-reductase thus leading to a stable adduct with concomitant deactivation of this enzyme.     

Characterization of three agave species by gas chromatography and solid-phase microextraction-gas chromatography-mass spectrometry

Steam distillation (SD) extraction-solid-phase microextraction coupled to GC-MS was developed for the determination of terpenes and Bligh-Dyer extraction-derivatization coupled with GC for the determination of fatty acids such as ethyl esters were used. It was found that the three different Agave species have the same profile of fatty acids; the quantity of these compounds is different in each Agave variety. On the other hand, different terpenes were identified in the three Agave plants studied: nine in A. salmiana, eight in A. angustifolia and 32 in A. tequilana Weber var. azul.     

Studying dispersoid systems

Summary Measurements of energy transformation in mitochondria are done on a capillary differential titration calorimeter CTD2156. It is important to mention that a sediment is quickly formed by the mitochondria suspension without mixing by means of a vibrating needle. During the measurements, the vibrating needle is located inside the working volume of the chamber. The design of the calorimeter is substantiated theoretically. It provides a new mode of a reagent input in the measuring volume of the calorimetric chambers. It expands the spectrum of tasks that can be solved using this instrument. In the capillary calorimeter the calorimetric chambers unit is simple and small in size. These advantages of capillary chambers provide an opportunity to unite 20 capillary calorimetric chambers in one calorimetric block. It allows designing a multi-channel titration calorimeter. There are obvious advantages of such a calorimeter over other instruments in screening researches and in researches of objects maintaining stability only for a short time.     

Towards the development of multisensor for drugs of abuse based on molecular imprinted polymers

The synthetic receptors for cocaine, deoxyephedrine, methadone and morphine were computationally designed and produced using molecular imprinting. The structure and energy of the molecular complexes were analysed by computational techniques. The possible structures of the binding sites in the synthetic receptors have been compared with those of corresponding natural receptors. The composition of imprinted polymers was optimised to allow adequate performance under the same experimental conditions. All selected molecular imprinting polymers (MIPs) demonstrated stronger affinity in comparison with corresponding blank polymers resulting in imprinted factors (I) equal to 1.2 (cocaine), 2.5 (deoxyephedrine), 3.5 (methadone) and 3 (morphine) which suggested that the specific binding site for each molecule was successfully created. The polymers studied possessed good selectivity and affinity towards their templates and could be recommended for the integration with sensor devices. From a practical point of view, especially for multisensor requirements, the synthetic receptors based on imprinted polymers could be superior to natural receptors due to their stability, robustness and compatibility with automation processes required for sensor fabrication.     

Weighted bounds for the carleson maximal operator inR n

The Carleson maximal operator is shown to be bounded inL ^p (w) for certain values ofp and certain radial weightsw when acting on products of radial functions and homogeneous harmonic polynomials. Partially supported by DGICYT (MEC Spain). PB 92/187.     

Thermodynamics of alpha-Cyclodextrin-p-Nitrophenyl Glycoside Complexes. A Simple System To Understand the Energetics of Carbohydrate Interactions in Water

Thermodynamic studies of the binding of a series of p-nitrophenyl glycosides (PNPGly) of varying stereochemistry to alpha-cyclodextrin (alpha-CD) were performed at three different temperatures (25, 35, and 42 degrees C) using a microcalorimetric technique. The system p-nitrophenol (PNP) at pH = 3 and alpha-CD was also studied for the sake of comparison. All these complexes were found to be enthalpy driven with a favorable enthalpic term clearly dominant over an unfavorable entropic term. A clear enthalpy-entropy compensation effect was observed at all the temperatures, with a slope close to unity (alpha = 1.02) and an intercept TDeltaS degrees (o) = 2.91 kcal mol(-)(1). This thermodynamic pattern is in agreement with those usually found for lectin-carbohydrate associations and for the binding processes of several host-guest systems. This pattern is explained in terms of the contribution of primarily two driving forces: the van der Waals interactions between the host and the guest, and the solvation/desolvation processes which accompany the association reaction. The presence of the carbohydrate molecule in the PNP ring causes a slight destabilization of the complex at 25 degrees C with respect to the alpha-CD-PNP (pH = 3) complex, although a different behavior has been observed depending on the axial/equatorial configuration of the glycoside and the temperature. This behavior is modulated by the stereochemistry of the glycoside. Differences were observed between the deoxy-derivatives (LAra and LFuc) and those derivatives with a hydroxymethyl group (Glc, Gal, Man). DeltaC(p) degrees values were obtained from the dependency of DeltaH degrees on temperature (=( partial differentialDeltaH degrees / partial differentialT)(p)). These values are small and negative except for alphaMan complex. For the latter complex, discrepancy between the calorimetric and the calculated van't Hoff enthalpies was observed. Parallels are drawn between the thermodynamics of our model and those proposed for carbohydrate-protein associations.     

Metal-containing ditopic receptors for molecular recognition of diammonium cations

Two new ditopic receptors for α,ω-alkanediyldiammonium cations based on a tetraazamacrocyclic (cyclidene) nickel(II) complex bearing two crown-ether residues were synthesized. The studies of the host-guest interaction between the receptors and a series of α,ω-diammonium salts by NMR titration in acetonitrile-d₃ showed that 1:1 complexes are formed with K_assoc∼10³-10⁵ M⁻¹. Receptor 1 with benzo-15-crown-5 arms showed substantial selectivity in binding of trimethylene- and tetramethylenediammonium dications, and 1-2 orders of magnitude weaker binding of shorter (C₂) or longer (C₅ and C₆) diammonium cations. Receptor 2 with benzo-18-crown-6 arms showed higher affinity to all studied diammonium cations, but the recognition of the length of α,ω-diammonium cations was less pronounced.     

Development and validation of a liquid chromatography-ultraviolet absorbance detection assay using derivatisation for the novel marine anticancer agent ES-285 x HCl [(2S,3R)-2-amino-3-octadecanol hydrochloride] and its pharmaceutical dosage form

ES-285 x HCl [(2S,3R)-2-amino-3-octadecanol hydrochloride] is a novel investigational anticancer agent, which has shown in vitro and in vivo cytotoxic activity against various tumor cell lines with selectivity for certain solid tumors. The pharmaceutical development of ES-285 x HCl warranted the availability of an assay for the quantification and purity determination of ES-285 x HCl active pharmaceutical ingredient (API) and its pharmaceutical dosage form. A liquid chromatographic method (LC) comprising of derivatisation of ES-285 x HCl with phenylisothiocyanate and UV-detection was developed. The method was found to be linear, precise and accurate. The assay also proved selectivity as determined by analysing ES-285 x HCl in combination with 15 analogues and in combination with hydroxypropyl-beta-cyclodextrin, the excipient used in the lyophilised pharmaceutical dosage form. Stress testing showed that the degradation products were separated from the parent compound, confirming its stability indicating capacity. The method was found robust as determined with design of experiments (DoE), which made it possible to predict system suitability responses in worst case experimental conditions and to define criteria for system suitability testing.