Assessment of supporting electrolyte contributions in electrochemically modulated liquid chromatography

This paper reports the results of an investigation on the role of the supporting electrolyte in separations using electrochemically modulated liquid chromatography (EMLC) with a porous graphitic carbon stationary phase. With respect to the identity of the supporting electrolyte, the elution strength of the electrolyte anion increased as F- < OH- < BF4- < ClO4- < PF6- for injections of negatively charged aromatic molecules, whereas a 10-fold increase in electrolyte concentration induced a 60% change in retention for the same solutes. Furthermore, both the concentration and composition of the supporting electrolyte affected retention in a manner that varied with the charge of the analyte and applied potential. This behavior is explained using Gouy-Chapman diffuse double layer theory, coupled with comparisons of this theory with closely related models for ion-pair chromatography. Insights into the retention mechanism reveal that an ion-exchange mechanism controls the retention of negatively charged solutes at applied potentials removed from the potential of zero charge (PZC). At potentials close to the PZC, the electrostatic model is less effective with the predominant retention mechanism likely involving hydrophobic interactions with the carbonaceous stationary phase. The combined effects of these findings are demonstrated by using a temporal gradient in supporting electrolyte concentration to optimize an EMLC separation.     

Field evaluations of the VDmax approach for substantiation of a 25 kGy sterilization dose and its application to other preselected doses

The International and European standards for radiation sterilization require evidence of the effectiveness of a minimum sterilization dose of 25 kGy but do not provide detailed guidance on how this evidence can be generated. An approach, designated VD_max, has recently been described and computer evaluated to provide safe and unambiguous substantiation of a 25 kGy sterilization dose. The approach has been further developed into a practical method, which has been subjected to field evaluations at three manufacturing facilities which produce different types of medical devices. The three facilities each used a different overall evaluation strategy: Facility A used VD_max for quarterly dose audits; Facility B compared VD_max and Method 1 in side-by-side parallel experiments; and Facility C, a new facility at start-up, used VD_max for initial substantiation of 25 kGy and subsequent quarterly dose audits. A common element at all three facilities was the use of 10 product units for irradiation in the verification dose experiment.

The field evaluations of the VD_max method were successful at all three facilities; they included many different types of medical devices/product families with a wide range of average bioburden and sample item portion values used in the verification dose experiments. Overall, around 500 verification dose experiments were performed and no failures were observed. In the side-by-side parallel experiments, the outcomes of the VD_max experiments were consistent with the outcomes observed with Method 1.

The VD_max approach has been extended to sterilization doses >25 and <25 kGy; verification doses have been derived for sterilization doses of 15, 20, 30, and 35 kGy. Widespread application of the VD_max method for doses other than 25 kGy must await controlled field evaluations and the development of appropriate specifications/standards.     

MS3 using the collision cell of a tandem mass spectrometer system

We report the feasibility of multistage fragmentation in combination with a fast background subtraction method, yielding the equivalent of MS3. The first quadrupole selects an ion of interest, and the ion is axially accelerated into Q2 to generate fragment ions. Subsequent stages of mass selection and fragmentation are obtained by quadrupolar resonant excitation within the Q2 collision cell. The fragments are analyzed downstream by either a resolving quadrupole or a time-of-flight (TOF) mass spectrometer, and multistage spectra are obtained by subtraction (MS(n) - MS(n-1)) for n = 3 or 4. We discuss the characterization of this method, including product ion arrival times, fragmentation efficiencies, and ion selectivity. We report accurate TOF mass spectra of background-subtracted MS3 for protonated molecules reserpine (m/z 609), bosentan (m/z 1552), and taxol (m/z 854).     

Glycol-based sol-gel process for the fabrication of ferroelectric PZT thin films

A new sol-gel system using ethylene glycol was developed for the fabrication of PZT thin films with compositions near the morphotropic phase boundary Pb(Zr_0.52Ti_0.48)O₃. Ethylene glycol was used as both a chelating agent and a solvent to replace the highly toxic methoxyethanol used in previous formulations. Thin films were deposited by spin coating the solutions onto platinized silicon substrates. Films were completely crystallized by about 600°C and contained the ferroelectric perovskite phase. A dielectric constant of about 750–800 at 1 KHz was obtained for thin films of 0.3 µm thickness. The hysteresis measurements revealed a remanent polarization of 15 mC/cm² with a coercive field of 60 kV/cm.     

Synthesis of novel 1,4‐dihydropyrido[3′,2′:5,6]thiopyrano[4,3‐c]‐pyrazoles and 5H‐pyrido[3′,2′:5,6]thiopyrano[4,3‐d]pyrimidines as potential antiproliferative agents

The synthesis of new planar derivatives characterized by the presence of a pyridothiopyranopyrazole or pyridothiopyranopyrimidine nucleus, carrying a substituted aryl group, is reported. The novel 1,4‐dihydropyrido[3′,2′:5,6]thiopyrano[4,3‐c]pyrazole derivatives were obtained by condensation of 2,3‐dihydro‐3‐hydroxymethylenethiopyrano[2,3‐b]pyridin‐4(4H)‐ones with appropriate hydrazines. The preparation of 2‐substituted pyrido[3′,2′:5,6]thiopyrano[4,3‐d]pyrimidines was accomplished from the intermediate 2,3‐dihy‐dro‐3‐dimethylaminomethylenethiopyrano[2,3‐b]pyridin‐4(4H)‐ones by reaction with the appropriate binucleophile amidines. The antiproliferative activity of some new products was tested by an in vitro assay on human tumour cell lines (HL‐60 and HeLa), but none of them showed any significant effects in the tests performed. Accordingly, linear flow dichroism measurements indicated their inability to form a molecular complex with DNA.     

Ganglioside analysis by thin-layer chromatography matrix-assisted laser desorption/ionization orthogonal time-of-flight mass spectrometry

Metastable decomposition of ions generated in matrix-assisted laser desorption/ionization (MALDI) mass spectrometers complicates analysis of biological samples that have labile bonds. Recently, several academic laboratories and manufacturers of commercial instruments have designed instruments that introduce a cooling gas into the ion source during the MALDI event and have shown that the resulting vibrational cooling stabilizes these labile bonds. In this study, we compared stabilization and detection of desorbed gangliosides on a commercial orthogonal time-of-flight (oTOF) instrument with results we reported previously that had been obtained on a home-built Fourier transform mass spectrometer. Decoupling of the desorption/ionization from the detection steps resulted in an opportunity for desorbing thin-layer chromatography (TLC)-separated gangliosides directly from a TLC plate without compromising mass spectral accuracy and resolution of the ganglioside analysis, thus coupling TLC and oTOF mass spectrometry. The application of a declustering potential allowed control of the matrix cluster and matrix adduct formation, and, thus, enhanced the detection of the gangliosides.     

The effect of thermal pretreatment on the electrochemical response for palladium in aqueous media

Previous work on the electrochemistry of palladium in aqueous acid solution demonstrated the existence of two multilayer hydrous oxide reduction peaks, one at ca. 0.24 V and another at ca. 0.55 V vs. RHE, plus the presence of a reversible active surface state transition at ca. 0.24 V. In the present work with thermally activated palladium it was observed that, in agreement with the hydrous oxide reduction behaviour of the system, there is a second active state transition at E≥ca. 0.45 V. In most of its reactions in aqueous acid solution, apart from its unusual capacity to absorb hydrogen, palladium exhibits properties very similar to those of platinum; however, palladium seems to be more prone to dissolution and subsurface oxygen formation. Also the premonolayer oxidation responses of these two metals are often different as the more active state of the palladium surface is not as readily generated as that of platinum. The electrocatalytic properties of palladium, as reported earlier, correlate quite well with the hydrous oxide and premonolayer oxidation behaviour of this electrode system. Electronic Publication     

Oxy-cope rearrangements of bicyclo[3.2.0]heptenones. Synthesis of bicyclo[4.2.1]non-1(4)-en-6-ones and bicyclo[5.2. 1]dec-1(10)-en-5-ones

6-exo-Methylbicyclo[3.2.0]hepten-7-ones and their 2-alkylidene analogues are readily prepared from dialkyl squarates. These compounds undergo facial oxy-Cope ring expansions upon treatment with vinyllithium; the former leads to bicyclo[4.2. 1]non-1(4)-en-6-ones and the latter to the first examples of bicyclo[5.2.1]dec-1(10)-en-5-ones, compounds having exceptionally strained bridgehead double bonds. The transformations are controlled by the 6-exo-methyl group in the starting material along with the substituent at position-1 (bridgehead) which force attack of the lithium reagent from the concave face of the starting material, thus allowing the cyclopentenyl or alkylidene groups to participate in the sigmatropic event.     

First row divalent transition metal complexes of aryl-appended tris((pyridyl)methyl)amine ligands: syntheses, structures, electrochemistry, and hydroxamate binding properties

Divalent manganese, cobalt, nickel, and zinc complexes of 6-Ph(2)TPA (N,N-bis((6-phenyl-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine; [(6-Ph(2)TPA)Mn(CH(3)OH)(3)](ClO(4))(2) (1), [(6-Ph(2)TPA)Co(CH(3)CN)](ClO(4))(2) (2), [(6-Ph(2)TPA)Ni(CH(3)CN)(CH(3)OH)](ClO(4))(2) (3), [(6-Ph(2)TPA)Zn(CH(3)CN)](ClO(4))(2) (4)) and 6-(Me(2)Ph)(2)TPA (N,N-bis((6-(3,5-dimethyl)phenyl-2-pyridyl)methyl)-N-((2-pyridyl)methyl)amine; [(6-(Me(2)Ph)(2)TPA)Ni(CH(3)CN)(2)](ClO(4))(2) (5) and [(6-(Me(2)Ph)(2)TPA)Zn(CH(3)CN)](ClO(4))(2) (6)) have been prepared and characterized. X-ray crystallographic characterization of 1A.CH(3)()OH and 1B.2CH(3)()OH (differing solvates of 1), 2.2CH(3)()CN, 3.CH(3)()OH, 4.2CH(3)()CN, and 6.2.5CH(3)()CN revealed mononuclear cations with one to three coordinated solvent molecules. In 1A.CH(3)()OH and 1B.2CH(3)()OH, one phenyl-substituted pyridyl arm is not coordinated and forms a secondary hydrogen-bonding interaction with a manganese bound methanol molecule. In 2.2CH(3)()CN, 3.CH(3)()OH, 4.2CH(3)()CN, and 6.2.5CH(3)()CN, all pyridyl donors of the 6-Ph(2)TPA and 6-(Me(2)Ph)(2)TPA ligands are coordinated to the divalent metal center. In the cobalt, nickel, and zinc derivatives, CH/pi interactions are found between a bound acetonitrile molecule and the aryl appendages of the 6-Ph(2)TPA and 6-(Me(2)Ph)(2)TPA ligands. (1)H NMR spectra of 4 and 6 in CD(3)NO(2) solution indicate the presence of CH/pi interactions, as an upfield-shifted methyl resonance for a bound acetonitrile molecule is present. Examination of the cyclic voltammetry of 1-3 and 5 revealed no oxidative (M(II)/M(III)) couples. Admixture of equimolar amounts of 6-Ph(2)TPA, M(ClO(4))(2).6H(2)O, and Me(4)NOH.5H(2)O, followed by the addition of an equimolar amount of acetohydroxamic acid, yielded the acetohydroxamate complexes [((6-Ph(2)TPA)Mn)(2)(micro-ONHC(O)CH(3))(2)](ClO(4))(2) (8), [(6-Ph(2)TPA)Co(ONHC(O)CH(3))](ClO(4))(2) (9), [(6-Ph(2)TPA)Ni(ONHC(O)CH(3))](ClO(4))(2) (10), and [(6-Ph(2)TPA)Zn(ONHC(O)CH(3))](ClO(4))(2) (11), all of which were characterized by X-ray crystallography. The Mn(II) complex 8.0.75CH(3)()CN.0.75Et(2)()O exhibits a dinuclear structure with bridging hydroxamate ligands, whereas the Co(II), Ni(II), and Zn(II) derivatives all exhibit mononuclear six-coordinate structures with a chelating hydroxamate ligand.     

Synthesis and characterization of some Cr(III), Fe(III) and Zr(IV) compounds with substituted o-hydroxy benzophenone

This work presents our data concerning the synthesis and characterization of some Cr(III), Fe(III) and Zr(IV) complexes with substituted (2-hydroxy-4-methoxy-phenyl)-phenyl-methanone - C₁₄H₁₂O₃, denoted by (L1). The synthesis of these complex compounds was performed using melted urea as reaction medium. The obtained complexes have been studied by chemical analysis, IR spectroscopy, X-ray diffraction and thermogravimetric analysis. Based on the data resulting from the thermal behaviour of the studied complex compounds, the kinetic parameters of the thermal decomposition reactions have been determined. This revised version was published online in July 2006 with corrections to the Cover Date.