Amino-Functionalized Monolithic Poly(glycidyl methacrylate-<Emphasis Type="Italic">co</Emphasis>-divinylbenzene) Ion-Exchange Stationary Phases for the Separation of Oligonucleotides

Monolithic capillary columns were prepared by thermal initiated copolymerization of glycidyl methacrylate (GMA) and divinylbenzene (DVB) inside silanized 200 µm i.d. fused silica capillaries. Polymerization mixtures containing different amounts of porogen (1-decanol and tetrahydrofuran (THF)) and different ratios of monomer and crosslinker were used for synthesis. For characterization the pore size distribution profiles of the resulting monoliths were determined by mercury intrusion porosimetry. The morphology of the copolymer was investigated by scanning electron micrographs (SEM). A high linear dependence between flow rate and pressure drop was achieved which indicates that the polymer is pressure-stable even at high flow rates. After characterization the produced GMA-DVB monoliths, which contain reactive epoxide groups, were modified by reaction with diethylamine to obtain a poly(3-diethylamino-2-hydroxypropyl methacrylate-co-divinylbenzene) ion-exchange monolithic stationary phase. The synthesized monoliths contain ionizable amino groups that are useful for anion-exchange chromatography (AEC). Poly(3-diethylamino-2-hydroxypropyl methacrylate-co-divinylbenzene) monolithic columns allowed a fast and highly efficient separation of a homologous series of phosphorylated oligothymidylic acids [d(pT)_12-18]. Since durability is an important parameter of chromatographic column characterization, the separation performance for d(pT)_12-18 in a freshly produced capillary column and on the same column after 100 chromatographic runs was compared.     

Ring-opening metathesis polymerization-derived monolithic strong anion exchangers for the separation of 5'-phosphorylated oligodeoxythymidylic acids fragments

Ring-opening metathesis polymerization (ROMP) derived monoliths were prepared from 5-norborn-2-enemethyl bromide (NBE-CH(2)Br) and tris(5-norborn-2-enemethoxy)methylsilane ((NBE-CH(2)O)(3)SiCH(3)) within the confines of surface-silanized borosilicate columns (100 mm × 3 mm I.D.), applying Grubbs' first generation benzylidene-type catalyst [RuCl(2)(PCy(3))(2)(CHPh)]. Two monoliths of the same recipe were converted into strong anion-exchangers applying two different approaches. Monolith I was prepared by a two-step reaction of the poly(NBE-CH(2)-Br) moieties with diethyl amine forming a weak-anion exchanger followed by reaction (quaternization) with ethyl iodide. Monolith II was prepared via a single-step reaction of the poly(NBE-CH(2)-Br) moieties with triethyl amine. The resulting monolithic anion-exchangers prepared demonstrated a good aptitude for the anion-exchange separation of single-stranded nucleic acids (ss-DNA). However, monolith II showed superior separation efficiency compared to monolith I indicated by sharper analyte peaks and better resolution values for the 5'-phosphorylated oligodeoxythymidylic acids fragments. On monolith II, the seven fragments of [d(pT)(12-18)] were baseline separated in less than 9 min. The influence of the buffer pH on the separation efficiency was studied applying a phosphate (0.05 mol/L, pH 7 and 8) and Tris-HCl buffer (0.05 mol/L, pH 9), respectively.     

Ring-opening metathesis polymerization-derived large-volume monolithic supports for reversed-phase and anion-exchange chromatography of biomolecules

Preparative-scale monolithic columns up to 433.5 mL in volume were prepared via transition metal-catalyzed ring-opening metathesis polymerization (ROMP) from norborn-2-ene (NBE) and trimethylolpropane-tris(5-norbornene-2-carboxylate) (CL) using the 1(st)-generation Grubbs initiator RuCl(2)(PCy(3))(2)(CHPh) (Cy = cyclohexyl) (1) in the presence of a macro- and microporogen, i.e. of 2-propanol and toluene. To prepare large-volume monoliths, bulk polymerizations were completed within borosilicate or PEEK column formats with diameters in the range of 3 to 49 mm. The pore structure of the large-volume monoliths was investigated by electron microscopy and inverse-size exclusion chromatography (ISEC), respectively. Monolithic columns with inner diameters (I.D.s) in the range of 10-49 mm were tested for the separation of a mixture of five proteins, i.e., insulin, cytochrome C, lysozyme, conalbumin, and β-lactoglobulin. Preparative separation of these proteins was achieved within less than 12 min in a 433.5 mL monolithic column by applying gradient elution in the RP-HPLC mode. Furthermore, weak and strong anion exchangers were prepared via post-synthesis grafting of bicyclo[2.2.1]hept-5-en-2-yl-methyl-N,N-dimethylammonium hydrochloride (4) and bicyclo[2.2.1]hept-5-en-2-ylmethyl-N,N,N-trimethylammonium iodide (5), respectively. The weak and strong anion exchangers were used for the preparative-scale separation of 5'-phosphorylated oligodeoxythymidylic acid fragments of d[pT](12-18) at pH values ranging from 5 to 9.     

Coordination complexes of molybdenum with 3,6-di-tert-butylcatechol. Addition products of DMSO, pyridine N-oxide, and triphenylarsine oxide to the putative [MoVIO(3,6-DBCat)2] monomer and self-assembly of the chiral [(MoVIO(3,6-DBCat)2)4] square

Molybdenum complexes of 3,6-di-tert-butylcatechol have been prepared from the reaction between [Mo(CO)(6)] and 3,6-di-tert-butyl-1,2-benzoquinone. A putative "[MoO(3,6-DBCat)(2)]" monomer is assumed to form initially by reaction with trace quantities of oxygen. Condensation of the reaction mixture leads to the formation of oligomeric products, including the [(MoO(3,6-DBCat)(2))(4)] chiral square isolated by chromatographic separation. Molybdenum centers at the corner of the square are bridged by oxo ligands centered along edges. Four-fold and inversion crystallographic symmetry gives tetramers as either LambdaLambdaLambdaLambda or DeltaDeltaDeltaDelta isomers, and the crystal structure consists of parallel columns of squares with the same chirality. Addition of O-Subst (O-Subst = dmso, pyridine N-oxide, triphenylarsine oxide) ligands to [MoO(3,6-DBCat)(2)] occurs selectively to give cis-[MoO(O-Subst)(3,6-DBCat)(2)] products. All three addition complexes are fluxional in solution. The temperature-dependent stereodymanic behavior of [MoO(dmso)(3,6-DBCat)(2)] has been shown to occur via a trigonal prismatic intermediate (Bailar twist) that conserves the cis disposition of oxo and dmso ligands. Electrochemical and chemical reduction reactions have been investigated for [MoO(dmso)(3,6-DBCat)(2)] with interest in displacement of SMe(2) with formation of cis-[MoO(2)(3,6-DBCat)(2)](2-). Cyclic voltammetry shows an irreversible two-electron reduction for the complex at -0.852 V (vs Fc/Fc(+)). Chemical reduction using CoCp(2) was observed to give a product with an electronic spectrum that is generally associated with cis-[MoO(2)(Cat)(2)](2-) complexes. Structural characterization revealed that the product was [CoCp(2)][MoO(3,6-DBCat)(2)], possibly formed as the product of dmso displacement upon one-electron reduction of [MoO(dmso)(3,6-DBCat)(2)].     

Homochiral column structure of rac- and lambda-tris(ethylenediamine)cobalt(III) cyclotriphosphate dihydrate in crystal structures and cation-anion association in aqueous solution

rac- and Lambda-tris(ethylenediamine)cobalt(III) cyclotriphosphate dihydrate with the chemical formulas rac-[Co(en)(3)]P(3)O(9).2H(2)O (1) and Lambda-[Co(en)(3)]P(3)O(9).2H(2)O (2) were synthesized, and their crystal structures were determined by single-crystal X-ray analyses. In 1, the cationic complex molecule [Co(en)(3)](3+) with the Delta or Lambda enantiomer and cyclotriphosphate anion are alternately arrayed and connected by multiple hydrogen bonds to form a homochiral column structure. Adjacent homochiral columns with different chirality for 1 are connected by intercolumn hydrogen bonds through P(3)O(9)(3)(-) anions, as the bridging groups, to form a tetrameric cyclic cylindrical structure, while the adjacent columns with the same chirality are connected for 2 to form the cyclic cylindrical structure. All 6 amino groups per [Co(en)(3)](3+) participate in the formation of 12 hydrogen bonds, in which 8 hydrogen bonds contribute to the construction of a homochiral column and the remaining 4 hydrogen bonds contribute to the intercolumn interactions. The circular dichroism spectrum of the aqueous solution of Lambda-[Co(en)(3)](3+) changes drastically when excess P(3)O(9)(3)(-) is added, and this change is explained by ion-pair formation. The thermodynamic association constant of [Co(en)(3)](3+) with P(3)O(9)(3)(-), calculated from the conductivity data, was log K = 4.26 at 25 degrees C.     

Monolithic capillary columns based on pentaerythritol acrylates for molecular‐size‐based separations of synthetic polymers

Monolithic capillary columns based on pentaerythritol triacrylate and pentaerythritol tetraacrylate were synthesized using different compositions of polymerization mixtures and different polymerization conditions. The impact of porogen type and porogen/monomer ratio on the porosity of synthesized monoliths was investigated. Porogen type appears to be the main factor influencing the separating properties of the monolithic sorbent. Using optimal polymerization conditions (porogen type, porogen/monomer ratio, reaction temperature, time etc.) monoliths with a porous structure optimized for polymer separations can be obtained. The monolithic capillary columns containing porous sorbents with optimized porosity are capable of separating 10 to 12 polystyrene standards in one chromatographic run utilizing both size exclusion chromatography and hydrodynamic chromatography separation mechanisms.     

Kinetics and Mechanism of the Reaction between Serum Albumin and Auranofin (and Its Isopropyl Analogue) in Vitro

The first detailed kinetic analysis and mechanistic interpretation of the reactions between serum albumin and the second-generation gold drug Auranofin [Et(3)PAuSATg = (triethylphosphine)(2,3,4,6-tetra-O-acetyl-1-beta-D-glucopyranosato-S-) gold(I)] and its triisopropylphosphine analogue, iPr(3)PAuSATg, in vitro are reported. The reactions were investigated using Penefsky spun columns and NMR saturation transfer methods. Under the Penefsky chromatography conditions with 0.4-0.6 mM albumin and a wide range of Et(3)PAuSATg concentrations, the reaction is biphasic. The fast phase is apparently first order in albumin with a rate constant [k(1) = 3.4 +/- 0.3 x 10(-)(2) s(-)(1)] that decreases slightly in magnitude and becomes intermediate in order at low gold concentrations, [Et(3)PAuSATg] < [AlbSH]; it accounts for approximately 95% of the Au(I) that binds. A minor, slower step [k(2) = 2.3 +/- 0.3 x 10(-)(3) s(-)(1)), which accounts for only 5% of the reaction, is also first order with respect to albumin, and zero order with respect to auranofin. For iPr(3)PAuSATg, only the first step was observed, k(1) = (1.4 +/- 0.1) x 10(-)(2) s(-)(1), and is first order in albumin and independent of the iPr(3)PAuSATg concentration. (31)P-NMR saturation transfer experiments utilizing iPr(3)PAuSATg, under equilibrium conditions, yielded second-order rate constants for both the forward (1.2 x 10(2) M(-)(1) s(-)(1)) and the reverse (3.9 x 10(1) M(-)(1) s(-)(1)) directions. A multistep mechanism involving a conformationally altered albumin species was developed. Albumin domain IA opens with concomitant Cys-34 rearrangement, allowing facile gold binding and exchange, and then closes. In conjunction with the steady-state approximation, this mechanism accounts for the different reaction orders observed under the two set of conditions. The rate-determining conformational change of albumin governs the reaction as monitored by the Penefsky columns. Rapid second order exchange of R(3)PAuSATg at the exposed Cys-34 residue is observed under the NMR conditions. The mechanism predicts that under physiological conditions where [Et(3)PAuSATg] is 10-25 &mgr;M, the reaction will be second order and rapid with a rate constant of 8 +/- 2 x 10(2) M(-)(1) s(-)(1). The Penefsky spun columns revealed a previously unreported and novel binding mechanism, association of auranofin in the pocket of albumin-disulfide species, which was confirmed by Hummel-Dreyer gel chromatographic techniques under equilibrium conditions. This albumin-auranofin complex (AlbSSR-Et(3)PAuSATg) is weakly bound and readily dissociates during conventional gel exclusion chromatography.     

Practical aspects of using methacrylate-ester-based monolithic columns in capillary electrochromatography

Methacrylate-ester-based monoliths containing quaternary ammonium groups were prepared in situ in capillary columns and in simultaneous experiments in vials, employing thermal initiation. The chromatographic properties of the monoliths were determined with capillary electrochromatography (CEC), and their morphology was studied with mercury-intrusion porosimetry on the bulk materials. Materials with different, well repeatable pore-size distributions could be prepared. A satisfactory column-to-column and run-to-run repeatability was obtained for the electro-osmotic mobility, the retention characteristics (k-values) and the efficiency on the columns prepared and tested in the CEC mode. A relatively high electro-osmotic flow was observed in the direction of the positive electrode. The electro-osmotic mobility was found to be influenced only marginally by mobile-phase parameters such as the pH, ionic strength, and acetonitrile content. The retention behavior of the monolithic columns was similar to that of columns packed with C18-modified silica particles. Columns could be prepared with optimum plate heights ranging from 6 microm for unretained compounds to 20 microm for well retained (k=2.5) polyaromatic hydrocarbons. However, for specific analytes a - still unexplained - lower chromatographic column efficiency was observed.     

Structure and performance of silica-based monolithic HPLC columns

Silica-based monolithic columns were prepared for HPLC with systematic variations of the tetramethoxysilane (TMOS) and polyethylene oxide (PEO) content as reactants in a sol-gel process accompanied by phase separation. The resulting monoliths showed differences in the macropore and silica skeleton diameter as well as in the corresponding domain sizes (the sum of macropore and skeleton diameter). All monoliths were synthesized with a diameter of 4.6 mm and cladded with a suitable polyaryletheretherketone (PEEK) polymer in a standardized and optimized manner for the subsequent chromatographic evaluation of the resulting monolithic HPLC columns. The columns were tested under normal phase conditions using n-heptane/dioxane (95:5 v/v) as a mobile phase and 2-nitroanisole as a test compound for the determination of separation efficiency and permeability. Two different sets of columns were prepared: the first one in which the amount of PEO was stepwise decreased to yield monoliths with identical macropore volumes and variations in the domain sizes. The second group of materials was synthesized adjusting both TMOS and PEO quantities to yield monolithic columns with identical macropore diameters of about 1.80 microm but different skeleton diameters and macropore volumes. The chromatographic results suggest that an increase in the column performance cannot be achieved by just arbitrarily decreasing the domain size of a given column. From a certain point of "downsizing" the monolithic structure a loss of structural homogeneity can be observed, which is apparently responsible for a lower chromatographic performance.     

Synthesis and structural characterization of integrally oxidized, metal-free phthalocyanine compounds: [H(2)(pc)][IBr(2)] and [H(2)(pc)](2)[IBr(2)]Br.C(10)H(7)Br

The first integrally oxidized metal-free phthalocyanine compounds have been synthesized by chemical oxidation. Phthalocyanine (H(2)(pc), pc = phthalocyaninato) was oxidized with IBr to afford the compounds [H(2)(pc)][IBr(2)] (1) and [H(2)(pc)](2)[IBr(2)]BrAC(10)H(7)Br (2), whose structures were determined by means of single-crystal X-ray diffraction methods: [H(2)(pc)][IBr(2)], P2(1)/c, a = 8.0272(9) A, b = 21.258(2) A, c = 18.1439(2) A, beta = 113.975(2) degrees, V = 2828.8(5) A(3), T = 153 K, Z = 4; [H(2)(pc)](2)[IBr(2)]Br.C(10)H(7)Br, P, a = 8.4724(6) A, b = 13.5794(10) A, c = 13.8403(10) A, alpha = 90.854(1) degrees, beta = 103.417(1) degrees, gamma = 97.049(1)E degrees, V = 1535.61(19) A(3), T = 153 K, Z = 1. The extended structure of [H(2)(pc)][IBr(2)] comprises slipped columns of pc rings stacked along the a axis in adjacent columns at approximately 70 degrees to one another. IBr(2-) ions occupy the interstitial columns. The extended structure of [H(2)(pc)](2)[IBr(2)]Br.C(10)H(7)Br comprises slant stacks of pc rings along the crystallographic a axis with IBr(2-) ions, Br(-) ions, and disordered 1-bromonaphthalene molecules in the adjacent, parallel columns. The overall reaction for the formation of 1 is 2H(2)(pc) + 4IBr --> 2[H(2)(pc)][IBr(2)] + I(2), and the overall reaction for the formation of 2 (not including solvent) is 2H(2)(pc) + 3IBr --> [H(2)(pc)](2)Br[IBr(2)] + I(2).     

Novel method to prepare polystyrene-based monolithic columns for chromatographic and electrophoretic separations by microwave irradiation

Microwave irradiation can provide a viable alternative to the traditional means such as ultraviolet light and thermal initiation for the preparation of monolithic capillary columns. Polystyrene-based monolithic stationary phases were prepared in situ in fused-silica capillaries and simultaneously in vials. The column permeability, electrophoretic and chromatographic behavior were evaluated using pressure-assisted capillary electrochromatography (pCEC), capillary electrochromatography (CEC) and low pressure liquid chromatography (LPLC). With an optimal monolithic material, the largest theoretical plates for preparing the column could be close to 18,000 plates/m for thiourea in the mode of pCEC. Furthermore, the influence of the composition of the porogenic solvents (toluene/isooctane) on the morphology of organic-based monoliths [poly(styrene-divinylbenzene-methacrylic acid)] was systematically studied with mercury intrusion porosimetry and scanning electron microscopy. The monoliths which were prepared with a high content of isooctane had a bigger pore size and better permeability, and hence resulted in a faster separation.     

Ring-opening metathesis polymerization-derived monolithic capillary columns for high-performance liquid chromatography. Downscaling and application in medical research

Monolithic capillary columns were prepared via ring-opening metathesis polymerization (ROMP) using norborn-2-ene (NBE) and 1, 4, 4a, 5, 8, 8a-hexahydro-1, 4, 5, 8-exo,endo-dimethanonaphthalene (DMN-H6) as monomers. The monolithic polymer was copolymerized with Grubbs-type initiator RuCl(2)(PCy(3))(2)(CHPh) and a suitable porogenic system within the confines of fused silica capillaries of different inner diameter (I.D.). The first part of the study focused on batch-to-batch reproducibility of ROMP-derived capillary monoliths. Capillary monoliths of 200 microm I.D. showed good reproducibility in terms of retention times, with relative standard deviations (RSD) of 1.9% for proteins and 2.2% for peptides. However, the separately synthesized capillary monoliths revealed pronounced variation in back pressure with RSD values of up to 31%. These variations were considerably reduced by cooling of the capillaries during polymerization. Using this optimized preparation procedure capillary monoliths of 100 and 50 microm I.D. were synthesized and the effects of scaling down the column I.D. on the morphology and on the reproducibility of the polymerization process were investigated. In the second part, the applicability of ROMP-derived capillary monoliths to a separation problem common in medical research was assessed. A 200 microm I.D. monolithic column demonstrated excellent separation behavior for insulin and various insulin analogs, showing equivalent separation performance to Vydac C4 and Zorbax C3-based stationary phases. Moreover, the high permeability of monoliths enabled chromatographic separations at higher flow rates, which shortened analysis time to about one third. For the analysis of insulin in human biofluid samples, enhanced sensitivity was achieved by using a 50 microm I.D. ROMP-derived monolith.     

HPLC analysis of synthetic polymers on short monolithic columns

Ultrashort monolithic columns (disks) were thoroughly studied as efficient stationary phases for precipitation–dissolution chromatography of synthetic polymers. Gradient elution mode was applied in all chromatographic runs. The mixtures of different flexible chain homopolymers, such as polystyrenes, poly(methyl methacrylates), and poly(tert‐butylmethacrylates) were separated according to their molecular weights on both commercial poly(styrene‐co‐divinylbenzene) disks (12 id × 3 mm and 5 × 5 mm) and lab‐made monolithic columns (4.6 id × 50 mm) filled with supports of different hydrophobicity. The experimental conditions were optimized to reach fast and highly efficient separation. It was observed that, similar to the separation of monoliths of other classes of (macro)molecules (proteins, DNA, oligonucleotides), the length of column did not affect the peak resolution. A comparison of the retention properties of the poly(styrene‐co‐divinylbenzene) disk‐shaped monoliths with those based on poly(lauryl methacrylate‐co‐ethylene dimethacrylate), poly(butyl methacrylate‐co‐ethylene dimethacrylate), and poly(glycidyl methacrylate‐co‐ethylene dimethacrylate) supports demonstrated the obvious effect of surface chemistry on the resolution factor. Additionally, the results of the discussed chromatographic mode on the fast determination of the molecular weights of homopolymers used in this study were compared to those established by SEC on columns packed with sorbent beads of a similar nature to the monoliths.     

Multinuclear NMR studies of the products resulting from the reaction of pyridine or 2,2'-bipyridine with [Rh4(CO)12

The progressive addition of anhydrous pyridine, (py), to a solution of [Rh(4)(CO)(12)] in CH(2)Cl(2) under CO, even at low temperature, results in immediate disproportionation to give cis-[Rh(CO)(2)py(2)][Rh(5)(CO)(15)]; further addition of pyridine results in the progressive replacement of CO's by py on the same apical rhodium in [Rh(5)(CO)(15)](-) to give cis-[Rh(CO)(2)py(2)][Rh(5)(CO)(15-x)py(x)] (x = 1, 2). The analogous reactions with 2,2'-bipyridine (bipy) give only [Rh(CO)(2)bipy][Rh(5)(CO)(13)bipy]. IR and low temperature, multinuclear NMR measurements have been used to establish the structures of all the above anions and the structures of [Rh(5)(CO)(13)(bipy)](-) and [Rh(5)(CO)(13)py(2)](-) are subtly different. Under N(2), [Rh(4)(CO)(12)] reacts with py to give [Rh(6)(CO)(16-y)py(y)] (y = 1, 2).     

Direct synthesis of NNN-donor enantiopure scorpionate ligands by an efficient diastereoselective nucleophilic addition to imines

New enantiopure imines (1-9) with a chiral substrate to control the stereochemistry of a newly created stereogenic center have been synthesized by reaction of the commercially available (1R)-(-)-myrtenal and different primary amines. The diastereomerically enriched lithium-scorpionate compounds [Li(κ(3)-mobpza)(THF)] (10) (mobpza = N-p-methylphenyl-(1R and 1S)-1-[(1R)-6,6-dimethylbicyclo[3.1.1]-2-hepten-2-yl]-2,2-bis(3,5-dimethylpyrazol-1-yl)ethylamide), [Li(κ(3)-mobpza)(THF)] (11) (mobpza = N-p-methoxyphenyl-(1R and 1S)-1-[(1R)-6,6-dimethylbicyclo[3.1.1]-2-hepten-2-yl]-2,2-bis(3,5-dimethylpyrazol-1-yl)ethylamide), [Li(κ(3)-fbpza)(THF)] (12) (fbpza = N-p-fluorophenyl-(1R and 1S)-1-[(1R)-6,6-dimethylbicyclo[3.1.1]-2-hepten-2-yl]-2,2-bis(3,5-dimethylpyrazol-1-yl)ethylamide), and [Li(κ(3)-clbpza)(THF)] (13) (clbpza = N-p-chlorophenyl-(1R and 1S)-1-[(1R)-6,6-dimethylbicyclo[3.1.1]-2-hepten-2-yl]-2,2-bis(3,5-dimethylpyrazol-1-yl)ethylamide) were obtained by a diastereoselective 1,2-addition of an organolithium reagent to imines in good yield and with good diastereomeric excess (ca. 80%). The complexes [LiCl(κ(2)-R,R-fbpzaH)(THF)] (14) and [LiCl(κ(2)-R,R-clbpzaH)(THF)] (15) were obtained in enantiomerically pure form by the treatment of THF solutions of 12 or 13 with NH(4)Cl. The enantiomerically pure amines (R,R-mbpzaH) (16), (R,R-mobpzaH) (17), (R,R-fbpzaH) (18), and (R,R-clbpzaH) (19) were obtained by hydrolysis of the lithium-scorpionate compounds 10-13 with H(2)O. The lithium compound 12 was reacted with [TiCl(4)(THF)(2)] or [ZrCl(4)] to give the enantiopure complexes [MCl(3)(κ(3)-R,R-fbpza)] [M = Ti (20), Zr (21)]. The amine compound 18 reacted with [MX(4)] (M = Ti, X = O(i)Pr, OEt; M = Zr; X = NMe(2)) to give the complexes [MX(3)(κ(3)-R,R-fbpza)] (22-24). The reaction of Me(3)SiCl with [Zr(NMe(2))(3)(κ(3)-R,R-fbpza)] (24) in different molar ratios led to the halide-amide-containing complexes [ZrCl(NMe(2))(2)(κ(3)-R,R-fbpza)] (25) and [ZrCl(2)(NMe(2))(κ(3)-R,R-fbpza)] (26) and the halide complex 21. The isolation of only one of the three possible diastereoisomers of complexes 25 and 26 revealed that chiral induction from the ligand to the zirconium center took place. The structures of these compounds were elucidated by (1)H and (13)C{(1)H} NMR spectroscopy, and the X-ray crystal structures of 5, 12, 14, 15, and 24 were also established.     

Sterically hindered electron-withdrawing ligands: the reactions of N-carbazolyl phosphines with rhodium and palladium centres

The series of N-carbazolyl phosphines PPh(3-n)(NC(12)H(8))(n)(n= 1, L1; n= 2, L2; n= 3, L3) has been synthesised using BuLi to generate the N-carbazolyl lithium salt, followed by reaction with the appropriate chlorophosphine. The reactions between [Rh(mu-Cl)(CO)(2)](2) and four equivalents of L1 or L2 gave [RhCl(CO)(L1)(2)] 1 and [RhCl(CO)(L2)(2)] 2, though attempts to synthesise the analogous complex using L3 resulted in the formation of [Rh(mu-Cl)(CO)(L3)](2) 3 instead. The inability of L3 to cleave the chloride bridges can be related to its considerable steric requirements. The electronic properties of L1-3 were assessed by comparison of the nu(CO) values of the [Rh(acac)(CO)(L1-3)] complexes 4-6. The increase in number of N-carbazolyl substituents at the phosphorus atom results in a decrease of the sigma-donor and increase in the pi-acceptor character in the order L1 < L2 < L3. In the reactions of L1-3 with [PdCl(2)(cod)] only L1 was able to displace cod from the metal centre and form [PdCl(2)(L1)(2)] 7. The use of [PdCl(2)(NCMe)(2)] instead of [PdCl(2)(cod)] resulted in the formation of the complexes [PdCl(2)(L1)(2)] 7 from L1, the cyclometallated complex [Pd(mu-Cl)[P(NC(12)H(8))(2)(NC(12)H(7))-kappa(2)P,C]](2) 8 from L3 , and a mixture of [PdCl(2)(L2)(2)] 9 and [Pd(mu-Cl)[PPh(NC(12)H(8))(NC(12)H(7))-kappa(2)P,C]](2) 10 from L2 . The reaction of L3 with [Pd(OAc)(2)] produced the cyclometallated complex [Pd(mu-O(2)CCH(3))[P(NC(12)H(8))(2)(NC(12)H(7))-kappa(2)P,C]](2) 11. The reaction of L3 with [Pd(2)(dba)(3)].CHCl(3) produced the 14-electron complex [Pd(L3)(2)] 12. The X-ray crystal structures of six complexes are reported, all of which show the presence of C-H...Pd hydrogen bonding.     

Novel monolithic poly(phenyl acrylate-co-1,4-phenylene diacrylate) capillary columns for biopolymer chromatography

Monolithic capillary columns were prepared by thermally initiated free radical polymerisation of phenyl acrylate (PA) and 1,4-phenylene diacrylate (PDA) in the confines of 200 microm I.D. fused silica capillaries. Polymerisation was performed in the presence of 2-propanol and tetrahydrofuran (THF) as inert diluents (porogens), using alpha,alpha'-azoisobutyronitrile (AIBN) as initiator. Morphology and porosity of the resulting monoliths were comprehensively studied by scanning electron microscopy (SEM), mercury intrusion porosimetry and inverse size-exclusion chromatography (ISEC). The novel poly(phenyl acrylate-co-1,4-phenylene diacrylate) (PA/PDA) monoliths showed high mechanical stability and were successfully applied to the separation of proteins and oligodeoxynucleotides, employing reversed-phase (RP) and ion-pair reversed-phase (IP-RP) conditions, respectively. Maximum loading capacities for cytochrome c and d(pT)(16) were evaluated and found to be in the region of 200 fmol. Batch-to-batch reproducibility was determined for three independently prepared PA/PDA monolithic capillary columns. Relative standard deviations (RSDs) of retention time (t(R)) of 0.7-1.6% for proteins and 0.2-2.5% for d(pT)(12-18) proved high reproducibility of the PA/PDA supports.     

Building a bridge between coordination compounds and clusters: bonding analysis of the icosahedral molecules [M(ER)12] (M = Cr, Mo, W; E = Zn, Cd, Hg)

The bonding situation of the icosahedral compounds [M(EH)(12)] (M = Cr, Mo, W; E = Zn, Cd, Hg), which are model systems for the isolated species [Mo(ZnCp*)(3)(ZnMe)(9)] possessing the coordination number 12 at the central atom M, have been analyzed with a variety of charge and energy decomposition methods (AIM, EDA-NOCV, WBI, MO). The results give a coherent picture of the electronic structure and the nature of the interatomic interactions. The compounds [M(EH)(12)] are transition metal complexes that possess 12 M-EH radial bond paths (AIM) that can be described as 6 three-center two-electron bonds (MO). The radial M-EH bonds come from the electron sharing interactions mainly between the singly occupied valence s and d AOs of the central atom M and the singly occupied EH valence orbitals (MO, EDA-NOCV). The orbital interactions provide ~42% of the total attraction, while the electrostatic attraction contributes ~58% to the metal-ligand bonding (EDA-NOCV). There is a weak peripheral E-E bonding in [M(EH)(12)] that explains the unusually high coordination number (MO). The peripheral bonding leads for some compounds [M(EH)(12)] to the emergence of E-E bond paths, while in others it does not (AIM). The relative strength of the radial and peripheral bonding in [Al(13)](-) and [Pt@Pb(12)](2-) is clearly different from the situation in [M(EH)(12)], which supports the assignments of the former species as cluster compounds or inclusion compounds (MO, WBI). The bonding situation in [WAu(12)] is similar to that in [M(EH)(12)].     

Synthesis, characterization and reactivity of tetranuclear ruthenium hydrido clusters containing chiral phosphine ligands

The chiral clusters [H(4)Ru(4)(CO)(12-n)(L)(n)] (n = 1, 2; L = NMDPP), 1,1-[H(4)Ru(4)(CO)(10)(L-L)] (L-L = DUPHOS, DIPAMP), 1,2-[H(4)Ru(4)(CO)(10)(DIOP)] and [{H(4)Ru(4)(CO)(10)(DIOP)}(2)] have been synthesized by derivatizing the parent carbonyl cluster [H(4)Ru(4)(CO)(12)] with the appropriate mono- or didentate chiral phosphine ligand. The phosphine-substituted clusters were found to be able to catalyze the (asymmetric) hydrogenation of tiglic acid albeit with relatively low selectivity (enantiomeric excesses varying from 0 to 23%). It was found that the stability of the chiral ruthenium hydride clusters and the product distribution obtained in the catalytic reactions are dependent on the nature of the chiral phosphine. The crystal structures of [H(4)Ru(4)(CO)(12-n)(L)(n)] (n = 1, 2; L = NMDPP), 1,1-[H(4)Ru(4)(CO)(10)(L-L)] (L-L = DUPHOS, O-DUPHOS (partially oxygenated ligand), DIPAMP), 1,2-[H(4)Ru(4)(CO)(10)(DIOP)] and [{H(4)Ru(4)(CO)(10)(DIOP)}(2)] are presented.     

Arene-ruthenium complexes with salicyloxazolines: diastereoselective synthesis, configurational stability and applications as asymmetric catalysts for Diels-Alder reactions

Reaction of the dimers [RuCl2(eta6-arene)]2 (arene = benzene, p-cymene, mesitylene) with salicyloxazolines in the presence of NaOMe gives complexes [RuCl(R-saloxaz)(arene)] (1-5) which have been fully characterised. Complexes [RuL(iPr-saloxaz)(mes)]Y (L = py, 2-Mepy, 4-Mepy; PPh3; Y- = SbF6 or BPh4) 6-9 were prepared by treating the chloride 2a with ligand L and NaY (Y- = SbF6 or BPh4) in methanol at reflux. Halide complexes [RuX(iPr-saloxaz)(mes)](X = Br, 10; X = I, 11) were synthesised by treating 2a with AgSbF6 then with 1.2 equivalents of KBr or NaI, the methyl complex [RuMe(iPr-saloxaz)(mes)] 12 was synthesised from 2a by reaction with MeLi. Five complexes, [RuCl(iPr-saloxaz)(mes)] 2a, [RuCl(tBu-saloxaz)(p-cymene)] 3b, [RuCl(Ph-saloxaz)(mes)] 5a, [Ru(4-Mepy)(iPr-saloxaz)(mes)][SbF6] 7, and [Ru(PPh3)(iPr-saloxaz)(mes)][SbF6] 9, have been characterised by X-ray crystallography. Treatment of complexes 1-5 with AgSbF6 gives cationic species which are enantioselective catalysts for the Diels-Alder reaction of acroleins with cyclopentadiene, the effect of substituents on enantioselectivity has been examined.