HPLC separations of meropenem and selected pharmaceuticals using a polar endcapped octadecylsilane narrow bore column

Summary Stability indicating high performance liquid chromatography methods have been developed for the assay of meropenem in combination with either dopamine (A), aminophylline (B), metoclopramide (C) or ranitidine (D) in intravenous fluid mixtures. Separations B, C and D were performed on a polar endcapped ODS column (150×2 mm) with aqueous, pH 3.0—acetonitrile (89∶11, 88∶12, and 92∶8) eluent and detection at 270, 290, 317 nm respectively. Meropenem was linear over the concentration ranges 126.88–507.50, 131.25–525, and 131.25–525 gmg mL⁻¹. Aminophylline, metoclopramide and ranitidine were linear over the concentration ranges 13–52, 37.5–150, and 25–100 μg mL⁻¹. Separation A was performed on a conventional ODS column (150×2.1 mm) with aqueous, pH 3.0—acetonitrile (85∶15) eluent and detection at 280 nm. Meropenem and dopamine were linear in the 61.25–245 and 10–40 μg mL⁻¹ ranges, respectively. Accuracy and precision for all methods were 0.20–3.30% and 0.10–1.58%, respectively. Accelerated stability studies have been carried out on each drug by exposure to acid, base, H₂O₂, and heat for different time periods.     

Solid Phase Peptide Synthesis

The last two decades have been an era of rapid progress in peptide research. This era was begun by the work of Sanger on the amino acid sequence determination of insulin and by du Vigneaud on the structure determination and synthesis of oxytocin. This period has seen impressive progress in the structure elucidation and synthesis of many peptides of natural origin and of great biological significance, as well as in methods for sequence determination and chemical synthesis of peptides [1–4]. Perfection of techniques and instruments for automatic determination of the amino acid sequence of peptides and proteins has made possible a greatly broadened understanding of genetics and evolution as well as the more chemical areas of mechanism of action of enzymes and hormones, and physical chemistry of peptides and proteins. Effective methods of peptide synthesis are crucial to progress in this area, because only by synthesis can adequate amounts of important peptides be made available for chemical, biological, and physical studies, as well as for exploration of the structure-function aspects of biological molecules. In general, progress in peptide synthesis has lagged far behind that in amino acid sequence determination. This is not surprising since effective peptide synthesis requires a very sophisticated system of selectively removable protecting groups for functions of the amino acids involved, and the synthesis of a large heteropolytner of defined sequence requires near perfection of each one of the many steps of the assembly. The classical approach to peptide synthesis, using standard organic chemical methods of synthesis and purification of intermediates, has yielded impressive results during these two decades. However, the special problems associated with the assembly of large molecules make staggering investments in time and materials necessary for the synthesis of large peptides or proteins by classical methods.     

Lithol Red: a systematic structural study on salts of a sulfonated azo pigment

The first systematic series of single-crystal diffraction structures of azo lake pigments is presented (Lithol Red with cations=Mg(II), Ca(II), Sr(II), Ba(II), Na(I) and Cd(II)) and includes the only known structures of non-Ca examples of these pigments. It is shown that these commercially and culturally important species show structural behaviour that can be predicted from a database of structures of related sulfonated azo dyes, a database that was specifically constructed for this purpose. Examples of the successful structural predictions from the prior understanding of the model compounds are that 1) the Mg salt is a solvent-separated ion pair, whereas the heavier alkaline-earth elements Ca, Sr and Ba form contact ion pairs, namely, low-dimensional coordination complexes; 2) all of the Lithol Red anions exist as the hydrazone tautomer and have planar geometries; and 3) the commonly observed packing mode of alternating inorganic layers and organic bilayers is as expected for an ortho-sulfonated azo species with a planar anion geometry. However, the literature database of dye structures has no predictive use for organic solvate structures, such as that of the observed Na Lithol Red DMF solvate. Interestingly, the Cd salt is isostructural with the Mg salt and not with the Ca salt. It is also observed that linked eight-membered [MOSO](2) rings are the basic coordination motif for all of the known structures of Ca, Sr and Ba salts of sulfonated azo pigments in which competing carboxylate groups are absent.     

Straightforward synthesis of sphinganines via a serine-derived Weinreb amide

Sphinganines can be synthesized in just three steps from easily prepared serine-derived Weinreb amide 4. Pre-deprotonation of the acidic (N-H and O-H) protons of 4 allows for its efficient conversion to amino ketones 5. Such ketones can be selectively reduced to either erythro- or threo-sphinganines. Partially protected sphinganines 11 are also readily accessible in five steps from 4. Thus, Weinreb amide 4 represents one of the most versatile templates described to date for sphinganine synthesis.     

Octanuclear and nonanuclear supramolecular copper(II) complexes with linear "tritopic" ligands: structural and magnetic studies

The structures and magnetic properties of self-assembled copper(II) clusters and grids with the "tritopic" ligands 2poap (a), Cl2poap (b), m2poap (c), Cl2pomp (d), and 2pomp (e) are described [ligands derived by reaction of 4-R-2,6-pyridinedicarboxylic hydrazide (R = H, Cl, MeO) with 2-pyridinemethylimidate (a-c, respectively) or 2-acetylpyridine (d, R = Cl; e, R = H)]. Cl2poap and Cl2pomp self-assemble with Cu(NO(3))(2) to form octanuclear "pinwheel" cluster complexes [Cu(8)(Cl2poap-2H)(4)(NO(3))(8)].20H(2)O (1) and [Cu(8)(Cl2pomp-2H)(4)(NO(3))(8)].15H(2)O (2), built on a square [2 x 2] grid with four pendant copper arms, using "mild" reaction conditions. Similar reactions of Cl2pomp and 2pomp with Cu(ClO(4))(2) produce pinwheel clusters [Cu(8)(Cl2pomp-2H)(4)(H(2)O)(8)](ClO(4))(8).7H(2)O (3) and [Cu(8)(2pomp-2H)(4)(H(2)O)(8)](ClO(4))(8) (4), respectively. Heating a solution of 1 in MeOH/H(2)O produces a [3 x 3] nonanuclear square grid complex, [Cu(9)(Cl2poap-H)(3)(Cl2poap-2H)(3)](NO(3))(9).18H(2)O (5), which is also produced by direct reaction of the ligand and metal salt under similar conditions. Reaction of m2poap with Cu(NO(3))(2) produces only the [3 x 3] grid [Cu(9)(m2poap-H)(2)(m2poap-2H)(4)](NO(3))(8).17H(2)O (6) under similar conditions. Mixing the tritopic ligand 2poap with pyridine-2,6-dicarboxylic acid (picd) in the presence of Cu(NO(3))(2) produces a remarkable mixed ligand, nonanuclear grid complex [Cu(9)(2poap-H)(4)(picd-H)(3)(picd-2H)](NO(3))(9).9H(2)O (7), in which aromatic pi-stacking interactions are important in stabilizing the structure. Complexes 1-3 and 5-7 involve single oxygen atom (alkoxide) bridging connections between adjacent copper centers, while complex 4 has an unprecedented mixed micro-(N-N) and micro-O metal ion connectivity. Compound 1 (C(76)H(92)N(44)Cu(8)O(50)Cl(4)) crystallizes in the tetragonal system, space group I, with a = 21.645(1) A, c = 12.950(1) A, and Z = 2. Compound 2 (C(84)H(88)N(36)O(44)Cl(4)Cu(8)) crystallizes in the tetragonal system, space group I, with a = 21.2562(8) A, c = 12.7583(9) A, and Z = 2. Compound 4 (C(84)H(120)N(28)O(66)Cl(8)Cu(8)) crystallizes in the tetragonal system, space group I4(1)/a, with a = 20.7790(4) A, c = 32.561(1) A, and Z = 4. Compound 7(C(104)H(104)N(46)O(56)Cu(9)) crystallizes in the triclinic system, space group P, with a = 15.473(1) A, b = 19.869(2) A, c = 23.083(2) A, alpha = 88.890(2) degrees, beta = 81.511(2) degrees, gamma = 68.607(1) degrees, and Z = 2. All complexes exhibit dominant intramolecular ferromagnetic exchange coupling, resulting from an orthogonal bridging arrangement within each polynuclear structure.     

High-density targeting of a viral multifunctional nanoplatform to a pathogenic, biofilm-forming bacterium

Nanomedicine directed at diagnosis and treatment of infections can benefit from innovations that have substantially increased the variety of available multifunctional nanoplatforms. Here, we targeted a spherical, icosahedral viral nanoplatform to a pathogenic, biofilm-forming bacterium, Staphylococcus aureus. Density of binding mediated through specific protein-ligand interactions exceeded the density expected for a planar, hexagonally close-packed array. A multifunctionalized viral protein cage was used to load imaging agents (fluorophore and MRI contrast agent) onto cells. The fluorescence-imaging capability allowed for direct observation of penetration of the nanoplatform into an S. aureus biofilm. These results demonstrate that multifunctional nanoplatforms based on protein cage architectures have significant potential as tools for both diagnosis and targeted treatment of recalcitrant bacterial infections.     

In situ auger electron spectroscopy study of atomic layer deposition: growth initiation and interface formation reactions during ruthenium ALD on Si-H, SiO2, and HfO2 surfaces

Growth initiation and film nucleation in atomic layer deposition (ALD) is important for controlling interface composition and achieving atomic-scale films with well-defined composition. Ruthenium ALD is studied here using ruthenocene and oxygen as reactants, and growth initiation and nucleation are characterized on several different growth surfaces, including SiO2, HfO2, and hydrogen terminated silicon, using on-line Auger electron spectroscopy and ex-situ X-ray photoelectron spectroscopy. The time needed to reach the full growth rate (typically approximately 1 A per deposition cycle) is found to increase as the surface energy of the starting surface (determined from contact angle measurements) decreased. Growth starts more readily on HfO2 than on SiO2 or Si-H surfaces, and Auger analysis indicates distinct differences in surface reactions on the various surfaces during film nucleation. Specifically, surface oxygen is consumed during ruthenocene exposure, so the nucleation rate will depend on the availability of oxygen and the energetics of surface oxygen bonding on the starting substrate surface.     

Spectrophotometric determination of aromatic primary amines and nitrite by flow injection analysis

Aromatic primary amines are determined by injection into dilute hydrochloric acid carrier which merges sequentially with 4-N-methylaminophenol and dichromate. The purple-red color formed by oxidative coupling of amines with 4-N-methylaminophenol is measured at 530 nm. In contrast to the manual procedure, the flow-injection procedure avoided errors arising from the instability of the coupling intermediate, oxidation of the amine, and too great an excess of the oxidant. The method improves the selectivity for certain amines in the presence of those which are sterically hindered or have an electron-deficient aromatic nucleus. Nitrite is determined by diazotization of sulfanilamide and quantifying the residual sulfanilamide by oxidative coupling. The sample thourghout for the assay of amines (0.05–20 μg ml^?1 NH₂-N) and nitrite (1–10 μg ml^?1 NO₂^--N) was 120 h^?1. A system for the consecutive determination of aromatic primary amines and nitrite is decribed.     

Simultaneous extraction and clean-up of polybrominated diphenyl ethers and polychlorinated biphenyls from sheep liver tissue by selective pressurized liquid extraction and analysis by gas chromatography-mass spectrometry

We describe a selective pressurized liquid extraction (SPLE) method, followed by gas chromatography–mass spectrometry (GC–MS), for the simultaneous extraction and clean-up of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) in sheep liver tissue samples. The on-line clean-up of liver tissue by SPLE was tested using differing amount of acid-modified silica (sulphuric acid:silica gel, 1:2, w/w), the most effective amount being 20 g. Different extraction solvents (iso-hexane and dichloromethane), either alone or in various combinations, were used to extract these target compounds from spiked liver samples. Variables affecting the SPLE extraction efficiency, including temperature, pressure, number of extraction cycles and static extraction time were studied; the optimum parameters were 80 °C, 10.3 MPa, 2 cycles and 5 min, respectively. The SPLE based method was compared with more traditional Soxhlet, off-line PLE, ultrasonic and heating extraction methods. Overall the mean percentage recoveries for all target chemicals using SPLE were 86–103% (n = 3, SD < 9%), and compared favourably with the Soxhlet (63–109%, n = 3, SD < 8%), off-line PLE (82–104%, n = 3, SD < 18%), ultrasonic (86–99%, n = 3, SD < 11%) and heating (72–102%, n = 3, SD < 21%) extraction methods. The limits of detection of the proposed method were 5–96 pg g⁻¹ and 2–29 pg g⁻¹ for the different PBDE and PCB chemicals studied, respectively. The outputs of the proposed method were linear over the range from 0.02 to 30 ng g⁻¹, for all PCB and PBDE congeners except for PBDE 100 and 153 (0.05–30 ng g⁻¹) and PBDE 183 (0.1–30 ng g⁻¹). The method was successfully applied to sheep liver samples for the determination of the target PBDE and PCB compounds.     

Stabilizing carbon-lithium stars

We have explored in silico the potential energy surfaces of the C(5)Li(n)(n-6) (n = 5, 6, and 7) clusters using the Gradient Embedded Genetic Algorithm (GEGA) and other computational strategies. The most stable forms of C(5)Li(5)(-) and C(5)Li(6) are two carbon chains linked by two lithium atoms in a persistent seven membered ring capped by two Li atoms. The other Li atoms are arrayed on the edge of the seven membered ring. In contrast, the global minimum structure for C(5)Li(7)(+) is a bicapped star of D(5h) symmetry. The molecular orbital analysis and computed magnetic field data suggest that electron delocalization, as well as the saturation of the apical positions of the five-membered carbon ring with lithium atoms in C(5)Li(7)(+) plays a key role in the stabilization of the carbon-lithium star. In fact, the planar star sub-structure for the carbon ring are unstable without the apical caps. This is also what has been found for the Si analogues. The split of the B(ind)(z) in its σ- and π-contribution indicates that C(5)Li(7)(+) is a π-aromatic and σ-nonaromatic system.