Direct determination of gentamicin components by capillary electrophoresis with potential gradient detection

A simple and fast method was developed to determine non-UV active compounds directly without derivatization. The usefulness of the method was demonstrated by detecting the major components in aminoglycoside antibiotic mixtures using capillary zone electrophoresis with potential gradient detection. Under optimized separation conditions (0.2 mM cetyltrimethylammonium bromide (CTAB), 1 mM ammonium citrate, pH 3.5), gentamicin was separated into three major peaks (C1, C1a, and C2+C2a) within 15 min. This method showed better sensitivity than other capillary electrophoresis (CE) methods for determining underivatized gentamicin. The linear range was from 10 to 500 ppm. Because of its good repeatability and simplicity, this new method could be a good alternative for the current assays given by US Pharmacopoeia and European Pharmacopoeia.     

The versatile chemistry of the [B20H18]2- ions: novel reactions and structural motifs

Among the polyhedral [closo-BnHn]2- ion series (n = 5-12 inclusive) the aromatic [closo-B10H10]2- ion is both readily available and quite reactive. Among its many reactions which retain its cage structure one finds the oxidative dimerization reaction in which two [closo-B10H12]2- ions each formally lose a hydride ion and undergo dimerization of the resulting [closo-B10H9]- ions to produce the [trans-B20H18]2- ion. The two-component [closo-B10H9]- ions of the latter are linked together by a pair of unique B-B-B bonds which provide unprecedented reactivity to the structure. Among these reactions are the two-electron reduction to a set of three interconvertible [B20H18]4- ions having intercage B-B bonds and the related reductive substitution reaction in which [trans-B20H18]2- undergoes attack by nucleophile, L, to produce [B20H18L]2-. The latter species is formally a substituted [B20H19]3- (L = H) ion formed by B-B bond protonation of one of the isomeric [B20H18]4- ions. These and a variety of novel reactions are described here along with interrelated reaction mechanisms considered for the first time.     

The Role of Chemistry in the Development of Boron Neutron Capture Therapy of Cancer

A therapeutic method that selectively destroys malignant cells in the presence of normal cells is a highly valued goal of oncologists and the possible salvation of cancer patients afflicted with some incurable forms of the disease. Selective cell destruction is, in principle, possible with a binary therapeutic strategy based upon the neutron capture reaction observed with the ¹⁰B nucleus and a neutron of low kinetic energy (thermal neutron). This nuclear fission reaction produces both ⁴He and ⁷Li⁺ nuclei along with about 2.4 MeV of kinetic energy and weak γ-radiation. Since the energetic and cytotoxic product ions travel only about one cell diameter in tissue one may specify the cell type to be destroyed by placing innocent ¹⁰B nuclei on or within only the doomed cells. This article describes the current status of chemical research aimed at the eventual adoption of this therapeutic method (boron neutron capture therapy or BNCT). The multidisciplinary nature of this research effort involves chemistry, biology, nuclear physics, medicine, and related specialties. Methods devised for bringing ¹⁰B nuclei to tumor cells in therapeutic amounts are correlated with the structure of a generalized cell and the various cellular compartments available for boron localization. The synthesis methods employed for the creation of boron-containing biomolecules and drugs are presented along with representative data concerning their efficacy in tumor localization. The outlook for BNCT is especially bright at this time because of rapid developments in the fields of bioorganometallic chemistry, microbiology, immunology, and nuclear science, to name but a few. Very effective boron delivery vehicles have been demonstrated, and through the interaction of chemistry and biology these species are undergoing further improvement and evaluation of their suitability for BNCT.     

High-resolution photoelectron spectroscopy through deconvolution

A new iterative deconvolution algorithm for the development of very high resolution Hc(I)-excited photoelectron spectra of gases is presented. The algorithm accepts as input a medium-resolution spectrum and an instrument function obtained by scanning intrinsically narrow line (e.g. the Ar²P_3/2 line) under conditions identical to those used to acquire the medium resolution spectrum. The deconvolved partial spectrum of an O₂H₂O mixture is presented as a test case prior to presentation of results for three nitrogen lines. For comparison purposes directly obtained high-resolution spectra of the nitrogen lines are included. The shapes of the nitrogen lines are discussed within the framework of a one-center expansion theory of photoionization. The conditions under which deconvolution can be profitably applied are briefly discussed and an attempt is made to establish the deconvolution (contrary to still popular belief) is not in any way equivalent to curve fitting.     

PHOTODYNAMIC THERAPY INDUCED ULTRASTRUCTURAL ALTERATIONS IN MICROVASCULATURE OF THE RAT CREMASTER MUSCLE

Abstract— Photodynamic therapy disrupts blood flow to tumors and produces tumor necrosis. These effects may be due to a localized generation of singlet oxygen. The current studies used direct observations of the rat cremaster microvasculature to examine the vascular effects of PDT. The objective of the morphological examination was to delineate the structural basis for the altered blood flow in photodynamic therapy. Dihematoporphyrin ether given 30 min or 48 h prior to the experiment was activated with green light (wavelength530–560 nm, 120 J/cm²). After the in vivo activation the tissues were prepared for electron microscopy. Light alone induced little or no change in the luminal content or vessel wall. On exposure to activating light both acute (30 min) and long term (48 h) dihematoporphyrin ether pretreated samples displayed formation of luminal aggregates, granulocyte margination and migration, and endothelial cell and smooth muscle cell damage. The latter was more pronounced in the arterioles than the venules. Perivascular changes included interstitial edema and damage to striated myocytes. Some of the alterations such as interstitial edema may be transient; however, smooth and skeletal muscle cell injury are important in normal and tumor tissue necrosis after photodynamic therapy.     

ULTRAVIOLET SOLAR RADIATION IN THE HIGH LATITUDES OF SOUTH AMERICA

Abstract Measurements of the UV solar irradiance are available from Ushuaia, Tierra del Fuego during the spring and summer seasons of 4 consecutive years beginning in 1989. In addition, column ozone amounts derived from satellite-based measurements exist for this location over the entire period from 1980 through 1991. Monthly mean column ozone over Ushuaia shows a general decline over the observing period, and a large day-to-day variability exists within a given month. Ozone amounts for the years 1980 through 1986 combined with a model of radiative transfer provide a climatological baseline against which to interpret the more recent ground-based irradiance data. We focus on monthly mean noontime irradiances integrated over 5 nm wide spectral bands near 305 nm and 340 nm, respectively. Measurements in the 340 nm band show that cloudiness has a large influence on both the absolute monthly mean irradiances and their interannual variability. For example, during December the 340 nm band irradiance varied from approximately 50% of the clear-sky value in 1992 to 65% in 1991. When the influence of cloudiness is removed, most of the months show irradiances in the 305 nm band that are larger than predicted from the climatological ozone amounts. The largest percentage enhancement occurred in October 1991 when the irradiance exceeded the baseline by 56%. The largest absolute irradiances occur in December, where the measurements range from 5.8% below the baseline in 1991 to 31% above in 1990.     

The synthesis and thermal curing parameters of a novel quinoxaline monomer with terminal ethynyl thermoset and phenylethynyl intramolecular cycloaddition postcure capability

The Synthesis of 3,3′-bis(4-[3-ethynylphenoxy]phenyl)-7,7′-bis(phenylethynyl)-2,2′-diphenyl-6,6′-biquinoxaline (I) was accomplished by the reaction of 2,2′-bis(phenylethynyl)-5,5′-diaminobenzidine (II) and 4-(3-ethynylphenoxy)benzil. Thermal analysis of I indicated a softening temperature of 107°C, followed by an exotherm above 150°C that corresponded to a independent crosslinking reaction of the terminal acetylene groups and an intramolecular cycloaddition (IMC) reaction of the 2,2′-bis(phenylethynyl)biphenyl moieties. In the synthetic work substantial improvements were made in the synthesis of II. The sample of I was cured at 200°C and the maximum partially cured transition temperature attained was 280°C. A sample of 3,3′-bis(4,[3-ethynylphenoxy]phenyl)-2,2′-diphenyl-6,6′-biquinoxaline (IV) was similarly tested as a model without IMC capability and its corresponding value was 250°C. The difference between these two values is discussed briefly.     

Solubility product relations in the rare earth hydrous hydroxides

The solubility products for some rare earth hydroxides and their temperature dependence have been shown. Greater solubility is shown for larger atomic radii and for lower temperature.     

Guest sorption and desorption in the metal-organic framework [Co(INA)(2)] (INA=isonicotinate)--evidence of intermediate phases during desorption

The metal-organic framework [Co(INA)(2)]x0.5EtOH (INA = isonicotinate, NC(5)H(4)-4-CO(2)(-)), was synthesised under solvothermal conditions. Its X-ray crystal structure shows channels containing ethanol guests which are hydrogen-bonded to carboxylate oxygens of the framework. The pyridyl rings of the framework alternate between 'open' and 'closed' positions along the channels resulting in large variation in the channel cross-sectional area from ca. 1.4 by 2.3 A at the narrowest point to 4.9 by 5.3 A at the widest. Despite the very small windows, the ethanol guests (of van der Waals diameter ca. 4.2-6.1 A) may be reversibly desorbed and sorbed into the structure quantitatively, as shown by in situ variable-temperture IR spectroscopy and XRPD. The single-crystal structure of the desolvated form [Co(INA)(2)] shows that there is no change in the overall connectivity on desolvation, but the rotational positions of the pyridine rings are altered. This suggests that pyridyl rotation may occur to allow guests to pass in and out. When the synthesis was conducted in 1-propanol solvent [Co(INA)(2)]x0.5Pr(n)OHxH(2)O, was obtained, and a single-crystal X-ray structure revealed the same overall connectivity as in but with pyridine rings disordered over closed and open positions. There was no evidence of included guests from X-ray crystallography, suggesting that they are also highly disordered. Variable-temperature XRPD performed on bulk samples showed peaks which were unsymmetrical and exhibited shoulders, suggesting that for each pattern obtained the material actually consisted of several closely-related phases. The movements of the peaks during desolvation showed the presence of intermediate phases before the final desolvated product was formed. The peak positions of the intermediate phases matched more closely with the calculated pattern for than with or, suggesting that they may have disordered structures similar to. The results also suggest that the intermediate phase represents an initial increase in volume before a larger decrease in volume occurs to give the final desolvated material.     

An Asymmetric Synthesis of L-694,458, a Human Leukocyte Elastase Inhibitor, via Novel Enzyme Resolution of beta-Lactam Esters

A convergent synthesis of [S-(R,S)]-2-[4-[(4-methylpiperazin-1-yl)carbonyl]phenoxy]-3,3-diethyl-N-[1-[3,4-(methylenedioxy)phenyl]butyl]-4-oxo-1-azetidinecarboxamide (L-694,458, 1), a potent human leukocyte elastase inhibitor, was achieved via chiral synthesis of key intermediates: (S)-3,3-diethyl-4-[4'-[(N-methylpiperazin-1-yl)carbonylphenoxy]-2-azetidinone (2) and (R)-alpha-propylpiperonyl isocyanate (3). Synthesis of beta-lactam 2 was achieved by a novel enantioselective lipase hydrolysis of ester 5 to produce (S)-3,3-diethyl-4-(4'-carboxyphenoxy)-2-azetidinone (6) (60% yield, three cycles, 93% ee) with isolation, epimerization, and recycling of the undesired (R)-ester 5. Isocyanate 3 was prepared by chiral addition of Zn(n-Pr)(2) to piperonal (98% yield, 99.2% ee), azide displacement and reduction to (R)-alpha-propylpiperonylamine (11) (58% yield, 85% ee), crystallization as the D-pyroglutamic acid salt (92% yield, 98.2% ee), and isocyanate formation (98% yield) with phosgene.